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https://www.readbyqxmd.com/read/27892699/genetics-of-consanguinity-and-inbreeding-in-health-and-disease
#1
Mohd Fareed, Mohammad Afzal
CONTEXT: Inbreeding increases the level of homozygotes for autosomal recessive disorders and is the major objective in clinical studies. The prevalence of consanguinity and the degree of inbreeding vary from one population to another depending on ethnicity, religion, culture and geography. Global epidemiological studies have revealed that consanguineous unions have been significantly associated with increased susceptibility to various forms of inherited diseases Objective: The study aimed to determine the role of consanguinity in human health and to highlight the associated risks for various diseases or disorders...
November 28, 2016: Annals of Human Biology
https://www.readbyqxmd.com/read/27872682/prophylactic-liver-transplantation-for-high-risk-recurrent-hepatocellular-carcinoma
#2
REVIEW
Po-Chih Yang, Cheng-Maw Ho, Rey-Heng Hu, Ming-Chih Ho, Yao-Ming Wu, Po-Huang Lee
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. Radical treatment of HCC in early stages results in a long disease-free period and improved overall survival. The choice of optimal management strategy for HCC mainly depends on the severity of the underlying liver disease. For patients with decompensated liver cirrhosis and HCC within Milan criteria (MC), liver transplant (LT) is the choice of treatment. However, for patients with good residual liver reserve and HCC within MC, selection of other curative treatments such as liver resection (LR) or radiofrequency ablation may be a reasonable alternative...
November 8, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27857060/identification-of-transcription-factors-tfs-and-targets-involved-in-the-cholangiocarcinoma-cca-by-integrated-analysis
#3
L Yang, S Feng, Y Yang
The present study was designed to investigate the upstream transcription factors (TFs) and the signature genes in cholangiocarcinoma (CCA), providing better clues on the regulatory mechanisms and therapeutic applications. Gene expression data sets of CCA were searched in the Gene Expression Omnibus database for integrated analysis. Functional annotation of differently expressed genes (DEGs) was then conducted and the TFs were identified. Moreover, a global transcriptional regulatory network of TFs-targets was constructed...
November 18, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27743920/development-and-validation-of-a-24-gene-predictor-of-response-to-postoperative-radiotherapy-in-prostate-cancer-a-matched-retrospective-analysis
#4
Shuang G Zhao, S Laura Chang, Daniel E Spratt, Nicholas Erho, Menggang Yu, Hussam Al-Deen Ashab, Mohammed Alshalalfa, Corey Speers, Scott A Tomlins, Elai Davicioni, Adam P Dicker, Peter R Carroll, Matthew R Cooperberg, Stephen J Freedland, R Jeffrey Karnes, Ashley E Ross, Edward M Schaeffer, Robert B Den, Paul L Nguyen, Felix Y Feng
BACKGROUND: Postoperative radiotherapy has an important role in the treatment of prostate cancer, but personalised patient selection could improve outcomes and spare unnecessary toxicity. We aimed to develop and validate a gene expression signature to predict which patients would benefit most from postoperative radiotherapy. METHODS: Patients were eligible for this matched, retrospective study if they were included in one of five published US studies (cohort, case-cohort, and case-control studies) of patients with prostate adenocarcinoma who had radical prostatectomy (with or without postoperative radiotherapy) and had gene expression analysis of the tumour, with long-term follow-up and complete clinicopathological data...
October 12, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27615397/autoantibody-signature-enhances-the-positive-predictive-power-of-computed-tomography-and-nodule-based-risk-models-for-detection-of-lung%C3%A2-cancer
#5
Pierre P Massion, Graham F Healey, Laura J Peek, Lynn Fredericks, Herb F Sewell, Andrea Murray, John F R Robertson
INTRODUCTION: The incidence of pulmonary nodules is increasing with the movement toward screening for lung cancer by low-dose computed tomography. Given the large number of benign nodules detected by computed tomography, an adjunctive test capable of distinguishing malignant from benign nodules would benefit practitioners. The ability of the EarlyCDT-Lung blood test (Oncimmune Ltd., Nottingham, United Kingdom) to make this distinction by measuring autoantibodies to seven tumor-associated antigens was evaluated in a prospective registry...
September 8, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27570551/peripheral-blood-cell-gene-expression-diagnostic-for-identifying-symptomatic-transthyretin-amyloidosis-patients-male-and-female-specific-signatures
#6
Sunil M Kurian, Marta Novais, Thomas Whisenant, Terri Gelbart, Joel N Buxbaum, Jeffery W Kelly, Teresa Coelho, Daniel R Salomon
BACKGROUND: Early diagnosis of familial transthyretin (TTR) amyloid diseases remains challenging because of variable disease penetrance. Currently, patients must have an amyloid positive tissue biopsy to be eligible for disease-modifying therapies. Endomyocardial biopsies are typically amyloid positive when cardiomyopathy is suspected, but this disease manifestation is generally diagnosed late. Early diagnosis is often difficult because patients exhibit apparent symptoms of polyneuropathy, but have a negative amyloid biopsy...
