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immune check point inhibitor

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https://www.readbyqxmd.com/read/28878676/pd-1-and-pd-l1-checkpoint-signaling-inhibition-for-cancer-immunotherapy-mechanism-combinations-and-clinical-outcome
#1
REVIEW
Hashem O Alsaab, Samaresh Sau, Rami Alzhrani, Katyayani Tatiparti, Ketki Bhise, Sushil K Kashaw, Arun K Iyer
Several cancers are highly refractory to conventional chemotherapy. The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. These checkpoint blockers are rapidly becoming a highly promising cancer therapeutic approach that yields remarkable antitumor responses with limited side effects...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28865357/check-point-inhibitors-as-therapies-for-infectious-diseases
#2
REVIEW
Maureen A Cox, Robert Nechanitzky, Tak W Mak
The recent successes of immune check point targeting therapies in treating cancer patients has driven a resurgence of interest in targeting these pathways in chronically infected patients. While still in early stages, basic and clinical data suggest that blockade of CTLA-4 and PD-1 can be beneficial in the treatment of chronic HIV, HBV, and HCV infection, as well as other chronic maladies. Furthermore, novel inhibitory receptors such as Tim-3, LAG-3, and TIGIT are the potential next wave of check points that can be manipulated for the treatment of chronic infection...
August 30, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28844952/targeting-cholangiocarcinoma
#3
REVIEW
Joachim C Mertens, Sumera Rizvi, Gregory J Gores
Cholangiocarcinoma (CCA) represents a diverse group of epithelial cancers associated with the biliary tract, and can best be stratified anatomically into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) subsets. Molecular profiling has identified genetic aberrations associated with these anatomic subsets. For example, IDH catalytic site mutations and constitutively active FGFR2 fusion genes are predominantly identified in iCCA, whereas KRAS mutations and PRKACB fusions genes are identified in pCCA and dCCA...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28823141/targeted-therapy-of-ovarian-cancer-including-immune-check-point-inhibitor
#4
REVIEW
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...
September 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28817445/the-safety-of-pembrolizumab-in-metastatic-melanoma-and-rheumatoid-arthritis
#5
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...
October 2017: Melanoma Research
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#6
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
#7
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/28603207/varied-immuno-related-adverse-events-induced-by-immune-check-point-inhibitors-nivolumab-associated-psoriasiform-dermatitis-related-with-increased-serum-level-of-interleukin-6
#8
REVIEW
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
#9
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/28421360/update-on-chemotherapy-induced-peripheral-neuropathy
#10
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/28405527/jak-stat-mediated-chronic-inflammation-impairs-cytotoxic-t-lymphocyte-activation-to-decrease-anti-pd-1-immunotherapy-efficacy-in-pancreatic-cancer
#11
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
#12
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/28351171/releasing-the-brake-safety-profile-of-immune-check-point-inhibitors-in-non-small-cell-lung-cancer
#13
REVIEW
Carlo Genova, Giovanni Rossi, Erika Rijavec, Federica Biello, Giulia Barletta, Marco Tagliamento, Francesco Grossi
Immune check-point inhibitors are now employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC), while combinations of different inhibitors are being evaluated in clinical trials. Although the safety profile of these compounds, with particular reference to drugs targeting programmed death protein 1 (PD-1) and its ligand (PD-L1), is generally considered manageable, peculiar, immune-related toxicities may onset. Areas covered: This review focuses on the immune-related adverse events (irAEs) observed during immune check-point blockade in NSCLC and their management...
