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https://www.readbyqxmd.com/read/28226733/association-between-tumor-heterogeneity-and-progression-free-survival-in-non-small-cell-lung-cancer-patients-with-egfr-mutations-undergoing-tyrosine-kinase-inhibitors-therapy
#1
Jiangdian Song, Di Dong, Yanqi Huang, Yali Zang, Zaiyi Liu, Jie Tian, Jiangdian Song, Di Dong, Yanqi Huang, Yali Zang, Zaiyi Liu, Jie Tian, Zaiyi Liu, Yanqi Huang, Yali Zang, Jiangdian Song, Jie Tian, Di Dong
For non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, current staging methods do not accurately predict the risk of disease recurrence after tyrosine kinase inhibitors (TKI) therapy. Developing a noninvasive method to predict whether individual could benefit from TKI therapy has great clinical significance. In this research, a radiomics approach was proposed to determine whether the tumor heterogeneity of NSCLC, which was measured by the texture on computed tomography (CT), could make an independent prediction of progression-free survival (PFS)...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225782/chronic-treatment-of-non-small-cell-lung-cancer-cells-with-gefitinib-leads-to-an-epigenetic-loss-of-epithelial-properties-associated-with-reductions-in-microrna-155-and-200c
#2
Michiko Narita, Eri Shimura, Atsumi Nagasawa, Toshiki Aiuchi, Yukari Suda, Yusuke Hamada, Daigo Ikegami, Chizuru Iwasawa, Kazuhiko Arakawa, Katsuhide Igarashi, Naoko Kuzumaki, Yusuke Yoshioka, Takahiro Ochiya, Hideyuki Takeshima, Toshikazu Ushijima, Minoru Narita
BACKGROUND: The EGFR tyrosine kinase inhibitor gefitinib is used in therapy for non-small-cell lung cancer (NSCLC). However, its application is limited by resistance-accelerated disease progression, which is accompanied by the epithelial-to-mesenchymal transition (EMT). In the present study, we performed multiple expression analyses of microRNAs (miRNAs) and quantified the expression of several related EMT players in gefitinib-resistant NSCLC cells. METHODS AND RESULTS: To establish gefitinib-resistant NSCLC cells, gefitinib-sensitive HCC827 cells, which exhibit an in-frame deletion [E746-A750] in EGFR exon 19, were exposed to gefitinib for at least 1...
2017: PloS One
https://www.readbyqxmd.com/read/28225753/complement-drives-glucosylceramide-accumulation-and-tissue-inflammation-in-gaucher-disease
#3
Manoj K Pandey, Thomas A Burrow, Reena Rani, Lisa J Martin, David Witte, Kenneth D Setchell, Mary A Mckay, Albert F Magnusen, Wujuan Zhang, Benjamin Liou, Jörg Köhl, Gregory A Grabowski
Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28225456/efficacy-of-bevacizumab-and-erlotinib-combination-for-leptomeningeal-carcinomatosis-after-failure-of-erlotinib
#4
Ryo Ariyasu, Atsushi Horiike, Junji Koyama, Masafumi Saiki, Tomoaki Sonoda, Yosuke Kawashima, Natsuki Takano, Tomoyo Oguri, Shingo Nishikawa, Satoru Kitazono, Noriko Yanagitani, Fumiyoshi Ohyanagi, Makoto Nishio
In patients with non-small-cell lung cancer harboring an epithelial growth factor receptor (EGFR) active mutation, central nervous system progression after a response to EGFR tyrosine kinase inhibitors is frequent. Central nervous system metastasis, especially leptomeningeal carcinomatosis (LMC), is a serious complication and no standard treatment has been established for LMC. Here, we report two cases in which the addition of bevacizumab to erlotinib enhanced the efficacy against LMC; as a result, radiographic abnormalities decreased markedly and symptoms were well controlled...
