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Zhen-Yao Chen, Xin Chen, Zhao-Xia Wang
MicroRNAs are a large group of non-coding RNAs that have emerged as regulators of various biological processes, especially carcinogenesis and cancer progression. Recent evidence has shown that microRNA-196a (miR-196a) is upregulated in most types of tumors and involved in multiple biological processes via translational inhibition and mRNA cleavage, such as cell proliferation, migration, and invasion, mostly functioning as an oncogene. Dysregulation of miR-196a promotes oncogenesis and tumor progression. In this review, we summarize the upstream regulators, target genes, signaling pathways, and single nucleotide polymorphisms of miR-196a, which collectively affect cell proliferation, migration, and invasion...
October 18, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Maureen O'Sullivan
Since its foundation by remarkably talented and insightful individuals, prominently including Pepper Dehner, pediatric soft tissue tumor pathology has developed at an immense rate. The morphologic classification of tumoral entities has extensively been corroborated, but has also evolved with refinement or realignment of these classifications, through accruing molecular data, with many derivative ancillary diagnostic assays now already well-established. Tumors of unclear histogenesis, classically morphologically undifferentiated, are prominent amongst pediatric sarcomas, however, the classes of undifferentiated round- or spindle-cell-tumors-not-otherwise-specified are being dismantled gradually with the identification of their molecular underpinnings...
September 5, 2016: Seminars in Diagnostic Pathology
Liang Wang, Changhua Zhang, Jianbo Xu, Hui Wu, Jianjun Peng, Shirong Cai, Yulong He
Chemokine (C-X-C motif) ligand 1 (CXCL1) is essential in oncogenesis and development of malignant tumors. The present study aimed to investigate CXCL1 expression in promoting lymph node metastasis in gastric cancer patients. Human gastric cancer cell lines were employed to detect CXCL1 expression. HGC803 cell migration and cell invasion were detected using a wound healing assay and Transwell invasion assay, respectively. A total of 100 patients who underwent radical gastric resection with lymph node dissection in the First Affiliated Hospital of Sun Yat‑Sen University (Guangzhou, China) between 2007 and 2008 were included...
October 13, 2016: Molecular Medicine Reports
Igor S Bryukhovetskiy, Inessa V Dyuizen, Valeriy E Shevchenko, Andrey S Bryukhovetskiy, Polina V Mischenko, Elena V Milkina, Yuri S Khotimchenko
Glioblastoma multiforme is an aggressive malignant brain tumor with terminal consequences. A primary reason for its resistance to treatment is associated with cancer stem cells (CSCs), of which there are currently no effective ways to destroy. It remains unclear what cancer cells become a target of stem cell migration, what the role of this process is in oncogenesis and what stem cell lines should be used in developing antitumor technologies. Using modern post‑genome technologies, the present study investigated the migration of human stem cells to cancer cells in vitro, the comparative study of cell proteomes of certain stem cells (including CSCs) was conducted and stem cell migration in vivo was examined...
October 13, 2016: Molecular Medicine Reports
James Sutherland Lawson, Wendy K Glenn, Noel James Whitaker
High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case-control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades...
2016: Frontiers in Oncology
Van Morris, Cathy Eng
Squamous cell carcinoma of the anal canal (SCCA) remains a less common gastrointestinal malignancy despite a continued increase in the annual incidence in the United States and globally. The vast majority of all cases are attributed to persistent infection and integration into host cell DNA by human papillomavirus (HPV). For patients with metastatic anal cancer, there is currently no accepted consensus standard of care. Given the viral etiology associated with the oncogenesis of this tumor, great interest exists for the development of immunotherapy as a novel approach to improving clinical outcomes for patients afflicted with this disease...
October 2016: Journal of Gastrointestinal Oncology
Wen-Chih Huang, Chien-Chen Tsai, Chih-Chieh Chan
BACKGROUND/PURPOSE: Cholangiocarcinoma (CC) is a fatal malignancy originating from biliary tracts and constitutes approximately 10-20% of hepatobiliary cancers. CC is characterized by a very poor prognosis. The definite molecular mechanisms leading to oncogenesis remain unclear. This study aimed to perform mutation analysis and copy number changes of KRAS and BRAF genes of CC in Taiwan. METHODS: A total of 182 cases of biliary tact CC were studied for point mutation and quantitative real-time polymerase chain reaction analysis of KRAS and BRAF genes...
