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https://www.readbyqxmd.com/read/29144562/mir-5100-increases-the-cisplatin-resistance-of-the-lung-cancer-stem-cells-by-inhibiting-the-rab6
#1
Lawei Yang, Ziying Lin, Yahong Wang, Shenglan Gao, Qinglan Li, Chunyan Li, Wenya Xu, Jie Chen, Tie Liu, Zeqing Song, Gang Liu
Cisplatin-based chemotherapy is the most commonly used treatment regimen for lung cancer. Cancer stem cells (CSCs) are postulated to be important promoters of drug resistance. We previously found that miR-5100 is overexpressed in lung cancer, but it is unknown whether and how miR-5100 regulates cisplatin resistance. Here, we demonstrated that miR-5100 was significantly up-regulated in CD44 + CD133+ lung cancer stem cells (LCSCs) compared with non-CSCs. Additionally, over-expression of miR-5100 increased CSC properties, cell growth and tumor sphere formation in lung cancer cell line A549 or H1299, and that miR-5100 inhibitor significantly increased sensitivity of LCSCs to cisplatin in vitro...
November 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29143897/anaplastic-lymphoma-kinase-testing-ihc-vs-fish-vs-ngs
#2
REVIEW
Xiaomin Niu, Jody C Chuang, Gerald J Berry, Heather A Wakelee
Personalized targeted therapy has emerged as a promising strategy in lung cancer treatment, with current attention focused on elucidation and detection of oncogenic drivers responsible for tumor initiation and maintenance and development of drug resistance. In lung cancer, several oncogenic drivers have been reported, triggering the application of tyrosine kinase inhibitors (TKIs) to target these dysfunctional genes. The anaplastic lymphoma kinase (ALK) rearrangement is responsible for about 4-7% of all non-small cell lung cancers (NSCLCs) and perhaps as high as a third in specific patient populations such as younger, male, non-smokers with advanced stage, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) wild type, and signet ring cell adenocarcinoma with abundant intracytoplasmic mucin...
November 16, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29143497/detection-and-monitoring-of-driver-mutations-by-next-generation-sequencing-in-squamous-cell-lung-cancer-patient-and-possible-predictive-biomarker-of-third-generation-egfr-tyrosine-kinase-inhibitors
#3
Xiaoyan Shen, Jie Shen, Hang Zhang, Yuxin Cheng, Yang Yang, Jiahui Gao, Yu Zhang, Rutian Li, Baorui Liu, Lifeng Wang
Driver mutation detection and the development of targeted drugs have significantly improved survival of advanced lung adenocarcinoma patients with driver mutations. However, we still lack understanding of druggable mutations in patients with advanced squamous cell lung cancer (SQCLC). Less than 10% of SQCLC patients have EGFR gene mutations, thus we have limited knowledge of biological molecular changes with first generation EGFR-tyrosine kinase inhibitor (TKI) resistance. We report a case of an SQCLC patient treated with first-line platinum-doublet chemotherapy...
November 16, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29142598/expression-profile-of-oct-4-lung-cancer-specific-marker-prior-and-subsequent-to-a-salirasib-treatment-regime
#4
Xiang Ao, Jie Zhou, Hong Ling Liang, Ming Jiang, Hong Sheng Li
Lung cancer is one of the leading types of cancer that lead to mortalities in the male and female populations. The existing lung cancer-specific markers are not able to accurately predict the condition of the disease, and the response of these markers can vary under various pathological conditions. The ability for tumors to regenerate following treatment can be more aggressive, and this may be due to the remaining lung cancer-specific stem cells, which are resistant to chemotherapeutic drugs. Evaluating cancer stem cells under various pathological conditions, as well as prior and subsequent to treatment, can help to increase the understanding of the underlying mechanisms...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29141888/lung-cancer-associated-pulmonary-hypertension-role-of-microenvironmental-inflammation-based-on-tumor-cell-immune-cell-cross-talk
#5
