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https://www.readbyqxmd.com/read/28750319/theoretically-obtained-insight-into-the-mechanism-and-dioxetanone-species-responsible-for-the-singlet-chemiexcitation-of-coelenterazine
#1
Chun-Gang Min, Paulo J O Ferreira, Luís Pinto da Silva
Coelenterazine is a widespread bioluminescent substrate for a diverse set of marine species. Moreover, its imidazopyrazinone core is present in eight phyla of bioluminescent organisms. Given their very attractive intrinsic properties, these bioluminescent systems have been used in bioimaging, photodynamic therapy of cancer, as gene reporter and in sensing applications, among others. While it is known that bioluminescence results from the thermolysis of high-energy dioxetanones, the mechanism and dioxetanone species responsible for the singlet chemiexcitation of Coelenterazine are not fully understood...
July 20, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28750271/safety-tolerability%C3%A2-and-antitumour-activity-of-ly2780301-p70s6k-akt-inhibitor-in-combination-with-gemcitabine-in-molecularly-selected-patients-with-advanced-or-metastatic-cancer-a-phase-ib-dose-escalation-study
#2
Eric Angevin, Philippe A Cassier, Antoine Italiano, Anthony Gonçalves, Anas Gazzah, Catherine Terret, Maud Toulmonde, Gwenaëlle Gravis, Andrea Varga, Cédric Parlavecchio, Angelo Paci, Vianney Poinsignon, Jean-Charles Soria, Damien Drubay, Antoine Hollebecque
BACKGROUND: LY2780301, a dual inhibitor of protein kinase B (AKT) and the downstream effector p70 ribosomal protein S6 kinase (p70S6K), may inhibit progression in tumours relying on phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signalling pathway activation. This phase IB trial investigated the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), safety, pharmacokinetics (PK) and antitumour activity of LY2780301 plus gemcitabine in patients with advanced/metastatic solid tumours...
July 24, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28750133/role-of-cytotoxic-tumor-infiltrating-lymphocytes-in-predicting-outcomes-in-metastatic-her2-positive-breast-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#3
Shuzhen Liu, Bingshu Chen, Samantha Burugu, Samuel Leung, Dongxia Gao, Shakeel Virk, Zuzana Kos, Wendy R Parulekar, Lois Shepherd, Karen A Gelmon, Torsten O Nielsen
Importance: Accumulating evidence indicates that tumor-infiltrating lymphocytes (TILs) are associated with clinical outcomes and may predict the efficacy of chemotherapy and human epidermal growth factor receptor 2 (HER2, encoded by the gene ERBB2)-targeted therapy in patients with HER2-positive breast cancer. Objective: To investigate the role of TILs, particularly cytotoxic CD8+ T cells, in the prediction of outcomes in patients with HER2-positive metastatic breast cancer randomized to an antibody-based (trastuzumab) vs a small molecule-based (lapatinib) anti-HER2 therapy...
July 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28750120/association-between-genomic-metrics-and-immune-infiltration-in-triple-negative-breast-cancer
#4
Thomas Karn, Tingting Jiang, Christos Hatzis, Nicole Sänger, Ahmed El-Balat, Achim Rody, Uwe Holtrich, Sven Becker, Giampaolo Bianchini, Lajos Pusztai
Importance: Why some triple-negative breast cancers (TNBCs) have high and others have low immune cell infiltration is unknown. Understanding how immune surveillance shapes the cancer genome could help in the selection of patients and the development of more effective immunotherapy strategies. Objective: To examine the association between genomic metrics and the extent of immune infiltration in TNBCs. Design, Setting, and Participants: This study, performed from June 1, 2015, through January 31, 2017, used DNA and RNA sequencing data and messenger RNA expression results from The Cancer Genome Atlas (TCGA) breast cancer data set (n = 1215) to calculate previously described immune metagene expression values and histologic lymphocyte counts to quantify immune infiltration and assign prognostic categories to TNBCs...
July 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28749961/prediction-of-novel-target-genes-and-pathways-involved-in-irinotecan-resistant-colorectal-cancer
#5
Precious Takondwa Makondi, Chi-Ming Chu, Po-Li Wei, Yu-Jia Chang
BACKGROUND: Acquired drug resistance to the chemotherapeutic drug irinotecan (the active metabolite of which is SN-38) is one of the significant obstacles in the treatment of advanced colorectal cancer (CRC). The molecular mechanism or targets mediating irinotecan resistance are still unclear. It is urgent to find the irinotecan response biomarkers to improve CRC patients' therapy. METHODS: Genetic Omnibus Database GSE42387 which contained the gene expression profiles of parental and irinotecan-resistant HCT-116 cell lines was used...
