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https://www.readbyqxmd.com/read/29356057/genetic-risk-of-prostate-cancer-in-ugandan-men
#1
Zhaohui Du, Alexander Lubmawa, Susan Gundell, Peggy Wan, Cissy Nalukenge, Proscovia Muwanga, Moses Lutalo, Deborah Nansereko, Olivia Ndaruhutse, Molly Katuku, Rosemary Nassanga, Frank Asiimwe, Benon Masaba, Sam Kaggwa, Dan Namuguzi, Vicky Kiddu, George Mutema, David V Conti, Asiimwe Luke, Kuteesa Job, Dabanja M Henry, Christopher A Haiman, Stephen Watya
BACKGROUND: Men of African-ancestry have elevated prostate cancer (PCa) incidence and mortality compared to men of other racial groups. There is support for a genetic contribution to this disparity, with evidence of genetic heterogeneity in the underlying risk alleles between populations. Studies of PCa among African men may inform the contribution of genetic risk factors to the elevated disease burden in this population. METHODS: We conducted an association study of >100 previously reported PCa risk alleles among 571 incidence cases and 485 controls among Uganda men...
January 21, 2018: Prostate
https://www.readbyqxmd.com/read/29355848/interactome-insider-a-structural-interactome-browser-for-genomic-studies
#2
Michael J Meyer, Juan Felipe Beltrán, Siqi Liang, Robert Fragoza, Aaron Rumack, Jin Liang, Xiaomu Wei, Haiyuan Yu
We present Interactome INSIDER, a tool to link genomic variant information with structural protein-protein interactomes. Underlying this tool is the application of machine learning to predict protein interaction interfaces for 185,957 protein interactions with previously unresolved interfaces in human and seven model organisms, including the entire experimentally determined human binary interactome. Predicted interfaces exhibit functional properties similar to those of known interfaces, including enrichment for disease mutations and recurrent cancer mutations...
January 1, 2018: Nature Methods
https://www.readbyqxmd.com/read/29355757/non-genomic-mechanisms-of-protein-phosphatase-2a-pp2a-regulation-in-cancer
#3
REVIEW
Otto Kauko, Jukka Westermarck
Propagation of transient signals requires coordinated suppression of antagonistic phosphatase activity. Protein phosphatase 2A (PP2A) is a broad specificity serine/threonine phosphatase that functions as an antagonist of many signaling pathways associated with growth and proliferation, and endogenous inhibitory mechanisms suppress PP2A activity in response to mitogenic stimuli. These inhibitory mechanisms, including expression and activation of endogenous inhibitor proteins and phosphoregulation of PP2A subunits, are also engaged by aberrant constitutive activation of mitogenic pathways in cancer...
January 17, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29355669/clinical-applications-of-the-cellsearch-platform-in-cancer-patients
#4
Sabine Riethdorf, Linda O'Flaherty, Claudia Hille, Klaus Pantel
The CellSearch® system (CS) enables standardized enrichment and enumeration of circulating tumor cells (CTCs) that are repeatedly assessable via non-invasive "liquid biopsy". While the association of CTCs with poor clinical outcome for cancer patients has clearly been demonstrated in numerous clinical studies, utilizing CTCs for the identification of therapeutic targets, stratification of patients for targeted therapies and uncovering mechanisms of resistance is still under investigation. Here, we comprehensively review the current benefits and drawbacks of clinical CTC analyses for patients with metastatic and non-metastatic tumors...
January 17, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29355614/head-and-neck-squamous-cell-carcinoma-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatments
#5
REVIEW
Benjamin Solomon, Richard J Young, Danny Rischin
Head and neck squamous cell carcinoma (HNSCC) comprises a heterogeneous group of tumors that arise from the squamous epithelium of the oral cavity, oropharynx, larynx and hypopharynx. While many HNSCCs are related to classical etiologic factors of smoking and alcohol, a clinically, genomically, and immunologically distinct subgroup of tumors arise from the epithelium of the tonsil and the base of tongue as a result of infection with Human Papilloma Virus (HPV). In this review we describe the genomic and immunologic landscape of HNSCC, highlighting differences between HPV-positive and HPV-negative HNSCC...
January 17, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29355591/chaperoning-the-guardian-of-the-genome-the-two-faced-role-of-molecular-chaperones-in-tumor-suppressor-p53-action
#6
REVIEW
Bartosz Wawrzynow, Alicja Zylicz, Maciej Zylicz
Organized networks of heat shock proteins, which possess molecular chaperone activity, protect cells from abrupt environmental changes. Additionally, molecular chaperones are essential during stress-free periods, where they moderate housekeeping functions. During tumorigenesis these chaperone networks are extensively remodeled in such a way that they are advantageous to the transforming cell. Molecular chaperones by buffering critical elements of signaling pathways empower tumor evolution leading to chemoresistance of cancer cells...
