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https://www.readbyqxmd.com/read/27922044/from-tumour-heterogeneity-to-advances-in-precision-treatment-of-colorectal-cancer
#1
REVIEW
Cornelis J A Punt, Miriam Koopman, Louis Vermeulen
In recent years, the high heterogeneity of colorectal cancer (CRC) has become evident. Hence, biomarkers need to be developed that enable the stratification of patients with CRC into different prognostic subgroups and in relation to response to therapies, according to the distinctive tumour biology. Currently, only RAS-mutation status is used routinely as a negative predictive marker to avoid treatment with anti-EGFR agents in patients with metastatic CRC, and mismatch-repair status can guide the use of adjuvant chemotherapy in patients with early stage colon cancer...
December 6, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27922010/mek-inhibitors-block-growth-of-lung-tumours-with-mutations-in-ataxia-telangiectasia-mutated
#2
Michal Smida, Ferran Fece de la Cruz, Claudia Kerzendorfer, Iris Z Uras, Barbara Mair, Abdelghani Mazouzi, Tereza Suchankova, Tomasz Konopka, Amanda M Katz, Keren Paz, Katalin Nagy-Bojarszky, Markus K Muellner, Zsuzsanna Bago-Horvath, Eric B Haura, Joanna I Loizou, Sebastian M B Nijman
Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27921166/outcome-in-unresectable-glioblastoma-mgmt-promoter-methylation-makes-the-difference
#3
Niklas Thon, Jun Thorsteinsdottir, Sabina Eigenbrod, Ulrich Schüller, Jürgen Lutz, Simone Kreth, Claus Belka, Jörg-Christian Tonn, Maximilian Niyazi, Friedrich Wilhelm Kreth
In 2011, we reported a predominant prognostic/predictive role of MGMT promoter methylation status on progression-free survival (PFS) in unresectable glioblastoma patients undergoing upfront radiotherapy plus concomitant and maintenance temozolomide (RTX/TMZ → TMZ). We, here, present the final results of this prospective study focussing on the prognostic/predictive value of MGMT promoter methylation status for death risk stratification. Overall, 56 adult patients with unresectable, biopsy proven glioblastoma were prospectively assigned to upfront RTX/TMZ → TMZ treatment between March 2006 and August 2008...
December 5, 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27920951/risk-factors-for-in-hospital-mortality-after-coronary-artery-bypass-grafting-in-patients-80%C3%A2-years-old-or-older-a-retrospective-case-series-study
#4
Jacek Piątek, Anna Kędziora, Janusz Konstanty-Kalandyk, Grzegorz Kiełbasa, Marta Olszewska, Bryan HyoChan Song, Karol Wierzbicki, Irena Milaniak, Tomasz Darocha, Dorota Sobczyk, Bogusław Kapelak
BACKGROUND: Age remains a significant and unmodifiable risk factor for cardiovascular diseases, and an increasing number of patients older than 80 years of age undergo Coronary Artery Bypass Grafting (CABG). Old age is also an independent risk factor for postoperative complications. The aim of this study is to describe the population of patients 80 years of age or older who underwent CABG procedure and to assess the mortality rate and risk factors for in-hospital mortality. METHODS: A retrospective case-series study analyzing 388 consecutive patients aged 80 years of age or older who underwent isolated CABG procedure between 2010 and 2014 in the Department of Cardiovascular Surgery and Transplantology, John Paul II Hospital, Krakow...
2016: PeerJ
https://www.readbyqxmd.com/read/27920215/plasma-nt-probnp-mirrors-the-deleterious-cardiovascular-and-renal-continuum-in-hypertension
#5
Pierre-Yves Courand, Brahim Harbaoui, Clément Bècle, Carine Mouly-Bertin, Pierre Lantelme
BACKGROUND: The aims of this study were (a) to test the ability of N-terminal pro-brain natriuretic peptide (NT-proBNP) to detect subclinical target organ damage (TOD) denoted by left ventricular hypertrophy (LVH), aortic stiffness or renal damage and (b) to test its reproducibility in two different conditions in an ancillary study. METHODS: The study included 837 patients (50.9% men) with hypertension aged 50 ± 24 years with a median 24-h ambulatory blood pressure (BP) of 148/90 mmHg...
