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non-small cell lung carcinoma

Katja Närhi, Ashwini S Nagaraj, Elina Parri, Riku Turkki, Petra W van Duijn, Annabrita Hemmes, Jenni Lahtela, Virva Uotinen, Mikko I Mäyränpää, Kaisa Salmenkivi, Jari Räsänen, Nina Linder, Jan Trapman, Antti Rannikko, Olli Kallioniemi, Taija Af Hällström, Johan Lundin, Wolfgang Sommergruber, Simon Anders, Emmy W Verschuren
A key question in precision medicine is how functional heterogeneity in solid tumors informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signaling and therapy response can be modeled in precision-cut slices from Kras-driven non-small cell lung cancer (NSCLC) of varying histopathologies. Unexpectedly, profiling of in situ tumors demonstrates that signaling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma (ASC), and MAPK activity in adenocarcinoma (AC)...
February 14, 2018: Journal of Pathology
Jeffrey M Clarke, Daniel J George, Stacey Lisi, April K S Salama
Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival...
February 13, 2018: Targeted Oncology
Young Kwang Chae, Sangmin Chang, Taeyeong Ko, Jonathan Anker, Sarita Agte, Wade Iams, Wooyoung M Choi, Kyoungmin Lee, Marcelo Cruz
Epithelial-mesenchymal transition (EMT) is able to drive metastasis during progression of multiple cancer types, including non-small cell lung cancer (NSCLC). As resistance to immunotherapy has been associated with EMT and immune exclusion in melanoma, it is important to understand alterations to T-cell infiltration and the tumor microenvironment during EMT in lung adenocarcinoma and squamous cell carcinoma. We conducted an integrated analysis of the immune landscape in NSCLCs through EMT scores derived from a previously established 16 gene signature of canonical EMT markers...
February 13, 2018: Scientific Reports
Joachim von Pawel, David R Spigel, Thomas Ervin, György Losonczy, Fabrice Barlesi, Erzsébet Juhász, Maria Anderson, Bruce McCall, Eric Wakshull, Priti Hegde, Weilan Ye, Daniel Chen, Ilsung Chang, Ina Rhee, Martin Reck
LESSONS LEARNED: The lack of efficacy associated with anti-EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non-small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations.Future efforts with agents like anti-EGFL7 should be guided by advances in pharmacodynamic and predictive biomarker development for antiangiogenic agents...
February 7, 2018: Oncologist
Marwa A Mohamed, Ehab I Mohamed, Samir A Abd El-Kaream, Mohamed I Badawi, Samy H Darwish
BACKGROUND: Evidence is increasing that microRNAs (miR) are particularly important in lung homeostasis and development and have been shown to be involved in many pulmonary diseases such as asthma, chronic obstructive pulmonary disease, sarcoidosis, lung cancer (LC) and other smoking-related diseases. OBJECTIVE: The objective of this study was to investigate the expression of miR-155 and miR-486-5p in tissues from LC patients and healthy endobronchial mucosa as prognostic biomarkers for diagnosing LC...
February 12, 2018: MicroRNA
Guoqiang Song, Honghui Lu, Fei Chen, Youmei Wang, Weibin Fan, Weifang Shao, Huoquan Lu, Bin Lin
Lung carcinoma is the leading cause of mortality due to cancer worldwide. Autophagy has a significant role in the development and progression of non‑small cell lung carcinoma (NSCLC). A previous study has revealed that tetrahydrocurcumin (THC), a traditional Chinese medicine isolated from Curcuma wenyujin (Chen & Ling, 1981), induces autophagy in human A549 NSCLC cells. The present study evaluated THC‑induced autophagy in A549 cells using various assays, including the Cell Counting Kit‑8, acridine orange staining, flow cytometry, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and western blot analysis of the markers of autophagy...
February 13, 2018: Molecular Medicine Reports
Jiangpeng Chen, Xiaoqi Dong, Xun Lei, Yinyin Xia, Qing Zeng, Ping Que, Xiaoyan Wen, Shan Hu, Bin Peng
Lung cancer is one of the most common malignant diseases and a major threat to public health on a global scale. Non-small-cell lung cancer (NSCLC) has a higher degree of malignancy and a lower 5-year survival rate compared with that of small-cell lung cancer. NSCLC may be mainly divided into two pathological subtypes, adenocarcinoma and squamous cell carcinoma. The aim of the present study was to identify disease genes based on the gene expression profile and the shortest path analysis of weighted functional protein association networks with the existing protein-protein interaction data from the Search Tool for the Retrieval of Interacting Genes...
