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Cancer discovery

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https://www.readbyqxmd.com/read/28088584/proton-pump-inhibition-and-cancer-therapeutics-a-specific-tumor-targeting-or-it-is-a-phenomenon-secondary-to-a-systemic-buffering
#1
REVIEW
Enrico Spugnini, Stefano Fais
One of the unsolved mysteries in oncology includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to the development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. In the last decades a primordial role for proton exchangers has been supported as a key tumor advantage in facing off the acidic milieu...
January 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28088463/stress-induced-egf-receptor-signaling-through-stat3-and-tumor-progression-in-triple-negative-breast-cancer
#2
Nikolas Balanis, Cathleen R Carlin
Elevated STAT3 activity is a hallmark of many epithelial carcinomas particularly in breast cancers where it is known to contribute to tumor progression through a variety of context-dependent biological responses. However, its role downstream of stress-exposed EGF receptors (EGFR) that are transactivated in endosomes independent of exogenous ligand has not been studied. This review discusses how STAT3 signaling induced by therapeutic stress in EGFR-driven triple-negative breast cancers (TNBC) might override normal epithelial homeostatic mechanisms and provide a survival advantage for tumor cells before they leave the primary tumor and spread to distant sites...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28088330/genomic-insights-in-gynecologic-cancer
#3
Erika Roddy, Jocelyn Chapman
Recent technological advances in DNA sequencing have enabled a remarkably detailed understanding of the molecular changes that define gynecologic and other cancers. Several groups have carried out large-scale genomic analyses of ovarian, uterine, and most recently, cervical cancer. These analyses have led to new insights into the molecular changes characterizing these cancers, which provide insight into clinical outcomes. These molecular characterizations have similarly led to new genomic-based classification schemas, which may better stratify clinical outcomes, help prognosticate and guide treatments...
November 11, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28088073/strategies-to-design-clinical-studies-to-identify-predictive-biomarkers-in-cancer-research
#4
REVIEW
Jose Luis Perez-Gracia, Miguel F Sanmamed, Ana Bosch, Ana Patiño-Garcia, Kurt A Schalper, Victor Segura, Joaquim Bellmunt, Josep Tabernero, Christopher J Sweeney, Toni K Choueiri, Miguel Martín, Juan Pablo Fusco, Maria Esperanza Rodriguez-Ruiz, Alfonso Calvo, Celia Prior, Luis Paz-Ares, Ruben Pio, Enrique Gonzalez-Billalabeitia, Alvaro Gonzalez Hernandez, David Páez, Jose María Piulats, Alfonso Gurpide, Mapi Andueza, Guillermo de Velasco, Roberto Pazo, Enrique Grande, Pilar Nicolas, Francisco Abad-Santos, Jesus Garcia-Donas, Daniel Castellano, María J Pajares, Cristina Suarez, Ramon Colomer, Luis M Montuenga, Ignacio Melero
The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers...
December 30, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28087881/role-of-stim2-in-cell-function-and-physiopathology
#5
Alejandro Berna-Erro, Isaac Jardin, Gines M Salido, Juan A Rosado
An endoplasmic reticulum (ER)-resident protein that regulates cytosolic and ER free-Ca(2+) concentration by induction of store-operated calcium entry. That is the original definition of STIM2 and its function. While its activity strongly depends on the amount of calcium stored in the ER, its function goes further to intracellular signalling and gene expression. Initially undercovered by the prominent function of STIM1, STIM2 became to be vital in mice, gradually emerging as an important player in the nervous system, and cooperating with STIM1 in the immune system...
January 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28087320/poly-adp-ribose-polymerase-activity-and-inhibition-in-cancer
#6
REVIEW
Caleb Dulaney, Samuel Marcrom, Jennifer Stanley, Eddy S Yang
Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining. The discovery that loss of PARP activity had cytotoxic effects in cells deficient in homologous recombination has sparked a decade of translational research efforts that culminated in the FDA approval of an oral PARP inhibitor for clinical use in patients with ovarian cancer and defective homologous recombination...
January 10, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28081215/genome-wide-association-studies-of-multiple-keratinocyte-cancers
#7
Luba M Pardo, Wen-Qing Li, Shih-Jen Hwang, Joris A C Verkouteren, Albert Hofman, André G Uitterlinden, Peter Kraft, Constance Turman, Jiali Han, Eunyoung Cho, Joanne M Murabito, Daniel Levy, Abrar A Qureshi, Tamar Nijsten
There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1)...
