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Cancer discovery

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https://www.readbyqxmd.com/read/28212542/two-stage-genome-wide-association-study-identifies-a-novel-susceptibility-locus-associated-with-melanoma
#1
Katherine J Ransohoff, Wenting Wu, Hyunje G Cho, Harvind C Chahal, Yuan Lin, Hong-Ji Dai, Christopher I Amos, Jeffrey E Lee, Jean Y Tang, David A Hinds, Jiali Han, Qingyi Wei, Kavita Y Sarin
Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212429/the-p53-isoform-delta133p53%C3%A3-regulates-cancer-cell-apoptosis-in-a-rhob-dependent-manner
#2
Nikola Arsic, Alexandre Ho-Pun-Cheung, Crapez Evelyne, Eric Assenat, Marta Jarlier, Christelle Anguille, Manon Colard, Mikaël Pezet, Pierre Roux, Gilles Gadea
The TP53 gene plays essential roles in cancer. Conventionally, wild type (WT) p53 is thought to prevent cancer development and metastasis formation, while mutant p53 has transforming abilities. However, clinical studies failed to establish p53 mutation status as an unequivocal predictive or prognostic factor of cancer progression. The recent discovery of p53 isoforms that can differentially regulate cell cycle arrest and apoptosis suggests that their expression, rather than p53 mutations, could be a more clinically relevant biomarker in patients with cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28212372/molecular-biology-of-gastroesophageal-cancers-opportunities-and-challenges
#3
Shaheer Khan, Sameh Mikhail, Joanne Xiu, Mohamed E Salem
Gastroesophageal (GE) malignancies make up a significant and growing segment of newly diagnosed cancers. Approximately 80% of patients who have GE cancers die within 5 years of diagnosis, which means that effective treatments for these malignancies need to be found. Currently, targeted therapies have a minimal role in this disease group. Intensive study of the molecular biology of GE cancers is a relatively new and ongoing venture, but it has already led to a significant increase in our understanding of these malignancies...
January 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28212270/antitumor-effects-of-laminaria-extract-fucoxanthin-on-lung-cancer
#4
ChengHan Mei, ShunChang Zhou, Lin Zhu, JiaXiong Ming, FanDian Zeng, Rong Xu
Lung cancer is the leading cause of cancer mortality worldwide and non-small-cell lung cancer (NSCLC) is the most common type. Marine plants provide rich resources for anticancer drug discovery. Fucoxanthin (FX), a Laminaria japonica extract, has attracted great research interest for its antitumor activities. Accumulating evidence suggests anti-proliferative effects of FX on many cancer cell lines including NSCLCs, but the detailed mechanisms remain unclear. In the present investigation, we confirmed molecular mechanisms and in vivo anti-lung cancer effect of FX at the first time...
February 15, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28212112/cancer-as-robust-intrinsic-state-shaped-by-evolution-a-key-issues-review
#5
Ruoshi Yuan, Xiaomei Zhu, Gaowei Wang, Site Li, Ping Ao
Cancer is a complex disease: its pathology cannot be properly understood in terms of independent players-genes, proteins, molecular pathways, or their simple combinations. This is similar to many-body physics of a condensed phase that many important properties are not determined by a single atom or molecule. The rapidly accumulating large 'omics' data also require a new mechanistic and global underpinning to organize for rationalizing cancer complexity. A unifying and quantitative theory was proposed by some of the present authors that cancer is a robust state formed by the endogenous molecular-cellular network, which is evolutionarily built for the developmental processes and physiological functions...
February 17, 2017: Reports on Progress in Physics
https://www.readbyqxmd.com/read/28211564/the-genomics-of-inherited-bone-marrow-failure-from-mechanism-to-the-clinic
#6
REVIEW
Talia Wegman-Ostrosky, Sharon A Savage
The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to pancytopenia, and are associated with increased risk of cancer. Although the clinical features of the IBMFS are often diagnostic, variable disease penetrance and expressivity may result in diagnostic dilemmas. The discovery of the genetic aetiology of the IBMFS has been greatly facilitated by next-generation sequencing methods. This has advanced understanding of the underlying biology of the IBMFS and been essential in improving clinical management and genetic counselling for affected patients...
