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https://www.readbyqxmd.com/read/28817755/measuring-toxic-effects-and-time-to-treatment-failure-for-nivolumab-plus-ipilimumab-in-melanoma
#1
Alexander N Shoushtari, Claire F Friedman, Pedram Navid-Azarbaijani, Michael A Postow, Margaret K Callahan, Parisa Momtaz, Katherine S Panageas, Jedd D Wolchok, Paul B Chapman
Importance: Nivolumab plus ipilimumab (nivo + ipi) is a standard treatment of advanced melanoma. Two randomized trials describe high objective response rates by Response Evaluation Criteria in Solid Tumors. The trials assessed toxic effects using the Common Terminology Criteria for Adverse Events (CTCAE), which may underestimate incidence of clinically significant immune-related adverse events (AEs). Objective: To describe detailed toxic effects and time to treatment failure of patients with melanoma treated with nivo + ipi in a prospective cohort...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28817753/efficacy-and-safety-of-durvalumab-in-locally-advanced-or-metastatic-urothelial-carcinoma-updated-results-from-a-phase-1-2-open-label-study
#2
Thomas Powles, Peter H O'Donnell, Christophe Massard, Hendrik-Tobias Arkenau, Terence W Friedlander, Christopher J Hoimes, Jae Lyun Lee, Michael Ong, Srikala S Sridhar, Nicholas J Vogelzang, Mayer N Fishman, Jingsong Zhang, Sandy Srinivas, Jigar Parikh, Joyce Antal, Xiaoping Jin, Ashok K Gupta, Yong Ben, Noah M Hahn
Importance: The data reported herein were accepted for assessment by the US Food and Drug Administration for Biologics License Application under priority review to establish the clinical benefit of durvalumab as second-line therapy for locally advanced or metastatic urothelial carcinoma (UC), resulting in its recent US approval. Objective: To report a planned update of the safety and efficacy of durvalumab in patients with locally advanced/metastatic UC. Design, Setting, and Participants: This is an ongoing phase 1/2 open-label study of 191 adult patients with histologically or cytologically confirmed locally advanced/metastatic UC whose disease had progressed on, were ineligible for, or refused prior chemotherapy from 60 sites in 9 countries as reported herein...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28817405/cutaneous-eruptions-in-patients-receiving-immune-checkpoint-blockade-clinicopathologic-analysis-of-the-nonlichenoid-histologic-pattern
#3
Genevieve J Kaunitz, Manisha Loss, Hira Rizvi, Sowmya Ravi, Jonathan D Cuda, Karen B Bleich, Jessica Esandrio, Inbal Sander, Dung T Le, Luis A Diaz, Julie R Brahmer, Charles G Drake, Travis J Hollmann, Mario E Lacouture, Matthew D Hellmann, Evan J Lipson, Janis M Taube
Cutaneous eruptions are among the most common immune-related adverse events (irAEs) associated with anti-programmed cell death protein 1/programmed cell death ligand 1 therapy, and are often clinically and histologically characterized as lichenoid. Nonlichenoid patterns may also occur and are likely to be encountered by surgical pathologists, given the increasing clinical use of these agents. The purpose of this study is to describe the histopathologic features of nonlichenoid cutaneous irAEs from patients receiving anti-programmed cell death protein 1/programmed cell death ligand 1 therapies for a variety of underlying advanced malignancies...
August 15, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28815434/measles-vaccination-is-best-for-children-the-argument-for-relying-on-herd-immunity-fails
#4
Johan Christiaan Bester
This article examines an argument which may negatively influence measles vaccination uptake. According to the argument, an individual child in a highly vaccinated society may be better off by being non-vaccinated; the child does not risk vaccine adverse effects and is protected against measles through herd immunity. Firstly, the conclusion of the argument is challenged by showing that herd immunity's protection is unreliable and inferior to vaccination. Secondly, the logic of the argument is challenged by showing that the argument is inherently self-defeating and therefore logically inconsistent...
