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https://www.readbyqxmd.com/read/28224235/oral-mucosal-changes-induced-by-anticancer-targeted-therapies-and-immune-checkpoint-inhibitors
#1
REVIEW
Emmanuelle Vigarios, Joel B Epstein, Vincent Sibaud
Development of biological targeted therapies and immune checkpoint inhibitors has redefined the treatment for many cancers; however, the increasing use of new protocols has led to physicians observing a new spectrum of toxicities. To date, oral adverse events induced by these new anticancer therapies have been mainly reported using nonspecific terminology ("stomatitis," "mucosal inflammation," "mucositis") and remain poorly characterized, with the exception of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis...
February 22, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28223846/prospect-of-the-use-of-checkpoint-inhibitors-in-hepatocellular-cancer-treatments
#2
REVIEW
Ali Raufi, Maria Tria Tirona
Hepatocellular cancer (HCC) is a very fatal disease due to limited therapeutic options as well as due to its association with underlying chronic liver disease in the majority of cases. The immune evasion in HCC signifies a major barrier to the delivery of effective immunotherapy. Sorafenib is the only Food and Drug Administration-approved drug available with an overall response rate of 2%-3% and overall survival of 2.8 months. Chemotherapy has not been used routinely because of the relative refractoriness of advanced HCC...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28223273/pd-l1-studies-across-tumor-types-its-differential-expression-and-predictive-value-in-patients-treated-with-immune-checkpoint-inhibitors
#3
Harriet M Kluger, Christopher R Zito, Gabriela Turcu, Marina Baine, Hongyi Zhang, Adebowale Adeniran, Mario Sznol, David L Rimm, Yuval Kluger, Lieping Chen, Justine V Cohen, Lucia B Jilaveanu
PURPOSE: With recent approval of inhibitors of PD-1 in melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC), extensive efforts are underway to develop biomarkers predictive of response. PD-L1 expression has been most widely studied, and is more predictive in NSCLC than RCC or melanoma. We therefore studied differences in expression patterns across tumor types. EXPERIMENTAL DESIGN: We employed tissue microarrays with tumors from NSCLC, RCC or melanoma and a panel of cell lines to study differences between tumor types...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28223073/immunotherapy-comes-of-age-immune-aging-checkpoint-inhibitors
#4
REVIEW
Rawad Elias, Theodoros Karantanos, Elizabeth Sira, Kevan L Hartshorn
Immune checkpoint inhibitors (ICIs) are based on the understanding that there are multilayered checks and balances which can be manipulated to unleash already existing, but paralyzed, immune responses to cancer. These agents are safer and more efficacious than classic cytotoxic drugs making them a very attractive therapeutic option, especially in older adults. Current available data do not suggest significant age-associated differences in the clinical profile of ICIs. It must be noted, however, that there is still relatively little information on the use of ICIs in adults over 75years of age and aging is associated with a decline in the immune system or "immunosenescence" which theoretically can reduce the efficacy of these immune based therapies...
February 17, 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/28223062/nivolumab-for-previously-treated-unresectable-metastatic-anal-cancer-nci9673-a-multicentre-single-arm-phase-2-study
#5
Van K Morris, Mohamed E Salem, Halla Nimeiri, Syma Iqbal, Preet Singh, Kristen Ciombor, Blase Polite, Dustin Deming, Emily Chan, James L Wade, Lianchun Xiao, Tanios Bekaii-Saab, Luis Vence, Jorge Blando, Armeen Mahvash, Wai Chin Foo, Chimela Ohaji, Manolo Pasia, Gail Bland, Aki Ohinata, Jane Rogers, Amir Mehdizadeh, Kimberly Banks, Richard Lanman, Robert A Wolff, Howard Streicher, James Allison, Padmanee Sharma, Cathy Eng
BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. METHODS: We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA...
February 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28222478/-possible-significance-of-bronchoalveolar-lavage-cytology-at-initial-diagnosis-and-follow-up-of-lung-cancer
#6
A Grünewaldt, C Hügel, E Hermann, T O F Wagner
Bronchoalveolar lavage [BAL] is an important procedure in the diagnosis of a variety of lung diseases. While it has enormous value in the diagnostics of inflammatory parenchymal diseases, its significance in lung cancer is unclear. Keeping in mind that immune therapy (e. g. application of checkpoint inhibitors) is gaining importance in the management of lung carcinoma, it is important to know if there are typical cellular patterns in BAL of lung cancer patients. Methods In a retrospective proof of principle-study, we analyzed 38 patients who underwent BAL at the initial diagnosis of lung cancer...
