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https://www.readbyqxmd.com/read/29235520/ubiquitin-conjugating-enzyme-e2t-ube2t-and-denticleless-protein-homolog-dtl-are-linked-to-poor-outcome-in-breast-and-lung-cancers
#1
Javier Perez-Peña, Verónica Corrales-Sánchez, Eitan Amir, Atanasio Pandiella, Alberto Ocana
Protein ubiquitination and degradation represent druggable vulnerabilities of cancer cells. We used gene expression and functional annotation analyses to identify genes in the ubiquitin pathway which are differentially expressed between normal breast and basal-like tumors. With this approach we identified 16 ubiquitin related genes overexpressed in basal-like breast cancers compared with normal breast. We then explored the association between these genes and outcomes using the KMPlotter online tool. Two genes, the ubiquitin-conjugating enzyme E2T (UBE2T) and the denticleless protein homolog (DTL) were overexpressed and linked with detrimental outcome in basal-like and luminal breast cancer patients...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234587/pulmonary-papillary-adenocarcinoma-with-aspergillus-versicolor-infection-in-a-dog
#2
Rathiymaler Maniam, Gayathri Thevi Selvarajah, Mazlina Mazlan, Leslie Thian Lung Than
Papillary adenocarcinoma of the lungs is the most common primary lung adenocarcinoma, with the feature of papillary-like structure formation by cells. A dog was presented with the primary complaint of vomiting, hyporexia and increased respiratory effort. Thoracic radiography revealed increased soft tissue radiopacity of the right cranial lung lobe suggestive of possible consolidation or collapsed lung lobe, with generalised miliary nodular pattern throughout the other lung fields. The dog was euthanized humanely and necropsy was performed...
March 2018: Medical Mycology Case Reports
https://www.readbyqxmd.com/read/29233112/napsin-a-levels-in-epithelial-lining-fluid-as-a-diagnostic-biomarker-of-primary-lung-adenocarcinoma
#3
Akifumi Uchida, Takuya Samukawa, Tomohiro Kumamoto, Masahiro Ohshige, Kazuhito Hatanaka, Yoshihiro Nakamura, Keiko Mizuno, Ikkou Higashimoto, Masami Sato, Hiromasa Inoue
BACKGROUND: It is crucial to develop novel diagnostic approaches for determining if peripheral lung nodules are malignant, as such nodules are frequently detected due to the increased use of chest computed tomography scans. To this end, we evaluated levels of napsin A in epithelial lining fluid (ELF), since napsin A has been reported to be an immunohistochemical biomarker for histological diagnosis of primary lung adenocarcinoma. METHODS: In consecutive patients with indeterminate peripheral lung nodules, ELF samples were obtained using a bronchoscopic microsampling (BMS) technique...
December 12, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29232915/histologic-grade-is-predictive-of-incidence-of-epidermal-growth-factor-receptor-mutations-in-metastatic-lung-adenocarcinoma
#4
Michelle Levy, Liisa Lyon, Erika Barbero, John Wong, Marie Suga, Danny Sam, Minggui Pan
Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The clinical characteristics including smoking status, histologic type, sex and ethnicity are known to be associated with the incidence of EGFR mutations. We retrospectively analyzed 277 patients with metastatic NSCLC within Kaiser Permanente Northern California (KPNC); among these patients, 83 were positive for EGFR mutations...
December 11, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29232579/structure-based-identification-of-a-nedd8-activating-enzyme-inhibitor-via-drug-repurposing
#5
Ke-Jia Wu, Hai-Jing Zhong, Guodong Li, Chenfu Liu, Hui-Min David Wang, Dik-Lung Ma, Chung-Hang Leung
NEDD8-activating enzyme (NAE) is an essential player of the NEDD8 conjugation pathway that regulates protein degradation. Meanwhile, drug repurposing is a cost-efficient strategy to identify new therapeutic uses for existing scaffolds. In this report, mitoxantrone (1) was repurposed as an inhibitor of NAE by virtual screening of an FDA-approved drug database. Compound 1 inhibited NAE activity in cell-free and cell-based systems with high selectivity and was competitive with ATP. Furthermore, compound 1 induced apoptosis of colorectal adenocarcinoma cancer cells through inhibiting the degradation of the neddylation substrate p53...
