Cancer Letters RSS feed: Current Issue. CANCER LETTERS is an international journal that considers full-length articles and Mini Reviews in the broad area of basic and translational oncology. Additionally, Special Issues highlight topical areas in cancer research. Basic areas of interest to a broad readership of Cancer Letters include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal places emphasis on experimental therapeutics, particularly targeted therapies for personalized cancer medicine. Cancer Letters now offers online submission for authors. Please submit manuscripts at http://www.ees.elsevier.com/can and follow the instructions on the site. http://www.cancerletters.info/?rss=yesElsevier Inc.en © 2012 Elsevier Ireland Ltd. All rights reserved. Cancer Letters0304-3835321228 August 2012 © 2012 Elsevier Ireland Ltd. All rights reserved. healthpermissions@elsevier.comhttp://www.cancerletters.info/article/PIIS0304383512000857/abstract?rss=yesAbstract: With the approval of the antiangiogenic antibody bevacizumab in non-small cell lung cancer (NSCLC) and other malignancies, the tumor vasculature has emerged as a worthwhile therapeutic target. Second-line therapies have the potential to improve overall survival and quality of life over best supportive care alone. Accordingly, phase II and phase III studies are actively evaluating antiangiogenic treatments in the second-line setting in NSCLC, and results are awaited. Such therapies include antiangiogenic antibodies, small molecule inhibitors, and vascular-disrupting agents. This review will present the current landscape of angiogenesis inhibition in NSCLC, focusing on use as second-line therapy.Antiangiogenic agents as second-line therapy for advanced non-small cell lung cancerKaren L. Reckamp10.1016/j.canlet.2012.01.041Cancer Letters 321, 2 (2012)2012-02-23Cancer Letters2012-02-233212S0304-3835(12)X0012-0Mini-reviews101109http://www.cancerletters.info/article/PIIS0304383512000845/abstract?rss=yesAbstract: Inflammation is underlying biological phenomenon common in infection and cancer. Mucins are glycoproteins which establish a physical barrier for undesirable entry of foreign materials through epithelial surfaces. A deregulated expression and an anomalous glycosylation pattern of mucins are known in large number of cancers. TLRs are class of receptors which recognize the molecular patterns of invading pathogens and activate complex inflammatory pathways to clear them. Aberrant expression of TLRs is observed in many cancers. A highly orchestrated action of mucins and TLRs is well evolved host defence mechanism; however, a link between the two in other non-infectious conditions has received less attention. Here we present an overview as to how mucins and TLRs give protection to the host and are deregulated during carcinogenesis. Further, we propose the possible mechanisms of cross-regulation between them in pathogenesis of cancer. As both mucins and TLRs are therapeutically important class of molecules, an understanding of the underlying molecular mechanisms connecting the two will open new avenues for the therapeutic targeting of cancer.Mucins and Toll-like receptors: Kith and kin in infection and cancerShikha Tarang, Sushil Kumar, Surinder K. Batra10.1016/j.canlet.2012.01.040Cancer Letters 321, 2 (2012)2012-04-26Cancer Letters2012-04-263212S0304-3835(12)X0012-0Mini-reviews110119http://www.cancerletters.info/article/PIIS0304383512000444/abstract?rss=yesAbstract: Targeted photosensitizer delivery to EGFR-expressing cells was achieved in the present study using a high purity, targeted photoimmunoconjugate (PIC). When the PDT agent, benzoporphyrin derivative monoacid ring A (BPD) was coupled to an EGFR-targeting antibody (cetuximab), we observed altered cellular localization and selective phototoxicity of EGFR-positive cells, but no phototoxicity of EGFR-negative cells. Cetuximab in the PIC formulation blocked EGF-induced activation of the EGFR and downstream signaling pathways. Our results suggest that photoimmunotargeting is a useful dual strategy for the selective destruction of cancer cells and also exerts the receptor-blocking biological function of the antibody.Epidermal growth factor receptor-targeted photosensitizer selectively