February 2017: Pneumologie
https://www.readbyqxmd.com/read/28222397/a-novel-approach-towards-design-synthesis-and-evaluation-of-some-schiff-base-analogues-of-2-aminopyridine-and-2-aminobezothiazole-against-hepatocellular-carcinoma
#7
Shinu Chacko, Subir Samanta
Hepatocellular carcinoma is the most common primary malignancy of the liver with poor prognosis. In this study novel, Schiff's bases of 2-aminopyridine (SSSC-26 to 31) and 2-aminobenzothiazole (SSSC-32 to 37) were designed, synthesised and evaluated for antioxidant potential using DPPH method, and anti-hepatocellular carcinoma property using diethylnitrosamine (DEN) induced hepatocellular carcinoma rat model. The in-silico pharmacokinetic, rule of five and toxicity studies reveals that all the leads have an excellent intrinsic quality and sufficient structural features necessary for an oral activity...
February 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28221865/cost-effectiveness-of-immune-checkpoint-inhibition-in-braf-wild-type-advanced-melanoma
#8
Christine G Kohn, Simon B Zeichner, Qiushi Chen, Alberto J Montero, Daniel A Goldstein, Christopher R Flowers
Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)-demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28220466/cardiovascular-toxicities-associated-with-cancer-immunotherapies
#9
REVIEW
Daniel Y Wang, Gosife Donald Okoye, Thomas G Neilan, Douglas B Johnson, Javid J Moslehi
PURPOSE OF REVIEW: We review the cardiovascular toxicities associated with cancer immune therapies and discuss the cardiac manifestations, potential mechanisms, and management strategies. RECENT FINDINGS: The recent advances in cancer immune therapy with immune checkpoint inhibitors and adoptive cell transfer have improved clinical outcomes in numerous cancers. The rising use of cancer immune therapy will lead to a higher incidence in immune-related adverse events...
March 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28220447/current-management-of-refractory-germ-cell-tumors-and-future-directions
#10
REVIEW
J Clayton Allen, Austin Kirschner, Kristen R Scarpato, Alicia K Morgans
PURPOSE OF REVIEW: We review current management strategies for patients with relapsed and refractory germ cell tumors (GCTs), defined as relapsed or persistent disease following at least one line of cisplatin-based chemotherapy. Additionally, we discuss future directions in the management of these patients. RECENT FINDINGS: Recent studies involving targeted therapies have been disappointing. Nevertheless, studies of the management of refractory germ cell cancer are ongoing, with a focus on optimal utilization of high-dose chemotherapy and autologous stem cell transplant, as well as the role of immune checkpoint inhibitors in refractory germ cell tumors...
February 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28220304/immunosenescence-and-cancer
#11
Graham Pawelec
Age is a major risk factor for solid cancers, hitherto conventionally viewed in the context of the cell biology of carcinogenesis. However, if cancers are immunogenic, the immune system could protect against tumorigenesis ("immunosurveillance"), and vaccination or other immunomodulatory treatments should be therapeutically beneficial, as has been recently dramatically documented in a fraction of patients with certain tumors responding to immune checkpoint blockade. This begs the question that if immunity decreases with age ("immunosenescence"), this may contribute to increased cancer disease in the elderly and a lower likelihood of clinical benefit from immunotherapy...
February 20, 2017: Biogerontology
https://www.readbyqxmd.com/read/28220209/s-phase-checkpoint-regulations-that-preserve-replication-and-chromosome-integrity-upon-dntp-depletion
#12
REVIEW
Michele Giannattasio, Dana Branzei
DNA replication stress, an important source of genomic instability, arises upon different types of DNA replication perturbations, including those that stall replication fork progression. Inhibitors of the cellular pool of deoxynucleotide triphosphates (dNTPs) slow down DNA synthesis throughout the genome. Following depletion of dNTPs, the highly conserved replication checkpoint kinase pathway, also known as the S-phase checkpoint, preserves the functionality and structure of stalled DNA replication forks and prevents chromosome fragmentation...
February 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#13
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28219375/state-of-the-art-in-anti-cancer-mabs
#14
REVIEW
S M Chiavenna, J P Jaworski, A Vendrell
Following Milstein's discovery, the monoclonal antibodies (mAbs) became a basic tool for biomedical science. In cancer field, since the first mAb was approved by the FDA a great improvement took place making of them a therapeutic option for many cancer types in the current clinical practice. Today, mAbs are being developed to target different molecules with different mechanisms of action and its target potential is unlimited. However, this huge and fast growing new field needs to be organized to better understand the treatment options we have to confront different cancer diseases...