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28211277/antineoplastic-agents-603-quinstatins-exceptional-cancer-cell-growth-inhibitors
#7
George R Pettit, Noeleen Melody, Jean-Charles Chapuis
Discovery of the exceptionally powerful anticancer drug dolastatin 10 (1), contained in the sea hare Dolabella auricularia, opened a new frontier needed for improving human cancer treatment. Subsequently, major advances have been achieved based on results of structurally modifying this unusual natural peptide while maintaining the remarkable anticancer activity necessary for preparation of successful monoclonal antibody drug conjugates (ADC). Among the first several hundred SAR products based on dolastatin 10 our group synthesized and termed auristatins was auristatin E (2a)...
February 17, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28210711/intergenically-spliced-chimeric-rnas-in-cancer
#8
Yuemeng Jia, Zhongqiu Xie, Hui Li
Gene fusions and their encoded products (fusion RNAs and proteins) are viewed as one of the hallmarks of cancer. Traditionally, they were thought to be generated solely by chromosomal rearrangements. However, recent discoveries of trans-splicing and cis-splicing events between neighboring genes, suggest that there are other mechanisms to generate chimeric fusion RNAs without corresponding changes in DNA. In addition, chimeric RNAs have been detected in normal physiology, complicating the use of fusions in cancer detection and therapy...
September 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28210259/resolution-of-cancer-promoting-inflammation-a-new-approach-for-anticancer-therapy
#9
REVIEW
Qi Zhang, Bo Zhu, Yongsheng Li
Inflammation is a protective response that eliminates harmful stimuli and restores tissue homeostasis, whereas the failure to resolve inflammation leads to the development of malignancies. Immune cells in the tumor inflammatory microenvironment endow cancer cells with their specific hallmarks, including mutations, metabolic reprograming, angiogenesis, invasion, and metastasis. Targeting the inflammatory microenvironment with anti-inflammatory drugs (e.g., aspirin) or by enhancing antitumor immunity (e.g., chimeric antigen receptor T cell therapy) has been extensively investigated and has achieved promising results in many cancers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209992/from-basic-apoptosis-discoveries-to-advanced-selective-bcl-2-family-inhibitors
#10
REVIEW
Avi Ashkenazi, Wayne J Fairbrother, Joel D Leverson, Andrew J Souers
Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-XL dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209991/microrna-therapeutics-towards-a-new-era-for-the-management-of-cancer-and-other-diseases
#11
REVIEW
Rajesha Rupaimoole, Frank J Slack
In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209987/targeting-phospholipase-d-in-cancer-infection-and-neurodegenerative-disorders
#12
REVIEW
H Alex Brown, Paul G Thomas, Craig W Lindsley
Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated phosphatidic acid (PtdOH) generation downstream of a variety of cell-surface receptors, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and integrins...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209803/correlation-between-membrane-protein-concentrations-and-transcellular-transport-activity-for-breast-cancer-resistance-protein
#13
Houfu Liu, Liang Huang, Yi Li, Tingting Fu, Xueying Sun, Yan-Yan Zhang, Ruina Gao, Qingfang Chen, Wandong Zhang, Jasminder Sahi, Scott Summerfield, Kelly Dong
Emerging evidence indicates an important role for breast cancer resistance protein (BCRP) in limiting brain penetration of substrate drugs. While in vitro Transwell® assays can provide an indication of BCRP substrate potential, the predictability of these to in vivo brain penetration is still under debate. The present study examines the correlation of BCRP protein concentration and transcellular transport activity across MDCKII monolayers. We expressed human BCRP or murine Bcrp1 in MDCKII wild-type cells using BacMam2 virus transduction...