December 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232215/pulmonary-tumor-thrombotic-microangiopathy-case-report-and-review-of-literature
#6
Josh Curtis Hutchinson, James W Fulcher, Jeff Hanna, Michael E Ward
Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare rapidly progressive fatal disease that is difficult to diagnosis antemortem. Activation of the coagulation cascade and fibrocellular intimal thickening caused by embolism of tumor cells into pulmonary vasculature leads to extensive pulmonary hypertension and eventually death. We describe a case of PTTM with association of a presumed lung adenocarcinoma primary. Although rare in nature, PTTM should be a considered diagnosis with chronic dyspnea of unknown origin, severe pulmonary hypertension coupled with right-side heart failure, in the absence of pulmonary embolism...
December 11, 2017: American Journal of Forensic Medicine and Pathology
https://www.readbyqxmd.com/read/29230631/the-investigation-of-ceranib-2-on-apoptosis-and-drug-interaction-with-carboplatin-in-human-non-small-cell-lung-cancer-cells-in-vitro
#7
Merve Yildiz-Ozer, Pinar Oztopcu-Vatan, Gokhan Kus
Ceramide is found to be involved in inhibition of cell division and induction of apoptosis in certain tumour cells. Ceranib-2 is an agent that increases ceramide levels by inhibiting ceramidase in cancer cells. Therefore, we aimed to investigate the effects of ceranib-2 on cell survival, apoptosis and interaction with carboplatin in human non-small cell lung cancer cells. The cytotoxic effect of ceranib-2 (1-100 µM) was determined by MTT assay in human lung adenocarcinoma (A549) and large cell lung carcinoma (H460) cells...
December 11, 2017: Cytotechnology
https://www.readbyqxmd.com/read/29230130/periampullary-carcinoma-unusual-sites-of-metastasis
#8
Anju Bansal, Varsha Dalal, Manveen Kaur, Fouzia Siraj
Background: Periampullary neoplasms include carcinomas of the duodenum, ampulla of Vater, distal common bile duct, and pancreas. The aggressive course of these neoplasms is attributable to the delay in diagnosis, as patients have no symptoms until advanced stages of the disease. More than half of patients have distant metastasis at the time of diagnosis. The most frequent sites of metastasis are the liver, lymph nodes, peritoneum, lung, bone, kidney, and, rarely the skin. Case Report: We report the case of a 45-year-old female patient with adenocarcinoma of the ampulla of Vater metastasizing to the right parietal skull with overlying cutaneous involvement 1 year after a Whipple procedure...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29229669/kras-the-critical-driver-and-therapeutic-target-for-pancreatic-cancer
#9
Andrew M Waters, Channing J Der
RAS genes (HRAS, KRAS, and NRAS) comprise the most frequently mutated oncogene family in human cancer. With the highest RAS mutation frequencies seen with the top three causes of cancer deaths in the United States (lung, colorectal, and pancreatic cancer), the development of anti-RAS therapies is a major priority for cancer research. Despite more than three decades of intense effort, no effective RAS inhibitors have yet to reach the cancer patient. With bitter lessons learned from past failures and with new ideas and strategies, there is renewed hope that undruggable RAS may finally be conquered...
December 11, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29229632/activation-of-the-aryl-hydrocarbon-receptor-leads-to-resistance-to-egfr-tkis-in-non-small-cell-lung-cancer-by-activating-src-mediated-bypass-signaling
#10
Mingxiang Ye, Yong Zhang, Hongjun Gao, Yan Xu, Pengyu Jing, Jianxiong Wu, Xinxin Zhang, Jie Xiong, Chenfang Dong, Libo Yao, Jian Zhang, Jian Zhang
PURPOSE: The aryl hydrocarbon receptor (AhR) has been generally recognized as a ligand-activated transcriptional factor that responds to xenobiotic chemicals. Recent studies have suggested that the expression of AhR varies widely across different cancer types and cancer cell lines, but its significance in cancer treatment has yet to be clarified. EXPERIMENTAL DESIGN: AhR expression in non-small-cell lung cancer (NSCLC) was determined by Western blotting and IHC staining...
