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https://www.readbyqxmd.com/read/28414610/clinical-calculator-for-early-mortality-in-metastatic-colorectal-cancer-an-analysis-of-patients-from-28-clinical-trials-in-the-aide-et-recherche-en-canc%C3%A3-rologie-digestive-database
#1
Lindsay A Renfro, Richard M Goldberg, Axel Grothey, Alberto Sobrero, Richard Adams, Matthew T Seymour, Volker Heinemann, Hans-Joachim Schmoll, Jean-Yves Douillard, Herbert Hurwitz, Charles S Fuchs, Eduardo Diaz-Rubio, Rainer Porschen, Christophe Tournigand, Benoist Chibaudel, Paulo M Hoff, Fairooz F Kabbinavar, Alfredo Falcone, Niall C Tebbutt, Cornelis J A Punt, J Randolph Hecht, John Souglakos, Carsten Bokemeyer, Eric Van Cutsem, Leonard Saltz, Aimery de Gramont, Daniel J Sargent
Purpose Factors contributing to early mortality after initiation of treatment of metastatic colorectal cancer are poorly understood. Materials and Methods Data from 22,654 patients enrolled in 28 randomized phase III trials contained in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were pooled. Multivariable logistic regression models for 30-, 60-, and 90-day mortality were constructed, including clinically and statistically significant patient and disease factors and interaction terms. A calculator (nomogram) for 90-day mortality was developed and validated internally using bootstrapping methods and externally using a 10% random holdout sample from each trial...
April 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28412591/baseline-%C3%AE-catenin-programmed-death-ligand-1-expression-and-tumour-infiltrating-lymphocytes-predict-response-and-poor-prognosis-in-braf-inhibitor-treated-melanoma-patients
#2
Daniela Massi, Emanuela Romano, Eliana Rulli, Barbara Merelli, Romina Nassini, Francesco De Logu, Ivan Bieche, Gianna Baroni, Laura Cattaneo, Gongda Xue, Mario Mandalà
BACKGROUND: The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. PATIENTS AND METHODS: Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome...
April 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28412197/an-uplc-ms-ms-method-for-the-quantification-of-braf-inhibitors-vemurafenib-dabrafenib-and-mek-inhibitors-cobimetinib-trametinib-binimetinib-in-human-plasma-application-to-treated-melanoma-patients
#3
Marine Rousset, Karine Titier, Stephane Bouchet, Caroline Dutriaux, Anne Pham-Ledard, Sorilla Prey, Mireille Canal-Raffin, Mathieu Molimard
Targeted therapies for cancers are fast-growing therapies. For instance kinase inhibitors such as BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are increasingly used to treat malignant melanoma. The metabolic profile of these drugs can result in great interindividual variability, justifying therapeutic drug monitoring (TDM). We describe a rapid and specific method for quantification of 2 BRAFi (vemurafenib, dabrafenib) and 3 MEKi (cobimetinib, trametinib and binimetinib). Chromatography was performed on a Waters Acquity-UPLC system with CORTECS C18+ column, under a gradient of 10% acetic acid in water/acetonitrile...
April 12, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28410231/genetic-alterations-in-seborrheic-keratoses
#4
Barbara Heidenreich, Evygenia Denisova, Sivaramakrishna Rachakonda, Onofre Sanmartin, Timo Dereani, Ismail Hosen, Eduardo Nagore, Rajiv Kumar
Seborrheic keratoses are common benign epidermal lesions that are associated with increased age and sun-exposure. Those lesions despite harboring multiple somatic alterations in contrast to malignant tumors appear to be genetically stable. In order to investigate and characterize the presence of recurrent mutations, we performed exome sequencing on DNA from one seborrheic keratosis lesion and corresponding blood cells from the same patients with follow up investigation of alterations identified by exome sequencing in 24 additional lesions from as many patients...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408301/impact-of-braf-kinase-inhibitors-on-the-mirnomes-and-transcriptomes-of-melanoma-cells
#5
Ines Kozar, Giulia Cesi, Christiane Margue, Demetra Philippidou, Stephanie Kreis
BACKGROUND: Melanoma is an aggressive skin cancer with increasing incidence worldwide. The development of BRAF kinase inhibitors as targeted treatments for patients with BRAF-mutant tumours contributed profoundly to an improved overall survival of patients with metastatic melanoma. Despite these promising results, the emergence of rapid resistance to targeted therapy remains a serious clinical issue. METHODS: To investigate the impact of BRAF inhibitors on miRNomes and transcriptomes, we used in vitro melanoma models consisting of BRAF inhibitor-sensitive and -resistant cell lines generated in our laboratory...