February 2018: Molecular and Clinical Oncology
Fei Liu, Liang Hu, Yuefan Ma, Bingyu Huang, Zihan Xiu, Peihua Zhang, Keyuan Zhou, Xudong Tang
Monoamine oxidase A (MAOA), a mitochondrial enzyme, is closely associated with neurological disorders. Recently, MAOA has been linked to the progression of prostate cancer, hepatocellular carcinoma, and cholangiocarcinoma. However, MAOA was reported to have different effects on the progression of these types of cancer, and the role of MAOA in non-small cell lung cancer (NSCLC) progression remains unclear. The present study determined the expression of MAOA and epithelial to mesenchymal transition (EMT) markers in 45 pairs of NSCLC and matched non-tumor adjacent lung tissues, and further analyzed the correlation between MAOA expression and the EMT or the development of clinicopathological features...
March 2018: Oncology Letters
Hai-Ming Feng, Ye Zhao, Jian-Ping Zhang, Jian-Hua Zhang, Peng Jiang, Bin Li, Cheng Wang
Cardiolipin (CL) is a phospholipid localized in the mitochondria, which is essential for mitochondrial structure and function. Human cardiolipin synthase 1 (CRLS1) is important in regulating phosphatidylglycerol (PG) remodeling and CL biosynthesis. However, the expression and distinct prognostic value of CRLS1 in neoplasms, including non-small cell lung cancer (NSCLC), is not well established. In the present study, the mRNA expression of CRLS1 was investigated using Oncomine analysis and the prognostic value was assessed using the Kaplan-Meier plotter database for patients with NSCLC...
February 2018: Oncology Letters
Xueping Quan, Hongjun Gao, Zhikuan Wang, Jie Li, Wentao Zhao, Wei Liang, Qiang Yu, Dongliang Guo, Zhanping Hao, Jingxin Liu
Lung cancer is one of the most common types of cancer worldwide, with the highest mortality rate of all types of cancer. In the present study, epidermal growth factor receptor (EGFR) mutations of 354 primary patients with non-small cell lung cancer (NSCLC) of Chinese ethnicity were detected following formalin-fixed and paraffin-embedded specimen DNA extraction, polymerase chain reaction amplification, and sanger sequencing. The total rate of occurrence of EGFR somatic mutation in these 354 patients was 48.02%...
February 2018: Oncology Letters
Tetsuo Fujita, Takuma Hiroishi, Kohei Shikano, Asako Yanagisawa, Noriko Hayama, Hiroyuki Amano, Makoto Nakamura, Satoshi Hirano, Hiroshi Tabeta, Sukeyuki Nakamura
Background Although lung squamous cell carcinoma (SCC) accounts for 20%-30% of lung cancer cases, new treatment options are limited. The CA031 study showed that nanoparticle albumin-bound-paclitaxel (nab-PTX) plus carboplatin produced a significantly higher overall response rate (41%) than solvent-based paclitaxel plus carboplatin in patients with lung SCC. However, the safety and efficacy of combination chemotherapy of nab-PTX and carboplatin has not yet been established for patients with concurrent lung SCC and idiopathic interstitial pneumonias (IIPs)...
February 9, 2018: Internal Medicine
Monica Khunger, Prantesh Jain, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
INTRODUCTION: Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small-cell lung carcinoma (NSCLC). However, there is a relative lack of data on comparative efficacy of these drugs in the first-line setting versus chemotherapy-treated patients. We compared the efficacy and toxicity of these drugs in these 2 distinct groups of patients. MATERIALS AND METHODS: Electronic databases (PubMed-Medline, EMBASE, Scopus) and major conference proceedings were systematically searched for all phase I to III clinical trials in NSCLC using PD-1/PD-L1 inhibitors...
January 10, 2018: Clinical Lung Cancer
Jingxia Chen, Hongfen Chen, Hanbing Yang, Huizhen Dai
In this study, we investigated the functional role and prognostic value of spindle pole body component 25 (SPC25) in non-small cell lung cancer (NSCLC). SPC25 expression profile in lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and normal lung tissues was examined by using data from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA). LUAD A549 cells and LUSC H520 cells were used to investigate the influence of SPC25 on cancer stem cell (CSC) properties in terms of the proportion of CD133+ cells, tumorsphere formation and CSC markers, including CD133, ALDH1 and Sox2...
February 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jitesh B Shewale, David B Nelson, David C Rice, Boris Sepesi, Wayne L Hofstetter, Reza J Mehran, Ara A Vaporciyan, Garrett L Walsh, Stephen G Swisher, Jack Roth, Mara B Antonoff
BACKGROUND: Among patients with previous lung cancer, the malignant potential of subsequent ground glass opacities (GGOs) on computed tomography (CT) remains unknown, with a lack of consensus regarding surveillance and intervention. We sought to describe the natural history of GGO in patients with a history of lung cancer. METHODS: A retrospective review was performed of 210 patients with a history of lung cancer and ensuing CT evidence of pure or mixed GGOs between 2007 and 2013...