2016: Theranostics
https://www.readbyqxmd.com/read/27544285/multigene-measurable-residual-disease-assessment-improves-acute-myeloid-leukemia-relapse-risk-stratification-in-autologous-hematopoietic-cell-transplantation
#7
Matthew P Mulé, Gabriel N Mannis, Brent L Wood, Jerald P Radich, Jimmy Hwang, Nestor R Ramos, Charalambos Andreadis, Lloyd Damon, Aaron C Logan, Thomas G Martin, Christopher S Hourigan
We report here the largest study to date of adult patients with acute myeloid leukemia (AML) tested for measurable residual disease (MRD) at the time of autologous hematopoietic cell transplantation (auto-HCT). Seventy-two adult patients who underwent transplantation between 2004 and 2013 at a single academic medical center (University of California San Francisco) were eligible for this retrospective study based on availability of cryopreserved granulocyte colony-stimulating factor (GCSF)-mobilized autologous peripheral blood progenitor cell (PBPC) leukapheresis specimens ("autografts")...
November 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27522582/topical-treatment-of-melanoma-metastases-with-imiquimod-plus-administration-of-a-cancer-vaccine-promotes-immune-signatures-in-the-metastases
#8
Ileana S Mauldin, Nolan A Wages, Anne M Stowman, Ena Wang, Walter C Olson, Donna H Deacon, Kelly T Smith, Nadedja Galeassi, Jessica E Teague, Mark E Smolkin, Kimberly A Chianese-Bullock, Rachael A Clark, Gina R Petroni, Francesco M Marincola, David W Mullins, Craig L Slingluff
INTRODUCTION: Infiltration of cancers by T cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T cell infiltration of tumors are not known. This study was designed to assess whether topical treatment of melanoma metastases with the TLR7 agonist imiquimod plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. PATIENTS AND METHODS: Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to metastatic tumors daily...
October 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27522581/intratumoral-interferon-gamma-increases-chemokine-production-but-fails-to-increase-t-cell-infiltration-of-human-melanoma-metastases
#9
Ileana S Mauldin, Nolan A Wages, Anne M Stowman, Ena Wang, Mark E Smolkin, Walter C Olson, Donna H Deacon, Kelly T Smith, Nadedja V Galeassi, Kimberly A Chianese-Bullock, Lynn T Dengel, Francesco M Marincola, Gina R Petroni, David W Mullins, Craig L Slingluff
INTRODUCTION: Optimal approaches to induce T cell infiltration of tumors are not known. Chemokines CXCL9, CXCL10, and CXCL11 support effector T cell recruitment and may be induced by IFN. This study tests the hypothesis that intratumoral administration of IFNγ will induce CXCL9-11 and will induce T cell recruitment and anti-tumor immune signatures in melanoma metastases. PATIENTS AND METHODS: Nine eligible patients were immunized with a vaccine comprised of 12 class I MHC-restricted melanoma peptides and received IFNγ intratumorally...
October 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27463019/plasma-mirna-alterations-between-nsclc-patients-harboring-del19-and-l858r-egfr-mutations
#10
Yihan Ma, Peiqi Xu, Yanjun Mi, Wenyi Wang, Xiaoyan Pan, Xiaoting Wu, Qi He, Hongming Liu, Weiwei Tang, Hanxiang An
Based on recognition of driver mutations, treatment paradigm for non-small-cell lung cancer (NSCLC) patients has been shifted. However, recently exon 19 deletion mutation (del19) of epidermal growth factor receptor (EGFR) clearly shows better clinical benefit over single-point substitution mutation L858R in exon 21 (L858R). The aim of this study was to investigate the difference by analyzing the expression of plasma microRNAs (miRNAs) of NSCLC patients with EGFR mutation del19 or L858R. MiRNA microarray of plasma from patients' blood identified 79 mapped, network-eligible miRNAs (fold > 5), of which 76 were up regulated and 3 were down regulated...