2017: PloS One
https://www.readbyqxmd.com/read/28081155/evaluation-of-bufadienolides-as-the-main-antitumor-components-in-cinobufacin-injection-for-liver-and-gastric-cancer-therapy
#8
Xiaolu Wei, Nan Si, Yuefei Zhang, Haiyu Zhao, Jian Yang, Hongjie Wang, Lianmei Wang, Linyu Han, Baolin Bian
BACKGROUND: Cinobufacin injection, also known as huachansu, is a preparation form of Cinobufacini made from Cinobufacin extract liquid. Despite that Cinobufacin injection is shown to shrink liver and gastric tumors, improving patient survival and life quality, the effective components in Cinobufacin remain elusive. In this study, we aim to screen antitumor components from Cinobufacin injection to elucidate the most effective antitumor components for treatment of liver and gastric cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28079877/genome-wide-transposon-screening-and-quantitative-insertion-site-sequencing-for-cancer-gene-discovery-in-mice
#9
Mathias J Friedrich, Lena Rad, Iraad F Bronner, Alexander Strong, Wei Wang, Julia Weber, Matthew Mayho, Hannes Ponstingl, Thomas Engleitner, Carolyn Grove, Anja Pfaus, Dieter Saur, Juan Cadiñanos, Michael A Quail, George S Vassiliou, Pentao Liu, Allan Bradley, Roland Rad
Transposon-mediated forward genetics screening in mice has emerged as a powerful tool for cancer gene discovery. It pinpoints cancer drivers that are difficult to find with other approaches, thus complementing the sequencing-based census of human cancer genes. We describe here a large series of mouse lines for insertional mutagenesis that are compatible with two transposon systems, PiggyBac and Sleeping Beauty, and give guidance on the use of different engineered transposon variants for constitutive or tissue-specific cancer gene discovery screening...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28079711/cell-signaling-pathways-in-brain-tumors
#10
Rebecca A Harrison, John F de Groot
Primary brain tumors, particularly glioblastoma, are associated with significant morbidity and are often recalcitrant to standard therapies. In recent years, brain tumors have been the focus of large-scale genomic sequencing efforts, providing unprecedented insight into the genomic aberrations and cellular signaling mechanisms that drive these cancers. Discoveries from these efforts have translated into novel diagnostic algorithms, biomarkers, and therapeutic strategies in Neuro-Oncology. However, the cellular mechanisms that drive brain tumors are heterogeneous and complex: applying this new knowledge to improve patient outcomes remains a challenge...
January 11, 2017: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/28079010/discovery-of-natural-product-proteasome-inhibitors-as-novel-anticancer-therapeutics-current-status-and-perspectives
#11
Hui Wang, Qingzhu Yang, Ping Dou, Huanjie Yang
Natural products serve as a main resource for drug discovery. The ubiquitin-proteasome system (UPS) is one of the primary intracellular protein degradation systems, which is responsible for the degradation of most short-lived, mis-folded and aged proteins. The proteasome is a validated target for cancer treatment, since cancer cells are more reliant on high levels of proteasome activity to maintain the dynamic protein homeostasis required for enhanced metabolism and unrestricted proliferation inherent in cancer cells...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28079003/colorectal-cancer-chemotherapy-the-evolution-of-treatment-and-new-approaches
#12
Rachel M McQuade, Vanesa Stojanovska, Joel C Bornstein, Kulmira Nurgali
Colorectal cancer (CRC) is one the greatest contributors to cancer related mortality. Although 5 year survival rate for patients at the early stage of CRC (stages I and II) is above 60%, more than 50% of patients are diagnosed at or beyond stage III when distant metastasis has already occurred, in which case 5 year survival rate drops to 10%. Chemotherapeutic intervention coupled with surgery is the backbone of metastatic CRC treatment and the only means of enhanced survival. For decades following its discovery, an antimetabolite 5-fluorouracil (5-FU) was the only chemotherapeutic agent available to successfully improve 12 month survival in CRC patients...
January 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28078645/parp-inhibitors-in-reproductive-system-cancers-current-use-and-developments
#13
REVIEW
Geraldine O'Sullivan Coyne, Alice P Chen, Robert Meehan, James H Doroshow
The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28077836/-decision-making-experience-on-breast-reconstruction-for-women-with-breast-cancer
#14
Myungsun Yi, Woo Joung Joung, Eun Young Park, Eun Jin Kwon, Haejin Kim, Ji Young Seo
PURPOSE: The purpose of this study was to explore decision making experiences of Korean women with breast cancer who underwent breast reconstruction with/after a mastectomy. METHODS: Data were collected during 2015-2016 through individual in-depth interviews with 10 women who had both mastectomy and breast reconstruction, and analyzed using phenomenological method to identify essential themes on experiences of making a decision to have breast reconstruction. RESULTS: Five theme clusters emerged...
