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(lung cancer) and (resistance)

Elena Guerini-Rocco, Antonio Passaro, Chiara Casadio, Valeria Midolo De Luca, Juliana Guarize, Filippo de Marinis, Davide Vacirca, Massimo Barberis
CONTEXT: - Molecular testing is essential for the diagnostic workup of patients with advanced non-small cell lung cancers. Cytology specimens from minimally invasive procedures, such as endobronchial ultrasound-guided transbronchial needle aspiration, are often the only available samples for these patients. The implementation of molecular diagnostic testing, and in particular next-generation sequencing-based testing, on these cytologic specimens is currently an evolving field for lung cytopathology...
April 2018: Archives of Pathology & Laboratory Medicine
Alaa Abd-Elsayed, Samuel Lee, Markus Jackson
Background: Intercostal neuralgia is a complex and difficult-to-treat condition. We present 2 cases that demonstrate the safe and effective use of thermal radiofrequency ablation (RFA) to achieve significant pain relief. Case Reports: Our first patient was a 62-year-old female who developed chronic chest pain following lumpectomy for breast cancer and failed conservative management. Two intercostal diagnostic nerve blocks were performed with good results. One block provided pain relief for 3 weeks, and the other provided pain relief for 5 weeks...
2018: Ochsner Journal
Mary Jo Fidler, Cristina L Fhied, Joanna Roder, Sanjib Basu, Selina Sayidine, Ibtihaj Fughhi, Mark Pool, Marta Batus, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The VeriStrat test is a serum proteomic signature originally discovered in non-responders to second line gefitinib treatment and subsequently used to predict differential benefit from erlotinib versus chemotherapy in previously treated advanced non-small cell lung cancer (NSCLC). Multiple studies highlight the clinical utility of the VeriStrat test, however, the mechanistic connection between VeriStrat-poor classification and poor prognosis in untreated and previously treated patients is still an active area of research...
March 20, 2018: BMC Cancer
Muge Yucel, Osman Akin, Mehmet Cayoren, Ibrahim Akduman, Alagappan Palaniappan, Bo Liedberg, Gurkan Hizal, Fatih Inci, Umit Hakan Yildiz
This study reports on a handheld volatilome analyzer for selective determination of clinically relevant biomarkers in exhaled breath. The sensing platform is based on electrospun polymer nanofiber-multi walled carbon nanotube (MWCNT) sensing micro-channels. Polymer nanofibers of poly(vinylidene fluoride) (PVDF), polystyrene (PS), and poly(methyl methacrylate) (PMMA) incorporated with MWCNT exhibits stable response to interferences of humidity and CO2 and provides selective deformations upon exposure of exhaled breath target volatilomes acetone and toluene, exhibiting correlation to diabetes and lung cancer, respectively...
March 20, 2018: Analytical Chemistry
Hitendra S Solanki, Remya Raja, Alex Zhavoronkov, Ivan V Ozerov, Artem V Artemov, Jayshree Advani, Aneesha Radhakrishnan, Niraj Babu, Vinuth N Puttamallesh, Nazia Syed, Vishalakshi Nanjappa, Tejaswini Subbannayya, Nandini A Sahasrabuddhe, Arun H Patil, T S Keshava Prasad, Daria Gaykalova, Xiaofei Chang, Rachana Sathyendran, Premendu Prakash Mathur, Annapoorni Rangarajan, David Sidransky, Akhilesh Pandey, Evgeny Izumchenko, Harsha Gowda, Aditi Chatterjee
EGFR-based targeted therapies have shown limited success in smokers. Identification of alternate signaling mechanism(s) leading to TKI resistance in smokers is critically important. We observed increased resistance to erlotinib in H358 NSCLC (non-small cell lung carcinoma) cells chronically exposed to cigarette smoke (H358-S) compared to parental cells. SILAC-based mass-spectrometry approach was used to study altered signaling in H358-S cell line. Importantly, among the top phosphosites in H358-S cells we observed hyperphosphorylation of EGFR (Y1197) and non-receptor tyrosine kinase FAK (Y576/577)...
January 2018: Oncoscience
Jiang-Kai Dong, Hui-Min Lei, Qian Liang, Ya-Bin Tang, Ye Zhou, Yang Wang, Shengzhe Zhang, Wen-Bin Li, Yunguang Tong, Guanglei Zhuang, Liang Zhang, Hong-Zhuan Chen, Liang Zhu, Ying Shen
How to improve the efficacy and reverse the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of lung adenocarcinoma with EGFR-activating mutation. Phosphoglycerate dehydrogenase (PHGDH) is the key enzyme of de novo serine biosynthesis over-expressed in various types of cancer including lung cancer. Elevated PHGDH expression is correlated with a worse overall survival in clinical lung adenocarcinoma patients...
