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Nsclc molecular markers

Luca Mazzarella, Alessandro Guida, Giuseppe Curigliano
Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials...
March 14, 2018: Expert Opinion on Biological Therapy
Edwin Roger Parra, Pamela Villalobos, Jiexin Zhang, Carmen Behrens, Barbara Mino, Stephen Swisher, Boris Sepesi, Annika Weissferdt, Neda Kalhor, John Victor Heymach, Cesar Moran, Jianjun Zhang, Jack Lee, Jaime Rodriguez-Canales, Don Gibbons, Ignacio Ivan Wistuba
BACKGROUND: The understanding of immune checkpoint molecules' co-expression in non-small cell lung carcinoma (NSCLC) is important to potentially design combinatorial immunotherapy approaches. MATERIAL AND METHODS: We studied 225 formalin-fixed, paraffin-embedded tumor tissues from stage I-III NSCLCs-142 adenocarcinomas (ADCs) and 83 squamous cell carcinomas (SCCs)-placed in tissue microarrays. Nine immune checkpoint markers were evaluated; 4 (PD-L1, B7-H3, B7-H4, and IDO-1) expressed predominantly in malignant cells (MCs) and 5 (ICOS, VISTA, TIM3, LAG3, and OX40) expressed mostly in stromal tumor-associated inflammatory cells (TAICs)...
March 8, 2018: Journal of Thoracic Oncology
Marta Román, Iosune Baraibar, Inés López, Ernest Nadal, Christian Rolfo, Silvestre Vicent, Ignacio Gil-Bazo
Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the majority of patients present advanced disease at onset. However, in the last decade, multiple oncogenic driver alterations have been discovered and each of them represents a potential therapeutic target. Although KRAS mutations are the most frequently oncogene aberrations in lung adenocarcinoma patients, effective therapies targeting KRAS have yet to be developed...
February 19, 2018: Molecular Cancer
Tatjana Vlajnic, Spasenija Savic, Audrey Barascud, Betty Baschiera, Michel Bihl, Bruno Grilli, Michelle Herzog, Julien Rebetez, Lukas Bubendorf
BACKGROUND: Rearrangements of the ROS1 oncogene are found in 1% to 2% of non-small cell lung cancers (NSCLC) and are regarded as mutually exclusive oncogenic driver mutations. Since the approval of targeted therapy for ROS1-positive NSCLC, ROS1 testing has become a part of the diagnostic routine. Fluorescence in situ hybridization (FISH), optionally selected for by immunohistochemistry on histological material, is a common practice for the detection of ROS1 rearrangements. However, NSCLC often is diagnosed by cytology alone, requiring predictive marker testing on cytological specimens...
February 16, 2018: Cancer Cytopathology
Xing-Guang Wang, Na-Xin Yuan, Xin-Peng Li, Fang-Fang Chen
Cancer initiating cell (CIC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in lung cancer cell invasion and metastasis. They have been shown to occur in gefitinib resistance. Studying the molecular mechanisms of CICs, EMT and acquired gefitinib resistance will enhance the understanding of the pathogenesis and progression of the disease and offer novel targets for effective therapies. TWIK-related acid-sensitive K(+) (TASK-1) is expressed in a subset of non-small-cell lung cancer (NSCLC) cell lines, where it promotes cell proliferation while inhibiting apoptosis...
January 2018: Experimental and Therapeutic Medicine
Donghua Wu, Baofeng Zhao, Xiaoyu Qi, Fang Peng, Hailu Fu, Xinming Chi, Qing Robert Miao, Shujuan Shao
Nogo-B receptor (NgBR) is a specific receptor of Nogo-B that regulates vascular remodeling and angiogenesis. Previously, we found that NgBR promotes the membrane translocation and activation of Ras in breast cancer cells and enhances the chemoresistance of hepatocellular carcinoma cells to 5-fluorouracil. However, the role of NgBR in lung cancer has not yet been elucidated. In the present study, we found that NgBR knockdown inhibited epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells in vitro and metastasis of NSCLC cells in vivo...
January 10, 2018: Cancer Letters
Sarah Jo Stephens, Michael J Moravan, Joseph K Salama
Metastatic lung cancer has long been considered incurable, with the goal of treatment being palliation. However, a clinically meaningful number of these patients with limited metastases (approximately 25%) are living long term after definitive treatment to all sites of active disease. These patients with so-called oligometastatic disease likely represent a distinct clinical group who may possess a more indolent biology compared with their more widely metastatic counterparts. Hellman and Weichselbaum proposed the existence of the oligometastatic state, on the basis of the spectrum theory of cancer spread...
