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Immune check points

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https://www.readbyqxmd.com/read/28823141/targeted-therapy-of-ovarian-cancer-including-immune-check-point-inhibitor
#1
Jin Young Kim, Chi Heum Cho, Hong Suk Song
Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects...
August 22, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28817445/the-safety-of-pembrolizumab-in-metastatic-melanoma-and-rheumatoid-arthritis
#2
Akshjot Puri, Jade Homsi
Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies...
August 16, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28736183/immunotherapy-targeting-immune-check-point-s-in-brain-metastases
#3
Anna Maria Di Giacomo, Monica Valente, Alessia Covre, Riccardo Danielli, Michele Maio
Immunotherapy with monoclonal antibodies (mAb) directed to different immune check-point(s) is showing a significant clinical impact in a growing number of human tumors of different histotype, both in terms of disease response and long-term survival patients. In this rapidly changing scenario, treatment of brain metastases remains an high unmeet medical need, and the efficacy of immunotherapy in these highly dismal clinical setting remains to be largely demonstrated. Nevertheless, up-coming observations are beginning to suggest a clinical potential of cancer immunotherapy also in brain metastases, regardless the underlying tumor histotype...
July 13, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28727142/genomic-and-transcriptomic-heterogeneity-of-colorectal-tumors-arising-in-lynch-syndrome
#4
Hans Binder, Lydia Hopp, Michal R Schweiger, Steve Hoffmann, Frank Jühling, Martin Kerick, Bernd Timmermann, Susann Siebert, Christina Grimm, Lilit Nersisyan, Arsen Arakelyan, Maria Herberg, Peter Buske, Henry Loeffler-Wirth, Maciej Rosolowski, Christoph Engel, Jens Przybilla, Martin Peifer, Nicolaus Friedrichs, Gabriela Moeslein, Margarete Odenthal, Michelle Hussong, Sophia Peters, Stefanie Holzapfel, Jacob Nattermann, Robert Hueneburg, Wolff Schmiegel, Brigitte Royer-Pokora, Stefan Aretz, Michael Kloth, Matthias Kloor, Reinhard Buettner, Jörg Galle, Markus Loeffler
Colorectal cancer (CRC) arising in Lynch Syndrome (LS) comprises tumors with constitutional mutations in DNA mismatch-repair genes. Whole-genome and transcriptome studies of LS-CRC are still missing to address questions about similarities and differences of mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch-repair in LS colonic mucosa and the possible role of immune editing...
July 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#5
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28709816/-current-knowledge-on-perioperative-treatments-of-non-small-cell-lung-carcinomas
#6
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%...
June 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28686285/toward-a-structural-understanding-of-nucleic-acid-sensing-toll-like-receptors-in-the-innate-immune-system
#7
REVIEW
Zhikuan Zhang, Umeharu Ohto, Toshiyuki Shimizu
The history of mankind has been plagued by the tug of war with viral infections. Toll-like receptors (TLRs) and other receptors of the innate immune system constitute an early defense system against invading viruses by recognizing the viral genetic material, the nucleic acids (NAs). Agonistic ligands of NA-sensing TLRs play an emerging role in the treatment of viral diseases, demonstrating a crucial role of these receptors. Recently, crystal structures have afforded new insights into TLR recognition of NAs...
July 7, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28683527/host-directed-therapeutics-as-novel-angle-for-tuberculosis-treatment
#8
REVIEW
Ye-Ram Kim, Chul-Su Yang
Despite significant efforts to improve tuberculosis (TB) treatment, it remains a worldwide infectious disease due to the limitations of current TB regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors is beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs are more beneficial than existed TB drugs, which are limited the long durations of treatment and the emergence of drug-resistant strains...
July 7, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28645484/immune-check-point-inhibition-in-sarcomatoid-renal-cell-carcinoma-a-new-treatment-paradigm
#9
Ruben Raychaudhuri, Matthew J Riese, Kathryn Bylow, John Burfeind, Alexander C Mackinnon, Parag P Tolat, Kenneth A Iczkowski, Deepak Kilari
No abstract text is available yet for this article.
