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https://www.readbyqxmd.com/read/29790694/advances-in-antibody-therapeutics-targeting-small-cell-lung-cancer
#1
REVIEW
Hongyang Lu, Zhiming Jiang
The proportion of small-cell lung cancer (SCLC) among all lung cancers decreased from 17.26% in 1986 to 12.95% in 2002. Chemotherapy is the key mode of treatment. However, novel therapeutic strategies and drugs are imperative, as the prognosis remains poor. In recent years, antibody therapies have shown promising prospects against malignancy. This review focuses on the advances in antibody therapies in SCLC. Although the results of pembrolizumab, nivolumab, ipilimumab, and rovalpituzumab tesirine are inspiring, all of the clinical trials on these drugs are phase I/II and have been verified for further phase III clinical trials...
May 16, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29789013/prognostic-significance-of-pd-l1-expression-and-cd8-t-cell-infiltration-in-pulmonary-neuroendocrine-tumors
#2
Haiyue Wang, Zhongwu Li, Bin Dong, Wei Sun, Xin Yang, Ruping Liu, Lixin Zhou, Xiaozheng Huang, Ling Jia, Dongmei Lin
BACKGROUND: Recent research supports a significant role of immune checkpoint inhibitors in the treatment of solid tumors. However, relevant reports for programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) in pulmonary neuroendocrine tumors (PNETs) have not been fully studied. Therefore, we investigated PNETs for the expression of PD-L1 and infiltration by CD8+ TILs as well as the prognostic value of both factors. METHODS: In total, 159 specimens of PNETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included in this study...
May 22, 2018: Diagnostic Pathology
https://www.readbyqxmd.com/read/29787820/clinicopathological-characteristics-of-thyroid-transcription-factor-1-negative-small-cell-lung-cancers
#3
Yuko Iida, Shinobu Masuda, Yoko Nakanishi, Tetsuo Shimizu, Haruna Nishimaki, Mai Takahashi, Mari Hikichi, Shuichiro Maruoka, Yasuhiro Gon, Noriaki Takahashi, Shu Hashimoto
Limitations in obtaining surgically resected or biopsy samples of small cell lung cancer (SCLC) tumors make comprehensive biological analyses difficult. The loss of thyroid transcription factor 1 (TTF-1) has been associated with the aggressive behavior of non-small cell lung cancer (NSCLC); however, clinicopathological features of TTF-1-negative SCLC remain unclear. This study aimed to elucidate the characteristics of TTF-1-negative SCLC. We studied the associations between the expression of TTF-1 and the clinicopathological factors associated with SCLC, including survival and expression of neuroendocrine markers (synaptophysin, chromogranin A, and CD56), neuroendocrine cell-specific transcription factors (achaete-scute homolog like 1 (ASCL1), BRN2), a proliferation marker (Ki-67 labeling index), and an oncogene (Nuclear Factor 1B (NF1B))...
May 19, 2018: Human Pathology
https://www.readbyqxmd.com/read/29776963/combined-vegf-and-pd-l1-blockade-displays-synergistic-treatment-effects-in-an-autochthonous-mouse-model-of-small-cell-lung-cancer
#4
Lydia Meder, Philipp Schuldt, Martin Thelen, Anna Schmitt, Felix Dietlein, Sebastian Klein, Sven Borchmann, Kerstin Wennhold, Ignacija Vlasic, Sebastian Oberbeck, Richard Riedel, Alexandra Florin, Kristina Golfmann, Hans Anton Schlößer, Margarete Odenthal, Reinhard Büttner, Juergen Wolf, Michael Hallek, Marco Herling, Michael von Bergwelt-Baildon, Hans Christian Reinhardt, Roland T Ullrich
Small cell lung cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. We show in an autochthonous mouse model of SCLC that combined anti-VEGF/anti-PD-L1 targeted therapy synergistically improves treatment outcome compared to anti-PD-L1 and anti-VEGF monotherapy. Mice treated with anti-PD-L1 alone relapsed after 3 weeks and were associated with a tumor-associated PD-1/TIM-3 double positive exhausted T cell phenotype...
