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https://www.readbyqxmd.com/read/28936567/metformin-as-a-repurposed-therapy-in-advanced-non-small-cell-lung-cancer-nsclc-results-of-a-phase-ii-trial
#1
Anish B Parikh, Peter Kozuch, Nicholas Rohs, Daniel J Becker, Benjamin P Levy
Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity...
September 22, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28927054/methylation-of-stk11-promoter-is-a-risk-factor-for-tumor-stage-and-survival-in-clear-cell-renal-cell-carcinoma
#2
Fufu Zheng, Xiaoxu Yuan, Enjing Chen, Yunlin Ye, Xiaofei Li, Yuping Dai
Inactivation of tumor suppressor gene serine-threonine kinase 11 (STK11) in clear cell renal cell carcinoma (ccRCC) has been demonstrated; however, the mechanism of this inactivation remains to be investigated. To investigate whether epigenetic alteration plays a role in the inactivation of STK11 in RCC, the present study aimed to investigate the methylation status of the STK11 promoter and its association with tumor stage and survival in ccRCC patients. Paraffin-embedded specimens were obtained from 42 ccRCC patients...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28921546/neuroblastoma-cells-undergo-transcriptomic-alterations-upon-dissemination-into-the-bone-marrow-and-subsequent-tumor-progression
#3
Fikret Rifatbegovic, Christian Frech, M Reza Abbasi, Sabine Taschner-Mandl, Tamara Weiss, Wolfgang M Schmidt, Iris Schmidt, Ruth Ladenstein, Inge M Ambros, Peter F Ambros
Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of metastatic (M) stage patients present with disseminated tumor cells (DTCs) in the bone marrow (BM) at diagnosis and relapse. Although these cells represent a major obstacle in the treatment of neuroblastoma patients, insights into their expression profile remained elusive. The present RNA-Seq study of stage 4/M primary tumors, enriched BM-derived diagnostic and relapse DTCs, as well as the corresponding BM-derived mononuclear cells (MNCs) from 53 patients revealed 322 differentially expressed genes in DTCs as compared to the tumors (q < 0...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28914263/coexistent-genetic-alterations-involving-alk-ret-ros1-or-met-in-15-cases-of-lung-adenocarcinoma
#4
Zhenya Tang, Jianjun Zhang, Xinyan Lu, Wei Wang, Hui Chen, Melissa K Robinson, Joanne Cheng, Guilin Tang, L Jeffrey Medeiros
In lung cancer, targetable activating alterations in cancer genes, such as EGFR, ALK, RET, ROS1 and MET, are usually mutually exclusive. Rare lung cancer cases with coexistent alterations of EGFR and ALK or EGFR mutations with RET or ROS1 rearrangements have been reported. In this study, we report 15 patients (3 men and 12 women; 14 Caucasians and 1 African American) with ages ranging from 43 to 81 years (median 60 years) with lung adenocarcinoma in which coexistent alterations of two cancer-associated genes, including ALK, ROS1, or RET rearrangement or MET amplification were present...
September 15, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28911955/brief-report-somatic-mutations-and-ancestry-markers-in-hispanic-lung-cancer-patients
#5
Nicholas T Gimbrone, Bhaswati Sarcar, Edna R Gordian, Jason I Rivera, Christian Lopez, Sean J Yoder, Jamie K Teer, Eric A Welsh, Alberto A Chiaporri, Matthew B Schabath, Gary W Reuther, Julie Dutil, Miosotis Garcia, Ronald Ventosilla-Villanueva, Luis Vera-Valdivia, Alejandro Yabar-Berrocal, Rodrigo Motta-Guerrero, Pedro G Santiago-Cardona, Teresita Muñoz-Antonia, W Douglas Cress
INTRODUCTION: To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from these patients. METHODS: This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, STK11, and TP53) and ancestry analysis. Mutation frequencies in this H/L cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients and were correlated with ancestry, sex, smoking status, and tumor histology...