May 25, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28627792/%C3%AE-catenin-in-desmoid-type-fibromatosis-deep-insights-on-the-role-of-t41a-and-s45f-mutations-on-protein-structure-and-gene-expression
#10
C Colombo, A Belfiore, N Paielli, L De Cecco, S Canevari, E Laurini, M Fermeglia, S Pricl, P Verderio, S Bottelli, M Fiore, S Stacchiotti, E Palassini, A Gronchi, S Pilotti, F Perrone
Desmoid- type fibromatosis (DF) is a rare mesenchymal lesion with high risk of local recurrence. Specific β-catenin mutations (S45F) appeared to be related to this higher risk compared to T41A mutated or wild type (WT). We explored the influence of both mutations and WT on structure stability and affinity of β-catenin for α-catenin and the pattern of gene expression that may influence DF behavior. Using 33 surgically resected primary DFs harboring T41A (n=14), S45F (n=10) or WT (n=9), we performed a comparative molecular analysis by protein/protein interaction modeling, gene expression by DASL microarrays, human inflammation gene panel and assessment of immune system-based biomarkers by immunohistochemistry...
June 19, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28603207/varied-immuno-related-adverse-events-induced-by-immune-check-point-inhibitors-nivolumab-associated-psoriasiform-dermatitis-related-with-increased-serum-level-of-interleukin-6
#11
Naoko Okiyama, Ryota Tanaka
  Nivolumab is a standard recombinant antibody treatment for patients with malignant melanoma (MM), which functions as an immune checkpoint inhibitor by blocking the programmed cell death-1 (PD-1) pathway in T cells. However, it leads to various immune-related adverse events (irAEs), and also exacerbates underlying autoimmune diseases. Herein we report cases of MM with irAE. Case 1: A 69-year-old woman with MM developed destructive thyroiditis resulting in hypothyroidism after 3 doses of nivolumab, and had been treated with thyroid gland auxiliary therapy...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28588151/in-vivo-imaging-of-the-programmed-death-ligand-1-by-18-f-positron-emission-tomography
#12
Dinko E Gonzalez Trotter, Xiangjun Meng, Paul McQuade, Daniel Rubins, Michael Klimas, Zhizhen Zhang, Brett M Connolly, Patricia J Miller, Stacey S O'Malley, Shu-An Lin, Krista L Getty, Laurence Fayadat-Dilman, Linda Liang, Elisabet Wahlberg, Olof Widmark, Caroline Ekblad, Fredrik Y Frejd, Eric D Hostetler, Jeffrey L Evelhoch
Introduction: PD-L1 (Programmed Death Ligand 1) is an immune regulatory ligand that binds to the T-cell immune check point PD-1 (Programmed Death 1). Tumor expression of PD-L1 is correlated with immune suppression and poor prognosis. It is also correlated with therapeutic efficacy of PD-1 and PD-L1 inhibitors. In vivo imaging may enable real-time follow-up of changing PD-L1 expression and heterogeneity evaluation of PD-L1 expression across tumors in the same subject. We have radiolabeled the PD-L1 binding Affibody® molecule NOTA-ZPD-L1_1 with (18)F and evaluated its in vitro and in vivo binding affinity, targeting and specificity...
June 6, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28472223/immune-check-point-associated-cardiotoxicity-case-report-with-systematic-review-of-literature
#13
A Chauhan, G Burkeen, J Houranieh, S Arnold, L Anthony
No abstract text is available yet for this article.
May 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28470464/expanding-diversity-and-common-goal-of-regulatory-t-and-b-cells-ii-in-allergy-malignancy-and-transplantation
#14
REVIEW
Grażyna Korczak-Kowalska, Anna Stelmaszczyk-Emmel, Katarzyna Bocian, Ewelina Kiernozek, Nadzieja Drela, Joanna Domagała-Kulawik
Regulation of immune response was found to play an important role in the course of many diseases such as autoimmune diseases, allergy, malignancy, organ transplantation. The studies on immune regulation focus on the role of regulatory cells (Tregs, Bregs, regulatory myeloid cells) in these disorders. The number and function of Tregs may serve as a marker of disease activity. As in allergy, the depletion of Tregs is observed and the results of allergen-specific immunotherapy could be measured by an increase in the population of IL-10(+) regulatory cells...