January 2018: Journal of Oncology Practice
Niraj Babu, Jayshree Advani, Hitendra S Solanki, Krishna Patel, Ankit P Jain, Aafaque Ahmad Khan, Aneesha Radhakrishnan, Nandini A Sahasrabuddhe, Premendu Prakash Mathur, Bipin Nair, T S Keshava Prasad, Xiaofei Chang, David Sidransky, Harsha Gowda, Aditi Chatterjee
BACKGROUND: Dysregulation of miRNAs is associated with the development of non-small cell lung cancer (NSCLC). It is imperative to study the dysregulation of miRNAs by cigarette smoke which will affect their targets, either leading to the overexpression of oncoproteins or downregulation of tumor suppressor proteins. OBJECTIVE AND METHODS: In this study, we carried out miRNA sequencing and SILAC-based proteomic analysis of H358 cells chronically exposed to cigarette smoke condensate...
January 3, 2018: MicroRNA
Xiangjun Guo, Jiaxin Shi, Yan Wen, Mengmeng Li, Qin Li, Xiaomei Li, Jiashu Li
BACKGROUND: High-mobility group A2 (HMGA2) has been investigated to be associated with tumorigenesis; however, the expression pattern and clinical significance of HMGA2 in non-small cell lung cancer (NSCLC) remains poorly understood. The purpose of this study is to examine the expression of HMGA2 and to analyze its relationships with respect to clinico-pathological features and patient survival in NSCLC. METHODS: The expression level of HMGA2 was examined by Western blot and immunohistochemistry in NSCLC cells and tissues...
December 15, 2017: Cancer Biomarkers: Section A of Disease Markers
Hanbo Le, Xiaoling Wang, Yao Zha, Jie Wang, Wangyu Zhu, Zhinan Ye, Xiaoguang Liu, Haijie Ma, Yongkui Zhang
Lung adenocarcinoma, characterized by its early and aggressive local invasion and high metastatic potential, is the most frequently observed histological type of non-small-cell lung cancer (NSCLC). Visceral pleural invasion (VPI) caused by peripheral lung adenocarcinomas is closely associated with the poor prognosis of patients with NSCLC. The association between VPI and some clinicopathological characteristics has been observed in the past few decades. However, the molecular mechanism of VPI in lung adenocarcinomas is unknown...
December 2017: Oncology Letters
Balaji Chandrasekaran, Ashish Tyagi, Arun K Sharma, Lu Cai, Murali Ankem, Chendil Damodaran
Epidermal growth factor receptor (EGFR) activation events and the mammalian target of rampamycin (mTOR) are considered important therapeutic targets in alleviating cancer conditions. The current treatment paradigm has shifted to personalized treatment strategies with tyrosine kinase inhibitors (TKIs) or anaplastic lymphoma kinase (ALK) inhibitors, due to low survival rates in non-small cell lung cancer (NSCLC) in terms of the prevailing platinum-based therapy. In the present study, we examined the anticancer potential of Verrucarin J (VJ), a small molecule, in NSCLC cell lines (H460 and A549)...
September 2017: Genes & Cancer
F Wang, J-G Chen, L-L Wang, Z-Z Yan, S-P Chen, X-G Wang
OBJECTIVE: To investigate the expression levels of LINCRNA00346 in tissues and cells in patients with non-small cell lung cancer (NSCLC) and its biological function. PATIENTS AND METHODS: The relative expression levels of LINC 00346 in 70 cases of tissues and cells in NSCLC patients were detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). The specific interference sequences of LINC 00346 were designed and the transfection efficiency after 48 h was detected...
November 2017: European Review for Medical and Pharmacological Sciences
Meng Xu-Welliver, David P Carbone
Despite recent advances, non-small cell lung cancer (NSCLC) remains a devastating disease with overall poor prognosis. Major contributing factors include obstacles to diagnosing the disease early in its course during the asymptomatic stage as well as diversity and complexity of its biology underlying tumorigenesis and tumor progression. Advances in molecularly targeted therapies which drives the development of personalized cancer care require precise and comprehensive understanding of tumor biology, not only at the time of diagnosis but also during treatment course and surveillance...
December 2017: Translational Lung Cancer Research
Xiaobin Guo, Limin Zhao, Dongjun Cheng, Qing Mu, Hongyan Kuang, Keqing Feng
Non-small-cell lung cancer (NSCLC) is one of the leading death-related malignancies worldwide with elusive molecular mechanisms. A-kinase interacting protein 1 (AKIP1) is an important regulator controlling metastasis, lymphangiogenesis and angiogenesis. However, the role of AKIP1 in NSCLC progression is still little known. Here, we found that AKIP1 was overexpressed in NSCLC specimens as well as cell lines. Overexpression of AKIP1 in NSLCC tissues was positively correlated with TNM stage, lymph node metastasis and poor prognosis...
