SGI-110 Priming Sensitizes Hepatocellular Carcinoma Cells to Oxaliplatin
Promoter DNA hypermethylation is an important biomarker of hepatocellular carcinoma (HCC), supporting the potential utility of demethylating agents in this disease. SGI-110 is a second-generation hypomethylating agent formulated as a dinucleotide of decitabine and deoxyguanosine that yields longer half-life and more extended decitabine exposure than decitabine IV infusion. Here we performed preclinical evaluation of SGI-110 in HCC models to guide the design of a phase I/II clinical trial. HCC cell lines and xenograft models were used to determine the antitumor activity of SGI-110 as a single agent and in combination with o...
Source: Molecular Oncology - June 15, 2015 Category: Cancer & Oncology Authors: Yuting Kuang, Anthony El-Khoueiry, Pietro Taverna, Mats Ljungman, Nouri Neamati Source Type: research
Src family kinases differentially influence glioma growth and motility
Src-family kinase (SFK) signaling impacts multiple tumor-related properties, particularly in the context of the brain tumor glioblastoma. Consequently, the pan-SFK inhibitor dasatinib has emerged as a therapeutic strategy, despite physiologic limitations to its effectiveness in the brain. We investigated the importance of individual SFKs (Src, Fyn, Yes, and Lyn) to glioma tumor biology by knocking down individual SFK expression both in culture (LN229, SF767, GBM8) and orthotopic xenograft (GBM8) contexts. (Source: Molecular Oncology)
Source: Molecular Oncology - June 9, 2015 Category: Cancer & Oncology Authors: Laura J. Lewis-Tuffin, Ryan Feathers, Priya Hari, Nisha Durand, Zhimin Li, Fausto J. Rodriguez, Katie Bakken, Brett Carlson, Mark Schroeder, Jann N. Sarkaria, Panos Z. Anastasiadis Source Type: research
Frequent expression of PD-L1 on circulating breast cancer cells
Immune checkpoint regulators such as PD-L1 have become exciting new therapeutic targets leading to long lasting remissions in patients with advanced malignancies. However, in view of the remarkable costs and the toxicity profiles of these therapies, predictive biomarkers able to discriminate responders from non-responders are urgently needed. In the present paper, we provide evidence that PD-L1 is frequently expressed on metastatic cells circulating in the blood of hormone receptor-positive, HER2-negative breast cancer patients. (Source: Molecular Oncology)
Source: Molecular Oncology - June 8, 2015 Category: Cancer & Oncology Authors: Martine Mazel, William Jacot, Klaus Pantel, Kai Bartkowiak, Delphine Topart, Laure Cayrefourcq, Delphine Rossille, Thierry Maudelonde, Thierry Fest, Catherine Alix-Panabières Source Type: research
Inhibition of ligand-independent constitutive activation of the met oncogenic receptor by the engineered chemically-modified antibody DN30
An awesome number of experimental and clinical evidences indicate that constitutive activation of the Met oncogenic receptor plays a critical role in the progression of cancer toward metastasis and/or resistance to targeted therapies. While mutations are rare, the common mechanism of Met activation is overexpression, either by gene amplification (‘addiction’) or transcriptional activation (‘expedience’). In the first instance ligand-independent kinase activation plays a major role in sustaining the transformed phenotype. (Source: Molecular Oncology)
Source: Molecular Oncology - June 4, 2015 Category: Cancer & Oncology Authors: Elisa Vigna, Cristina Chiriaco, Simona Cignetto, Lara Fontani, Cristina Basilico, Fiorella Petronzelli, Paolo M. Comoglio Source Type: research
Tamoxifen induces a pluripotency signature in breast cancer cells and human tumors
Tamoxifen is the treatment of choice in estrogen receptor alpha breast cancer patients that are eligible for adjuvant endocrine therapy. However, ∼50% of ERα-positive tumors exhibit intrinsic or rapidly acquire resistance to endocrine treatment. Unfortunately, prediction of de novo resistance to endocrine therapy and/or assessment of relapse likelihood remain difficult. While several mechanisms regulating the acquisition and the maintenance of endocrine resistance have been reported, there are several aspects of this phenomenon that need to be further elucidated. (Source: Molecular Oncology)
Source: Molecular Oncology - June 4, 2015 Category: Cancer & Oncology Authors: George Notas, Vassiliki Pelekanou, Marilena Kampa, Konstantinos Alexakis, Stelios Sfakianakis, Aggelos Laliotis, John Askoxilakis, Eleftheria Tsentelierou, Maria Tzardi, Andreas Tsapis, Elias Castanas Source Type: research