2017: PloS One
https://www.readbyqxmd.com/read/28749946/genome-wide-association-analysis-identifies-genetic-correlates-of-immune-infiltrates-in-solid-tumors
#6
Nathan O Siemers, James L Holloway, Han Chang, Scott D Chasalow, Petra B Ross-MacDonald, Charles F Voliva, Joseph D Szustakowski
Therapeutic options for the treatment of an increasing variety of cancers have been expanded by the introduction of a new class of drugs, commonly referred to as checkpoint blocking agents, that target the host immune system to positively modulate anti-tumor immune response. Although efficacy of these agents has been linked to a pre-existing level of tumor immune infiltrate, it remains unclear why some patients exhibit deep and durable responses to these agents while others do not benefit. To examine the influence of tumor genetics on tumor immune state, we interrogated the relationship between somatic mutation and copy number alteration with infiltration levels of 7 immune cell types across 40 tumor cohorts in The Cancer Genome Atlas...
2017: PloS One
https://www.readbyqxmd.com/read/28749936/mir-1254-suppresses-ho-1-expression-through-seed-region-dependent-silencing-and-non-seed-interaction-with-tfap2a-transcript-to-attenuate-nsclc-growth
#7
Mengfan Pu, Chenggang Li, Xinming Qi, Jing Chen, Yizheng Wang, Lulu Gao, Lingling Miao, Jin Ren
MicroRNAs (miRNAs) are a class of small non-coding RNAs, which direct post-transcriptional gene silencing (PTGS) and function in a vast range of biological events including cancer development. Most miRNAs pair to the target sites through seed region near the 5' end, leading to mRNA cleavage and/or translation repression. Here, we demonstrated a miRNA-induced dual regulation of heme oxygenase-1 (HO-1) via seed region and non-seed region, consequently inhibited tumor growth of NSCLC. We identified miR-1254 as a negative regulator inhibiting HO-1 translation by directly targeting HO-1 3'UTR via its seed region, and suppressing HO-1 transcription via non-seed region-dependent inhibition of transcriptional factor AP-2 alpha (TFAP2A), a transcriptional activator of HO-1...
July 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28749919/philadelphia-chromosome-like-acute-lymphoblastic-leukemia-progress-in-a-new-cancer-subtype
#8
Julia Wells, Nitin Jain, Marina Konopleva
Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a newly described, high-risk subtype of B-cell ALL. It is characterized by a gene expression profile similar to that of Ph-positive ALL; however, the BCR-ABL1 fusion is not present. The World Health Organization classification of myeloid neoplasms and acute leukemia recently was updated to include the Ph-like or BCR-ABL1-like ALL subtype of B-cell ALL as a provisional entity. Unlike Ph-positive ALL, which is characterized by the pathognomonic BCR-ABL1 fusion, Ph-like ALL is characterized by a multitude of different genetic rearrangements and mutations...
July 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28749573/il-6-stat3-signaling-as-a-promising-target-to-improve-the-efficacy-of-cancer-immunotherapy
#9
REVIEW
Hidemitsu Kitamura, Yosuke Ohno, Yujiro Toyoshima, Junya Ohtake, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi
Overcoming the immunosuppressive state in tumor microenvironments is a critical issue to improve the efficacy of cancer immunotherapy. Interleukin (IL)-6, a pleiotropic cytokine, is highly produced in the tumor-bearing host. Previous studies have indicated that IL-6 suppresses the antigen presentation ability of dendritic cells (DCs) through activation of signal transducer and activator of transcription 3 (STAT3). Thus, we focused on the precise effect of the IL-6/STAT3 signaling cascade on human DCs and the subsequent induction of antitumor T cell immune responses...
July 27, 2017: Cancer Science
https://www.readbyqxmd.com/read/28749548/c-myc-positive-relapsed-and-refractory-diffuse-large-b-cell-lymphoma-impact-of-additional-hits-and-outcomes-with-subsequent-therapy
#10
Narendranath Epperla, Kami J Maddocks, Mohammed Salhab, Julio C Chavez, Nishitha Reddy, Reem Karmali, Elvira Umyarova, Veronika Bachanova, Cristiana Costa, Martha Glenn, Oscar Calzada, Ana C Xavier, Zheng Zhou, Nasheed M Hossain, Francisco J Hernandez-Ilizaliturri, Zeina Al-Mansour, Stefan K Barta, Saurabh Chhabra, Frederick Lansigan, Amitkumar Mehta, Michael V Jaglal, Andrew Evans, Christopher R Flowers, Jonathon B Cohen, Timothy S Fenske, Mehdi Hamadani, Luciano J Costa
BACKGROUND: The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS: This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy...
