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https://www.readbyqxmd.com/read/28723866/a-case-of-resistance-to-tyrosine-kinase-inhibitor-therapy-small-cell-carcinoma-transformation-concomitant-with-plasma-genotyped-t790m-positivity
#1
Yanjun Xu, Zhiyu Huang, Lei Gong, Yun Fan
Although non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations are responsive to EGFR-tyrosine kinase inhibitors, drug resistances are always inevitable. The secondary somatic EGFR threonine-methionine substitution at position 790 (T790M) mutation accounts for ∼50% of acquired resistance mechanisms. Small cell lung cancer (SCLC) transformation is a relatively rare mechanism, but has recently attracted considerable attention. The coexistence of both the mechanisms in one patient is much more scarce in clinic...
July 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28720391/recommendations-for-the-management-of-rare-kidney-cancers
#2
REVIEW
Rachel H Giles, Toni K Choueiri, Daniel Y Heng, Laurence Albiges, James J Hsieh, W Marston Linehan, Sumanta Pal, Deborah Maskens, Bill Paseman, Eric Jonasch, Gabriel Malouf, Ana M Molina, Lisa Pickering, Brian Shuch, Sandy Srinivas, Ramaprasad Srinivasan, Nizar M Tannir, Axel Bex
CONTEXT: The European Association of Urology Renal Cell Carcinoma Guideline Panel recently conducted a systematic review of treatment options for patients with advanced non-clear-cell renal cell carcinomas (RCCs), which showed a substantial lack of evidence for management recommendations. OBJECTIVE: To improve the outcomes of patients with rare kidney cancers (RKCs), we performed a subsequent unstructured review to determine current treatment strategies and druggable pathways, involving key stakeholders with a global perspective to generate recommendations...
July 15, 2017: European Urology
https://www.readbyqxmd.com/read/28719469/insm1-demonstrates-superior-performance-to-the-individual-and-combined-use-of-synaptophysin-chromogranin-and-cd56-for-diagnosing-neuroendocrine-tumors-of-the-thoracic-cavity
#3
Lisa M Rooper, Rajni Sharma, Qing Kay Li, Peter B Illei, William H Westra
Despite the importance of recognizing neuroendocrine differentiation when diagnosing tumors of the thoracic cavity, the sensitivity of traditional neuroendocrine markers is suboptimal, particularly for high-grade neuroendocrine carcinomas such as small cell lung carcinoma and large cell neuroendocrine carcinoma. To increase sensitivity, neuroendocrine markers are routinely ordered as panels of multiple immunostains where any single positive marker is regarded as sufficient evidence of neuroendocrine differentiation...
July 17, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28719468/etv6-gene-rearrangements-characterize-a-morphologically-distinct-subset-of-sinonasal-low-grade-non-intestinal-type-adenocarcinoma-a-novel-translocation-associated-carcinoma-restricted-to-the-sinonasal-tract
#4
Simon Andreasen, Alena Skálová, Abbas Agaimy, Justin A Bishop, Jan Laco, Ilmo Leivo, Alessandro Franchi, Stine R Larsen, Daiva Erentaite, Benedicte P Ulhøi, Christian von Buchwald, Linea C Melchior, Michal Michal, Katalin Kiss
Low-grade sinonasal adenocarcinomas (low-grade SNACs) of the sinonasal tract comprise a poorly characterized and histologically heterogeneous group of tumors. We describe three cases of a histologically distinct variant of low-grade SNAC characterized by ETV6 gene rearrangements. The patients included 2 women (aged 32 and 88 y) and a man (aged 75 y); all were initially treated with surgery alone. Follow-up ranged from 9 to 170 months with one patient having 2 local recurrences and none experiencing distant or regional metastases...
July 17, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28719380/comparison-of-different-antibody-clones-for-immunohistochemistry-detection-of-programmed-cell-death-ligand-1-pd-l1-on-non-small-cell-lung-carcinoma
#5
Edwin R Parra, Pamela Villalobos, Barbara Mino, Jaime Rodriguez-Canales
Programmed cell death ligand 1 (PD-L1) is a major immune checkpoint protein that mediates antitumor immune suppression and response. Preliminary data suggest that its detection using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded tissues may predict clinical response to PD-1/PD-L1 therapy. In diagnostic pathology, it is essential to count with a validated IHC that can reliably detect PD-L1-positive cases. The present study was conducted to compare and validate different PD-L1 commercial clones and identify which ones can be reliably used by surgical pathologist to detect PD-L1 expression in human cancer tissues...