Identification of Major Factors Associated with Failed Clinical Molecular Oncology Testing Performed by Next Generation Sequencing (NGS)
DNA analysis by NGS has become important to direct the clinical care of cancer patients. However, NGS is not successful in all cases, and the factors responsible for test failures have not been systematically evaluated. (Source: Molecular Oncology)
Source: Molecular Oncology - May 25, 2015 Category: Cancer & Oncology Authors: Hussam Al-Kateb, TuDung T. Nguyen, Karen Steger-May, John D. Pfeifer Source Type: research
Anticancer activity of Pyrithione Zinc in oral cancer cells identified in small molecule screens and xenograft model: Implications for oral cancer therapy
Oral squamous cell carcinoma (OSCC) patients diagnosed in late stages have limited chemotherapeutic options, underscoring the great need for development of new anticancer agents for more effective disease management. We aimed to identify novel anticancer agents for OSCC using quantitative high throughput assays for screening six chemical libraries consisting of 5170 small molecule inhibitors. In depth characterization resulted in identification of pyrithione zinc (PYZ) as the most effective cytotoxic agent inhibiting cell proliferation and inducing apoptosis in OSCC cells in vitro. (Source: Molecular Oncology)
Source: Molecular Oncology - May 20, 2015 Category: Cancer & Oncology Authors: Gunjan Srivastava, Ajay Matta, Guodong Fu, Raj Thani Somasundaram, Alessandro Datti, Paul G. Walfish, Ranju Ralhan Source Type: research
Loss of SOX2 expression induces cell motility via vimentin up-regulation and is an unfavorable risk factor for survival of head and neck squamous cell carcinoma
Recurrent gain on chromosome 3q26 encompassing the gene locus for the transcription factor SOX2 is a frequent event in human squamous cell carcinoma, including head and neck squamous cell carcinoma (HNSCC). Numerous studies demonstrated that SOX2 expression and function is related to distinct aspects of tumor cell pathophysiology. However, the underlying molecular mechanisms are not well understood, and the correlation between SOX2 expression and clinical outcome revealed conflicting data. Transcriptional profiling after silencing of SOX2 expression in a HNSCC cell line identified a set of up-regulated genes related to cel...
Source: Molecular Oncology - May 19, 2015 Category: Cancer & Oncology Authors: Pilar Bayo, Adriana Jou, Albrecht Stenzinger, Chunxuan Shao, Madeleine Gross, Alexandra Jensen, Niels Grabe, Christel Herold Mende, Pantelis Varvaki Rados, Juergen Debus, Wilko Weichert, Peter K. Plinkert, Peter Lichter, Kolja Freier, Jochen Hess Source Type: research
Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - May 16, 2015 Category: Cancer & Oncology Source Type: research
PTEN loss is a context-dependent outcome determinant in obese and non-obese endometrioid endometrial cancer patients
Endometrial cancer incidence is increasing, due in part to a strong association with obesity. Mutations in the phosphatidylinositol 3-kinase (PI3K) pathway, the central relay pathway of insulin signals, occur in the majority of endometrioid adenocarcinomas, the most common form of endometrial cancer. We sought to determine the impact of PI3K pathway alterations on progression free survival in a cohort of endometrioid endometrial cancers. Prognostic utility of PIK3CA, PIK3R1, and PTEN mutations, as well as PTEN protein loss by immunohistochemistry, was explored in the context of patient body mass index. (Source: Molecular Oncology)
Source: Molecular Oncology - May 16, 2015 Category: Cancer & Oncology Authors: Shannon N. Westin, Zhenlin Ju, Russell R. Broaddus, Camilla Krakstad, Jane Li, Navdeep Pal, Karen H. Lu, Robert L. Coleman, Bryan T. Hennessy, Samuel J. Klempner, Henrica M.J. Werner, Helga B. Salvesen, Lewis C. Cantley, Gordon B. Mills, Andrea P. Myers Source Type: research
The miR-200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells
We studied the role of miRNA-200 family members in cellular sensitivity to paclitaxel and carboplatin, using two ovarian cancer cell lines, OVCAR-3 and MES-OV, and their paclitaxel resistant variants OVCAR-3/TP and MES-OV/TP. Both resistant variants display a strong epithelial-mesenchymal transition (EMT) phenotype, with marked decreases in expression of miR-200c and miR-141 in OVCAR-3/TP, and down-regulation of all five members of the miR-200 family in MES-OV/TP. Lentiviral transfection of inhibitors of miR-200c or miR-141 in parental OVCAR-3 triggered EMT and rendered the cells resistant to paclitaxel and carboplatin. (S...