October 10, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
A S Mansfield, S J Murphy, F R Harris, S I Robinson, R S Marks, S H Johnson, J B Smadbeck, G C Halling, E S Yi, D Wigle, G Vasmatzis, J Jen
BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRβ fusions and may benefit from targeted therapy...
October 14, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Robert M Nevels, Samuel T Gontkovsky, Bryman E Williams
Paroxetine, also known by the trade names Aropax, Paxil, Pexeva, Seroxat, Sereupin and Brisdelle, was first marketed in the U.S. in 1992. Effective for major depression and various anxiety disorders, it quickly gained a sizable share of the antidepressant prescription market. By the late 1990s, paroxetine frequently was being associated with serious drug interactions and medication side effects. Most significantly, in a major Canadian epidemiological study examining the relationship between antidepressants and diseases, paroxetine was associated with a 620 percent increase in the rate of breast cancer in women who had taken it over a four-year period...
March 1, 2016: Psychopharmacology Bulletin
Ameer L Elaimy, Aarif Ahsan, Katherine Marsh, William B Pratt, Dipankar Ray, Theodore S Lawrence, Mukesh K Nyati
Heat shock protein 90 is a chaperone that plays an essential role in the stabilization of a large number of signal transduction molecules, many of which are associated with oncogenesis. An Hsp90 isoform (Hsp90α) has been shown to be selectively phosphorylated on two N-terminal threonine residues (threonine 5 and 7) and is involved in the DNA damage response and apoptosis. However, the kinase that phosphorylates Hsp90α after ionizing radiation (IR) and its role in post-radiation DNA repair remains unclear...
October 11, 2016: Oncotarget
Dieter Zopf, Iduna Fichtner, Ajay Bhargava, Wolfram Steinke, Karl-Heinz Thierauch, Konstanze Diefenbach, Scott Wilhelm, Frank-Thorsten Hafner, Michael Gerisch
Regorafenib is an orally administered inhibitor of protein kinases involved in tumor angiogenesis, oncogenesis, and maintenance of the tumor microenvironment. Phase III studies showed that regorafenib has efficacy in patients with advanced gastrointestinal stromal tumors or treatment-refractory metastatic colorectal cancer. In clinical studies, steady-state exposure to the M-2 and M-5 metabolites of regorafenib was similar to that of the parent drug; however, the contribution of these metabolites to the overall observed clinical activity of regorafenib cannot be investigated in clinical trials...
October 13, 2016: Cancer Medicine
Heather M Byers, Margaret P Adam, Amy LaCroix, Sarah E S Leary, Bonnie Cole, William B Dobyns, Heather C Mefford
Atypical teratoid rhabdoid tumors of the central nervous system are rare, highly malignant, embryonal tumors most often occurring in children under age 3 years. Most are due to a somatic change in tumor suppressor gene SMARCB1 followed by a second-hit, typically loss of heterozygosity, best detected on immunohistochemical staining. Despite the noteworthy genetic homogeneity of atypical teratoid rhabdoid tumors, relatively little is known about the oncogenic mechanisms that lead to biallelic inactivation of SMARCB1...
October 12, 2016: American Journal of Medical Genetics. Part A
Bradley Smith, Xenia L Schafer, Aslihan Ambeskovic, Cody M Spencer, Hartmut Land, Joshua Munger
Metabolic reprogramming is critical to oncogenesis, but the emergence and function of this profound reorganization remain poorly understood. Here we find that cooperating oncogenic mutations drive large-scale metabolic reprogramming, which is both intrinsic to cancer cells and obligatory for the transition to malignancy. This involves synergistic regulation of several genes encoding metabolic enzymes, including the lactate dehydrogenases LDHA and LDHB and mitochondrial glutamic pyruvate transaminase 2 (GPT2)...
October 11, 2016: Cell Reports
Kyoung-Bun Lee
A bile duct lesion originating from intrahepatic bile ducts is generally regarded as an incidental pathologic finding in liver specimens. However, a recent study on the molecular classification of intrahepatic cholangiocarcinoma has focused on the heterogeneity of this carcinoma and has suggested that the cells of different origins present in the biliary tree may have a major role in the mechanism of oncogenesis. In this review, benign intrahepatic bile duct lesions-regarded in the past as reactive changes or remnant developmental anomalies and now noted to have potential for developing precursor lesions of intrahepatic cholangiocarcinoma-are discussed by focusing on the histopathologic features and its implications in clinical practice...
