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https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#1
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28428185/investments-in-cancer-research-awarded-to-uk-institutions-and-the-global-burden-of-cancer-2000-2013-a-systematic-analysis
#2
Mahiben Maruthappu, Michael G Head, Charlie D Zhou, Barnabas J Gilbert, Majd A El-Harasis, Rosalind Raine, Joseph R Fitchett, Rifat Atun
OBJECTIVES: To systematically categorise cancer research investment awarded to United Kingdom (UK) institutions in the period 2000-2013 and to estimate research investment relative to disease burden as measured by mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs). DESIGN: Systematic analysis of all open-access data. SETTING AND PARTICIPANTS: Public and philanthropic funding to all UK cancer research institutions, 2000-2013...
April 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28410823/the-case-for-performing-pleural-biopsies-for-the-aetiological-diagnosis-of-exudates-yes
#3
F Rodriguez-Panadero
Pleural biopsies are especially indicated in the following circumstances: a) inconclusive pleural fluid analysis and negative sputum study, if adenosine deaminase (ADA) levels are unavailable; b) suspected multi-resistant tuberculosis; c) a need for differentiating tuberculous pleurisy (if it progresses with neutrophilia) and complicated parapneumonic effusion; d) malignant pleural effusion coexisting with very high ADA levels; e) effusion coexisting with lung cancer and negative pleural cytology; f) suspected mesothelioma; and g) need for implementing re-treatment for patients with relapse after chemotherapy...
April 12, 2017: Revista Clínica Española
https://www.readbyqxmd.com/read/28403901/cd44-and-its-ligand-hyaluronan-as-potential-biomarkers-in-malignant-pleural-mesothelioma-evidence-and-perspectives
#4
REVIEW
Lourdes Cortes-Dericks, Ralph Alexander Schmid
Malignant pleural mesothelioma (MPM) is a rare and highly drug resistant tumor arising from the mesothelial surfaces of the lung pleura. The standard method to confirm MPM is the tedious, time-consuming cytological examination of cancer biopsy. Biomarkers that are detectable in pleural effusion or patient serum are reasonable options to provide a faster and noninvasive diagnostic approach. As yet, the current biomarkers for MPM lack specificity and sensitivity to discriminate this neoplasm from other lung tumors...
April 12, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28395242/analysis-of-fibulin-3-after-exposure-to-asbestos-like-fibers
#5
Venerando Rapisarda, Rosario Caltabiano, Giuseppe Musumeci, Paola Castrogiovanni, Margherita Ferrante, Caterina Ledda, Claudia Lombardo, Adriana Carol Eleonora Graziano, Venera Cardile, Carla Loreto
A significantly increased incidence of malignant mesothelioma in Biancavilla (Sicily, Italy) has been ascribed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. Fibulin-3 is a highly conserved glycoprotein proposed as a biomarker for malignant mesothelioma that belongs to the family of extracellular matrix proteins. Previous studies demonstrated high Fibulin-3 plasma levels in workers with pleural plaques exposed to fluoro-edenite. Therefore, in order to gain insight into the biomolecular mechanisms of fluoro-edenite toxicity, we performed the analysis of Fibulin-3 expression by immunohistochemistry in the lung samples derived from sheep belonging to the area of Biancavilla...
April 7, 2017: Environmental Research
https://www.readbyqxmd.com/read/28388291/phase-1-dose-escalation-study-of-pegylated-arginine-deiminase-cisplatin-and-pemetrexed-in-patients-with-argininosuccinate-synthetase-1-deficient-thoracic-cancers
#6
Emma Beddowes, James Spicer, Pui Ying Chan, Ramsay Khadeir, Javier Garcia Corbacho, Dimitra Repana, Jeremy P Steele, Peter Schmid, Teresa Szyszko, Gary Cook, Monica Diaz, Xiaoxing Feng, Amanda Johnston, Jim Thomson, Michael Sheaff, Bor-Wen Wu, John Bomalaski, Simon Pacey, Peter W Szlosarek
Purpose Pegylated arginine deiminase (ADI-PEG 20) depletes essential amino acid levels in argininosuccinate synthetase 1 (ASS1) -negative tumors by converting arginine to citrulline and ammonia. The main aim of this study was to determine the recommended dose, safety, and tolerability of ADI-PEG 20, cisplatin, and pemetrexed in patients with ASS1-deficient malignant pleural mesothelioma (MPM) or non-small-cell lung cancer (NSCLC). Patients and Methods Using a 3 + 3 + 3 dose-escalation study, nine chemotherapy-naïve patients (five MPM, four NSCLC) received weekly ADI-PEG 20 doses of 18 mg/m(2), 27 mg/m(2), or 36 mg/m(2), together with pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) which were given every three weeks (maximum of six cycles)...
