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Molecular Cancer

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https://www.readbyqxmd.com/read/27919264/acidic-tumor-microenvironment-abrogates-the-efficacy-of-mtorc1-inhibitors
#1
Seraina Faes, Adrian P Duval, Anne Planche, Emilie Uldry, Tania Santoro, Catherine Pythoud, Jean-Christophe Stehle, Janine Horlbeck, Igor Letovanec, Nicolo Riggi, Nicolas Demartines, Olivier Dormond
BACKGROUND: Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. The tumor microenvironment is characterized by an acidic pH which interferes with cancer therapies. The consequences of acidity on the anti-cancer efficacy of mTORC1 inhibitors have not been characterized and are thus the focus of our study. METHODS: Cancer cell lines were treated with rapamycin in acidic or physiological conditions and cell proliferation was investigated...
December 5, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27912767/lipocalin2-suppresses-metastasis-of-colorectal-cancer-by-attenuating-nf-%C3%AE%C2%BAb-dependent-activation-of-snail-and-epithelial-mesenchymal-transition
#2
Meibao Feng, Jieqiong Feng, Wuzhen Chen, Wubin Wang, Xuesong Wu, Jing Zhang, Fangying Xu, Maode Lai
BACKGROUND: Lipocalin2 (LCN2) is a secretory protein that is aberrantly expressed in several types of cancer and has been involved in metastatic progression. However, neither mechanisms nor the role that LCN2 plays in the metastasis of colorectal cancer are clear. METHODS: LCN2 expression in colorectal cancer was detected by immunohistochemistry in 400 tissue specimens and Kaplan-Meier survival analysis was performed. In vitro, real-time PCR, western blot, colony formation assay, immunofluorescence assay, wound healing assay, migration and invasion experiment were performed to investigate the effects of LCN2 in epithelial mesenchymal transition (EMT), migration and invasion, respectively...
December 3, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27887606/cancer-somatic-mutations-cluster-in-a-subset-of-regulatory-sites-predicted-from-the-encode-data
#3
Nisar A Shar, M S Vijayabaskar, David R Westhead
BACKGROUND: Transcriptional regulation of gene expression is essential for cellular differentiation and function, and defects in the process are associated with cancer. The ENCODE project has mapped potential regulatory sites across the complete genome in many cell types, and these regions have been shown to harbour many of the somatic mutations that occur in cancer cells, suggesting that their effects may drive cancer initiation and development. The ENCODE data suggests a very large number of regulatory sites, and methods are needed to identify those that are most relevant and to connect them to the genes that they control...
November 25, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27871326/tryptophan-hydroxylase-1-and-5-ht7-receptor-preferentially-expressed-in-triple-negative-breast-cancer-promote-cancer-progression-through-autocrine-serotonin-signaling
#4
Jaya Gautam, Suhrid Banskota, Sushil Chandra Regmi, Subi Ahn, Yong Hyun Jeon, Hyunyoung Jeong, Seung Joo Kim, Tae-Gyu Nam, Byeong-Seon Jeong, Jung-Ae Kim
BACKGROUND: Triple-negative breast cancer (TNBC) has a high risk of relapse and there are few chemotherapy options. Although 5-hydroxytryptamine (5-HT, serotonin) signaling pathways have been suggested as potential targets for anti-cancer drug development, the mechanism responsible for the action of 5-HT in TNBC remains unknown. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to measure mRNA and protein levels, respectively...
November 21, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27871300/pi3-kinase-pathway-regulated-mirnome-in-glioblastoma-identification-of-mir-326-as-a-tumour-suppressor-mirna
#5
Zahid Nawaz, Vikas Patil, Yashna Paul, Alangar S Hegde, Arimappamagan Arivazhagan, Vani Santosh, Kumaravel Somasundaram
BACKGROUND: Glioblastomas (GBM) continue to remain one of the most dreaded tumours that are highly infiltrative in nature and easily preclude comprehensive surgical resection. GBMs pose an intricate etiology as they are being associated with a plethora of genetic and epigenetic lesions. Misregulation of the PI3 kinase pathway is one of the most familiar events in GBM. While the PI3 kinase signalling regulated pathways and genes have been comprehensively studied, its impact on the miRNome is yet to be explored...