August 16, 2017: Journal of Bioethical Inquiry
https://www.readbyqxmd.com/read/28814524/mutation-of-the-putative-immunosuppressive-domain-of-the-retroviral-envelope-glycoprotein-compromises-infectivity
#5
Urszula Eksmond, Bryony Jenkins, Julia Merkenschlager, Walther Mothes, Jonathan P Stoye, George Kassiotis
The envelope glycoprotein of diverse endogenous and exogenous retroviruses is considered inherently immunosuppressive. Extensive work mapped the immunosuppressive activity to a highly conserved domain, termed the immunosuppressive domain (ISD), in the transmembrane (TM) subunit of the envelope glycoprotein and identified two naturally polymorphic key residues that afford immunosuppressive activity to distinct envelope glycoproteins. Concurrent mutation of these two key residues (E14R and A20F) in the envelope glycoprotein of Friend murine leukemia virus (F-MLV) ISD has been reported to abolish its immunosuppressive activity, without affecting its fusogenicity, and to weaken the ability of the virus to replicate specifically in immunocompetent hosts...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28811898/lentinula-edodes-mycelia-extract-plus-adjuvant-chemotherapy-for-breast-cancer-patients-results-of-a-randomized-study-on-host-quality-of-life-and-immune-function-improvement
#6
Yukiko Nagashima, Shigehumi Yoshino, Shigeru Yamamoto, Noriko Maeda, Tatsuya Azumi, Yoshifumi Komoike, Kiyotaka Okuno, Tsutomu Iwasa, Junji Tsurutani, Kazuhiko Nakagawa, Oka Masaaki, Nagano Hiroaki
Anthracycline-based chemotherapies for breast cancer are known to adversely affect patients' quality of life (QOL) and immune function. For that reason, adjuvants that improve those impairments are required. A randomized double-blind study was conducted to evaluate the effectiveness of Lentinula edodes mycelia extract (LEM), which is an oral biological response modifier (BRM) medicine for cancer patients as such an adjuvant. A total of 47 breast cancer patients who were scheduled to receive postoperative adjuvant anthracycline-based chemotherapy, i...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28807514/highly-selective-activation-of-heat-shock-protein-70-by-allosteric-regulation-provides-an-insight-into-efficient-neuroinflammation-inhibition
#7
Li-Chao Wang, Li-Xi Liao, Hai-Ning Lv, Dan Liu, Wei Dong, Jian Zhu, Jin-Feng Chen, Meng-Ling Shi, Ge Fu, Xiao-Min Song, Yong Jiang, Ke-Wu Zeng, Peng-Fei Tu
Heat shock protein 70 (Hsp70) is widely involved in immune disorders, making it as an attractive drug target for inflammation diseases. Nonselective induction of Hsp70 upregulation for inflammation therapy could cause extensive interference in inflammation-unrelated protein functions, potentially resulting in side effects. Nevertheless, direct pharmacological activation of Hsp70 via targeting specific functional amino acid residue may provide an insight into precise Hsp70 function regulation and a more satisfactory treatment effect for inflammation, which has not been extensively focused...
August 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28807164/effect-of-chinese-herbal-medicine-on-male-infertility
#8
Dan Jiang, Alberto Coscione, Lily Li, Bai-Yun Zeng
Male infertility normally refers a male's inability to cause pregnancy in a fertile female partner after 1 year of unprotected intercourse. Male infertility in recent years has been attracting increasing interest from public due to the evidence in decline in semen quality. There are many factors contributing to the male infertility including abnormal spermatogenesis; reproductive tract anomalies or obstruction; inadequate sexual and ejaculatory functions; and impaired sperm motility, imbalance in hormone levels, and immune system dysfunction...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28806684/photochemical-inactivation-of-lymphocytes-by-riboflavin-with-visible-light-for-ta-gvhd-prevention
#9
Qin Mo, Yuwen Huang, Li Wang, Zhenzhen Cheng, Xiaofei Wu, Yao Jia, Xun Wang, Bo Zhang
Transfusion-associated graft-versus-host disease (TA-GVHD) is a life-threatening complication caused by the input of a number of immunocompetent allogeneic lymphocytes. This study focus on the photochemical effects of riboflavin excited by visible light (RB+L) treatment on human lymphocytes, to study the feasibility of using RB+L treatment to prevent adverse immune reactions caused by transfused lymphocytes. 100μM riboflavin was added to lymphocyte suspensions. After exposure to 400-580nm visible light with a total energy of 40J/mL, cells were cultured and the ability of proliferation and cytokine secretion were assayed upon stimuli...