May 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29775808/phase-ii-study-of-maintenance-pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-sclc
#5
Shirish M Gadgeel, Nathan A Pennell, Mary Jo Fidler, Balazs Halmos, Philip Bonomi, James Stevenson, Bryan Schneider, Ammar Sukari, Jaclyn Ventimiglia, Wei Chen, Cathy Galasso, Antoinette Wozniak, Julie Boerner, Gregory P Kalemkerian
PURPOSE: To assess the efficacy of maintenance pembrolizumab in extensive-stage small cell lung cancer (SCLC) patients, after treatment with platinum/etoposide. PATIENTS AND METHODS: Extensive-stage SCLC patients with a response or stable disease following induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg IV every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary endpoint of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary endpoint...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29774395/early-versus-late-prophylactic-cranial-irradiation-in-patients-with-extensive-small-cell-lung-cancer
#6
Yi Chen, Jinyu Li, Yibao Zhang, Yi Hu, Guoqing Zhang, Xiang Yan, Zhi Lin, Zhifei Zhao, Shunchang Jiao
OBJECTIVE: Previous studies demonstrated that prophylactic cranial irradiation (PCI) significantly reduced the incidence of brain metastases in patients with extensive disease small cell lung cancer (ED-SCLC). However, the appropriate timing for PCI in treating ED-SCLC is still unclear. This study aimed to compare the effect and safety of early versus late PCI. METHODS: Between November 2011 and July 2016, 103 patients with ED-SCLC were reviewed, receiving appropriate imaging tests to exclude brain metastases prior to cranial irradiation...
May 17, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29770597/comparison-and-discussion-of-the-treatment-guidelines-for-small-cell-lung-cancer
#7
Honglin Zhao, Dian Ren, Hongyu Liu, Jun Chen
Small cell lung cancer (SCLC), which accounts for 15% to 17% of all lung cancers, is one of the leading causes of cancer-related death worldwide. More than 130 000 new diagnoses of SCLC and 100 000 deaths from the disease were estimated to have occurred in China in 2013. The existing guidelines of SCLC therapeutic principles differ by region. In recent years, new immunotherapy and targeted therapy treatments have been lacking. In order to understand the current status of SCLC treatment in more detail, we identified the similarities and differences among the latest National Comprehensive Cancer Network Clinical Practice Guidelines for SCLC, the Chinese Society of Clinical Oncology Lung Cancer Guidelines, and the European Society for Medical Oncology Clinical Practice Guidelines for Metastatic SCLC, and present a reference of treatment strategies that should prove beneficial for the treatment of patients with SCLC...
May 16, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29766359/two-types-of-ectopic-cushing-syndrome-or-a-continuum-review
#8
REVIEW
Marta Araujo Castro, Mónica Marazuela Azpiroz
BACKGROUND: Two types of ectopic Cushing syndrome (ECS) are described: ECS associated with aggressive neoplasms, and ECS with indolent and occult tumors, however, there is a lack of studies that thoroughly review their characteristics. METHODS: A systematic review was carried out on PUBMED of all the papers about the ECS, in order to better define the types of this subcategory of Cushing's syndrome, highlighting the differential aspects between these subgroups. RESULTS: It was found that in 50% of cases the prototypic "aggressive" ECS is caused by small cell lung carcinomas (SCLC)...
May 15, 2018: Pituitary
https://www.readbyqxmd.com/read/29765230/clinical-and-radiological-characteristics-of-central-pulmonary-adenocarcinoma-a-comparison-with-central-squamous-cell-carcinoma-and-small-cell-lung-cancer-and-the-impact-on-treatment-response
#9
Zhe Wang, Minghuan Li, Yong Huang, Li Ma, Hui Zhu, Li Kong, Jinming Yu
Purpose: The proportion of central pulmonary adenocarcinoma (ADC) in central-type lung cancer has been gradually increasing due to the overall increasing incidence of pulmonary ADC. But the clinical and radiological characteristics of central ADCs remain unclear. In this study, we compared the clinical and radiological characteristics of central ADCs with those of small cell lung cancers (SCLCs) and squamous cell carcinomas (SQCCs) and investigated the impact of these characteristics on patients' treatment response...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29764854/preclinical-antitumor-activity-of-a-novel-anti-c-kit-antibody-drug-conjugate-against-mutant-and-wild-type-c-kit-positive-solid-tumors
#10
Tinya J Abrams, Anu Connor, Christie P Fanton, Steven B Cohen, Thomas Huber, Kathy Miller, E Erica Hong, Xiaohong Niu, Janine Kline, Marjorie Ison-Dugenny, Sarah Harris, Dana B Walker, Klaus R Krauser, Francesco Galimi, Zhen Wang, Majid Ghoddusi, Keith G Mansfield, Si Tuen Lee-Hoeflich, Jocelyn Holash, Nancy Pryer, William Kluwe, Seth A Ettenberg, William R Sellers, Emma Lees, Paul Kwon, Judith A Abraham, Siew Schleyer