December 5, 2016: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/27920066/new-concepts-for-an-old-problem-the-diagnosis-of-endometrial-hyperplasia
#6
REVIEW
Peter A Sanderson, Hilary O D Critchley, Alistair R W Williams, Mark J Arends, Philippa T K Saunders
BACKGROUND: Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in the endometrial gland-to-stroma ratio when compared to normal proliferative endometrium. The clinical significance of EH lies in the associated risk of progression to endometrioid endometrial cancer (EC) and 'atypical' forms of EH are regarded as premalignant lesions. Traditional histopathological classification systems for EH exhibit wide and varying degrees of diagnostic reproducibility and, as a consequence, standardized patient management can be challenging...
December 4, 2016: Human Reproduction Update
https://www.readbyqxmd.com/read/27920003/clinical-significance-of-the-glasgow-prognostic-score-in-patients-with-gastrointestinal-stromal-tumors
#7
Takaaki Arigami, Yoshikazu Uenosono, Sumiya Ishigami, Shigehiro Yanagita, Keishi Okubo, Yasuto Uchikado, Yoshiaki Kita, Shinichiro Mori, Hiroshi Kurahara, Kosei Maemura, Shoji Natsugoe
AIM: To assess the clinical utility of the Glasgow prognostic score (GPS) as a blood predictor of postoperative recurrence in patients with gastric gastrointestinal stromal tumors (GISTs). PATIENTS AND METHODS: Twenty-nine patients with gastric GISTs undergoing gastrectomy were retrospectively reviewed. Patients were classified based on GPS criteria as follows: GPS of 2: elevated C-reactive protein (>1.0 mg/dl) and hypoalbuminemia (<3.5 g/dl), GPS of 1: one of these hematological abnormalities, and GPS of 0: neither elevated CRP nor hypoalbuminemia...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919245/one-day-workshop-based-training-improves-physical-activity-prescription-knowledge-in-latin-american-physicians-a-pre-test-post-test-study
#8
Maria C Arciniegas Calle, Felipe Lobelo, Mario A Jiménez, Diana C Páez, Sebastian Cortés, Andrés de Lima, John Duperly
BACKGROUND: The physical inactivity pandemic and related non-communicable diseases have made it imperative for medical doctors (MDs) to effectively provide lifestyle counseling as part of prevention and treatment plans for patients. A one-day certification workshop was designed to improve MDs PA prescription knowledge, as part of the Exercise is Medicine® (EIM®) global health initiative. The objective was to determine knowledge gain of MDs participating in a standardized, one-day PA prescription workshop performed throughout Latin America (LA)...
December 5, 2016: BMC Public Health
https://www.readbyqxmd.com/read/27919174/outcome-of-pediatric-advanced-hodgkin-lymphoma-treated-with-abvd-and-predictors-of-inferior-survival-a-multicenter-study-of-186-patients
#9
Sainath Bhethanabhotla, Sandeep Jain, Gauri Kapoor, Amita Mahajan, Anita Chopra, Sreenivas Vishnubhatla, Sameer Bakhshi
Clinical stage alone is used for risk stratification in treatment of pediatric advanced Hodgkin lymphoma (HL). To identify other risk factors, we collected data from three tertiary centers on 186 patients with advanced stage (IIB-IV) consecutively treated with Adriamycin, bleomycin, vinblastine, Dacarbazine (ABVD) chemotherapy ± radiotherapy. Freedom from treatment failure (FFTF) and overall survival (OS) were end points. With median follow-up period of 57.9 months (range: 1-151 months), five-year FFTF and OS was 84...