2017: American Journal of Cancer Research
Cristina Raimondi, Guido Carpino, Chiara Nicolazzo, Angela Gradilone, Walter Gianni, Alain Gelibter, Eugenio Gaudio, Enrico Cortesi, Paola Gazzaniga
The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway has emerged as a critical inhibitory pathway regulating T-cell response in non-small-cell lung cancer (NSCLC), and the development of PD-1/PD-L1 inhibitors has changed the landscape of NSCLC therapy. Nevertheless, the high degree of non-responders demonstrates that we are still far from completely understanding the events underlying tumor immune resistance. Although the expression of PD-L1 in tumor tissue has been correlated with clinical response to anti PD-1 inhibitors, the ability of this marker to discriminate the subgroup of patients who derive benefit from immunotherapy is suboptimal...
2017: Oncoimmunology
Haochang Hu, Xiaoying Chen, Cong Zhou, Bin Li, Yong Yang, Xiuru Ying, Yiyi Mao, Yihan Zhang, Jie Zhong, Jie Dai, Hang Yu, Boyi Wu, Xiaodong Li, Tiangong Wang, Shiwei Duan
BACKGROUND: Non-small cell lung cancer (NSCLC) is a common malignant tumor. DNA hypermethylation in the promoter region has been served as a potential molecular marker for several tumors. The goal of the current study was to assess the diagnostic ability of mutL homolog 1 (MLH1) promoter methylation in NSCLC. METHODS: A total of 111 NSCLC patients' paired tissue samples were obtained to explore the association between MLH1 promoter methylation and NSCLC by methylation-specific polymerase chain reaction (MSP) method...
December 5, 2017: Journal of Clinical Laboratory Analysis
Franz Villarroel-Espindola, Xiaoqing Yu, Ila Datar, Nikita Mani, Miguel Sanmamed, Vamsidhar Velcheti, Konstantinos Syrigos, Maria Toki, Hongyu Zhao, Lieping Chen, Roy S Herbst, Kurt A Schalper
Purpose: Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human non-small cell lung cancer (NSCLC). Experimental Design: Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1, and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T cells, CD4+ T-helper cells, CD8+ cytotoxic T cells, CD20+ B lymphocytes and CD68+ tumor-associated macrophages...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Lais Osmani, Frederic Askin, Edward Gabrielson, Qing Kay Li
Recent large scale genomic studies from the Clinical Lung Cancer Genome Project have identified different driver gene mutations in the subtypes of non-small cell lung carcinoma (NSCLC). These findings not only lead to remarkable progress in targeted therapies for lung cancer patients, but also provide fundamental knowledge for the subclassification of NSCLC. More recently, the advancement and clinical application of immunotherapy have reinforced the need for the accurate subclassification of NSCLC. In 2015, the World Health Organization (WHO) and the International Association for the Study of Lung Cancer (IASLC) updated their guidelines for the subclassification of lung cancers...
November 26, 2017: Seminars in Cancer Biology
Ritika Walia, Deepali Jain, Karan Madan, Mehar C Sharma, Sandeep R Mathur, Anant Mohan, Venkateswaran K Iyer, Lalit Kumar
BACKGROUND & OBJECTIVES: Accurate histopathological subtyping of non-small cell lung carcinoma (NSCLC) is essential for targeted therapeutic agents. Immunohistochemistry (IHC) is helpful in identification of different tumour subtypes. In this study two marker approaches, one each for glandular and squamous cell differentiation was applied to maximize the proportion of accurately subtyped NSCLC not otherwise specified (NOS) tumours on small biopsy samples. METHODS: Two hundred and sixty three consecutive lung biopsies of primary lung carcinoma were prospectively studied...
July 2017: Indian Journal of Medical Research
Yingchang Li, Zhihua Ye, Shuai Chen, Zhiwen Pan, Qianghua Zhou, Yi-Zhuo Li, Wen-di Shuai, Chun-Mei Kuang, Qi-Hua Peng, Wei Shi, Xueli Mao, Ran-Yi Liu, Wenlin Huang
Rho guanine nucleotide exchange factors (RhoGEFs) are proteins that activate Rho GTPases in response to extracellular stimuli and regulate various biologic processes. ARHGEF19, one of RhoGEFs, was reported to activate RhoA in the Wnt-PCP pathway controlling convergent extension in Xenopus gastrulation. The goal of our study was to identify the role and molecular mechanisms of ARHGEF19 in the tumorigenesis of non-small cell lung cancer (NSCLC). ARHGEF19 expression was significantly elevated in NSCLC tissues, and ARHGEF19 levels were significantly associated with lymph node status, distant metastasis and TNM stage; Patients with high ARHGEF19 levels had poor overall survival (OS) and progression-free survival (PFS)...
April 1, 2018: International Journal of Cancer. Journal International du Cancer
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