May 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28290625/treatment-of-metastatic-melanoma-a-multi-disciplinary-approach
#14
Paolo Fava, Chiara Astrua, Martina Sanlorenzo, Simone Ribero, Matteo Brizio, Andrea R Filippi, Elena Marra, Franco Picciotto, Dario Sangiolo, Fabrizio Carnevale-Schianca, Massimo Aglietta, Sergio Sandrucci, Umberto Ricardi, Virginia Caliendo, Pietro Quaglino, Maria T Fierro
The prognosis of stage IV metastatic melanoma is poor. An overal 1-year survival of 25.5% and a median survival of 6.2 months were reported without any significant improvement during the last 30 years before the introduction of new drugs (immune check point inhibitors and targeted therapies) which completely modified the therapeutic approach and induced an overwhelming improvement on the survival rates of these patients. This review will analyse the therapeutic tools available for the treatment of patients with metastatic melanoma, including adjuvant interferon and loco-regional therapies (surgery, radiotherapy and electrochemotherapy) and will mainly focus on the presentation of results obtained by the new treatments (check point inhibitors and targeted therapies)...
March 14, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28274139/immune-and-viral-therapies-for-malignant-primary-brain-tumors
#15
REVIEW
Andrew M Gardeck, Jordan Sheehan, Walter C Low
Glioblastoma multiforme (GBM) is a primary brain tumor with great lethality. Current standard of care with surgery, radiation therapy, and chemotherapy are ineffective in curing this disease. Recent advancements in biological therapies show promise in treating brain tumors. Areas covered: This article provides a review of: the peripheral activation of antigen presenting cells such as dendritic cells to stimulate T cells to recognize and destroy tumor cells within the brain; the ex vivo expansion and transfer of dendritic cells, T cells, and engineered T cells expressing chimeric antigen receptors to target cells bearing specific tumor antigens as well as monoclonal antibodies as immune check point inhibitors...
April 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28258697/tim-3-and-its-role-in-regulating-anti-tumor-immunity
#16
REVIEW
Madhumita Das, Chen Zhu, Vijay K Kuchroo
Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28243590/second-line-treatment-of-nsclc-the-pan-erbb-inhibitor-afatinib-in-times-of-shifting-paradigms
#17
REVIEW
Jens Köhler
In contrast to the established role of epidermal growth factor receptor (EGFR) inhibitors for the first-line treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR blockade and of EGFR molecular testing in the second-line treatment remains less clear. The irreversible pan-ErbB family inhibitor afatinib (Gi(l)otrif(®)) was recently FDA- and EMA-approved for the second-line treatment of NSCLC with squamous cell histology irrespective of the EGFR mutational status (LUX-Lung 8)...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28199990/activation-of-nk-cells-and-disruption-of-pd-l1-pd-1-axis-two-different-ways-for-lenalidomide-to-block-myeloma-progression
#18
REVIEW
Massimo Giuliani, Bassam Janji, Guy Berchem
Natural Killer (NK) cells play a critical role against tumor cells in hematological malignancies. Their activating receptors are essential in tumor cell killing. In Multiple Myeloma (MM) patients, NK cell differentiation, activation and cytotoxic potential are strongly impaired leading to MM escape from immune surveillance in tissues and bone marrow. Mechanisms used by MM to affect NK cell functions are mediated by the release of soluble factors, the expression of activating and inhibitory NK cell ligands, and the expression of immune check-point inhibitors...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098061/prostate-cancer-immunotherapy-particularly-in-combination-with-androgen-deprivation-or-radiation-treatment-customized-pharmacogenomic-approaches-to-overcome-immunotherapy-cancer-resistance
#19
REVIEW
C Alberti
Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation...
September 2017: Il Giornale di Chirurgia
https://www.readbyqxmd.com/read/28011498/metastatic-pattern-of-stage-iv-colorectal-cancer-with-high-frequency-microsatellite-instability-as-a-prognostic-factor
#20
Kenji Fujiyoshi, Gou Yamamoto, Takashi Takenoya, Akemi Takahashi, Yoshiko Arai, Mina Yamada, Miho Kakuta, Kensei Yamaguchi, Yoshito Akagi, Yoji Nishimura, Hirohiko Sakamoto, Kiwamu Akagi
BACKGROUND: A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear. PATIENTS AND METHODS: A total of 2,439 surgically resected CRC tissues were analyzed for MSI status, and mutational status of V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF)...
2017: Anticancer Research
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