July 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27432924/association-between-results-of-a-gene-expression-signature-assay-and-recurrence-free-interval-in-patients-with-stage-ii-colon-cancer-in-cancer-and-leukemia-group-b-9581-alliance
#11
Donna Niedzwiecki, Wendy L Frankel, Alan P Venook, Xing Ye, Paula N Friedman, Richard M Goldberg, Robert J Mayer, Thomas Anthony Colacchio, Jude Marie Mulligan, Timothy S Davison, Eamonn O'Brien, Peter Kerr, Patrick G Johnston, Richard D Kennedy, D Paul Harkin, Richard L Schilsky, Monica M Bertagnolli, Robert S Warren, Federico Innocenti
PURPOSE: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27421833/sputum-rna-signature-in-allergic-asthmatics-following-allergen-bronchoprovocation-test
#12
Rob G J A Zuiker, Catherine Tribouley, Zuzana Diamant, J Diderik Boot, Adam F Cohen, K Van Dyck, I De Lepeleire, Veronica M Rivas, Vladislav A Malkov, Jacobus Burggraaf, Marcella K Ruddy
BACKGROUND: Inhaled allergen challenge is a validated disease model of allergic asthma offering useful pharmacodynamic assessment of pharmacotherapeutic effects in a limited number of subjects. OBJECTIVES: To evaluate whether an RNA signature can be identified from induced sputum following an inhaled allergen challenge, whether a RNA signature could be modulated by limited doses of inhaled fluticasone, and whether these gene expression profiles would correlate with the clinical endpoints measured in this study...
2016: European Clinical Respiratory Journal
https://www.readbyqxmd.com/read/27406347/adaptive-randomization-of-veliparib-carboplatin-treatment-in-breast-cancer
#13
RANDOMIZED CONTROLLED TRIAL
Hope S Rugo, Olufunmilayo I Olopade, Angela DeMichele, Christina Yau, Laura J van 't Veer, Meredith B Buxton, Michael Hogarth, Nola M Hylton, Melissa Paoloni, Jane Perlmutter, W Fraser Symmans, Douglas Yee, A Jo Chien, Anne M Wallace, Henry G Kaplan, Judy C Boughey, Tufia C Haddad, Kathy S Albain, Minetta C Liu, Claudine Isaacs, Qamar J Khan, Julie E Lang, Rebecca K Viscusi, Lajos Pusztai, Stacy L Moulder, Stephen Y Chui, Kathleen A Kemmer, Anthony D Elias, Kirsten K Edmiston, David M Euhus, Barbara B Haley, Rita Nanda, Donald W Northfelt, Debasish Tripathy, William C Wood, Cheryl Ewing, Richard Schwab, Julia Lyandres, Sarah E Davis, Gillian L Hirst, Ashish Sanil, Donald A Berry, Laura J Esserman
BACKGROUND: The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin...
July 7, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27406346/adaptive-randomization-of-neratinib-in-early-breast-cancer
#14
RANDOMIZED CONTROLLED TRIAL
John W Park, Minetta C Liu, Douglas Yee, Christina Yau, Laura J van 't Veer, W Fraser Symmans, Melissa Paoloni, Jane Perlmutter, Nola M Hylton, Michael Hogarth, Angela DeMichele, Meredith B Buxton, A Jo Chien, Anne M Wallace, Judy C Boughey, Tufia C Haddad, Stephen Y Chui, Kathleen A Kemmer, Henry G Kaplan, Claudine Isaacs, Rita Nanda, Debasish Tripathy, Kathy S Albain, Kirsten K Edmiston, Anthony D Elias, Donald W Northfelt, Lajos Pusztai, Stacy L Moulder, Julie E Lang, Rebecca K Viscusi, David M Euhus, Barbara B Haley, Qamar J Khan, William C Wood, Michelle Melisko, Richard Schwab, Teresa Helsten, Julia Lyandres, Sarah E Davis, Gillian L Hirst, Ashish Sanil, Laura J Esserman, Donald A Berry
BACKGROUND: The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery). METHODS: We used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control...
July 7, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27354021/a-phase-i-study-of-cd25-regulatory-t-cell-depleted-donor-lymphocyte-infusion-for-relapse-after-allogeneic-stem-cell-transplantation
#15
Sarah Nikiforow, Haesook T Kim, Heather Daley, Carol Reynolds, Kyle Thomas Jones, Philippe Armand, Vincent T Ho, Edwin P Alyea, Corey S Cutler, Jerome Ritz, Joseph H Antin, Robert J Soiffer, John Koreth
Donor lymphocyte infusions are used to treat relapse after allogeneic hematopoietic stem cell transplantation, but responses are inadequate. In addition to effector cells, infusions contain CD25+ regulatory T cells (Tregs) that may suppress graft-versus-tumor responses. We undertook a Phase I study of donor lymphocyte infusion depleted of CD25+ T cells in hematologic malignancies relapsed after transplantation. Twenty-one subjects received CD25/Treg-depleted infusion following removal of CD25+ cells using antibody-conjugated magnetic beads...
