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CYT997 Causes apoptosis in human multiple myelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 proli...
Source: Investigational New Drugs - November 11, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Astaxanthin inhibits tumor invasion by decreasing extracellular matrix production and induces apoptosis in experimental rat colon carcinogenesis by modulating the expressions of ERK-2, NFkB and COX-2Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 - October 30, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Inhibition of MDR1 activity and induction of apoptosis by analogues of nifedipine and diltiazem: an in vitro analysisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Bol...
Source: Investigational New Drugs - October 29, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

A coumarin derivative (RKS262) inhibits cell-cycle progression, causes pro-apoptotic signaling and cytotoxicity in ovarian cancer cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 o...
Source: Investigational New Drugs - October 29, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNGEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-kapp...
Source: Investigational New Drugs - October 22, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Tolfenamic acid decreases c-Met expression through Sp proteins degradation and inhibits lung cancer cells growth and tumor formation in orthotopic miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 nu...
Source: Investigational New Drugs - October 22, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Phase II trial of pyrazoloacridine (NSC#366140) in patients with metastatic breast cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Investigational New Drugs - October 21, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Efficacy of Caffeic Acid Phenethyl Ester (CAPE) in skin B16-F0 melanoma tumor bearing C57BL/6 miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 an...
Source: Investigational New Drugs - October 21, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

TNF-blockade in patients with advanced hormone refractory prostate cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Baltim...
Source: Investigational New Drugs - October 21, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Characterization of the cell growth inhibitory effects of a novel DNA-intercalating bipyridyl-thiourea-Pt(II) complex in cisplatin-sensitive and—resistant human ovarian cancer cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Investigational New Drugs - October 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

A phase II, multicenter study of cetuximab monotherapy in patients with refractory, metastatic colorectal carcinoma with absent epidermal growth factor receptor immunostainingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Centr...
Source: Investigational New Drugs - October 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, Universi...
Source: Investigational New Drugs - October 14, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Phase I trial of vinflunine and pemetrexed in refractory solid tumorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Nor...
Source: Investigational New Drugs - October 14, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Initial cytoreductive treatment with thalidomide plus bolus vincristine/doxorubicin and reduced dexamethasone followed by autologous stem cell transplantation for multiple myelomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, Severa...
Source: Investigational New Drugs - October 13, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Mechanisms for the activity of heterocyclic cyclohexanone curcumin derivatives in estrogen receptor negative human breast cancer cell linesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Dep...
Source: Investigational New Drugs - October 9, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Chemopreventive doses of resveratrol do not produce cardiotoxicity in a rodent model of hepatocellular carcinomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 che...
Source: Investigational New Drugs - October 8, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Role of Neridronate on MCF-7 estrogen dependent breast cancer model of bone metastasis: a preliminary studyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Investigational New Drugs - October 1, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

PKC-alpha inhibitor MT477 slows tumor growth with minimal toxicity in in vivo model of non-Ras-mutated cancer via induction of apoptosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Investigational New Drugs - September 30, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Antitumor activity and toxicity of anti-HER2 immunoRNase scFv 4D5-dibarnase in mice bearing human breast cancer xenograftsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Investigational New Drugs - September 29, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Antimetastatic activity of MONCPT in preclinical melanoma mice modelEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Investigational New Drugs - September 29, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

TAE226-mediated inhibition of focal adhesion kinase interferes with tumor angiogenesis and vasculogenesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, Hubertu...
Source: Investigational New Drugs - September 29, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Structure-activity relationships between the Aconitum C20-diterpenoid alkaloid derivatives and the growth suppressive activities of Non-Hodgkin’s lymphoma Raji cells and human hematopoietic stem/progenitor cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 positi...
Source: Investigational New Drugs - September 29, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Preclinical activity of F14512, designed to target tumors expressing an active polyamine transport systemEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 majo...
Source: Investigational New Drugs - September 24, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplificationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Investigational New Drugs - September 24, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