Soni Savai Pullamsetti, Baktybek Kojonazarov, Samantha Storn, Henning Gall, Ylia Salazar, Janine Wolf, Andreas Weigert, Nefertiti El-Nikhely, Hossein Ardeschir Ghofrani, Gabriele A Krombach, Ludger Fink, Stefan Gattenlöhner, Ulf R Rapp, Ralph Theo Schermuly, Friedrich Grimminger, Werner Seeger, Rajkumar Savai
Dyspnea is a frequent, devastating, and poorly understood symptom of advanced lung cancer. In our cohort, among 519 patients who underwent a computed tomography scan for the diagnosis of lung cancer, 250 had a mean pulmonary artery diameter of >28 mm, indicating pulmonary hypertension (PH). In human lung cancer tissue, we consistently observed increased vascular remodeling and perivascular inflammatory cell accumulation (macrophages/lymphocytes). Vascular remodeling, PH, and perivascular inflammatory cell accumulation were mimicked in three mouse models of lung cancer (LLC1, KRas(LA2) , and cRaf-BxB)...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29140271/molecular-targeted-therapies-for-epidermal-growth-factor-receptor-and-its-resistance-mechanisms
#6
REVIEW
Toshimitsu Yamaoka, Motoi Ohba, Tohru Ohmori
Cancer therapies targeting epidermal growth factor receptor (EGFR), such as small-molecule kinase inhibitors and monoclonal antibodies, have been developed as standard therapies for several cancers, such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, breast cancer, and squamous cell carcinoma of the head and neck. Although these therapies can significantly prolong progression-free survival, curative effects are not often achieved because of intrinsic and/or acquired resistance. The resistance mechanisms to EGFR-targeted therapies can be categorized as resistant gene mutations, activation of alternative pathways, phenotypic transformation, and resistance to apoptotic cell death...
November 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29138515/targeting-a-non-oncogene-addiction-to-the-atr-chk1-axis-for-the-treatment-of-small-cell-lung-cancer
#7
Fabian Doerr, Julie George, Anna Schmitt, Filippo Beleggia, Tim Rehkämper, Sarah Hermann, Vonn Walter, Jean-Philip Weber, Roman K Thomas, Maike Wittersheim, Reinhard Büttner, Thorsten Persigehl, H Christian Reinhardt
Small cell lung cancer (SCLC) is a difficult to treat subtype of lung cancer. One of the hallmarks of SCLC is its almost uniform chemotherapy sensitivity. However, chemotherapy response is typically transient and patients frequently succumb to SCLC within a year following diagnosis. We performed a transcriptome analysis of the major human lung cancer entities. We show a significant overexpression of genes involved in the DNA damage response, specifically in SCLC. Particularly CHEK1, which encodes for the cell cycle checkpoint kinase CHK1, is significantly overexpressed in SCLC, compared to lung adenocarcinoma...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138417/association-of-predicted-pathogenic-mutations-in-mitochondrial-nd-genes-with-distant-metastasis-in-nsclc-and-colon-cancer
#8
Nobuko Koshikawa, Miho Akimoto, Jun-Ichi Hayashi, Hiroki Nagase, Keizo Takenaga
Cancer cells have more mutations in their mitochondrial DNA (mtDNA) than do normal cells, and pathogenic mutations in the genes encoding mitochondrial NADH dehydrogenase (ND) subunits have been found to enhance the invasive and metastatic ability of various tumour cells in animal experiments. However, it is unknown whether single-nucleotide variants (SNVs) of the ND genes that decrease complex I activity are involved in distant metastasis in human clinical samples. Here, we demonstrated the enhancement of the distant metastasis of Lewis lung carcinoma cells by the ND6 13885insC mutation, which is accompanied by the overexpression of metastasis-related genes, metabolic reprogramming, the enhancement of tumour angiogenesis and the acquisition of resistance to stress-induced cell death...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137407/lncrna-snhg12-contributes-to-multidrug-resistance-through-activating-the-mapk-slug-pathway-by-sponging-mir-181a-in-non-small-cell-lung-cancer
#9
Pei Wang, Dong Chen, Hongbing Ma, Yong Li