inhibits EGFR signaling and induces targeted phototoxicity in ovarian cancer cellsAdnan O. Abu-Yousif, Anne C.E. Moor, Xiang Zheng, Mark D. Savellano, Weiping Yu, Pål K. Selbo, Tayyaba Hasan10.1016/j.canlet.2012.01.014Cancer Letters 321, 2 (2012)2012-03-29Cancer Letters2012-03-293212S0304-3835(12)X0012-0Regular Articles120127http://www.cancerletters.info/article/PIIS0304383512000523/abstract?rss=yesAbstract: We evaluated the effects of sunitinib monotherapy and in combination with cisplatin in human gastric cancer cell lines. Sunitinib showed antiproliferative effect in gastric cancer cells line with high PDGFRA expression. Knockdown of PDGFRA showed that sunitinib sensitivity was correlated with the basal expression of PDGFRA. Synergistic growth inhibitory activity in combination with cisplatin was identified. We further explored how sunitinib potentiated the activity of cisplatin. We found that sunitinib treatment resulted in the down-regulation of ERCC1 expression via the modulation of PDGFRA expression in gastric cancer cells. The effect was verified via SNU484 xenograft model. Our data support the rationale of clinical trial using sunitinib in combination of cisplatin in gastric cancer.Sunitinib synergizes the antitumor effect of cisplatin via modulation of ERCC1 expression in models of gastric cancerYoung-Kwang Yoon, Seock-Ah Im, Ahrum Min, Hwang-Phill Kim, Hyung-Seok Hur, Kyung-Hun Lee, Sae-Won Han, Sang-Hyun Song, Do Youn Oh, Tae-You Kim, Woo Ho Kim, Yung-Jue Bang10.1016/j.canlet.2012.01.019Cancer Letters 321, 2 (2012)2012-03-22Cancer Letters2012-03-223212S0304-3835(12)X0012-0Regular Articles128136http://www.cancerletters.info/article/PIIS0304383512000742/abstract?rss=yesAbstract: Cisplatin can induce apoptosis in ovarian cancer cells through the mitochondrial death pathway, and dysregulation of this pathway contributes to cisplatin resistance in ovarian cancer cells. Here we show that cisplatin induces mitochondrial proteins such as Smac/DIABLO, Cytochrome c, and HrtA2/Omi release to the cytosol and apoptosis in cisplatin-sensitive, but not -resistant ovarian cancer cells. Bax translocation to mitochondria is required for mitochondrial protein release and cisplatin-induced apoptosis in human ovarian cancer cells. Hsp70 is highly expressed in cisplatin-resistant cells. Hsp70 promotes chemoresistance, in part, by blocking Bax translocation to the mitochondria and mitochondrial protein release to cytosol in human ovarian cancer cells.Hsp70 promotes chemoresistance by blocking Bax mitochondrial translocation in ovarian cancer cellsXiaokui Yang, Jiandong Wang, Ying Zhou, Yamei Wang, Shuyu Wang, Weiyuan Zhang10.1016/j.canlet.2012.01.030Cancer Letters 321, 2 (2012)2012-03-23Cancer Letters2012-03-233212S0304-3835(12)X0012-0Regular Articles137143http://www.cancerletters.info/article/PIIS0304383512001000/abstract?rss=yesAbstract: Ginsenoside F2 (F2) was assessed for its antiproliferative activity against breast cancer stem cells (CSCs). F2 induced apoptosis in breast CSCs by activating the intrinsic apoptotic pathway and mitochondrial dysfunction. Concomitantly, F2 induced the formation of acidic vesicular organelles, recruitment of GFP-LC3-II to autophagosomes, and elevation of Atg-7 levels, suggesting that F2 initiates an autophagic progression in breast CSCs. Treatment with an inhibitor of autophagy enhanced F2-induced cell death. Our findings provide new insights into the anti-cancer activity of F2 and may contribute to the rational use and pharmacological study of F2.Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cellsTrang Thi Mai, JeongYong Moon, YeonWoo Song, Pham Quoc Viet, Pham Van Phuc, Jung Min Lee, Tae-Hoo Yi, Moonjae Cho, Somi Kim Cho10.1016/j.canlet.2012.01.045Cancer Letters 321, 2 (2012)2012-04-23Cancer Letters2012-04-233212S0304-3835(12)X0012-0Regular Articles144153http://www.cancerletters.info/article/PIIS0304383512000997/abstract?rss=yesAbstract: Hepatitis C virus Core plays a vital role in the development of hepatocellular carcinoma; however, the mechanism is still controversial. Here, we show that Core overcomes premature senescence provoked by a reactive oxygen species inducer, H2O2, in human liver cells. For this effect, Core down-regulated levels of