December 6, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27918534/multiethnic-genome-wide-meta-analysis-of-ectopic-fat-depots-identifies-loci-associated-with-adipocyte-development-and-differentiation
#10
Audrey Y Chu, Xuan Deng, Virginia A Fisher, Alexander Drong, Yang Zhang, Mary F Feitosa, Ching-Ti Liu, Olivia Weeks, Audrey C Choh, Qing Duan, Thomas D Dyer, John D Eicher, Xiuqing Guo, Nancy L Heard-Costa, Tim Kacprowski, Jack W Kent, Leslie A Lange, Xinggang Liu, Kurt Lohman, Lingyi Lu, Anubha Mahajan, Jeffrey R O'Connell, Ankita Parihar, Juan M Peralta, Albert V Smith, Yi Zhang, Georg Homuth, Ahmed H Kissebah, Joel Kullberg, René Laqua, Lenore J Launer, Matthias Nauck, Michael Olivier, Patricia A Peyser, James G Terry, Mary K Wojczynski, Jie Yao, Lawrence F Bielak, John Blangero, Ingrid B Borecki, Donald W Bowden, John Jeffrey Carr, Stefan A Czerwinski, Jingzhong Ding, Nele Friedrich, Vilmunder Gudnason, Tamara B Harris, Erik Ingelsson, Andrew D Johnson, Sharon L R Kardia, Carl D Langefeld, Lars Lind, Yongmei Liu, Braxton D Mitchell, Andrew P Morris, Thomas H Mosley, Jerome I Rotter, Alan R Shuldiner, Bradford Towne, Henry Völzke, Henri Wallaschofski, James G Wilson, Matthew Allison, Cecilia M Lindgren, Wolfram Goessling, L Adrienne Cupples, Matthew L Steinhauser, Caroline S Fox
Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits)...
December 5, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27917904/glycoprotein-130-is-associated-with-adverse-postoperative-clinical-outcomes-of-patients-with-late-stage-non-metastatic-gastric-cancer
#11
Yifan Cao, Heng Zhang, Hao Liu, Chao Lin, Ruochen Li, Songyang Wu, Hongyong He, He Li, Jiejie Xu
The interaction of glycoprotein 130 (gp130) with the cytokines of Interleukin-6 (IL-6) family has proved to play a crucial part in several cancers. Our current study is designed to discover the clinical prognostic significance of gp130 in non-metastatic gastric cancer. We examined intratumoral gp130 expression in retrospectively enrolled 370 gastric cancer patients who underwent radical gastrectomy with standard D2 lymphadenectomy at Zhongshan Hospital of Fudan University during 2007 and 2008 by immunohistochemical staining...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917723/rising-incidence-of-head-and-neck-mucosal-melanoma-in-australia
#12
D Youssef, S Vasani, J Marquess, A Cervin
OBJECTIVE: To establish Australian population-based incidence trends for mucosal melanoma of the head and neck. METHODS: Cases between 1985 and 2009 were identified in the Australian Cancer Database. Age-standardised incidence trends were established, including subgroup stratification by sex and site. RESULTS: A continuously progressive increase in incidence was evident in the 353 cases identified over the 25-year study period. This was particularly evident in sinonasal mucosal melanoma in men, despite the overall incidence remaining higher in women...
December 5, 2016: Journal of Laryngology and Otology
https://www.readbyqxmd.com/read/27917519/leveraging-population-information-in-family-based-rare-variant-association-analyses-of-quantitative-traits
#13
Yu Jiang, Yunqi Ji, Alexander B Sibley, Yi-Ju Li, Andrew S Allen
Confounding due to population substructure is always a concern in genetic association studies. Although methods have been proposed to adjust for population stratification in the context of common variation, it is unclear how well these approaches will work when interrogating rare variation. Family-based association tests can be constructed that are robust to population stratification. For example, when considering a quantitative trait, a linear model can be used that decomposes genetic effects into between- and within-family components and a test of the within-family component is robust to population stratification...
December 5, 2016: Genetic Epidemiology
https://www.readbyqxmd.com/read/27917296/stat1-associated-intratumoural-th1-immunity-predicts-chemotherapy-resistance-in-high-grade-serous-ovarian-cancer
#14
Katrina K Au, Cécile Le Page, Runhan Ren, Liliane Meunier, Isabelle Clément, Kathrin Tyrishkin, Nichole Peterson, Jennifer Kendall-Dupont, Timothy Childs, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Jeremy A Squire, Anne-Marie Mes-Masson, Madhuri Koti
High-grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predictive biomarker and its correlation with intratumoural CD8(+) T cells in a second independent biomarker validation study. Tumour STAT1 expression and intratumoural CD8(+) T cell infiltration were assessed by immunohistochemistry as a multicentre validation study conducted on 734 chemotherapy-naïve HGSCs...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27916725/prognostic-value-of-a-category-based-on-electron-microscopic-features-of-clival-chordomas
#15
Jiwei Bai, Yixuan Zhai, Shuai Wang, Hua Gao, Jiang Du, Junmei Wang, Mingxuan Li, Chuzhong Li, Songbai Gui, Cuiping Zhang, Yilin Sun, Yazhuo Zhang
OBJECTIVE: Skull base chordomas are clinically malignant because of the difficulty of total removal and the high recurrence rate. Because the disease-free survival after surgery is currently unpredictable, there is a need for new parameters obtained from histological analyses of the resection specimen that allows a risk stratification of patients with chordoma. METHODS: Electron microscopic diagnoses were introduced into the clinical practice for the diagnosis of chordoma in our department in recent years...