February 9, 2018: Annals of Thoracic Surgery
Paloma Del C Monroig-Bosque, Brandon Driver, Joel A Morales-Rosado, Michael Deavers, David Tacha, Eric Bernicker, Philip T Cagle, Ross A Miller
CONTEXT: - The interaction between programmed death ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) on activated T cells sends an inhibitory signal that dampens the immune response. Tumors can express PD-L1 and evade the immune system. In advanced non-small cell lung carcinoma, expression of PD-1 in tumor-infiltrating lymphocytes (TILs) correlates with PD-L1 expression in tumor cells (TCs). However, this relationship has not been thoroughly explored in early disease. OBJECTIVE: - To investigate the correlation of PD-1 and PD-L1 in non-small cell lung carcinoma tumor samples, with emphasis on stage I disease...
February 12, 2018: Archives of Pathology & Laboratory Medicine
Daniel J Pelletier, Thomas W Czeczok, Andrew M Bellizzi
AIMS: Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis other polyomavirus-associated diseases including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but if SV40 immunohistochemistry also cross-reacted with MCPyV that would be advantageous from a resource-utilization perspective...
February 11, 2018: Histopathology
Yanlong Yang, Kai Chen, Yongchun Zhou, Zaoxiu Hu, Shuai Chen, Yunchao Huang
Purpose: Xuanwei City is located in late Permian coal-accumulating areas of the northeastern region of Yunnan Province. In China, morbidity and mortality from lung cancer are highest in Yunnan. Identifying useful circulating markers suitable for the diagnosis of lung cancer in this region is quite meaningful. In this study, we evaluated diagnostic roles of serum miR-9-5p, 21-5p, 223-3p, 135b-5p, 339-5p, and 501-5p in patients with non-small-cell lung cancer (NSCLC) in Yunnan. Moreover, we evaluated the diagnostic performance of several tumor markers, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), and squamous cell carcinoma-related antigen (SCC)...
2018: OncoTargets and Therapy
Ezra Ella, Yaniv Harel, Michal Abraham, Hanna Wald, Ofra Benny, Adi Karsch-Bluman, Dive Vincent, Devel Laurent, Gail Amir, Uzi Izhar, Oz M Shapira, David Yoon, Hyun-Sung Lee, David J Sugarbaker, Bryan Burt, Amnon Peled, Ori Wald
OBJECTIVE: Past studies are inconsistent with regard to the role of matrix metalloproteinase 12 in lung tumorigenesis. This is due, in part, to differential tumorigenesis based on tumor-derived versus immune-derived matrix metalloproteinase 12 expression. Our study aims to thoroughly dissect the role of matrix metalloproteinase 12 in lung tumorigenesis. METHODS: We tested matrix metalloproteinase 12 expression and the association with prognosis using a tissue array and a published non-small cell lung cancer gene expression database...
February 8, 2018: Journal of Thoracic and Cardiovascular Surgery
Mark Chan, Matthew Wong, Ronnie Leung, Steven Cheung, Oliver Blanck
BACKGROUND: To derive and exploit the optimal prescription isodose level (PIL) in inverse optimization of volumetric modulated arc radiotherapy (VMAT) as a potential approach to dose de-escalation in stereotactic body radiotherapy for non-small cell lung carcinomas (NSCLC). METHODS: For ten patients, inverse Monte Carlo dose optimization was performed to cover 95% PTV by varying prescription isodose lines (PIL) at 60 to 80% and reference 85%. Subsequently, these were re-normalized to the median gross tumor volume dose (GTV-based prescription) to assess the impacts of PTV and normal tissue dose reduction...
February 9, 2018: Radiation Oncology
Jing He, Lei Huo, Junsheng Ma, Jun Zhao, Roland L Bassett, Xiaoping Sun, Naoto T Ueno, Bora Lim, Yun Gong
Objectives: Inflammatory breast carcinoma (IBC) is rare but is the most lethal type of breast cancer. Programmed death ligand 1 (PD-L1) expression in IBCs has been understudied. Methods: In this study, tissue microarrays of 68 IBCs were immunostained with a PD-L1 antibody using an antibody clone (28-8) and detection system approved by the US Food and Drug Administration for selecting patients with non-small cell lung cancer and melanoma for anti-PD-L1 therapy. Results: Positive PD-L1 expression was found in 25 (36...
February 7, 2018: American Journal of Clinical Pathology
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