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Cancer genetics

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https://www.readbyqxmd.com/read/28434142/cancer-genetic-counseling-and-testing-in-an-era-of-rapid-change
#1
Gillian W Hooker, Keelia Rhoads Clemens, John Quillin, Kristen J Vogel Postula, Pia Summerour, Rebecca Nagy, Adam H Buchanan
The impacts of the Association for Molecular Pathology vs. Myriad Supreme Court decision regarding patenting DNA segments and multi-gene testing on cancer genetic counseling practice have not been well described. We aimed to assess genetic counselors' perceptions of how their genetic testing-related practices for hereditary breast and/or ovarian cancer (HBOC) changed after these events. One-hundred fifty-two genetic counselors from the National Society of Genetic Counselors Cancer Special Interest Group completed an anonymous, online, mixed-methods survey in November 2013...
April 22, 2017: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/28434047/late-renal-toxicity-of-treatment-for-childhood-malignancy-risk-factors-long-term-outcomes-and-surveillance
#2
Roderick Skinner
Chronic glomerular and tubular nephrotoxicity is reported in 20-50% and 20-25%, respectively, of children and adolescents treated with ifosfamide and 60-80% and 10-30%, respectively, of those given cisplatin. Up to 20% of children display evidence of chronic glomerular damage after unilateral nephrectomy for a renal tumour. Overall, childhood cancer survivors have a ninefold higher risk of developing renal failure compared with their siblings. Such chronic nephrotoxicity may have multiple causes, including chemotherapy, radiotherapy exposure to kidneys, renal surgery, supportive care drugs and tumour-related factors...
April 22, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28433941/self-assembled-dual-responsive-micelles-stabilized-with-protein-for-co-delivery-of-drug-and-sirna-in-cancer-therapy
#3
M R Aji Alex, Chetan Nehate, Srivani Veeranarayanan, D Sakthi Kumar, Ritu Kulshreshtha, Veena Koul
Design of safe and efficient vehicles for the combinatorial delivery of drugs and genetic agents is an emerging requisite for achieving enhanced therapeutic effect in cancer. Even though several nanoplatforms have been explored for the co-delivery of drugs and genetic materials the translation of these systems to clinical phase is still a challenge, mainly due to tedious synthesis procedures, lack of serum stability, inefficient scalability etc. Here in, we report development of reduction and pH sensitive polymeric graft of low molecular weight poly (styrene -alt -maleic anhydride) and evaluation of its efficacy in co-delivering drug and siRNA...
April 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28433665/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#4
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart Lung Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016 in Bethesda Maryland to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
April 19, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28433570/association-between-environmental-tobacco-smoke-exposure-and-the-occurrence-of-egfr-mutations-and-alk-rearrangements-in-never-smokers-with-non-small-cell-lung-cancer-analyses-from-a-prospective-multinational-ets-registry
#5
Ross A Soo, Akihito Kubo, Masahiko Ando, Tomoya Kawaguchi, Myung-Ju Ahn, Sai-Hong Ignatius Ou
BACKGROUND: Molecular studies have demonstrated actionable driver oncogene alterations are more frequent in never-smokers with non-small-cell lung cancer (NSCLC). The etiology of these driver oncogenes in patients with NSCLC remains unknown, and environmental tobacco smoke (ETS) is a potential cause in these cases. MATERIALS AND METHODS: We assembled clinical and genetic information for never-smoker patients with NSCLC accrued in Japan, Korea, Singapore, and the United States...
January 19, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28433505/chemotherapy-induces-alternative-transcription-and-splicing-facts-and-hopes-for-cancer-treatment
#6
Charles A Lambert, Nancy Garbacki, Alain C Colige
Alternative promoter usage, alternative splicing and alternative cleavage/polyadenylation (referred here as to alternative transcription and splicing) are main instruments to diversify the transcriptome from a limited set of genes. There is a good deal of evidence that chemotherapeutic drugs affect these processes, but the therapeutic incidence of these effects is poorly documented. The scope of this study is to review the impact of chemotherapy on alternative transcription and splicing and to discuss potential implications in cancer therapy...
April 19, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28433369/fertility-preservation-and-refreezing-of-transplanted-ovarian-tissue-a-potential-new-way-of-managing-patients-with-low-risk-of-malignant-cell-recurrence
#7
Stine Gry Kristensen, Veronica Giorgione, Peter Humaidan, Birgit Alsbjerg, Anne-Mette Bay Bjørn, Erik Ernst, Claus Yding Andersen
OBJECTIVE: To report the first successful refreezing of ovarian tissue recovered more than 3 years after transplantation in a woman previously treated for early-stage ovarian cancer. DESIGN: Evaluation of cryopreserved and grafted ovarian tissue. SETTING: University hospital. PATIENT(S): A 23-year-old woman diagnosed with stage 1C ovarian mucinous cystadenocarcinoma. INTERVENTION(S): The patient underwent ovarian tissue cryopreservation for fertility preservation and subsequent heterotopic transplantation for fertility restoration 9 years after freezing...