April 7, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28371288/intensity-modulated-radiation-therapy-after-extra-pleural-pneumonectomy-for-malignant-pleural-mesothelioma-is-feasible-without-fatal-pulmonary-toxicity-and-provides-good-survival
#7
Sameer Jhavar, Jessica Pruszynski, Alan Gowan, Teresa Boyle, Niloyjyoti Deb, Mehul Patel
AIM: To analyze patterns of failure, toxicity, relapse-free survival (RFS), and overall survival (OS) in malignant pleural mesothelioma (MPM) patients treated with intensity-modulated radiation therapy following extrapleural pneumonectomy (EPP). METHODS: We reviewed 18 charts of patients with MPM from 2005 to 2014 who underwent EPP followed by hemithoracic intensity-modulated radiation therapy. Intensity-modulated radiation therapy dose delivery adhered to published lung dose constraints...
March 29, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28361465/antibody-drug-conjugates-adcs-for-personalized-treatment-of-solid-tumors-a-review
#8
REVIEW
John M Lambert, Charles Q Morris
Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial...
March 30, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#9
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28293731/physical-function-and-health-related-quality-of-life-in-patients-undergoing-surgical-treatment-for-malignant-pleural-mesothelioma
#10
Takashi Tanaka, Shinichiro Morishita, Masaki Hashimoto, Yusuke Itani, Satoshi Mabuchi, Norihiko Kodama, Seiki Hasegawa, Kazuhisa Domen
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare cancer that affects the thin cell wall lining of internal organs and structures. Studies have shown that patients with lung cancer have decreased pulmonary function and exercise capacity after pneumonectomy. However, to date, physical function and health-related quality of life (HRQOL) in surgically treated MPM patients have not been evaluated in detail. The aim of this study was to assess physical function and HRQOL of MPM patients following pleurectomy/decortication (P/D)...
March 14, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28293123/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cancer-patient-selection-and-perspectives
#11
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28289713/th17-cells-are-refractory-to-senescence-and-retain-robust-antitumor-activity-after-long-term-ex-vivo-expansion
#12
Jacob S Bowers, Michelle H Nelson, Kinga Majchrzak, Stefanie R Bailey, Baerbel Rohrer, Andrew D M Kaiser, Carl Atkinson, Luca Gattinoni, Chrystal M Paulos
Adoptive immunotherapy for solid tumors relies on infusing large numbers of T cells to mediate successful antitumor responses in patients. While long-term rapid-expansion protocols (REPs) produce sufficient numbers of CD8(+) T cells for treatment, they also cause decline in the cell's therapeutic fitness. In contrast, we discovered that IL-17-producing CD4(+) T cells (Th17 cells) do not require REPs to expand 5,000-fold over 3 weeks. Also, unlike Th1 cells, Th17 cells do not exhibit hallmarks of senescence or apoptosis, retaining robust antitumor efficacy in vivo...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28288645/mesothelin-promotes-epithelial-to-mesenchymal-transition-and-tumorigenicity-of-human-lung-cancer-and-mesothelioma-cells
#13
Xiaoqing He, Liying Wang, Heimo Riedel, Kai Wang, Yong Yang, Cerasela Zoica Dinu, Yon Rojanasakul
BACKGROUND: Lung cancer and pleural mesothelioma are two of the most deadly forms of cancer. The prognosis of lung cancer and mesothelioma is extremely poor due to limited treatment modalities and lack of understanding of the disease mechanisms. We have identified mesothelin as a potentially unique therapeutic target that as a specific advantage appears nonessential in most cell types. Mesothelin (MSLN), a plasma membrane differentiation antigen, is expressed at a high level in many human solid tumors, including 70% of lung cancer and nearly all mesotheliomas...
March 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28252315/checkpoint-blockade-in-lung-cancer-and-mesothelioma
#14
Lysanne A Lievense, Daniel H Sterman, Robin Cornelissen, Joachim G Aerts
In the past decade, immunotherapy has emerged as a new treatment modality in cancer. The most success has been achieved with the class of checkpoint inhibitors; antibodies which unleash the anti-tumor immune response. Following the success in melanoma, numerous clinical trials are being conducted investigating checkpoint inhibitors in lung cancer and mesothelioma. The programmed death protein 1-protein death ligand 1/2 (PD-1 - PD-L1/2) pathway and cytotoxic T-lymphocyte associated protein 4 (CTLA4) are currently the most studied immunotherapeutic targets in these malignancies...
March 2, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28223140/reduced-cell-viability-and-apoptosis-induction-in-human-thyroid-carcinoma-and-mesothelioma-cells-exposed-to-cidofovir
#15
Simona Catalani, Francesco Palma, Serafina Battistelli, Barbara Nuvoli, Rossella Galati, Serena Benedetti
Besides its well-recognized antiviral activity, Cidofovir (CDV) has been shown to exert anticancer properties both within in vitro and in vivo models. The aim of this study was to evaluate the effects of CDV on still unexplored cultured cancer cells from human mesothelioma as well as breast, colon, liver, lung, prostate, and thyroid carcinomas. Overall, a dose- and time-dependent inhibition of cell viability was observed after CDV exposure. To clarify the mechanisms underlying CDV action, apoptotic cell death was investigated in two infected cell lines [Ist-Mes1 and Ist-Mes2 mesothelioma cells (SV40+)] and in two uninfected cell lines (NCI-H2425 mesothelioma cells and FTC-133 thyroid cancer cells), which resulted the most sensitive to CDV treatment...