November 21, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27852311/caveolin-1-in-the-regulation-of-cell-metabolism-a-cancer-perspective
#6
REVIEW
Zeribe Chike Nwosu, Matthias Philip Ebert, Steven Dooley, Christoph Meyer
Caveolin-1 (CAV1) is an oncogenic membrane protein associated with endocytosis, extracellular matrix organisation, cholesterol distribution, cell migration and signaling. Recent studies reveal that CAV1 is involved in metabolic alterations - a critical strategy adopted by cancer cells to their survival advantage. Consequently, research findings suggest that CAV1, which is altered in several cancer types, influences tumour development or progression by controlling metabolism. Understanding the molecular interplay between CAV1 and metabolism could help uncover druggable metabolic targets or pathways of clinical relevance in cancer therapy...
November 16, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27852308/systems-analysis-identifies-mir-29b-regulation-of-invasiveness-in-melanoma
#7
Miles C Andrews, Joseph Cursons, Daniel G Hurley, Matthew Anaka, Jonathan S Cebon, Andreas Behren, Edmund J Crampin
BACKGROUND: In many cancers, microRNAs (miRs) contribute to metastatic progression by modulating phenotypic reprogramming processes such as epithelial-mesenchymal plasticity. This can be driven by miRs targeting multiple mRNA transcripts, inducing regulated changes across large sets of genes. The miR-target databases TargetScan and DIANA-microT predict putative relationships by examining sequence complementarity between miRs and mRNAs. However, it remains a challenge to identify which miR-mRNA interactions are active at endogenous expression levels, and of biological consequence...
November 16, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27852271/comprehensive-screening-of-target-molecules-by-next-generation-sequencing-in-patients-with-malignant-solid-tumors-guiding-entry-into-phase-i-clinical-trials
#8
LETTER
Yuko Tanabe, Hitoshi Ichikawa, Takashi Kohno, Hiroshi Yoshida, Takashi Kubo, Mamoru Kato, Satoru Iwasa, Atsushi Ochiai, Noboru Yamamoto, Yasuhiro Fujiwara, Kenji Tamura
It is still controversial whether comprehensive genome screening of target molecules by next generation sequencing (NGS) is needed to increase clinical efficacy of investigational drugs or accelerate drug development, although several studies are being carried out. Therefore, we performed a prospective study to evaluate the feasibility of comprehensive gene screening in this setting. Our findings indicate that actionable alterations were identified in 45% of the analyzed patients, most frequently in those with breast cancer...
November 16, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27832783/mir-375-induces-docetaxel-resistance-in-prostate-cancer-by-targeting-sec23a-and-yap1
#9
Yuan Wang, Rachel Lieberman, Jing Pan, Qi Zhang, Meijun Du, Peng Zhang, Marja Nevalainen, Manish Kohli, Niraj K Shenoy, Hui Meng, Ming You, Liang Wang
BACKGROUND: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically are centered on docetaxel-based chemotherapy. We previously reported that elevated miR-375 levels were significantly associated with poor overall survival of mCRPC patients. In this study, we evaluated if miR-375 induced chemo-resistance to docetaxel through regulating target genes associated with drug resistance. METHODS: We first compared miR-375 expression level between prostate cancer tissues and normal prostate tissues using data from The Cancer Genome Atlas (TCGA)...
November 10, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27825361/cancer-stem-cell-metabolism-a-potential-target-for-cancer-therapy
#10
REVIEW
Abhijeet Deshmukh, Kedar Deshpande, Frank Arfuso, Philip Newsholme, Arun Dharmarajan
Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as key tumour initiating cells that may also play an integral role in tumour recurrence following chemotherapy. Cancer cells have the ability to alter their metabolism in order to fulfil bio-energetic and biosynthetic requirements. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilisation...
November 8, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27809841/pharmacological-targeting-of-cxcl12-cxcr4-signaling-in-prostate-cancer-bone-metastasis
#11
M Katie Conley-LaComb, Louie Semaan, Rajareddy Singareddy, Yanfeng Li, Elisabeth I Heath, Seongho Kim, Michael L Cher, Sreenivasa R Chinni
BACKGROUND: The CXCL12/CXCR4 axis transactivates HER2 and promotes intraosseous tumor growth. To further explore the transactivation of HER2 by CXCL12, we investigated the role of small GTP protein Gαi2 in Src and HER2 phosphorylation in lipid raft membrane microdomains and the significance of CXCR4 in prostate cancer bone tumor growth. METHODS: We used a variety of methods such as lipid raft isolation, invasion assays, an in vivo model of intratibial tumor growth, bone histomorphometry, and immunohistochemistry to determine the role of CXCR4 signaling in lipid raft membrane microdomains and effects of targeting of CXCR4 for bone tumor growth...