PURPOSE: c-KIT overexpression is well-recognized in cancers such as GIST, SCLC, melanoma, NSCLC and AML. Treatment with the small molecule inhibitors imatinib, sunitinib and regorafenib result in resistance (c-KIT mutant tumors) or limited activity (c-KIT wildtype tumors). We selected an anti-c-KIT ADC approach to evaluate the anti-cancer activity in multiple disease models. EXPERIMENTAL DESIGN: A humanized anti-c-KIT antibody LMJ729 was conjugated to the microtubule destabilizing maytansinoid, DM1, via a non-cleavable linker (SMCC)...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29764591/-clinical-analysis-of-small-cell-lung-cancer-with-bone-marrow-metastases
#11
Yiqun Che, Yang Luo, Di Wang, Di Shen, Lin Yang
BACKGROUND: Small cell lung cancer (SCLC) is highly malignant and prone to bone marrow metastasis in early stage, but its related reports are limited. This study analyzed the clinical feature, laboratory examination, treatment and prognosis of SCLC patients with bone marrow metastasis. METHODS: The clinical data of 26 SCLC patients with bone marrow metastasis were analyzed retrospectively. Prognostic factors were evaluated. RESULTS: The median age of 26 patients was 57 years and the median time from diagnosis of SCLC to confirmed bone marrow metastases was 8 d...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29764484/selection-of-candidates-for-surgery-as-local-therapy-among-early-stage-small-cell-lung-cancer-patients-a-population-based-analysis
#12
Kaiqi Jin, Kaixuan Zhang, Feng Zhou, Jie Dai, Peng Zhang, Gening Jiang
BACKGROUND: Surgery and radiotherapy are considered local therapies for small cell lung cancer (SCLC). The present study aimed to select candidates for surgery as local therapy among patients with stage I or II SCLC, based on the eighth edition of the TNM classification for lung cancer. METHODS: Patients diagnosed with SCLC between 2004 and 2013 were selected from the Surveillance, Epidemiology, And End Results database. The TNM stage of SCLC in these patients was re-classified according to the eighth edition of the TNM classification for lung cancer...
March 31, 2018: Cancer communications
https://www.readbyqxmd.com/read/29762727/development-of-targeted-therapy-and-immunotherapy-for-treatment-of-small-cell-lung-cancer
#13
Motonobu Saito, Kouya Shiraishi, Akiteru Goto, Hiroyuki Suzuki, Takashi Kohno, Koji Kono
Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC...
May 14, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29761043/differential-expression-patterns-of-housekeeping-genes-increase-diagnostic-and-prognostic-value-in-lung-cancer
#14
Yu-Chun Chang, Yan Ding, Lingsheng Dong, Lang-Jing Zhu, Roderick V Jensen, Li-Li Hsiao
Background: Using DNA microarrays, we previously identified 451 genes expressed in 19 different human tissues. Although ubiquitously expressed, the variable expression patterns of these "housekeeping genes" (HKGs) could separate one normal human tissue type from another. Current focus on identifying "specific disease markers" is problematic as single gene expression in a given sample represents the specific cellular states of the sample at the time of collection. In this study, we examine the diagnostic and prognostic potential of the variable expressions of HKGs in lung cancers...
2018: PeerJ
https://www.readbyqxmd.com/read/29760044/nk-cells-mediate-synergistic-antitumor-effects-of-combined-inhibition-of-hdac6-and-bet-in-a-sclc-preclinical-model
#15
Yan Liu, Yuyang Li, Shengwu Liu, Dennis O Adeegbe, Camilla L Christensen, Max M Quinn, Ruben Dries, Shiwei Han, Kevin Buczkowski, Xiaoen Wang, Ting Chen, Peng Gao, Hua Zhang, Fei Li, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Small cell lung cancer (SCLC) has the highest malignancy among all lung cancers, exhibiting aggressive growth and early metastasis to distant sites. For 30 years, treatment options for SCLC have been limited to chemotherapy, warranting the need for more effective treatments. Frequent inactivation of TP53 and RB1 as well as histone dysmodifications in SCLC suggest that transcriptional and epigenetic regulations play a major role in SCLC disease evolution. Here we performed a synthetic lethal screen using the BET inhibitor JQ1 and an shRNA library targeting 550 epigenetic genes in treatment-refractory SCLC xenograft models and identified HDAC6 as a synthetic lethal target in combination with JQ1...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29753578/racial-ethnic-disparities-in-end-of-life-care-quality-among-lung-cancer-patients-a-seer-medicare-based-study
#16
Siddharth Karanth, Suja S Rajan, Gulshan Sharma, Jose-Miguel Yamal, Robert O Morgan
INTRODUCTION: Cancer end-of-life care and associated racial-ethnic disparities have been in focus during the last few years due to concerns regarding subjective care variations and poor quality of care. Given the high mortality rate and disease burden of lung cancer, end-of-life care quality is particularly crucial for this disease. This study uses previously validated measures and examines racial-ethnic disparities in lung cancer end-of-life care quality. METHODS: This study involves retrospective analysis of patients ≥66 years, who were diagnosed with stage I-IV lung cancer, and who died on or before December 31, 2013, using the Surveillance Epidemiology and End Result-Medicare data from 1991-2013...