September 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28900777/an-exploration-of-genotype-phenotype-link-between-peutz-jeghers-syndrome-and-stk11-a-review
#6
REVIEW
Julian Daniell, John-Paul Plazzer, Anuradha Perera, Finlay Macrae
Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome. Clinical features include hamartomatous polyps, mucocutaneous pigmentation and an increased predisposition towards developing malignancy. Variants in STK11, a tumour suppressor gene, located on Chromosome 19, predispose to PJS. Peutz-Jeghers Syndrome is associated with increased rates of malignancy, particularly gastrointestinal. However, PJS is also associated with increased gynaecological, testicular and thyroid papillary malignancy...
September 12, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28891274/breast-cancer-risk-and-germline-genomic-profiling-of-women-with-neurofibromatosis-type-1-who-developed-breast-cancer
#7
Xia Wang, Jamie K Teer, Renee N Tousignant, Albert M Levin, David Boulware, Dhananjay A Chitale, Brandon M Shaw, Zhihua Chen, Yonghong Zhang, Jaishri O Blakeley, Maria T Acosta, Ludwine M Messiaen, Bruce R Korf, Michael A Tainsky
NF1 mutations predispose to neurofibromatosis type1 (NF1) and women with NF1 have a moderately elevated risk for breast cancer, especially under age 50. Germline genomic analysis may better define the risk so screening and prevention can be applied to the individuals who benefit the most. Survey conducted in several neurofibromatosis clinics in the United States has demonstrated a 17.2% lifetime risk of breast cancer in women affected with NF1. Cumulated risk to age 50 is estimated to be 9.27%. For genomic profiling, fourteen women with NF1 and a history of breast cancer were recruited and underwent whole exon sequencing (WES), targeted genomic DNA based and RNA based analysis of the NF1 gene...
September 10, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28884744/pulmonary-large-cell-neuroendocrine-carcinoma-with-adenocarcinoma-like-features-napsin-a-expression-and-genomic-alterations
#8
Natasha Rekhtman, Catherine M Pietanza, Joshua Sabari, Joseph Montecalvo, Hangjun Wang, Omar Habeeb, Kyuichi Kadota, Prasad Adusumilli, Charles M Rudin, Marc Ladanyi, William D Travis, Philippe Joubert
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive malignancy, which was recently found to comprise three major genomic subsets: small cell carcinoma-like, non-small cell carcinoma (predominantly adenocarcinoma)-like, and carcinoid-like. To further characterize adenocarcinoma-like subset, here we analyzed the expression of exocrine marker napsin A, along with TTF-1, in a large series of LCNECs (n=112), and performed detailed clinicopathologic and genomic analysis of napsin A-positive cases...
September 8, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28870692/distinct-patterns-of-acral-melanoma-based-on-site-and-relative-sun-exposure
#9
Alexandra M Haugh, Bin Zhang, Victor L Quan, Erin M Garfield, Jeffrey A Bubley, Emily Kudalkar, Anna Elisa Verzi, Kara Walton, Timothy VandenBoom, Emily A Merkel, Christina Y Lee, Timothy Tan, Maria Cristina Isales, Betty Y Kong, Alexander T Wenzel, Christopher G Bunick, Jaehyuk Choi, Jeffrey Sosman, Pedram Gerami
Acral melanoma is distinct from melanoma of other cutaneous sites, yet there is considerable variation within this category. To better define this variation, we assessed melanomas occurring on dorsal (n=21), volar (n=9), and subungual/interdigital (n=13) acral skin as well as acral nevi (n=24) for clinical, histologic, and molecular features. Melanomas on dorsal acral surfaces demonstrated clear differences compared to volar and subungual/interdigital melanomas. The latter two groups exhibited significantly less frequent BRAF mutations (p=...
September 1, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28869103/clinical-manifestations-and-stk11-germline-mutations-in-taiwanese-patients-with-peutz-jeghers-syndrome
#10
Jy-Ming Chiang, Tse-Ching Chen
BACKGROUNDS: Clinical manifestations and molecular basis of Taiwanese patients with Peutz-Jeghers syndrome (PJS) were investigated to add the knowledge of phenotype and genotype of the disease. METHODS: Based on the Pathology Data Bank and the Colorectal Cancer Register, we collected their clinical data. The entire coding sequence of the STK11 gene was amplified and analyzed by sequencing using the genomic DNA. RESULTS: Fifteen patients diagnosed with PJS from 11 unrelated families were collected until 2015...