May 3, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28421360/update-on-chemotherapy-induced-peripheral-neuropathy
#15
REVIEW
Comana Cioroiu, Louis H Weimer
PURPOSE OF REVIEW: The purpose of this study was to briefly discuss chemotherapy-induced peripheral neuropathy (CIPN) and detail the most important and most recent chemotherapeutic agents implicated. This review will examine neuropathy mechanisms, risk factors, and clinical patterns; novel and prospective drugs with similar effects that are less well known to neurologists are discussed. RECENT FINDINGS: CIPN is increasingly recognized for its clinical importance and effect on patient quality of life...
June 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28419095/effectiveness-of-a-live-oral-human-rotavirus-vaccine-after-programmatic-introduction-in-bangladesh-a-cluster-randomized-trial
#16
RANDOMIZED CONTROLLED TRIAL
K Zaman, David A Sack, Kathleen M Neuzil, Mohammad Yunus, Lawrence H Moulton, Jonathan D Sugimoto, Jessica A Fleming, Ilias Hossain, Shams El Arifeen, Tasnim Azim, Mustafizur Rahman, Kristen D C Lewis, Andrea J Feller, Firdausi Qadri, M Elizabeth Halloran, Alejandro Cravioto, John C Victor
BACKGROUND: Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO's Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia...
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28405527/jak-stat-mediated-chronic-inflammation-impairs-cytotoxic-t-lymphocyte-activation-to-decrease-anti-pd-1-immunotherapy-efficacy-in-pancreatic-cancer
#17
Chunwan Lu, Asif Talukder, Natasha M Savage, Nagendra Singh, Kebin Liu
Human pancreatic cancer does not respond to immune check point blockade immunotherapy. One key feature of pancreatic cancer is the association between its progression and chronic inflammation. Emerging evidence supports a key role for the JAK-STAT pathway in pancreatic cancer inflammation. We aimed at testing the hypothesis that sustained JAK-STAT signaling suppresses cytotoxic T lymphocyte (CTL) activation to counteract anti-PD-1 immunotherapy-induced CTL activity in pancreatic cancer. We show that human pancreatic carcinomas express high level of PD-L1 and exhibit low level of CTL infiltration...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401443/prevalence-of-hypophysitis-in-a-cohort-of-patients-with-metastatic-melanoma-and-prostate-cancer-treated-with-ipilimumab
#18
Lucia Brilli, Riccardo Danielli, Cristina Ciuoli, Luana Calabrò, Anna Maria Di Giacomo, Alfonso Cerase, Patrizia Paffetti, Fausta Sestini, Brunetta Porcelli, Michele Maio, Furio Pacini
OBJECTIVE: Ipilimumab is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4, that has been shown to significantly improve survival in patients with metastatic melanoma. Blocking cytotoxic T-lymphocyte antigen-4 elicits T cell activation, proliferation and anti-tumor response, but can also trigger immune-related adverse events. Among immune-related endocrinopathies, hypophysitis represents the most frequent, with an incidence up to 17% in patients treated with ipilimumab...
April 12, 2017: Endocrine
https://www.readbyqxmd.com/read/28384630/esophageal-cancer-new-insights-into-a-heterogenous-disease
#19
Sebastian Krug, Patrick Michl
BACKGROUND: Esophageal cancer represents a heterogeneous malignancy mostly diagnosed in advanced stages. Worldwide, squamous cell carcinomas (SCCs) continue to be the most prevalent subtype; however, in the Western countries, the incidence of adenocarcinomas is increasing and will exceed that of SCC in the near future. During the last decade, several landmark trials contributed to a better understanding of the disease and emphasized the importance of multimodal treatment protocols. SUMMARY: With the introduction of perioperative or neoadjuvant approaches, the survival of both subtypes of esophageal cancer has significantly improved...
2017: Digestion
https://www.readbyqxmd.com/read/28363334/novel-immune-check-point-inhibiting-antibodies-in-cancer-therapy-opportunities-and-challenges
#20
Yael Diesendruck, Itai Benhar
Drug resistance of tumor cells to chemotherapy is limiting the therapeutic efficacy of most anticancer drugs and represents a major obstacle in medical oncology. However, treatment of various human malignancies with biologics, mostly monoclonal antibodies (mAbs), is not limited by such chemoresistance mechanisms. However, other resistance or evasion mechanisms limit the efficacy to anticancer therapeutic mAbs that engage tumor-associated antigens on the surface of the malignant cells. Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology...
January 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
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