Small nucleolar RNA host gene 12 (SNHG12), as one of the long non-coding RNAs (lncRNAs), plays an oncogenic role in various cancers, however, its role in the chemoresistance of non-small cell lung cancer (NSCLC) is unclear. In this study, we investigated the effect of SNHG12 on multidrug resistance (MDR) in NSCLC. The results showed that SNHG12 was high-expressed and miR-181a was low-expressed in NSCLC tumor tissues and cell lines. Knockdown of SNHG12 reversed the resistance to cisplatin, paclitaxel and gefitinib in A549/DDP, A549/PTX and PC9/AB2 cells through inducing cell apoptosis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137296/early-detection-of-thymidylate-synthase-resistance-in-non-small-cell-lung-cancer-with-flt-pet-imaging
#10
Xiao Chen, Yizeng Yang, Sharyn Katz
Introduction: Inhibition of thymidylate synthase (TS) results in a transient compensatory "flare" in thymidine salvage pathway activity measureable with (18)F-thymidine (FLT)- positron emission tomography (PET) at 2hrs. of therapy which may predict non-small cell lung cancer (NSCLC) sensitivity to TS inhibition. Materials and Methods: Resistance to TS inhibition by pemetrexed was induced in NSCLC cell lines H460 and H1299 through TS overexpression. TS overexpression was confirmed with RT-PCR and Western blotting and pemetrexed resistance confirmed with IC50 assays...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137103/crizotinib-resistance-overcome-by-ceritinib-in-an-alk-positive-non-small-cell-lung-cancer-patient-with-brain-metastases-a-case-report
#11
Zhouyu Zhu, Ying Chai
RATIONALE: The treatment of non-small cell lung cancer (NSCLC) has now changed dramatically in recent years and anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitors are developing rapidly. PATIENT CONCERNS: Here we reported a 57-year-old ALK-positive NSCLC man with brain metastases. DIAGNOSES: A case of lung adenocarcinoma with brain metastases. INTERVENTIONS: Crizotinib was administered orally at a dose of 250mg twice a day until the brain metastases were found...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29136529/yap-dependent-axl-overexpression-mediates-resistance-to-egfr-inhibitors-in-nsclc
#12
Elena Ghiso, Cristina Migliore, Vito Ciciriello, Elena Morando, Annalisa Petrelli, Simona Corso, Emmanuele De Luca, Gaia Gatti, Marco Volante, Silvia Giordano
The Yes-associated protein (YAP) is a transcriptional co-activator upregulating genes that promote cell growth and inhibit apoptosis. The main dysregulation of the Hippo pathway in tumors is due to YAP overexpression, promoting epithelial to mesenchymal transition, cell transformation, and increased metastatic ability. Moreover, it has recently been shown that YAP plays a role in sustaining resistance to targeted therapies as well. In our work, we evaluated the role of YAP in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer...
November 11, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29136465/recent-progress-of-small-molecule-epidermal-growth-factor-receptor-egfr-inhibitors-against-c797s-resistance-in-non-small-cell-lung-cancer
#13
Lingfeng Chen, Weitao Fu, Lulu Zheng, Zhiguo Liu, Guang Liang
The epidermal growth factor receptor (EGFR) has been a particular interest for drug development for treatment of non-small-cell lung cancer (NSCLC). The current third-generation EGFR small-molecule inhibitors, especially osimertinib, are at the forefront clinically for treatment of patients with NSCLC. However, a high percentage of these treated patients developed a tertiary cystein797 to serine790 (C797S) mutation in the EGFR kinase domain. This C797S mutation is thought to induce resistance to all current irreversible EGFR TKIs...
November 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29135607/targeting-the-perivascular-niche-in-brain-tumors
#14
Giorgio Seano
PURPOSE OF REVIEW: Brain tumors are composed of primary tumors of the central nervous system, such us glioblastoma (GBM), and secondary metastatic tumors, such as melanoma, non-Hodgkin lymphoma as well as lung and breast cancers. Brain tumors are highly deadly, and unfortunately not many improvements have been achieved to improve the survival of patients with brain tumors. Chemoradiation resistance is one of the most clinically relevant challenges faced in patients with brain tumors. The perivascular niche is one of the most relevant microenvironment hubs in brain tumors...