December 2016: Journal of Korean Academy of Nursing
https://www.readbyqxmd.com/read/28077788/androgen-receptor-splice-variants-and-prostate-cancer-from-bench-to-bedside
#15
REVIEW
Kristine M Wadosky, Shahriar Koochekpour
Therapeutic interventions for advanced prostate cancer (PCa) center on inhibiting androgen receptor (AR) and downstream signaling pathways. Resistance to androgen deprivation therapy and/or AR antagonists is inevitable and molecular mechanisms driving castration-resistant PCa (CR-PCa) primarily involve alterations in AR expression and activity. Detailed molecular biology work over the past decade, discussed at length in this review article, has revealed several AR transcripts that result from alternative splicing...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077782/serum-and-tissue-markers-in-hepatocellular-carcinoma-and-cholangiocarcinoma-clinical-and-prognostic-implications
#16
REVIEW
Massimiliano Berretta, Carla Cavaliere, Lara Alessandrini, Brigida Stanzione, Gaetano Facchini, Luca Balestreri, Tiziana Perin, Vincenzo Canzonieri
HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers...
December 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/28077642/studies-on-the-interaction-of-tumor-derived-hd5-alpha-defensins-with-adenoviruses-and-implications-for-oncolytic-adenovirus-therapy
#17
Charles Vragniau, Jens-Martin Hübner, Peter Beidler, Sucheol Gil, Kamola Saydaminova, Zhuo-Zhuang Lu, Roma Yumul, Hongjie Wang, Maximilian Richter, Pavel Sova, Charles Drescher, Pascal Fender, André Lieber
: Defensins are small anti-microbial peptides capable of neutralizing human adenovirus (HAdV) in vitro by binding capsid proteins and blocking endosomal escape of virus. In humans, the alpha defensin HD5 is produced by specialized epithelial cells of the gastro-intestinal and genito-urinary tracts. Here we demonstrate that HD5 is also expressed as an active, secreted peptide by epithelial ovarian and lung cancer cells in situ, in patient biopsies. This finding triggered us to study the role of HD5 in infection and spread of replication-competent, oncolytic HAdV type 3 virus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077100/incidence-of-solitary-pulmonary-nodules-in-northeastern-france-a-population-based-study-in-five-regions
#18
Émilie Marrer, Damien Jolly, Patrick Arveux, Catherine Lejeune, Marie-Christine Woronoff-Lemsi, Jérémie Jégu, Francis Guillemin, Michel Velten
BACKGROUND: The discovery of a solitary pulmonary nodule (SPN) on a chest imaging exam is of major clinical concern. However, the incidence rates of SPNs in a general population have not been estimated. The objective of this study was to provide incidence estimates of SPNs in a general population in 5 northeastern regions of France. METHODS: This population-based study was undertaken in 5 regions of northeastern France in May 2002-March 2003 and May 2004-June 2005...
January 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28076849/a-plasma-metabolomic-signature-discloses-human-breast-cancer
#19
Mariona Jové, Ricardo Collado, José Luís Quiles, Mari-Carmen Ramírez-Tortosa, Joaquim Sol, Maria Ruiz-Sanjuan, Mónica Fernandez, Capilla de la Torre Cabrera, Cesar Ramírez-Tortosa, Sergio Granados-Principal, Pedro Sánchez-Rovira, Reinald Pamplona
PURPOSE: Metabolomics is the comprehensive global study of metabolites in biological samples. In this retrospective pilot study we explored whether serum metabolomic profile can discriminate the presence of human breast cancer irrespective of the cancer subtype. METHODS: Plasma samples were analyzed from healthy women (n = 20) and patients with breast cancer after diagnosis (n = 91) using a liquid chromatography-mass spectrometry platform. Multivariate statistics and a Random Forest (RF) classifier were used to create a metabolomics panel for the diagnosis of human breast cancer...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076321/secretion-modification-region-derived-peptide-blocks-exosome-release-and-mediates-cell-cycle-arrest-in-breast-cancer-cells
#20
Ming-Bo Huang, Ruben R Gonzalez, James Lillard, Vincent C Bond
PURPOSE: Discovery and development of a novel anticancer PEG-SMR-Clu peptide to prevent breast cancer metastasis. How breast cancer cells and primary mammary epithelial cells interact and communicate with each other to promote tumorigenesis and how to prevent tumor metastasis has long been a concern of researchers. Cancer cells secrete exosomes containing proteins and RNA. These factors can influence tumor development by directly targeting cancer cells and tumor stroma. In this study, we determined the effects of a peptide as an inhibitor of exosome secretion on breast tumors...
January 5, 2017: Oncotarget
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