July 17, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28719055/endocrine-toxicity-of-immune-checkpoint-inhibitors-essential-crosstalk-between-endocrinologists-and-oncologists
#6
REVIEW
Frédéric Illouz, Claire Briet, Lucie Cloix, Yannick Le Corre, Nathalie Baize, Thierry Urban, Ludovic Martin, Patrice Rodien
Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T-lymphocyte antigen-4 and those that target programmed cell death-protein 1, have been approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma as first-line or second-line therapy. Their adverse events are primarily regarded as immune-related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28717395/brain-imaging-before-primary-lung-cancer-resection-a-controversial-topic
#7
Zoe Hudson, Eveline Internullo, Anthony Edey, Isabel Laurence, Davide Bianchi, Alfredo Addeo
OBJECTIVE: International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in EnglandClin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28716649/blood-platelet-volume-represents-a-novel-prognostic-factor-in-non-metastatic-renal-cell-carcinoma-patients-and-improves-the-predictive-ability-of-established-prognostic-scores
#8
Maximilian Seles, Florian Posch, Georg P Pichler, Thomas Gary, Karl Pummer, Richard Zigeuner, Georg C Hutterer, Martin Pichler
PURPOSE: The average size of blood platelets determined by the mean platelet volume (MPV), might represent a biologically meaningful parameter in carcinogenesis and potentially serve as novel prognostic biomarker in renal cell carcinoma (RCC). MATERIALS AND METHODS: In this retrospective analysis (n=652) we evaluated the potential prognostic value of MPV and its ability to improve existing risk assessment tools used in adjuvant clinical trials in non-metastatic RCC...
July 14, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28716121/identification-of-trunk-mutations-in-gastric-carcinoma-a-case-study
#9
Zhan Zhou, Shanshan Wu, Jun Lai, Yuan Shi, Chixiao Qiu, Zhe Chen, Yufeng Wang, Xun Gu, Jie Zhou, Shuqing Chen
BACKGROUND: Intratumor heterogeneity (ITH) poses an urgent challenge for cancer precision medicine because it can cause drug resistance against cancer target therapy and immunotherapy. The search for trunk mutations that are present in all cancer cells is therefore critical for each patient. CASE PRESENTATION: In this study, we aimed to evaluate the efficiency of multiregional sequencing for the identification of trunk mutations present in all regions of a tumor as a case study...
July 17, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28714960/bin1-reverses-pd-l1-mediated-immune-escape-by-inactivating-the-c-myc-and-egfr-mapk-signaling-pathways-in-non-small-cell-lung-cancer
#10
J Wang, Y Jia, S Zhao, X Zhang, X Wang, X Han, Y Wang, M Ma, J Shi, L Liu
Non-small cell lung cancer (NSCLC) is one of the most common and malignant carcinoma worldwide, and the incidence and mortality are increasing rapidly. Immunotherapy targeting programmed death 1/programmed death ligand 1 (PD-L1) signaling has shown prominent clinical effects in treating NSCLC; however, a poor understanding of the associated regulating molecular mechanisms of PD-L1 has become one of the biggest obstacles for further improving efficacy. Bridging integrator-1 (BIN1) can regulate numerous cancer-related molecules to exert multiple tumor-suppressing effects by either interacting or not interacting with c-MYC...
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28714950/tid1-s-regulates-the-mitochondrial-localization-of-egfr-in-non-small-cell-lung-carcinoma
#11
T-H Wang, Y-H Lin, S-C Yang, P-C Chang, T-Cv Wang, C-Y Chen
The epidermal growth factor receptor (EGFR) is the major driver of non-small cell lung carcinoma (NSCLC). Mitochondrial accumulation of EGFR has been shown to promote metastasis in NSCLC, yet little is known about how the mitochondrial localization of EGFR is regulated. In this work, we show that Tid1 (also known as mitochondrial HSP40) is involved in the mitochondrial localization of EGFR, and that the DnaJ domain of Tid1-S is essential for the Tid1-S-mediated transportation of EGFR into mitochondria. Overexpression of Tid1-S increased the migration and invasion of NSCLC cells cultured in vitro...