p16 via promoter hypermethylation and subsequently induced phosphorylation of Rb in the presence of H2O2. Levels of p21 and p27, however, were little affected by Core under the condition. The potentials of Core to inactivate Rb and suppress H2O2-mediated cellular senescence were abolished when levels of p16 were recovered by either exogenous complementation or inhibition of DNA methylation. Considering that cellular senescence provoked by oxidative stresses is an important tumor suppression process, our present study provides a new strategy by which HCV promotes development of hepatocellular carcinoma.Hepatitis C virus Core protein overcomes stress-induced premature senescence by down-regulating p16 expression via DNA methylationJoo Song Lim, Sun-Hye Park, Kyung Lib Jang10.1016/j.canlet.2012.01.044Cancer Letters 321, 2 (2012)2012-02-27Cancer Letters2012-02-273212S0304-3835(12)X0012-0Regular Articles154161http://www.cancerletters.info/article/PIIS0304383512000985/abstract?rss=yesAbstract: Giant cell tumor (GCT) derived stromal cells (GCTSCs) have been identified as the neoplastic cell population of GCTs. Within these stromal cells a subpopulation has been identified that shares several features with mesenchymal stem cells (MSCs) indicating that these neoplastic cells develop from MSCs. Although spontaneous transformations of MSC have already been observed in vitro and in vivo the underlying molecular mechanisms are poorly understood. As microRNAs are crucially involved in tumorigenesis and the modulation of stem cell fate and behavior, they represent promising candidates for the regulation of this process. Therefore, the aim of this study was the comparative analysis of the microRNA expression profiles of GCTSCs and MSCs in order to identify differentially expressed microRNAs and their target genes. We could identify a microRNA signature consisting of 26 differentially expressed microRNAs that perfectly separates these two cell types. One of the microRNAs with the most pronounced differences in expression levels was miR-224. We could confirm the already known regulation of the apoptosis inhibitor API5 by miR-224 and could further identify three novel miR-224 target genes (SMAD5, SLMAP, H3.3B). The involvement of these genes in the regulation of apoptosis resistance, proliferation, differentiation and the regulation of gene transcription suggests pivotal roles of these genes in the neoplastic transformation of MSCs during GCT development.A microRNA signature differentiates between giant cell tumor derived neoplastic stromal cells and mesenchymal stem cellsJoerg Fellenberg, Heiner Saehr, Burkhard Lehner, Daniela Depeweg10.1016/j.canlet.2012.01.043Cancer Letters 321, 2 (2012)2012-02-27Cancer Letters2012-02-273212S0304-3835(12)X0012-0Regular Articles162168http://www.cancerletters.info/article/PIIS0304383512000973/abstract?rss=yesAbstract: Previous studies have shown that excess calcineurin subunit B (CnB) associates with mitochondria. Here, CnB overexpression increased CN activity in cells and enhanced TNF-alpha-induced cell death independent of CN activity. Overexpression of CnB increased intracellular Ca2+ concentration, enhanced caspase-3 activity, reduced Bcl-2 expression, and decreased mitochondrial membrane potential, with no change of caspase-8 or p53. CnB bound to isolated mitochondria in a Ca2+-dependent manner, and stimulated cytochrome c release from the mitochondria. Altogether, these results demonstrate that CnB is capable of promoting TNF-alpha-induced apoptosis, possibly through effects on mitochondrial functions.Calcineurin subunit B promotes TNF-alpha-induced apoptosis by binding to mitochondria and causing mitochondrial Ca2+ overloadJinbo Cheng, Wei Tang, Zhenyi Su, Junxia Guo, Li Tong, Qun Wei10.1016/j.canlet.2012.01.042Cancer Letters 321, 2 (2012)2012-02-23Cancer Letters2012-02-233212S0304-3835(12)X0012-0Regular Articles169178http://www.cancerletters.info/article/PIIS0304383512001048/abstract?rss=yesAbstract: Calcineurin inhibitors (CNIs) may promote post-transplantation cancer through altered expression of cytokines and chemokines in tumor cells. We found that there is a potential cross-talk among CNI-induced signaling molecules and mTOR. Here, we utilized a murine