February 20, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28219022/rationale-for-stimulator-of-interferon-genes-targeted-cancer-immunotherapy
#15
REVIEW
Thaiz Rivera Vargas, Isis Benoit-Lizon, Lionel Apetoh
The efficacy of checkpoint inhibitor therapy illustrates that cancer immunotherapy, which aims to foster the host immune response against cancer to achieve durable anticancer responses, can be successfully implemented in a routine clinical practice. However, a substantial proportion of patients does not benefit from this treatment, underscoring the need to identify alternative strategies to defeat cancer. Despite the demonstration in the 1990's that the detection of danger signals, including the nucleic acids DNA and RNA, by dendritic cells (DCs) in a cancer setting is essential for eliciting host defence, the molecular sensors responsible for recognising these danger signals and eliciting anticancer immune responses remain incompletely characterised, possibly explaining the disappointing results obtained so far upon the clinical implementation of DC-based cancer vaccines...
February 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28218707/fkbp51-immunohistochemical-expression-a-new-prognostic-biomarker-for-oscc
#16
Daniela Russo, Francesco Merolla, Massimo Mascolo, Gennaro Ilardi, Simona Romano, Silvia Varricchio, Virginia Napolitano, Angela Celetti, Loredana Postiglione, Pier Paolo Di Lorenzo, Luigi Califano, Giovanni Orabona Dell'Aversana, Fabio Astarita, Maria Fiammetta Romano, Stefania Staibano
Up-to-date, several molecular markers of prognosis have been studied in Oral Squamous Cell Carcinoma (OSCC), but none entered in the clinical setting. Therapy of OSCC tumors mainly relies on surgery, radiotherapy and partially on chemotherapy; there is an urgent need for biomarkers able to better stratify OSCC patients' risk to address targeted therapeutic strategies. The role of immune response in the pathogenesis and biological behavior of OSCC has been investigated by several authors, and promising results have been obtained with immune checkpoint inhibitors...
February 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218681/the-intra-s-checkpoint-responses-to-dna-damage
#17
REVIEW
Divya Ramalingam Iyer, Nicholas Rhind
Faithful duplication of the genome is a challenge because DNA is susceptible to damage by a number of intrinsic and extrinsic genotoxins, such as free radicals and UV light. Cells activate the intra-S checkpoint in response to damage during S phase to protect genomic integrity and ensure replication fidelity. The checkpoint prevents genomic instability mainly by regulating origin firing, fork progression, and transcription of G1/S genes in response to DNA damage. Several studies hint that regulation of forks is perhaps the most critical function of the intra-S checkpoint...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28218625/egress-of-sperm-autoantigen-from-seminiferous-tubules-maintains-systemic-tolerance
#18
Kenneth S K Tung, Jessica Harakal, Hui Qiao, Claudia Rival, Jonathan C H Li, Alberta G A Paul, Karen Wheeler, Patcharin Pramoonjago, Constance M Grafer, Wei Sun, Robert D Sampson, Elissa W P Wong, Prabhakara P Reddi, Umesh S Deshmukh, Daniel M Hardy, Huanghui Tang, C Yan Cheng, Erwin Goldberg
Autoimmune responses to meiotic germ cell antigens (MGCA) that are expressed on sperm and testis occur in human infertility and after vasectomy. Many MGCA are also expressed as cancer/testis antigens (CTA) in human cancers, but the tolerance status of MGCA has not been investigated. MGCA are considered to be uniformly immunogenic and nontolerogenic, and the prevailing view posits that MGCA are sequestered behind the Sertoli cell barrier in seminiferous tubules. Here, we have shown that only some murine MGCA are sequestered...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28218255/approvals-in-2016-the-march-of-the-checkpoint-inhibitors
#19
Gideon M Blumenthal, Richard Pazdur
No abstract text is available yet for this article.
February 20, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28217764/vpreb-serves-as-an-invariant-surrogate-antigen-for-selecting-immunoglobulin-antigen-binding-sites
#20
Mohamed Khass, Tessa Blackburn, Peter D Burrows, Mark R Walter, Emidio Capriotti, Harry W Schroeder
Developmental checkpoints eliminate B cells synthesizing defective immunoglobulin heavy (HC) and light (LC) chains. The first checkpoint tests for formation of a VpreB/λ5/µHC-containing preB-cell receptor (preBCR) and predicts whether µHCs will bind conventional LCs to form membrane IgM. VpreB and λ5 also create a sensing site that interacts with µHC antigen-binding region CDR-H3, but whether it plays a role in immunoglobulin repertoire selection and function is unknown. On a position-by-position basis, we analyzed the amino acid content of CDR-H3s from H chains cloned from living and apoptotic preB cells and from IgG:Antigen structures...
July 14, 2016: Science Immunology
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