November 14, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29133033/design-synthesis-and-evaluation-of-a-ring-modified-lamellarin-n-analogues-as-noncovalent-inhibitors-of-the-egfr-t790m-l858r-mutant
#15
Tsutomu Fukuda, Teppei Umeki, Keiji Tokushima, Gao Xiang, Yuki Yoshida, Fumito Ishibashi, Yusuke Oku, Naoyuki Nishiya, Yoshimasa Uehara, Masatomo Iwao
A series of A-ring-modified lamellarin N analogues were designed, synthesized, and evaluated as potential noncovalent inhibitors of the EGFR T790M/L858R mutant, a causal factor in the drug-resistant non-small cell lung cancer. Several water-soluble ammonium- or guanidinium-tethered analogues exhibited good kinase inhibitory activities. The most promising analogue, 14f, displayed an excellent inhibitory profile against the T790M/L858R mutant [IC50 (WT) = 31.8 nM; IC50 (T790M/L858R) = 8.9 nM]. The effects of A-ring-substituents on activity were rationalized by docking studies...
October 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29132432/ac-93253-iodide-a-novel-src-inhibitor-suppresses-nsclc-progression-by-modulating-multiple-src-related-signaling-pathways
#16
Yi-Hua Lai, Sih-Yin Lin, Yu-Shan Wu, Huei-Wen Chen, Jeremy J W Chen
BACKGROUND: The tyrosine kinase Src is involved in the progression of many cancers. Moreover, inhibiting Src activity has been shown to obstruct several signaling pathways regulated by the EGFR. Thus, Src is a valuable target molecule in drug development. The purpose of this study was to identify compounds that directly or indirectly modulate Src to suppress lung cancer cell growth and motility and to investigate the molecular mechanisms underlying the effects of these compounds. METHODS: Human non-small cell lung cancer (NSCLC) cell lines (PC9, PC9/gef, A549, and H1975) with different EGFR statuses were tested by cytotoxicity and proliferation assays after AC-93253 iodide treatment...
November 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29132337/gene-expression-signatures-of-neuroendocrine-prostate-cancer-and-primary-small-cell-prostatic-carcinoma
#17
Harrison K Tsai, Jonathan Lehrer, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, Tamara L Lotan
BACKGROUND: Neuroendocrine prostate cancer (NEPC) may be rising in prevalence as patients with advanced prostate cancer potentially develop resistance to contemporary anti-androgen treatment through a neuroendocrine phenotype. While prior studies comparing NEPC and prostatic adenocarcinoma have identified important candidates for targeted therapy, most have relied on few NEPC patients due to disease rarity, resulting in thousands of differentially expressed genes collectively and offering an opportunity for meta-analysis...
November 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29132176/verapamil-ver-enhances-the-cytotoxic-effects-of-docetaxel-and-vinblastine-combined-therapy-against-non-small-cell-lung-cancer-cell-lines
#18
Soleiman Jaferian, Maryam Soleymaninejad, Hadis Daraee
Lung cancer is one of the foremost tumor-associated cause of death in the world. Most of the patients with NSCLC possesses an advanced disease at diagnosis, and are thus probable subject for systemic therapy. This study aims to evaluate the cytotoxicity of vinblastine and docetaxel combined therapy for the treatment of NSCLC, as well as verapamil (VER) enhancement of the combined therapy. We conducted P-glycoprotein (P-gp) gene expression, protein expression with RT-PCR and western blot respectively, apoptotic response of the combined therapy with VER is also determined using DAPI staining (%)...
November 13, 2017: Drug Research
https://www.readbyqxmd.com/read/29130967/endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reduces-chemotherapy-resistance-in-mutant-p53-lung-cancer-cells
#19
Ping-Ping Gan, Yang-Ying Zhou, Mei-Zuo Zhong, Yun Peng, Li Li, Jian-Huang Li
BACKGROUND/AIMS: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. METHODS: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53)...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29130102/knockdown-of-lncrna-xist-enhances-the-chemosensitivity-of-nsclc-cells-via-suppression-of-autophagy
#20
Wei Sun, Yukun Zu, Xiangning Fu, Yu Deng
Drug resistance is the major factor contributing to the failure of chemotherapy in non-small cell lung cancer (NSCLC) patients. Emerging evidence suggests that autophagy plays a vital role in the chemoresistance of many types of tumors. However, the exact mechanism underlying the chemoresistance of NSCLC is still elusive, and it is unclear whether lncRNA-XIST is involved in autophagy and chemoresistance of NSCLC. In the present study, we demonstrated that lncRNA-XIST was overexpressed in NSCLC tumor samples, and knockdown of lncRNA-XIST significantly decreased autophagy by regulation of ATG7 as determined by qPCR and by western blotting...
December 2017: Oncology Reports
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