December 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29228697/egfr-mutation-smoking-and-gender-in-advanced-lung-adenocarcinoma
#11
Chien-Hua Tseng, Chun-Ju Chiang, Jeng-Sen Tseng, Tsung-Ying Yang, Kuo-Hsuan Hsu, Kun-Chieh Chen, Chih-Liang Wang, Chih-Yi Chen, Sang-Hue Yen, Chun-Ming Tsai, Ming-Shyan Huang, Chao-Chi Ho, Chong-Jen Yu, Ying-Huang Tsai, Jin-Shing Chen, Teh-Ying Chou, Ming-Hsun Tsai, Hsuan-Yu Chen, Kang-Yi Su, Jeremy J W Chen, Huei-Wen Chen, Sung-Liang Yu, Tsang-Wu Liu, Gee-Chen Chang
Purpose: In the current targeted therapy era, information on the effect of smoking in epidermal growth factor receptor (EGFR)-mutant lung cancer patients is scarce. Results: In total, 11,678 adenocarcinoma patients were enrolled. Of these, 33.3% and 91.8% of male and female patients were non-smokers, respectively. An increased amount of smoking (P < 0.001 for trend), fewer smoke-free years (P < 0.001 for trend), and younger age of smoking initiation (P = 0...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228652/clinical-characteristics-and-programmed-cell-death-ligand-1-expression-in-adenocarcinoma-in-situ-and-minimally-invasive-adenocarcinoma-of-lung
#12
Renke Yu, Zhengfu He, Ying Lou, Hanliang Jiang, Yuhui Wu, Zhen Liu, Hongming Pan, Weidong Han
Objectives: According to the IASLC/ATS/ERS 2011 classification, there are two new conceptions of lung adenocarcinoma, adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), which are very early stages of lung adenocarcinoma. This study aimed to analyze clinical features of AIS and MIA and determine the expression profile of PD-L1 in AIS and MIA. Results: In all 274 patients, 77 were diagnosed as AIS and 197 as MIA. We accidentally found 4 patients with recurrence, which were all MIA...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228636/the-efficacy-of-40-mg-versus-dose-de-escalation-to-less-than-40-mg-of-afatinib-giotrif-as-the-first-line-therapy-for-patients-with-primary-lung-adenocarcinoma-harboring-favorable-epidermal-growth-factor-mutations
#13
Chien-Ying Liu, Chih-Liang Wang, Shih-Hong Li, Ping-Chih Hsu, Chih-Hung Chen, Ting-Yu Lin, Chih-Hsi Kuo, Yueh-Fu Fang, How-Wen Ko, Chih-Teng Yu, Tai-Yun Yang, Cheng-Ta Yang
The choice of a first-line therapy for lung cancer is a crucial decision that can impact the survival as well as the quality of life of a patient. Inhibitors of epidermal growth factor receptor (EGFR) such as afatinib, erlotinib, and gefitinib have previously been used to treat non-small cell lung cancer harboring favorable EGFR mutations. Although afatinib has greater efficacy than other EGFR inhibitors, adverse events related to its use can result in the discontinuation of the therapy. In this study, we compared the therapeutic efficacy in lung cancer patients of a regimen of 40 mg/day of afatinib with that of a lower dose regimen of <40 mg/day resulting either from a lower starting dose of 30 mg/day or dose adjustment...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228607/clinical-significance-and-biological-function-of-fucosyltransferase-2-in-lung-adenocarcinoma
#14
Wenyuan Zhou, Huijun Ma, Guoqing Deng, Lili Tang, Jianxin Lu, Xiaoming Chen
Fucosylation, which is catalyzed by fucosyltransferases (FUTs), is one of the most important glycosylation events involved in cancer. Studies have shown that fucosyltransferase 8 (FUT8) is overexpressed in NSCLC and promotes lung cancer progression. However, there are no reports about the pathological role of fucosyltransferase 2 (FUT2) in lung cancer. To identify FUT2 associated with lung cancer, the expression and clinical significance of FUT2 in lung cancer was investigated by Real-Time PCR, Immunohistochemistry and Western Blot...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228562/clinical-mutational-profiling-of-1006-lung-cancers-by-next-generation-sequencing