February 20, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28213004/pharmacokinetic-evaluation-of-intrapleural-perfusion-with-hyperthermic-chemotherapy-using-cisplatin-in-patients-with-malignant-pleural-effusion
#16
Hirozo Sakaguchi, H Ishida, H Nitanda, N Yamazaki, K Kaneko, Kunihiko Kobayashi
OBJECTIVES: Malignant pleural effusion (MPE) has a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy, although its success rate is around 64%. We have investigated intrapleural perfusion with hyperthermic chemotherapy (IPHC) using cisplatin in a study with a pharmacokinetic evaluation. METHODS: Patients with MPE, performance status of 0-1, possibility of good lung expansion and Cr<1.2mg/dL were treated with IPHC. The circuit was filled with 2000mL of normal saline containing cisplatin at a dose of 80mg/m(2)...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28166467/mortality-among-coast-guard-shipyard-workers-a-retrospective-cohort-study-of-specific-exposures
#17
Jennifer Rusiecki, Patricia Stewart, Dara Lee, Melannie Alexander, Srmena Krstev, Debra Silverman, Aaron Blair
In a previous analysis of a cohort of shipyard workers, we found excess mortality from all causes, lung cancer, and mesothelioma for longer work durations and in specific occupations. Here, we expand the previous analyses by evaluating mortality associated with five chemical exposures: asbestos, solvents, lead, oils/greases, and wood dust. Data were gathered retrospectively for 4,702 workers employed at the Coast Guard Shipyard, Baltimore, MD (1950-1964). The cohort was traced through 2001 for vital status...
February 6, 2017: Archives of Environmental & Occupational Health
https://www.readbyqxmd.com/read/28162296/-efficacy-of-pd-1-pd-l1%C3%A2-immune-checkpoint-inhibitors-and-pd-l1%C3%A2-testing-in-thoracic-cancers
#18
Michaël Duruisseaux, Isabelle Rouquette, Julien Adam, Alexis Cortot, Aurélie Cazes, Laure Gibault, Diane Damotte, Sylvie Lantuejoul
Tumoral immune environment is a major component of cancer. Its composition and its organization represent a reproducible characteristic of tumors and a validated prognostic factor. In non-small cell lung cancer (NSCLC), cytotoxic T CD8+ lymphocyte density, associated with a Th1 environment and tertiary lymphoid structures impacts survival. Tumor cell-immune cell interaction is targeted by PD1/PD-L1 inhibitors. In advanced NSCLC, PD1/PD-L1 inhibitors are more effective than second-line chemotherapy. Pembrolizumab outperforms first-line chemotherapy in NSCLC strongly positive for PD-L1...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28162043/chest-ultrasonography-in-health-surveillance-of-asbestos-related-lung-diseases
#19
Andrea Smargiassi, Giuliana Pasciuto, Ilaria Pedicelli, Erminia Lo Greco, Mariarosaria Calvello, Riccardo Inchingolo, Gioacchino Schifino, Patrizio Capoluongo, Pasquale Patriciello, Maurizio Manno, Alfonso Cirillo, Giuseppe Maria Corbo, Gino Soldati, Ivo Iavicoli
OBJECTIVES: Exposure to asbestos fibers can lead to different lung diseases, such as pleural thickening and effusion, asbestosis, mesothelioma, and lung cancer. These diseases are expected to peak in the next few years. The aim of the study was to validate ultrasonography (US) as a diagnostic tool in the management of lung diseases in subjects with a history of occupational exposure to asbestos. METHODS: Fifty-nine retired male workers previously exposed to asbestos were enrolled in the study...
January 1, 2017: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/28158568/pemetrexed-related-interstitial-lung-disease-reported-from-post-marketing-surveillance-malignant-pleural-mesothelioma-non-small-cell-lung-cancer
#20
Keisuke Tomii, Terufumi Kato, Masashi Takahashi, Satoshi Noma, Yoichiro Kobashi, Sotaro Enatsu, Sumiko Okubo, Noriko Kobayashi, Shoji Kudoh
Background: Interstitial lung disease (ILD) is important drug related toxicity because it commonly forced to discontinue the treatment. Methods: To characterize the prevalence and patterns of pemetrexed induced ILD, an independent ILD advisory board composed of external experts performed reassessment of ILD in two post marketing surveillance (PMS) studies for malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). Results: ILD incidences were originally 1...
April 1, 2017: Japanese Journal of Clinical Oncology
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