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 'Cancer Biology and Therapy' source. Sun, 21 Mar 2010 13:51:56 +0100 http://www.medworm.com/index.php?rid=3363023&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20224297%26dopt%3DAbstract Authors: He Q, Shi J, Shen XL, An J, Sun H, Wang L, Hu YJ, Sun Q, Fu LC, Sheikh MS, Huang Y Dihydroartemisinin (DHA) is a derivative of artemisinin and is an effective anti-malaria therapeutic used worldwide. In this paper, we report that DHA is as a potential anti-cancer drug for prostate cancer. Our data indicate that DHA suppresses the PI3-K/Akt and ERK cell survival pathways and triggers the induction of death receptor DR5 and activation of extrinsic and intrinsic cell death signaling. DHA-mediated DR5 induction appears to occur via increased transcriptional activity of DR5 promoter. Our data also show that, while DHA has strong cytotocixity in tumor cells, it exhibits minimal cytotoxic effects on normal prostate epithelial cells. Our studies also demonstrate that DHA worked cooper... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3363023 Sun, 14 Mar 2010 07:02:04 +0100 3363023 http://www.medworm.com/index.php?rid=3355245&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20215859%26dopt%3DAbstract Authors: Kaul D, Wu CL, Adkins CB, Jordan KW, Defeo EM, Habbel P, Peterson RT, McDougal WS, Pohl U, Cheng LL Statistical data from prostate cancer (PCa) clinics indicates that a large patient population discovered by annual prostate specific antigen (PSA ) screening may have a latent form of the disease. However, current medical tests cannot differentiate slow from fast growing PCa, resulting in many unnecessary radical treatments and morbidities. It is thus necessary to find new screening tests that enable us to differentiate between fast- and slow-growing tumors. Inspired by the reported functions of spermine in carcinogenesis, we analyzed spermine and mRNA expression levels of rate-limiting enzymes in the spermine metabolic pathway for nine cases of PCa with accurately defined PSA v... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3355245 Fri, 12 Mar 2010 10:04:11 +0100 3355245 http://www.medworm.com/index.php?rid=3355244&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20215863%26dopt%3DAbstract Conclusion: Compliant with previous published data concerning VDA and chemotherapy treatment, liver surgery induces an instantaneous release of EPCs, conceivably in response to elevated G-CSF levels. This suggests the value of exploring therapeutic avenues to prevent this process. PMID: 20215863 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3355244 Fri, 12 Mar 2010 10:04:08 +0100 3355244 http://www.medworm.com/index.php?rid=3355243&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20215864%26dopt%3DAbstract Authors: Mackintosh C, Madoz-Gúrpide J, Ordóñez JL, Osuna D, Herrero-Martín D Ewing's sarcoma family tumors (ESFT) are a group of aggressive solid bone and soft tissue malignancies of children and young adults characterized by specific chromosomal translocations that give rise to EWS-ETS aberrant transcription factors. Identification of EWS-ETS target genes and their role in tumor signaling networks together with the unravelling of the cell of origin will facilitate the translation into new treatment modalities for these neoplasms. PMID: 20215864 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3355243 Fri, 12 Mar 2010 10:04:05 +0100 3355243 http://www.medworm.com/index.php?rid=3338567&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20200483%26dopt%3DAbstract Authors: David KA, Mongan NP, Smith C, Gudas LJ, Nanus DM Retinoic acid derivatives have shown their greatest benefit in acute promyelocytic leukemia, but have also demonstrated pre-clinical anti-cancer effects in some solid tumors. Histone deacetylase inhibitors, by upregulating gene expression, are able to limit cancer cell proliferation and induce apoptosis. The combination of all-trans retinoic acid (ATRA) and the histone deacetylase inhibitor valproic acid has been previously studied in hematologic malignancies. We conducted a phase I two-step dose escalation trial of the liposomal ATRA analog ATRA-IV and divalproex sodium (Depakote((R))) in nine patients with advanced solid tumors refractory to prior therapy. Side effects attributed to therapy had a severity </=grade 2 and inc... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3338567 Sat, 06 Mar 2010 19:28:14 +0100 3338567 http://www.medworm.com/index.php?rid=3338566&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20200484%26dopt%3DAbstract Authors: Yan X, Shah W, Jing L, Chen H, Wang Y The tumor suppressor p27(Kip1) is an inhibitor of cyclin/cyclin-dependent kinase (CDK) complexes and plays a crucial role in cell cycle regulation. Nevertheless, p27 function in the tumorigenesis of the uterine cervix has been poorly defined. Some phenomenon hints that HPV E7 protein can enhance p27 expression, which is contradictory to HPV E7's property of increasing cell proliferation rate. So, in the present study, we have examined the effect of E7 on p27 expression. Though the levels of p27 are increased after HPV E7 expression, most of the p27 protein localized in the cytoplasm and have no function on cell cycle arrest and contact inhibition. The cell migration rate is elevated when p27 is high expression and located in cytoplasm. The... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3338566 Sat, 06 Mar 2010 19:28:11 +0100 3338566 http://www.medworm.com/index.php?rid=3338565&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20200485%26dopt%3DAbstract Authors: Yuan W, Wu S, Guo J, Chen Z, Ge J, Yang P, Hu B, Chen Z Tumorigenesis requires energy production via aerobic glycolysis (the Warburg effect) in malignant tumors. Recent research has demonstrated that the pentose phosphate pathway (PPP ) is augmented in some tumors, especially the non-oxidative part of the PPP which is controlled by transketolase (TKT) enzyme reactions. One TKT isoform, transketolase-like protein 1 (TKTL1), is specifically upregulated in different human cancers, and its overexpression predicts poor patient survival. To further define the function of in malignant progression, we employed the small interference RNA (siRNA) technique to knockdown gene expression of TKTL1 in the gastric cancer cell line AGS. We used TKTL1 siRNA to observe the effect of reduced TKTL... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3338565 Sat, 06 Mar 2010 19:28:08 +0100 3338565 http://www.medworm.com/index.php?rid=3338564&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20200495%26dopt%3DAbstract Authors: Carney BK, Cassimeris L Stathmin, a microtubule regulatory protein, is overexpressed in many cancers and required for survival of several cancer lines. In a study of breast cancer cell lines, Alli et al. (Oncogene. 26:1003-12) proposed that stathmin is required for survival of cells lacking p53, but this hypothesis was not tested directly. Here we tested their hypothesis by examining cell survival in cells depleted of stathmin, p53 or both proteins. Comparing HCT116 colon cancer cell lines differing in TP53 genotype, stathmin depletion resulted in significant death only in cells lacking p53. As a second experimental system, we compared the effects of stathmin depletion from HeLa cells, which normally lack detectable levels of p53 due to expression of the HPV E6 protein. Stathm... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3338564 Sat, 06 Mar 2010 19:28:05 +0100 3338564 http://www.medworm.com/index.php?rid=3288313&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160495%26dopt%3DAbstract Authors: Nair BC, Vadlamudi RK PMID: 20160495 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3288313 Fri, 19 Feb 2010 19:22:05 +0100 3288313 http://www.medworm.com/index.php?rid=3270192&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20150760%26dopt%3DAbstract Authors: Holland PM, Miller R, Jones J, Douangpanya H, Piasecki J, Roudier M, Dougall WC In bone metastases, tumor cells interact with the bone microenvironment to induce osteoclastogenesis, leading to bone destruction and growth factor release. RANK ligand (RANKL) is essential for osteoclast formation, function and survival. Tumor cell-mediated osteolysis is thought to occur ultimately via induction of RANKL within the bone stroma, and inhibition of RANKL in models of breast cancer bone metastases blocks tumor-induced osteolysis and reduces skeletal tumor burden. In addition, the skeleton is co-opted by tumor cells and functions as a supportive tumor microenvironment. Inhibition of RANKL, by reducing tumor-induced osteoclastogenesis, may reduce the local release of growth factors and ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3270192 Sun, 14 Feb 2010 05:16:17 +0100 3270192 http://www.medworm.com/index.php?rid=3270191&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20150761%26dopt%3DAbstract Authors: Indovina P, Giordano A PMID: 20150761 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3270191 Sun, 14 Feb 2010 05:16:14 +0100 3270191 http://www.medworm.com/index.php?rid=3270190&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20150762%26dopt%3DAbstract In this study, we demonstrate that conatumumab binds to DR5, activating intracellular caspases in vitro in the presence of a cross-linker. We also show that conatumumab has activity in vivo and inhibits tumor growth in colon (Colo205 and HCT-15), lung (H2122) and pancreatic (MiaPaCa2/T2) xenograft models. Conatumumab also enhances the anti-tumor activity of chemotherapeutics in vivo. Caspase activation in Colo205 tumors is dose-dependent and correlated with serum concentrations of conatumumab. We demonstrate for the first time that increases in serum caspase-3/7 activity and levels of M30 (neoepitope of caspase-cleaved cytokeratin-18) are linked to activation of the extrinsic apoptotic pathway using conatumumab in a preclinical model. These data suggest that conatumumab has potential as a ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3270190 Sun, 14 Feb 2010 05:16:11 +0100 3270190 http://www.medworm.com/index.php?rid=3270189&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20150764%26dopt%3DAbstract Conclusion: The antitumor activity of Ad-miR122 was probably due to the induction of apoptosis and/or cell cycle arrest in cancer cells through inhibiting Bcl-W and/or CCNG1 expression. We concluded that expression of therapeutic microRNA, such as miR-122, via adenoviral vector is a promising strategy for cancer treatment. PMID: 20150764 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3270189 Sun, 14 Feb 2010 05:16:08 +0100 3270189 http://www.medworm.com/index.php?rid=3270188&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20150768%26dopt%3DAbstract Authors: Roh M, Abdulkadir SA PMID: 20150768 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3270188 Sun, 14 Feb 2010 05:16:05 +0100 3270188 http://www.medworm.com/index.php?rid=3255551&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20139704%26dopt%3DAbstract Authors: Drake JM, Danke JR, Henry MD Advanced prostate cancer frequently metastasizes to bone and remains an incurable disease. One recent experimental therapy involves endothelin receptor A (ETA) antagonists (e.g., atrasentan). Clinical results to date have been mixed, with atrasentan not meeting its primary endpoints in a Phase III trial. It remains an open question whether some patients might benefit from this therapy, while others may not. Preclinical data supports the concept that the endothelin signaling axis may be particularly important for tumor growth in bone, but the extent to which it is involved in metastatic colonization of other organ sites in prostate cancer remains unclear. Here we evaluate the efficacy of atrasentan in a mouse model of prostate cancer metastatic colo... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3255551 Wed, 10 Feb 2010 11:02:10 +0100 3255551 http://www.medworm.com/index.php?rid=3255550&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20139705%26dopt%3DAbstract Authors: Sarkar S, Mazumdar A, Dash R, Sarkar D, Fisher PB, Mandal M Abnormalities in gene expression and signaling pathways downstream of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) contribute to the progression, invasion, and maintenance of the malignant phenotype in human cancers, including breast. Consequently, the dual kinase inhibitor of EGFR and VEGFR ZD6474 represents a promising biologically-based treatment that is currently undergoing clinical trials for non-small cell lung cancer. Patients suffering from breast cancers have a poor prognosis because of the lack of effective agents and treatment strategies. We hypothesized that inhibition of phosphorylation of the EGFR and VEGFR by ZD6474 would inhibit breast cancer cell ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3255550 Wed, 10 Feb 2010 11:02:08 +0100 3255550 http://www.medworm.com/index.php?rid=3255549&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20139722%26dopt%3DAbstract Authors: Cherrin C, Haskell K, Howell B, Jones R, Leander K, Robinson R, Watkins A, Bilodeau M, Hoffman J, Sanderson P, Hartman G, Mahan E, Prueksaritanont T, Jiang G, She QB, Rosen N, Sepp-Lorenzino L, Defeo-Jones D, Huber HE The PI3K-Akt pathway is dysregulated in the majority of solid tumors. Pharmacological inhibition of Akt is a promising strategy for treating tumors resistant to growth factor receptor antagonists due to mutations in PI3K or PTEN. We have developed allosteric, isozyme-specific inhibitors of Akt activity and activation, as well as ex vivo kinase assays to measure inhibition of individual Akt isozymes in tissues. Here we describe the relationship between PK, Akt inhibition, hyperglycemia and tumor efficacy for a selective inhibitor of Akt1 and Akt2 (AKTi). In nude m... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3255549 Wed, 10 Feb 2010 11:02:05 +0100 3255549 http://www.medworm.com/index.php?rid=3221260&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20107314%26dopt%3DAbstract Authors: Hamed HA, Yacoub A, Park MA, Eulitt P, Sarkar D, Dimitriev IP, Chen CS, Grant S, Curiel DT, Fisher PB, Dent P The present studies focused on determining whether the autophagy-inducing drug OSU-03012 (AR-12) could enhance the toxicity of recombinant adenoviral delivery of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) in glioblastoma multiforme (GBM) cells. The toxicity of a recombinant adenovirus to express MDA-7/IL-24 (Ad.mda-7) was enhanced by OSU-03012 in a diverse panel of primary human GBM cells. The enhanced toxicity correlated with reduced ERK1/2 phosphorylation and expression of MCL-1 and BCL-X(L), and was blocked by molecular activation of ERK1/2 and by inhibition of the intrinsic, but not the extrinsic, apoptosis pathway. Both OSU-03012 and e... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3221260 Sat, 30 Jan 2010 06:06:09 +0100 3221260 http://www.medworm.com/index.php?rid=3221259&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20107315%26dopt%3DAbstract In this study, the effects of MK-1775 on 5-fluorouracil (5-FU) and other DNA-damaging agents with different modes of action were determined. MK-1775 enhanced the cytotoxic effects of 5-FU in p53-deficient human colon cancer cells. MK-1775 inhibited CDC2 Y15 phosphorylation in cells, abrogated DNA damaged checkpoints induced by 5-FU treatment, and caused premature entry of mitosis determined by induction of Histone H3 phosphorylation. Enhancement by MK-1775 was specific for p53-deficient cells since this compound did not sensitize p53-wild type human colon cancer cells to 5-FU in vitro. In vivo, MK-1775 potentiated the anti-tumor efficacy of 5-FU or its prodrug, capecitabine, at tolerable doses. These enhancements were well correlated with inhibition of CDC2 phosphorylation and induction of... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3221259 Sat, 30 Jan 2010 06:06:05 +0100 3221259 http://www.medworm.com/index.php?rid=3198030&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20087061%26dopt%3DAbstract Authors: Shi Y, Amin K, Sato BG, Samuelsson SJ, Sambucetti L, Haroon ZA, Laderoute K, Murphy BJ We previously identified metal-responsive transcription factor-1 (MTF-1) as a positive contributor to mouse fibrosarcoma growth through effects on cell survival, proliferation, tumor angiogenesis and extracellular matrix remodeling. In the present study, we investigated MTF-1 protein expression in human tissues by specific immunostaining of both normal and tumor tissue samples. Immunohistochemical (IHC) staining of a human tissue microarray (TMA), using a unique anti-human MTF-1 antibody, indicated constitutive MTF-1 expression in most normal tissues, with liver and testis displaying comparatively high levels of expression. Nevertheless, MTF-1 protein levels were found to be significantly el... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3198030 Fri, 22 Jan 2010 19:06:05 +0100 3198030 http://www.medworm.com/index.php?rid=3164785&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061791%26dopt%3DAbstract Authors: Baum CE, Ockers SB, English BC, Price DK, Sartor O, Figg WD The androgen receptor gene (AR) plays an important role in molecular signaling and regulation and the subsequent cellular growth of prostate cancer. In addition, it is a highly variable region of the genome. We used direct nucleotide sequencing to genotype the entire exogenous coding region of the androgen receptor in ten commonly used prostate cancer cell lines. Our analysis confirmed the presence or absence of several known SNPs in the cell lines studied. We also assayed the number of CAG-repeat and GGC-repeat sequences for each for the ten cell lines. Our analysis identified three new mutations, one each in the DU145, LnCAP and RWPE-2 cell lines. In DU145, the DNA isolated in our lab was heterozygous at G527G (T&gt... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3164785 Wed, 13 Jan 2010 11:50:21 +0100 3164785 http://www.medworm.com/index.php?rid=3164784&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061804%26dopt%3DAbstract Authors: Long X, Fan M, Nephew KP Fulvestrant (ICI 182, 780) is a selective estrogen receptor downregulator (SERD) and potent antiestrogen. In estrogen receptor alpha positive ERalpha(+) breast cancer, the drug immobilizes ERalpha in the nuclear matrix, inducing receptor polyubiquitination and subsequent degradation via the 26S proteasome. We previously reported that fulvestrant-induced ERalpha degradation depends on the interaction of ERalpha with cytokeratins 8 and 18 (CK8/CK18). Here we further investigate the role of these two cytokeratins in the antagonistic activity of the SERD. Using ER-responsive reporter assays, we demonstrate greater antiestrogenic activity of fulvestrant in CK8/CK18(+) vs. CK8/CK18(-) cancer cells and loss of CK8/CK18 expression was observed in a breast canc... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3164784 Wed, 13 Jan 2010 11:50:18 +0100 3164784 http://www.medworm.com/index.php?rid=3164783&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061812%26dopt%3DAbstract Authors: Tan L, Xu B, Liu R, Liu H, Tan H, Huang W AML has a dismal prognosis. It was previously shown that the expression of gene coding for the hyperfusogenic gibbon ape leukemia virus envelope glycoprotein (GALV.fus) can efficiently kill leukemic cells. However, target killing effect of GALV.fus on leukemia cells may be limited. Viral vectors, such as retroviruses and adenoviruses, have been developed to deliver heterologous genes into tumors in vivo, but these vectors have some limitations for gene therapy of leukemia. Another virus that has drawn interest as a gene transfer vector is the Sindbis virus. Sindbis virus efficiently infects human tumor cells through the high-affinity 67 kDa Laminin receptor. We found that Laminin-R was obviously expressed in HL-60 and primary human AML... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3164783 Wed, 13 Jan 2010 11:50:15 +0100 3164783 http://www.medworm.com/index.php?rid=3164782&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061814%26dopt%3DAbstract This study explores expression of glutamate receptor subunits in pediatric CNS tumors. Samples from 8 ependymomas, 4 glioblastomas, 6 medulloblastomas and 8 low grade astrocytomas were analysed. RNA was used for semiquantitative and quantitative RT-PCR. We examined expression of NMDA receptor subunits NR1-NR3B, AMPA receptor subunits GluR1-GluR4, kainate receptor subunits GluR5-GluR7, KA1, KA2 and metabotropic receptor subunits mGluR1-8. Paraffin embedded samples were immunohistochemically stained for selected subunits. All glutamate receptor subunits were differentially expressed in the tumors examined. Expression of NR2D, NR3A, KA1, GluR4, mGluR1, mGluR4, mGluR5 and mGluR6 was higher in the high grade tumors compared to human brain (HB). In low grade astrocytomas expression of glutamate ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3164782 Wed, 13 Jan 2010 11:50:12 +0100 3164782 http://www.medworm.com/index.php?rid=3164781&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061818%26dopt%3DAbstract Conclusion: More than 10% RTA in SLN, extranodal invasion and centripetal metastasis thickness all predict additional lymph node metastases in melanoma site draining basins. Moreover, high CXCR4 expression is correlated to shorter DFS and could be used as a prognostic marker in order to stratify melanoma patients at higher progression risk. PMID: 20061818 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3164781 Wed, 13 Jan 2010 11:50:09 +0100 3164781 http://www.medworm.com/index.php?rid=3164780&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20061819%26dopt%3DAbstract Authors: Gabarra V, Cho S, Ramirez M, Ren Y, Chen LL, Cheung A, Cao X, Rennard R, Unruh KR, Graff CP, Browning B, Huet HA, McLachlan K Integrin alpha6beta4 signaling interactions have been implicated in tumor progression, and beta4 expression has been linked to poor prognosis in certain breast cancer subtypes. We generated human antibodies to alpha6beta4 to further evaluate its role in tumor cell signaling. Biochemical characterization indicated these antibodies are specific for alpha6beta4, recognize distinct epitopes and have low nanomolar affinities for both human and murine protein. The antibodies demonstrated differing effects on alpha6beta4-mediated cellular adhesion, highlighting the existence of different functional epitopes on alpha6beta4. Interestingly however both antibodies... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3164780 Wed, 13 Jan 2010 11:50:06 +0100 3164780 http://www.medworm.com/index.php?rid=3130302&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20038821%26dopt%3DAbstract Authors: De Larco JE, Park CA, Dronava H, Furcht LT Antioxidants have been shown to provide protection against carcinogens, toxic xenobiotics and oxidative stress. This has led to the hypothesis that the addition of antioxidants to cancer chemotherapeutic regimens could increase their efficacy while reducing the side effects often encountered during treatment. The work described in this study set out to test this hypothesis using two different chemotherapeutics, Paclitaxel and FUdR, and three different antioxidants, epigallocatechin gallate, phenethyl isothiocyanate and tert-butylhydroquinone. Experiments were carried out on two different breast carcinoma cell lines, MCF-7 and MDA MB435S. Importantly, we did not observe an enhancement of the efficacy of the chemotherapeutic agents in t... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3130302 Thu, 31 Dec 2009 11:50:05 +0100 3130302 http://www.medworm.com/index.php?rid=3115726&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20023412%26dopt%3DAbstract Conclusions: The DDR pathway was activated during cancer progression, but no apoptosis was detected, even among the cells with activated DDR. It is likely that activation of DDR was induced by stress signaling as a consequence of oxidative, replication and mechanical stresses occurring during growth and expansion of the colorectal cancer. PMID: 20023412 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3115726 Thu, 24 Dec 2009 01:48:16 +0100 3115726 http://www.medworm.com/index.php?rid=3115725&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20023417%26dopt%3DAbstract In this study, we found that the CaMKII inhibitor KN-93 has a broader effect on apoptosis than just inhibition of CaMKII: first, KN-93 inhibits AR activity and induces cell death in PCa cells after androgen deprivation when many other drugs fail to kill prostate cancer cells; second, KN-93 inhibits expression of the anti-apoptotic protein Mcl-1 and induces expression of the pro-apoptotic protein PUMA; third, KN-93-mediated cell death is p53-independent; and fourth, KN-93 induces the generation of ROS. The ROS induction allows KN-93 to circumvent the activation of Akt, which occurs in prostate cancer cells under androgen deprivation, since Akt could not inhibit ROS-mediated apoptosis. KN-93 also synergistically induces cell death in combination with low doses of doxorubicin and converts the... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3115725 Thu, 24 Dec 2009 01:48:13 +0100 3115725 http://www.medworm.com/index.php?rid=3115724&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20023433%26dopt%3DAbstract In this study, we further investigated the key molecules regulated by ZIP4 in pancreatic cancer angiogenesis and metastasis. We found that overexpression of ZIP4 caused significantly increased expression of NRP-1, VEGF, MMP-2 and MMP-9 in both pancreatic cancer cell lines and xenografts. Conversely, silencing of ZIP4 by short hairpin RNA (shRNA) was associated with decreased expression of NRP-1 and VEGF in pancreatic cancer xenografts. The ZIP4 expression and NRP-1 level are also correlated in established human pancreatic cancer cell lines. These results indicate that ZIP4-mediated pancreatic cancer growth might involve angiogenesis, invasion and metastasis pathways, and NRP-1, VEGF and MMPs are important intermediate molecules in transducing the ZIP4 initiated signal cascades in pancreati... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3115724 Thu, 24 Dec 2009 01:48:11 +0100 3115724 http://www.medworm.com/index.php?rid=3115723&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20026900%26dopt%3DAbstract We examined the expression of PHD2, HIF-1alpha, and several other hypoxia induced biomarkers in a series of clinically characterized, retroperitoneal sarcomas with immunohistochemical methods. Expression of these proteins was analyzed and correlated with clinical outcome. Increased HIF-1alpha expression was associated with shorter overall and disease free survival. PHD2 expression was detected in the majority of sarcoma cases, with increased expression correlating with high tumor grade but not with survival. Though changes in PHD2 expression alone did not correlate with overall and disease free survival, reduced/absent PHD2 expression in the presence of HIF-1alpha expression was associated with shorter overall and disease-free survival than that of other HIF-1alpha/PHD2 expression profiles... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3115723 Thu, 24 Dec 2009 01:48:08 +0100 3115723 http://www.medworm.com/index.php?rid=3115722&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20026908%26dopt%3DAbstract Conclusion: Reduced expression of PCAF plays an important role in the development of ITGC and correlates with a poor clinical outcome. PMID: 20026908 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3115722 Thu, 24 Dec 2009 01:48:05 +0100 3115722 http://www.medworm.com/index.php?rid=3012859&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19923925%26dopt%3DAbstract Authors: Yang D, Wang MT, Tang Y, Chen Y, Jiang H, Jones TT, Rao K, Brewer GJ, Singh KK, Nie D A common metabolic change in cancer is the acquisition of glycolytic phenotypes. Increased expression of glycolytic enzymes is considered as one contributing factor. The role of mitochondrial defects in acquisition of glycolytic phenotypes has been postulated but remains controversial. Here we show that functional defects in mitochondrial respiration could be induced by oncogenic H-Ras(Q61L) transformation, even though the mitochondrial contents or mass was not reduced in the transformed cells. First, mitochondrial respiration, as measured by mitochondrial oxygen consumption, was suppressed in NIH-3T3 cells transformed with H-Ras(Q61L). Second, oligomycin or rotenone did not reduce the cellul... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=3012859 Fri, 20 Nov 2009 17:32:05 +0100 3012859 http://www.medworm.com/index.php?rid=2978337&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19901561%26dopt%3DAbstract Conclusion: The recommended dose of curcumin is 6,000 mg/d for 7 consecutive days every 3 weeks in combination with a standard dose of docetaxel. From the encouraging efficacy results, a comparative phase II trial of this regimen plus docetaxel versus docetaxel alone is ongoing in advanced and metastatic breast cancer patients. PMID: 19901561 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2978337 Wed, 11 Nov 2009 11:24:10 +0100 2978337 http://www.medworm.com/index.php?rid=2978336&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19901562%26dopt%3DAbstract Authors: Ren F, Xu Y, Mao L, Ou R, Ding Z, Zhang X, Tang J, Li B, Jia Z, Tian Z, Ni B, Wu Y Several strategies have been used to enhance the vaccine-induced immunity of peptide vaccines and effective therapeutic benefits, including the utilization of heat shock proteins (HSP), especially the HSP70 family. HSP110 exhibits a higher binding affinity with protein and is capable of enhancing the immunogenicity of protein antigens; however, whether HSP110 can also increase the efficiency of peptide vaccine remains unclear. Here, we investigated mHSP110 as a chaperone immunoadjuvant to enhance the immune response to HPV16 oncoprotein E7-derived CTL epitope E7(49-57) in a mouse model. We developed the HSP110-E7(49-57) complex and demonstrated that mHSP110 could form complexes with peptide E7(4... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2978336 Wed, 11 Nov 2009 11:24:08 +0100 2978336 http://www.medworm.com/index.php?rid=2978335&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19901563%26dopt%3DAbstract Authors: Tang S, Yang G, Meng Y, Du R, Li X, Fan R, Zhao L, Bi Q, Jin J, Gao L, Zhang L, Li H, Fan M, Wang Y, Wu K, Liu J, Fan D Gankyrin, a small and highly conserved protein which is identical to the p28 gene product, was found to be related with the malignant phenotypes in liver and esophageal carcinoma. However, the roles of gankyrin in colorectal carcinoma (CRC) are still unknown. In the present study, the gankyrin mRNA and protein expression in human CRC cell lines and clinical tissue samples were evaluated and correlated with clinicopathological features. Possible mechanisms by which gankyrin regulates the malignant phenotype of CRC cells were also investigated. The results demonstrated that gankyrin was obviously overexpressed in CRC tissues and cell lines compared to controls,... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2978335 Wed, 11 Nov 2009 11:24:05 +0100 2978335 http://www.medworm.com/index.php?rid=2930415&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19855155%26dopt%3DAbstract Authors: Aragon-Ching JB Bisphosphonates have a firm role in the treatment of metastatic prostate cancer as it has been shown to retard skeletal events secondary to prostate cancer. Recent studies also show possible anti-tumor and anti-angiogenic effects from the use of bisphosphonates, specifically with the aminobisphosphonates. Clodronate is an older first-generation bisphosphonate that has recently been shown to improve overall survival in metastatic prostate cancer as reported by Dearnaley and colleagues in the September issue of The Lancet Oncology. The finding of improved overall survival has significant implications since no therapy to date, except for docetaxel-based regimens, has been shown to improve overall survival in metastatic prostate cancer. However, this trial also mer... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2930415 Tue, 27 Oct 2009 16:08:12 +0100 2930415 http://www.medworm.com/index.php?rid=2930414&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19855192%26dopt%3DAbstract Authors: Suojanen J, Salo T, Koivunen E, Sorsa T, Pirilä E Matrix metalloproteinases (MMPs), and especially membrane type-1 matrix metalloproteinase (MT1-MMP, MMP-14), play a role in cancer progression and can have a prognostic value. Various synthetic broad-spectrum MMP inhibitors have been developed but have had little success in cancer patient treatment owing to side effects. Until recently, selective targeting of specific MMPs has not been possible due to lack of specific inhibitors. Here we have developed a selective MT1-MMP peptide-inhibitor GACFSIAHECGA, which did not affect the activities of many other MMPs including MMP-1, -2, -3, -7, -8, -9, -10, -11, -12, -13, -15, -17 or -20. In a fluorescent peptide cleavage assay it displayed an IC(50) value of 150 muM. The peptide e... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2930414 Tue, 27 Oct 2009 16:08:09 +0100 2930414 http://www.medworm.com/index.php?rid=2930413&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19855194%26dopt%3DAbstract Authors: Zhang J, Li Y, Guo L, Cao R, Zhao P, Jiang W, Ma Q, Yi H, Li Z, Jiang J, Wu J, Wang Y, Si S A better way to treat complex diseases such as cancer is to aim for several targets at once. Beta-carboline derivatives have been shown to have anticancer activity, but these compounds may target several enzymes required for cell division. Polo-like kinases (PLKs) are well conserved serine/threonine kinases and PLK1 plays multiple roles in cell proliferation. Thus, PLK1 is one of the attractive mitotic targets for anticancer drugs. We found that DH166, a beta-carboline derivative, inhibits the growth of cdc5-2 temperature-sensitive mutant more profoundly than wild-type yeast cells. Because Cdc5 is the human PLK1 homologue in budding yeast, this observation indicates that DH166 might be ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2930413 Tue, 27 Oct 2009 16:08:06 +0100 2930413 http://www.medworm.com/index.php?rid=2896933&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19829046%26dopt%3DAbstract In this study, a comparative quantitative methylation profiling of inflammatory breast cancer (IBC) and non-IBC was set up for the identification of tumor-specific methylation patterns. Methylation ratios of six genes (DAPK, TWIST, HIN-1, RASSF1A, RARbeta2 and APC) were measured in benign breast tissues (n = 9) and in tumor samples from non-IBC (n = 81) and IBC (n = 19) patients using quantitative methylation-specific PCR. Median methylation ratios observed in breast cancer (n = 100) were significantly higher than those observed in benign breast tissues for 5 of 6 genes (TWIST, HIN-1, RASSF1A, RARbeta2 and APC). Only one of the individual genes studied, RARbeta2, showed differential methylation ratios in IBC and non-IBC (p = 0.016). Using the maximal methylation ratio observed in benign br... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2896933 Fri, 16 Oct 2009 13:44:10 +0100 2896933 http://www.medworm.com/index.php?rid=2896932&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19829059%26dopt%3DAbstract Conclusions: Bevacizumab and etaracizumab are more effective in combination than individually in some ovarian cancer models, but not all. Both can sensitize taxane-resistant ovarian cancer cells to paclitaxel, though bevacizumab was superior to etaracizumab in this regard. Further study of this dual anti-angiogenic therapy is warranted. PMID: 19829059 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2896932 Fri, 16 Oct 2009 13:44:08 +0100 2896932 http://www.medworm.com/index.php?rid=2896931&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19829072%26dopt%3DAbstract Authors: Seshadri M, Merzianu M, Tang H, Rigual NR, Sullivan M, Loree TR, Popat SR, Repasky EA, Hylander BL The overall purpose of this study was to establish human head and neck squamous cell carcinoma (HNSCC) xenografts in mice by transplantation of surgical tumor tissue and to characterize the growth, histologic and vascular properties of these xenografts. Primary surgical specimens of HNSCC were xenografted into eight-to-twelve week old severe combined immunodeficiency (SCID) mice. Histologic features of primary HNSCC specimens, initial and established xenografts were compared for tumors established from three different head and neck subsites, namely, oral cavity, larynx and base of tongue (one tumor per site). Growth rates of xenografts were compared along with magnetic resonance ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2896931 Fri, 16 Oct 2009 13:44:05 +0100 2896931 http://www.medworm.com/index.php?rid=2891140&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19823027%26dopt%3DAbstract In this study, we performed a 3D analysis of the response to the CDC25 phosphatase inhibitor IRC-083864 in HCT116 spheroids. Continuous exposure to IRC-083864 strongly inhibits the growth of spheroids and is shown to correlate with a decrease in Ki-67 positive cells. The cytotoxicity induced by IRC-083864 was examined by two-photon laser microscopy imaging and 3D reconstruction. Visualization in 3D allowed us to demonstrate that IRC-083864 treatment results in the inhibition of mitosis and induces cell death specifically localized in the outer proliferative cell layers of the spheroid structure. These results emphasize the importance of 3D models and of in toto analysis for the evaluation of anticancer drugs cytotoxicity. PMID: 19823027 [PubMed - as supplied by publisher] (Source: Canc... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2891140 Wed, 14 Oct 2009 17:30:11 +0100 2891140 http://www.medworm.com/index.php?rid=2891139&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19823028%26dopt%3DAbstract Authors: Gong J, Yang DJ, Kohanim S, Angelo LS, Kurzrock R Finding noninvasive methods to discern which patients' tumors bear a specific target molecule, and are presumably more likely to respond, remains a critical challenge. An anti-phospho-tyrosine antibody was labeled with indium ((111)In) using ethylenedicysteine (EC) as a chelator ((111)In-EC-P-Tyr). We hypothesized that tumor phosphokinase activity would be discernible by imaging with (111)In-EC-P-Tyr. A xenograft of A431 cells, a human epithelial carcinoma cell line overexpressing epidermal growth factor receptor (EGFR), was employed. Biodistribution studies confirmed increased tumor/muscle ratios of (111)In-EC-P-Tyr in the A431 model. Imaging demonstrated that a marked decrease in tumor uptake of (111)In-EC-P-Tyr occurred afte... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2891139 Wed, 14 Oct 2009 17:30:08 +0100 2891139 http://www.medworm.com/index.php?rid=2891138&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19823045%26dopt%3DAbstract Authors: Skourou C, Hoopes PJ, Paulsen KD Fibrosis is a pathological condition resulting from radiation injury which often limits the prescription of higher (or boost) doses of radiation, risking inadequate tumor control in patients. Recent studies have documented reduction in fibrotic lesions after administration of pentoxyfilline and tocopherol combinations to breast cancer patients receiving adjuvant radiation therapy. Despite the promise of these findings, no techniques or markers are available which can be used to identify the onset or progression of fibrosis in such patients at stages early enough to allow maximum benefit from these types of pharmacological agents. Relative permittivity of skeletal muscle has been investigated in an animal model utilizing high dose rate radiation... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2891138 Wed, 14 Oct 2009 17:30:05 +0100 2891138 http://www.medworm.com/index.php?rid=2842759&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19783897%26dopt%3DAbstract Authors: Bunz F PMID: 19783897 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2842759 Tue, 29 Sep 2009 19:18:22 +0100 2842759 http://www.medworm.com/index.php?rid=2842758&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19783898%26dopt%3DAbstract Authors: Meng J, Peng H, Dai B, Guo W, Wang L, Ji L, Minna JD, Chresta CM, Smith PD, Fang B, Roth JA MEK/ERK activities are increased in many primary lung cancers, and MEK inhibitors have been tested clinically for treatment of non-small cell lung cancers. The molecular mechanisms of resistance to MEK inhibitors have not been clearly demonstrated, however, and no molecular biomarker that can predict lung cancer response to MEK inhibitors is available. By determining the dose-responses of 35 human lung cancer cell lines to MEK-specific inhibitor AZD6244, we identified subsets of lung cancer cell lines that are either sensitive or resistant to this agent. Subsequent molecular characterization showed that treatment with AZD6244 suppressed ERK phosphorylation in both sensitive and resistan... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2842758 Tue, 29 Sep 2009 19:18:19 +0100 2842758 http://www.medworm.com/index.php?rid=2842757&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19783899%26dopt%3DAbstract Authors: Donaldson JM, Kari C, Fragoso RC, Rodeck U, Williams JC Therapeutic antibodies frequently cause side effects by binding antigen in non-target tissues. Here we demonstrate a novel molecular design of antibodies that addresses this problem by reversibly "masking" antibody complementarity determining regions until they reach diseased tissues containing disease-associated proteases. Specifically, two distinct single-chain Fv (scFv) fragments derived from antibodies against the epidermal growth factor receptor (cetuximab and 425) were fused with a protease susceptible linker to their epitopes engineered to encourage intermolecular association. Surface plasmon resonance and flow cytometry were used to confirm that the masked complex poorly interacts native antigen whereas protease t... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2842757 Tue, 29 Sep 2009 19:18:17 +0100 2842757 http://www.medworm.com/index.php?rid=2842756&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19783900%26dopt%3DAbstract Authors: Mohla S, Stearns V, Sathyamoorthy N, Rosenfeld MG, Nelson P The molecular regulation of growth and progression of hormone refractory breast and prostate cancers remains challenging. The Division of Cancer Biology, NCI organized a small "think tank" style workshop and invited scientists in relevant areas to assess the state of science on the biology of hormone refractory tumors and to identify potential research opportunities to enhance a better understanding of the molecular regulation of these tumors. The meeting, held on May 27-29, 2008 in Bethesda, MD, was co-chaired by Drs. Michael Geoffrey Rosenfeld and Michael Press. While expression of estrogen or progesterone receptors (ER/PR) is required for benefit from endocrine manipulations, many women with breast cancer will not ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2842756 Tue, 29 Sep 2009 19:18:15 +0100 2842756 http://www.medworm.com/index.php?rid=2842755&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19783901%26dopt%3DAbstract In this study, we extended these studies to explore the possibility that manipulation of the Notch signaling by GSI would prevent the growth of the PEL tumors in vivo. We observed that the onset of tumorigenesis of KSHV infected PELs was significantly delayed in GSI treated SCID mice harboring the PEL cell lines. We also found that GSI treatment resulted in necrosis as well as apoptosis in tumors generated by the xenotransplanted KSHV positive PEL cell lines. In contrast, GSI had no effect on mice harboring BJAB cells, a KSHV negative Burkitt's lymphoma cell line where ICN levels were negligible. Our study provides further evidence to suggest that targeted downregulation of abnormal Notch signaling has therapeutic potential for KSHV related primary effusion lymphomas. PMID: 19783901 [P... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2842755 Tue, 29 Sep 2009 19:18:12 +0100 2842755 http://www.medworm.com/index.php?rid=2842754&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19783902%26dopt%3DAbstract Authors: Dong W, Shen R, Wang Q, Gao Y, Qi X, Jiang H, Yao J, Lin X, Wu Y, Wang L Experimental design: Telomere repeat binding factor 2 (TRF2) plays a key role in the protective activity of telomere and is overexpression in several kinds of solid cancer cells. However, the role of overexpressed TRF2 in colorectal carcinoma remains unclear. The aim of this study was to determine the expression of TRF2, address the mechanism of TRF2 overexpression in human colorectal carcinoma. In present study, we examined the expression of TRF2 in colorectal cancer tissues from 39 patients, peritumoral normal tissues from 21 patients, and colon carcinoma SW480 cell line by quantitative PCR, immunohistochemistry and western blot. After siRNA silencing TRF2 expression in SW480, tumorigenesis of TRF2 was ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2842754 Tue, 29 Sep 2009 19:18:10 +0100 2842754 http://www.medworm.com/index.php?rid=2842753&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19783903%26dopt%3DAbstract Authors: Panelos J, Massi D Signaling mediated by the Notch receptor governs tissue development during embryonal organogenesis, while in adult tissues it contributes to maintenance of cellular differentiation, proliferation and apoptosis. In addition, control by the Notch pathway of stem cell self-renewal and multi-potency points to an expanding role of Notch signaling in the progression of solid tumors. Notch and its ligands are abundantly expressed in the epidermis, where Notch signaling functions as a molecular switch that intervenes in cell transition between different skin layers during the epidermal differentiation process. More recent findings obtained in melanoma and non-melanoma skin cancers show that Notch signaling has a dual action (either as an oncogene or as a tumor suppr... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2842753 Tue, 29 Sep 2009 19:18:08 +0100 2842753 http://www.medworm.com/index.php?rid=2842752&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19783906%26dopt%3DAbstract Authors: Soundararajan R, Sayat R, Robertson GS, Marignani PA Triptolide, a diterpene triepoxide derived from Trypterygium wilfordii, is documented to have antitumor activity in a broad range of solid tumors and leukemia. The mechanisms that are involved in triptolide-mediated apoptosis or growth inhibition in cancer cells are not fully understood. We identified a disintegrin and metalloproteinase 10 (ADAM10) as a novel molecular target of triptolide using affinity chromatography and mass spectrometry. The identification was confirmed by western blot analysis using an anti-ADAM10 antibody. The expression of ADAM10 is enhanced in several tumors including leukemia and is involved in malignant cell growth and cancer progression. ADAM10 is a type 1 transmembrane glycoprotein that cleaves s... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2842752 Tue, 29 Sep 2009 19:18:05 +0100 2842752 http://www.medworm.com/index.php?rid=2807886&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19755854%26dopt%3DAbstract In this study, we evaluated the antitumor effect of IL-12 electrogene therapy (EGT) on murine SA-1 fibrosarcoma. The therapeutic plasmid was injected either intratumorally into subcutaneous SA-1 nodules or intradermally into the peritumoral region. We achieved a remarkable local and systemic antitumor effect with both approaches after single plasmid DNA application, with significant intratumoral and systemic production of IL-12 and IFNgamma. Intratumoral IL-12 EGT resulted in over 90% complete response rate of the treated tumors with 60% of cured mice being resistant to challenge with SA-1 tumor cells. Peritumoral EGT resulted in a lower complete response rate (16%), with significant growth delay of remaining tumors. Both therapies also resulted in significant inhibition of growth of untre... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2807886 Fri, 18 Sep 2009 18:32:10 +0100 2807886 http://www.medworm.com/index.php?rid=2807885&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19755855%26dopt%3DAbstract Authors: Ramos AH, Dutt A, Mermel C, Perner S, Cho J, Lafargue CJ, Johnson LA, Stiedl AC, Tanaka KE, Bass AJ, Barretina J, Weir BA, Beroukhim R, Thomas RK, Minna JD, Chirieac LR, Lindeman NI, Giordano T, Beer DG, Wagner P, Wistuba II, Rubin MA, Meyerson M In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCLC). Single nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA an... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2807885 Fri, 18 Sep 2009 18:32:08 +0100 2807885 http://www.medworm.com/index.php?rid=2807884&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19755863%26dopt%3DAbstract Authors: Westin SN, Broaddus RR, Deng L, McCampbell A, Lu KH, Lacour RA, Milam MR, Urbauer DL, Mueller P, Pickar JH, Loose DS Identification of biomarkers potentially provides prognostic information that can help guide clinical decision-making. Given the relationship between estrogen exposure and endometrial cancer, especially low grade endometrioid carcinoma, we hypothesized that high expression of genes induced by estrogen would identify low risk endometrioid endometrial cancers. cDNA microarray and qRT-PCR verification were used to identify six genes that are highly induced by estrogen in the endometrium. These estrogen-induced biomarkers were quantified in 72 endometrial carcinomas by qRT-PCR. Unsupervised cluster analysis was performed, with expression data correlated to tumor cha... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2807884 Fri, 18 Sep 2009 18:32:05 +0100 2807884 http://www.medworm.com/index.php?rid=2782818&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19738415%26dopt%3DAbstract In this study, two HLA-A11-restricted epitopes derived from human papillomavirus (HPV)18 E6 oncoprotein were identified. HLA-A11-transgenic mice immunized with these epitopes could specifically induce interferon-gamma (IFNgamma) production, cytotoxicity and peptide/HLA-A11 tetramer binding in CD8(+) T cells. To study intracellular processing of CTL epitopes, we constructed a DNA plasmid containing an endoplasmic reticulum (ER) targeting sequence as well as the HPV18 E6 and E7 genes (pEK/HPV18E6E7). CTL responses against peptide-pulsed T2/A11 cells could be detected after immunizing HLA-A11-transgenic mice with pEK/HPV18E6E7. Furthermore, the identified peptides could stimulate T cells to secrete IFNgamma from HPV18-infected patients. Our results demonstrate that the antigenic E6 peptides d... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2782818 Fri, 11 Sep 2009 10:08:14 +0100 2782818 http://www.medworm.com/index.php?rid=2782817&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19738430%26dopt%3DAbstract Conclusions: In advanced hepatocarcinoma, we report SRS uptake in 35.7% of livers and 41.2% of metastatic sites. SRS value in screening patients for somatostatin analogue treatment remains to be assessed. PMID: 19738430 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2782817 Fri, 11 Sep 2009 10:08:09 +0100 2782817 http://www.medworm.com/index.php?rid=2743925&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713740%26dopt%3DAbstract Authors: Brandon EL, Gu JW, Cantwell L, He Z, Wallace G, Hall JE Epidemiological studies suggest that obesity increases the risk of developing several cancers, including melanoma. Obesity increases the expression of angiogenic factors, such as leptin, that may contribute to tumor growth. However, a direct cause and effect relationship between obesity and tumor growth has not been clearly established and the role of leptin in accelerating tumor growth is unclear. Our objective in the present study was to examine the rate of melanoma tumor growth in lean and obese mice with leptin deficiency or high levels of plasma leptin. We injected 1 x 10(6) B16F10 melanoma cells subcutaneously into lean wild type (WT), obese melanocortin receptor 4 knockout (MC4R(-/-)), which have high leptin levels... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2743925 Sat, 29 Aug 2009 13:38:49 +0100 2743925 http://www.medworm.com/index.php?rid=2743924&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713742%26dopt%3DAbstract Authors: Chan VS, Tsao SW, Lin CL PMID: 19713742 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2743924 Sat, 29 Aug 2009 13:38:44 +0100 2743924 http://www.medworm.com/index.php?rid=2743923&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713746%26dopt%3DAbstract Authors: Efferth T PMID: 19713746 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2743923 Sat, 29 Aug 2009 13:38:22 +0100 2743923 http://www.medworm.com/index.php?rid=2743922&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713753%26dopt%3DAbstract Authors: Olaussen KA PMID: 19713753 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2743922 Sat, 29 Aug 2009 13:38:11 +0100 2743922 http://www.medworm.com/index.php?rid=2743921&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713755%26dopt%3DAbstract Authors: Ozer J, Eisner N, Ostrozhenkova E, Ostrozhenkova E, Bacher A, Eisenreich W, Benharroch D, Golan-Goldhirsh A, Gopas J We screened thirty-four methanolic plant extracts for inhibition of the constitutive nuclear factor kappaB (NFkappaB) activity by a NFkappaB-luciferase reporter gene assay. Strong inhibition of NFkappaB activity was found in extracts of leaf and rhizome from Nuphar lutea L. SM. (Nuphar). The inhibitory action was narrowed down to a mixture of thionupharidines and/or thionuphlutidines that were identified in chromatography fractions by one- and two-dimensional NMR analysis. Dimeric sesquiterpene thioalkaloids were identified as the major components of the mixture. The Nuphar alkaloids mixture (NUP) showed a dose dependent inhibition of NFkappaB activity in a luci... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2743921 Sat, 29 Aug 2009 13:38:09 +0100 2743921 http://www.medworm.com/index.php?rid=2743920&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19713764%26dopt%3DAbstract Authors: Stein EV, Price DK, Figg WD PMID: 19713764 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2743920 Sat, 29 Aug 2009 13:38:06 +0100 2743920 http://www.medworm.com/index.php?rid=2709442&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19684476%26dopt%3DAbstract Authors: Moschos SJ, Dodd NR, Jukic DM, Fayewicz SL, Wang X, Becker D Melanoma in its advanced stages is resistant not only to chemotherapy but also to radiation treatment. In line with efforts to identify genes that are key regulators of the disease and as such, may prove valuable targets for adjuvant and neo-adjuvant therapy of melanomas, we previously reported the presence of Serial Analysis of Gene Expression (SAGE) tags, corresponding to the Ataxia Telangiectasia Mutated (ATM) gene, in SAGE libraries generated from tissues representing primary and metastatic melanomas. In the present study, we document that ATM is expressed at high levels in advanced-stage melanomas. Given its crucial role in the cellular response to DNA double-strand breaks (DSB), ionizing radiation, and UV damag... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2709442 Tue, 18 Aug 2009 13:14:04 +0100 2709442 http://www.medworm.com/index.php?rid=2682758&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19657234%26dopt%3DAbstract Authors: Li J, Chigurupati S, Agarwal R, Mughal MR, Mattson MP, Becker KG, Wood WH, Zhang Y, Morin PJ Claudin proteins are frequently overexpressed in various tumors such as breast, prostate and ovarian cancer. While their functions in cancer have not been completely elucidated, roles in survival, adhesion and invasion have been suggested. In order to clarify the roles of claudins in ovarian cancer, we have performed gene expression profiling of ovarian surface epithelial cells overexpressing claudin-4 and compared the expression patterns to the parental, non-expressing cells. Claudin-4 expression leads to the differential expression of several genes, including many that have previously been implicated in angiogenesis. In particular, angiogenic cytokines, such as IL-8, were found eleva... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2682758 Sun, 09 Aug 2009 07:22:07 +0100 2682758 http://www.medworm.com/index.php?rid=2671301&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19652552%26dopt%3DAbstract In this study, we examined the effect of TLR3 activation on the metastasis of nasopharyngeal carcinoma (NPC). We found that NPC cells expressed TLR3 gene transcript and protein. TLR3 activation downregulated the expression of chemokine receptor CXCR4 in a dose-dependent manner, and inhibited cell migration in response to CXCR4 ligand stromal cell-derived factor-1alpha (SDF-1alpha) in chemotaxis assays. Furthermore, TLR3 activation significantly reduced the capacity of NPC cells to form metastasis in draining lymph nodes when injected in athymic mice. The anti-metastasis activity of endogenous human TLR3 expression in cancer cells reveals a novel aspect of the multiple-faced TLR biology, which may open new clinical prospects for using TLR3 agonists to control cancer metastasis in selected c... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2671301 Wed, 05 Aug 2009 15:02:05 +0100 2671301 http://www.medworm.com/index.php?rid=2638046&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19625764%26dopt%3DAbstract Authors: Wheeler DL, Dunn EF PMID: 19625764 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2638046 Sat, 25 Jul 2009 13:22:08 +0100 2638046 http://www.medworm.com/index.php?rid=2603325&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19597348%26dopt%3DAbstract Authors: Wang Y, Cao W, Yu Z, Liu Z Results from tissue microarray in this study and our previous reports revealed that stomatin-like protein 2 (SLP-2) is notably associated with tumorigenesis and metastasis. Many members of stomatin family are involved in tumor as mitochondrial component, and recent study has revealed that SLP-2 may also function in mitochondria. To further investigate the function of SLP-2, we used siRNA target SLP-2. Data showed that knock-down of SLP-2 potently inhibited cell motility, proliferation and slightly altered cell cycle without any significant change of apoptosis. Moreover, by combined application with different chemotherapeutic reagents, we observed the enhancement of cell chemosensitivity by SLP-2 depletion. We also confirmed that, SLP-2 localizes in m... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2603325 Thu, 16 Jul 2009 07:50:05 +0100 2603325 http://www.medworm.com/index.php?rid=2275884&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19287209%26dopt%3DAbstract Authors: Jorgensen TJ Radiotherapy is very effective in local control of cancerous tumors, but its curative potential is often limited by intrinsic radioresistance of the tumor cells. Since DNA repair pathways remove radiation-induced DNA lesions and protect cells from lethality, these pathways represent potential therapeutic targets to radiosensitize tumors. In order to achieve a therapeutic gain, however, there must be a differential between tumor and normal cells that can be exploited to preferentially target the DNA repair of the tumor, while sparing surrounding normal tissues, and this has represented a significant challenge to progress. Nevertheless, recent advances in our understanding of DNA repair mechanisms and tumor biology, on both the biochemical and genetic levels, have i... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2275884 Fri, 20 Mar 2009 09:06:17 +0100 2275884 http://www.medworm.com/index.php?rid=2262396&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19276650%26dopt%3DAbstract Authors: Cheah PY PMID: 19276650 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2262396 Sat, 14 Mar 2009 21:25:38 +0100 2262396 http://www.medworm.com/index.php?rid=2250943&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19270499%26dopt%3DAbstract Authors: Beeharry N, Yen TJ PMID: 19270499 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2250943 Wed, 11 Mar 2009 10:00:23 +0100 2250943 http://www.medworm.com/index.php?rid=2250942&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19270501%26dopt%3DAbstract Authors: Wolf FI, Trapani V PMID: 19270501 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2250942 Wed, 11 Mar 2009 10:00:14 +0100 2250942 http://www.medworm.com/index.php?rid=2201906&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19223770%26dopt%3DAbstract Authors: Zhang Y, Qu ZH, Cui M, Guo C, Zhang XM, Ma CH, Sun WS Endostatin can inhibit tumor growth by blocking angiogenesis, whereas tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may function as a soluble cytokine to selectively kill cancer cells without toxicity to most normal cells. To establish the combined anti-tumor therapeutic effect of endostatin and soluble TRAIL (sTRAIL), we performed intra-tumoral human endostatin and sTRAIL gene transfer using plasmid pVAX1 as a vector in a nude mouse model of human liver cancer. For subcutaneously inoculated human BEL7402 cancer, co-expression of both transgenes conferred marked anti-tumor activity with a significant reduction in tumor vessel density and an increase in apoptotic rates, which was accompanied with a strong a... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2201906 Sat, 21 Feb 2009 05:33:37 +0100 2201906 http://www.medworm.com/index.php?rid=2195862&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19221468%26dopt%3DAbstract Authors: Plasencia C, Grande F, Oshima T, Cao X, Yamada R, Sanchez T, Aiello F, Garofalo A, Neamati N Previously, we discovered a novel class of salicylhydrazide compounds with remarkable activity in hormone-dependent and -independent human cancer cells. We then designed and synthesized numerous analogues. Among these analogues, a quinoxalinhydrazide compound, SC144, exhibited desirable physicochemical and drug-like properties and therefore, was selected for further preclinical investigation. In the present study, we evaluated the in vitro activity of SC144 in a range of drug-sensitive and -resistant cancer cell lines as well as its in vivo efficacy in MDA-MB-435 and HT29 mice xenograft models. The broad-spectrum cytotoxicity of SC144 is especially highlighted by its potency in ovarian... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2195862 Thu, 19 Feb 2009 04:47:55 +0100 2195862 http://www.medworm.com/index.php?rid=2195861&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19221469%26dopt%3DAbstract Authors: Fendri A, Masmoudi A, Khabir A, Sellami-Boudawara T, Daoud J, Frikha M, Ghorbel A, Gargouri A, Mokdad-Gargouri R Epigenetic modification is one of the mechanisms leading to gene silencing in neoplastic cells. By methylation-specific PCR, we analyzed the promoter methylation of three cancer-related genes: Ras Association domain Family 1A (RASSF1A), Death Associated Protein kinase (DAP-kinase) and Retinoic Acid Receptor beta2 (RARbeta2) in two NPC xenografts (C15 and C17), 68 primary NPC tumors, and 9 normal nasopharyngeal epithelia. We showed that C15 and C17 displayed a complete promoter methylation of RASSF1A, RARbeta2 and DAP-kinase genes. In primary NPC tumors, the incidence of promoter methylation was very high for all three tested genes: 91% for RASSF1A, 88% for both RARb... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2195861 Thu, 19 Feb 2009 04:47:24 +0100 2195861 http://www.medworm.com/index.php?rid=2157478&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19182534%26dopt%3DAbstract Authors: Adamo V, Franchina T, Adamo B, Denaro N, Gambadauro P, Chiofalo G, Scimone A, Caristi N, Russo A, Giordano A Over the past few years, epidermal growth factor receptor has emerged as one of the most important targets in tumorgenesis and several drugs targeting signal transduction pathways have been developed. The first among these agents to be approved for the treatment of NSCLC was gefitinib, a potent, selective and reversible inhibitor of HER1/EGFR tyrosine kinase activity. The review summarizes its clinical development and the new therapeutic options, with particular focus on predictive markers of susceptibility to this drug. PMID: 19182534 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2157478 Wed, 04 Feb 2009 14:19:30 +0100 2157478 http://www.medworm.com/index.php?rid=2131927&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19164933%26dopt%3DAbstract Authors: Hendrikse AS, Renan MJ, Hunter AJ The sensitivity of cells to radiation-induced apoptosis is considered to be low in solid tumors. This is thought to arise largely from inherent resistance caused by apoptotic pathway mutations. However, other factors may contribute to apoptotic resistance. Poor vasculature and abnormal tumor metabolism lead to a tumor microenvironment characterized by conditions of hypoxia, low glucose and extracellular acidosis. Hypoxia during irradiation is well known to cause resistance and is a barrier to successful treatment. We hypothesized that post-irradiation microenvironmental conditions can modulate radiation-induced apoptosis and that this may in part contribute to therapeutic resistance. In order to test this, radiation-induced apoptosis was asses... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2131927 Sun, 25 Jan 2009 11:56:50 +0100 2131927 http://www.medworm.com/index.php?rid=2131926&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19164937%26dopt%3DAbstract Authors: Ghiotto F, Fais F, Tenca C, Tomati V, Morabito F, Casciaro S, Mumot A, Zoppoli G, Ciccone E, Parodi S, Bruno S B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in human adults of the Western world and no definitive cure is yet available. The disease is characterized by accumulation of clonal malignant B lymphocytes resistant to apoptosis. Strategies to hit the anti-apoptotic drift of the Bcl-2 family in B-CLL cells are being explored. A novel peptidomimetic based on the BH3 domain of the pro-apoptotic protein Bim and recently shown to exert significant apoptotic activity on acute myeloid leukemia cells, both in vitro and in vivo, was assayed on ex-vivo derived leukemic cells from untreated B-CLL patients (n = 7). We found that this peptide, named 072RB, ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2131926 Sun, 25 Jan 2009 11:56:44 +0100 2131926 http://www.medworm.com/index.php?rid=2065929&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19106636%26dopt%3DAbstract This article reviews the common science supporting miRNAs and their potantial target genes in leukemia pathogenesis. PMID: 19106636 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2065929 Fri, 26 Dec 2008 13:50:46 +0100 2065929 http://www.medworm.com/index.php?rid=2065928&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19106637%26dopt%3DAbstract Authors: Brüning A, Burger P, Vogel M, Rahmeh M, Gingelmaiers A, Friese K, Lenhard M, Burges A Proteasome inhibitors and protease inhibitors are currently being discussed to be useful to sensitize drug-resistant cancer cells to chemotherapeutic agents or to act independently as single agents on drug resistant cancer cells. We tested the effect of the clinically applied HIV protease inhibitor nelfinavir on ovarian cancer cells. Nelfinavir efficiently induced cell death in carboplatin- sensitive (SKOV3, OV-GH-5) and carboplatin-resistant (OVCAR3, OV-GH-1) ovarian cancer cell lines as well as in cancer biopsies and ascites samples from patients with recurrent ovarian cancer. Nelfinavir significantly changed the morphology of ovarian cancer cells, resulting in formation of large ER-de... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2065928 Fri, 26 Dec 2008 13:50:41 +0100 2065928 http://www.medworm.com/index.php?rid=2065927&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19106638%26dopt%3DAbstract Authors: Driscoll M, Hansen R, Ding C, Cramer DE, Yan J Combined beta-glucan with anti-tumor mAb therapy has demonstrated therapeutic efficacy in murine tumor models. The current study was designed to compare the therapeutic efficacy of various sources of beta-glucans. Our studies demonstrated that yeast beta-glucan, in combination with anti-tumor mAb, resulted in significantly smaller tumor burdens and achieved enhanced long-term survival compared to mAb alone or beta-glucan extracts from mushrooms. Further studies indicated that yeast beta-glucan particle was superior to mushroom extracts in inducing cytokine secretion, particularly IL-12 production in dendritic cells (DCs). In addition, results showed that cytokine production was markedly decreased in MyD88-deficient macrophages and... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2065927 Fri, 26 Dec 2008 13:50:37 +0100 2065927 http://www.medworm.com/index.php?rid=2065926&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19106639%26dopt%3DAbstract Authors: Kisslinger A, Cantile M, Sparaneo G, Vitale N, Fabbrocini G, Chieffi P, Cillo C, Mancini FP, Tramontano D In cultured prostate cancer cells cAMP blocks proliferation and induces neuroendocrine differentiation. Pyk2 expression inversely correlates with malignancy of prostate cancer. The aim of this study was to investigate the interaction between cAMP and Pyk2 in the prostate. EPN cells, a line derived from human normal prostate expressing Pyk2, and EPN-PKM3 cells, an EPN clone bearing a Pyk2 kinase-negative mutant, were adopted as model system. cAMP inhibited cell growth in both prostate cell lines, and activated Pyk2, but not ERK1/2, in EPN cells. cAMP treatment, abolished the activation of AKT1, an important component of the pro-survival pathway, in the EPN cells but not in ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2065926 Fri, 26 Dec 2008 13:50:32 +0100 2065926 http://www.medworm.com/index.php?rid=2065925&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19106640%26dopt%3DAbstract Authors: Pataer A, Swisher SG, Roth JA, Logothetis CJ, Corn P RNA-dependent protein kinase is an interferon-induced, double-stranded (ds), RNA-activated serine/threonine protein kinase involved in the eukaryotic response to viral infection. While PKR also functions in cellular differentiation, growth control and apoptosis, its role in human cancer remains poorly understood. To explore a role for PKR in human cancer, we evaluated PKR expression and function in a series of cancer cell lines from different tumor types. We observed that PKR protein expression is high in various cancer cells and low in normal cells. Knockdown of PKR protein expression by PKR siRNA induced cell death, indicating a PKR-dependent survival pathway under normal growth conditions. Inhibition of PKR signaling usin... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2065925 Fri, 26 Dec 2008 13:50:28 +0100 2065925 http://www.medworm.com/index.php?rid=2065924&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19106647%26dopt%3DAbstract Conclusions: Aberrant miRNA expression is an early event in the multistage progression of pancreatic cancer, and miR-155 warrants further evaluation as a biomarker for IPMNs in clinical samples. PMID: 19106647 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=2065924 Fri, 26 Dec 2008 13:50:22 +0100 2065924 http://www.medworm.com/index.php?rid=1992630&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029792%26dopt%3DAbstract Authors: Katz J, Chan E PMID: 19029792 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992630 Thu, 27 Nov 2008 15:29:07 +0100 1992630 http://www.medworm.com/index.php?rid=1992629&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029813%26dopt%3DAbstract Authors: Balko JM, Black EP Gene expression predictors of response (GEPR) are an exciting and developing area of personalized cancer therapy. Genome-wide expression data can predict drug response and may segregate inter-patient heterogeneity better than single biomarkers alone. Generation of GEPRs frequently employs cell culture systems but validation requires tumor samples from treated patients. We hypothesize that GEPR validation requires tissue acquisition immediately prior to treatment, representing a significant obstacle for validation of GEPRs of second- or third-line therapeutics. To test whether expression data obtained prior to first line therapy can predict response to subsequent lines of therapy, chemo-stability of the signature must first be assessed. Publicly-available mic... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992629 Thu, 27 Nov 2008 15:29:03 +0100 1992629 http://www.medworm.com/index.php?rid=1992628&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029816%26dopt%3DAbstract Authors: Christian PA, Thorpe JA, Schwarze SR Inducing apoptosis via the extrinsic death receptor pathway is an attractive anti-cancer treatment strategy, however, numerous cancer cells exhibit significant resistance to death ligand stimuli. Here, we investigated the anti-neoplastic capability of proteasome inhibition, through the administration of Velcade, to synergize with a death receptor agonist in vivo. The death ligand-resistant LNCaP prostate xenograft model was utilized. Tumors were established and mice were treated with Velcade, TRAIL (TNF-Related Apoptosis Inducing Ligand) or the combined regimen. Only mice treated with a combination of Velcade and TRAIL was tumor growth inhibited with a corresponding loss of the hemorrhagic phenotype, decreased tumor cell proliferation and i... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992628 Thu, 27 Nov 2008 15:28:59 +0100 1992628 http://www.medworm.com/index.php?rid=1992627&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029817%26dopt%3DAbstract Authors: Ben-Izhak O, Akrish S, Gan S, Nagler RM Salivary malignancies are rare, heterogeneous, unpredictable in clinical behavior and seldom studied. Skp2 expression was examined in salivary malignancies (n = 75) for a prolonged period (20 years). In 40/75 (53%) cases Skp2 expression rate (staining level) was </=4% while in the remainder (47%) it was >4%. Correlation between enhanced Skp2 and enhanced p53 staining levels was significant (p = 0.042), as were correlation rates between enhanced Skp2 and reduced p27 staining levels (p = 0.01) and enhanced Skp2 and enhanced TUNEL staining levels (p = 0.008). Survival probability rates dropped when Skp2 expression increased. Median patient survival for reduced-stained-tumor patients (</=4%) was 143 months and significantly lower, 4... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992627 Thu, 27 Nov 2008 15:28:56 +0100 1992627 http://www.medworm.com/index.php?rid=1992626&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029822%26dopt%3DAbstract Conclusion: The higher association of TMPRSS2-ERG with Gleason score 6 and 7 should be further investigated. If confirmed, this could have significant clinical impact in further stratifying patients with PCA should the TMPRSS2-ERG be confirmed as a prognostic biomarker. PMID: 19029822 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992626 Thu, 27 Nov 2008 15:28:49 +0100 1992626 http://www.medworm.com/index.php?rid=1992625&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029826%26dopt%3DAbstract Authors: Meng F, Dong B, Li H, Fan D, Ding J Tumor angiogenesis plays an important role in the malignancy of solid tumors. A number of recent studies including our own have suggested that Raf-1 is involved in this process, and may be critical in regulating gene activation of several angiogenesis factors. RNA interference (RNAi) provides a powerful method for gene silencing in eukaryotic cells, including proliferating mammalian cells. To further define Raf-1 function in angiogenesis and to explore novel approaches to modulate angiogenesis, we employed the small interference RNA technique to knockdown gene expression of Raf-1 in gastric cancer cells and observed the effect of silencing Raf-1 on gastric cancer tumorigenesis and angiogenesis in vitro and in nude mice. We found that the exp... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992625 Thu, 27 Nov 2008 15:28:46 +0100 1992625 http://www.medworm.com/index.php?rid=1992624&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029829%26dopt%3DAbstract In this study, we investigated the enhanced anti-tumor efficacy by adoptive transfer of Treg-depleted autologous tumor infiltrating lymphocytes in advanced murine breast cancer. We found that, compared to bulk cell transfer, Treg-depleted cell transfer enhanced the activation and proliferation of both CD4(+) and CD8(+) T cells. Most importantly, the immune response deviated towards the Th1 response reflected by increased IFNgamma and reduced IL-4 secretion in both CD4(+) and CD8(+) T cells and an enhanced granzyme B release of CTL. Furthermore, the elicited Th1 response subsequently resulted in delayed tumor growth and prolonged mice survival as well as reduced lung metastasis in tumor-bearing nude mice. These results strongly indicated that Treg-depleted autologous cell transfer greatly e... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992624 Thu, 27 Nov 2008 15:28:41 +0100 1992624 http://www.medworm.com/index.php?rid=1992623&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029834%26dopt%3DAbstract In this study, we constructed a novel oncolytic adenovirus-based shRNA expression system, ZD55-hTERT, and to explore ZD55-hTERT-mediated RNAi for hTERT gene silencing. Our results showed that ZD55-hTERT could induce silencing of hTERT gene effectively, allow for efficient tumor-specific viral replication and induce the apoptosis of tumor cells effectively in vitro and in nude mice. We conclude that combining shRNA gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and shRNA antitumor responses. PMID: 19029834 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992623 Thu, 27 Nov 2008 15:28:37 +0100 1992623 http://www.medworm.com/index.php?rid=1992622&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029835%26dopt%3DAbstract Authors: Truman JP, Rotenberg SA, Kang JH, Lerman G, Fuks Z, Kolesnick R, Marquez VE, Haimovitz-Friedman A We previously demonstrated that treatment of human androgen-responsive prostate cancer cell lines LNCaP and CWR22-Rv1 with 12-O-tetradecanoylphorbol 13-acetate (TPA), a known protein kinase C (PKC) activator, decreases ATM protein levels, thus de-repressing the enzyme ceramide synthase (CS) and promoting apoptosis as well as radio-sensitizing these cells.(1) Here we show that PKCalpha mediates the TPA effect on ATM expression, since ATM suppression and apoptosis induced by either TPA or Diacylglycerol-lactone (DAG-lactone), both inducing PKCalpha activation,(2) are abrogated in LNCaP cells following transfection of a kinase-dead PKCalpha mutant (KD-PKCalpha). Similarly, KD-PKCalph... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992622 Thu, 27 Nov 2008 15:28:33 +0100 1992622 http://www.medworm.com/index.php?rid=1992621&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029836%26dopt%3DAbstract Authors: Axilbund JE, Argani P, Kamiyama M, Palmisano E, Raben M, Borges M, Brune KA, Goggins M, Hruban RH, Klein AP Recent studies have suggested that germ line mutations in the BRCA1 gene may confer an increased risk of developing pancreatic cancer. To determine if BRCA1 mutations explain a significant proportion of familial pancreatic cancer, we sequenced the BRCA1 gene in a large series of well-characterized patients with familial pancreatic cancer and we evaluated the pathology of breast neoplasms that developed in relatives of pancreatic cancer patients. The BRCA1 gene was fully sequenced in 66 pancreatic cancer patients enrolled in the National Familial Pancreas Tumor Registry who had at least two additional relatives with pancreatic cancer. None of the 66 (0/66: 97.5% one-side ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992621 Thu, 27 Nov 2008 15:28:29 +0100 1992621 http://www.medworm.com/index.php?rid=1992620&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029838%26dopt%3DAbstract Authors: Kolasa IK, Rembiszewska A, Felisiak A, Ziolkowska-Seta I, Murawska M, Moes J, Timorek A, Dansonka-Mieszkowska A, Kupryjanczyk J PI3K/AKT signalling pathway controls important cellular processes such as the cell proliferation and apoptosis. PIK3CA gene encoding a catalytic subunit of the PI3K is mutated and/or amplified in various neoplasms, including ovarian cancer. We aimed to evaluate PIK3CA alterations and their clinical importance in ovarian cancer patients. Molecular analysis was performed on 117 ovarian carcinomas with the use of qPCR, SSCP and sequencing. In a group of 98 patients with complete clinical data, 62 patients were treated with standard taxane-platinum regimens and 36 patients with platinum-cyclophosphamide regimens. A multivariate analysis was performed by t... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992620 Thu, 27 Nov 2008 15:28:22 +0100 1992620 http://www.medworm.com/index.php?rid=1992619&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19029839%26dopt%3DAbstract In this report we assessed the ability of Vpr protein or peptides, with or without conjugation to a PTD, to mediate anti-cancer activity against several tumor cell lines. Specifically, several Vpr peptides spanning carboxy amino acids 65-83 induced significant (i.e., greater than 50%) in vitro growth inhibition/toxicity of murine B16.F10 melanoma cells. Likewise, in in vitro experiments with other tumor cell lines, conjugation of Vpr to the Tat derived PTD and transfection of this construct into cells enhanced the induction of in vitro apoptosis by this protein when compared to the effects of transfection of cells with unconjugated Vpr. These results underscore the potential for Vpr based reagents as well as PTDs to enhance anti-tumor activity, and warrants further examination of Vpr prote... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1992619 Thu, 27 Nov 2008 15:28:09 +0100 1992619 http://www.medworm.com/index.php?rid=1940410&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981713%26dopt%3DAbstract In this study, we examined STAT3 activation in endothelial cells (EC) during angiogenic activation and therapeutic angiogenesis inhibition. VEGF stimulation of cultured EC induced STAT3 phosphorylation by a VEGFR2- and Src-dependent mechanism. FGF2 but not PlGF also induced EC STAT3 activation in vitro. Activated STAT3 mediated VEGF induction of EC Bcl-2 and contributed to VEGF protection of EC from apoptosis. In vivo, p-STAT3 was absent by immunohistological staining in the vascular EC of most normal mouse organs but was present in the vessels of mouse and human tumors. Tumor vascular p-STAT3 increased as tumors were induced to overexpress VEGF, indicating that VEGF is an activator of EC p-STAT3 in vivo. Tumor vascular p-STAT3 decreased during angiogenesis inhibition by antagonists of VEG... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940410 Fri, 07 Nov 2008 17:20:38 +0100 1940410 http://www.medworm.com/index.php?rid=1940409&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981716%26dopt%3DAbstract Authors: Esposito L, Giordano A PMID: 18981716 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940409 Fri, 07 Nov 2008 17:20:35 +0100 1940409 http://www.medworm.com/index.php?rid=1940408&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981718%26dopt%3DAbstract Conclusion: The present data demonstrate a high expression of D2R in NETs; this finding is of clinical relevance in view of the potential role of dopaminergic drugs in inhibiting secretion and/or cell proliferation in NETs. PMID: 18981718 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940408 Fri, 07 Nov 2008 17:20:31 +0100 1940408 http://www.medworm.com/index.php?rid=1940407&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981719%26dopt%3DAbstract Conclusions: Treatment with epoetin beta safely and effectively corrects anemia in patients with advanced cervical cancer receiving chemoradiotherapy and is not associated with adverse effects on response rate, overall survival, disease free survival and chemoradiotherapy related acute and late toxicities. PMID: 18981719 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940407 Fri, 07 Nov 2008 17:20:12 +0100 1940407 http://www.medworm.com/index.php?rid=1940406&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981721%26dopt%3DAbstract Authors: Kashyap MK, Marimuthu A, Kishore CJ, Peri S, Keerthikumar S, Prasad TS, Mahmood R, Rao S, Ranganathan P, Vijayakumar M, Kumar KV, Montgomery E, Kumar RV, Pandey A Cancer of the esophagus is of two main types, each with distinct etiological and pathological characteristics. Esophageal squamous cell carcinoma (ESCC) is predominant type of esophageal cancers worldwide comprising almost 95% of cases. While ESCC is prevalent in the developing world, esophageal adenocarcinoma is commonly seen in the developed country, usually in association with Barrett's esophagus. In spite of its higher prevalence, ESCC has not been studied as intensively as esophageal adenocarcinoma. ESCC and esophageal adenocarcinoma are common cancers worldwide with poor survival rate among patients mainly beca... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940406 Fri, 07 Nov 2008 17:20:00 +0100 1940406 http://www.medworm.com/index.php?rid=1940405&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981722%26dopt%3DAbstract Authors: Lee JC, Krochak R, Blouin A, Kanterakis S, Chatterjee S, Arguiri E, Vachani A, Solomides CC, Cengel KA, Christofidou-Solomidou M Flaxseed (FS) has high contents of omega-3 fatty acids and lignans with antioxidant properties. Its use in preventing thoracic X-ray radiation therapy (XRT)-induced pneumonopathy has never been evaluated. We evaluated FS supplementation given to mice given before and post-XRT. FS-derived lignans, known for their direct antioxidant properties, were evaluated in abrogating ROS generation in cultured endothelial cells following gamma radiation exposure. Mice were fed 10% FS or isocaloric control diet for three weeks and given 13.5 Gy thoracic XRT. Lungs were evaluated at 24 hours for markers of radiation-induced injury, three weeks for acute lung damage... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940405 Fri, 07 Nov 2008 17:19:34 +0100 1940405 http://www.medworm.com/index.php?rid=1940404&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981726%26dopt%3DAbstract Authors: Park SH, Wang X, Liu R, Lam KS, Weiss RH Kidney cancer is notoriously difficult to treat when metastatic due to its resistance to conventional chemotherapy. p21 is a cyclin kinase inhibitor which, in many tumor cell lines, conveys an antiapoptotic function through its induction by the DNA damage responsive p53 pathway, such that attenuation of p21 sensitizes several disparate cancer cell lines to DNA-damaging chemotherapy. Since clinical applications with therapeutic antisense and siRNA approaches are problematic, we sought to discover other methods to inhibit p21 which are more readily translatable to the clinic. Utilizing an on-bead enzyme-linked colorimetric binding assay, we screened a diverse one-bead-one-compound combinatorial small molecule library, and identified 12 ca... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940404 Fri, 07 Nov 2008 17:19:23 +0100 1940404 http://www.medworm.com/index.php?rid=1940403&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981727%26dopt%3DAbstract Authors: Raina D, Ahmad R, Chen D, Kumar S, Kharbanda S, Kufe D The MUC1 oncoprotein interacts with the c-Abl tyrosine kinase and blocks nuclear targeting of c-Abl in the apoptotic response to DNA damage. Mutation of the MUC1 cytoplasmic domain at Tyr-60 disrupts the MUC1-c-Abl interaction. The present results demonstrate that the MUC1(Y60F) mutant is a potent inducer of the ARF tumor suppressor. MUC1(Y60F) induces transcription of the ARF locus by a c-Abl-dependent mechanism that promotes CUL-4A-mediated nuclear export of the replication protein Cdc6. The functional significance of these findings is that MUC1(Y60F)-induced ARF expression and thereby inhibition of MDM2 results in the upregulation of p53 and the homeodomain interacting protein kinase 2 (HIPK2) serine/threonine kinase. H... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940403 Fri, 07 Nov 2008 17:19:16 +0100 1940403 http://www.medworm.com/index.php?rid=1940402&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981728%26dopt%3DAbstract Authors: Ribeiro-Oliveira A, Korbonits M, Grossman AB PMID: 18981728 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940402 Fri, 07 Nov 2008 17:19:12 +0100 1940402 http://www.medworm.com/index.php?rid=1940401&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981731%26dopt%3DAbstract In conclusion, the entrapment of endogenous wt p53 in cytoplasm by the low risk HPV11-E6 may be one of the reasons why low risk HPV is not able to induce malignant transformation. PMID: 18981731 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940401 Fri, 07 Nov 2008 17:19:07 +0100 1940401 http://www.medworm.com/index.php?rid=1940400&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981733%26dopt%3DAbstract Authors: Wang J, Yi J Reactive oxygen species (ROS) act as a second messenger in cell signaling and are essential for various biological processes in normal cells. Any aberrance in redox balance may relate to human pathogenesis including cancers. Since ROS are usually increased in cancer cells due to oncogene activation, relative lack of blood supply or other variances, and ROS do involve in initiation, progression and metastasis of cancers, ROS are considered oncogenic. Ironically, ROS production is a mechanism shared by all non-surgical therapeutic approaches for cancers, including chemotherapy, radiotherapy and photodynamic therapy, due to their implication in triggering cell death, therefore ROS are also used to kill cancer cells. Because of the double-edged sword property of ROS i... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940400 Fri, 07 Nov 2008 17:19:02 +0100 1940400 http://www.medworm.com/index.php?rid=1940399&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981734%26dopt%3DAbstract Authors: Weichselbaum RR PMID: 18981734 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940399 Fri, 07 Nov 2008 17:18:59 +0100 1940399 http://www.medworm.com/index.php?rid=1940398&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18981735%26dopt%3DAbstract In this study, we report that mTOR inhibition also induced activations of the MEK/ERK signaling pathway in some cancer cell lines after a prolonged treatment. The combination of rapamycin with the MEK inhibitor U0126 significantly enhanced growth inhibitory effects of cancer cells, suggesting that MEK/ERK activation may counteract mTOR inhibitors' anticancer efficacy. Similarly, the combination of an mTOR inhibitor with the EGF receptor inhibitor erlotinib synergistically inhibited the growth of both human cancer cells in cell cultures and xenografts in nude mice. Moreover, the presence of erlotinib suppressed rapamycin-induced phosphorylation of Akt, ERK and eIF4E as well, implying that erlotinib can suppress mTOR inhibition-induced feedback activation of several survival signaling pathwa... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1940398 Fri, 07 Nov 2008 17:18:54 +0100 1940398 http://www.medworm.com/index.php?rid=1887069&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18927497%26dopt%3DAbstract Conclusions: Puralpha has a role in the cellular response to cisplatin-induced DNA damage and may provide new therapeutic modalities for cisplatin-resistant tumors. PMID: 18927497 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1887069 Sat, 18 Oct 2008 15:02:40 +0100 1887069 http://www.medworm.com/index.php?rid=1856947&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18836295%26dopt%3DAbstract Authors: Li H, Wang J, Zhou T, Zhang Y, Zhang Z Telomerase is an RNA-dependent DNA polymerase that synthesizes telomeric DNA sequences, which provide tandem GT-rich repeats (TTAGGG)n to compensate telomere shortening, and play an important role in cellular aging and carcinogenesis (Cong YS, 2002). Recent studies demonstrated that telomerase activity is absent in most normal human somatic cells but present in over 90% of tumor cells and immortalized cells.Human telomerase reverse transcriptase (hTERT) is the rate-limiting factor of telomerase activity, and also ASODN (antisense oligodeoxynucleotides) targeting to hTERT gene represent a promising approach to tumor therapy (Tamm I, 2001; Kraemer K, 2003). However, the use of ASODN is determined by combination of biological stability, succ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1856947 Tue, 07 Oct 2008 17:43:50 +0100 1856947 http://www.medworm.com/index.php?rid=1856946&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18836304%26dopt%3DAbstract Authors: Wang J, Han Y, Liang J, Cheng X, Yan L, Wang Y, Liu J, Luo G, Chen X, Zhao L, Zhou X, Wu K, Fan D Hepatocellular carcinoma (HCC) represents a worldwide health problem. F1F0 ATPase, one of the most unique supermolecule enzymes in the inner mitochondrial membrane, was recently found located also on the plasma membrane of some tumor and epithelial cells. Ecto-F1F0 ATPase might play the major role in maintaining the normal average intracellular pH in those cells relative to tumor acidic extracellular microenviroment. Inhibiting the extracellular F1F0 ATPase on tumor exhibits both antiangiogenic and antitumorigenic activities. We found previously a strain of murine mAb, mAb6F2C4, which binds with beta-catalytic subunit of F1F0 ATPase. Immunofluorescence and flow cytometry assay sho... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1856946 Tue, 07 Oct 2008 17:43:46 +0100 1856946 http://www.medworm.com/index.php?rid=1856945&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18836306%26dopt%3DAbstract Authors: Xing Y, Liu M, Du Y, Qu F, Li Y, Xiao Y, Zhao J, Zeng F, Xiao C Stromal cell-derived factor-1 (SDF-1)/CXCR4 pathway has been showed to play an important role in prostate cancer (PCa) metastasis, and siRNA expression using cell-specific promoters has been demonstrated to be a potential tool for targeted gene therapy. Here, we illustrate that human telomerase reverse transcriptase (hTERT) promoter-induced CXCR4 knockdown inhibits PCa bone metastasis. We first investigated CXCR4 expressions and interactions of CXCR4/SDF-1 in PCa cells, developed a retrovirus system that could stably express CXCR4 small hairpin RNA driven by hTERT promoter, and then determined the inhibitory effects of cell-specific blockade of CXCR4/SDF-1 pathway on PCa metastasis. It was shown that both PCa tiss... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1856945 Tue, 07 Oct 2008 17:43:39 +0100 1856945 http://www.medworm.com/index.php?rid=1856944&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18836307%26dopt%3DAbstract Authors: Zhao Y, Rangnekar VM Par-4 is a tumor suppressor protein with a pro-apoptotic function. Epigenetic silencing of Par-4 is seen in diverse tumors, and Par-4 knockout mice develop spontaneous tumors in various tissues. Endogenous Par-4 is essential for sensitization of cells to diverse apoptotic stimuli, whereas ectopic expression of Par-4 can selectively induce apoptosis in cancer cells. The cancer-specific pro-apoptotic action of Par-4 resides in its centrally located SAC domain. This review emphasizes the role of Par-4/SAC in apoptosis and tumor resistance. SAC transgenic mice display normal development and life span, and, most importantly, are resistant to spontaneous, as well as oncogene-induced, autochthonous tumors. The tumor resistant phenotype and undetectable toxicity o... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1856944 Tue, 07 Oct 2008 17:43:17 +0100 1856944 http://www.medworm.com/index.php?rid=1789223&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787394%26dopt%3DAbstract Authors: Alvarez H, Koorstra JB, Hong SM, Boonstra JJ, Dinjens WN, Wu TT, Montgomery E, Eshleman JR, Maitra A Esophageal adenocarcinoma currently has one of the most rapidly increasing tumor incidences in the United States, with the vast majority of cases occurring on the backdrop of metaplastic epithelium (Barrett esophagus). The availability of appropriate cell line models is essential for maintaining the pace of esophageal cancer research and for pre-clinical validation of new therapeutic modalities. The identity of several of the widely utilized esophageal adenocarcinoma cell lines (BIC-1, SEG-1 and TE-7) have recently been called into question. Here we describe the establishment and characterization of a bona fide esophageal cancer cell line, JH-EsoAd1, from a patient with Barrett... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789223 Sat, 13 Sep 2008 14:07:27 +0100 1789223 http://www.medworm.com/index.php?rid=1789222&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787399%26dopt%3DAbstract In conclusion, the data reveal that the novel Top2 inhibitor R16 induces degradation of Chk1 via the ubiquitin-proteasome pathway, impairing the function of Chk1 and thus contributing to the anticancer activity of R16. PMID: 18787399 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789222 Sat, 13 Sep 2008 14:07:23 +0100 1789222 http://www.medworm.com/index.php?rid=1789221&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787400%26dopt%3DAbstract Authors: Gao Y, Li L, Zhang LL, He DL Obesity is considered one of the risk factors for many cancers. Serum leptin levels are often elevated in obese people. Leptin has been reported to act as a mitogenic agent and promote renal cancer cell proliferation, whereas the detailed mechanisms still remain to be elucidated. The purpose of this study is to investigate the proliferation and mobility effects in leptin-treated Caki-2 renal cell carcinoma and analyze the alterations of leptin-inducible STAT3 pathways and mitogenic signaling ERK pathways. Our results indicate the constitutive expression of leptin receptor could not be upregulated upon the stimulation of leptin in Caki-2 cells. Leptin increases the proliferation and mobility capabilities of Caki-2 cells via upregulating the expressi... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789221 Sat, 13 Sep 2008 14:07:20 +0100 1789221 http://www.medworm.com/index.php?rid=1789220&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787401%26dopt%3DAbstract In this report, we show that BLM-knockout colorectal cancer cells exhibited endogenous, ATM-dependent double-strand DNA break responses similar to those recently observed in Bloom syndrome patient-derived cells. Xenograft tumors established from BLM-deficient cancer cells were not radiosensitive, but exhibited growth impairment that was comparable to that of wild type tumors treated with a single, high dose of ionizing radiation. These results suggest that pharmacological inhibitors of BLM would have a radiomimetic effect, and that transient inhibition of BLM activity might be a viable strategy for anticancer therapy. PMID: 18787401 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789220 Sat, 13 Sep 2008 14:07:17 +0100 1789220 http://www.medworm.com/index.php?rid=1789219&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787402%26dopt%3DAbstract Authors: Itani WS, El-Banna SH, Hassan SB, Larsson RL, Bazarbachi A, Gali-Muhtasib HU Lebanese sage essential oil possesses antitumor properties, however, the bioactive components and antitumor mechanisms are not known. Here we show that combining the three sage bioactive compounds, Linalyl acetate (Ly), Terpeniol (Te) and Camphor (Ca), caused synergistic inhibition of the growth of two isogenic human colon cancer cell lines HCT-116 (p53(+/+) and p53(-/-)), and had no effect on growth of FHs74Int normal human intestinal cell line. In p53(+/+) cells, the combination of Ly + Te + Ca (10(-3) M of each) caused significant accumulation of cells in PreG(1) (64% at 48 h); less preG(1) increase was observed in response to Ly + Te (25%) or Ly + Ca (14%). In p53(-/-) cells, Ly + Te + Ca caused c... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789219 Sat, 13 Sep 2008 14:07:14 +0100 1789219 http://www.medworm.com/index.php?rid=1789218&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787403%26dopt%3DAbstract Authors: Kinsella TJ PMID: 18787403 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789218 Sat, 13 Sep 2008 14:07:08 +0100 1789218 http://www.medworm.com/index.php?rid=1789217&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787406%26dopt%3DAbstract Authors: Lu H, Shi M, Wang M, Xie Z, Hu M, Yu M, Shen B, Ma Y, Guo N In order to optimize the structure of bispecific antibody (BsAb) and minimize its toxicity, we developed a trivalent anti-ErbB2/anti-CD16 BsAb. This BsAb possesses three antigen binding sites, two antigen binding sites in the form of scFvs targeting the tumor cells overexpressing ErbB2 and a monovalent Fab fragment redirecting NK cells. Critical for this BsAb is its capacity to trigger cytotoxicity of the effector cells in vitro and in vivo. In the present study, we demonstrated that the BsAb is capable of binding to ErbB2 extracellular domain on SKBR3 cells and effectively direct the cytotoxic activities of effector cells to SKBR3 cells even at a low concentration. The BsAb was more effective to SKBR3 cells than to M... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789217 Sat, 13 Sep 2008 14:07:05 +0100 1789217 http://www.medworm.com/index.php?rid=1789216&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787407%26dopt%3DAbstract Conclusions: Our hypothesis of a detrimental effect of PSC on patient survival in LAPC after chemoradiation is supported by the inverse correlation of SPARC in distal stromal cells with patients survival. Furthermore in vitro data indicate that paracrine SPARC from PSC increases the invasion of pancreatic cancer cells. PMID: 18787407 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789216 Sat, 13 Sep 2008 14:06:56 +0100 1789216 http://www.medworm.com/index.php?rid=1789215&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787408%26dopt%3DAbstract Authors: Mariadason JM PMID: 18787408 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789215 Sat, 13 Sep 2008 14:06:53 +0100 1789215 http://www.medworm.com/index.php?rid=1789214&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787415%26dopt%3DAbstract Authors: Shan LQ, Qiu XC, Xu YM, Ji ZG, Yang TT, Chen X, Ma BA, Zhou Y, Fan QY, Yang AG Osteosarcoma is the most common primary malignant bone tumor, with high rates of metastasis. Here, we examined the expression of human epidermal growth factor receptor-2 (HER-2) in osteosarcoma cell lines with different metastatic potential, finding that the expression was correlated with metastasis of implanted tumors. We then introduced an expression vector encoding the e23sFv-PEA II-Bid Delta1-60 gene, composed of a HER2-specific single-chain antibody fused with domain II of Pseudomonas exotoxin A (PEA) and the carboxy end of truncated active Bid. We demonstrated that the e23sFv-PEA II-Bid Delta1-60 molecule selectively recognized and killed HER2-overexpressing osteosarcoma cells in vitro. Subseq... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789214 Sat, 13 Sep 2008 14:06:49 +0100 1789214 http://www.medworm.com/index.php?rid=1789213&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787417%26dopt%3DAbstract Authors: Shekhar MP, Tait L, Pauley RJ, Wu GS, Santner SJ, Nangia-Makker P, Shekhar V, Nassar H, Visscher DW, Heppner GH, Miller FR Comedo-DCIS is a histologic subtype of preinvasive breast neoplasia that is characterized by prominent apoptotic cell death and has greater malignant potential than other DCIS subtypes. We investigated the mechanisms of apoptosis in comedo-DCIS and its role in conversion of comedo-DCIS to invasive cancer. Clinical comedo-DCIS excisions, and the MCF10DCIS.com human breast cancer model which produces lesions resembling comedo-DCIS were analyzed. Apoptotic luminal and myoepithelial cells were identified by TUNEL and reactivity to cleaved PARP antibody, and cell death assessed by Western blotting, Mitocapture, and immunohistochemical assays. MCF10DCIS.com cell... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789213 Sat, 13 Sep 2008 14:06:46 +0100 1789213 http://www.medworm.com/index.php?rid=1789212&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787418%26dopt%3DAbstract Authors: Yu H, Gong X, Luo X, Han W, Hong G, Singh B, Tang CK Elevated levels of epidermal growth factor receptor (EGFR) have been detected in a variety of human cancers. Several reports have demonstrated that the Type III EGF receptor deletion-mutant (EGFRvIII) is frequently detected in various human cancers, including breast cancer. We generated and characterized monoclonal antibody against EGFRvIII. We demonstrated that 29% of DCIS, 40% of primary invasive breast cancers and 54% of metastatic lymph nodes express EGFRvIII by immunohistochemical analysis with two monoclonal antibodies. High levels of EGFRvIII expression were detected in about 5% of primary breast cancer and 27% of metastatic lymph-nodes. Furthermore, in the positive samples, the normal mammary gland exhibited negative... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789212 Sat, 13 Sep 2008 14:06:43 +0100 1789212 http://www.medworm.com/index.php?rid=1789211&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18787419%26dopt%3DAbstract Authors: Zhang J, Park HK, Sun H, Fei P PMID: 18787419 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1789211 Sat, 13 Sep 2008 14:06:40 +0100 1789211 http://www.medworm.com/index.php?rid=1764765&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769112%26dopt%3DAbstract This article discusses how aging predisposes one to cancer. In principle, inhibition of aging should delay cancer. But is it possible to slow aging? As recently proposed, the nutrient-sensing TOR (target of rapamycin) pathway is involved in cellular and organismal aging. In rodents, certain conditions that interfere with the TOR pathway slow aging and prevent cancer. Retrospective analysis of clinical data reveals that inhibitors of TOR prevent cancer in humans. This article envisions a potential clinical use of TOR inhibitors in order to slow aging and delay cancer. PMID: 18769112 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764765 Fri, 05 Sep 2008 15:01:56 +0100 1764765 http://www.medworm.com/index.php?rid=1764764&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769113%26dopt%3DAbstract Authors: Chow JY, Cabral JA, Chang J, Carethers JM Signaling pathways enabling transforming growth factor-beta (TGFbeta)'s conversion from a tumor suppressor to a tumor promoter are not well characterized. TGFbeta utilizes intracellular SMADs to mediate growth suppression; however, TGFbeta-induced proliferative pathways may become more apparent when SMAD signaling is abrogated. Here, we determined regulation of the tumor suppressor PTEN by TGFbeta utilizing SMAD4-null colon cancer cells. TGFbeta downregulated PTEN mRNA and simultaneously induced growth proliferation. TGFbeta also induced both SMAD2 and SMAD3 nuclear translocation, but only triggered SMAD2-specific transcriptional activity in the absence of SMAD4. Interference of SMAD2 with DN-SMAD2 enhanced TGFbeta-induced cell prolife... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764764 Fri, 05 Sep 2008 15:01:54 +0100 1764764 http://www.medworm.com/index.php?rid=1764763&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769114%26dopt%3DAbstract Authors: Kast RE This note mechanistically accounts for recent unexplained findings that all-trans retinoic acid [ATRA, also termed tretinoin] exerts an anti-viral effect against hepatitis C virus [HCV] in chronically infected patients, in whom ATRA also showed synergy with interferon-alpha. How HCV replication was suppressed was unclear. Both effects of ATRA can be accounted for by ATRA's upregulation of RIG protein, an 18 kDa product of retinoic induced gene-1. Increased RIG then couples ATRA to increased Type 1 interferons' production. Details of this mechanism predict that ATRA will similarly augment interferon-alpha activity in treating chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma and that the addition of ribavirin and/or bexarotene will each incrementa... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764763 Fri, 05 Sep 2008 15:01:48 +0100 1764763 http://www.medworm.com/index.php?rid=1764762&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769115%26dopt%3DAbstract In this report, we explored whether RCK/p54 plays a role in maintaining the malignant phenotype and functions in the canonical Wnt signaling pathway of colorectal cancer cells harboring an APC mutation. The ectopic overexpression of RCK/p54 gene in colorectal cancer cells by transfection with RCK/p54 cDNA could lead to a significant increase of Tcf transcriptional activity and expression levels of Wnt target genes. By RNAi assay, we also observed that the Tcf transcriptional activity in LoVo-shRNA cells was significantly decreased by approximately 61.3%, while the mRNA and protein expression levels of Wnt target genes were also obviously decreased. Furthermore, the anti-tumour effects and its possible mechanisms of actions in LoVo cells elicited by a decrease in the level of RCK/p54 by RNA... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764762 Fri, 05 Sep 2008 15:01:43 +0100 1764762 http://www.medworm.com/index.php?rid=1764761&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769116%26dopt%3DAbstract The objective of this study was to identify novel targets of genetic alteration that contribute to pancreatic cancer development or progression. We used Representational Oligonucleotide Microarray Analysis (ROMA) to identify copy number changes in pancreatic cancer xenografts, and validated these findings using FISH, quantitative PCR, Western blotting and immunohistochemical labeling. With this approach, we identified a 0.36-Mb amplification at 18q11.2 containing two known genes, GATA-6 and cTAGE1. Using a cutoff value of 3.0 fold compared to haploid controls, copy number gain or amplification was confirmed in 4 of 42 (9.5%) pancreatic carcinomas analyzed. Combined genetic and transcriptional analyses showed consistent overexpression of GATA-6 in all carcinomas with 18q11.2 gain, as well a... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764761 Fri, 05 Sep 2008 15:01:40 +0100 1764761 http://www.medworm.com/index.php?rid=1764760&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769117%26dopt%3DAbstract Authors: Godman CA, Joshi R, Tierney BR, Greenspan E, Rasmussen TP, Wang HW, Shin DG, Rosenberg DW, Giardina C Histone deacetylase 3 (HDAC3) is overexpressed in approximately half of all colon adenocarcinomas. We took an RNAi approach to determine how HDAC3 influenced chromatin modifications and the expression of growth regulatory genes in colon cancer cells. A survey of histone modifications revealed that HDAC3 knockdown in SW480 cells significantly increased histone H4-K12 acetylation, a modification present during chromatin assembly that has been implicated in imprinting. This modification was found to be most prominent in proliferating cells in the intestinal crypt and in APC(Min) tumors, but was less pronounced in the tumors that overexpress HDAC3. Gene expression profiling of SW4... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764760 Fri, 05 Sep 2008 15:01:37 +0100 1764760 http://www.medworm.com/index.php?rid=1764759&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769118%26dopt%3DAbstract In conclusions, low level expression of p27 protein may partially attribute to latent EBV infection in ENKL. EBNA1 may be a good target for the treatment of EBV associated ENKL. PMID: 18769118 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764759 Fri, 05 Sep 2008 15:01:34 +0100 1764759 http://www.medworm.com/index.php?rid=1764758&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769119%26dopt%3DAbstract Authors: Keen J PMID: 18769119 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764758 Fri, 05 Sep 2008 15:01:31 +0100 1764758 http://www.medworm.com/index.php?rid=1764757&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769120%26dopt%3DAbstract Authors: Ren XY, Liang ZY, Shi XH, Liu TH It has been reported that the local introduction of a promoterless DNA containing the complementary DNA (cDNA) sequence of a gene could induce gene-specific silencing in plants. The feasibility of this kind of silencing in human cancer cells is as yet unknown. The current study was designed to investigate the antitumor effects of a homologous promoterless K-ras cDNA system on pancreatic cancer. A full-length K-ras cDNA fragment was cloned into the promoterless plasmid puc19 to yield puc-K-ras. This construct was then transfected into pancreatic cancer cells. Our results demonstrated that the transfection of a promoterless K-ras cDNA resulted in a significant decrease in endogenous K-ras in a dose- and time-dependent manner and induced pancreati... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764757 Fri, 05 Sep 2008 15:01:28 +0100 1764757 http://www.medworm.com/index.php?rid=1764756&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769121%26dopt%3DAbstract This report shows for the first time that radiation sensitizers like BrdU enhance and modify radiation-induced cell death by accelerating an increased bax/bcl-2 ratio in unirradiated cells, and subsequently increasing radiation-induced apoptosis and/or autophagy depending on radiation dosage. PMID: 18769121 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764756 Fri, 05 Sep 2008 15:01:24 +0100 1764756 http://www.medworm.com/index.php?rid=1764755&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769122%26dopt%3DAbstract Authors: Tavares TS, Nanus D, Yang XJ, Gudas LJ Histone deacetylase (HDAC) inhibitor treatments can augment the anti-tumor effects of retinoids in renal cancer cells. We studied the effects of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and 13-cis retinoic acid (cRA) on two human renal cell carcinoma (RCC) lines. Cells were cultured in the presence of each drug for six days to determine the responses to monotherapy and to combination therapy. The proliferation of SKRC06 was inhibited with cRA treatment; SKRC39 was not. However, both RCC lines were sensitive to growth inhibition by dibutyryl cyclic AMP, with or without 13-cis RA. SAHA alone also reduced cell proliferation in both cell lines. To identify the alterations in gene expression that correlate with the responsiven... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764755 Fri, 05 Sep 2008 15:01:21 +0100 1764755 http://www.medworm.com/index.php?rid=1764754&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769123%26dopt%3DAbstract In this study, we found that the FTIs manumycin A, FTI-276, and lonafarnib induced autophagy in two human cancer cell lines. We also found that neither inhibition of apoptosis with a pan-caspase inhibitor nor inhibition of autophagy increased the number of clones of lonafarnib-treated U2OS osteosarcoma cells that formed in soft agar. Although whether autophagy is a cell death or cell survival mechanism after FTI treatment remains unresolved, our data show that cancer cells apparently can shift between apoptosis and autophagy once they are committed to die after FTI treatment. PMID: 18769123 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764754 Fri, 05 Sep 2008 15:01:16 +0100 1764754 http://www.medworm.com/index.php?rid=1764753&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769124%26dopt%3DAbstract We present biochemical and cell biological evidence that combined 17-AAG and Trastuzumab treatment of ErbB2-overexpressing breast cancer cell lines leads to enhanced ubiquitinylation, downregulation from the cell surface and lysosomal degradation of ErbB2. Importantly, combined 17-AAG and Trastuzumab treatment induced synergistic growth arrest and cell death specifically in ErbB2-overexpressing but not in ErbB2-low breast cancer cells. Our results suggest the 17-AAG and Trastuzumab combination as a mechanism-based combinatorial targeted therapy for ErbB2-overexpressing breast cancer patients. PMID: 18769124 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764753 Fri, 05 Sep 2008 15:01:13 +0100 1764753 http://www.medworm.com/index.php?rid=1764752&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769126%26dopt%3DAbstract Authors: Aggarwal BB PMID: 18769126 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764752 Fri, 05 Sep 2008 15:01:10 +0100 1764752 http://www.medworm.com/index.php?rid=1764751&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769129%26dopt%3DAbstract Authors: Hostetter C, Licata LA, Witkiewicz A, Costantino CL, Yeo CJ, Brody JR, Keen JC With prolonged exposure, a majority of estrogen receptor positive cancers develop resistance to tamoxifen and subsequent therapies including selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). While much is known about overexpression of key growth promoting receptors including EGF, erbB2/Her2 and IGF receptors and subsequent activation of MAPK signaling associated with resistance, the underlying mechanism in the development of resistance still remains unknown. We found that inhibition of JNK, a member of the MAPK family, decreases cytoplasmic accumulation of the RNA binding protein HuR. This data combined with previous reports that erbB2/Her2 and IGF-IR signals through JNK... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764751 Fri, 05 Sep 2008 15:01:05 +0100 1764751 http://www.medworm.com/index.php?rid=1764750&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18769132%26dopt%3DAbstract Authors: Warnock LJ, Knox A, Mee TR, Raines SA, Milner J The tumour suppressor protein p53 is considered the "Guardian of the Genome", crucial for cell cycle control and mutated in over 50% of human cancers. Following cellular stress, post-translational modifications such as phosphorylation and acetylation stabilise and activate p53 for cell cycle arrest, DNA repair, apoptosis or senescence. p53 protein functions as a tetramer and we have shown that loss of tetramerisation and changes at the N-terminus influence the recovery of wild type p53 'status'. To investigate the relationship between tetramerisation and post-translational modifications we examined a range of site-specific modifications in wild type and dimeric mutant (M340Q/L344R) murine p53 expressed in MEFs p53(-/-) and in wil... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1764750 Fri, 05 Sep 2008 15:01:02 +0100 1764750 http://www.medworm.com/index.php?rid=1726944&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719359%26dopt%3DAbstract Authors: Maclachlan TK PMID: 18719359 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1726944 Sat, 23 Aug 2008 16:28:04 +0100 1726944 http://www.medworm.com/index.php?rid=1726941&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719363%26dopt%3DAbstract Authors: Dannenmann C, Shabani N, Friese K, Jeschke U, Mylonas I, Brüning A The metastasis-associated genes MTA1 and MTA3 are transcriptional repressors with potential effects on cancer. We analyzed the expression of MTA1, MTA3, ERalpha, ERbeta and E-cadherin in a total of 115 paraffin-embedded ovarian cancer tissues with respect to cancer staging and FIGO grading. Expression of MTA1, but not that of MTA3, was found to be significantly enhanced in ovarian cancer tissues with advanced cancer stages and higher FIGO grading, indicating an important role of MTA1 in the progression of ovarian cancer. To get further insights into the function of MTA1 in ovarian cancer, MTA1-overexpressing cancer cell clones were generated. In vitro, overexpression of exogenous MTA1 in OVCAR-3 cells had ... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1726941 Sat, 23 Aug 2008 16:27:55 +0100 1726941 http://www.medworm.com/index.php?rid=1726940&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719364%26dopt%3DAbstract Authors: Germano IM, Uzzaman M, Keller G Patients with glioblastomas have a poor prognosis and new treatments paradigms are needed. The futility of current treatments lies in part on the difficulty of delivering therapeutic agents to the tumor. In this article, we review and discuss current knowledge of adjuvant treatment for glioblastomas including gene therapy and viral vectors. Additionally, this review provides an update on recent progress, which has focused on improving delivery methods including the development of new approaches such as stem cells. Particular emphasis is given to laboratory data showing the use of embryonic stem cells used as vectors to deliver pro-apoptotic genes to glioblastoma cells. PMID: 18719364 [PubMed - as supplied by publisher] (Source: Cancer Biolog... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1726940 Sat, 23 Aug 2008 16:27:49 +0100 1726940 http://www.medworm.com/index.php?rid=1726939&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719365%26dopt%3DAbstract In this study, we evaluated the combined effects of LTalpha and ten chemotherapeutic drugs on cell growth in a panel of human epithelial tumor cells, and explored the molecular mechanism of their mutual action. The results showed that platinums (cisplatin, carboplatin, oxaliplatin) are more universally effective than other chemotherapeutic drugs (doxorubicin, epi-doxorubicin, 5-flourouracil, mitomycin, cyclophosphamide, vincristine and vinorelbine) to enhance the response of six human epithelial tumor cell lines (A375, Bcap37, NCI-H157, SW480, BGC-823 and HeLa) to LTalpha. A systemic treatment with a combination of LTalpha and cisplatin in a human Bcap37 breast cancer xenograft nude mice model dramatically improved the therapeutic efficacy of LTalpha. Further analysis revealed that the sen... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1726939 Sat, 23 Aug 2008 16:27:45 +0100 1726939 http://www.medworm.com/index.php?rid=1726938&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719366%26dopt%3DAbstract This report for the first time establishes novel features of Cu-GER in prostate cancer cells of varying tumorigenic phenotypes and provides potentially novel read-outs for assessing effectiveness of curcumin in prostate cancer and likely in other cancers. Importantly, new gene-networks identified here further delineate molecular mechanism(s) of action of curcumin in prostate cancer cells. PMID: 18719366 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy) Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1726938 Sat, 23 Aug 2008 16:27:42 +0100 1726938 http://www.medworm.com/index.php?rid=1726937&cid=s_37752_6_f&fid=37752&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18719367%26dopt%3DAbstract Authors: Zhang J, Zafrullah M, Yang X, Yin X, Zhang Z, Fuks Z, Kolesnick R While antisense oligonucleotide (AS-ODN) technology holds promise for the treatment of cancer, to date there have been no clinical successes. Unfortunately, current assays are not sufficiently sensitive to measure tissue ODN levels. Hence it has not been possible to ascertain whether treatment failures result from failure of drug delivery. To investigate the relationship between drug uptake and therapeutic effect, we developed an ultrasensitive noncompetitive hybridization-ligation enzyme-linked immunosorbent assay (NCHL-ELISA) to quantify Kinase Suppressor of Ras1 (KSR1) AS-ODN drug uptake in plasma and tumor tissues. In mice harboring PANC-1 pancreatic cancer xenografts and continuously infused with AS-ODN, ou... Cancer Biology and Therapy journals http://www.medworm.com/rss/comments.php?id=1726937 Sat, 23 Aug 2008 16:27:33 +0100 1726937