MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Investigational New Drugs' source. Sat, 20 Mar 2010 14:09:57 +0100 http://www.medworm.com/index.php?rid=3375700&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F302271715j349411%2F We describe the biological activity of some furylbenzo- and naphthoquinones (furylquinones) on hepatocarcinoma cells and healthy rat liver slices. The effects of furylquinones on cancer cells (Transplantable Liver Tumor, TLT) were assessed by measuring cell death (membrane cell lysis); intracellular contents of ATP and GSH and the activity of caspase-3 were used to determine the type of cell death. Most of the furylquinones tested (at a concentration of 25 μg/ml) induced caspase-independent cell death but compound 4 had no cytotoxic effects. The levels of both ATP and GSH were severely affected by quinones 1, 2 and 5, while no effect was observed with compound 4. These cytotoxic properties of quinones are associated with physico-chemical properties as shown by the LUMO energies a... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3375700 Tue, 16 Mar 2010 14:49:53 +0100 3375700 http://www.medworm.com/index.php?rid=3375701&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr645t8542557v330%2F Summary  The aim of this study was to evaluate the biological activity and pharmacological activity of several amphiphilic liquid-crystalline compounds (LCs), i.e. phenylpyrimidine derivatives possessing D-glucamine and cyanobiphenyl derivatives with a terminal hydroxyl unit, to explore novel anti-cancer functions of the LCs. The anti-cancer properties of the LCs were investigated in A549 human lung cancer cells by assessing cell growth, cell cycle distribution, and cell signaling pathways using a flow cytometer and a Western blot analysis. In addition, the effect of LCs on the growth of WI-38 normal fibroblasts was examined. Consequently, the phenylpyrimidine derivatives and cyanobiphenyl derivatives showed cytostatic effects, causing the suppression of cell growth through ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3375701 Tue, 16 Mar 2010 14:49:52 +0100 3375701 http://www.medworm.com/index.php?rid=3371573&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4k62708430252t80%2F Summary  PABA/NO is a diazeniumdiolate selectively activated by glutathione S-transferase P (GSTP) to release nitric oxide (NO) and is a potent inducer of protein S-glutathionylation, a redox-sensitive post-translational modification of cysteine residues. Using a procedure that incrementally increased exposure of cells to PABA/NO, an acquired drug resistant human promyelocytic leukemia HL60 cell line (HL60PABA) that exhibited 1.9-fold resistance to the drug (IC50 ∼15 μM vs ∼8 μM for wild-type) was created. HL60PABA cells had a decreased growth rate attributable to altered cellular differentiation, as measured by increased expression of CD11b; decreased expression of CD14; decreased nuclear to cytoplasmic ratios and a condensation of nuclear chromatin. This wa... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3371573 Mon, 15 Mar 2010 17:56:38 +0100 3371573 http://www.medworm.com/index.php?rid=3371574&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg7348rq4750v6552%2F Summary  Overexpression of HER-2 in breast cancer is frequently associated with expression of EGFR, and EGFR expression influences response to HER-2 inhibition. The aim of this study was to examine the effects of combining dual inhibition of EGFR and HER-2, using trastuzumab, gefitinib and lapatinib, in HER-2 overexpressing breast cancer cells. Combination proliferation assays were performed in two HER-2 positive breast cancer cell lines, SKBR-3 and BT-474. Trastuzumab combined with lapatinib was also tested in BT-474 xenografts. In proliferation assays, dual targeting with trastuzumab and gefitinib or lapatinib showed synergy or additivity in both SKBR-3 and BT-474 cells. Trastuzumab (10 nM) or gefitinib (5 µM) alone did not induce significant apoptosis, whereas lapatinib... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3371574 Mon, 15 Mar 2010 05:32:53 +0100 3371574 http://www.medworm.com/index.php?rid=3363294&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F82t6011238500t26%2F Summary  Three stable mononuclear hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) complexes of PtIII, namely cis-[ PtIII(NH3)2(Hp−3H)(H2O)2].H2O 1, [PtIII(Hp−3H)(H2O)2].H2O 2 and [PtIII((O,O)Hp−2H)Cl(H2O)3] 3 with distorted octahedral structure and (dz2)1 ground state have been tested in vitro for antineoplastic activity in a panel of tumor cell lines. The novel platinum(III) complexes showed cytotoxic activity in a concentration-dependent manner with IC50 values comparable to those of referent cytotoxic agent cisplatin together with lower cytotoxicity against renal cells. Further detailed evaluation of the active analogue 2 and the less active complex 3 showed that their potency greatly correlates with the ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3363294 Fri, 12 Mar 2010 06:51:33 +0100 3363294 http://www.medworm.com/index.php?rid=3360613&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq749567q668617k7%2F Conclusion The combination of raltitrexed and gefitinib was well tolerated although was not associated with improved progression free survival in patients with refractory CRC. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-010-9400-zAuthors José María Viéitez, Hospital Universitario Central de Asturias Medical Oncology Service C/ Celestino Villamil s/n 33006 Oviedo SpainManuel Valladares, Hospital Juan Canalejo Department of Medical Oncology A Coruña SpainIgnacio Peláez, Hospital de Cabueñes Department of Medical Oncology Gijón SpainLuis de Sande González, Hospital de León Department of Medical Oncology León SpainJesús García-Foncillas, University Clinic of Navarra Department of Medical Oncology Pamplona SpainJosé Luis García-López, Hospital ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3360613 Wed, 10 Mar 2010 16:20:52 +0100 3360613 http://www.medworm.com/index.php?rid=3360614&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg46163607928120j%2F Summary  Mucoepidermoid carcinoma (MEC) is the most common malignant tumor in salivary glands and high-grade MEC in particular demonstrates little response to chemotherapy which has been used largely for palliative treatment of metastatic disease. Baicalin, one of the main active compounds of Scutellaria baicalensis, possesses anti-inflammatory, antioxidant and antitumor properties. In the present study, we investigated the growth inhibiting and apoptosis-inducing effects of baicalin on a highly metastatic human mucoepidermoid carcinoma cell line Mc3 for the first time. Baicalin exerted dose- and time-dependent antiproliferative potential against Mc3 cells as assessed by MTT assay. Baicalin treatment of Mc3 cells resulted in an accumulation of cells at the G0/G1 and G2/M pha... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3360614 Wed, 10 Mar 2010 16:20:51 +0100 3360614 http://www.medworm.com/index.php?rid=3324072&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5h68713760v38221%2F Summary  We evaluated the combination treatment of ethaselen (BBSKE) as a thioredoxin reductase (TrxR) inhibitor plus cisplatin (CDDP) on the human colon adenocarcinoma cell line LoVo. Therapeutic effects ranging from nearly additive to clearly synergistic demonstrated an effective combination, i.e., the cytostatic dose of CDDP could be reduced without a loss in efficacy. To further investigate the cellular response mechanisms of these favorable outcomes, we analyzed the cell-cycle profiles, mRNA expression patterns, and protein levels of several key genes after incubation with BBSKE or CDDP separately and in combination. In appropriate conditions, CDDP induced arrest at the G2/M phase accompanied by the enhanced inhibitory phosphorylation of Cdk1 and the elevated protein e... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3324072 Mon, 01 Mar 2010 18:09:21 +0100 3324072 http://www.medworm.com/index.php?rid=3315526&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe7434r8w62g52145%2F Conclusions Sorafenib does not show sufficient activity as a single agent in first-line metastatic urothelial cancer to warrant further investigation. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-010-9408-4Authors Srikala S. Sridhar, Princess Margaret Hospital, Phase II Consortium 610 University Avenue, Suite 5-222 Toronto Ontario M5G 2M9 CanadaEric Winquist, London Regional Cancer Center London ON CanadaAndrea Eisen, Odette Cancer Center Toronto ON CanadaSebastien J. Hotte, Juravinski Cancer Center Hamilton ON CanadaElaine McWhirter, Juravinski Cancer Center Hamilton ON CanadaIan F. Tannock, Princess Margaret Hospital, Phase II Consortium 610 University Avenue, Suite 5-222 Toronto Ontario M5G 2M9 CanadaSom D. Mukherjee, Juravinski Cancer Center Hamilton ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3315526 Fri, 26 Feb 2010 09:42:57 +0100 3315526 http://www.medworm.com/index.php?rid=3312951&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F62k3365p2340229j%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s10637-010-9404-8Authors Simona Potenza, Second University of Naples Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine Via Costantinopoli 16 80138 Naples ItalyGuglielmo Nasti, National Cancer Institute of Naples Colorectal Department, ‘G. Pascale’ Foundation Via M. Semmola 80131 Naples ItalyAlessandro Ottaiano, National Cancer Institute of Naples Colorectal Department, ‘G. Pascale’ Foundation Via M. Semmola 80131 Naples ItalyAmelia Filippelli, Second University of Naples Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine Via Costantinopoli 16 80138 Naples ItalyFrancesco Rossi, Second University of Naples Section of Pharmacology “L. Donatelli”, Department of Exp... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3312951 Thu, 25 Feb 2010 06:55:13 +0100 3312951 http://www.medworm.com/index.php?rid=3312950&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx408prl60k4hl2uk%2F Conclusions As we did not find any major correlations between pharmacogenetic variability in the studied enzymes and transporters and pharmacokinetics nor toxicity, it is unlikely that danusertib is highly susceptible for pharmacogenetic variation. Therefore, no dosing alterations of danusertib are expected in the future, based on the polymorphisms studied. However, the relationship between FMO3 polymorphisms and clearance of danusertib warrants further research, as we could study only a small group of patients. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-010-9405-7Authors Neeltje Steeghs, Leiden University Medical Center Department of Clinical Oncology, K1-P P.O Box 9600 2300 RC Leiden The NetherlandsRon H. J. Mathijssen, Erasmus University Medical Ce... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3312950 Thu, 25 Feb 2010 06:55:13 +0100 3312950 http://www.medworm.com/index.php?rid=3308390&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F45253069545459jp%2F Summary  In the course of screening for novel anticancer compounds, B1 (N-(2-(Dimethylamino)ethyl)-2-aminothiazonaphthalimide), a novel naphthalimide-based DNA intercalator, was generated as a new anticancer candidate. For the first time, our investigation demonstrates that B1 inhibited the growth of HeLa cells by the induction of cell cycle arrest and apoptosis. Analysis of flow cytometry and western blots of HeLa cells treated with B1 revealed an appreciable cell cycle arrest and apoptotic induction in dose and time-dependent manner via the p53-dependent pathway. Furthermore, the release of cytochrome c from mitochondria was detected using confocal microscopy in HeLa cells treated with B1. Accordingly, these data demonstrate that the anticancer activity of B1 is associated... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3308390 Wed, 24 Feb 2010 06:50:31 +0100 3308390 http://www.medworm.com/index.php?rid=3308391&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk12v783q73485470%2F Conclusion SP1049C has a notable single-agent activity in patients with adenocarcinoma of the esophagus and GEJ, as well as an acceptable safety profile. These results, in addition to the results of preclinical studies demonstrating superior antitumor activity of SP1049C compared with doxorubicin in a standard formulation, indicate that further evaluations of SP1049C alone or combined with other relevant therapeutics in this disease setting are warranted. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-010-9399-1Authors Juan W. Valle, Christie Hospital NHS Trust Department of Medical Oncology Wilmslow Road Manchester M20 4BX UKAnne Armstrong, Christie Hospital NHS Trust Department of Medical Oncology Wilmslow Road Manchester M20 4BX UKChris Newman, Suprate... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3308391 Wed, 24 Feb 2010 06:50:30 +0100 3308391 http://www.medworm.com/index.php?rid=3304002&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh667w20762778507%2F Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-010-9406-6Authors Olivier Mir, Université Paris Descartes, AP-HP, Teaching Hospital Cochin Department of Medical Oncology CERIA (Centre for Research on Angiogenesis Inhibitors) 27, rue du faubourg Saint Jacques F75014 Paris FranceRomain Coriat, Université Paris Descartes, AP-HP, Teaching Hospital Cochin Department of Medical Oncology CERIA (Centre for Research on Angiogenesis Inhibitors) 27, rue du faubourg Saint Jacques F75014 Paris FranceThomas Gregory, Université Paris Descartes, AP-HP Teaching European Hospital Georges Pompidou, Department of Orthopaedic Surgery Paris FranceStanislas Ropert, Université Paris Descartes, AP-HP, Teaching Hospital Cochin Department of Medical Oncology CERIA (Centre for Research on ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3304002 Tue, 23 Feb 2010 07:47:34 +0100 3304002 http://www.medworm.com/index.php?rid=3291605&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F80477822m11j03n7%2F Summary  Cribrostatin 6 is a quinone-containing natural product that induces the death of cancer cell lines in culture, and its mechanism of action and scope of activity are unknown. Here we show that cribrostatin 6 has broad anticancer activity, potently inducing apoptotic cell death that is not preceded by any defined cell cycle arrest. Consistent with this data, we find that cribrostatin 6 treated cells have large amounts of reactive oxygen species (ROS) and, based on transcript profiling experiments and other data, this ROS generation is likely the primary mechanism by which cribrostatin 6 induces apoptosis. Given the success of certain ROS producers as anticancer agents, cribrostatin 6 has potential as a novel chemotherapeutic agent. Content Type Journal ArticleCat... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3291605 Fri, 19 Feb 2010 06:43:06 +0100 3291605 http://www.medworm.com/index.php?rid=3291604&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fql3g171l35k26196%2F Summary  Natural products discovered from medicinal plants have played an important role in the treatment of cancer. In an effort to identify novel small molecules which can affect the proliferation of lymphoma cells, we tested methyl angolensate (MA), a plant derived tetranortriterpenoid, purified from the crude extract of the root callus of Soymida febrifuga commonly known as Indian red wood tree. We have tested MA for its cytotoxic properties on Burkitt’s lymphoma cell lines, using various cellular assays. We observed that MA induces cytotoxicity in Daudi cells in a dose-dependent manner using trypan blue, MTT and LDH assays. We find that the treatment with MA led to activation of DNA double-strand break repair proteins including KU70 and KU80, suggesting the activation... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3291604 Fri, 19 Feb 2010 06:43:06 +0100 3291604 http://www.medworm.com/index.php?rid=3291606&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpup2641566111155%2F Summary  Peloruside A (PelA), a novel microtubule-stabilizing agent and potential anti-cancer drug, isolated from the marine sponge Mycale hentscheli, binds to a distinct, non-taxoid binding site on tubulin. Using live-cell confocal microscopy, the effects of PelA on microtubule dynamics were quantified in a human breast adenocarcinoma cell line (MCF7) stably expressing GFP-α-tubulin. Changes in microtubule length were tracked over time in cells treated with PelA concentrations ranging from 3.8–100 nM. As with other microtubule-targeting drugs like paclitaxel and epothilone B, microtubule dynamics were suppressed in a concentration-dependent manner. At the PelA IC50 concentrations for cell proliferation (3.8 nM) and G2/M block (25 nM), PelA inhibited dynami... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3291606 Fri, 19 Feb 2010 06:43:05 +0100 3291606 http://www.medworm.com/index.php?rid=3281183&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Feq7g737857h71r82%2F Summary  Titanocenes constitute a class of metal-based anticancer agents that seem to display a mode of action distinct from that of platinum complexes and to be more tolerable with a differing spectrum of activity. In the present study, titanocene C (bis-(N,N-dimethylamino-2(N-methylpyrrolyl)-methyl-cyclopentadienyl) titanium(IV) dichloride) was shown to exhibit antiproliferative activity against human tumor cell lines with a mean IC50 value of 48.3 ± 32.5 µM. In particular, high activity was found against small cell lung cancer (SCLC) cell lines with a profile different from cisplatin. Titanocene C induced cell cycle arrest at the G1/0-S interphase. Cross-resistance to either cisplatin or oxoplatin, respectively, was low for titanocene C and absent for titanocene... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3281183 Tue, 16 Feb 2010 18:07:16 +0100 3281183 http://www.medworm.com/index.php?rid=3277317&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft2480l4201180224%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s10637-010-9397-3Authors Brigette B. Y. Ma, Chinese University of Hong Kong State Key Laboratory in Oncology in South China, Sir Y.K. Pao, Centre for Cancer, Department of Clinical Oncology, Cancer Drug, Testing Unit, Hong Kong Cancer Institute and Li Ka Shing, Institute of Health Sciences Ngan Shing Street, Shatin New Territories Hong Kong SAR ChinaVivian W. Y. Lui, Chinese University of Hong Kong State Key Laboratory in Oncology in South China, Sir Y.K. Pao, Centre for Cancer, Department of Clinical Oncology, Cancer Drug, Testing Unit, Hong Kong Cancer Institute and Li Ka Shing, Institute of Health Sciences Ngan Shing Street, Shatin New Territories Hong Kong SAR ChinaFan Fong Poon, Chinese University of Hong Kong State Key Labor... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3277317 Mon, 15 Feb 2010 06:42:48 +0100 3277317 http://www.medworm.com/index.php?rid=3270471&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe78r18715214u82w%2F Conclusions Cetuximab administered at 400 mg/m2 IV as a loading dose with weekly maintenance dose of 400 mg/m2 is feasible and well tolerated. There was no direct correlation of the grade of rash with dose in this group of patients with heterogenous solid tumors. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-010-9396-4Authors Cheryl Ho, British Columbia Cancer Agency Vancouver BC CanadaRandeep Sangha, Cross Cancer Institute Edmonton AB CanadaLaurel Beckett, University of California Davis Campus Sacramento CA USAMichael Tanaka, University of California Davis Campus Sacramento CA USADerick H. Lau, University of California Davis Campus Sacramento CA USADaniel B. Eisen, University of California Davis Campus Sacramento CA USARachel A. Burich, University ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3270471 Thu, 11 Feb 2010 11:49:26 +0100 3270471 http://www.medworm.com/index.php?rid=3270472&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5xm30nm13k710526%2F Conclusion Treatment with AEE788 could be a potential strategy for adjuvant treatment after oncological liver resection, as liver regeneration was not impaired. Our results suggest a liver-size-dependent metabolism of AEE788 leading to drug accumulation and subsequently to severe side effects. It calls for therapeutic drug monitoring in the early postoperative phase after extended resection. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-010-9394-6Authors Meihong Deng, University Hospital Essen Department of General, Visceral and Transplantation Surgery Hufelandstrasse 55 45122 Essen GermanyHai Huang, University Hospital Essen Department of General, Visceral and Transplantation Surgery Hufelandstrasse 55 45122 Essen GermanyHao Jin, University Hospital Ess... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3270472 Thu, 11 Feb 2010 11:49:25 +0100 3270472 http://www.medworm.com/index.php?rid=3264148&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4514732771126q47%2F Conclusions Intetumumab was generally safe and well tolerated in combination with docetaxel, with a higher incidence of TEAEs in the 10 mg/kg dose cohort. The efficacy of 10 mg/kg intetumumab in combination with docetaxel appears to warrant further study. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-010-9388-4Authors Franklin M. Chu, San Bernardino Urological Associates Medical Group San Bernardino CA USAJoel Picus, Washington University School of Medicine Alvin J. Siteman Cancer Center St. Louis MO USAPaula M. Fracasso, Washington University School of Medicine Alvin J. Siteman Cancer Center St. Louis MO USARobert Dreicer, Cleveland Clinic Cleveland OH USAZhihui Lang, Centocor Research and Development, Inc Malvern PA USABrenda Foster, Centocor Rese... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3264148 Wed, 10 Feb 2010 06:48:14 +0100 3264148 http://www.medworm.com/index.php?rid=3241161&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0mw8841723786q34%2F Summary  The effect of the single-chain alkylphospholipid perifosine was analyzed in p53wild-type (SKW6.4, OCI and MOLM), p53mutated (BJAB, MAVER) and p53null (HL-60) leukemic cell lines. Perifosine promoted cytotoxicity with a combination of apoptosis induction in all cell lines and cell cycle block at the G2M checkpoint, which was selectively observed in p53mutated BJAB and MAVER cell lines. At the molecular level, perifosine induced hypophosphorylation of retinoblastoma protein and the degradation of E2F1 protein in p53mutated but not in p53wild-type cells. These data indicate that perifosine potentially represents an innovative therapeutic approach for p53mutated hematological malignancies. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9370-1Aut... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3241161 Wed, 03 Feb 2010 17:56:35 +0100 3241161 http://www.medworm.com/index.php?rid=3232993&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb17728104n06571r%2F Conclusions AZD6244 showed similar efficacy to capecitabine in terms of the number of patients with a disease progression event and of progression-free survival. AZD6244 is currently undergoing evaluation in Phase II trials in combination with other chemotherapeutic agents. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-010-9392-8Authors Jaafar Bennouna, Centre Rene Gauducheau Medical Oncology Branch Bd J. Monod 44805 Saint Herblain FranceIstvan Lang, National Institute of Oncology Budapest HungaryManuel Valladares-Ayerbes, Hospital Universitario La Coruna SpainKatalin Boer, St. John Hospital, site of St. Margit Budapest HungaryAntoine Adenis, Centre Oscar Lambret Lille FrancePilar Escudero, Hospital Clinico Lozano Blesa Zaragoza SpainTae-You Kim, National U... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3232993 Mon, 01 Feb 2010 18:04:34 +0100 3232993 http://www.medworm.com/index.php?rid=3232994&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh7r3704154402763%2F Conclusion This simple tool could provide a justification for the sample size of an expanded cohort when DLT remains the metric for dose-seeking. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9385-7Authors Nicolas Penel, Département de Cancérologie Générale, Centre Oscar Lambret Lille FranceCharles Fournier, Unité de Biostatistique, Centre Oscar Lambret rue Frédéric Combemale 509020 Lille Cedex FranceJocelyne Bérille, Bureau des Etudes Cliniques et Thérapeutiques, Fédération Nationale des Centres de Lutte Contre le Cancer Paris France Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3232994 Mon, 01 Feb 2010 06:46:33 +0100 3232994 http://www.medworm.com/index.php?rid=3232995&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F15552r70r4jj2317%2F Conclusion: AC480 significantly enhanced the radiosensitivity of HN-5 cells, expressing both EGFR and Her2. The mechanisms involved in the enhancement included cell cycle redistribution and inhibition of DNA repair. Both in vitro and in vivo data from our study suggest that AC480 has potential to increase tumor response to radiotherapy. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-010-9389-3Authors Mylin A. Torres, Winship Cancer Institute of Emory University Department of Radiation Oncology Atlanta GA USAUma Raju, The University of Texas MD Anderson Cancer Center Department of Experimental Radiation Oncology Houston TX USADavid Molkentine, The University of Texas MD Anderson Cancer Center Department of Experimental Radiation Oncology Houston TX USAOliv... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3232995 Mon, 01 Feb 2010 06:46:32 +0100 3232995 http://www.medworm.com/index.php?rid=3224016&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F547205426751897j%2F Summary  LYP is a bestatin dimethylaminoethyl ester which inhibits aminopeptidase N (APN/CD13). Our goal in this study was to evaluate LYP as a candidate compound for cancer treatment, beginning by studying its inhibitory effects on tumors and then comparing it to bestatin. Experiments were performed on human ovarian carcinoma (OVCA) ES-2 and SKOV-3 cell lines, which have high and low levels of APN/CD13 respectively. LYP effectively inhibited ES-2 cell growth as estimated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the trypan blue dye-exclusion test. LYP significantly suppressed APN/CD13 activity on the surface of ES-2 cells as measured by quantifying the enzymatic cleavage of the substrate L-leucine-p-nitroanilide. The inhibitory effe... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3224016 Thu, 28 Jan 2010 18:01:00 +0100 3224016 http://www.medworm.com/index.php?rid=3224017&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4u26485813472031%2F Summary  Peloruside A, isolated from the marine sponge Mycale hentscheli, has a similar mechanism of action to paclitaxel (Taxol®), a drug used clinically to treat tumors of the breast, ovary and lung. Paclitaxel and peloruside stabilize the polymerized form of tubulin and arrest cells in G2/M of the cell cycle. We have therefore used two-dimensional electrophoresis of proteins to examine the effect of peloruside A on the human HL-60 promyeloid leukemic cell line. Our goals included investigation whether affected proteins could be mapped onto pathways that predicted the cellular effects of this compound. In response to 100 nM peloruside A treatment for 24 h, seventeen identified proteins showed significant change in abundance with fourteen increases and three decre... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3224017 Wed, 27 Jan 2010 20:30:28 +0100 3224017 http://www.medworm.com/index.php?rid=3224018&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu0r8v00247m5p051%2F Conclusions: The addition of soy isoflavones to gemcitabine and erlotinib did not appear to increase the survival of patients with advanced pancreatic cancer. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-010-9386-6Authors Bassel Fuad El-Rayes, Wayne State University Karmanos Cancer Institute Detroit MI USAPhilip A. Philip, Wayne State University Karmanos Cancer Institute Detroit MI USAFazlul H. Sarkar, Wayne State University Karmanos Cancer Institute Detroit MI USAAnthony F. Shields, Wayne State University Karmanos Cancer Institute Detroit MI USAAnn Marie Ferris, Wayne State University Karmanos Cancer Institute Detroit MI USAKenneth Hess, University of Texas M. D. Anderson Cancer Center Houston TX USAAhmad O. Kaseb, University of Texas M. D. Anderson Cancer... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3224018 Wed, 27 Jan 2010 20:30:27 +0100 3224018 http://www.medworm.com/index.php?rid=3206025&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F858hm1k36hh81163%2F Conclusions The addition of erlotinib to a standard chemotherapy regimen for NSCLC did not alter the systemic exposures ( AUC0 - ¥ ) of paclitaxel (p = 0.80) and carboplatin (p = 0.756) when erlotinib-treated patients were compared to placebo-treated patients. The pharmacokinetics of erlotinib and its metabolite OSI-420 did not appear to be altered by the concomitant administration of paclitaxel and carboplatin. Content Type Journal ArticleCategory PHASE III STUDIESDOI 10.1007/s10637-009-9380-zAuthors Hai T. Tran, The University of Texas M. D. Anderson Cancer Center Department of Thoracic/Head and Neck Medical Oncology 1515 Holcombe Blvd Box 432 Houston TX 77030 USARalph G. Zinner, The University of Texas M. D. Anderson Cancer Center Department of Thoracic/Head and Neck ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3206025 Fri, 22 Jan 2010 10:10:41 +0100 3206025 http://www.medworm.com/index.php?rid=3206026&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm5r7117585411488%2F Conclusions The recommended phase II dose of pemetrexed for future leukemia studies is 2,700 mg/m2 IV over 25 min every 3 to 4 weeks with vitamin supplementation. Deoxyuridine levels did not increase with increasing pemetrexed dose, suggesting pemetrexed inhibition of thymidylate synthase (TS) may be saturated by the 900 mg/m2 dose level. However, no firm conclusion can be made regarding TS saturation in tumor cells. While tolerable, pemetrexed monotherapy had limited activity in this highly refractory population. Exploration of pemetrexed in combination with other active agents in leukemia is a reasonable future endeavor. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9369-7Authors Isam Abdel-Karim, San Antonio Cancer Center San Anto... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3206026 Fri, 22 Jan 2010 02:09:53 +0100 3206026 http://www.medworm.com/index.php?rid=3190787&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq4024j0h71304362%2F Conclusion ENMD-1198 is well-tolerated with a pharmacokinetic exposure profile compatible with once daily dosing. The recommended phase II dose of ENMD-1198 is 425 mg/m2/d. Early evidence of prolonged disease stabilization in pre-treated patients suggests ENMD-1198 is worthy of additional investigation. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9383-9Authors Qing Zhou, University of Colorado Developmental Therapeutics Program, Division of Medical Oncology Aurora CO 80045 USADaniel Gustafson, Colorado State University University of Colorado Comprehensive Cancer Center Pharmacology Core Fort Collins CO 80523-1620 USASujatha Nallapareddy, University of Colorado Developmental Therapeutics Program, Division of Medical Oncology Aurora CO 80045 USASami ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3190787 Mon, 18 Jan 2010 18:47:28 +0100 3190787 http://www.medworm.com/index.php?rid=3190788&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy8832437158x4476%2F Summary  Deregulation of cell-cycle control is a hallmark of cancer. Thus, cyclin-dependent kinases (Cdks) are an attractive target for the development of anti-cancer drugs. Here, we report the biological characterization of a highly potent pan-Cdk inhibitor with a macrocycle-quinoxalinone structure. Compound M inhibited Cdk1, 2, 4, 5, 6, and 9 with equal potency in the nM range and was selective against kinases other than Cdks. This compound inhibited multiple events in the cell cycle in vitro, including retinoblastoma protein (pRb) phosphorylation, E2F-dependent transcription, DNA replication (determined by bromodeoxyuridine incorporation), and mitosis completion (assayed by flow cytometry) in the 10 nM range. Moreover, this compound induced cell death, as determined... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3190788 Mon, 18 Jan 2010 18:47:26 +0100 3190788 http://www.medworm.com/index.php?rid=3190790&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv039085hk930t231%2F Conclusion: Ipilimumab therapy resulted in clinically meaningful responses in advanced melanoma patients, and the results support further investigations of ipilimumab in combination with DTIC. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9376-8Authors Evan M. Hersh, University of Arizona Arizona Cancer Center 1515 North Campbell Avenue Tucson AZ 85724 USASteven J. O’Day, The Angeles Clinic and Research Institute 2001 Santa Monica Blvd, Suite 560W Santa Monica CA 90404 USAJohn Powderly, Cancer Therapy & Research Center Carolina Bio-Oncology Institute 9801 W. Kincey Ave, Suite 145 Huntersville NC 28078 USAKhuda D. Khan, St. Francis Hospital & Health Centers 8111 S. Emerson Ave Indianapolis IN 46237 USAAnna C. Pavlick, New York University Medical Center ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3190790 Fri, 15 Jan 2010 18:00:57 +0100 3190790 http://www.medworm.com/index.php?rid=3190789&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F51872173h54205h0%2F Conclusions: 17-AAG in combination with gemcitabine and cisplatin demonstrated antitumor activity, but significant hematologic toxicities were encountered. 17-AAG combined with gemcitabine is tolerable and has demonstrated evidence of activity at the MTD. The recommended phase II dose is defined as 154 mg/m2 of 17-AAG and 750 mg/m2 of gemcitabine, and is currently being investigated in phase II studies in ovarian and pancreatic cancers. There is no recommended phase II dose for the cisplatin-containing combinations. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9381-yAuthors Joleen Hubbard, Mayo Clinic College of Medicine Division of Medical Oncology 200 First Street SW Rochester MN 55905 USACharles Erlichman, Mayo Clinic College of Medicine D... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3190789 Fri, 15 Jan 2010 18:00:57 +0100 3190789 http://www.medworm.com/index.php?rid=3177198&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu6236rp0774w7131%2F Summary  The aim of this study was to prospectively evaluate the efficacy of combination irinotecan and cetuximab chemotherapy in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. KRAS status was evaluated using the Cycleave PCR method; only patients without KRAS mutations were included. Cetuximab was administered initially at 400 mg/m2 followed by weekly 250 mg/m2 infusions. Irinotecan was administered biweekly. From October 2008 to April 2009, a total of 30 patients were enrolled. The objective response rate was 30.0% (95% confidence interval [CI], 14.7–49.4%) and the disease control rate... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3177198 Wed, 13 Jan 2010 17:54:03 +0100 3177198 http://www.medworm.com/index.php?rid=3168873&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk2504773m2825q84%2F Summary  DNA intercalating molecules are promising chemotherapeutic agents. In the present study, a novel DNA intercalating compound of pyrimido[4′,5′:4,5]selenolo(2,3-b)quinoline series having 8-methyl-4-(3 diethylaminopropylamino) side chain is studied for its chemotherapeutic properties. Our results showed that 8-methyl-4-(3 diethylaminopropylamino) pyrimido [4′,5′:4,5] selenolo(2,3-b)quinoline (MDPSQ) induces cytotoxicity in a time- and concentration-dependent manner on leukemic cell lines. Both cell cycle analysis and tritiated thymidine assays revealed that MDPSQ affects DNA replication. Treatment with MDPSQ resulted in both elevated levels of DNA strand breaks and repair proteins, further indicating its cytotoxic effects. Besides, Annexin V/PI staining reveal... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3168873 Tue, 12 Jan 2010 18:19:24 +0100 3168873 http://www.medworm.com/index.php?rid=3168872&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F46144731mq748515%2F Conclusion The recommended dose of ispinesib is 7 mg/m2 over 1 h weekly for three consecutive weeks of a 28 day treatment cycle. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9374-xAuthors Howard A. Burris, The Sarah Cannon Research Institute 250 25th Avenue North, Suite 110 Nashville TN 37203 USASuzanne F. Jones, The Sarah Cannon Research Institute 250 25th Avenue North, Suite 110 Nashville TN 37203 USADaphne D. Williams, GlaxoSmithKline Research Triangle Park NC USASteven J. Kathman, GlaxoSmithKline Research Triangle Park NC USAJeffrey P. Hodge, GlaxoSmithKline Research Triangle Park NC USALini Pandite, GlaxoSmithKline Research Triangle Park NC USAPeter T. C. Ho, GlaxoSmithKline Research Triangle Park NC USAScott A. Boerner, Karmanos Cance... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3168872 Tue, 12 Jan 2010 18:19:24 +0100 3168872 http://www.medworm.com/index.php?rid=3168875&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb802h520v954r6r6%2F Summary  A series of ten chloroalkyl 1H-benz[de]isoquinoline-1,3-diones (naphthalimides) were synthesized and evaluated for antitumor activity. Amongst them, new compounds 2d and 2i carrying a 6-NO2 substituent in the aromatic portion of the molecule possessed significant antineoplastic activity. The most active compound 2i had elicited significant cytotoxicity in 15 human tumor cell lines namely Leukemia: MOLT-4, HL-60; Lymphoma: U-937; Colon: 502713, HT-29, SW-620, HCT-15, COLO-205; Liver: Hep-2; Prostate DU-145, PC-3; Breast: MCF-7; Neuroblastoma: IMR-32, SK-N-SH and Ovary: OVCAR-5 out of the 17 cell lines screened. Flow cytometric analysis performed to study the effect of compound 2i on the progression of cell cycle of MOLT-4 cells, revealed rise in sub-G1 fraction and co... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3168875 Mon, 11 Jan 2010 18:21:43 +0100 3168875 http://www.medworm.com/index.php?rid=3168874&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbk76230748113520%2F In conclusion, CP-4126 is membrane transporter independent. Intraperitoneally administered CP-4126 was as effective as gemcitabine in several xenografts and CP-4126 is tolerated when orally administered. CP-4126 seems to be a promising new anticancer drug. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9377-7Authors Andries M. Bergman, VU University Medical Center Department of Medical Oncology P.O. Box 7057 1007 MB Amsterdam The NetherlandsAuke D. Adema, VU University Medical Center Department of Medical Oncology P.O. Box 7057 1007 MB Amsterdam The NetherlandsJan Balzarini, Katholieke Universiteit Leuven Rega Institute for Medical Research Leuven BelgiumSkjalg Bruheim, Radium Hospital Oslo NorwayIduna Fichtner, Max-Delbrück-Center for Molecular Me... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3168874 Mon, 11 Jan 2010 18:21:43 +0100 3168874 http://www.medworm.com/index.php?rid=3130931&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbl071r3k27763041%2F Summary  Sphingosine-1-phosphate (S1P) is an important regulator of cancer development and progression. Its cellular concentration is controlled predominantly by sphingosine kinase (SK) and sphingosine-1-phosphate lyase (SPL). In the current study we showed that mRNA expressions for both SK and SPL were up-regulated throughout all four disease stages in human breast cancer patients. Exogenous administration of S1P produced a bell-shaped dose response for apoptosis in normal mammary gland MCF12A cells but a sigmoid-shaped apoptotic response in breast cancer MCF7 cells. Co-administration of S1P enhanced the cytotoxicity of anticancer drug docetaxel against MCF7 cells. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9375-9Authors Binbing Ling, Unive... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3130931 Tue, 29 Dec 2009 17:57:06 +0100 3130931 http://www.medworm.com/index.php?rid=3130932&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3k436lu877654713%2F Conclusions The MTDs for a 3 week schedule of S-1 treatment were defined in patients with or without hepatic dysfunction. A 3 week treatment regimen of S-1 might be a platform for combination with newer cytotoxic agents or biologics. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9378-6Authors Dok Hyun Yoon, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 86 Asanbyeongwon-gil, Songpa-gu Seoul 138-736 KoreaHyo Jung Lee, University of Ulsan College of Medicine Department of Pharmacy, Asan Medical Center Seoul KoreaYong Sang Hong, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 86 Asanbyeongwon-gil, Songpa-gu Seoul 138-736 KoreaKyu-pyo Kim, University of Ulsan College of Medicin... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3130932 Tue, 29 Dec 2009 17:57:05 +0100 3130932 http://www.medworm.com/index.php?rid=3130933&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm01563t72046x752%2F Summary  In this work, nanoparticles with a positive surface charge were prepared through the electrostatic interaction of a new cisplatin-hyaluronate complex with N-trimethyl chitosan (substitution degree of 85%). Mean particle diameter was approximately 195 nm. Drug loading of nanoparticles, which had a zeta potential of about 27 mV, was equal to 6% w/w. After 24 h, while the cisplatin-hyaluronate complex released approximately 60% w/w drug in phosphate buffered saline at pH 7.4, approximately 40% w/w of total cisplatin was released from nanoparticles. The same cumulative amounts of released drug were found after 48 h. These nanoparticles, as well as the starting cisplatin-hyaluronate complex, were active on all cell lines tested (P388, A2780, A549), wi... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3130933 Mon, 28 Dec 2009 19:26:07 +0100 3130933 http://www.medworm.com/index.php?rid=3121285&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6136k2184w1r8283%2F Summary  Our strategy is to increase drug accumulation in target tumour cells using specific “vectors” tailored to neoplastic tissue characteristics, which ideally are not found in healthy tissues. The aim of this work was to use 2-fluoro-2-deoxyglucose (FDG) as a drug carrier, in view of its well-known accumulation by most primary and disseminated human tumours. We had previously selected two FDG-cytotoxic conjugates of chlorambucil (CLB), i.e. compounds 21a and 40a, on the basis of their in vitro profiles. Here we investigated the antitumour profile and tolerance of these compounds in vitro and in vivo in two murine cell lines of solid tumours. In vitro, we found that micromolar concentrations of compounds 21a and 40a inhibited proliferation of B16F0 and CT-26 cell li... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3121285 Wed, 23 Dec 2009 22:36:20 +0100 3121285 http://www.medworm.com/index.php?rid=3112540&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd4x03021r33q4pl5%2F In conclusion, our data showed that inhibition of Chk2 activity by XL-844 enhanced cancer cell radiosensitivity that was associated with inhibition of DNA repair and induction of mitotic catastrophe. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9361-2Authors Oliver Riesterer, The University of Texas M. D. Anderson Cancer Center Department of Experimental Radiation Oncology Unit 66, 1515 Holcombe Blvd. Houston TX 77030 USAFumihiko Matsumoto, The University of Texas M. D. Anderson Cancer Center Department of Experimental Radiation Oncology Unit 66, 1515 Holcombe Blvd. Houston TX 77030 USALi Wang, The University of Texas M. D. Anderson Cancer Center Department of Experimental Radiation Oncology Unit 66, 1515 Holcombe Blvd. Houston TX 77030 USAJessica Pickett, ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3112540 Mon, 21 Dec 2009 06:44:44 +0100 3112540 http://www.medworm.com/index.php?rid=3105997&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5k815u5h70856876%2F Conclusions There was evidence of disease activity in STS as defined by tumor regressions including one objective partial response. Further investigation in STS is warranted. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9367-9Authors Simon Pacey, The Royal Marsden Hospital Downs Rd Sutton Surrey SM2 5PT UKMark J. Ratain, University of Chicago Hospitals 5841 S. Maryland Avenue, MC2115 Chicago IL 60637 USAKeith T. Flaherty, Abramson Cancer Center of the University of Pennsylvania 1222 Penn Tower, 34th & Spruce Streets Philadelphia PA 19104 USAStanley B. Kaye, The Royal Marsden Hospital Downs Rd Sutton Surrey SM2 5PT UKLisa Cupit, Bayer Pharmaceuticals Corporation 6 West Belt Wayne NJ 07470 USAEric K. Rowinsky, ImClone Systems 33 ImClone Drive Branchburg N... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3105997 Thu, 17 Dec 2009 07:04:36 +0100 3105997 http://www.medworm.com/index.php?rid=3105998&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2rx4428u818g576g%2F Summary  Hypoxia is commonly developed in solid tumors, which contributes to metastasis as well as radio- and chemo-resistance. Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic head and neck cancer prevalent in Southeast Asia with a high incidence rate of 15–30/100,000 persons/year (comparable to that of pancreatic cancer in the US). Previous clinical studies in NPC showed that hypoxia is detected in almost 100% of primary tumors and overexpression of hypoxia markers correlated with poor clinical outcome. Tirapazamine (TPZ) is a synthetic hypoxia-activated prodrug, which preferentially forms cytotoxic and DNA-damaging free radicals under hypoxia, thus selectively eradicate hypoxic cells. Here, we hypothesized that specific hypoxia-targeting by this clini... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3105998 Wed, 16 Dec 2009 07:02:08 +0100 3105998 http://www.medworm.com/index.php?rid=3105999&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg112l30271216138%2F Summary  The aim of this study is to compare the effects of new fluorinated taxanes SB-T-12851, SB-T-12852, SB-T-12853, and SB-T-12854 with those of the classical taxane paclitaxel and novel non-fluorinated taxane SB-T-1216 on cancer cells. Paclitaxel-sensitive MDA-MB-435 and paclitaxel-resistant NCI/ADR-RES human cancer cell lines were used. Cell growth and survival evaluation, colorimetric assessment of caspases activities, flow cytometric analyses of the cell cycle and the assessment of mitochondrial membrane potential, reactive oxygen species (ROS) and the release of cytochrome c from mitochondria were employed. Fluorinated taxanes have similar effects on cell growth and survival. For MDA-MB-435 cells, the C50 of SB-T-12851, SB-T-12852, SB-T-12853 and SB-T-12854 was 3&nb... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3105999 Wed, 16 Dec 2009 07:02:06 +0100 3105999 http://www.medworm.com/index.php?rid=3097957&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhpk383332401932w%2F In conclusion, the protective effect of LUT could be attributed to inhibition of AOM-induced cellular proliferation probably through the involvement of β-catenin, GSK-3β and cyclin D1. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9359-9Authors Pandurangan Ashokkumar, University of Madras Department of Biochemistry Guindy campus Chennai 600 025 Tamil Nadu IndiaGanapasam Sudhandiran, University of Madras Department of Biochemistry Guindy campus Chennai 600 025 Tamil Nadu India Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3097957 Tue, 15 Dec 2009 07:07:52 +0100 3097957 http://www.medworm.com/index.php?rid=3086182&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9770h15h2l2748h2%2F Summary  Dibutyltin(IV) complexes of composition Bu2Sn(LH)2, where LH is a carboxylate residue derived from 2-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L1H) with water molecule (1), 4-[(E)-(5-tert-butyl-2-hydroxyphenyl)diazenyl]benzoate (L2H) (2) and 4-[(E)-(4-hydroxy-5-methylphenyl)diazenyl]benzoate (L3H) (3), were synthesized and characterized by spectroscopic (1H, 13C and 119Sn NMR, IR, 119Sn Mössbauer) techniques. A full characterization was accomplished from the crystal structure of complex 1. The molecular structures and geometries of the complexes (1a i.e. 1 without water molecule and 3) were fully optimized using the quantum mechanical method (PM6). Complexes 1 and 3 were found to exhibit stronger cytotoxic activity in vitro across a panel of human tumor cell... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3086182 Thu, 10 Dec 2009 15:10:06 +0100 3086182 http://www.medworm.com/index.php?rid=3086181&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh121425tv755j25n%2F Summary  Vascular disrupting agents (VDAs) have emerged as a new kind of anti-cancer drug in recent years. Structural modification of an active parent compound is an effective approach to developing new agents with more activity and fewer adverse reactions. In our study, six synthesized stilbene derivatives were screened for their cytotoxic activity against human tumor cells, and their mechanisms of action were investigated. The MTT assay was used to determine the anti-proliferative activity of these compounds. Polymerization of tubulin was detected by a tubulin assembly assay, and the cellular microtubule network was observed by immunocytochemical analyses. Cell-cycle distribution was detected by flow cytometry. A nude mouse model with xenografted colon cancer was used to ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3086181 Thu, 10 Dec 2009 15:10:06 +0100 3086181 http://www.medworm.com/index.php?rid=3086183&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F164827361t383702%2F Conclusion: The combination of everolimus with imatinib in previously treated patients with advanced renal carcinoma did not result in a sufficient 3-month progression-free rate to warrant further investigation of this combination. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9365-yAuthors Christopher W. Ryan, Oregon Health and Science University Knight Cancer Institute 3303 SW Bond Ave., CH14R Portland OR 97239 USAJacqueline Vuky, Virginia Mason Medical Center Seattle WA USAJoseph S. Chan, Kaiser Permanente, Southern California Permanente Medical Group Fontana CA USAZunqiu Chen, Oregon Health and Science University Knight Cancer Institute 3303 SW Bond Ave., CH14R Portland OR 97239 USATomasz M. Beer, Oregon Health and Science University Knight Cancer In... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3086183 Thu, 10 Dec 2009 15:10:05 +0100 3086183 http://www.medworm.com/index.php?rid=3080561&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv08vv54x5jw22435%2F Conclusions The combination of MGd and doxorubicin was fairly well tolerated. However, due to emerging preclinical data suggesting that MGd inhibits ribonucleotide reductase, further development of the combination of MGd plus doxorubicin is not recommended. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9364-zAuthors Anne M. Traynor, University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K6/568 CSC, #5669, 600 Highland Avenue Madison WI 53792 USAJames P. Thomas, University of Wisconsin Paul P. Carbone Comprehensive Cancer Center K6/568 CSC, #5669, 600 Highland Avenue Madison WI 53792 USARamesh K. Ramanathan, University of Pittsburgh Cancer Institute Pittsburgh PA USATarak D. Mody, Pharmacyclics, Inc. Sunnyvale CA USADona Alberti, University of... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3080561 Wed, 09 Dec 2009 06:48:36 +0100 3080561 http://www.medworm.com/index.php?rid=3080562&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv7r167441n045x18%2F Conclusion The duplex drugs 5-FdU(5´-5´)ECyd and ECyd-lipid-5-FdU represent potential new chemotherapeutic drugs for breast and ovarian cancer cells which are comparable to currently used drug combinations and more potent in comparison to some monocytostatica used in cancer therapy. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9355-0Authors Sarah Schott, University of Heidelberg Medical School, Department of Gynecology and Obstetrics Heidelberg 69115 GermanyMarkus Wallwiener, University of Tuebingen Department of Obstetrics and Gynecology Tuebingen 72076 GermanyBeate Kootz, University of Tuebingen Department of Obstetrics and Gynecology Tuebingen 72076 GermanyHarald Seeger, University of Tuebingen Department of Obstetrics and Gynecology Tuebingen 72076 G... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3080562 Tue, 08 Dec 2009 19:48:24 +0100 3080562 http://www.medworm.com/index.php?rid=3080564&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F468736717h548246%2F Conclusions Cetuximab in combination with XELOX chemotherapy was active and safe as first-line treatment of metastatic and/or recurrent AGC patients. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9363-0Authors Chul Kim, Asan Medical Center, University of Ulsan College of Medicine Department of Oncology 86 Asanbyeongwon-gil, Songpa-gu Seoul 138-736 South KoreaJae-Lyun Lee, Asan Medical Center, University of Ulsan College of Medicine Department of Oncology 86 Asanbyeongwon-gil, Songpa-gu Seoul 138-736 South KoreaMin-Hee Ryu, Asan Medical Center, University of Ulsan College of Medicine Department of Oncology 86 Asanbyeongwon-gil, Songpa-gu Seoul 138-736 South KoreaHeung Moon Chang, Asan Medical Center, University of Ulsan College of Medicine Department of O... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3080564 Tue, 08 Dec 2009 19:48:23 +0100 3080564 http://www.medworm.com/index.php?rid=3080563&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc8256263487j41v0%2F Conclusion The shifting of patient characteristics especially as related to tumor types enrolled and number of prior therapies has important implications for future design of studies and inadequate attention to these issues may slow the accrual process. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9362-1Authors Afshin Dowlati, Case Western Reserve University, University Hospitals Case Medical Center Division of Hematology/Oncology 11100 Euclid Avenue Cleveland OH 44106 USAMadappa Kundranda, Case Western Reserve University, University Hospitals Case Medical Center Division of Hematology/Oncology 11100 Euclid Avenue Cleveland OH 44106 USASudhir Manda, Case Western Reserve University, University Hospitals Case Medical Center Division of Hematology/Oncology ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3080563 Tue, 08 Dec 2009 19:48:23 +0100 3080563 http://www.medworm.com/index.php?rid=3064438&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk424v5673q7kgt10%2F In conclusion, in this present study we have demonstrated that BPR-DC-2, derived from a series of novel synthetic cyclic cyanoguanidine compounds, has proved its potential as an anti-tumor drug candidate in treating lung cancer. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9337-2Authors Shun-Lai Li, Southern Taiwan University Institute of Biotechnology, College of Engineering No.1, Nantai St Yung-Kang City Tainan county 710 TaiwanChia-Hsin Huang, National Cheng Kung University Institute of Biomedical Engineering, College of Engineering No.1, University Road Tainan City 701 TaiwanChih-Chan Lin, Chi-Mei Medical Center Department of Medical Research No. 901, Zhong Hua Rd Yong Kang City Tainan county 710 TaiwanZih-Ning Huang, Southern Taiwan University ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3064438 Fri, 04 Dec 2009 07:19:59 +0100 3064438 http://www.medworm.com/index.php?rid=3064439&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F555786g833881p76%2F Summary  In the present investigation the antiproliferative activity of thirteen derivatives of betulinic acid and betulin was tested against five different tumor cell lines. The toxicity against normal human fibroblasts (WWO70327) and the mode of cell death on HT-29 (colon cancer) as well as caspase activity induced by the most active compounds, 9 (3-O-chloroacetylbetulinic acid) and 15 (28-O-chloroacetylbetulin) were determined. Investigated derivatives exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. Treatment of HT-29 cells for 24 h with 9 and 15 induced apoptosis, as observed by dye exclusion test (trypan blue) and confirmed by the appearance of a typical ladder pattern in the DNA fragmentation assay. ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3064439 Thu, 03 Dec 2009 12:50:11 +0100 3064439 http://www.medworm.com/index.php?rid=3064440&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6776522658725712%2F Summary  Prodrugs can have the advantage over parent drugs in increased activation and cellular uptake. The multidrug ETC-L-FdUrd and the duplex drug ETC-FdUrd are composed of two different monophosphate-nucleosides, 5-fluoro-2′deoxyuridine (FdUrd) and ethynylcytidine (ETC), coupled via a glycerolipid or phosphodiester, respectively. The aim of the study was to determine cytotoxicity levels and mode of drug cleavage. Moreover, we determined whether a liposomal formulation of ETC-L-FdUrd would improve cytotoxic activity and/or cleavage. Drug effects/cleavage were studied with standard radioactivity assays, HPLC and LC-MS/MS in FM3A/0 mammary cancer cells and their FdUrd resistant variants FM3A/TK−. ETC-FdUrd was active (IC50 of 2.2 and 79 nM) in FM3A/0 and TK− cell... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3064440 Wed, 02 Dec 2009 08:36:06 +0100 3064440 http://www.medworm.com/index.php?rid=3041177&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fag771r218518354m%2F Summary  We performed a single-institution phase II study to evaluate the efficacy and toxicities of vinorelbine monotherapy in patients previously treated with anthracyclines and taxanes. Vinorelbine was administered at a dose level of 25 mg/m2 intravenously on days 1, 8, 15 and 22, every four weeks, and responses were assessed after every two cycles of treatment. All of the patients had previously been treated with anthracyclines and taxanes. A total of 26 patients were enrolled in this study between April 2004 and August 2009. The median age of the patients was 47 years (range, 37 to 71 years), and 80.8% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Out of 24 evaluable patients, five partial responses were observed, giving an overa... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3041177 Fri, 27 Nov 2009 07:04:36 +0100 3041177 http://www.medworm.com/index.php?rid=3041176&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftm541r5m397vq124%2F This study was undertaken to investigate the inhibitory effects of triterpenoid compound oleanolic acid and its synthetic derivatives on osteosarcoma cells in order to identify new therapeutic candidates for the treatment of this disease. We used the 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl tetrazolium bromide assay to assess the effect of oleanolic acid compounds on the proliferation of osteosarcoma cells. The effect of dextrose-oleanolic acid (the most potent oleanolic acid derivative) on apoptosis of osteosarcoma cells was evaluated using the Annexin-V method. The cell cycle of dextrose-oleanolic acid-treated cells was examined by flow cytometry, and the in vivo effects of dextrose-oleanolic acid were evaluated in a mouse osteosarcoma model. Oleanolic acid compounds had an overall... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3041176 Fri, 27 Nov 2009 07:04:36 +0100 3041176 http://www.medworm.com/index.php?rid=3041178&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh160794661504060%2F Summary  Cancer stem cells are expected to be responsible for tumor initiation and metastasis. These cells are therefore potential targets for innovative anticancer therapies. However, the absence of bona fide cancer stem cell lines is a real problem for the development of such approaches. Since teratocarcinoma cells are totipotent stem cells with a high degree of malignancy, we used them as a model of cancer stem cells in order to evaluate the anticancer chemopreventive activity of red wine polyphenols (RWPs) and to determine the underlying cellular and molecular mechanisms. We therefore investigated the effects of RWPs on the embryonal carcinoma (EC) cell line P19 which was grown in the same culture conditions as the most appropriate normal cell line counterpart, the pluri... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3041178 Fri, 27 Nov 2009 07:04:34 +0100 3041178 http://www.medworm.com/index.php?rid=3041179&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh07260257m0q3727%2F Conclusions Eribulin mesylate given on Days 1 and 8 of a twenty-one day cycle in metastatic or recurrent SCCHN was well tolerated, but did not result in a clinically significant median PFS. Studies of other agents should be considered in this setting. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9348-zAuthors Susanne M. Arnold, University of Kentucky Lexington KY USAJames Moon, Southwest Oncology Group Statistical Center Seattle WA USAStephen K. Williamson, University of Kansas Medical Center Kansas City KS USAJames N. Atkins, Inc. CCOP Southeast Cancer Control Consortium Winston-Salem NC USASai-Hong I. Ou, University of California at Irvine Orange CA USAMichael LeBlanc, Southwest Oncology Group Statistical Center Seattle WA USASusan G. Urba, University... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3041179 Wed, 25 Nov 2009 16:51:27 +0100 3041179 http://www.medworm.com/index.php?rid=3031869&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw547225611l87j82%2F Summary  Malignant ascites resistant to conventional drugs frequently affects ovarian cancer patients at the end of life. Here we report the case of a patient who benefited from complete resolution of ascites after low dose intraperitoneal administration of bevacizumab. Immunological analyses showed an initial increase in proportion and function of CD8+ effector T cells and a reduction of circulating Treg cells. A review of the current literature regarding bevacizumab in ovarian cancer is reported. Bevacizumab has shown a high efficacy in the treatment of ovarian cancer. Intraperitoneal administration induces an immune activation and appears promising in the treatment of malignant ascites. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9351-4Author... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3031869 Mon, 23 Nov 2009 16:47:03 +0100 3031869 http://www.medworm.com/index.php?rid=3016087&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F107812531635t764%2F Summary  Breast cancer has become the second leading cause of cancer-related deaths worldwide. The control of this disease can be achieved through chemoprevention, which refers to the consumption of synthetic or naturally occurring agents to block, reverse, or delay the process of tumor development. Tea (Camellia sinensis), the most widely consumed beverage, has shown promises in the field of cancer chemoprevention. Inhibition of tumorigenesis by green or black tea polyphenols has been demonstrated in various in vitro and in vivo models. Here, we examined the inhibitory effect of green tea polyphenol (GTP) and black tea polyphenol (BTP) on the development of mammary tumors- induced by 7, 12-dimethylbenz (a) anthracene (DMBA) in female, Wistar rats. 13% and 33% of animals deve... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3016087 Thu, 19 Nov 2009 20:05:50 +0100 3016087 http://www.medworm.com/index.php?rid=3016088&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg161g23q6w416351%2F Conclusions Our pharmacogenetic analysis could not reveal a correlation between relevant gene polymorphisms and clinical and pharmacokinetic observations of telatinib. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9347-0Authors Neeltje Steeghs, Leiden University Medical Centre Department of Clinical Oncology K1-P P.O Box 9600 2300 RC Leiden The NetherlandsHans Gelderblom, Leiden University Medical Centre Department of Clinical Oncology K1-P P.O Box 9600 2300 RC Leiden The NetherlandsJudith Wessels, Leiden University Medical Center Department of Clinical Pharmacy and Toxicology Leiden The NetherlandsFerry A. L. M. Eskens, Erasmus University Medical Center Department of Medical Oncology Rotterdam The NetherlandsNatasja de Bont, Bayer Pharmaceuticals Corpo... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=3016088 Thu, 19 Nov 2009 07:50:09 +0100 3016088 http://www.medworm.com/index.php?rid=2986477&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp05770h3618064p0%2F Summary  Multiple Myeloma (MM) is an incurable malignancy of mature plasma cells. Microtubule targeting agents (MTAs) are an established class of drug that include many conventional and some novel compounds. MTAs function by inhibiting the polymerisation or depolymerisation of microtubules (MTs) within the cell, disrupting various important cellular functions. We have investigated pre-clinically the novel tubulin polymerisation inhibitor CYT997 for the potential treatment of MM. Here we demonstrate the promising anti-myeloma activity of CYT997 as evidenced by tubulin disruption, inhibition of growth and proliferation, cell cycle arrest and most importantly apoptosis of both human myeloma cell lines (HMCLs) and primary MM cells using nanomolar drug concentrations. CYT997 als... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2986477 Wed, 11 Nov 2009 19:27:58 +0100 2986477 http://www.medworm.com/index.php?rid=2947913&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2r314432lu202211%2F In conclusion, astaxanthin exhibits anti-inflammatory and anti-cancer effects by inducing apoptosis in DMH-induced rat colon carcinogenesis by modulating the expressions of NFkB, COX-2, MMPs-2/9, Akt and ERK-2. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9342-5Authors Ponnuraj Nagendraprabhu, University of Madras Department of Biochemistry Guindy campus Chennai 600 025 Tamil nadu IndiaGanapasam Sudhandiran, University of Madras Department of Biochemistry Guindy campus Chennai 600 025 Tamil nadu India Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2947913 Fri, 30 Oct 2009 07:49:39 +0100 2947913 http://www.medworm.com/index.php?rid=2947914&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl0358090k6n382q2%2F In conclusion, our results identify two new molecules structurally related to the calcium-channel blocker nifedipine, but characterized by a very low LTCC blockers activity, able to potentiate the antiproliferative and apoptotic activities of doxorubicin through an increase of its intracellular concentration likely caused by the inhibition of MDR1 function. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9340-7Authors Maurizio Viale, S.C. Terapia Immunologica Istituto Nazionale per la Ricerca sul Cancro L.go R. Benzi 10 16132 Genova ItalyCinzia Cordazzo, Università degli Studi di Bologna Dipartimento di Chimica Organica “A. Mangini” Via San Giacomo 11 40126 Bologna ItalyDaniela de Totero, S.C. Terapia Immunologica Istituto Nazionale per la Ricerc... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2947914 Thu, 29 Oct 2009 19:50:13 +0100 2947914 http://www.medworm.com/index.php?rid=2945063&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm6v46624v28p81v7%2F Summary  Coumarin derivative RKS262 belongs to a new class of potential anti-tumor agents. RKS262 was identified by structural optimization of Nifurtimox which is currently undergoing phase II clinical trials to treat high-risk neuroblastoma. In a NCI60 cell-line assay RKS262 exhibited significant cytotoxicity in ovarian cancer cells and a variety of other cell lines exceeding effects of commercial drugs such as cisplatin, 5-FU, cyclophosphamide or sapacitabine. Various leukemia cell-lines were most sensitive (GI50: ~ 10 nM) while several non-small cell lung cancer cell lines and few cell lines from other tissues were relatively resistant (GI50 > 1 µM) to RKS262 treatment. The mechanism of cytotoxicity was examined using ovarian cancer cell-line OVCAR-3 as ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2945063 Thu, 29 Oct 2009 07:22:20 +0100 2945063 http://www.medworm.com/index.php?rid=2924241&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F530075238uqk7525%2F Summary  The modulation of intracellular nuclear factor-kappaB (NF-κB) signaling pathway involved in the deregulated expression of cell proliferation and cell cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of cloves is known to possess attractive remedial features. In the present study, we investigated the modulatory effects of eugenol on NF-κB signaling in a rat model of gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) by analysing the expression of nuclear factor-kappaB (NF-κB) family members ((NF-κB (p50 and p65), inhibitor of kappaB alpha (IκBα), phosphorylated IκBα (p-IκBα), IκB kinase β (IKKβ)) and the NF-κB target ge... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2924241 Thu, 22 Oct 2009 19:03:35 +0100 2924241 http://www.medworm.com/index.php?rid=2924242&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flk560583357m8223%2F In this study we have evaluated the effect of TA on lung cancer using both in vitro and in vivo models. TA in a dose dependent manner inhibited proliferation and cell viability of two different lung cancer cells, A549 and CRL5803. TA treatment for 48 h significantly decreased the expression of Sp1, Sp3 and Sp4. The hepatocyte growth factor receptor, c-Met is overexpressed in a variety of cancers including lung cancer and Sp proteins mediate the regulation of c-Met. TA diminished the expression of c-Met protein and modulates its downstream signaling pathway. Furthermore, TA treatment significantly increased the number of apoptotic cells and pro-apoptotic markers c-PARP and Bax confirming the activation of apoptotic pathways. In vivo studies using the orthotopic mice model for lun... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2924242 Thu, 22 Oct 2009 19:03:34 +0100 2924242 http://www.medworm.com/index.php?rid=2917680&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff23h8x24lmku5056%2F Conclusions: Pyrazoloacridine demonstrated modest activity in patients with metastatic breast cancer. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9338-1Authors Bhuvaneswari Ramaswamy, Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Division of Hematology and Oncology Columbus OH 43210 USAEwa Mrozek, Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Division of Hematology and Oncology Columbus OH 43210 USAJohn Philip Kuebler, Columbus Oncology Associates Columbus OH 43214 USATanios Bekaii-Saab, Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Division of Hematology and On... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2917680 Wed, 21 Oct 2009 12:15:43 +0100 2917680 http://www.medworm.com/index.php?rid=2917681&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn5258145802q7526%2F Summary  In current work, we investigated the in-vitro efficacy of Caffeic acid Phenethyl Ester (CAPE) as an anti-melanoma agent in five melanoma cell lines B16-F0, B16F10, SK-MEL-28, SK-MEL-5, and MeWo and in-vivo efficacy study in skin B16-F0 melanoma tumor model in C57BL/6 mice. The IC50 (48 h) of CAPE in above five melanoma cell lines was 15 µM. CAPE (20–200 µM) led to intracellular GSH depletion of 16–54%, and 10–25 fold increase in Reactive Oxygen Species (ROS) formation in B16-F0 cells. CAPE (15–30 µM) caused 5–7 fold increase in apoptosis in B16-F0 cells. CAPE (10, 20 and 30 mg/Kg/day) led to tumor size growth inhibition by 39 ± 33%, 54 ± 36%, and 57 ± 18%, respectively. The respective therapies led to plasma Alanine... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2917681 Wed, 21 Oct 2009 12:15:41 +0100 2917681 http://www.medworm.com/index.php?rid=2917682&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F644wv33885550505%2F Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9346-1Authors Luis A. Diaz, The Ludwig Center for Cancer Genetics & Therapeutics at Johns Hopkins Baltimore MD 21231 USAWells Messersmith, University of Colorado Cancer Center Division of Medical Oncology Aurora CO 80045 USALori Sokoll, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Department of Oncology Baltimore MD 21231 USAVicki Sinibaldi, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Department of Oncology Baltimore MD 21231 USASandy Moore, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Department of Oncology Baltimore MD 21231 USAMichael Carducci, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Department of Oncology Baltimore MD 21231 USAMario Eisenberger, Johns Hopkins Si... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2917682 Wed, 21 Oct 2009 12:15:40 +0100 2917682 http://www.medworm.com/index.php?rid=2906183&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx1133w2226232016%2F Summary  The cellular effects of a novel DNA-intercalating agent, the bipyridyl complex of platinum(II) with diphenyl thiourea, [Pt(bipy)(Ph2-tu)2]Cl2, has been analyzed in the cisplatin (cDDP)—sensitive human ovarian carcinoma cell line, 2008, and its—resistant variant, C13* cells, in which the highest accumulation and cytotoxicity was found among six related bipyridyl thiourea complexes. We also show here that this complex causes reactive oxygen species to form and inhibits topoisomerase II activity to a greater extent in the sensitive than in the resistant line. The impairment of this enzyme led to DNA damage, as shown by the comet assay. As a consequence, cell cycle distribution has also been greatly perturbed in both lines. Morphological analysis revealed deep cellu... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2906183 Thu, 15 Oct 2009 18:12:57 +0100 2906183 http://www.medworm.com/index.php?rid=2906184&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F211380r443352xhu%2F Conclusion Cetuximab monotherapy produces objective antitumor activity in patients with mCRC that does not express EGFR as determined by IHC. The activity and safety profiles of cetuximab monotherapy in mCRC lacking EGFR immunostaining are similar to previous observations in EGFR IHC-positive disease that was not selected based on K-ras mutation status. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9341-6Authors Rafal Wierzbicki, Consultant Medical Oncologist Durham Regional Cancer Centre 1 Hospital Court Oshawa ON L1G 2B9 CanadaDerek J. Jonker, The Ottawa Hospital Regional Cancer Centre Gastrointestinal Disease Site Group, Cancer Care Ontario, Program in Evidence-Based Care 501 Smyth Road Ottawa ON K1H 8L6 CanadaMalcolm J. Moore, Princess Margaret Hosp... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2906184 Thu, 15 Oct 2009 06:13:09 +0100 2906184 http://www.medworm.com/index.php?rid=2896257&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd885540651656317%2F Conclusions: YM155 was well tolerated in subjects with advanced melanoma; however, the pre-specified primary end-point for efficacy which required two responders in 29 evaluable subjects was not achieved. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9333-6Authors Karl D. Lewis, University of Colorado Health Sciences Center Aurora CO USAWolfram Samlowski, Huntsman Cancer Institute Salt Lake City UT USAJohn Ward, Huntsman Cancer Institute Salt Lake City UT USAJoseph Catlett, Washington Hospital Center Washington DC USALee Cranmer, Arizona Cancer Center Tucson AZ USAJohn Kirkwood, University of Pittsburgh Cancer Institute Pittsburgh PA USADavid Lawson, Emory University School of Medicine Atlanta GA USAEric Whitman, Mountainside Hospital Montclair NJ USARen... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2896257 Wed, 14 Oct 2009 17:08:06 +0100 2896257 http://www.medworm.com/index.php?rid=2896258&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F524x650567234065%2F Conclusions Based on this experience we recommend vinflunine 300 mg/m2 and pemetrexed 500 mg/m2 in combination every 3 weeks for future study. At these doses, the combination of vinflunine and pemetrexed was tolerable in this heavily pretreated population. Hematologic toxicity, including febrile neutropenia, was prominent. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9344-3Authors Hanna K. Sanoff, The University of North Carolina at Chapel Hill Department of Medicine, Division of Hematology-Oncology, School of Medicine Chapel Hill NC USAJanine Davies, The University of North Carolina at Chapel Hill Department of Medicine, Division of Hematology-Oncology, School of Medicine Chapel Hill NC USAChristine Walko, The University of North Carolina... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2896258 Wed, 14 Oct 2009 17:08:04 +0100 2896258 http://www.medworm.com/index.php?rid=2896259&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa27438r7vgr02g43%2F Conclusions Induction therapy with T-bVAd, administered as an outpatient regimen, was efficient and relatively well tolerated in the treatment of MM. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9343-4Authors Jae-Cheol Jo, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center Seoul KoreaByung Woog Kang, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center Seoul KoreaSun Jin Sym, Gachon University Gil Hospital Department of Oncology Incheon KoreaSung Sook Lee, Yonsei University College of Medicine Department of Oncology, Severance Hospital Seoul KoreaGeundoo Jang, Hallym University Chunchon Sacred Heart Hospital Department of Oncology Chunchon KoreaShin Kim, University of Ulsan College of Medic... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2896259 Tue, 13 Oct 2009 10:35:24 +0100 2896259 http://www.medworm.com/index.php?rid=2880538&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F344612501l8404t5%2F In conclusion replacement of the phenyl group of cyclohexanone derived curcumin derivatives with heterocyclic rings forms a class of second-generation analogs that are more potent than both curcumin and other derivatives. These new derivatives provide a platform for the further development of drugs for the treatment of ER-negative breast cancer. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9339-0Authors Tiffany J. Somers-Edgar, University of Otago Department of Pharmacology & Toxicology 18 Frederick Street, Adams Building Dunedin New ZealandSebastien Taurin, University of Otago Department of Pharmacology & Toxicology 18 Frederick Street, Adams Building Dunedin New ZealandLesley Larsen, New Zealand Institute for Plant and Food Research Ltd. Dunedin ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2880538 Fri, 09 Oct 2009 06:19:06 +0100 2880538 http://www.medworm.com/index.php?rid=2877565&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4811324451558675%2F Summary  Hepatocellular carcinoma (HCC), one of the most lethal cancers, results in more than one million fatalities worldwide every year. In view of the limited therapeutic alternatives and poor prognosis of liver cancer, preventive control approaches, notably chemoprevention, have been considered to be the best strategy in lowering the present prevalence of the disease. Resveratrol, a naturally occurring antioxidant and antiinflammatory agent found in grapes and red wine, inhibits carcinogenesis with a pleiotropic mode of action. Recently, we have reported that dietary resveratrol significantly prevents chemically-induced liver tumorigenesis in rats. One of the mechanisms of resveratrol-mediated chemoprevention of hepatocarcinogenesis could be related to its antiinflammat... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2877565 Thu, 08 Oct 2009 07:04:47 +0100 2877565 http://www.medworm.com/index.php?rid=2863705&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F542x79012107j516%2F Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9325-6Authors Vanessa Nicolin, University of Trieste Clinical Department of Biomedicine, School of Medicine Via Manzoni 16 34138 Trieste ItalyPaola Narducci, University of Trieste Clinical Department of Biomedicine, School of Medicine Via Manzoni 16 34138 Trieste ItalyRenato Bareggi, University of Trieste Clinical Department of Biomedicine, School of Medicine Via Manzoni 16 34138 Trieste Italy Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2863705 Thu, 01 Oct 2009 18:16:30 +0100 2863705 http://www.medworm.com/index.php?rid=2853371&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F32117240lp512851%2F Summary  MT477 is a novel thiopyrano[2,3-c]quinoline with anti-cancer activity. The purpose of the present study was to evaluate different doses and treatment schedules of MT477 in an in vivo xenograft model of non-Ras-mutated cancer, as well as determine its biological effects and mechanism of action via the four conventional PKC isoforms: α, βI, βII, and γ. Here, we show that MT477 inhibits the activity of PKC-α and its downstream targets, ERK1/2 and Akt, before it has an effect on Ras activity. MT477 treatment of cultured H226 cells induced apoptosis and increased focal cell adhesion and formation of actin stress fibers. H226 tumor size in mice continuously treated with intraperitoneal MT477 (1 mg/kg) was 62.1 ± 15.3% smaller than the average tumor size in... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2853371 Wed, 30 Sep 2009 18:27:56 +0100 2853371 http://www.medworm.com/index.php?rid=2848186&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk2815m053jv80152%2F Summary  Ribonucleases (RNases) are a non-mutagenic alternative to harmful DNA-damaging anticancer drugs. Targeting of RNases with antibodies to surface antigens that are selectively expressed on tumor cells endows specificity to the cytotoxic actions of RNases. Barnase, a ribonuclease from Bacillus amyloliquefaciens, is a promising candidate for targeted delivery to cancer cells because of its insusceptibility to the ubiquitous cytoplasmic ribonuclease inhibitor, and its high stability and catalytic activity. Here, we characterized in vitro and in vivo an immunoRNase, scFv 4D5-dibarnase, which consists of two barnase molecules that are fused serially to the single-chain variable fragment (scFv) of humanized 4D5 antibody. The latter is directed against the extracellular domai... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2848186 Tue, 29 Sep 2009 16:56:45 +0100 2848186 http://www.medworm.com/index.php?rid=2848187&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft0448j62277u6m55%2F In this study, we report the efficacy of MONCPT against the development of melanoma metastasis by an intravenous injection of green fluorescent protein-transfected mice melanoma carcinoma (B16F10-GFP) cells in C57BL/6 mice. MONCPT (2.0, 5.0 and 12.5 mg/kg/2 days) markedly decreased B16F10-GFP pulmonary metastases by 12.8%, 53.1% and 76.3%, respectively; whereas higher doses of MONCPT (31.0 mg/kg/2 days) significantly inhibited the tumor growth of B16F10 xenograft model. In the in vitro experiment, MONCPT suppressed the B16F10-GFP cell invasion and migration without affecting cell survival. Further studies demonstrated that MONCPT decreased the secretion of matrix metalloproteinase (MMP)-9 and VEGF, and reduced the protein expression of HIF-1α as well as the phosp... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2848187 Tue, 29 Sep 2009 16:56:43 +0100 2848187 http://www.medworm.com/index.php?rid=2848188&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvg27235730786n21%2F In conclusion, we have shown that treatment with TAE leads to a reduction of neoangiogenesis in vitro and in a mouse model. The effects are mediated by inhibition of angiogenesis and vasculogenic OEC and EPC. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9326-5Authors Alexander Schultze, Dept. of Oncology/Hematology with sections BMT and Pneumology University Medical Center Hamburg-Eppendorf, Hubertus Wald University Cancer Center Hamburg Hamburg GermanySebastian Decker, Dept. of Oncology/Hematology with sections BMT and Pneumology University Medical Center Hamburg-Eppendorf, Hubertus Wald University Cancer Center Hamburg Hamburg GermanyJasmin Otten, Dept. of Oncology/Hematology with sections BMT and Pneumology University Medical Center Hamburg-Eppen... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2848188 Tue, 29 Sep 2009 01:08:09 +0100 2848188 http://www.medworm.com/index.php?rid=2848189&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1236p8815354p20%2F Summary  The anti-tumor properties of novel derivatives prepared from Aconitum C20-diterpenoid alkaloid, which show the least toxicity among the Aconitum alkaloids, were investigated in the Non-Hodgkin’s lymphoma cell line Raji cells. Two novel Aconitum C20-diterpenoid alkaloid derivatives, 11-m-Trifluorometylbenzoyl (Mb)-pseudokobuisne and 11-Anisoyl (As)-pseudokobusine, showed significant suppressive effects and their 50% inhibitory concentrations were 2.2 μg/ml and 2.4 μg/ml against Raji cells, respectively. Both compounds have the same structure except for a functional group in the C-11 position. One of the active compounds, 11-Mb-pseudokobusine, clearly inhibited the phosphorylation of extracellular signal-regulated kinase, induced enhanced phosphoinositide ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2848189 Tue, 29 Sep 2009 01:08:08 +0100 2848189 http://www.medworm.com/index.php?rid=2835110&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft42w366745l56031%2F This study was aimed to define F14512 anticancer efficacy against tumor models and to investigate whether fluorophor-labeled polyamine probes could be used to identify tumors expressing a highly active PTS and that might be sensitive to F14512 treatments. Eighteen tumor models were used to assess F14512 antitumor activity. Cellular uptake of spermine-based fluorescent probes was measured by flow cytometry in cells sampled from tumor xenografts by needle biopsy. The accumulation of the fluorescent probe within B16 tumors in vivo was assessed using infrared fluorescence imaging. This study has provided evidence of a major antitumor activity for F14512. Significant responses were obtained in 67% of the tumor models evaluated, with a high level of activity recorded in 33% of the responsi... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2835110 Thu, 24 Sep 2009 05:50:40 +0100 2835110 http://www.medworm.com/index.php?rid=2835111&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F253713l311452620%2F We examined the synergistic efficacy of combination of sorafenib (SF) and genistein (GST) in human malignant neuroblastoma SK-N-DZ (N-Myc amplified) and SH-SY5Y (N-Myc non-amplified) cell lines. MTT assay showed dose-dependent decrease in cell viability and the combination therapy more prominently inhibited the cell proliferation in both cell lines than either treatment alone. Apoptosis was confirmed morphologically by Wright staining. Flow cytometric analysis of cell cycle phase distribution and Annexin V-FITC/PI staining showed increase in subG1 DNA content and early apoptosis, respectively, after treatment with the combination of drugs. Apoptosis was further confirmed by scanning electron microscopy. Combination therapy showed activation of caspase-8, cleavage of Bid to tBid, inc... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2835111 Thu, 24 Sep 2009 05:50:39 +0100 2835111 http://www.medworm.com/index.php?rid=2833209&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F741574n0q18166t2%2F Summary  Rebeccamycin analog (RA) is an antitumor antibiotic with both topoisomerase I and II inhibiting activity. Topoisomerase inhibitors have demonstrated synergy with platinum agents. We performed a phase I trial of combination RA with oxaliplatin in patients with refractory solid tumors. RA was administered as a 1-hour infusion daily on days 1–5 with oxaliplatin administered on day 5. Cycles were repeated every 21 days. A total of 17 patients were enrolled. The MTD for RA was 80 mg/m2/d for five days along with oxaliplatin 130 mg/m2 on day 5. Myelosuppression was a common occurrence but was mild except in one instance. Dose limiting toxicities included atrial fibrillation and hypophosphatemia. There was evidence of antitumor activity including 3 partial ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2833209 Wed, 23 Sep 2009 06:04:37 +0100 2833209 http://www.medworm.com/index.php?rid=2833211&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F75371547mpr04547%2F Summary  Extracts from Pygeum africanum are used in the treatment of prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The ligand-activated human androgen receptor (AR) is known to control the growth of the prostate gland. Inhibition of human AR is therefore a major goal in treatment of patients. Here, we characterize the compound N-butylbenzene-sulfonamide (NBBS) isolated from P. africanum as a specific AR antagonist. This antihormonal activity inhibits AR- and progesterone receptor- (PR) mediated transactivation, but not the related human glucocorticoid receptor (GR) or the estrogen receptors (ERα or ERβ). Importantly, NBBS inhibits both endogenous PSA expression and growth of human PCa cells. Mechanistically, NBBS binds to AR and inhibits its tra... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2833211 Tue, 22 Sep 2009 15:41:51 +0100 2833211 http://www.medworm.com/index.php?rid=2810806&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb374623m4245475q%2F Conclusions The MWTD for zibotentan was 15 mg orally daily. The predominant adverse events observed were consistent with those reported for this class of drugs, and prolonged stable disease was noted in some patients. Phase III studies with zibotentan in men with metastatic CRPC are ongoing. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9318-5Authors William R. Schelman, University of Wisconsin Paul P. Carbone Comprehensive Cancer Center 600 Highland Avenue, K6/534 CSC Madison WI 53792 USAGlenn Liu, University of Wisconsin Paul P. Carbone Comprehensive Cancer Center 600 Highland Avenue, K6/534 CSC Madison WI 53792 USAGeorge Wilding, University of Wisconsin Paul P. Carbone Comprehensive Cancer Center 600 Highland Avenue, K6/534 CSC Madison WI 53792 U... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810806 Fri, 18 Sep 2009 06:14:41 +0100 2810806 http://www.medworm.com/index.php?rid=2810808&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe701620475407744%2F Conclusion Enrolled patients’ comprehension of the goals and means of RCTs is actually better than controls’. Nevertheless, additional efforts should be made to enhance information about clinical research to patients as well as to the main population. Practice Implications Having better knowledge about patients’ difficulties in understanding RCTs would allow physicians to adjust the information they give and then to enhance patients’ well-being. Content Type Journal ArticleCategory PHASE III STUDIESDOI 10.1007/s10637-009-9315-8Authors Tanguy Leroy, Univ Lille Nord de France—Université de Lille 3 URECA EA 1059—Staff “Family, Health & Emotion” BP 60149 59653 Villeneuve d’Ascq Cedex FranceVéronique Christophe, Univ Lille Nord de France—Université de Lille 3 URECA... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810808 Thu, 17 Sep 2009 12:19:55 +0100 2810808 http://www.medworm.com/index.php?rid=2810807&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx622161tw2760317%2F In this study, we investigated the effect of combining lovastatin with gefitinib on gefitinib-resistant human non-small cell lung cancer (NSCLC) cell lines with K-Ras mutations. Antitumor effects were measured by growth inhibition and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Effects on apoptosis were determined by flow cytometry, DNA fragmentation, and immunoblots. Protein levels of RAS, AKT/pAKT, and RAF/ERK1/2 in cancer cells were analyzed by immunoblot. Compared with gefitinib alone, a combination of gefitinib with lovastatin showed significantly enhanced cell growth inhibition and cytotoxicity in gefitinib-resistant A549 and NCI-H460 human NSCLC cells. In addition, lovastatin combination treatment significantly increased gefitinib-related apoptosis, as... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810807 Thu, 17 Sep 2009 12:19:55 +0100 2810807 http://www.medworm.com/index.php?rid=2810809&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm464843868k62087%2F Conclusion The present study confirmed that sorafenib at 400 mg once daily in combination with carboplatin AUC 5 mg min mL−1 and paclitaxel 200 mg/m2 is feasible in Japanese patients with advanced NSCLC. The results of this study also showed that this combination therapy had encouraging antitumor activity and was not associated with relevant pharmacokinetic interaction in Japanese NSCLC patients. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9321-xAuthors Isamu Okamoto, Kinki University School of Medicine Department of Medical Oncology 377-2 Ohno-higashi Osaka-Sayama Osaka 589-8511 JapanMasaki Miyazaki, Kinki University School of Medicine Department of Medical Oncology 377-2 Ohno-higashi Osaka-Sayama Osaka 589-8511 JapanRyotaro Morin... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810809 Thu, 17 Sep 2009 12:19:51 +0100 2810809 http://www.medworm.com/index.php?rid=2810811&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn7624w32687612h3%2F In this study, we tested the hypothesis that osteosarcoma progression may be delayed by disrupting the Wnt/β-catenin pathway using small molecule inhibitors such as curcumin and PKF118-310. Effective inhibitions of the Wnt/β-catenin pathway by curcumin and PKF118-310 in osteosarcoma cells were shown by the suppression of both intrinsic and activated β-catenin/Tcf transcriptional activities using luciferase reporter assays. Western blot analysis revealed that there was no change in the amount of cytosolic β-catenin, although nuclear β-catenin was markedly reduced by treatment with either compounds. We next performed wound healing and Matrigel invasion assays and observed a dose-dependent decrease in osteosarcoma cell migration and invasion with curcumin and PKF118-310 treatment.... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810811 Tue, 15 Sep 2009 21:59:47 +0100 2810811 http://www.medworm.com/index.php?rid=2810810&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx12nk33j825w2163%2F Summary  Many naturally occurring substances of plant origin ingested in human diet, exhibit anticarcinogenic and antimutagenic effects. One of the active phytochemical which shows the active anticarcinogenic role is Piper longum Linn. (Pl). Pl is widely used in ayurvedic industry due to its property in healing some of the bodily ailments. Despite being known for the antioxidant, antimicrobial and anticarcinogenic effects, its relation to brain and its tumour development is still scarce. Hence, the experimental glioma model was developed in rats using C6 glioma cells and the effect of Pl was evaluated in the brain tissue of experimental group of rats. From the study, the glioma induced animals showed an increased level of lipid peroxides (LPO), tissue marker enzymes lactate ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810810 Tue, 15 Sep 2009 21:59:47 +0100 2810810 http://www.medworm.com/index.php?rid=2810812&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6m53x15620564220%2F Conclusions: The pharmacokinetics observed and clinical outcomes achieved in Japanese GIST patients on sunitinib (50 mg/day, Schedule 4/2) after imatinib failure appeared similar to those of Western patients in previous sunitinib trials. Although some serious AEs were observed, AEs were generally manageable using dose interruption/modification and/or standard medical treatments. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9306-9Authors Kuniaki Shirao, National Cancer Center Hospital Medical Oncology Division Tokyo JapanToshirou Nishida, Osaka University Graduate School of Medicine Department of Surgery Osaka JapanToshihiko Doi, National Cancer Center Hospital East Division of Digestive Endoscopy/Gastrointestinal Oncology Kashiwa JapanYoshito Koma... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810812 Tue, 15 Sep 2009 21:59:45 +0100 2810812 http://www.medworm.com/index.php?rid=2810815&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc56482j1146k2pkq%2F Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9314-9Authors Dana M. Hartl, Institut Gustave Roussy Department of Otolaryngology Head & Neck Surgery Paris FranceCharles Ferté, Institut Gustave Roussy Department of Medicine, Phase I Unit (SITEP) Paris FranceYohann Loriot, Institut Gustave Roussy Department of Medicine, Phase I Unit (SITEP) Paris FranceCarlos Gomez Roca, Institut Gustave Roussy Department of Medicine, Phase I Unit (SITEP) Paris FranceRastislav Bahleda, Institut Gustave Roussy Department of Medicine, Phase I Unit (SITEP) Paris FranceCristian Moldovan, Institut Gustave Roussy Department of Medicine, Phase I Unit (SITEP) Paris FranceOlivier Mir, Institut Gustave Roussy Department of Medicine, Phase I Unit (SITEP) Paris FranceJean-Charles Soria, Ins... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810815 Tue, 15 Sep 2009 21:59:44 +0100 2810815 http://www.medworm.com/index.php?rid=2810814&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv071104846276022%2F Summary  Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease that exclusively progresses to renal failure. An important target for the treatment of ADPKD is to reduce cystic cell proliferation. PPARγ agonists such as TZDs are insulin sensitizing agents that have also been reported to decrease tumor growth. Here we tested DH9, a newly synthesized PPARγ agonist on the proliferation of an ADPKD cell line, WT9-12. DH9 showed a potent anti-proliferative activity against ADPKD cells. At high concentration, DH9 also induced apoptotic cell death. The effect of DH9 on cell proliferation was mediated by a PPARγ independent mechanism. Since DH9 decreased the levels of β-catenin in cells via a GSK3β mediated degradation pathway, this acts as a mechanism for g... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810814 Tue, 15 Sep 2009 21:59:44 +0100 2810814 http://www.medworm.com/index.php?rid=2810813&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F516161r67n15u1r7%2F This study evaluated the preclinical activity and molecular predictors of response to gefitinib (Iressa®, Astra Zeneca Inc, UK) in nasopharyngeal carcinoma (NPC). The activity of gefitinib was evaluated in four human NPC cell lines—HK1, HONE-1, CNE2, C666-1. A representative gefitinib-sensitive (HK1, IC50 = 250 nM) and gefitinib-resistant cell line (HONE-1, IC50 > 15 μM) were selected and compared for expression of epidermal growth factor receptor (EGFR) and related ligands, and activation of downstream proteins. Gefitinib induced G1 cycle arrest, apoptosis and inhibited cell invasion more significantly in HK1 than HONE-1 cells. HK1 expressed higher levels of p-EGFR, lower p-AKT and phospho-signal transducer and activator of transcription 3 (p-STAT3) than othe... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810813 Tue, 15 Sep 2009 21:59:44 +0100 2810813 http://www.medworm.com/index.php?rid=2810816&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F44jq5105543423q0%2F Conclusions: GIDOX is an active salvage regimen for aggressive B-cell NHL and can be tolerated by patients with acceptable toxicity. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9320-yAuthors Byeong-Bae Park, Hanyang University College of Medicine Division of Hematology/Oncology, Department of Internal Medicine Seoul South KoreaWon Seog Kim, Sungkyunkwan University School of Medicine Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center Seoul South KoreaHyeon Seok Eom, National Cancer Center Hematology–Oncology Clinic, Research Institute and Hospital Goyang South KoreaJin Seok Kim, Yonsei University College of Medicine Division of Hematology, Department of Internal Medicine Seoul South KoreaYoung Yiul Lee, Hanyang University C... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810816 Tue, 15 Sep 2009 21:59:43 +0100 2810816 http://www.medworm.com/index.php?rid=2810817&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk9775781881p7814%2F Conclusion Few parameters influence the accrual time of dose-escalation phase-1 trials. Real first-in-man phase 1 studies based on starting dose estimated from animal toxicological data require longer accrual time. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9317-6Authors Nicolas Penel, Centre Oscar Lambret Département de Cancérologie Générale 3, Rue F Combemale 59020 Lille FrancePierre Leblond, Centre Oscar Lambret Unité d’Oncologie Pédiatrique Lille FranceAmélie Lansiaux, Centre Oscar Lambret Laboratoire de Pharmacologie anti-tumorale Lille FranceStéphanie Clisant, Centre Oscar Lambret Unité de Recherche Clinique Lille FranceEric Dansin, Centre Oscar Lambret Département de Cancérologie Générale 3, Rue F Combemale 59020 Lille FranceAntoi... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810817 Tue, 15 Sep 2009 21:59:42 +0100 2810817 http://www.medworm.com/index.php?rid=2810818&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3w61842536145332%2F In conclusion, meta-analysis suggested benefits of a carefully managed bevacizumab-containing salvage regimen for patients with histologically or cytologically confirmed Her-2 negative MBC who have not received previous cytotoxic therapy. This treatment could improve both progression free survival and overall survival rates. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9310-0Authors Jae-Bok Lee, Korea University Department of Surgery, College of Medicine Seoul KoreaOk Hee Woo, Korea University Department of Radiology, College of Medicine Seoul KoreaKyong Hwa Park, Korea University Division of Medical Oncology & Department of Internal Medicine, College of Medicine Seoul KoreaSang Uk Woo, Korea University Department of Surgery, College of Medicine Seoul Kore... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810818 Tue, 15 Sep 2009 21:59:41 +0100 2810818 http://www.medworm.com/index.php?rid=2810819&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa751704513nx3p3g%2F Summary  Newer series of 9-ethyl-9H-purine derivatives (EPD) were synthesized and screened for their efficacy in inhibiting the proliferation of various tumor cells in vitro. We evaluated the effects of EPD against HeLa, SiHa, CaSki (human cervical cancer cells), LM8, LM8G7 (murine osteosarcoma cells), OVSAHO and SKOV-3 (human ovarian cancer cells). The chemical structures of the EPD were confirmed by 1H NMR and LCMS analyses. The inhibitory effects of EPD were studied by using trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and TetraColor One reagents. Furthermore, SAR studies revealed that the presence of trifluoromethoxy and trifluromethyl group in 4b and 4g, respectively are responsible for the significant activity of the EPD agai... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2810819 Tue, 15 Sep 2009 21:59:39 +0100 2810819 http://www.medworm.com/index.php?rid=2767257&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft1w8230240285q71%2F Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9312-yAuthors Carlos Eduardo Paiva, São Paulo State University Oncological and Hemato-oncological Center Botucatu SP BrazilYara Cristina de Paiva Maia, Federal University of Ouro Preto Center for Research in Biological Sciences Ouro Preto MG BrazilBianca Sakamoto Ribeiro Paiva, São Paulo State University Department of Nursing Botucatu SP BrazilMauro Masson Lerco, São Paulo State University Department of Surgery Botucatu SP Brazil Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2767257 Thu, 03 Sep 2009 06:14:27 +0100 2767257 http://www.medworm.com/index.php?rid=2744980&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw7n7629712v62807%2F Conclusions OS, PFS, QOL, and RR were comparable between arms. Adding E to G did not increase hematologic toxicities. GE does not warrant further investigation in unselected pancreatic cancer patients. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9307-8Authors Donald A. Richards, US Oncology Research, Inc. The Woodlands TX USAPaul R. Kuefler, US Oncology Research, Inc. The Woodlands TX USACarlos Becerra, US Oncology Research, Inc. The Woodlands TX USALalan S. Wilfong, US Oncology Research, Inc. The Woodlands TX USARobert H. Gersh, US Oncology Research, Inc. The Woodlands TX USAKristi A. Boehm, US Oncology Research, Inc. The Woodlands TX USAFeng Zhan, US Oncology Research, Inc. The Woodlands TX USALina Asmar, US Oncology Research, Inc. The Woodlands TX U... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2744980 Fri, 28 Aug 2009 15:00:38 +0100 2744980 http://www.medworm.com/index.php?rid=2742619&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj30503g0q0182681%2F Summary  Oxazolinodaunorubicin, a new daunorubicin derivative with a modified daunosamine moiety, was synthesized. The biological properties of this derivative and the parent daunorubicin were compared. The results showed antiproliferative activity of the derivative with significantly lower toxicity (an LD50 value ca. 20 times higher than that of parent daunorubicin) and an ability to completely overcome the resistance of cancer cells to this drug in vitro. Cardiotoxicity determination using male mice treated with a single dose of 75% of the LD50 value indicated that the cardiotoxicity of new analog was much lower than that of the parent drug. Preliminary results in transplanted murine tumor models revealed that a single-dose injection of the tested compounds exhibited antitu... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2742619 Thu, 27 Aug 2009 15:44:21 +0100 2742619 http://www.medworm.com/index.php?rid=2742621&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh823lj861l05807q%2F Conclusions This method for interspecies scaling was successful in predicting the time-course of myelosuppression in patients based on rat data. Predictions improved when species differences in protein binding and CFU-GM assay sensitivity were accounted for. The approach appears promising for predicting myelosuppression in patients early in development. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9308-7Authors Lena E. Friberg, Uppsala University Department of Pharmaceutical Biosciences SE-75124 Uppsala SwedenMarie Sandström, Uppsala University Department of Pharmaceutical Biosciences SE-75124 Uppsala SwedenMats O. Karlsson, Uppsala University Department of Pharmaceutical Biosciences SE-75124 Uppsala Sweden Journal Investigational New DrugsO... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2742621 Thu, 27 Aug 2009 15:44:19 +0100 2742621 http://www.medworm.com/index.php?rid=2742620&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr1n5p2x21k961nm5%2F Summary  The present report overviews the studies on diorganotin(IV) complexes of N-(2-pyridylmethylene)arylamine, R2SnCl2.L (R = Me (1), Et (2), Bu (3) or Ph (4)) as cytotoxic agents. This family of complexes was designed to include highly electron-donating N^Nchelating ligand to afford octahedral R2SnCl2.L complexes of relatively high hydrolytic stability, with the aim to retain ligand binding throughout the biological activity for achieving controlled processes and allowing mechanistic evaluation. It is observed that the high cytotoxic activity is dependent on the Sn-R groups and Sn-N bond lengths, and which is related to the cytotoxic potential. Complex (2) was found to exhibit stronger cytotoxic activity in vitro particularly for A498 (renal cancer), IGROV (ovarian cancer... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2742620 Thu, 27 Aug 2009 15:44:19 +0100 2742620 http://www.medworm.com/index.php?rid=2731848&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk01j210675363113%2F Summary  Targeting cellular mitosis is an attractive antitumor strategy. Here, we reported MT7, a novel compound from the 6H-Pyrido[2′,1′:2,3]imidazo [4,5-c]isoquinolin- 5(6H)-one library generated by using the multi-component reaction strategy, as a new mitotic inhibitor. MT7 elicited apparent inhibition of cell proliferation by arresting mitosis specifically and reversibly in various tumor cell lines originating from different human tissues. Detailed mechanistic studies revealed that MT7 induced typical gene expression profiles related to mitotic arrest shown by cDNA microarray assays. Connectivity Map was used to analyze the microarray data and suggested that MT7 was possibly a tubulin inhibitor due to its similar gene expression profiles to those of the known tubulin ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2731848 Mon, 24 Aug 2009 17:36:03 +0100 2731848 http://www.medworm.com/index.php?rid=2731849&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj500368706373414%2F Conclusion Gemcitabine combined with carboplatin has promising efficacy in MBC with prior treatment with anthracyclines and taxanes but has significant haematological toxicities requiring dose modifications. The regimen may be modified to gemcitabine 800 mg/m2 days 1 and 8 to improve tolerability. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9305-xAuthors Daniel Chan, National University Hospital, Singapore Department of Haematology-Oncology 5, Lower Kent Ridge Road Singapore 119074 SingaporeWee-Lee Yeo, National University Hospital, Singapore Department of Haematology-Oncology 5, Lower Kent Ridge Road Singapore 119074 SingaporeMaricel Tiemsim Cordero, National University Hospital, Singapore Department of Haematology-Oncology 5, Lower Kent Rid... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2731849 Mon, 24 Aug 2009 17:36:02 +0100 2731849 http://www.medworm.com/index.php?rid=2731850&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F24l157122u571428%2F Summary  Honey is a complex mixture of different biologically active constituents. Honey possesses anti-inflammatory, antioxidant and antitumor properties. Our chief investigation was to assess the honey induced apoptosis and its molecular mechanism in colon cancer cell growth inhibition. Honey exerted antiproliferative potential against the HCT-15 and HT-29 colon cancer cells as assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometric analysis showed the increasing accumulation of hypodiploid nuclei in the sub-G1 phase of cell cycle indicating apoptosis. Honey transduced the apoptotic signal via initial depletion of intracellular non protein thiols, consequently reducing the mitochondrial membrane potential (MMP) and increasin... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2731850 Mon, 24 Aug 2009 17:36:01 +0100 2731850 http://www.medworm.com/index.php?rid=2697390&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff6x742m914868402%2F Conclusion Cyclophosphamide in metronomic schema showed good safety results for this frail population. Oral treatment enabled patients to stay at home longer and limited hospitalisation time. A larger controlled study will be necessary to confirm these encouraging results in elderly with MM, a classical chemoresistant tumor. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9298-5Authors Estelle Borne, Université Lille 2 Clinique de Dermatologie, Centre Hospitalier Régional et Universitaire Lille FranceEve Desmedt, Université Lille 2 Clinique de Dermatologie, Centre Hospitalier Régional et Universitaire Lille FranceAlain Duhamel, Université Lille 2 Département de Biostatistiques Lille FranceXavier Mirabel, Centre Oscar Lambret Département de Radio... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2697390 Tue, 11 Aug 2009 08:32:49 +0100 2697390 http://www.medworm.com/index.php?rid=2697391&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu0v02241188772p1%2F Conclusion Single agent ixabepilone has limited activity in advanced hepatobiliary cancers. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9297-6Authors Halla S. Nimeiri, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center 676 North St. Clair Street, suite 850 Chicago IL 60611 USADeepti A. Singh, University of Chicago Medical Center 5841 S. Maryland Ave., MC 2115 Chicago IL 60637 USAKristen Kasza, University of Chicago 5841 S. Maryland Ave. MC 2007 Chicago IL 60637 USADavid A. Taber, Northern Indiana Cancer Research Consortium 100Navarre Place Suite 5550 South Bend IN 46601 USARafat H. Ansari, Northern Indiana Cancer Research Consortium 100Navarre Place Suite 5550 South Bend IN 46601 USAEverett E. Vokes, Univers... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2697391 Tue, 11 Aug 2009 01:37:49 +0100 2697391 http://www.medworm.com/index.php?rid=2669053&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F602257p42h443465%2F Conclusions Sunitinib had low single agent activity in SCCHN necessitating early closure of cohort A at interim analysis. Sunitinib was well tolerated in PS 2 patients. Further evaluation of single agent sunitinib in head and neck is not supported by the results of this trial. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9296-7Authors Nicholas W. Choong, University of Chicago Medical Center Section of Hematology-Oncology and Phase II network MC 2115, 5841, S. Maryland Avenue Chicago IL 60637 USAMark Kozloff, Ingalls Hospital 1 Ingalls Drive Harvey IL 60430 USADavid Taber, Michiana Hematology Oncology 100 Navarre Pl Ste 5550 South Bend IN 46601 USAH. Shawn Hu, David C. Pratt Cancer Center 607 S. New Ballas Road, Suite 3300 St. Louis MO 63141 USAJames Wa... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2669053 Mon, 03 Aug 2009 10:17:08 +0100 2669053 http://www.medworm.com/index.php?rid=2665126&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0413216363h88772%2F Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9295-8Authors Christophe Massard, Institut Gustave Roussy Département de Médecine Villejuif FranceKarim Fizazi, Institut Gustave Roussy Département de Médecine Villejuif FranceMarine Gross-Goupil, Institut Gustave Roussy Département de Médecine Villejuif FranceBernard Escudier, Institut Gustave Roussy Département de Médecine Villejuif France Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Investigational New Drugs) Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2665126 Fri, 31 Jul 2009 19:56:39 +0100 2665126 http://www.medworm.com/index.php?rid=2661579&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv46j5u8036633ut2%2F Summary  Triphenyltin(IV) complexes of composition [Ph3SnL1H]n (1) and [Ph3SnL2H]n (2) (where L1H = 2-[(E)-2-(3-formyl-4-hydroxyphenyl)-1-diazenyl]benzoate and L2H = 2-[(E)-2-(4-Hydroxy-5-methylphenyl)-1-diazenyl]benzoate) were synthesized and characterized by spectroscopic (1H, 13C and 119Sn NMR, IR, 119Sn Mössbauer) techniques in combination with elemental analysis. The molecular structures and geometries of the complexes (1 and 2) were fully optimized using the quantum mechanical method (PM3). Complexes (1 and 2) were found to exhibit stronger cytotoxic activity in vitro across a panel of human tumour cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. The test compounds 1 and 2 exhibit comparable results and both the compounds are found to be far super... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2661579 Thu, 30 Jul 2009 10:14:09 +0100 2661579 http://www.medworm.com/index.php?rid=2651494&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3316mn54513301m3%2F Summary  We previously identified the induction of senescence in melanoma cell lines sensitive to diterpene esters, indicating a therapeutic potential. Here we compared the cytostatic effects of two diterpene esters: the prototypic PKC-activating drug TPA (12-O-tetradecanoylphorbol-13-acetate), and the novel compound PEP008 (20-O-acetyl-ingenol-3-angelate) in cell lines derived from melanoma, breast cancer and colon cancer. The diterpene esters induced permanent growth arrest with characteristics of senescence in a subset of cell lines in all three solid tumor models at 100–1000 ng/ml. Use of the PKC inhibitor bisindolylmaleimide-l demonstrated that activation of PKC was required for growth arrest. Full genome expression profiling identified pivotal genes involved in D... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2651494 Mon, 27 Jul 2009 22:55:54 +0100 2651494 http://www.medworm.com/index.php?rid=2642651&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F44v44m4186r1k972%2F Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9294-9Authors Maria Alessandra Santucci, Università di Bologna Policlinico S.Orsola Istituto di Ematologia “Lorenzo e Ariosto Seragnoli” Via Massarenti 9 40138 Bologna ItalyManuela Mancini, Università di Bologna Policlinico S.Orsola Istituto di Ematologia “Lorenzo e Ariosto Seragnoli” Via Massarenti 9 40138 Bologna ItalyValentina Corradi, Università di Siena Dipartimento Farmaco Chimico Tecnologico Via Alcide De Gasperi, 2 Siena ItalyIlaria lacobucci, Università di Bologna Policlinico S.Orsola Istituto di Ematologia “Lorenzo e Ariosto Seragnoli” Via Massarenti 9 40138 Bologna ItalyGiovanni Martinelli, Università di Bologna Policlinico S.Orsola Istituto di Ematologia “Lorenzo e Ariosto Seragnoli�... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2642651 Sat, 25 Jul 2009 08:46:07 +0100 2642651 http://www.medworm.com/index.php?rid=2642652&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F30p404457x48v897%2F Summary  Despite the widespread use of rituximab, a chimeric monoclonal antibody with demonstrated efficacy in the treatment of non-Hodgkin’s lymphomas, there is a recognized need to develop new agents with improved efficacy. Towards this end, using XenoMouse® technology, a fully human IgG1 anti-CD20 monoclonal antibody was generated. This antibody, denoted mAb 1.5.3, evoked enhanced pro-apoptotic activity in vitro, as compared to rituximab, in the Ramos lymphoma cell line. Also, mAb 1.5.3 mediated both complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) similar to rituximab in human B-lymphoma lines. Interestingly, mAb 1.5.3 demonstrated superior ADCC compared to rituiximab when FcγRIIIa F/F allotype donors were profiled and super... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2642652 Fri, 24 Jul 2009 23:52:07 +0100 2642652 http://www.medworm.com/index.php?rid=2612406&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fnn38353436606725%2F Conclusion Sunitinib and/or lapatinib appear to exhibit significant effects on proliferation, apoptosis and migration of glioma cells. When applied alone, sunitinib appears to be a more potent inhibitor than lapatinib. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9290-0Authors Efstathia Giannopoulou, University Hospital of Patras, Patras Medical School Clinical Oncology Laboratory, Division of Oncology, Department of Medicine Rion 26504 GreeceKonstantinos Dimitropoulos, University Hospital of Patras, Patras Medical School Clinical Oncology Laboratory, Division of Oncology, Department of Medicine Rion 26504 GreeceAndreas A. Argyriou, University Hospital of Patras, Patras Medical School Clinical Oncology Laboratory, Division of Oncology, Department of ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2612406 Wed, 15 Jul 2009 13:53:15 +0100 2612406 http://www.medworm.com/index.php?rid=2592359&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe1176h2027m81823%2F Summary  Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxicant and a renal carcinogen that induces its effect by causing oxidative stress. The present study was undertaken to explore protective effect of silymarin, a flavonolignan from milk thistle (Silybum marianum), against Fe-NTA mediated renal oxidative stress, inflammation and tumor promotion response along with elucidation of the implicated mechanism(s). Administration of Fe-NTA (10 mg/kg bd wt, i.p.) to Swiss albino mice induced marked oxidative stress in kidney, evident from augmentation in renal metallothionein (MT) expression, depletion of glutathione content and activities of antioxidant and phase II metabolizing enzymes, and enhancement in production of aldehyde products such as 4-hydroxy-2-nonenal. F... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2592359 Fri, 10 Jul 2009 08:15:31 +0100 2592359 http://www.medworm.com/index.php?rid=2592360&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7052q55083008k31%2F Summary  We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m2 given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m2. The area under the concentration-time curve (AUC) and maximum concentration (C... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2592360 Thu, 09 Jul 2009 14:09:17 +0100 2592360 http://www.medworm.com/index.php?rid=2589699&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F72q15xq10011m035%2F Conclusions The combination of intravenous Myocet 40 mg/m2 on day 1 and ifosfamide 3,000 mg/m2 on days 1–3 every 3 weeks is safe and feasible; a phase II study is ongoing. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9288-7Authors Elisa Stroppa, Istituto Clinico Humanitas Department of Medical Oncology and Haematology Via Manzoni 56 Rozzano (Milan) 20089 ItalyAlexia Bertuzzi, Istituto Clinico Humanitas Department of Medical Oncology and Haematology Via Manzoni 56 Rozzano (Milan) 20089 ItalyGabriele Di Comite, Istituto Clinico Humanitas Department of Medical Oncology and Haematology Via Manzoni 56 Rozzano (Milan) 20089 ItalyChiara Mussi, Istituto Clinico Humanitas Department of Surgical Oncology Via Manzoni 56 Rozzano (Milan) 20... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2589699 Tue, 07 Jul 2009 15:38:57 +0100 2589699 http://www.medworm.com/index.php?rid=2589700&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn1042m157xv71118%2F The objective of the present study was to test the hypothesis that Calcidiol derivative B3CD qualifies as a potential anti-cancer drug in vivo employing an ovarian cancer xenograft model in mice. In addition, the selectivity of B3CD on viability and proliferation of platinum-resistant human ovarian cancer cell lines in comparison to control cell lines was analyzed in vitro. B3CD displayed cell line-specific cytotoxicity screened against a panel of ovarian and other carcinoma cell lines, endothelial and control cells. B3CD, at sub-cytotoxic concentrations, revealed stronger effects on the proliferation of SKOV-3 ovarian cancer cells vs. primary fibroblasts as determined by BrdU incorporation analysis. Treatment with B3CD at 0.5 µM resulted in highly condensed chromatin and fragme... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2589700 Tue, 07 Jul 2009 15:38:56 +0100 2589700 http://www.medworm.com/index.php?rid=2578137&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F41533720247256u4%2F Conclusion Reolysin administered monthly as a one-hour infusion is safe and well-tolerated even in multiple doses. Reolysin has anti-tumor activity as a single agent warranting further evaluation, including in combination with chemotherapy. Viral shedding may suggest intrapatient replication yielding a benefit and should be studied carefully in future studies. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9279-8Authors Radharani Gollamudi, Montefiore Medical Center Department of Oncology Bronx NY USAMohammad H. Ghalib, Montefiore Medical Center Department of Oncology Bronx NY USAKavita K. Desai, Montefiore Medical Center Department of Oncology Bronx NY USAImran Chaudhary, Montefiore Medical Center Department of Oncology Bronx NY USABenny Wong, Montefiore... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2578137 Mon, 06 Jul 2009 17:08:30 +0100 2578137 http://www.medworm.com/index.php?rid=2578138&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5447881626041l88%2F Conclusions Combined gemcitabine and vinorelbine therapy appears comparable to sequential monotherapy for heavily pretreated patients with metastatic breast cancer as demonstrated by improved quality of life outcomes with similar therapeutic efficacies and incidences of adverse events. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9285-xAuthors In Hae Park, Center for Breast Cancer, National Cancer Center 111 Jungbalsan-ro, Ilsandong-gu Goyang-si Gyeonggi-do 410-769 KoreaJungsil Ro, Center for Breast Cancer, National Cancer Center 111 Jungbalsan-ro, Ilsandong-gu Goyang-si Gyeonggi-do 410-769 KoreaKeun Seok Lee, Center for Breast Cancer, National Cancer Center 111 Jungbalsan-ro, Ilsandong-gu Goyang-si Gyeonggi-do 410-769 KoreaShi Nae Kim, Center for Clin... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2578138 Mon, 06 Jul 2009 16:17:09 +0100 2578138 http://www.medworm.com/index.php?rid=2564769&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2630282n61310155%2F Conclusions Darinaparsin could be safely administered with tolerable toxicity profiles, and no QTc prolongation in patients with advanced HCC. However, at this dose and schedule, it has shown no objective responses in HCC and this trial was terminated as planned after the first stage of efficacy analysis. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9286-9Authors Jennifer Wu, NYU School of Medicine Department of Medical Oncology New York NY USACharles Henderson, Piedmont Hospital Research Institute Department of Medical Oncology Atlanta GA USALynn Feun, University of Miami Hospital and Clinics Department of Medical Oncology Miami FL USAPeter Van Veldhuizen, Kansas City Veterans Administration Medical Center Department of Hematology and Medical Oncology... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2564769 Tue, 30 Jun 2009 15:44:48 +0100 2564769 http://www.medworm.com/index.php?rid=2549617&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa1224t6u5364n257%2F Conclusion: We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9282-0Authors Joseph A. Bauer, Akron Innovation Campus Bauer Research Foundation 411 Wolf Ledges Pkwy, suite 105 Akron OH 44311 USAGerald Frye, PetsDx Veterinary Imaging Pittsburgh PA 15237 USAAnne Bahr, PetRays Veterinary Radiology Consultants Spring TX 77386 USAJennifer Gieg, The Ohio State University Department of Veterinary Clin... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2549617 Fri, 26 Jun 2009 06:37:45 +0100 2549617 http://www.medworm.com/index.php?rid=2549618&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F30148104n171h085%2F Summary  The HIV protease inhibitor nelfinavir is an investigational drug for cancer treatment. We have previously demonstrated induction of apoptosis by nelfinavir even in chemo-resistant ovarian cancer cells. In contrast to the pro-apoptotic effect of nelfinavir on human cancer cells, we noticed a significant upregulation of the anti-apoptotic mitochondrial membrane protein mcl-1 by nelfinavir, resulting in a mitochondria-independent induction of apoptosis. Upregulation of mcl-1 was associated with enhanced phosphorylation of both mcl-1 and of ERK1/2 (extracellular signal-regulated kinases 1/2). ERK1/2 enhanced stability of mcl-1 protein expression by serine-163 phosphorylation. The combination of nelfinavir with sorafenib, a clinically applied inhibitor of the RAS/RAF/ER... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2549618 Thu, 25 Jun 2009 07:39:49 +0100 2549618 http://www.medworm.com/index.php?rid=2489028&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu2521m7061n01v46%2F Conclusion In conclusion, 90Y-ibritumomab with Bu/Cy/E and ASCT is feasible in patients with relapsed or refractory B-cell NHL, without increased toxicity. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9283-zAuthors Byung Woog Kang, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 388-1 Pungnap-2dong, Songpa-gu Seoul 138-736 KoreaWon Seog Kim, University of Sungkyunkwan University School of Medicine Department of Internal Medicine, Samsung Medical Center Seoul KoreaChul Kim, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 388-1 Pungnap-2dong, Songpa-gu Seoul 138-736 KoreaGeundoo Jang, University of Ulsan College of Medicine Department of Oncology, Asan Medical Center 388-1 Pungnap-2don... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2489028 Tue, 23 Jun 2009 06:08:40 +0100 2489028 http://www.medworm.com/index.php?rid=2489027&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4468212471876773%2F We report a case of patient with metastatic RCC treated with sunitinib with a diagnosis of tumor lysis syndrome. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9275-zAuthors Judith Michels, Département de Médecine Institut Gustave Roussy Villejuif FranceNathalie Lassau, Département d’Imagerie Institut Gustave Roussy Villejuif FranceMarine Gross-Goupil, Département de Médecine Institut Gustave Roussy Villejuif FranceChristophe Massard, Département de Médecine Institut Gustave Roussy Villejuif FranceArnaud Mejean, Service de Chirurgie Urologique, Hopital Necker Paris FranceBernard Escudier, Département de Médecine Institut Gustave Roussy Villejuif France Journal Investigational New DrugsOnline ISSN 1573-0646Print ISSN 0167-6997 (Source: Invest... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2489027 Tue, 23 Jun 2009 06:08:40 +0100 2489027 http://www.medworm.com/index.php?rid=2489026&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4n134qt7r22mx815%2F Summary  Vascular endothelial growth factor (VEGF) overexpression and increased angiogenesis have been proposed as having biologic importance in germ cell tumors (GCT). We conducted a single-institution phase II trial of sunitinib, an oral inhibitor of the VEGF receptor, in patients with relapsed or refractory GCT. A Simon’s two-stage design was used to determine the number of patients for enrollment. Responses were assessed using a modified version of Response Evaluation Criteria in Solid Tumors (RECIST), taking into account tumor marker changes. Dose modifications were made according to a nomogram for adverse events. Ten patients were enrolled. The first five received sunitinib 50 mg for four consecutive weeks, followed by a two-week break (4/2). Since four of five... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2489026 Tue, 23 Jun 2009 06:08:40 +0100 2489026 http://www.medworm.com/index.php?rid=2489030&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw2h2805230314332%2F Summary  The resistant cell line NCI-H460/R and its counterpart NCI-H460 were used to investigate the ability of purine analogs to overcome multidrug resistance (MDR) that seriously limit the efficacy of lung cancer regimens with chemotherapeutic agents. Two purine analogs, sulfinosine (SF) and 8-Cl-cAMP, exerted dose-dependent effects on cell growth in both parental and resistant cell lines. They significantly decreased mdr1 expression in NCI-H460/R cells. Low concentrations (1 µM) of SF and 8-Cl-cAMP in combination with doxorubicin (DOX) exerted synergistic growth inhibition in both cell lines. Pretreatment with SF and 8-Cl-cAMP improved the sensitivity to DOX more than verapamil (VER), the standard modulator of MDR. The increased accumulation of DOX observed after t... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2489030 Wed, 17 Jun 2009 09:44:59 +0100 2489030 http://www.medworm.com/index.php?rid=2489029&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F612531751484121x%2F In this study, we hypothesized that there might exist some compounds with less PPARγ agonistic activity but potent antitumor activity. Thereafter, we evaluated the PPARγ agonistic and antitumor activity of a novel series of α-aryloxy-α-methylhydrocinnamic acid derivatives synthesized with the initial aim of developing novel PPARγ agonists as hypoglycemic agents. MTT assay results revealed that several compounds were able to inhibit cell proliferation in a dose-dependent manner with IC50 12.7–29.7 μM, better than that of rosiglitazone (45.9–141 μM), although the PPARγ agonistic activity of most compounds is much lower than rosiglitazone. Some compounds induced cell cycle arrest and apoptosis tested by Flow Cytometry. Oral administration of DH9 (100 mg/kg/d) ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2489029 Wed, 17 Jun 2009 09:44:59 +0100 2489029 http://www.medworm.com/index.php?rid=2476893&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F412q26788m852403%2F Conclusion Thus, the study suggests that polyphenolic constituents of both cultivars of tea, i.e. green and black, have chemopreventive effects in DEN induced lung tumorigenesis in Swiss albino mice. Content Type Journal ArticleCategory PRECLINICAL STUDIESDOI 10.1007/s10637-009-9274-0Authors Preeti Roy, Indian Institute of Toxicology Research, (Council of Scientific & Industrial Research) Proteomics Laboratory P.O. Box 80 M.G. Marg, Lucknow 226001 IndiaNidhi Nigam, Indian Institute of Toxicology Research, (Council of Scientific & Industrial Research) Proteomics Laboratory P.O. Box 80 M.G. Marg, Lucknow 226001 IndiaMadhulika Singh, Indian Institute of Toxicology Research, (Council of Scientific & Industrial Research) Proteomics Laboratory P.O. Box 80 M.G. Marg, Lucknow 226001 IndiaJas... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2476893 Thu, 11 Jun 2009 14:19:05 +0100 2476893 http://www.medworm.com/index.php?rid=2476895&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk7510x3wp0024887%2F Summary  Benzothiazoles are multitarget agents with broad spectrum of biological activity. Among the antitumor agents discovered in recent years, the identification of various 2-(4-aminophenyl) benzothiazoles as potent and selective antitumor drugs against different cancer cell lines has stimulated remarkable interest. Some of the benzothiazoles are known to induce cell cycle arrest, activation of caspases and interaction with DNA molecule. Based on these interesting properties of benzothiazoles and to obtain new biologically active agents, a series of novel 4,5,6,7-tetrahydrobenzo[d]thiazole derivatives 5(a–i) were synthesized and evaluated for their efficacy as antileukemic agents in human leukemia cells (K562 and Reh). The chemical structures of the synthesized compoun... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2476895 Tue, 09 Jun 2009 16:09:50 +0100 2476895 http://www.medworm.com/index.php?rid=2459845&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F538432r42017vv72%2F Summary  To investigate the interactions of Epidermal Growth Factor Receptor (EGFR)-inhibiting tyrosine kinase inhibitors (TKIs) on P-gp-mediated drug resistance, we tested three TKIs, lapatinib, gefitinib and erlotinib in direct ATPase assays and in Non-Small Cell Lung Cancer (NCSLC) cell lines with defined low levels of growth factor receptor expression. The three TKIs potentiated the action of known P-gp substrate cytotoxic drugs at therapeutically-relevant concentrations. However, more detailed analysis revealed that the interaction of lapatinib with P-gp was distinct from that of gefitinib and erlotinib, and was characterised by direct inhibition of the stimulated P-gp ATPase activity. Lapatinib proved the most potent P-gp modulator of the TKIs examined. Drug transport... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2459845 Fri, 05 Jun 2009 08:58:42 +0100 2459845 http://www.medworm.com/index.php?rid=2459847&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc72627143l07t835%2F We report the case of reversible cardiogenic shock following 5-FU administration and discuss the different pitfalls of such toxicity. Oncologist should be aware of that rare but potentially lethal adverse event. Content Type Journal ArticleCategory SHORT REPORTDOI 10.1007/s10637-009-9271-3Authors Charles Ferté, Institut Gustave Roussy Phase I unit (SITEP), Department of Medicine 94805 Villejuif FranceCarlos Gomez Roca, Institut Gustave Roussy Phase I unit (SITEP), Department of Medicine 94805 Villejuif FranceYohann Loriot, Institut Gustave Roussy Phase I unit (SITEP), Department of Medicine 94805 Villejuif FranceRastislav Bahleda, Institut Gustave Roussy Phase I unit (SITEP), Department of Medicine 94805 Villejuif FranceCristian Moldovan, Institut Gustave Roussy Phase I unit (SITEP... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2459847 Fri, 05 Jun 2009 08:58:41 +0100 2459847 http://www.medworm.com/index.php?rid=2459846&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv205t323p373281q%2F Conclusion The MTD of combination therapy is imexon 1,300 mg/m2 IV on days 1–5 with docetaxel 75 mg/m2 IV on day 1 of a 21 day treatment cycle. Demonstrated responses warrant further investigation in phase II trials of which a phase II trial in NSCLC is planned. Content Type Journal ArticleCategory PHASE I STUDIESDOI 10.1007/s10637-009-9273-1Authors Stacy Moulder, University of Texas M. D. Anderson Cancer Center Breast Medical Oncology Unit 1354, 1155 Pressler Street P.O. Box 301438 Houston TX 77030 USANavneet Dhillon, University of Texas M. D. Anderson Cancer Center Investigational Cancer Therapeutics (Phase I Program) Houston USAChaan Ng, University of Texas M. D. Anderson Cancer Center Diagnostic Radiology Houston USADavid Hong, University of Texas M. D. Anderson ... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2459846 Fri, 05 Jun 2009 08:58:41 +0100 2459846 http://www.medworm.com/index.php?rid=2459848&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F403q243l318w27l0%2F In this study, we characterized the effects of LA-12 on tumor cell lines possessing wild type p53 and on p53-deficient/mutant cell lines and the results were compared to those obtained using cisplatin. We have determined changes of p53 levels, of its transcriptional activity, of its posttranscriptional modifications and the effect of the treatment on the cell cycle, on the induction of apoptosis and on gene expression. LA-12 induces weak accumulation of both transcriptionally active p53 tumor suppressor and of p21WAF1/CIP1 protein. LA-12 and cisplatin also significantly differ in their effects on apoptosis and cell cycle and on gene expression spectra in studied cell lines. LA-12 induces higher apoptosis levels in comparison with those induced by cisplatin, especially in p53-deficien... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2459848 Fri, 05 Jun 2009 08:58:40 +0100 2459848 http://www.medworm.com/index.php?rid=2459849&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F266l256u01158122%2F Summary  The S-methyl-thiosemicarbazones of the 2-hydroxy-R-benzaldehyde (R= H, 3-OH 3-OCH3 or 4-OCH3) reacted with the corresponding aldehydes in the presence of FeCl3 and NiCl2. New ONNO chelates of iron(III) and nickel(II) with hydroxy- or methoxy-substitued N 1,N 4-diarylidene-S-methyl-thiosemicarbazones were characterized by means of elemental analysis, conductivity and magnetic measurements, UV-Vis, IR and 1H-NMR spectroscopies. Cytotoxic activities of the compounds were determined using K562 chronic myeloid leukemia and ECV304 human endothelial cell lines by MTT assay. It was determined that monochloro N 1-4-methoxysalicylidene-N 4-4-methoxysalicylidene-S-methyl-thiosemicarbazidato-iron(III) complex showed selective anti-leukemic effects in K562 cells while has no ef... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2459849 Thu, 04 Jun 2009 11:19:45 +0100 2459849 http://www.medworm.com/index.php?rid=2443858&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp1hh3866523j6028%2F This study evaluated the activity of an mTOR inhibitor, RAD001 (Everolimus, Novartis Pharma AG, Switzerland), in 5 NPC cell lines (HK1, HONE-1, CNE-1, CNE-2, C666-1), 2 cisplatin-resistant NPC cell lines and their respective parental cell lines (HK1-LMP1, HONE-1-EBV). RAD001 inhibited cell growth in a dose-dependent manner at nanomolar concentrations in all cell lines. HONE-1 was most sensitive to RAD001 (IC50 = 0.63 nM, 60% maximal inhibition), while Het-1A (a normal esophageal epithelial cell line) was relatively resistant. No consistent relationship between sensitivity to RAD001 and basal expression of pi-mTOR and pi-p70S6 Kinase-1 (p70S6K) was found. Exposure to RAD001 at picomolar concentrations for 48 h resulted in reduction of pi-mTOR and pi-p70S6K1 expression, b... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2443858 Wed, 27 May 2009 06:10:39 +0100 2443858 http://www.medworm.com/index.php?rid=2437730&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvw834pvj56129719%2F Summary  There are two highly selective antibodies to the epidermal growth factor receptor (EGFR) now available for use in metastatic colorectal cancer (mCRC). In KRAS wild type patients, cetuximab (Cmab)-an IgG1 chimeric molecule—has activity alone and in combination with chemotherapy for the first, second and third-line settings. Panitumumab (Pmab)-a fully humanized IgG2 molecule-has activity as a single agent in chemorefractory mCRC and shows promising activity in combination with chemotherapy. It remains unclear which antibody to use. This retrospective review of our experience with Pmab in 13 EGFR antibody-naive patients and in 22 patients previously treated with Cmab for mCRC highlights a lack of hypersensitivity reactions (HSR) with Pmab, even in patients who exper... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2437730 Tue, 26 May 2009 07:40:11 +0100 2437730 http://www.medworm.com/index.php?rid=2437731&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk0r7txr487342884%2F Summary  Arsenic trioxide (ATO) is an inorganic arsenic derivative that is highly effective against PML-RARα-positive leukemia but much less against other hematological malignancies. We synthesized an organic arsenic derivative (OAD), S-dimethylarsino-thiosuccinic acid (MER1), which offers a superior toxicity profile and comparable in vitro activity relative to ATO. In Swiss Webster mice, maximally-tolerated cumulative dose of MER1 when given IV for 5 days was 100 mg/kg/d. We demonstrated that MER1 induced apoptosis and dose- and time-dependent inhibition of survival and growth in a panel of myeloid leukemia cell lines. Unlike ATO, this activity was independent of PML-RARα status and was not associated with induction of myeloid maturation. In NB4 and HL60 cells, ME... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2437731 Tue, 26 May 2009 07:40:09 +0100 2437731 http://www.medworm.com/index.php?rid=2429437&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk000h5474w571887%2F Summary  Limonoids from the neem tree (Azadirachta indica) have attracted considerable research attention for their cytotoxicity against human cancer cell lines. However, the antiproliferative and apoptosis inducing effects of neem limonoids have not been tested in animal tumour models. The present study was therefore designed to evaluate the relative chemopreventive potential of the neem limonoids azadirachtin and nimbolide in the hamster buccal pouch (HBP) carcinogenesis model by analyzing the expression of proliferating cell nuclear antigen (PCNA), p21waf1, cyclin D1, glutathione S-transferase pi (GST-P), NF-κB, inhibitor of κB (IκB), p53, Fas, Bcl-2, Bax, Bid, Apaf-1, cytochrome C, survivin, caspases-3, −6, −8 and −9, and poly(ADP-ribose) polymerase (PARP) by RT-... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2429437 Thu, 21 May 2009 06:11:20 +0100 2429437 http://www.medworm.com/index.php?rid=2418793&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh66h325234706302%2F Conclusion The IROX regimen appears to constitute a feasible and tolerable salvage therapy in patients with advanced pancreatic cancer who have been previously treated with gemcitabine- and 5-FU-based chemotherapy. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9265-1Authors Sung Yong Oh, Dong-A University College of Medicine Department of Internal Medicine Busan KoreaHyun Jin Kim, Gyeongsang National University School of Medicine Department of Internal Medicine Jinju KoreaTae Hyo Kim, Gyeongsang National University School of Medicine Department of Internal Medicine Jinju KoreaGyeong-Won Lee, Gyeongsang National University School of Medicine Department of Internal Medicine Jinju KoreaHoon Gu Kim, Gyeongsang National University School of Medicine Departmen... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2418793 Fri, 15 May 2009 06:17:40 +0100 2418793 http://www.medworm.com/index.php?rid=2418794&cid=s_33392_13_f&fid=33392&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3m047327w13675u6%2F Summary  Here, we synthesized two phospha sugar derivatives, 2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide (TMPP) and 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (DMPP) by reacting 3-methyl-1-phenyl-2-phospholene 1-oxide with bromine, and investigated their potential as antileukemic agents in cell lines. Both agents showed inhibitory effects on leukemia cell proliferation, with mean IC50 values of 6.25 μmol/L for TMPP and 23.7 μmol/L for DMPP, indicating that inhibition appeared to be dependent on the number of bromine atoms in the structure. Further, TMPP at 10 μmol/L and DMPP at 20 μmol/L induced G2/M cell cycle block in leukemia cells, and TMPP at 20 μmol/L induced apoptosis in these cells. TMPP treatment effected a reduction in bot... Investigational New Drugs journals http://www.medworm.com/rss/comments.php?id=2418794 Wed, 13 May 2009 06:19:44 +0100 2418794