August 28, 2017: Asian Journal of Surgery
https://www.readbyqxmd.com/read/28860410/next-generation-sequencing-for-patients-with-sarcoma-a-single-center-experience
#11
Gregory M Cote, Jie He, Edwin Choy
BACKGROUND: Sarcomas comprise over 50 subtypes of mesenchymal cancers. For the majority of sarcomas, the driver mutations remain unknown. In this article, we describe our experience with a targeted next-generation sequencing (NGS) platform in clinic patients. MATERIALS AND METHODS: We retrospectively analyzed results of NGS using 133 tumor samples from patients diagnosed with a variety of sarcomas that were analyzed with targeted NGS covering over 400 cancer-related genes (405 DNA, 265 RNA) on a commercially available platform...
August 31, 2017: Oncologist
https://www.readbyqxmd.com/read/28818315/screening-for-familial-cancer-risk-focus-on-breast-cancer
#12
REVIEW
Christine Rousset-Jablonski, Anne Gompel
A breast or an ovarian cancer occurring at a young age and/or in a family where other cases preexist suggests that those patients should be candidates for screening for mutations. Despite decades of medical research, less than 30% of cases with a suggestive personal and/or family history of hereditary breast cancer have an identified causative gene mutation. The vast majority of these cases are due to a mutation in one of the highly penetrant breast cancer genes (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11) and various guidelines direct the management of these patients...
August 7, 2017: Maturitas
https://www.readbyqxmd.com/read/28754670/gemcitabine-and-chk1-inhibitor-azd7762-synergistically-suppress-the-growth-of-lkb1-deficient-lung-adenocarcinoma
#13
Yan Liu, Yuyang Li, Xiaoen Wang, Feiyang Liu, Peng Gao, Max M Quinn, Fei Li, Ashley A Merlino, Cyril Benes, Qingsong Liu, Nathanael S Gray, Kwok-Kin Wong
Cells lacking the tumor suppressor gene LKB1/STK11 alter their metabolism to match the demands of accelerated growth, leaving them highly vulnerable to stress. However, targeted therapy for LKB1-deficient cancers has yet to be reported. In both Kras/p53/Lkb1 cell lines and a genetically engineered mouse model of Kras/p53/Lkb1-induced lung cancer, much higher rates of DNA damage occur, resulting in increased dependence on Chk1 checkpoint function. Here we demonstrate that short-term treatment with the Chk1 inhibitor AZD7762 reduces metabolism in pembrolizumab tumors, synergizing with the DNA-damaging drug gemcitabine to reduce tumor size in these models...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28706734/brca1-and-brca2-mutations-and-treatment-strategies-for-breast-cancer
#14
Inês Godet, Daniele M Gilkes
Breast cancer is a global burden with a woman's lifetime risk of developing breast cancer at 1 in 8. Although breast cancer is a disease that affects mostly women, the lifetime risk in men is about 1 in 1000. Most cases of breast cancer are associated with somatic mutations in breast cells that are acquired during a person's lifetime. In this scenario, the mutations are not inherited and they do not cluster in families. In hereditary breast cancer, the specific genetic factors involved will determine the inherited cancer risk...
February 2017: Integrative Cancer Science and Therapeutics
https://www.readbyqxmd.com/read/28696138/adipoq-adiponectin-induces-cytotoxic-autophagy-in-breast-cancer-cells-through-stk11-lkb1-mediated-activation-of-the-ampk-ulk1-axis
#15
Seung J Chung, Ganji Purnachandra Nagaraju, Arumugam Nagalingam, Nethaji Muniraj, Panjamurthy Kuppusamy, Alyssa Walker, Juhyung Woo, Balázs Győrffy, Ed Gabrielson, Neeraj K Saxena, Dipali Sharma
ADIPOQ/adiponectin, an adipocytokine secreted by adipocytes in the breast tumor microenvironment, negatively regulates cancer cell growth hence increased levels of ADIPOQ/adiponectin are associated with decreased breast cancer growth. However, its mechanisms of action remain largely elusive. We report that ADIPOQ/adiponectin induces a robust accumulation of autophagosomes, increases MAP1LC3B-II/LC3B-II and decreases SQSTM1/p62 in breast cancer cells. ADIPOQ/adiponectin-treated cells and xenografts exhibit increased expression of autophagy-related proteins...