A phase I study of rebeccamycin analog in combination with oxaliplatin in patients with refractory solid tumorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 w...
Source: Investigational New Drugs - September 23, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity, inhibits AR nuclear translocation and prostate cancer cell growthEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Investigational New Drugs - September 22, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

A phase I study of zibotentan (ZD4054) in patients with metastatic, castrate-resistant prostate cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Ave...
Source: Investigational New Drugs - September 18, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Factual understanding of randomized clinical trials: a multicenter case-control study in cancer patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Investigational New Drugs - September 17, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Lovastatin overcomes gefitinib resistance in human non-small cell lung cancer cells with K-Ras mutationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 cytoto...
Source: Investigational New Drugs - September 17, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Phase I clinical and pharmacokinetic study of sorafenib in combination with carboplatin and paclitaxel in patients with advanced non–small cell lung cancerEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Investigational New Drugs - September 17, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Antitumor activity of natural compounds, curcumin and PKF118-310, as Wnt/β-catenin antagonists against human osteosarcoma cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 perform...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Studies on the neuroprotective role of Piper longum in C6 glioma induced ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Phase I/II study of sunitinib malate in Japanese patients with gastrointestinal stromal tumor after failure of prior treatment with imatinib mesylateEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Medicin...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Dysphonia induced by vascular endothelium growth factor/vascular endothelium growth factor receptor inhibitorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Depa...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

DH9, a novel PPARγ agonist suppresses the proliferation of ADPKD epithelial cells: An association with an inhibition of β-catenin signalingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 med...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Preclinical activity of gefitinib in non-keratinizing nasopharyngeal carcinoma cell lines and biomarkers of responseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 signi...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Salvage therapy with gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for B-cell non-Hodgkin’s lymphoma: a consortium for improving survival of lymphoma (CISL) trialEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 So...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Justification of the starting dose as the main determinant of accrual time in dose-seeking oncology phase 1 trialsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Os...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Bevacizumab for salvage treatment of metastatic breast cancer: a systemic review and meta-analysis of randomized controlled trialsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Synthesis, characterization and in vitro anti-tumor activities of novel 9-ethyl-9H-purine derivativesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, SA...
Source: Investigational New Drugs - September 15, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Painful cervical esophageal erosion in a patient with advanced colorectal cancer treated with bevacizumabEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Investigational New Drugs - September 3, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Gemcitabine plus enzastaurin or single-agent gemcitabine in locally advanced or metastatic pancreatic cancer: Results of a Phase II, randomized, noncomparative studyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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....
Source: Investigational New Drugs - August 28, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Synthesis and biological properties of oxazolinodaunorubicin—a new derivative of daunorubicin with a modified daunosamine moietyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 l...
Source: Investigational New Drugs - August 27, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Scaling the time-course of myelosuppression from rats to patients with a semi-physiological modelEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Bioscien...
Source: Investigational New Drugs - August 27, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

In vitro cytotoxic evaluation of novel dichlorodiorgano[N-(2-pyridylmethylene)arylamine]tin(IV) derivatives in human tumor cell linesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 whic...
Source: Investigational New Drugs - August 27, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

MT7, a novel compound from a combinatorial library, arrests mitosis via inhibiting the polymerization of microtubulesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 w...
Source: Investigational New Drugs - August 24, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Phase II study of gemcitabine and carboplatin in metastatic breast cancers with prior exposure to anthracyclines and taxanesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-Oncolog...
Source: Investigational New Drugs - August 24, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Involvement of non-protein thiols, mitochondrial dysfunction, reactive oxygen species and p53 in honey-induced apoptosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Investigational New Drugs - August 24, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

Oral metronomic cyclophosphamide in elderly with metastatic melanomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Régio...
Source: Investigational New Drugs - August 11, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals

The epothilone B analogue ixabepilone in patients with advanced hepatobiliary cancers: a trial of the University of Chicago Phase II ConsortiumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 S...
Source: Investigational New Drugs - August 11, 2009 Category: Drugs & Pharmacology Tags: Investigational New Drugs Source Type: journals