August 7, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28805662/clinical-and-immunological-responses-after-cd30-specific-chimeric-antigen-receptor-redirected-lymphocytes
#10
Carlos A Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley, Catherine M Bollard, Bill H Chang, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Gianpietro Dotti, Barbara Savoldo
BACKGROUND: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS: We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28803328/traditional-chinese-medicine-as-adjunctive-therapy-improves-the-long-term-survival-of-lung-cancer-patients
#11
Yueh-Hsiang Liao, Chia-Ing Li, Cheng-Chieh Lin, Jaung-Geng Lin, Jen-Huai Chiang, Tsai-Chung Li
PURPOSE: Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients. METHODS: This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000-2009 from National Health Insurance Program database...
August 12, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28802908/apoptosis-signaling-and-bcl-2-pathways-provide-opportunities-for-novel-targeted-therapeutic-strategies-in-hematologic-malignances
#12
REVIEW
Huanling Wu, L Jeffrey Medeiros, Ken H Young
Apoptosis is an essential biological process involved in tissue homeostasis and immunity. Aberrations of the two main apoptotic pathways, extrinsic and intrinsic, have been identified in hematological malignancies; many of these aberrations are associated with pathogenesis, prognosis and resistance to standard chemotherapeutic agents. Targeting components of the apoptotic pathways, especially the chief regulatory BCL-2 family in the intrinsic pathway, has proved to be a promising therapeutic approach for patients with hematological malignances, with the expectation of enhanced efficacy and reduced adverse events...
August 8, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28801523/dietary-modulation-of-oxylipins-in-cardiovascular-disease-and-aging
#13
Stephanie P B Caligiuri, Mihir Parikh, Aleksandra Stamenkovic, Grant N Pierce, Harold M Aukema
Oxylipins are a group of fatty acid metabolites generated via oxygenation of polyunsaturated fatty acids and are involved in processes such as inflammation, immunity, pain, vascular tone and coagulation. As a result, oxylipins are implicated in many conditions characterized by these processes including cardiovascular disease and aging. The best characterized oxylipins in relation to cardiovascular disease are derived from the ω-6 fatty acid arachidonic acid. These oxylipins generally increase inflammation, hypertension and platelet aggregation, although not universally...
August 11, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28800677/levothyroxine-enhances-glucose-clearance-and-blunts-the-onset-of-experimental-type-1-diabetes-mellitus-in-mice
#14
Livia López-Noriega, Nadia Cobo-Vuilleumier, Álvaro Jesús Narbona-Pérez, Juan Luis Araujo-Garrido, Petra Isabel Lorenzo, José Manuel Mellado-Gil, José Carlos Moreno, Benoit R Gauthier, Alejandro Martín-Montalvo
BACKGROUND AND PURPOSE: Thyroid hormones induce several changes in whole body metabolism that are known to improve metabolic homeostasis. However, adverse side effects have prevented its use in the clinic. In view of the promising effects of thyroid hormones, we investigated the effects of levothyroxine supplementation in glucose. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with levothyroxine from birth to 24 weeks of age, when mice were euthanized. The effects of levothyroxine supplementation on metabolic health were determined...
August 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28800058/effectiveness-of-mifamurtide-in-addition-to-standard-chemotherapy-for-high-grade-osteosarcoma-a-systematic-review
#15
Rincy Jimmy, Cindy Stern, Karolina Lisy, Sarahlouise White
BACKGROUND: Osteosarcoma mostly occurs during the period of rapid bone growth in children and adolescents as high-grade osteosarcomas. Current treatment recommended for high-grade non-metastatic and metastatic and/or relapsed osteosarcoma involves neoadjuvant multiagent conventional chemotherapy, followed by surgical resection of macroscopically detected tumor and postoperative adjuvant chemotherapy. However, residual micrometastatic deposits that develop following surgery have shown resistance to postoperative/adjuvant chemotherapy...