January 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29355525/negative-regulation-of-brca1-by-transforming-acidic-coiled-coil-protein-3-tacc3
#7
Jung-Lye Kim, Geun-Hyoung Ha, Loredana Campo, Eun-Kyoung Breuer
In spite of the push to identify modifiers of BRCAness, it still remains unclear how tumor suppressor BRCA1 is lost in breast cancers in the absence of genetic or epigenetic aberrations. Mounting evidence indicates that the transforming acidic coiled-coil 3 (TACC3) plays an important role in the centrosome-microtubule network during mitosis and gene expression, and that deregulation of TACC3 is associated with breast cancer. However, the molecular mechanisms by which TACC3 contributes to breast cancer development have yet to be elucidated...
January 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29355244/a-game-of-substrates-replication-fork-remodeling-and-its-roles-in-genome-stability-and-chemo-resistance
#8
Julia Sidorova
During the hours that human cells spend in the DNA synthesis (S) phase of the cell cycle, they may encounter adversities such as DNA damage or shortage of nucleotides. Under these stresses, replication forks in DNA may experience slowing, stalling, and breakage. Fork remodeling mechanisms, which stabilize slow or stalled replication forks and ensure their ability to continue or resume replication, protect cells from genomic instability and carcinogenesis. Fork remodeling includes DNA strand exchanges that result in annealing of newly synthesized strands (fork reversal), controlled DNA resection, and cleavage of DNA strands...
December 2017: Cell Stress
https://www.readbyqxmd.com/read/29354499/online-tools-for-patient-counseling-in-bladder-and-kidney-cancer-ready-for-prime-time
#9
REVIEW
Philipp Gild, Michael Rink, Christian P Meyer
Gauging prognosis is a key element when facing treatment decisions in cancer care. Several prognostic tools, such as risk tables and nomograms are at hand to aid this process. In the context of patient-centered care, prognostic tools are of great interest to caregivers and -providers alike, as they can convey sizeable amounts of information and provide tailored, accurate estimates of prognosis. Given the rising number of prognostic tools in cancer care over the last two decades, and similarly, ever increasing presence of the Internet, we aimed to assess how this would translate into the availability of online tools for patient counseling...
December 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/29354493/different-stages-in-drug-development-for-muscle-invasive-bladder-cancer
#10
REVIEW
Gallus Beatus Ineichen, Raphael Röthlisberger, Kevin Fabian Johner, Roland Seiler
Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease. Despite optimal therapy, half of the patients will succumb to disease. This prognosis could not be improved over the last three decades. Therefore, MIBC is left behind from other cancers such as prostate, where novel treatment options were discovered and improve patient outcomes. While being aware of the recent emerging evidence of checkpoint inhibition in MIBC, we aim to describe different stages of drug development in MIBC by using three specific targets...
December 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/29354491/opportunities-of-next-generation-sequencing-in-non-muscle-invasive-bladder-cancer-outcome-prediction
#11
REVIEW
Karl H Pang, Francesco Esperto, Aidan P Noon
Bladder cancer (BC) is a common disease in both sexes and majority of cases present as non-muscle invasive BC (NMIBC). The percentage of NMIBC progressing to muscle invasive BC (MIBC) varies between 25% and 75% and currently there are no reliable biomarkers that may predict the outcome of high-risk (HR) NMIBC. Whilst The Cancer Genome Atlas (TCGA) project has identified genetic alteration in MIBC using next-generation sequencing (NGS), genetic data in HR-NMIBC outcome prediction using this new technology are limited...
December 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/29354286/pan-cancer-screen-for-mutations-in-non-coding-elements-with-conservation-and-cancer-specificity-reveals-correlations-with-expression-and-survival
#12
Henrik Hornshøj, Morten Muhlig Nielsen, Nicholas A Sinnott-Armstrong, Michał P Świtnicki, Malene Juul, Tobias Madsen, Richard Sallari, Manolis Kellis, Torben Ørntoft, Asger Hobolth, Jakob Skou Pedersen
Cancer develops by accumulation of somatic driver mutations, which impact cellular function. Mutations in non-coding regulatory regions can now be studied genome-wide and further characterized by correlation with gene expression and clinical outcome to identify driver candidates. Using a new two-stage procedure, called ncDriver, we first screened 507 ICGC whole-genomes from 10 cancer types for non-coding elements, in which mutations are both recurrent and have elevated conservation or cancer specificity. This identified 160 significant non-coding elements, including the TERT promoter, a well-known non-coding driver element, as well as elements associated with known cancer genes and regulatory genes (e...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29353739/generation-of-matched-patient-derived-xenograft-in%C3%A2-vitro-in%C3%A2-vivo-models-using-3d-macroporous-hydrogels-for-the-study-of-liver-cancer
#13
Eliza Li Shan Fong, Tan Boon Toh, Xiaoxuan Lin, Zheng Liu, Lissa Hooi, Masturah Bte Mohd Abdul Rashid, Touati Benoukraf, Edward Kai-Hua Chow, The Hung Huynh, Hanry Yu
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, often manifesting at the advanced stage when cure is no longer possible. The discrepancy between preclinical findings and clinical outcome in HCC is well-recognized. So far, sorafenib is the only targeted therapy approved as first-line therapy for patients with advanced HCC. There is an urgent need for improved preclinical models for the development of HCC-targeted therapies. Patient-derived xenograft (PDX) tumor models have been shown to closely recapitulate human tumor biology and predict patient drug response...