June 27, 2016: Haematologica
https://www.readbyqxmd.com/read/27232913/hypertensive-retinopathy-and-cerebral-small-vessel-disease-in-amerindians-living-in-rural-ecuador-the-atahualpa-project
#16
Oscar H Del Brutto, Robertino M Mera, Eduardo M Viteri, Joaquín Pólit, Ernesto A Ledesma, José A Cano, Karin J Plaza, Mauricio Zambrano, Aldo F Costa
BACKGROUND: Diagnosis of cerebral small vessel disease (SVD) is a challenge in remote areas where MRI is not available. Hypertensive retinopathy (HTRP) has shown to correlate with SVD in different ethnic groups, but there is no information from indigenous Latin American people. We assessed the usefulness of retinal photographs to detect cases with SVD among Amerindians living in rural Ecuador. METHODS: Atahualpa residents aged ≥60years with arterial hypertension or prehypertension were identified during a door-to-door survey...
September 1, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27221279/microrna-17-92-cluster-regulates-proliferation-and-differentiation-of-bovine-granulosa-cells-by-targeting-pten-and-bmpr2-genes
#17
Eryk Andreas, Michael Hoelker, Christiane Neuhoff, Ernst Tholen, Karl Schellander, Dawit Tesfaye, Dessie Salilew-Wondim
Granulosa cell proliferation and differentiation are key developmental steps involved in the formation of the dominant follicle eligible for ovulation. This process is, in turn, regulated by spatiotemporally emerging molecular events. MicroRNAs (miRNAs) are one of the molecular signatures believed to regulate granulosa cell function by fine-tuning gene expression. Previously, we showed that the miR-17-92 cluster was differentially expressed in granulosa cells from subordinate and dominant follicles at day 19 of the estrous cycle...
October 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27132212/efficacy-of-the-mage-a3-cancer-immunotherapeutic-as-adjuvant-therapy-in-patients-with-resected-mage-a3-positive-non-small-cell-lung-cancer-magrit-a-randomised-double-blind-placebo-controlled-phase-3-trial
#18
Johan F Vansteenkiste, Byoung Chul Cho, Tonu Vanakesa, Tommaso De Pas, Marcin Zielinski, Moon Soo Kim, Jacek Jassem, Masahiro Yoshimura, Jubrail Dahabreh, Haruhiku Nakayama, Libor Havel, Haruhiko Kondo, Tetsuya Mitsudomi, Konstantinos Zarogoulidis, Oleg A Gladkov, Katalin Udud, Hirohito Tada, Hans Hoffman, Anders Bugge, Paul Taylor, Emilio Esteban Gonzalez, Mei Lin Liao, Jianxing He, Jean-Louis Pujol, Jamila Louahed, Muriel Debois, Vincent Brichard, Channa Debruyne, Patrick Therasse, Nasser Altorki
BACKGROUND: Fewer than half of the patients with completely resected non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant chemotherapy in 2004, no substantial progress has been made in adjuvant treatment. We aimed to assess the efficacy of the MAGE-A3 cancer immunotherapeutic in surgically resected NSCLC. METHODS: In this randomised, double-blind, placebo-controlled trial, we recruited patients aged at least 18 years with completely resected stage IB, II, and IIIA MAGE-A3-positive NSCLC who did or did not receive adjuvant chemotherapy from 443 centres in 34 countries (Europe, the Americas, and Asia Pacific)...
June 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27036030/microrna-375-sec23a-as-biomarkers-of-the-in-vitro-efficacy-of-vandetanib
#19
Sandra Lassalle, Joséphine Zangari, Alexandra Popa, Marius Ilie, Véronique Hofman, Elodie Long, Martine Patey, Frédérique Tissier, Geneviève Belléannée, Hélène Trouette, Bogdan Catargi, Isabelle Peyrottes, Jean-Louis Sadoul, Olivier Bordone, Christelle Bonnetaud, Catherine Butori, Alexandre Bozec, Nicolas Guevara, José Santini, Imène Sarah Hénaoui, Géraldine Lemaire, Olivier Blanck, Philippe Vielh, Pascal Barbry, Bernard Mari, Patrick Brest, Paul Hofman
In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27027250/gene-expression-risk-signatures-maintain-prognostic-power-in-multiple-myeloma-despite-microarray-probe-set-translation
#20
N E U Hermansen, R Borup, M K Andersen, A J Vangsted, N T Clausen, D L Kristensen, F C Nielsen, P Gimsing
INTRODUCTION: Gene expression profiling (GEP) risk models in multiple myeloma are based on 3'-end microarrays. We hypothesized that GEP risk signatures could retain prognostic power despite being translated and applied to whole-transcript microarray data. METHODS: We studied CD138-positive bone marrow plasma cells in a prospective cohort of 59 samples from newly diagnosed patients eligible for high-dose therapy (HDT) and 67 samples from previous HDT patients with progressive disease...
June 2016: International Journal of Laboratory Hematology
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