December 1, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27916360/combined-resection-and-rfa-in-colorectal-liver-metastases-stratification-of-long-term-outcomes
#16
Kazunari Sasaki, Georgios A Margonis, Nikolaos Andreatos, Yuhree Kim, Ana Wilson, Faiz Gani, Neda Amini, Timothy M Pawlik
BACKGROUND: Combined hepatic resection and radiofrequency ablation (resection-RFA) is a widely accepted multidisciplinary treatment for unresectable colorectal cancer liver metastases. Worse prognosis after resection-RFA is correlated to tumor morphology, although unfavorable morphology is inherent to this patient cohort. This study aimed to select patients who may or may not benefit from resection-RFA with the aid of tumor biology. METHOD: Data from 485 patients who underwent curative hepatectomy with or without concurrent RFA were retrospectively collected and analyzed...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27916321/exercise-induced-quantitative-microvolt-t-wave-alternans-in-hypertrophic-cardiomyopathy
#17
Murillo de Oliveira Antunes, Nelson Samesima, Horacio Gomes Pereira Filho, Afonso Yoshikiro Matsumoto, Richard L Verrier, Carlos Alberto Pastore, Edmundo Arteaga-Fernández, Charles Mady
BACKGROUND/PURPOSE: Patients with hypertrophic cardiomyopathy (HCM) have elevated risk for sudden cardiac death (SCD). Our study aimed to quantitatively characterize microvolt T-wave alternans (TWA), a potential arrhythmia risk stratification tool, in this HCM patient population. METHODS: TWA was analyzed with the quantitative modified moving average (MMA) in 132 HCM patients undergoing treadmill exercise testing, grouped according to Maron score risk factors as high-risk (H-Risk, n=67,), or low-risk (L-Risk, n=65, without these risk factors)...
October 28, 2016: Journal of Electrocardiology
https://www.readbyqxmd.com/read/27916292/cancer-prognosis-defined-by-the-combined-analysis-of-8q-pten-and-erg
#18
Maria P Silva, João D Barros-Silva, Elin Ersvær, Wanja Kildal, Tarjei Sveinsgjerd Hveem, Manohar Pradhan, Joana Vieira, Manuel R Teixeira, Håvard E Danielsen
Overtreatment is a major concern in men diagnosed with prostate cancer. The aim of this study was to evaluate the combined prognostic role of three frequent molecular alterations in prostate cancer, namely relative 8q gain, ERG overexpression, and loss of PTEN expression, in a series of 136 patients with prostate cancer treated with prostatectomy and with a long follow-up. Fluorescent in situ hybridization was used to detect the relative copy number of 8q and immunohistochemistry was used for quantitative assessment of ERG and PTEN expression...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27916210/heart-type-fatty-acid-binding-protein-in-the-assessment-of-acute-pulmonary-embolism
#19
Hai-Yan Qian, Ji Huang, Yue-Jin Yang, Yan-Min Yang, Zhi-Zhong Li, Jing-Mei Zhang
OBJECTIVE: To explore the predictive value of heart-type fatty acid binding protein (H-FABP) in the stratification and prognosis of patients with acute pulmonary embolism (APE). METHODS: According to risk stratification, 69 patients with APE admitted into the emergency department within 24 hours after onset were divided into the following 3 groups: high-risk group, moderate-risk group and low-risk group. H-FABP- and cardiac troponin I (cTNI)-positive rates of all groups were analyzed and compared, and the correlation between major adverse events (death, endotracheal intubation and cardiopulmonary resuscitation) and the cardiac markers (heart rate, arterial partial pressure of oxygen, right ventricular dimension, pulmonary arterial pressure, etc...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27915475/how-precisely-can-prostate-cancer-be-managed
#20
REVIEW
Liyan Zhuang, Matthew T Johnson
Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2- ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy...
November 2016: International Neurourology Journal
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