2018: Theranostics
Wei Chen, Xiaoqun Liu, Sujuan Yuan, Tiankui Qiao
Although cisplatin (CDDP) is widely used for non-small-cell lung cancer (NSCLC) treatment, resistance remains a major problem that restricts its efficacy. Therefore, identification of drugs that reverse or prevent resistance to CDDP in NSCLC has been a focus of a number of studies. The results of the present study revealed the effect of heat shock protein family A member 12B (HSPA12B) overexpression on chemoresistance in A549 cells in vitro . The effect of HSPA12B overexpression on chemoresistance in mice bearing A549 xenografted tumors was then determined via stable HSPA12B transfection...
March 2018: Oncology Letters
Ruilian Xu, Guolin Zhong, Tanxiao Huang, Wan He, Cheng Kong, Xiaoni Zhang, Ying Wang, Ming Liu, Mingyan Xu, Shifu Chen
Lung cancer is the most commonly occurring type of cancer worldwide and also has the highest mortality rate. Although targeted therapy of non-small cell lung carcinoma (NSCLC) has become common, the majority of patients receiving first-line epithelial growth factor receptor (EGFR)-TKI treatment develop drug resistance. The EGFR T790M (NM_005228.4(EGFR):c.2369C>T (p.Thr790Met)) mutation accounts for half of all reported resistance cases; however, the molecular mechanism resulting in the drug resistance remains to be characterized...
March 2018: Oncology Letters
Madiha Kanwal, Xiao-Jie Ding, Xin Song, Guang-Biao Zhou, Yi Cao
Air pollution is one of the leading causes of lung cancer. Air pollution-related lung cancer is a deteriorating public health problem, particularly in developing countries. The MUC16 gene is one of the most frequently mutated genes in air pollution-related lung cancer. In the present study, MUC16 mRNA expression was increased in ∼50% of air pollution-related lung cancer samples obtained from patients residing in air-polluted regions (Xuanwei and Fuyuan, Yunnan, China), and MUC16 mRNA levels were correlated with the degree of air pollution...
February 23, 2018: Oncotarget
Mengfan Qi, Ye Tian, Wang Li, Dan Li, Tian Zhao, Yuxin Yang, Qiwen Li, Sujun Chen, Yan Yang, Zhixiong Zhang, Liang Tang, Zhonghua Liu, Bo Su, Fei Li, Yonghong Feng, Ke Fei, Peng Zhang, Fan Zhang, Lei Zhang
Gefitinib, an EGFR tyrosine kinase inhibitor, is used to treat non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, the resistance to gefitinib eventually emerges in most of the patients. To understand its mechanism, we generated two acquired gefitinib-resistant NSCLC cell lines. The resistant cells have slower growth rates, but are more resistant to apoptosis in the presence of gefitinib, compared with their sensitive counterparts. In addition, our genome-wide transcriptome analysis reveals unexpected pathways, particularly autophagy, are dysregulated in the gefitinib-resistant cells...
February 23, 2018: Oncotarget
Hongyang Lu, Bo Chen, Jing Qin, Fajun Xie, Na Han, Zhiyu Huang
The present study describes the case of a 48-year-old man who was diagnosed with lung adenocarcinoma with an epidermal growth factor receptor (EGFR) 21 L858R mutation. The patient received surgery and adjuvant chemotherapy. When multiple lung metastases appeared, icotinib was administered. Following resistance to icotinib, biopsy by endobroncheal ultrasonography for a right lung hilar lymph node revealed transformation to a neuroendocrine morphology. Neuron-specific enolase (NSE) levels were elevated, accompanied with disease progression following transformation to the neuroendocrine morphology...
April 2018: Oncology Letters
Songcheng Yu, Zhen Yan, Feifei Feng, Jing Ni, Wei Wang, Kadijatu Nabie, Yiguo Zhang, Lingbo Qu, Yongjun Wu
Coal tar pitch (CTP) is a key factor in the development of occupational lung cancer. In order to investigate the function of the anti-oxidative signaling pathway regulated by NF-E2-related factor 2 (Nrf2) during cancer development, BEAS-2B cells were cultured with CTP extract for 30 passages. It was revealed that malignant transformation occurred in cells between the 20 and 30th passage. The expression levels of Nrf2 and NAD(P)H:quinone oxidoreductase 1 (NQO1) were promoted throughout the CTP exposure culture, and there was a positive linear correlation between the expression levels of Nrf2 and NQO1...