July 27, 2017: Cancer
https://www.readbyqxmd.com/read/28749535/inhibition-of-histone-deacetylases-sensitizes-egfr-tki-resistant-non-small-cell-lung-cancer-cells-to-erlotinib-in-vitro-and-in-vivo
#11
Weiwei Yu, Weiqiang Lu, Guoliang Chen, Feixiong Cheng, Hui Su, Yihua Chen, Mingyao Liu, Xiufeng Pang
BACKGROUND AND PURPOSE: Intrinsic and/or acquired resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in patients with non-small-cell lung cancer (NSCLC). Here, we develop a combined therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with erlotinib to overcome EGFR-TKI resistance in NSCLC. EXPERIMENTAL APPROACH: The sensitization of erlotinib by YF454A was examined in a panel of EGFR-TKI-resistant NSCLC cell lines in vitro and two different erlotinib-resistant NSCLC xenograft mouse models in vivo...
July 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28749474/racial-ethnic-differences-in-multiple-gene-sequencing-results-for-hereditary-cancer-risk
#12
Jennifer L Caswell-Jin, Tanya Gupta, Evan Hall, Iva M Petrovchich, Meredith A Mills, Kerry E Kingham, Rachel Koff, Nicolette M Chun, Peter Levonian, Alexandra P Lebensohn, James M Ford, Allison W Kurian
PurposeWe examined racial/ethnic differences in the usage and results of germ-line multiple-gene sequencing (MGS) panels to evaluate hereditary cancer risk.MethodsWe collected genetic testing results and clinical information from 1,483 patients who underwent MGS at Stanford University between 1 January 2013 and 31 December 2015.ResultsAsians and Hispanics presented for MGS at younger ages than whites (48 and 47 vs. 55; P = 5E-16 and 5E-14). Across all panels, the rate of pathogenic variants (15%) did not differ significantly between racial groups...
July 27, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28749468/wwox-sensitises-ovarian-cancer-cells-to-paclitaxel-via-modulation-of-the-er-stress-response
#13
Szymon Janczar, Jaya Nautiyal, Yi Xiao, Edward Curry, Mingjun Sun, Elisa Zanini, Adam Jw Paige, Hani Gabra
There are clear gaps in our understanding of genes and pathways through which cancer cells facilitate survival strategies as they become chemoresistant. Paclitaxel is used in the treatment of many cancers, but development of drug resistance is common. Along with being an antimitotic agent paclitaxel also activates endoplasmic reticulum (ER) stress. Here, we examine the role of WWOX (WW domain containing oxidoreductase), a gene frequently lost in several cancers, in mediating paclitaxel response. We examine the ER stress-mediated apoptotic response to paclitaxel in WWOX-transfected epithelial ovarian cancer (EOC) cells and following siRNA knockdown of WWOX...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28749464/the-cohesin-complex-prevents-myc-induced-replication-stress
#14
Sara Rohban, Aurora Cerutti, Marco J Morelli, Fabrizio d'Adda di Fagagna, Stefano Campaner
The cohesin complex is mutated in cancer and in a number of rare syndromes collectively known as Cohesinopathies. In the latter case, cohesin deficiencies have been linked to transcriptional alterations affecting Myc and its target genes. Here, we set out to understand to what extent the role of cohesins in controlling cell cycle is dependent on Myc expression and activity. Inactivation of the cohesin complex by silencing the RAD21 subunit led to cell cycle arrest due to both transcriptional impairment of Myc target genes and alterations of replication forks, which were fewer and preferentially unidirectional...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28749454/the-association-of-low-penetrance-variants-in-dna-repair-genes-with-colorectal-cancer-a-systematic-review-and-meta-analysis
#15
Nikhil Aggarwal, Neil D Donald, Salim Malik, Subothini S Selvendran, Mark Jw McPhail, Kevin J Monahan
OBJECTIVES: Approximately 35% of colorectal cancer (CRC) risk is attributable to heritable factors known hereditary syndromes, accounting for 6%. The remainder may be due to lower penetrance polymorphisms particularly of DNA repair genes. DNA repair pathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), direct reversal repair (DRR), and double-strand break repair are complex, evolutionarily conserved, and critical in carcinogenesis. Germline mutations in these genes are associated with high-penetrance CRC syndromes such as Lynch syndrome...