April 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28397788/over-expression-of-microrna-1-causes-arrhythmia-by-disturbing-intracellular-trafficking-system
#6
Xiaomin Su, Haihai Liang, He Wang, Guizhi Chen, Hua Jiang, Qiuxia Wu, Tianyi Liu, Qiushuang Liu, Tong Yu, Yunyan Gu, Baofeng Yang, Hongli Shan
Dysregulation of intracellular trafficking system plays a fundamental role in the progression of cardiovascular disease. Up-regulation of miR-1 contributes to arrhythmia, we sought to elucidate whether intracellular trafficking contributes to miR-1-driven arrhythmia. By performing microarray analyses of the transcriptome in the cardiomyocytes-specific over-expression of microRNA-1 (miR-1 Tg) mice and the WT mice, we found that these differentially expressed genes in miR-1 Tg mice were significantly enrichment with the trafficking-related biological processes, such as regulation of calcium ion transport...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28395087/retrospective-analysis-of-molecular-and-immunohistochemical-characterization-of-381-primary-brain-tumors
#7
Leomar Y Ballester, Gregory N Fuller, Suzanne Z Powell, Erik P Sulman, Keyur P Patel, Rajyalakshmi Luthra, Mark J Routbort
The classification of brain tumors has traditionally depended on microscopic examination of hematoxylin and eosin-stained tissue sections. The increased understanding of clinically relevant genetic alterations has led to the incorporation of molecular signatures as part of the diagnosis of brain malignancies. Advances in sequencing technologies have facilitated the use of next-generation sequencing (NGS) assays in clinical laboratories. We performed a retrospective analysis of sequencing results for 381 brain tumors tested by NGS at our institution using a validated, commercially available panel...
March 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28387310/targeting-bmk1-impairs-the-drug-resistance-to-combined-inhibition-of-braf-and-mek1-2-in-melanoma
#8
Chengli Song, Lina Wang, Qiang Xu, Kai Wang, Dan Xie, Zhe Yu, Kui Jiang, Lujian Liao, John R Yates, Jiing-Dwan Lee, Qingkai Yang
Combined inhibition of BRAF and MEK1/2 (CIBM) improves therapeutic efficacy of BRAF-mutant melanoma. However, drug resistance to CIBM is inevitable and the drug resistance mechanisms still remain to be elucidated. Here, we show that BMK1 pathway contributes to the drug resistance to CIBM. Considering that ERK1/2 pathway regulates cellular processes by phosphorylating, we first performed a SILAC phosphoproteomic profiling of CIBM. Phosphorylation of 239 proteins was identified to be downregulated, while phosphorylation of 47 proteins was upregulated...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28383426/a-meta-analysis-of-the-association-between-braf-mutation-and-nonsmall-cell-lung-cancer
#9
Guanghui Cui, Donglei Liu, Weihao Li, Xiao Fu, Youguang Liang, Yuhang Li, Wensong Shi, Xiaofang Chen, Song Zhao
BACKGROUND: Previous studies investigating the association between BRAF mutations and nonsmall cell lung cancer (NSCLC) remain controversial. To address the issue, we performed an updated meta-analysis of related articles. METHODS: We conducted a comprehensive literature search in the electronic databases including ISI Science Citation Index, EMBASE, PubMed, and CNKI (up to January 2016). The odds ratios (ORs) and 95% confidence interval (CI) were assessed based on random-effects or fixed-effects models according to the heterogeneity of eligible studies...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28378527/the-prognostic-value-of-simultaneous-tumor-and-serum-ras-raf-mutations-in-localized-colon-cancer
#10
Caroline Emilie B Thomsen, Ane Lindegaard Appelt, Rikke Fredslund Andersen, Jan Lindebjerg, Lars Henrik Jensen, Anders Jakobsen
The impact of RAS/RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor-specific DNA, this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations. The study retrospectively included 294 patients with curatively resected stage I-III adenocarcinoma of the colon. Mutations in tumor and serum were determined at time of surgery. Analyses were performed with droplet digital PCR technology. Hazard ratio (HR) for the association between mutational status and survival was estimated in multivariate analysis taking known prognostic factors into account...
April 4, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28376906/braf-v600e-expression-in-histiocytic-sarcoma-associated-with-splenic-marginal-zone-lymphoma-a-case-report
#11
John L Vaughn, C Eric Freitag, Jessica A Hemminger, Jeffrey A Jones
BACKGROUND: Histiocytic sarcoma is a rare histiocytic neoplasm of unknown etiology that constitutes less than 1% of hematologic malignancies. A few cases of histiocytic sarcoma harboring the BRAF (V600E) mutation have been reported, but this finding has not been confirmed in all studies. CASE PRESENTATION: We report the case of a 63-year-old white woman with a history of splenic marginal zone lymphoma who presented with 2 weeks of right-sided neck swelling. Positron emission tomography revealed an intensely hypermetabolic and destructive soft tissue mass in her right skull base...