April 2018: Oncology Letters
Victor O Oria, Paul Lopatta, Oliver Schilling
A disintegrin and a metalloprotease (ADAM) 9 is a metzincin cell-surface protease involved in several biological processes such as myogenesis, fertilization, cell migration, inflammatory response, proliferation, and cell-cell interactions. ADAM9 has been found over-expressed in several solid tumors entities such as glioma, melanoma, prostate cancer, pancreatic ductal adenocarcinoma, gastric, breast, lung, and liver cancers. Immunohistochemical analyses highlight ADAM9 expression by actual cancer cells and associate its abundant presence with clinicopathological features such as shortened overall survival, poor tumor grade, de-differentiation, therapy resistance, and metastasis formation...
March 17, 2018: Cellular and Molecular Life Sciences: CMLS
Xiaoyuan Wang, Hang Yin, Hongxia Zhang, Jing Hu, Hailing Lu, Chunhong Li, Mengru Cao, Shi Yan, Li Cai
Acquired resistance to epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, is a critical obstacle in the treatment of EGFR mutant-positive non-small cell lung cancer (NSCLC). EHD1, a protein of the C-terminal Eps15 homology domain-containing (EHD) family, plays a role in regulating endocytic recycling, but the mechanistic details involved in EGFR-TKI resistance and cancer stemness remain largely unclear. Here, we found that a lower EHD1 expression improved both EGFR-TKIs sensitivity, which is consistent with a lower CD133 expression, and progression-free survival in NSCLC patients...
March 16, 2018: Cell Death & Disease
Lin Bai, Aihua Wang, Yali Zhang, Xiaofeng Xu, Xiao Zhang
Long non-coding RNAs (lncRNAs) are critical regulators in chemoresistance of various tumors including ovarian cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be upregulated and contributed to ovarian cancer tumorigenesis. The aim of this study was to explore the roles of MALAT1 and the underlying molecular regulatory mechanism in the chemoresistance of ovarian cancer cells. Our data demonstrated that MALAT1 and Notch1 mRNA were upregulated in ovarian cancer tissues, as well as cisplatin (CDDP)-resistant ovarian cancer cells...
March 13, 2018: Experimental Cell Research
Meng-Shih Weng, Jer-Hwa Chang, Wen-Yueh Hung, Yi-Chieh Yang, Ming-Hsien Chien
BACKGROUND: The epidermal growth factor receptor (EGFR) plays important roles in cell survival, growth, differentiation, and tumorigenesis. Dysregulation of the EGFR is a common mechanism in cancer progression especially in non-small cell lung cancer (NSCLC). MAIN BODY: Suppression of the EGFR-mediated signaling pathway is used in cancer treatment. Furthermore, reactive oxygen species (ROS)-induced oxidative stress from mitochondrial dysfunction or NADPH oxidase (NOX) overactivation and ectopic expression of antioxidative enzymes were also indicated to be involved in EGFR-mediated tumor progression (proliferation, differentiation, migration, and invasion) and drug resistance (EGFR tyrosine kinase inhibitor (TKI))...
March 16, 2018: Journal of Experimental & Clinical Cancer Research: CR
Midori Tanaka, Hidenobu Ishii, Hayato Moribuchi, Yoshiko Naito, Norikazu Matsuo, Masayuki Nakamura, Takaaki Tokito, Koichi Azuma, Kazuhiko Yamada, Tomoaki Hoshino
Small-cell lung cancer (SCLC) combined with epidermal growth factor receptor (EGFR) mutations is extremely rare, and standard chemotherapeutic strategies have not yet been established. In the present study, we report a case of a 67-year-old man who presented with combined SCLC with EGFR mutation (exon 19 deletion). Systemic chemotherapy with cisplatin and irinotecan was initiated as first-line chemotherapy, and computed tomography findings revealed tumor shrinkage after two cycles of chemotherapy. However, after the third cycle of the treatment, disease progression was observed including the appearance of pleural and pericardial effusion...
March 15, 2018: Investigational New Drugs
Jing Zhu, Ying Xin, Xiaoliang Liu, Ying Wang, Ying Liu
Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancer cases worldwide. Current guidelines recommend the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for patients with NSCLC. The EGF/EGFR signaling pathway has been demonstrated to activate nuclear factor (NF)-κB, which may inhibit tumor necrosis factor (TNF)-α induced cell apoptosis. The aim of the present study was to investigate whether inhibiting the EGF/EGFR signaling pathway sensitizes NSCLC cell lines to TNF-α-induced apoptosis...
April 2018: Experimental and Therapeutic Medicine
Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
Yuta Takashima, Jun Sakakibara-Konishi, Yutaka Hatanaka, Kanako C Hatanaka, Yoshihito Ohhara, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Yoshihiro Matsuno, Masaharu Nishimura
BACKGROUND: Approximately 20% to 30% of non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC...
February 19, 2018: Clinical Lung Cancer
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