February 20, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28225269/indazole-based-covalent-inhibitors-to-target-drug-resistant-epidermal-growth-factor-receptor
#5
Stefano Tomassi, Jonas Lategahn, Julian Engel, Marina Keul, Hannah Lea Tumbrink, Julia Ketzer, Thomas Mühlenberg, Matthias Baumann, Carsten Schultz-Fademrecht, Sebastian Bauer, Daniel Rauh
The specific targeting of oncogenic mutant epidermal growth factor receptor (EGFR) is a breakthrough in targeted cancer therapy and marks a drastic change in the treatment of non-small cell lung cancer (NSCLC). The recurrent emergence of resistance to these targeted drugs requires the development of novel chemical entities that efficiently inhibit drug-resistant EGFR. Herein, we report the optimization process for a hit compound that has emerged from a phenotypic screen resulting in indazole-based compounds...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28225258/nanoparticle-based-discrimination-of-single-nucleotide-polymorphism-in-long-dna-sequences
#6
Maria Sanroman-Iglesias, Charles Lawrie, Luis M Liz-Marzán, Marek Grzelczak
Circulating DNA (ctDNA) and specifically the detection cancer-associated mutations in liquid biopsies promises to revolutionize cancer detection. The main difficulty however is that the length of typical ctDNA fragments (~150 bases) can form secondary structures potentially obscuring the mutated fragment from detection. We show that an assay based on gold nanoparticles (65 nm) stabilized with DNA (Au@DNA) can discriminate single nucleotide polymorphism in clinically-relevant DNA sequences (70-140 bases). The preincubation step was crucial to this process, allowing sequential bridging of Au@DNA, so that single base mutation can be discriminated, down to 100 pM concentration...
February 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28224663/loss-of-mlh1-sensitizes-colon-cancer-cells-to-dna-pkcs-inhibitor-ku60648
#7
Inga Hinrichsen, Anne Ackermann, Tonja Düding, Annika Graband, Natalie Filmann, Guido Plotz, Stefan Zeuzem, Angela Brieger
Germline mutations of MLH1 are responsible for tumor generation in nearly 50% of patients with Lynch Syndrome, and around 15% of sporadic colorectal cancers show MLH1-deficiency due to promotor hypermethylation. Although these tumors are of lower aggressiveness the benefit for these patients from standard chemotherapy is still under discussion. Recently, it was shown that the sensitivity to the DNA-PKcs inhibitor KU60648 is linked to loss of the MMR protein MSH3. However, loss of MSH3 is rather secondary, as a consequence of MMR-deficiency, and frequently detectable in MLH1-deficient tumors...
February 22, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28224616/critical-cholangiocarcinogenesis-control-by-cryptochrome-clock-genes
#8
Ali Mteyrek, Elisabeth Filipski, Catherine Guettier, Malgorzata Oklejewicz, Gijsbertus T J van der Horst, Alper Okyar, Francis Lévi
A coordinated network of molecular circadian clocks in individual cells generates 24-hour rhythms in liver metabolism and proliferation. Circadian disruption through chronic jet lag or Per2 clock gene mutation was shown to accelerate hepatocarcinoma development in mice. Since divergent effects were reported for clock genes Per and Cry regarding xenobiotic toxicity, we questioned the role of Cry1 and Cry2 in liver carcinogenesis. Male WT and Cry1(-/-) Cry2(-/-) mice (C57Bl/6 background) were chronically exposed to diethylnitrosamine (DEN) at ZT11...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28224495/hidden-markov-models-in-bioinformatics-snv-inference-from-next-generation-sequence
#9
Jiawen Bian, Xiaobo Zhou
The rapid development of next generation sequencing (NGS) technology provides a novel avenue for genomic exploration and research. Hidden Markov models (HMMs) have wide applications in pattern recognition as well as Bioinformatics such as transcription factor binding sites and cis-regulatory modules detection. An application of HMM is introduced in this chapter with the in-deep developing of NGS. Single nucleotide variants (SNVs) inferred from NGS are expected to reveal gene mutations in cancer. However, NGS has lower sequence coverage and poor SNV detection capability in the regulatory regions of the genome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28224382/retrospective-review-of-genomic-testing-in-breast-cancer-does-it-improve-outcome
#10
Grady M Gastelum, Cyrus Iqbal, Susan G Hilsenbeck, Mothaffar F Rimawi, Polly Niravath
PURPOSE: Tumor genomic testing has become widely available in many clinical settings. However, we do not yet understand how to best harness the information yielded from this testing. We retrospectively investigated the clinical courses of 24 patients who underwent tumor genomic testing to determine whether targeted therapy is associated with improved progression free survival (PFS) compared to standard therapy. METHODS: The patient population comprised metastatic breast cancer patients who underwent tumor genomic testing (testing biopsy specimens of primary or metastatic lesions for 50 commonly mutated genes) at our institution between September 1, 2010 and June 1, 2015...