May 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29749569/postoperative-hypofractionated-stereotactic-brain-radiation-hsrt-for-resected-brain-metastases-improved-local-control-with-higher-bed-10
#17
Aryavarta M S Kumar, Jonathan Miller, Seth A Hoffer, David B Mansur, Michael Coffey, Simon S Lo, Andrew E Sloan, Mitchell Machtay
INTRODUCTION: HSRT directed to large surgical beds in patients with resected brain metastases improves local control while sparing patients the toxicity associated with whole brain radiation. We review our institutional series to determine factors predictive of local failure. METHODS: In a total of 39 consecutive patients with brain metastases treated from August 2011 to August 2016, 43 surgical beds were treated with HSRT in three or five fractions. All treatments were completed on a robotic radiosurgery platform using the 6D Skull tracking system...
May 10, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29748024/expression-of-brain-derived-neurotrophic-factor-and-its-receptor-trkb-is-associated-with-poor-prognosis-and-a-malignant-phenotype-in-small-cell-lung-cancer
#18
Shinichi Kimura, Taishi Harada, Kayo Ijichi, Kentaro Tanaka, Renpeng Liu, Daisuke Shibahara, Yuko Kawano, Kohei Otsubo, Yasuto Yoneshima, Eiji Iwama, Yoichi Nakanishi, Isamu Okamoto
OBJECTIVES: TrkB is a receptor for brain-derived neurotrophic factor (BDNF) and is highly expressed in various cancers, with BDNF-TrkB signaling having been implicated in tumor progression and metastasis. The role of the BDNF-TrkB system in small cell lung cancer (SCLC), a neuroendocrine cancer, has remained unclear, however. We examined BDNF and TrkB expression in SCLC patients as well as the function of BDNF-TrkB signaling in SCLC cell lines. MATERIALS AND METHODS: BDNF and TrkB expression in tumor specimens of 58 SCLC patients and 20 non-small cell lung cancer (NSCLC) patients was examined by immunohistochemistry and was scored on the basis of the distribution and intensity of staining...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29748022/radiosurgery-alone-is-associated-with-favorable-outcomes-for-brain-metastases-from-small-cell-lung-cancer
#19
Tyler P Robin, Bernard L Jones, Arya Amini, Matthew Koshy, Laurie E Gaspar, Arthur K Liu, Sameer K Nath, Brian D Kavanagh, D Ross Camidge, Chad G Rusthoven
INTRODUCTION: Whole-brain radiation therapy (WBRT) is the standard approach for brain metastases (BM) arising in patients with small-cell lung cancer (SCLC), but the neurocognitive toxicities of WBRT are well documented. For this reason, stereotactic radiosurgery (SRS) alone is the preferred modality for limited BM in most histologies, but in SCLC there are few data exploring this approach. METHODS: We queried the National Cancer Database (NCDB) for patients with SCLC with BM at diagnosis and stratified by upfront SRS compared with upfront WBRT ± SRS...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29748020/validation-of-the-8th-tnm-classification-for-small-cell-lung-cancer-in-a-retrospective-material-from-sweden
#20
Salomon Tendler, Vitali Grozman, Rolf Lewensohn, Georgios Tsakonas, Kristina Viktorsson, Luigi De Petris
BACKGROUND: The purpose of this study was to evaluate on a Swedish cohort of small cell lung cancer (SCLC) patients whether the 8th TNM staging system can provide additional prognostic information in comparison with the previous 6th and 7th TNM versions and the older 2-stage LD vs ED system. METHODS: We reviewed the medical records of patients (pts) with SCLC diagnosed between January 2008 and February 2016 in the Stockholm and Gotland region. Each patient file was revised and reclassified from the VASGL system to the 6th , 7th and 8th TNM system respectively...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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