August 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28674119/cancer-screening-recommendations-and-clinical-management-of-inherited-gastrointestinal-cancer-syndromes-in-childhood
#16
REVIEW
Maria Isabel Achatz, Christopher C Porter, Laurence Brugières, Harriet Druker, Thierry Frebourg, William D Foulkes, Christian P Kratz, Roland P Kuiper, Jordan R Hansford, Hector Salvador Hernandez, Katherine L Nathanson, Wendy K Kohlmann, Leslie Doros, Kenan Onel, Kami Wolfe Schneider, Sarah R Scollon, Uri Tabori, Gail E Tomlinson, D Gareth R Evans, Sharon E Plon
Hereditary gastrointestinal cancer predisposition syndromes have been well characterized, but management strategies and surveillance remain a major challenge, especially in childhood. In October 2016, the American Association for Cancer Research organized the AACR Childhood Cancer Predisposition Workshop in which international experts in care of children with a hereditary risk of cancer met to define surveillance strategies and management of children with cancer predisposition syndromes. In this article, we review the current literature in polyposis syndromes that can be diagnosed in childhood and may be associated with an increased incidence of gastrointestinal neoplasms and other cancer types...
July 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28652249/wee1-kinase-inhibitor-azd1775-has-preclinical-efficacy-in-lkb1-deficient-non-small-cell-lung-cancer
#17
Amanda L Richer, Jacqueline M Cala, Kelley O'Brien, Vashti M Carson, Landon J Inge, Timothy G Whitsett
G1-S checkpoint loss contributes to carcinogenesis and increases reliance upon the G2-M checkpoint for adaptation to stress and DNA repair, making G2-M checkpoint inhibition a target for novel therapeutic development. AZD1775, an inhibitor against the critical G2-M checkpoint protein WEE1, is currently in clinical trials across a number of tumor types. AZD1775 and DNA-damaging agents have displayed favorable activity in several preclinical tumor models, often in the molecular context of TP53 loss. Whether AZD1775 efficacy is modulated by other molecular contexts remains poorly understood...
September 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28619980/pan-cancer-analysis-pinpoints-targets-in-pi3k-pathway
#18
(no author information available yet)
A new study of all 32 cancer types in The Cancer Genome Atlas identifies genomic alterations that increase the activity of the PI3K/AKT/mTOR pathway. The study, which combines mutation data with measures of protein levels and phosphorylation status, suggests that mutations in IDH1, VHL, and STK11 promote activation of the pathway and may point to new drug targets.
June 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28619094/morphologic-and-molecular-study-of-lung-cancers-associated-with-idiopathic-pulmonary-fibrosis-and-other-pulmonary-fibroses
#19
Alice Guyard, Claire Danel, Nathalie Théou-Anton, Marie-Pierre Debray, Laure Gibault, Pierre Mordant, Yves Castier, Bruno Crestani, Gérard Zalcman, Hélène Blons, Aurélie Cazes
BACKGROUND: Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS). METHODS: Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group...
June 15, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28580595/mutation-screening-of-10-cancer-susceptibility-genes-in-unselected-breast-cancer-patients
#20
Yueliang Xie, Li Guoli, Ming Chen, Xinwu Guo, Lili Tang, Xipeng Luo, Shouman Wang, Wenjun Yi, Lizhong Dai, Jun Wang
Variants of cancer susceptibility genes other than BRCA1/2 have been proved to be associated with increased risks of breast cancer. This study was performed to investigate the spectrum and prevalence of mutations in 10 cancer susceptibility genes in paired tumor/normal tissues of 292 unselected Chinese breast cancer patients. We performed an analysis of germline and somatic variants in ATM, CDH1, CHEK2, ESR1, GATA3, MAP3K1, MSH2, PALB2, RB1 and STK11 genes by integrating microfluidic PCR-based target enrichment and next-generation sequencing technologies...
June 5, 2017: Clinical Genetics
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