February 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28223670/-clinical-management-of-hboc-in-our-hospital
#11
Hidetaka Nomura, Nobuhiro Takeshima
The cumulative risks of developing epithelial ovarian cancer in women aged 70-75years with BRCA1 and BRCA2 germline mutations are approximately 39-40% and 11-18%, respectively. Here, we present the management of hereditary breast and ovarian cancer(HBOC)in our hospital. HBOC management commences with the selection of appropriate candidates for genetic testing, based on personal and familial characteristics that determine the individual's probability of being a mutation carrier. Pre-test counseling, which is an essential element of genetic counseling, should include discussion of why the test is being offered, how the test results may affect medical management, and the cancer risks associated with the gene mutation...
February 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28223669/-diagnosis-and-treatment-of-hboc-syndrome-by-a-breast-surgical-oncologist
#12
Kumiko Kida, Michiko Murai, Hideko Yamauchi
Of all breast cancer cases, 5-10% occur because of inherited germline mutation. For hereditary breast and ovarian cancer (HBOC)syndrome, congenital knowledge and strategies for breast cancer treatment and risk reduction are necessary. Regarding the surgical procedure for the cancer site, the ipsilateral breast tumor recurrence rate following breast-conserving surgery in breast cancers with BRCA1/2 mutation is not significantly higher than that in sporadic breast cancers. In addition, prognosis did not differ according to surgical methods...
February 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28223668/-genetic-counseling-of-hboc-and-japanese-organization-of-hboc
#13
Yoshimitsu Fukushima
Genetic testing, which reveals germline mutations, is extremely important for HBOC patients and their families. The evolution of this field has created a need for accurate cancer genetic counseling and risk assessment. Prevention and early therapy are possible in HBOC. If a patient has BRCA1 or BRCA2 mutations, the at-risk relatives should receive the information through genetic counseling. Genetic counseling provides not only information but also psychological and social support so that the patient or subject can autonomously decide...
February 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28223667/-molecular-diagnosis-and-treatment-of-hboc-syndrome
#14
Yoshio Miki
Hereditary breast and ovarian cancer(HBOC)is an inherited cancer caused by mutations of the BRCA1 or BRCA2 genes. BRCA genetic testing is used for HBOC diagnosis and continues to progress such as the annotation of VUS. In HBOC clinical practice, surveillance methods have been established through collaboration between genetic medicine and cancer medicine, and treatment, including options based on genetic diagnosis, has advanced significantly. Furthermore, the analysis of BRCA1 and BRCA2 function has progressed, and a novel therapeutic method based on synthetic lethality, such as a PARP inhibitor use, has been developed...