November 3, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27784305/emerging-roles-of-t-helper-17-and-regulatory-t-cells-in-lung-cancer-progression-and-metastasis
#12
REVIEW
Erin A Marshall, Kevin W Ng, Sonia H Y Kung, Emma M Conway, Victor D Martinez, Elizabeth C Halvorsen, David A Rowbotham, Emily A Vucic, Adam W Plumb, Daiana D Becker-Santos, Katey S S Enfield, Jennifer Y Kennett, Kevin L Bennewith, William W Lockwood, Stephen Lam, John C English, Ninan Abraham, Wan L Lam
Lung cancer is a leading cause of cancer-related deaths worldwide. Lung cancer risk factors, including smoking and exposure to environmental carcinogens, have been linked to chronic inflammation. An integral feature of inflammation is the activation, expansion and infiltration of diverse immune cell types, including CD4(+) T cells. Within this T cell subset are immunosuppressive regulatory T (Treg) cells and pro-inflammatory T helper 17 (Th17) cells that act in a fine balance to regulate appropriate adaptive immune responses...
October 27, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27756408/prediction-of-chemo-response-in-serous-ovarian-cancer
#13
Jesus Gonzalez Bosquet, Andreea M Newtson, Rebecca K Chung, Kristina W Thiel, Timothy Ginader, Michael J Goodheart, Kimberly K Leslie, Brian J Smith
BACKGROUND: Nearly one-third of serous ovarian cancer (OVCA) patients will not respond to initial treatment with surgery and chemotherapy and die within one year of diagnosis. If patients who are unlikely to respond to current standard therapy can be identified up front, enhanced tumor analyses and treatment regimens could potentially be offered. Using the Cancer Genome Atlas (TCGA) serous OVCA database, we previously identified a robust molecular signature of 422-genes associated with chemo-response...
October 19, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27756406/spatio-temporal-mutation-profiles-of-case-matched-colorectal-carcinomas-and-their-metastases-reveal-unique-de-novo-mutations-in-metachronous-lung-metastases-by-targeted-next-generation-sequencing
#14
Valentina Kovaleva, Anna-Lena Geissler, Lisa Lutz, Ralph Fritsch, Frank Makowiec, Sebastian Wiesemann, Ulrich T Hopt, Bernward Passlick, Martin Werner, Silke Lassmann
BACKGROUND: Targeted next generation sequencing (tNGS) has become part of molecular pathology diagnostics for determining RAS mutation status in colorectal cancer (CRC) patients as predictive tool for decision on EGFR-targeted therapy. Here, we investigated mutation profiles of case-matched tissue specimens throughout the disease course of CRC, to further specify RAS-status dynamics and to identify de novo mutations associated with distant metastases. METHODS: Case-matched formalin-fixed and paraffin-embedded (FFPE) resection specimens (n = 70; primary tumours, synchronous and/or metachronous liver and/or lung metastases) of 14 CRC cases were subjected to microdissection of normal colonic epithelial, primary and metastatic tumour cells, their DNA extraction and an adapted library protocol for limited DNA using the 48 gene TruSeq Amplicon Cancer Panel(TM), MiSeq sequencing and data analyses (Illumina)...
October 18, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27756327/esculetin-induces-antiproliferative-and-apoptotic-response-in-pancreatic-cancer-cells-by-directly-binding-to-keap1
#15
Rashi Arora, Sharad Sawney, Vikas Saini, Chris Steffi, Manisha Tiwari, Daman Saluja
BACKGROUND: A handful of studies have exploited antitumor potential of esculetin, a dihydroxy coumarine derivative; the targets to which it binds and the possible downstream mechanism for its cytotoxicity in cancer cells remain to be elucidated. Using pancreatic cancer cell lines as a model system, herein the study was initiated to check the efficacy of esculetin in inhibiting growth of these cancer cells, to decipher mechanism of its action and to predict its direct binding target protein...
