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check point blockade

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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
#1
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/28470464/expanding-diversity-and-common-goal-of-regulatory-t-and-b-cells-ii-in-allergy-malignancy-and-transplantation
#2
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/28405527/jak-stat-mediated-chronic-inflammation-impairs-cytotoxic-t-lymphocyte-activation-to-decrease-anti-pd-1-immunotherapy-efficacy-in-pancreatic-cancer
#3
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/28363334/novel-immune-check-point-inhibiting-antibodies-in-cancer-therapy-opportunities-and-challenges
#4
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
https://www.readbyqxmd.com/read/28351171/releasing-the-brake-safety-profile-of-immune-check-point-inhibitors-in-non-small-cell-lung-cancer
#5
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/28259300/immunotherapy-for-the-treatment-of-multiple-myeloma
#6
REVIEW
Sung-Hoon Jung, Hyun-Ju Lee, Manh-Cuong Vo, Hyeoung-Joon Kim, Je-Jung Lee
Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28258697/tim-3-and-its-role-in-regulating-anti-tumor-immunity
#7
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
#8
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/28098061/prostate-cancer-immunotherapy-particularly-in-combination-with-androgen-deprivation-or-radiation-treatment-customized-pharmacogenomic-approaches-to-overcome-immunotherapy-cancer-resistance
#9
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/27754760/combining-mpdl3280a-with-adoptive-cell-immunotherapy-exerts-better-antitumor-effects-against-cervical-cancer
#10
Yi Zheng, Yicheng Yang, Shu Wu, Yongqiang Zhu, Xiaolong Tang, Xiaopeng Liu
As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immune-based approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated...
October 18, 2016: Bioengineered
https://www.readbyqxmd.com/read/27647396/-current-status-and-future-prospect-of-internal-medicine-treatment-for-advanced-esophageal-cancer
#11
F Wang, Q X Fan
Esophageal cancer (EC) is one of common malignant tumors, and the incidence and mortality of EC in China rank the first place in the world. Because of the occult onset, the early atypical symptoms, and the lack of effective early diagnostic methods, most of patients are diagnosed at an advanced stage of the disease and lost the chance of surgery. Comprehensive treatment including palliative medical treatment, molecular targeted therapy, immunotherapy and so on is appropriate for these patients. How to choose the chemotherapy regimen and formulate reasonable treatment plan has become a hot spot in clinical research...
September 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/27411023/recent-advances-and-future-of-immunotherapy-for-glioblastoma
#12
REVIEW
Neha Kamran, Alexandra Calinescu, Marianela Candolfi, Mayuri Chandran, Yohei Mineharu, Antonela S Asad, Carl Koschmann, Felipe J Nunez, Pedro R Lowenstein, Maria G Castro
INTRODUCTION: Outcome for glioma (GBM) remains dismal despite advances in therapeutic interventions including chemotherapy, radiotherapy and surgical resection. The overall survival benefit observed with immunotherapies in cancers such as melanoma and prostate cancer has fuelled research into evaluating immunotherapies for GBM. AREAS COVERED: Preclinical studies have brought a wealth of information for improving the prognosis of GBM and multiple clinical studies are evaluating a wide array of immunotherapies for GBM patients...
October 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/26916881/predictive-efficacy-biomarkers-of-programmed-cell-death-1-programmed-cell-death-1-ligand-blockade-therapy
#13
REVIEW
Xiao-Na Fang, Li-Wu Fu
Inhibitors of immune check-point molecule, programmed cell death 1 (PD-1) and its ligand, programmed cell death ligand 1 (PD-L1) have attracted much attention in cancer immunotherapy recently due to their durable antitumor effects in various malignances, especially the advanced ones. Unfortunately, only a fraction of patients with advanced tumors could benefit from anti-PD-1/PD-L1 therapy, while others still worsened. The key to this point is that there are no efficient biomarkers for screening anti-PD-1/PD-L1-sensitive patients...
2016: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/26236401/immunotherapy-treatments-for-small-cell-lung-cancer-past-present-and-future
#14
Matthew Whitehurst, Alberto Chiappori
Small-cell lung cancer remains a considerable cause of morbidity and mortality. To this day, first-line therapy continues to be a platinum agent with etoposide, combined with radiation therapy in cases of limited stage disease. Numerous, largely unsuccessful, attempts at controlling the disease have included different chemotherapy strategies, the utilization of antiangiogenic agents, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors and other treatment modalities. Immunotherapy, including vaccines, immune response modifiers, inhibitors of check point blockades and immunologic-targeted toxins may well be the future of treatment, not only to enhance the proven chemotherapy effects, but to improve the control of minimal residual disease and the response with salvage chemotherapy...