July 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28714414/role-of-mirna-in-lung-cancer-potential-biomarkers-and-therapies
#12
Xiaohong Du, Jitai Zhang, Juping Wang, Xiaoming Lin, Feng Ding
MicroRNAs (miRNAs) are small noncoding RNAs, which downregulate gene expression by repressing or degrading mRNA targets. Lung cancer (LC), together with liver and colorectal cancers are the three leading causes of cancer death worldwide, and 80% of LCs belong to non-small cell lung cancers (NSCLCs). Despite a great advancement in developing distinct and delicate tools for early diagnosis and targeted therapies over the last decade, only about 15% of the NSCLC patients eventually survived. MiRNAs are frequently dysregulated in carcinoma, including LC...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714373/targeting-mir-21-decreases-expression-of-multi-drug-resistant-genes-and-promotes-chemosensitivity-of-renal-carcinoma
#13
Kelly Gaudelot, Jean-Baptiste Gibier, Nicolas Pottier, Brigitte Hémon, Isabelle Van Seuningen, François Glowacki, Xavier Leroy, Christelle Cauffiez, Viviane Gnemmi, Sébastien Aubert, Michaël Perrais
Renal cell carcinoma, the most common neoplasm of adult kidney, accounts for about 3% of adult malignancies and is usually highly resistant to conventional therapy. MicroRNAs are a class of small non-coding RNAs, which have been previously shown to promote malignant initiation and progression. In this study, we focused our attention on miR-21, a well described oncomiR commonly upregulated in cancer. Using a cohort of 99 primary renal cell carcinoma samples, we showed that miR-21 expression in cancer tissues was higher than in adjacent non-tumor tissues whereas no significant difference was observed with stages, grades, and metastatic outcome...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28714370/phosphatase-and-tensin-homolog-deleted-on-chromosome-10-degradation-induced-by-nedd4-promotes-acquired-erlotinib-resistance-in-non-small-cell-lung-cancer
#14
Huake Sun, Huiwen Ma, Jianmin Wang, Liqin Xia, Guangkuo Zhu, Zhoufei Wang, Jianguo Sun, Zhengtang Chen
Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors, such as gefitinib and erlotinib, is a critical issue in the treatment of patients with epidermal growth factor receptor mutant-positive non-small-cell lung cancer. Recent evidence suggests that downregulation of gene of phosphatase and tensin homolog deleted on chromosome 10 plays an important role in acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in various types of cancers, including lung cancer...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28713974/mirna-125b-regulates-apoptosis-of-human-non-small-cell-lung-cancer-via-the-pi3k-akt-gsk3%C3%AE-signaling-pathway
#15
Yingyi Wang, Ming Zhao, Jieying Liu, Zhao Sun, Jianjiao Ni, Hongsheng Liu
The present investigation demonstrated that regulation of microRNA (miR)-125b affected the apoptosis of human non-small cell lung cancer (NSCLC) through targeting of the PI3K/Akt and Wnt/β-catenin signaling pathways. The expression of miR-125b was assessed in patients with NSCLC, which demonstrated that miR-125b expression in NSCLC tissue was higher than that in para-carcinoma tissue. Furthermore, survival analysis of patients with NSCLC over 3 years indicated that the overall survival (OS) and disease-free survival (DFS) rates of patients with low miR-125b expression were higher than those of patients with high miR-125b expression...
July 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28711968/local-and-systemic-immunity-predict-survival-in-patients-with-pulmonary-sarcomatoid-carcinoma
#16
Erin Schenk, Jennifer Boland, Aaron Mansfield, Marie Christine Aubry, Allan Dietz
Pulmonary sarcomatoid cancer (PSC) is a rare, aggressive subtype of non-small cell lung cancer, and measures of local and systemic immunity as biomarkers are incompletely known. We performed this study to characterize the leukocyte composition within the tumor, stroma, and peripheral blood in patients with PSC and correlated our findings with overall survival. Tissue from 30 patients diagnosed with PSC was evaluated by IHC for the presence of CD3(+), CD14(+), and CD19(+) cells and PD-L1 expression. A lymphocyte-to-monocyte ratio (LMR) was calculated for the tumor microenvironment (TME) and peripheral blood...
August 2017: Medical Oncology
https://www.readbyqxmd.com/read/28709816/-current-knowledge-on-perioperative-treatments-of-non-small-cell-lung-carcinomas
#17
REVIEW
S Brosseau, C Naltet, M Nguenang, V Gounant, P Mordant, B Milleron, Y Castier, G Zalcman
Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%...
July 11, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28707652/thermal-ablation-in-the-management-of-adrenal-metastasis-originating-from-non-small-cell-lung-cancer-a-5-year-single-center-experience
#18
Evanthia I Botsa, Ioanna L Thanou, Aspasia T Papatheodoropoulou, Loukas I Thanos
BACKGROUND: Treatment of adrenal metastasis from lung carcinoma may prolong survival in the selected patients. However, not all patients can undergo surgery; thus, minimally invasive ablation procedures such as radiofrequency ablation (RFA) and microwave ablation (MWA) have gained acceptance as alternative treatment methods. This study summarized a 5-year single-center experience regarding the evaluation of safety and efficacy of computed tomography (CT)-guided thermal ablation in the management of adrenal metastasis originating from non-small cell lung cancer (NSCLC)...
July 13, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28707167/supportive-care-for-patients-undergoing-immunotherapy
#19
Bernardo Leon Rapoport, Ronwyn van Eeden, Vincent Sibaud, Joel B Epstein, Jean Klastersky, Matti Aapro, Devan Moodley
Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents. Topics in the workshop included the mechanism of action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint inhibitor toxicities, including skin adverse events, gastrointestinal toxicities, oral complications, pulmonary toxicities, and endocrinological and immune-related infections...
July 13, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28707078/ctla-4-expression-in-the-non-small-cell-lung-cancer-patient-tumor-microenvironment-diverging-prognostic-impact-in-primary-tumors-and-lymph-node-metastases
#20
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee, Elin Richardsen, Sigurd M Hald, Sigve Andersen, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
The immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 patients with primary resected stage I-IIIA NSCLC. Expression of CTLA-4 was analyzed in tumor and stromal primary tumor tissue and in locoregional metastatic lymph nodes...
July 13, 2017: Cancer Immunology, Immunotherapy: CII
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