April 5, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28376192/deciphering-the-role-of-oncogenic-mitfe318k-in-senescence-delay-and-melanoma-progression
#12
Caroline Bonet, Flavie Luciani, Jean-François Ottavi, Justine Leclerc, Fanélie-Marie Jouenne, Marina Boncompagni, Karine Bille, Véronique Hofman, Guillaume Bossis, Gian Marco de Donatis, Thomas Strub, Yann Cheli, Mickaël Ohanna, Frédéric Luciano, Sandrine Marchetti, Stéphane Rocchi, Marie-Christine Birling, Marie-Françoise Avril, Nicolas Poulalhon, Thomas Luc, Corine Bertolotto
Background: MITF encodes an oncogenic lineage-specific transcription factor in which a germline mutation ( MITFE318K ) was identified in human patients predisposed to both nevus formation and, among other tumor types, melanoma. The molecular mechanisms underlying the oncogenic activity of MITF E318K remained uncharacterized. Methods: Here, we compared the SUMOylation status of endogenous MITF by proximity ligation assay in melanocytes isolated from wild-type (n = 3) or E318K (n = 4) MITF donors...
August 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28373299/integrated-genomic-analyses-reveal-frequent-tert-aberrations-in-acral-melanoma
#13
Winnie S Liang, William Hendricks, Jeffrey Kiefer, Jessica Schmidt, Shobana Sekar, John Carpten, David W Craig, Jonathan Adkins, Lori Cuyugan, Zarko Manojlovic, Rebecca F Halperin, Adrienne Helland, Sara Nasser, Christophe Legendre, Laurence H Hurley, Karthigayini Sivaprakasam, Douglas B Johnson, Holly Crandall, Klaus J Busam, Victoria Zismann, Valerie Deluca, Jeeyun Lee, Aleksandar Sekulic, Charlotte E Ariyan, Jeffrey Sosman, Jeffrey Trent
Genomic analyses of cutaneous melanoma (CM) have yielded biological and therapeutic insights, but understanding of non-ultraviolet (UV)-derived CMs remains limited. Deeper analysis of acral lentiginous melanoma (ALM), a rare sun-shielded melanoma subtype associated with worse survival than CM, is needed to delineate non-UV oncogenic mechanisms. We thus performed comprehensive genomic and transcriptomic analysis of 34 ALM patients. Unlike CM, somatic alterations were dominated by structural variation and absence of UV-derived mutation signatures...
April 2017: Genome Research
https://www.readbyqxmd.com/read/28362711/ectopic-thyroid-tissue-immunohistochemistry-and-molecular-analysis
#14
Diana M Lin, Sara Javidiparsijani, Alexandra Vardouniotis, Lela Buckingham, Swathi B Reddy, Paolo Gattuso
Ectopic thyroid tissue is rare and controversial. Some experts consider it to always be metastatic thyroid carcinoma, whereas others consider it benign as long as it is restricted to few follicles without cytoarchitectural features of papillary thyroid carcinoma. Immunohistochemistry (IHC) and molecular studies have not yet been performed to further characterize this entity. We retrospectively searched our pathology files for all ectopic thyroid inclusions and reviewed clinicopathologic characteristics and concurrent thyroid pathologic findings...
March 30, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28359784/ipilimumab-10-mg-kg-versus-ipilimumab-3-mg-kg-in-patients-with-unresectable-or-metastatic-melanoma-a-randomised-double-blind-multicentre-phase-3-trial
#15
Paolo A Ascierto, Michele Del Vecchio, Caroline Robert, Andrzej Mackiewicz, Vanna Chiarion-Sileni, Ana Arance, Céleste Lebbé, Lars Bastholt, Omid Hamid, Piotr Rutkowski, Catriona McNeil, Claus Garbe, Carmen Loquai, Brigitte Dreno, Luc Thomas, Jean-Jacques Grob, Gabriella Liszkay, Marta Nyakas, Ralf Gutzmer, Joanna Pikiel, Florent Grange, Christoph Hoeller, Virginia Ferraresi, Michael Smylie, Dirk Schadendorf, Laurent Mortier, Inge Marie Svane, Delphine Hennicken, Anila Qureshi, Michele Maio
BACKGROUND: A phase 2 trial suggested increased overall survival and increased incidence of treatment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma. We report a phase 3 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg. METHODS: This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors, were randomly assigned (1:1) with an interactive voice response system by the permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intravenous infusion for 90 min every 3 weeks for four doses...