July 27, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28749424/drug-discovery-by-molecular-imaging-and-monitoring-therapy-response-in-lymphoma
#16
REVIEW
Senthilkumar Kalimuthu, Ju Hye Jeong, Ji Min Oh, Byeong-Cheol Ahn
Molecular imaging allows a noninvasive assessment of biochemical and biological processes in living subjects. Treatment strategies for malignant lymphoma depend on histology and tumor stage. For the last two decades, molecular imaging has been the mainstay diagnostic test for the staging of malignant lymphoma and the assessment of response to treatment. This technology enhances our understanding of disease and drug activity during preclinical and clinical drug development. Here, we review molecular imaging applications in drug development, with an emphasis on oncology...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28749408/clinical-role-of-asct2-slc1a5-in-kras-mutated-colorectal-cancer
#17
Kosuke Toda, Gen Nishikawa, Masayoshi Iwamoto, Yoshiro Itatani, Ryo Takahashi, Yoshiharu Sakai, Kenji Kawada
Mutation in the KRAS gene induces prominent metabolic changes. We have recently reported that KRAS mutations in colorectal cancer (CRC) cause alterations in amino acid metabolism. However, it remains to be investigated which amino acid transporter can be regulated by mutated KRAS in CRC. Here, we performed a screening of amino acid transporters using quantitative reverse-transcription polymerase chain reaction (RT-PCR) and then identified that ASCT2 (SLC1A5) was up-regulated through KRAS signaling. Next, immunohistochemical analysis of 93 primary CRC specimens revealed that there was a significant correlation between KRAS mutational status and ASCT2 expression...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28749203/cb002-a-novel-p53-tumor-suppressor-pathway-restoring-small-molecule-induces-tumor-cell-death-through-the-pro-apoptotic-protein-noxa
#18
Liz J Hernandez-Borrero, Shengliang Zhang, Amriti Lulla, David T Dicker, Wafik S El-Deiry
P53 tumor suppressor gene mutations occur in the majority of human cancers and contribute to tumor development, progression and therapy resistance. Direct functional restoration of p53 as a transcription factor has been difficult to achieve in the clinic. We performed a functional screen using a bioluminescence-based transcriptional read-out to identify small molecules that restore the p53 pathway in mutant p53-bearing cancer cells. We identified CB002, as a candidate that restores p53 function in mutant p53-expressing colorectal cancer cells and without toxicity to normal human fibroblasts...
July 27, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28749120/effects-of-tobacco-habits-on-the-polymorphism-of-nfkb1-and-nfkb1a-gene-of-head-and-neck-squamous-cell-carcinoma-in-indian-population
#19
Abhishek Gupta, Vertica Agnihotri, Rahul Kumar, Ashish Datt Upadhyay, Suman Bhaskar, Sadanand Dwivedi, Sharmistha Dey
Background: Polymorphism of NFKB1 and NFKB1A are highly associated with cancer. We have assessed polymorphism in the promoter region of NFKB1 -94 del/ins ATTG (rs28362491) and NFKB1A -826 C/T (rs2233406) with the risk of HNSCC in Indian population. Methods: Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method was used for the genotyping NFKB1 -94 del/ins ATTG and NFKB1A -826 C/T. Sequencing was done to validate the results of PCR-RFLP. Statistical analysis of data was done by Stata/SE-14...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28749119/antitumor-exopolysaccharides-derived-from-novel-marine-bacillus-isolation-characterization-aspect-and-biological-activity
#20
Salma M Abdelnasser, Shaymaa M M Yahya, Wafaa F Mohamed, Mohsen MS Asker, Hala M Abu Shady, Manal G Mahmoud, Magdy A Gadallah
Objective: Exopolysaccharides gained attention as new source for cancer treatment as recent treatments cause side effects and multidrug resistance. Polysaccharides containing sulfur and uronic acids exhibited antioxidant activity, by restoring cell redox regulation, thus inhibiting cell proliferation and cancer formation. Following this context, our study was performed to assess the cytotoxic activity of exopolysaccharides produced by novel Egyptian marine bacterial strains on HepG2 cells. Methods: Bacteria were isolated, purified and cultured through routine microbiological techniques...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
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