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https://www.readbyqxmd.com/read/28891712/molecular-and-clinical-features-of-second-generation-anaplastic-lymphoma-kinase-inhibitors-ceritinib
#1
Tommaso De Pas, Laura Pala, Chiara Catania, Fabio Conforti
The discovery of ALK rearrangement in non-small-cell lung cancer (NSCLC) triggered rapid clinical development of a family of specific drugs targeting this alteration, called ALK inhibitors. Despite high rate of responses, the vast majority of patients treated with first-generation ALK inhibitor crizotinib will ultimately develop disease progression. The second-generation ALK inhibitor, ceritinib, is an oral, small-molecule that inhibits the ALK kinase activity with a potency 20-fold greater than crizotinib, being able to tackle some of the principal mechanisms of resistance to crizotinib...
September 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28883747/proton-beam-therapy-in-non-small-cell-lung-cancer-state-of-the-art
#2
REVIEW
Hideyuki Harada, Shigeyuki Murayama
This review summarizes the past and present status of proton beam therapy (PBT) for lung cancer. PBT has a unique characteristic called the Bragg peak that enables a reduction in the dose of normal tissue around the tumor, but is sensitive to the uncertainties of density changes. The heterogeneity in electron density for thoracic lesions, such as those in the lung and mediastinum, and tumor movement according to respiration necessitates respiratory management for PBT to be applied in lung cancer patients. There are two types of PBT - a passively scattered approach and a scanning approach...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28862766/genomic-profiles-of-lung-cancer-associated-with-idiopathic-pulmonary-fibrosis
#3
Ji An Hwang, Deokhoon Kim, Sung-Min Chun, SooHyun Bae, Joon Seon Song, Mi Young Kim, Hyun Jung Koo, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang
Little is known on the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC using targeted exome sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively...
September 1, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28860940/limbic-encephalitis-a%C3%A2-report-of-four-cases
#4
Żanna Pastuszak, Adam Stępień, Kazimierz Tomczykiewicz, Renata Piusińska-Macoch, Joanna Kordowska, Dariusz Galbarczyk, Jarosław Świstak
Usually limbic encephalitis (LE) is a paraneoplastic neurologic syndrome. LE symptoms can precede cancer even by a few years. Almost 50% of LE cases are connected with small cell lung carcinoma. Testis and breast cancers, granulomatous disease, thymoma, and teratomas are also often connected with LE. Other cases have infectious and autoimmunological aetiology. In LE limbic system dysfunction is observed, and it is accompanied by cerebellum and brain stem abnormalities as well as polyneuropathy. Paraneoplastic limbic encephalitis is sometimes a part of larger syndrome in which brain stem and spinal cord are involved in an inflammatory process called paraneoplastic encephalomyelitis...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28859986/kribb11-accelerates-mcl-1-degradation-through-an-hsf1-independent-mule-dependent-pathway-in-a549-non-small-cell-lung-cancer-cells
#5
Min-Jung Kang, Hye Hyeon Yun, Jeong-Hwa Lee
The Bcl-2 family protein, Mcl-1 is known to have anti-apoptotic functions, and depletion of Mcl-1 by cellular stresses favors the apoptotic process. Moreover, Mcl-1 levels are frequently increased in various cancer cells, including non-small cell lung cancer (NSCLC), and is implicated in resistance to conventional chemotherapy and in cancer metastasis. In this study, we demonstrated that KRIBB11 accelerates the proteasomal degradation of Mcl-1 in the NSCLC cell line, A549. While KRIBB11 is an inhibitor of HSF1, we found that KRIBB11 induced Mcl-1 degradation in an HSF1-independent manner...
August 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28825843/immunopet-imaging-of-cd146-in-murine-models-of-intrapulmonary-metastasis-of-non-small-cell-lung-cancer
#6
Christopher Gene England, Dawei Jiang, Reinier Hernandez, Haiyan Sun, Hector F Valdovinos, Emily B Ehlerding, Jonathan W Engle, Yunan Yang, Peng Huang, Weibo Cai
CD146 has been identified as an excellent biomarker for lung cancer as its overexpression in solid tumors has been linked to disease progression, invasion, and metastasis. Previously, our group described a positive correlation between (64)Cu-labeled YY146 uptake and increased expression of CD146 in six human lung cancer cell lines using subcutaneous tumor models. In this study, we investigate a monoclonal antibody called YY146 for immunoPET imaging of CD146 in two intrapulmonary metastasis models of non-small cell lung cancer (NSCLC)...
August 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28820254/blockade-of-asparagine-endopeptidase-inhibits-cancer-metastasis
#7
Qi Qi, Obiamaka Obianyo, Yuhong Du, Haian Fu, Shiyong Li, Keqiang Ye
Asparagine endopeptidase (AEP), also called legumain, is highly expressed in various solid tumors, promoting cancer cell invasion, migration, and metastasis. It has been proposed to be a prognostic marker and therapeutic target for cancer treatment. However, an effective nonpeptide, small-molecule inhibitor against this protease has not yet been identified. Here we show that a family of xanthine derivatives selectively inhibit AEP and suppress matrix metalloproteinase (MMP) cleavage, leading to the inhibition of cancer metastasis...