September 2016: Clinical and Molecular Hepatology
Wei Kevin Zhang, Hong-Wei Gu, Xiao-Jun Li, Yu-Sang Li, He-Bin Tang, Gui-Hua Tian, Hong-Cai Shang
Nano-carriers, especially lipid nanoparticles have been used widely in "a good manner", for instance in the treatment of cancer, by enhancing the targetability and reducing required dose. Here in the contrary, we presented a new possibility: nanoDEN, a nanoparticle-packed "bad guy", which is more effective and efficient in generating liver tumor in mice. We have shown that nanoDEN, same as diethylnitrosamine (DEN), induced overexpression of multiple pivotal factors (including COX-2, β-catenin and PCNA) during oncogenesis...
October 8, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Maximilian Stahl, Nathan Kohrman, Steven D Gore, Tae Kon Kim, Amer M Zeidan, Thomas Prebet
For several decades, we have known that epigenetic regulation is disrupted in cancer. Recently, an increasing body of data suggests epigenetics might be an intersection of current cancer research trends: next generation sequencing, immunology, metabolomics, and cell aging. The new emphasis on epigenetics is also related to the increasing production of drugs capable of interfering with epigenetic mechanisms and able to trigger clinical responses in even advanced phase patients. In this review, we will use myeloid malignancies as proof of concept examples of how epigenetic mechanisms can trigger or promote oncogenesis...
October 2016: PLoS Genetics
Kaja Blagotinšek, Damjana Rozman
BACKGROUND: Hepatocellular carcinoma (HCC) represents the most common malignant liver tumor in humans, which incidence and mortality have increased in Europe and United States in the last years. Most patients are diagnosed at an advanced stage, when it is not amenable to curative therapies, so there is an urgent need for new, more effective therapeutic tools and strategies. The molecular mechanisms of hepatocarinogenesis and HCC progression have been increasingly understood with intense research in recent years...
October 6, 2016: Current Pharmaceutical Design
Elmer Hoekstra, Asha M Das, Marcella Willemsen, Marloes Swets, Peter J K Kuppen, Christien J van der Woude, Marco J Bruno, Jigisha P Shah, Timo L M Ten Hagen, John D Chisholm, William G Kerr, Maikel P Peppelenbosch, Gwenny M Fuhler
Colorectal cancer (CRC) is the second most common cause of cancer-related death, encouraging the search for novel therapeutic targets affecting tumor cell proliferation and migration. These cellular processes are under tight control of two opposing groups of enzymes; kinases and phosphatases. Aberrant activity of kinases is observed in many forms of cancer and as phosphatases counteract such "oncogenic" kinases, it is generally assumed that phosphatases function as tumor suppressors. However, emerging evidence suggests that the lipid phosphatase SH2-domain-containing 5 inositol phosphatase (SHIP2), encoded by the INPPL1 gene, may act as an oncogene...
September 28, 2016: Oncotarget
Matthias G Beuerle, Neil P Dufton, Anna M Randi, Ian R Gould
The ETS family of transcription factors regulate gene targets by binding to a core GGAA DNA-sequence. The ETS factor ERG is required for homeostasis and lineage-specific functions in endothelial cells, some subset of haemopoietic cells and chondrocytes; its ectopic expression is linked to oncogenesis in multiple tissues. To date details of the DNA-binding process of ERG including DNA-sequence recognition outside the core GGAA-sequence are largely unknown. We combined available structural and experimental data to perform molecular dynamics simulations to study the DNA-binding process of ERG...
October 3, 2016: Molecular BioSystems
Jingxuan Wang, Xiao Zhang, Jinming Shi, Paul Cao, Meimei Wan, Qiang Zhang, Yunxuan Wang, Steven J Kridel, Wennuan Liu, Jianfeng Xu, Qingyuan Zhang, Guangchao Sui
Fatty acid synthase (FASN) is upregulated in breast cancer and correlates with poor prognosis. FASN contributes to mammary oncogenesis and serves as a bona fide target in cancer therapies. MicroRNAs inhibit gene expression through blocking mRNA translation or promoting mRNA degradation by targeting their 3'-UTRs. We identified four microRNAs in two microRNA clusters miR-15a-16-1 and miR-497-195 that share a common seed sequence to target the 3'-UTR of the FASN mRNA. In reporter assays, both of these microRNA clusters inhibited the expression of a reporter construct containing the FASN 3'-UTR...
October 5, 2016: Oncotarget
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