February 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28223542/the-in-vitro-and-vivo-effects-of-nuclear-and-cytosolic-parafibromin-expression-on-the-aggressive-phenotypes-of-colorectal-cancer-cells-a-search-of-potential-gene-therapy-target
#15
Hua-Chuan Zheng, Jia-Jie Liu, Jing Li, Ji-Cheng Wu, Lei Yang, Gui-Feng Zhao, Xin Zhao, Hua-Mao Jiang, Ke-Qiang Huang, Zhi-Jie Li
Down-regulated parafibromin is positively linked to the pathogenesis of parathyroid, lung, breast, ovarian, gastric and colorectal cancers. Here, we found that wild-type (WT) parafibromin overexpression suppressed proliferation, tumor growth, induced cell cycle arrest and apoptosis in colorectal cancer cells (p<0.05), but it was the converse for mutant-type (MT, mutation in nucleus localization sequence) parafibromin (p<0.05). Both WT and MT transfectants inhibited migration and invasion, and caused better differentiation (p<0...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223509/high-throughput-screening-of-rare-metabolically-active-tumor-cells-in-pleural-effusion-and-peripheral-blood-of-lung-cancer-patients
#16
Yin Tang, Zhuo Wang, Ziming Li, Jungwoo Kim, Yuliang Deng, Yan Li, James R Heath, Wei Wei, Shun Lu, Qihui Shi
Malignant pleural effusion (MPE), the presence of malignant cells in pleural fluid, is often the first sign of many cancers and occurs in patients with metastatic malignancies. Accurate detection of tumor cells in pleural fluid is crucial because the presence of MPE denotes an advanced stage of disease and directs a switch in clinical managements. Cytology, as a traditional diagnostic tool, has limited sensitivity especially when tumor cells are not abundant, and may be confounded by reactive mesothelial cells in the pleural fluid...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223427/calcium-dependent-enhancement-by-extracellular-acidity-of-the-cytotoxicity-of-mitochondrial-inhibitors-against-melanoma
#17
Fumihito Noguchi, Shigeki Inui, Clare Fedele, Mark Shackleton, Satoshi Itami
Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Since acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH and in vivo systemic alkalinization with NaHCO3 enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223411/pentraxin-3-is-a-pi3k-signaling-target-that-promotes-stem-cell-like-traits-in-basal-like-breast-cancers
#18
Clémence Thomas, Whitney Henry, Benjamin G Cuiffo, Anthony Y Collmann, Elisabetta Marangoni, Vanessa Benhamo, Manoj K Bhasin, Cheng Fan, Laetitia Fuhrmann, Albert S Baldwin, Charles Perou, Anne Vincent-Salomon, Alex Toker, Antoine E Karnoub
Basal-like breast cancers (BLBCs) exhibit hyperactivation of the phosphoinositide 3-kinase (PI3K) signaling pathway because of the frequent mutational activation of the PIK3CA catalytic subunit and the genetic loss of its negative regulators PTEN (phosphatase and tensin homolog) and INPP4B (inositol polyphosphate-4-phosphatase type II). However, PI3K inhibitors have had limited clinical efficacy in BLBC management because of compensatory amplification of PI3K downstream signaling loops. Therefore, identification of critical PI3K mediators is paramount to the development of effective BLBC therapeutics...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28223310/overexpression-of-vitamin-d-receptor-mrna-correlates-with-poor-prognosis-in-ptc
#19
June Young Choi, Jin Wook Yi, Joon-Hyop Lee, Ra-Yeong Song, Hyeong Won Yu, Hyungju Kwon, Young Jun Chai, Su-Jin Kim, Kyu Eun Lee
The purpose of this study was to assess the relationship between vitamin D receptor (VDR) mRNA expression and prognosis in papillary thyroid cancer. RNA sequencing and somatic mutation data from TCGA (the Cancer Genome Atlas) were analyzed. VDR mRNA expression was compared to clinicopathologic variables by linear regression. Tree-based classification was applied to find VDR cutoff and patients were split into low and high VDR group. Logistic regression, Kaplan-Meier analysis, differentially expressed gene (DEG) test, and pathway analysis were performed to assess differences between groups...
February 21, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28223274/long-term-responders-on-olaparib-maintenance-in-high-grade-serous-ovarian-cancer-clinical-and-molecular-characterization
#20
Stephanie Lheureux, Zhongwu Lai, Brian A Dougherty, Sarah Runswick, Darren Hodgson, Kirsten M Timms, Jerry S Lanchbury, Stanley B Kaye, Charlie Gourley, David D L Bowtell, Elise C Kohn, Clare L Scott, Ursula A Matulonis, Tony Panzarella, Katherine Karakasis, Julia V Burnier, Blake Gilks, Mark J O'Connor, Jane D Robertson, Jonathan Ledermann, J Carl Barrett, Tony W Ho, Amit M Oza
PURPOSE: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. EXPERIMENTAL DESIGN: A comparative molecular analysis of Study 19 (NCT00753545), a randomized Phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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