March 27, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28358874/prognostic-implication-of-histological-features-associated-with-ehd2-expression-in-papillary-thyroid-carcinoma
#16
Yourha Kim, Min-Hee Kim, Sora Jeon, Jeeyoon Kim, Chankyung Kim, Ja Seong Bae, Chan Kwon Jung
Papillary thyroid carcinoma (PTC) is a heterogeneous tumor with various histological and molecular subtypes. EHD2 is involved in endocytosis and endosomal recycling. This study aimed to investigate the prognostic significance of EHD2 expression in PTC and develop a new model for predicting persistent/recurrent disease after thyroidectomy. Pathologic slides of 512 consecutive patients with PTC ≥ 1 cm were retrospectively reviewed. BRAF mutation analysis and immunohistochemistry for EHD2 were performed. Clinical significance of EHD2 mRNA expression was analyzed in 388 PTC patients using The Cancer Genome Atlas dataset...
2017: PloS One
https://www.readbyqxmd.com/read/28356599/towards-personalized-medicine-in-melanoma-implementation-of-a-clinical-next-generation-sequencing-panel
#17
Blanca de Unamuno Bustos, Rosa Murria Estal, Gema Pérez Simó, Inmaculada de Juan Jimenez, Begoña Escutia Muñoz, Mercedes Rodríguez Serna, Victor Alegre de Miquel, Margarita Llavador Ros, Rosa Ballester Sánchez, Eduardo Nagore Enguídanos, Sarai Palanca Suela, Rafael Botella Estrada
Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. The development of next-generation sequencing (NGS) technologies has enabled to sequence multiple cancer-driving genes in a single assay, with improved sensitivity in mutation detection. The main objective of this study was the design and implementation of a melanoma-specific sequencing panel, and the identification of the spectrum of somatic mutations in a series of primary melanoma samples...
March 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28351340/molecular-pathology-of-anaplastic-thyroid-carcinomas-a-retrospective-study-of-144-cases
#18
Benjamin Bonhomme, Yann Godbert, Gaelle Perot, Abir Alghuzlan, Stéphane Bardet, Geneviève Belleannée, Lise Criniere, Christine Do Cao, Geneviève Fouilhoux, Serge Guyetant, Antony Kelly, Sophie Leboulleux, Camille Buffet, Emmanuelle Leteurtre, Jean-Jacques Michels, Frédérique Tissier, Marie-Elisabeth Toubert, Michel Wassef, Clémence Pinard, Isabelle Hostein, Isabelle Soubeyran
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare tumor with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aim of this retrospective study was to determine the frequency of anaplastic lymphoma kinase (ALK) translocations and identify the mutational profile of ATC including TERT promoter mutation. METHODS AND MATERIALS: One hundred and forty-four ATC cases were collected from 10 centers that are a part of the national French network for management of refractory thyroid tumors (TUTHYREF)...
March 28, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28347233/glycolysis-related-protein-expression-in-thyroid-cancer
#19
Ji Hae Nahm, Hye Min Kim, Ja Seung Koo
We aimed to demonstrate the differences in the expression of glucose metabolism-related proteins according to the thyroid cancer subtypes and investigate the implications of these differences. A total of 566 thyroid cancer patients, including 342 cases of papillary thyroid carcinoma, 112 cases of follicular carcinoma, 70 cases of medullary carcinoma, 23 cases of poorly differentiated carcinoma, 19 cases of anaplastic carcinoma, and 152 cases of follicular adenoma, were enrolled in the study. Immunohistochemical staining for glucose transporter 1, hexokinase II, carbonic anhydrase IX, and monocarbonylate transporter 4 was performed, and the relationship between immunoreactivity and clinicopathologic parameters was analyzed...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28339824/a-phase-i-trial-of-the-mek-inhibitor-selumetinib-azd6244-in-pediatric-patients-with-recurrent-or-refractory-low-grade-glioma-a-pediatric-brain-tumor-consortium-pbtc-study
#20
Anuradha Banerjee, Regina I Jakacki, Arzu Onar-Thomas, Shengjie Wu, Theodore Nicolaides, Tina Young Poussaint, Jason Fangusaro, Joanna Phillips, Arie Perry, David Turner, Michael Prados, Roger J Packer, Ibrahim Qaddoumi, Sridharan Gururangan, Ian F Pollack, Stewart Goldman, Lawrence A Doyle, Clinton F Stewart, James M Boyett, Larry E Kun, Maryam Fouladi
Background.: Activation of the mitogen-activated protein kinase pathway is important for growth of pediatric low-grade gliomas (LGGs). The aim of this study was to determine the recommended phase II dose (RP2D) and the dose-limiting toxicities (DLTs) of the MEK inhibitor selumetinib in children with progressive LGG. Methods.: Selumetinib was administered orally starting at 33 mg/m2/dose b.i.d., using the modified continual reassessment method. Pharmacokinetic analysis was performed during the first course...
February 28, 2017: Neuro-oncology
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