Source: Molecular Oncology - May 16, 2015 Category: Cancer & Oncology Authors: Anamaria Brozovic, George E. Duran, Yan C. Wang, E. Brian Francisco, Branimir I. Sikic Source Type: research
An Integrated Genomic Analysis of Papillary Renal Cell Carcinoma Type 1 Uncovers the Role of Focal Adhesion and Extracellular Matrix Pathways
Papillary renal cell carcinoma (pRCC) is the second most common RCC subtype and can be further classified as type 1 (pRCC1) or 2 (pRCC2). There is currently minimal understanding of pRCC1 pathogenesis, and treatment decisions are mostly empirical. The aim of this study was to identify biological pathways that are involved in pRCC1 pathogenesis using an integrated genomic approach. By microarray analysis, we identified a number of significantly dysregulated genes and microRNAs (miRNAs) that were unique to pRCC1. (Source: Molecular Oncology)
Source: Molecular Oncology - May 13, 2015 Category: Cancer & Oncology Authors: Samantha Jane Wala, Jason Raj Karamchandani, Rola Saleeb, Andrew Evans, Qiang Ding, Rania Ibrahim, Michael Jewett, Maria Pasic, Antonio Finelli, Kenneth Pace, Evi Lianidou, George Makram Yousef Source Type: research
Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer
In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p=0.0003). (Source: Molecular Oncology)
Source: Molecular Oncology - May 13, 2015 Category: Cancer & Oncology Authors: Jay Pundavela, Severine Roselli, Sam Faulkner, John Attia, Rodney J. Scott, Rick F. Thorne, John F. Forbes, Ralph A. Bradshaw, Marjorie M. Walker, Phillip Jobling, Hubert Hondermarck Source Type: research
BRCA1 regulates Transforming Growth Factor-β (TGF-β1) Signaling through Gadd45a by enhancing the protein stability of Smad4
BRCA1 is a well established tumor suppressor gene, which is involved in many cellular processes, including DNA damage repair, cell cycle control, apoptosis, as well as transcriptional control. In this work, we have found that BRCA1 is involved in regulating TGF-β1/Smad pathway. The loss of endogenous BRCA1 greatly attenuated TGF-β1-induced growth inhibition and cell cycle G1 arrest. BRCA1 greatly maintains stability of Smad4 protein, and the loss of BRCA1 results in Smad4 down-regulation, which is likely related to its downstream gene Gadd45a. (Source: Molecular Oncology)
Source: Molecular Oncology - May 13, 2015 Category: Cancer & Oncology Authors: Dan Li, Nan Kang, Junfang Ji, Qimin Zhan Source Type: research
High level PHGDH expression in breast is predominantly associated with keratin 5-positive cell lineage independently of malignancy
We have previously reported the 2D PAGE-based proteomic profiling of a prospective cohort of 78 triple negative breast cancer (TNBC) patients, and the establishment of a cumulative TNBC protein database. Analysis of this database identified a number of proteins as being specifically overexpressed in TNBC samples. One such protein was D-3-phosphoglycerate dehydrogenase (Phgdh), a candidate oncogene. We analysed expression of Phgdh in normal and TNBC mammary tissue samples by 2D gel-based proteomics and immuhistochemistry (IHC), and show here that high-level expression of Phgdh in mammary epithelial cells is primarily associ...
Source: Molecular Oncology - May 13, 2015 Category: Cancer & Oncology Authors: Irina Gromova, Pavel Gromov, Naoko Honma, Sudha Kumar, David Rimm, Maj-Lis Møller Talman, Vera Timmermans Wielenga, José M.A. Moreira Source Type: research