April 19, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28433077/development-and-clinical-utility-of-a-blood-based-test-service-for-the-rapid-identification-of-actionable-mutations-in-non-small-cell-lung-carcinoma
#8
Hestia Mellert, Trudi Foreman, Leisa Jackson, Dianna Maar, Scott Thurston, Kristina Koch, Amanda Weaver, Samantha Cooper, Nicholas Dupuis, Ubaradka G Sathyanarayana, Jakkie Greer, Westen Hahn, Dawne Shelton, Paula Stonemetz, Gary A Pestano
Nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder the ability to pursue optimal treatment strategies. This study validates a blood-based genome-testing service that provides accurate results within 72 hours. We focused on targetable variants in advanced non-small cell lung carcinoma-epidermal growth factor receptor gene (EGFR) variant L858R, exon 19 deletion (ΔE746-A750), and T790M; GTPase Kirsten ras gene (KRAS) variants G12C/D/V; and echinoderm microtubule associated protein like and 4 anaplastic lymphoma receptor tyrosine kinase fusion (EML4-ALK) transcripts 1/2/3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28432752/incretin-based-glucose-lowering-medications-and-the-risk-for-acute-pancreatitis-and-or-pancreatic-cancer-risk-reassuring-data-from-cardio-vascular-outcome-trials
#9
Michael A Nauck, Juris J Meier, Wolfgang E Schmidt
Incretin-based medications (glucagon-like peptide-1 [GLP-1] receptor agonists and inhibitors of dipeptidyl peptidase-4 [DPP-4] are glucose-lowering drugs approved and introduced after 2006 (1). Although both classes of drugs appeared to be relatively safe based on results from clinical trials and standard animal toxicology studies, epidemiological data (2, 3) and histological findings (4) in genetically modified rodents exposed to such agents have raised concern that pancreatitis and pancreatic cancer may be long-term risks associated with this therapy...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432594/microrna-transfer-between-bone-marrow-adipose-and-multiple-myeloma-cells
#10
REVIEW
Luna Soley, Carolyne Falank, Michaela R Reagan
PURPOSE OF REVIEW: Multiple myeloma remains an incurable disease, largely due to the tumor-supportive role of the bone marrow microenvironment. Bone marrow adipose tissue (BMAT) is one component of the fertile microenvironment which is believed to contribute to myeloma progression and drug resistance, as well as participate in a vicious cycle of osteolysis and tumor growth. RECENT FINDINGS: MicroRNAs (miRNAs) have recently emerged as instrumental regulators of cellular processes that enable the development and dissemination of cancer...
April 21, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28432456/deregulated-bcl-2-family-proteins-impact-on-repair-of-dna-double-strand-breaks-and-are-targets-to-overcome-radioresistance-in-lung-cancer
#11
Sarah A Wieczorek, Frank Breitenbuecher, Aashish Soni, Katja Paul-Konietzko, Sophie Ziegler, Ali Sak, George Iliakis, Martin Schuler
PURPOSE: DNA damage-induced cell death is a major effector mechanism of radiotherapy. Aberrant expression of anti-apoptotic BCL-2 family proteins is frequently observed in lung cancers. Against this background, we studied radioresistance mediated by BCL-2 family proteins at the mechanistic level and its potential as target for radiochemotherapy. METHODS: Lung cancer models stably expressing BCL-xL or MCL-1 were irradiated to study cell death, clonogenic survival, and DNA repair kinetics in vitro, and growth suppression of established tumors in vivo...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28432052/genomic-instability-in-cancer-teetering-on-the-limit-of-tolerance
#12
REVIEW
Noemi Andor, Carlo C Maley, Hanlee P Ji
Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection, and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared with intermediate levels under this threshold...