February 16, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28208771/detecting-blood-based-biomarkers-in-metastatic-breast-cancer-a-systematic-review-of-their-current-status-and-clinical-utility
#14
REVIEW
A M Sofie Berghuis, Hendrik Koffijberg, Jai Prakash, Leon W M M Terstappen, Maarten J IJzerman
Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208712/emerging-cytotoxic-alkaloids-in-the-battle-against-cancer-overview-of-molecular-mechanisms
#15
REVIEW
Zeina Habli, Georgio Toumieh, Maamoun Fatfat, Omar Nasser Rahal, Hala Gali-Muhtasib
Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an excess of unique secondary metabolites with remarkable biological applications. Alkaloids, one of the most abundant metabolites, constitute a large conglomerate of basic heterocyclic nitrogen-containing natural compounds which are normally produced by plants as toxic substances...
February 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28208579/role-of-autophagy-and-apoptosis-in-non-small-cell-lung-cancer
#16
REVIEW
Guangbo Liu, Fen Pei, Fengqing Yang, Lingxiao Li, Amit Dipak Amin, Songnian Liu, J Ross Buchan, William C Cho
Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208262/prussian-blue-as-a-highly-sensitive-and-background-free-resonant-raman-reporter
#17
Yongmei Yin, Qiang Li, Sisi Ma, Huiqiao Liu, Bo Dong, Jie Yang, Dingbin Liu
We report a surprising discovery that Prussian blue (PB) can be employed as a highly sensitive and background-free resonant Raman reporter. Conventional Raman reporters show multiple spectral bands in the fingerprint region, which are generally overlapped with those from dominant endogenous biomolecules, and are thus difficult to be separated. Herein, we found that PB only possesses a strong and sharp single-band in the cellular Raman-silent region, where no Raman signals from biological species were observed...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28207290/fatty-acid-and-mineral-receptors-as-drug-targets-for-gastrointestinal-disorders
#18
Pawin Pongkorpsakol, Aekkacha Moonwiriyakit, Chatchai Muanprasat
Nutrient-sensing receptors, including fatty acid receptors (FFA1-FFA4), Ca(2+)-sensing receptors and Zn(2+)-sensing receptors, are involved in several biological processes. These receptors are abundantly expressed in the GI tract, where they have been shown to play crucial roles in regulating GI function. This review provides an overview of the GI functions of fatty acid and mineral receptors, including the regulation of gastric and enteroendocrine functions, GI motility, ion transport and cell growth. Recently, several lines of evidence have implicated these receptors as promising therapeutic targets for the treatment of GI disorders, for example, inflammatory bowel disease, colorectal cancer, metabolic syndrome and diarrheal diseases...
February 16, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28205554/the-oncoppi-network-of-cancer-focused-protein-protein-interactions-to-inform-biological-insights-and-therapeutic-strategies
#19
Zenggang Li, Andrei A Ivanov, Rina Su, Valentina Gonzalez-Pecchi, Qi Qi, Songlin Liu, Philip Webber, Elizabeth McMillan, Lauren Rusnak, Cau Pham, Xiaoqian Chen, Xiulei Mo, Brian Revennaugh, Wei Zhou, Adam Marcus, Sahar Harati, Xiang Chen, Margaret A Johns, Michael A White, Carlos Moreno, Lee A D Cooper, Yuhong Du, Fadlo R Khuri, Haian Fu
As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute to dysregulated oncogenic pathways. Integration of cancer genes into networks offers opportunities to reveal protein-protein interactions (PPIs) with functional and therapeutic significance. Here, we report the generation of a cancer-focused PPI network, termed OncoPPi, and identification of >260 cancer-associated PPIs not in other large-scale interactomes. PPI hubs reveal new regulatory mechanisms for cancer genes like MYC, STK11, RASSF1 and CDK4...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28202539/parps-and-adp-ribosylation-recent-advances-linking-molecular-functions-to-biological-outcomes
#20
REVIEW
Rebecca Gupte, Ziying Liu, W Lee Kraus
The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates...
January 15, 2017: Genes & Development
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