August 2017: JBI Database of Systematic Reviews and Implementation Reports
https://www.readbyqxmd.com/read/28799125/non-polymer-drug-eluting-coronary-stents
#16
REVIEW
Nagavendra Kommineni, Raju Saka, Wahid Khan, Abraham J Domb
Cardiovascular complications are leading causes of most fatalities. Coronary artery disease and surgical failures contribute to the death of the majority of patients. Advanced research in the field of medical devices like stents has efficiently resolved these problems. Clinically, drug-eluting stents have proven their efficacy and safety compared to bare metal stents, which have problems of in-stent restenosis. However, drug-loaded stents coated with polymers have shown adverse effects related to the stability and deterioration of the polymer coating over time...
August 10, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28797029/successful-use-of-equine-anti-thymocyte-globulin-atgam-for-fulminant-myocarditis-secondary-to-nivolumab-therapy
#17
Rebecca Y Tay, Elizabeth Blackley, Catriona McLean, Maggie Moore, Peter Bergin, Sanjeev Gill, Andrew Haydon
BACKGROUND: Immune-mediated myocarditis is an uncommon adverse effect of immune checkpoint inhibition and is associated with a high rate of mortality. METHODS: In this reported case, a 64-year-old woman with right temporo-parietal glioblastoma IDH-WT was treated with nivolumab, temozolomide and radiation therapy on a clinical trial. She developed malignant arrhythmias secondary to histologically confirmed severe immune-mediated myocarditis. She was treated with equine anti-thymocyte globulin (ATGAM) due to development of malignant arrhythmias refractory to high-dose corticosteroids...
August 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28794555/itolizumab-in-psoriasis
#18
Ankita Srivastava
A number of biologics is being used for the treatment of psoriasis. Itolizumab is one such agent which has been approved in India. It is an anti-CD6 monoclonal antibody that acts by binding to scavenger receptor cysteine-rich (SRCR) distal domain 1 of CD6. Itolizumab has been found to be safe, with infusion reactions as the most common adverse effect. However, its advantages and disadvantages over other biologicals and immunosuppressants need to be established. Also, its utility in treating other immune-mediated disorders is being explored...
July 2017: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/28794234/deep-immune-profiling-of-an-arginine-enriched-nutritional-intervention-in-patients-undergoing-surgery
#19
Nima Aghaeepour, Cindy Kin, Edward A Ganio, Kent P Jensen, Dyani K Gaudilliere, Martha Tingle, Amy Tsai, Hope L Lancero, Benjamin Choisy, Leslie S McNeil, Robin Okada, Andrew A Shelton, Garry P Nolan, Martin S Angst, Brice L Gaudilliere
Application of high-content immune profiling technologies has enormous potential to advance medicine. Whether these technologies reveal pertinent biology when implemented in interventional clinical trials is an important question. The beneficial effects of preoperative arginine-enriched dietary supplements (AES) are highly context specific, as they reduce infection rates in elective surgery, but possibly increase morbidity in critically ill patients. This study combined single-cell mass cytometry with the multiplex analysis of relevant plasma cytokines to comprehensively profile the immune-modifying effects of this much-debated intervention in patients undergoing surgery...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28793897/aqueous-extract-of-phragmitis-rhizoma-ameliorates-myelotoxicity-of-docetaxel-in-vitro-and-in-vivo
#20
Jinhee Kim, You Jin Lee, Young Ah Kim, Eun-Sang Cho, Eunna Huh, Ok-Sun Bang, No Soo Kim
BACKGROUND: A variety of anticancer chemotherapeutics induce adverse side effects including myelotoxicity. Dried roots of Phragmites communis Trinius, Phragmitis rhizoma, have been clinically used in traditional folk medicine to relieve various symptoms like fever. In this study, we evaluated the protective effect of the aqueous extract of Phragmitis rhizoma (EPR) against docetaxel-induced myelotoxicity in vitro and in vivo. METHODS: The in vitro myelo-protective effect of EPR was evaluated using the colony forming unit (CFU) assay with hematopoietic progenitor cells...
August 9, 2017: BMC Complementary and Alternative Medicine
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