April 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28431245/host-microbe-co-metabolism-dictates-cancer-drug-efficacy-in-c-%C3%A2-elegans
#13
Timothy A Scott, Leonor M Quintaneiro, Povilas Norvaisas, Prudence P Lui, Matthew P Wilson, Kit-Yi Leung, Lucia Herrera-Dominguez, Sonia Sudiwala, Alberto Pessia, Peter T Clayton, Kevin Bryson, Vidya Velagapudi, Philippa B Mills, Athanasios Typas, Nicholas D E Greene, Filipe Cabreiro
Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed three-way high-throughput screens that unraveled the complexity underlying host-microbe-drug interactions. We report that microbes can bolster or suppress the effects of fluoropyrimidines through metabolic drug interconversion involving bacterial vitamin B6, B9, and ribonucleotide metabolism...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431244/bacterial-metabolism-affects-the-c-%C3%A2-elegans-response-to-cancer-chemotherapeutics
#14
Aurian P García-González, Ashlyn D Ritter, Shaleen Shrestha, Erik C Andersen, L Safak Yilmaz, Albertha J M Walhout
The human microbiota greatly affects physiology and disease; however, the contribution of bacteria to the response to chemotherapeutic drugs remains poorly understood. Caenorhabditis elegans and its bacterial diet provide a powerful system to study host-bacteria interactions. Here, we use this system to study how bacteria affect the C. elegans response to chemotherapeutics. We find that different bacterial species can increase the response to one drug yet decrease the effect of another. We perform genetic screens in two bacterial species using three chemotherapeutic drugs: 5-fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FUDR), and camptothecin (CPT)...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#15
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430867/emerging-evidence-for-the-role-of-differential-tumor-microenvironment-in-breast-cancer-racial-disparity-a-closer-look-at-the-surroundings
#16
Sachin Kumar Deshmukh, Sanjeev K Srivastava, Nikhil Tyagi, Aamir Ahmad, Ajay P Singh, Ahmed Al Ghadhban, Donna L Dyess, James E Carter, Kari Dugger, Seema Singh
Although increased awareness leading to early detection and prevention, as well as advancements in treatment strategies, have resulted in superior clinical outcomes, African American women with breast cancer continue to have greater mortality rates, compared to Caucasian American counterparts. Moreover, African American women are more likely to have breast cancer at a younger age and be diagnosed with aggressive tumor sub-types. Such racial disparities can be attributed to socioeconomic differences, but it is increasingly being recognized that these disparities may indeed be due to certain genetic and other non-genetic biological differences...
April 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28430823/modulation-the-alternative-splicing-of-gla-ivs4-919g-a-in-fabry-disease
#17
Wen-Hsin Chang, Dau-Ming Niu, Chi-Yu Lu, Shyr-Yi Lin, Ta-Chih Liu, Jan-Gowth Chang
While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant alternative splicing resulting in Fabry disease has been reported, its molecular mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion, H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with GLA...
2017: PloS One
https://www.readbyqxmd.com/read/28430650/the-p-g534e-variant-of-habp2-is-not-associated-with-sporadic-papillary-thyroid-carcinoma-in-a-polish-population
#18
Artur Kowalik, Danuta Gąsior-Perczak, Martyna Gromek, Monika Siołek, Agnieszka Walczyk, Iwona Pałyga, Małgorzata Chłopek, Janusz Kopczyński, Ryszard Mężyk, Aldona Kowalska, Stanisław Góźdź
Thyroid cancer is one of the most frequently diagnosed cancers of the endocrine system. There are no known genetic risk factors for non-medullary thyroid cancer, other than a small number of hereditary syndromes; however, approximately 5% of non-medullary thyroid cancer, designated familial non-medullary thyroid cancer, exhibits heritability. The p.G534E (c.1601G>A) variant of HABP2 was recently reported as a risk factor for familial non-medullary thyroid cancer, including papillary thyroid carcinoma. We analyzed the incidence of the c...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430642/immunocompetent-mouse-allograft-models-for-development-of-therapies-to-target-breast-cancer-metastasis
#19
Yuan Yang, Howard H Yang, Ying Hu, Peter H Watson, Huaitian Liu, Thomas R Geiger, Miriam R Anver, Diana C Haines, Philip Martin, Jeffrey E Green, Maxwell P Lee, Kent W Hunter, Lalage M Wakefield
Effective drug development to combat metastatic disease in breast cancer would be aided by the availability of well-characterized preclinical animal models that (a) metastasize with high efficiency, (b) metastasize in a reasonable time-frame, (c) have an intact immune system, and (d) capture some of the heterogeneity of the human disease. To address these issues, we have assembled a panel of twelve mouse mammary cancer cell lines that can metastasize efficiently on implantation into syngeneic immunocompetent hosts...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430593/genetic-variants-within-the-cancer-susceptibility-region-8q24-and-ovarian-cancer-risk-in-han-chinese-women
#20
Jing Han, Jing Zhou, Hua Yuan, Longbiao Zhu, Hongxia Ma, Dong Hang, Dake Li
Accumulating evidence suggests that genetic variants at chromosome 8q24 confer susceptibility to various types of cancer. This case-control study was designed to explore the relationship between genetic variants at 8q24 and ovarian cancer risk in Han Chinese women. Two variants (rs13281615 A > G and rs6983267 T > G) were genotyped in 377 ovarian cancer cases and 1034 cancer-free controls using TaqMan allelic discrimination assay. Logistic regression analysis revealed that the G allele of rs6983267 was significantly associated with increased risk of ovarian cancer (additive model: adjusted OR = 1...
April 5, 2017: Oncotarget
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