January 4, 2018: Biomaterials
https://www.readbyqxmd.com/read/29353317/tumor-suppressor-c-rassf-proteins
#14
REVIEW
Hiroaki Iwasa, Shakhawoat Hossain, Yutaka Hata
Human genome has ten genes that are collectedly called Ras association domain family (RASSF). RASSF is composed of two subclasses, C-RASSF and N-RASSF. Both N-RASSF and C-RASSF encode Ras association domain-containing proteins and are frequently suppressed by DNA hypermethylation in human cancers. However, C-RASSF and N-RASSF are quite different. Six C-RASSF proteins (RASSF1-6) are characterized by a C-terminal coiled-coil motif named Salvador/RASSF/Hippo domain, while four N-RASSF proteins (RASSF7-10) lack it...
January 20, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29352488/understanding-intratumor-heterogeneity-by-combining-genome-analysis-and-mathematical-modeling
#15
REVIEW
Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy...
January 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#16
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352368/endocrine-therapy-and-related-issues-in-hormone-receptor-positive-early-breast-cancer-a-roundtable-discussion-by-the-breast-cancer-therapy-expert-group-bcteg
#17
REVIEW
Jame Abraham, Humberto Caldera, Robert Coleman, Anthony Elias, Matthew P Goetz, Muaiad Kittaneh, Elyse Lower, Reshma Mahtani, E Terry Mamounas, Mark Pegram, Hope Rugo, Lee Schwartzberg, Tiffany Traina, Chuck Vogel
PURPOSE: Management of breast cancer is a rapidly evolving field, and, although evidence-based guidelines are available for clinicians to provide direction on critical issues in patient care, clinicians often left to address these issues in the context of community practice situations with their patients. These include the patient's comorbid conditions, actual versus perceived benefit of treatments, patient's compliance as well as financial/reimbursement issues, and long-term tolerability of therapy...
January 19, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29352080/functional-analysis-of-cancer-associated-dna-polymerase-%C3%AE%C2%B5-variants-in-saccharomyces-cerevisiae
#18
Stephanie R Barbari, Daniel P Kane, Elizabeth A Moore, Polina V Shcherbakova
DNA replication fidelity relies on base selectivity of the replicative DNA polymerases, exonucleolytic proofreading, and post-replicative DNA mismatch repair (MMR). Ultramutated human cancers without MMR defects carry alterations in the exonuclease domain of DNA polymerase ε (Polε). They have been hypothesized to result from defective proofreading. However, modeling in yeast of the most common variant, Polε-P286R, produced an unexpectedly strong mutator effect that exceeded the effect of proofreading deficiency by two orders of magnitude and indicated the involvement of other infidelity factors...
January 19, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29352063/arabidopsis-thaliana-fancd2-promotes-meiotic-crossover-formation
#19
Marie-Therese Kurzbauer, Monica Pradillo, Claudia Kerzendorfer, Jason Sims, Rene Ladurner, Cecilia Oliver, Michael Peter Janisiw, Magdalena Mosiolek, Dieter Schweizer, Gregory P Copenhaver, Peter Schlogelhofer
Fanconi anemia (FA) is a human autosomal recessive disorder characterized by chromosomal instability, developmental pathologies, predisposition to cancer and reduced fertility. So far, nineteen genes have been implicated in FA, most of them involved in DNA repair. Some are conserved across higher eukaryotes, including plants. The Arabidopsis thaliana genome encodes a homologue of the Fanconi anemia D2 gene (FANCD2) whose function in DNA repair is not yet fully understood. Here we provide evidence that AtFANCD2 is required for meiotic homologous recombination...
January 19, 2018: Plant Cell
https://www.readbyqxmd.com/read/29351920/exceptional-response-to-pembrolizumab-in-a-metastatic-chemotherapy-radiation-resistant-ovarian-cancer-patient-harboring-a-cd274-pd-l1-genetic-rearrangement
#20
Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia A Elvin, David L Rimm, Yuting Liu, Elena Ratner, Peter E Schwartz, Alessandro D Santin
PURPOSE: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. EXPERIMENTAL DESIGN: We describe a heavily pretreated ovarian cancer patient with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune check-point inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (ie, automated quantitative analysis, AQUA) and whole exome sequencing (WES) techniques...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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