October 18, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27756325/less-is-more-low-expression-of-mt1-mmp-is-optimal-to-promote-migration-and-tumourigenesis-of-breast-cancer-cells
#16
Mario A Cepeda, Jacob J H Pelling, Caitlin L Evered, Karla C Williams, Zoey Freedman, Ioana Stan, Jessica A Willson, Hon S Leong, Sashko Damjanovski
BACKGROUND: Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease implicated in metastatic progression ostensibly due to its ability to degrade extracellular matrix (ECM) components and allow migration of cells through the basement membrane. Despite in vitro studies demonstrating this principle, this knowledge has not translated into the use of MMP inhibitors (MMPi) as effective cancer therapeutics, or been corroborated by evidence of in vivo ECM degradation mediated by MT1-MMP, suggesting that our understanding of the role of MT1-MMP in cancer progression is incomplete...
October 18, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27686855/synthetic-lethality-in-lung-cancer-and-translation-to-clinical-therapies
#17
Ada W Y Leung, Tanya de Silva, Marcel B Bally, William W Lockwood
Lung cancer is a heterogeneous disease consisting of multiple histological subtypes each driven by unique genetic alterations. Despite the development of targeted therapies that inhibit the oncogenic mutations driving a subset of lung cancer cases, there is a paucity of effective treatments for the majority of lung cancer patients and new strategies are urgently needed. In recent years, the concept of synthetic lethality has been established as an effective approach for discovering novel cancer-specific targets as well as a method to improve the efficacy of existing drugs which provide partial but insufficient benefits for patients...
September 29, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27686732/long-non-coding-rnas-potential-new-biomarkers-for-predicting-tumor-invasion-and-metastasis
#18
Chunyang Jiang, Xin Li, Hui Zhao, Huibin Liu
Long non-coding RNAs (lncRNAs) play important roles in malignant neoplasia. Indeed, many hallmarks of cancer define that the malignant phenotype of tumor cells are controlled by lncRNAs. Despite a growing number of studies highlighting their importance in cancer, there has been no systematic review of metastasis-associated lncRNAs in various cancer types. Accordingly, we focus on the key metastasis-related lncRNAs and outline their expression status in cancer tissues by reviewing the previous stuides, in order to summarize the nowadays research achivements for lncRNAs related to cancer metastasis...
September 29, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27629044/rac1-mediated-cytoskeleton-rearrangements-induced-by-intersectin-1s-deficiency-promotes-lung-cancer-cell-proliferation-migration-and-metastasis
#19
Niranjan Jeganathan, Dan Predescu, Jin Zhang, Fei Sha, Cristina Bardita, Monal Patel, Stephen Wood, Jeffrey A Borgia, Robert A Balk, Sanda Predescu
BACKGROUND: The mechanisms involved in lung cancer (LC) progression are poorly understood making discovery of successful therapies difficult. Adaptor proteins play a crucial role in cancer as they link cell surface receptors to specific intracellular pathways. Intersectin-1s (ITSN-1s) is an important multidomain adaptor protein implicated in the pathophysiology of numerous pulmonary diseases. To date, the role of ITSN-1s in LC has not been studied. METHODS: Human LC cells, human LC tissue and A549 LC cells stable transfected with myc-ITSN-1s construct (A549 + ITSN-1s) were used in correlation with biochemical, molecular biology and morphological studies...
September 14, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27343009/clinical-relevance-of-circulating-cell-free-micrornas-in-ovarian-cancer
#20
REVIEW
Koji Nakamura, Kenjiro Sawada, Akihiko Yoshimura, Yasuto Kinose, Erika Nakatsuka, Tadashi Kimura
Ovarian cancer is the leading cause of death among gynecologic malignancies. Since ovarian cancer develops asymptomatically, it is often diagnosed at an advanced and incurable stage. Despite many years of research, there is still a lack of reliable diagnostic markers and methods for early detection and screening. Recently, it was discovered that cell-free microRNAs (miRNAs) circulate in the body fluids of healthy and diseased patients, suggesting that they may serve as a novel diagnostic marker. This review summarizes the current knowledge regarding the potential clinical relevance of circulating cell-free miRNA for ovarian cancer diagnosis, prognosis, and therapeutics...
June 24, 2016: Molecular Cancer
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