September 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28797700/4dct-imaging-to-assess-radiomics-feature-stability-an-investigation-for-thoracic-cancers
#8
Ruben T H M Larue, Lien Van De Voorde, Janna E van Timmeren, Ralph T H Leijenaar, Maaike Berbée, Meindert N Sosef, Wendy M J Schreurs, Wouter van Elmpt, Philippe Lambin
BACKGROUND AND PURPOSE: Quantitative tissue characteristics derived from medical images, also called radiomics, contain valuable prognostic information in several tumour-sites. The large number of features available increases the risk of overfitting. Typically test-retest CT-scans are used to reduce dimensionality and select robust features. However, these scans are not always available. We propose to use different phases of respiratory-correlated 4D CT-scans (4DCT) as alternative. MATERIALS AND METHODS: In test-retest CT-scans of 26 non-small cell lung cancer (NSCLC) patients and 4DCT-scans (8 breathing phases) of 20 NSCLC and 20 oesophageal cancer patients, 1045 radiomics features of the primary tumours were calculated...
August 7, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28790336/identifying-the-mirna-signature-associated-with-survival-time-in-patients-with-lung-adenocarcinoma-using-mirna-expression-profiles
#9
Srinivasulu Yerukala Sathipati, Shinn-Ying Ho
Lung adenocarcinoma is a multifactorial disease. MicroRNA (miRNA) expression profiles are extensively used for discovering potential theranostic biomarkers of lung cancer. This work proposes an optimized support vector regression (SVR) method called SVR-LUAD to simultaneously identify a set of miRNAs referred to the miRNA signature for estimating the survival time of lung adenocarcinoma patients using their miRNA expression profiles. SVR-LUAD uses an inheritable bi-objective combinatorial genetic algorithm to identify a small set of informative miRNAs cooperating with SVR by maximizing estimation accuracy...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760000/cholesterol-derivative-based-liposomes-for-gemcitabine-delivery-preparation-in-vitro-and-in-vivo-characterization
#10
Tang Li, Li Chen, Yihui Deng, Xinrong Liu, Xiaoyun Zhao, Yiwen Cui, Jia Shi, Rui Feng, Yanzhi Song
As an anti-tumor drug, gemcitabine (Gem) is commonly used for the treatment of non-small cell lung cancer and pancreatic cancer. However, there are several clinical drawbacks to using Gem, including its extremely short plasma half-life and side effects. To prolong its half-life and reduce its side effects, we synthesized a derivative of Gem using cholesterol (Chol). This derivative, called gemcitabine-cholesterol (Gem-Chol) was entrapped into liposomes by a thin-film dispersion method. The particle size of the Gem-Chol liposomes was 112...
August 1, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28723342/molecular-analysis-of-circulating-free-dna-from-lung-cancer-patients-in-routine-laboratory-practice-a-cross-platform-comparison-of-three-different-molecular-methods-for-mutation-detection
#11
Stephan Bartels, Sascha Persing, Britta Hasemeier, Elisa Schipper, Hans Kreipe, Ulrich Lehmann
Cell-free DNA (cfDNA), which is isolated from blood plasma, represents a noninvasive source for the detection of mutations conferring resistance against epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small-cell lung cancer patients. In advanced disease stages, performing regular biopsies is often not possible because of the general health condition of the patients. Furthermore, a biopsy of a single tumor lesion or metastasis may not reflect the heterogeneous genotype of the tumor and its metastases...
July 16, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28721899/gaps-in-radiation-therapy-awareness-results-from-an-educational-multi-institutional-survey-of-us-internal-medicine-residents
#12
MULTICENTER STUDY
Narek Shaverdian, Sun Mi Yoo, Ryan Cook, Eric M Chang, Naomi Jiang, Ye Yuan, Kiri Sandler, Michael Steinberg, Percy Lee
PURPOSE: Internists and primary care providers play a growing role in cancer care. We therefore evaluated the awareness of radiation therapy in general and specifically the clinical utility of stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) among current US internal medicine residents. METHODS AND MATERIALS: A web-based institutional review board-approved multi-institutional survey was distributed to US internal medicine residency programs...
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28712978/local-radiotherapy-intensification-for-locally-advanced-non-small-cell-lung-cancer-a-call-to-arms
#13
REVIEW
Noah S Kalman, Elisabeth Weiss, Paul R Walker, Julian G Rosenman
Chemoradiotherapy, the standard of care for locally advanced non-small-cell lung cancer (NSCLC), often fails to eradicate all known disease. Despite advances in chemotherapeutic regimens, locally advanced NSCLC remains a difficult disease to treat, and locoregional failure remains common. Improved radiographic detection can identify patients at significant risk of locoregional failure after definitive treatment, and newer methods of escalating locoregional treatment may allow for improvements in locoregional control with acceptable toxicity...