2013: Lung Cancer Management
https://www.readbyqxmd.com/read/26060497/evolving-concepts-immunity-in-oncology-from-targets-to-treatments
#15
REVIEW
Hina Khan, Rasim Gucalp, Iuliana Shapira
Cancer is associated with global immune suppression of the host. Malignancy-induced immune suppressive effect can be circumvented by blocking the immune checkpoint and tip the immune balance in favor of immune stimulation and unleash cytotoxic effects on cancer cells. Human antibodies directed against immune checkpoint proteins: cytotoxic T lymphocytes antigen-4 (CTLA-4) and programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), have shown therapeutic efficacy in advanced melanoma and non-small-cell lung cancer and other malignancies...
2015: Journal of Oncology
https://www.readbyqxmd.com/read/25697485/tlr3-triggering-regulates-pd-l1-cd274-expression-in-human-neuroblastoma-cells
#16
Marianne Boes, Friederike Meyer-Wentrup
Neuroblastoma is the most common extracranial solid tumor in children, causing 12% of all pediatric cancer mortality. Neuroblastoma specific T-cells have been detected in patients, but usually fail to attack and eradicate the tumors. Tumor immune evasion may thus play an important role in neuroblastoma pathogenicity. Recent research in adult cancer patients shows that targeting T-cell check-point molecules PD-1/PD-L1 (or CD279/CD274) may bolster immune reactivity against solid tumors. Also, infections can be associated with spontaneous neuroblastoma regression...
May 28, 2015: Cancer Letters
https://www.readbyqxmd.com/read/25247880/health-care-workers-in-danger-zones-a-special-report-on-safety-and-security-in-a-changing-environment
#17
Lynda J Redwood-Campbell, Sharonya N Sekhar, Christine R Persaud
INTRODUCTION: Violence against humanitarian health care workers and facilities in situations of armed conflict is a serious humanitarian problem. Targeting health care workers and destroying or looting medical facilities directly or indirectly impacts the delivery of emergency and life-saving medical assistance, often at a time when it is most needed. PROBLEM: Attacks may be intentional or unintentional and can take a range of forms from road blockades and check points which delay or block transport, to the direct targeting of hospitals, attacks against medical personnel, suppliers, patients, and armed entry into health facilities...
October 2014: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/25069255/-analysis-of-the-cardiac-side-effects-of-antipsychotics-japanese-adverse-drug-event-report-database-jader
#18
Takashi Ikeno, Yasuyuki Okumura, Kiyotaka Kugiyama, Hiroto Ito
We analyzed the cases of side effects due to antipsychotics reported to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) from Jan. 2004 to Dec. 2012. We used the Japanese Adverse Drug Event Report Database (JADER) and analyzed 136 of 216,945 cases using the defined terms. We also checked the cardiac adverse effects listed in the package inserts of the antipsychotics involved. We found cases of Ikr blockade resulting in sudden death (49 cases), electrocardiogram QT prolonged (29 cases), torsade de pointes (TdP, 19 cases), ventricular fibrillation (VF, 10 cases)...
August 2013: Nihon Shinkei Seishin Yakurigaku Zasshi, Japanese Journal of Psychopharmacology
https://www.readbyqxmd.com/read/24990616/phospho-flow-detection-of-constitutive-and-cytokine-induced-pstat3-5-pakt-and-perk-expression-highlights-novel-prognostic-biomarkers-for-patients-with-multiple-myeloma
#19
R Brown, S Yang, C Weatherburn, J Gibson, P J Ho, H Suen, D Hart, D Joshua
Identifying check points in cell signal transduction pathways has led to the development of new cancer therapies; however, relatively few studies have determined the diagnostic and prognostic significance of analysing phosphorylated signaling proteins in patient blood and bone marrow (BM) samples. This is the first comprehensive phospho-flow study of both constitutive and cytokine-induced pSTAT3, pSTAT5, pAKT and phosphorylated extracellular signal-regulated kinase (pERK) expression in malignant plasma cells of patients with monoclonal gammopathies...
February 2015: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/24737949/braf-and-beyond-tailoring-strategies-for-the-individual-melanoma-patient
#20
REVIEW
Anthony Jarkowski, Nikhil I Khushalani
Until recently, options for therapy in metastatic melanoma were limited. The understanding of immune check-point blockade and the discovery of molecular pathways involving driver mutations like BRAF has transformed the therapeutic landscape in this disease. Ipilimumab was the first drug shown to improve survival while vemurafenib demonstrated rapid responses never seen before in melanoma. Drugs from these classes and others are now in advanced stages of development and primed to positively impact patient survival in an incremental fashion...
2014: Journal of Carcinogenesis
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