model of post-transplantation cancer to examine the effect of a combination therapy (CNI+mTOR-inhibitor rapamycin) on allograft survival and renal cancer progression. The therapy prolonged allograft survival; and significantly attenuated CNI-induced post-transplantation cancer progression, with down-regulation of mTOR and S6-kinase phosphorylation. Also, rapamycin inhibited CNI-induced over-expression of the angiogenic cytokine VEGF, and the chemokine receptor CXCR3 and its ligands in post-transplantation tumor tissues.Effectiveness of a combination therapy using calcineurin inhibitor and mTOR inhibitor in preventing allograft rejection and post-transplantation renal cancer progressionAninda Basu, Tao Liu, Pallavi Banerjee, Evelyn Flynn, David Zurakowski, Dipak Datta, Ondrej Viklicky, Martin Gasser, Ana Maria Waaga-Gasser, Jun Yang, Soumitro Pal10.1016/j.canlet.2012.02.004Cancer Letters 321, 2 (2012)2012-03-05Cancer Letters2012-03-053212S0304-3835(12)X0012-0Regular Articles179186http://www.cancerletters.info/article/PIIS0304383512001036/abstract?rss=yesAbstract: The ability to induce changes in cell membrane properties is nowadays considered an additional mechanism to explain the pharmacological effects of non-steroidal anti-inflammatory drugs (NSAIDs). We previously demonstrated that the NSAID Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, triggers apoptosis in HCA-7 colon cancer cells independently from the inhibition of these enzymes. Here, we provide evidence that, in HCA-7 cells, the pro-apoptotic effect of this drug relies, at least in part, on its ability to inhibit epidermal growth factor receptor (EGFR) signalling by a decrease of cell membrane fluidity. Indeed, Licofelone induced a relevant change in the relative proportions of some saturated, monounsaturated and polyunsaturated fatty acids constituting HCA-7 phospholipid fraction and significantly increased the levels of cholesterol in HCA-7 cell membrane. All of these changes resulted in a remarkable decrease of membrane fluidity. Such phenomenon was associated with the block of EGFR kinase activity and of its downstream targets, the p44-42 mitogen-activated protein kinase (MAPK) and AKT cascades, whose inhibitions were found to induce apoptosis in HCA-7 cells. Overall, these findings provide a new additional mechanism by which NSAIDs are effective toward colon cancer cells.The decrease of cell membrane fluidity by the non-steroidal anti-inflammatory drug Licofelone inhibits epidermal growth factor receptor signalling and triggers apoptosis in HCA-7 colon cancer cellsSimona Tavolari, Alessandra Munarini, Gianluca Storci, Stefan Laufer, Pasquale Chieco, Tiziana Guarnieri10.1016/j.canlet.2012.02.003Cancer Letters 321, 2 (2012)2012-03-05Cancer Letters2012-03-053212S0304-3835(12)X0012-0Regular Articles187194http://www.cancerletters.info/article/PIIS0304383512001097/abstract?rss=yesAbstract: Med1/TRAP220 is an essential component of the TRAP/Mediator complex. In this study, we present a novel function of Med1 in human non-small-cell lung cancer (NSCLC) progression. We found that the loss of Med1 expression was strongly associated with increased rates of invasion and metastasis in NSCLC patients. Consistent with lung cancer patient data, the knockdown of Med1 in NSCLC cell lines led to an increase in cell migration and invasion. Med1-depleted cells displayed an increase in metastasis in a xenograft tumor model and in an in vivo metastasis assay. Moreover, a microarray analysis revealed that the mRNA levels of the metastasis-related genes uPAR, ID2, ID4, PTP4A1, PKP3, TGM2, PLD1, TIMP2, RGS2, and HOXA4 were altered upon Med1 knockdown. Collectively, these results suggest that the loss of Med1 increases the invasive potential of human NSCLC cells by modulating the expression of metastasis-related genes.Loss of Med1/TRAP220 promotes the invasion and metastasis of human non-small-cell lung cancer cells by modulating the expression of metastasis-related genesHyun-Ju Kim, Mee Sook Roh, Choon Hee Son, Ae Jeong Kim, Hye Jin Jee, Naree Song, Minjee Kim, Su-Young Seo, Young Hyun Yoo, Jeanho Yun10.1016/j.canlet.2012.02.009Cancer Letters 321, 2 (2012)2012-03-19Cancer Letters2012-03-193212S0304-3835(12)X0012-0Regular Articles195202