June 16, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28696308/tsrna-signatures-in-cancer
#14
Veronica Balatti, Giovanni Nigita, Dario Veneziano, Alessandra Drusco, Gary S Stein, Terri L Messier, Nicholas H Farina, Jane B Lian, Luisa Tomasello, Chang-Gong Liu, Alexey Palamarchuk, Jonathan R Hart, Catherine Bell, Mariantonia Carosi, Edoardo Pescarmona, Letizia Perracchio, Maria Diodoro, Andrea Russo, Anna Antenucci, Paolo Visca, Antonio Ciardi, Curtis C Harris, Peter K Vogt, Yuri Pekarsky, Carlo M Croce
Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that the ts-4521/3676 cluster (now called "ts-101" and "ts-53," respectively), ts-46, and ts-47 are down-regulated in these malignancies...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28692419/long-term-cigarette-smoke-exposure-and-changes-in-mirna-expression-and-proteome-in-non-small-cell-lung-cancer
#15
Jayshree Advani, Yashwanth Subbannayya, Krishna Patel, Aafaque Ahmad Khan, Arun H Patil, Ankit P Jain, Hitendra S Solanki, Aneesha Radhakrishnan, Sneha M Pinto, Nandini A Sahasrabuddhe, Joji K Thomas, Premendu P Mathur, Bipin G Nair, Xiaofei Chang, T S Keshava Prasad, David Sidransky, Harsha Gowda, Aditi Chatterjee
Chronic exposure to cigarette smoke markedly increases the risk for lung cancer. Regulation of gene expression at the post-transcriptional level by miRNAs influences a variety of cancer-related interactomes. Yet, relatively little is known on the effects of long-term cigarette smoke exposure on miRNA expression and gene regulation. NCI-H292 (H292) is a cell line sensitive to cigarette smoke with mucoepidermoid characteristics in culture. We report, in this study, original observations on long-term (12 months) cigarette smoke effects in the H292 cell line, using microarray-based miRNA expression profiling, and stable isotopic labeling with amino acids in cell culture-based quantitative proteomic analysis...
July 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#16
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28637023/cationic-liquid-crystalline-nanoparticles-for-the-delivery-of-synthetic-rnai-based-therapeutics
#17
Emanuela Gentile, Taro Oba, Jing Lin, Ruping Shao, Feng Meng, Xiaobo Cao, Heather Y Lin, Majidi Mourad, Apar Pataer, Veerabhadran Baladandayuthapani, Dong Cai, Jack A Roth, Lin Ji
RNA interference (RNAi)-based therapeutics have been used to silence the expression of targeted pathological genes. Small interfering RNA (siRNAs) and microRNA (miRNAs) inhibitor have performed this function. However, short half-life, poor cellular uptake, and nonspecific distribution of small RNAs call for the development of novel delivery systems to facilitate the use of RNAi. We developed a novel cationic liquid crystalline nanoparticle (CLCN) to efficiently deliver synthetic siRNAs and miRNAs. CLCNs were prepared by using high-speed homogenization and assembled with synthetic siRNA or miRNA molecules in nuclease-free water to create CLCN/siRNA or miRNA complexes...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28613923/the-era-of-checkpoint-blockade-in-lung-cancer-taking-the-brakes-off-the-immune-system
#18
Edmund K Moon, Corey J Langer, Steven M Albelda
Despite recent advances with targeted kinase inhibitors and better-tolerated chemotherapy, the treatment of metastatic non-small-cell lung cancer remains suboptimal. One recent advance that holds great promise is immunotherapy-an approach that enhances a patient's immune system to better recognize and react to abnormal cells. The most successful immunotherapeutic strategy to date uses antibodies to block inhibitory receptors (also called "checkpoints") that are up-regulated on the T cells that infiltrate the tumor...
August 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28612050/a-rapid-segmentation-insensitive-digital-biopsy-method-for-radiomic-feature-extraction-method-and-pilot-study-using-ct-images-of-non-small-cell-lung-cancer
#19
Sebastian Echegaray, Viswam Nair, Michael Kadoch, Ann Leung, Daniel Rubin, Olivier Gevaert, Sandy Napel
Quantitative imaging approaches compute features within images' regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called "digital biopsy," that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non-small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule...
December 2016: Tomography: a Journal for Imaging Research
https://www.readbyqxmd.com/read/28609759/combination-of-platelet-count-and-lymphocyte-to-monocyte-ratio-is-a-prognostic-factor-in-patients-undergoing-surgery-for-non-small-cell-lung-cancer
#20
Wei Liu, Minwen Ha, Nanchang Yin
The aim of this study was to investigate the usefulness of a novel inflammation-based prognostic system, called COP-LMR (combination of platelet count and lymphocyte to monocyte ratio), for predicting postoperative survival of patients with non-small cell lung cancer (NSCLC). COP-LMR was calculated on the basis of the obtained data. Patients with both an elevated platelet count (PLT) (>30 × 104mm-3) and a low LMR (<3.6) were assigned a score of 2, and patients with one or none of the parameters were assigned a score of 1 or 0, respectively...
June 1, 2017: Oncotarget
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