#15
Peter B Illei, Deborah Belchis, Li-Hui Tseng, Doreen Nguyen, Federico De Marchi, Lisa Haley, Stacy Riel, Katie Beierl, Gang Zheng, Julie R Brahmer, Frederic B Askin, Christopher D Gocke, James R Eshleman, Patrick M Forde, Ming-Tseh Lin
Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine AKT1, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity. Among 760 mutations detected, the variant allele frequency (VAF) was 2-5% in 33 (4.3%) mutations and 2-10% in 101 (13%) mutations. A single bioinformatics pipeline using Torrent Variant Caller, however, missed a variety of EGFR mutations...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228521/intercalated-treatment-following-rebiopsy-is-associated-with-a-shorter-progression-free-survival-of-osimertinib-treatment
#16
Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kuo-Hsuan Hsu, Yen-Hsiang Huang, Kang-Yi Su, Sung-Liang Yu, Gee-Chen Chang
Purpose: Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment. Materials and Methods: Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients' characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription...
December 11, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29228209/cd38-knockout-suppresses-tumorigenesis-in-mice-and-clonogenic-growth-of-human-lung-cancer-cells
#17
Xiangning Bu, Jiro Kato, Julie A Hong, Maria J Merino, David S Schrump, Frances E Lund, Joel Moss
The ectodomain of the plasma membrane ecto-enzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development...
December 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29227908/the-selectivity-of-artemisinin-based-drugs-on-human-lung-normal-and-cancer-cells
#18
Xinyang Li, Shiyan Gu, Donglei Sun, Huangmei Dai, Hongyu Chen, Zunzhen Zhang
Artemisinin-based drugs are documented to possess anticancer potential that is selectively effective to cancer cells. However, this selectivity is disputable in different studies and the mechanism is still unclear. To clarify this discrepancy, this study employed five assays to evaluate the cytotoxic effects of artemisinin and artesunate on normal human bronchial epithelial (HBE) cells and lung adenocarcinoma A549 cells. The results of five cytotoxic assays coherently showed that artemisinin and artesunate caused dose-dependent cytotoxicity in both HBE and A549 cells with a slight selectivity to A549 cells...
December 7, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29227119/-molecular-pathology-of-lung-cancer-in-routine-diagnostic-practice-2017-update
#19
Radoslav Matěj, Zdeněk Rohan, Kristýna Němejcová, Pavel Dundr
The group of non-small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Analysis of EGFR gene mutations and ALK rearrangement in lung adenocarcinomas are already routinely performed and are closely related to the indication for the administration of tyrosinkinase inhibitors...
2017: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/29225472/18f-fluorodeoxyglucose-uptake-predicts-met-expression-in-lung-adenocarcinoma
#20
Shuxian An, Xiang Zhou, Jianjun Liu, Gang Huang
Objective: MET is a member of the receptor tyrosine kinases. Several MET-targeting inhibitors and antagonistic antibodies have shown promising data in clinical trials of lung adenocarcinoma. Finding noninvasive diagnostic tools to estimate the status of MET is helpful in clinical practice. 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) has been used routinely for the diagnosis and staging of tumors. However, the relationship between MET expression and 18F-FDG uptake has not been investigated yet...
2017: OncoTargets and Therapy
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