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check point blockade

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]
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
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
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
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
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
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
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
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
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
Marc Pracht, Dominik Berthold
Until recently, the standard treatment for metastatic renal cell carcinoma (RCC) was nonspecific immunotherapy based on interleukin-2 or interferon-α. This was associated with a modest survival benefit and with significant clinical toxicities. The understanding of numerous molecular pathways in RCC, including HIF, VEGF, mTOR, and the consecutive use of targeted therapies since the beginning of 2005 have significantly improved outcomes for patients with metastatic RCC with an overall survival greater than 2 years...
2014: Progress in Tumor Research
Lucia Gelao, Carmen Criscitiello, Angela Esposito, Aron Goldhirsch, Giuseppe Curigliano
Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific "immune-related adverse events" (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique "innocent bystander" effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include symptomatic therapies or systemic corticosteroids...
March 2014: Toxins
Jose Luis Perez-Gracia, Sara Labiano, Maria E Rodriguez-Ruiz, Miguel F Sanmamed, Ignacio Melero
Inhibitory receptors on immune system cells respond to membrane-bound and soluble ligands to abort or mitigate the intensity of immune responses by raising thresholds of activation, halting proliferation, favoring apoptosis or inhibiting/deviating effector function differentiation. Such evolutionarily selected inhibitory mechanisms are termed check-points and therefore check-point inhibitors empower any ongoing anti-cancer immune response that might have been too weak or exhausted. Monoclonal antibodies (mAb) interfering with CTLA-4-CD80/86, PD-1 - PD-L1, TIM-3-GAL9 and LAG3-MHC-II belong to this category of check-point inhibitors...
April 2014: Current Opinion in Immunology
Jason John Luke, Patrick Alexander Ott
In recent years, therapeutic approaches for many tumors have broadened or even shifted entirely from cytotoxic chemotherapy to specific targeting of dysregulated proteins (predominately kinases), and more recently, harnessing of the anti-tumor immune response. The most prominent example of this shift is the management of metastatic melanoma, where BRAF and MEK inhibition and CLTA-4 blockade have established an entirely new standard of care in the last 3 years. Targeted kinase inhibition and immune checkpoint blockade have different strengths and weaknesses...
December 2013: Expert Opinion on Pharmacotherapy
Thumwadee Tangsiriwatthana, Ussanee S Sangkomkamhang, Pisake Lumbiganon, Malinee Laopaiboon
BACKGROUND: Cervical dilatation and uterine intervention can be performed under sedation, local or general anaesthesia for obstetrics and gynaecological conditions. Many gynaecologists use paracervical local anaesthesia but its effectiveness is unclear. This review was originally published in 2009 and was updated in 2013. OBJECTIVES: The objectives of this review were to determine the effectiveness and safety of paracervical local anaesthesia for cervical dilatation and uterine intervention, versus no treatment, placebo, other methods of regional anaesthesia, sedation and systemic analgesia, and general anaesthesia...
2013: Cochrane Database of Systematic Reviews
Jason J Luke, Gary K Schwartz
The recent past has witnessed unprecedented clinical progress in the treatment of advanced malignant melanoma through targeting of mutant BRAF in approximately 50% of patients and immune check point blockade in all patients. As has been well documented, responses to targeted therapy are of limited duration, and rates of clinical benefit to immunotherapy are modest. Given these factors, palliation of patients with chemotherapy remains an essential aspect of melanoma oncology. Many chemotherapeutics (and combinations with other agents, such as immunotherapy) have been evaluated in melanoma, although no chemotherapy regimen has been documented to provide an overall survival benefit in a prospective, randomized, well-controlled phase III study...
May 2013: Clinics in Dermatology
Sheng Yao, Lieping Chen
A dilemma in cancer immunology is that, although patients often develop active antitumor immune responses, the tumor still outgrows. It has become clear that under the pressure of the host's immune system, cancer cells have adapted elaborate tactics to reduce their immunogenicity (also known as immunoselection) and/or to actively suppress immune cells and promote immune tolerance (also known as immunosubversion). In this issue of the European Journal of Immunology, Dolen and Esendagli [Eur. J. Immunol. 2013...
March 2013: European Journal of Immunology
Michal Lotem, Sharon Merims, Steven Frank, Inna Ospovat, Tamar Peretz
Ipilimumab (Yervoy) is a monocLonal antibody designed to block cytotoxic T cell antigen 4 (CTLA-4), an inhibitory receptor of T lymphocytes. This drug is the first to receive US FDAs approval for advanced stage malignant melanoma in the last 13 years. So far, no survival benefit was achieved for this patient group with single drug or combination chemo- and chemo-immunotherapy. In phase II and III trials, up to 15% of patients had melanoma regressions, with a decreased hazard ratio of death of 0.72 compared to the standard chemotherapy with Dacarbazine...
October 2012: Harefuah
Xiang-Yang Wang, Daming Zuo, Devanand Sarkar, Paul B Fisher
INTRODUCTION: The incidence of melanoma continues to rise, and prognosis in patients with metastatic melanoma remains poor. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) serves as one of the primary immune check points and downregulates T-cell activation pathways. Enhancing T-cell activation by antibody blockade of CTLA-4 provides a new approach to overcome tumor-induced immune tolerance. Recently, anti-CTLA-4 therapy demonstrated significant clinical benefits in patients with metastatic melanoma, which led to the approval of ipilimumab by the FDA in early 2011...
December 2011: Expert Opinion on Pharmacotherapy
Jorge A Garcia, Robert Dreicer
The availability of several novel antibodies, coupled with viral, DNA, and dendritic-cell vaccines, has renewed interest in immunotherapeutic approaches to the treatment of advanced prostate cancer. Although promising, none of these approaches have led to major clinical activity, and in the case of cell-based immunotherapy with GVAX, new concerns about safety arose when this therapy was used in the castration-resistant setting. A more attractive yet toxic approach has also utilized a check-point blockade with CTLA-4 antibodies...
March 2011: Oncology (Williston Park, NY)
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