keyword
MENU ▼
Read by QxMD icon Read
search

Checkpoint

keyword
https://www.readbyqxmd.com/read/28454438/chk2-is-involved-in-the-p53-independent-radiosensitizing-effects-of-valproic-acid
#1
Dong Wan Choo, Sung Ho Goh, Young Woo Cho, Hye Jung Baek, Eun Jung Park, Noboru Motoyama, Tae Hyun Kim, Joo Young Kim, Sang Soo Kim
Radiotherapy is an effective treatment for the majority of types of localized solid cancer. However, the risk of side effects to the surrounding normal tissues limits radiotherapeutic approaches. Whilst the mechanism of action of valproic acid, an inhibitor of histone deacetylase, remains unknown, the inhibitor is a potential antineoplastic radiosensitizer. The present study demonstrated the in vitro radiosensitizing effects of valproic acid on the human breast cancer MCF7 cell line, and revealed that valproic acid increased the level of DNA breakage, apoptosis and senescence...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454371/synergistic-effects-of-a-novel-lipid-soluble-extract-from-pinellia-pedatisecta-schott-and-cisplatin-on-human-cervical-carcinoma-cell-lines-through-the-regulation-of-dna-damage-response-signaling-pathway
#2
Mingxing Zhang, Hongwei Zhang, Yi Yu, Haixia Huang, Guiling Li, Congjian Xu
Herbal medicines have been recognized as an attractive approach for cancer therapy with minimal side effects. The present study investigated the type of interaction between a novel lipid-soluble extract from Pinellia pedatisecta Schott (PE) and cisplatin (CDDP) on human cervical cancer SiHa and CaSki cell lines in vitro. The mechanism of this combination was studied using cell proliferation, invasion and apoptosis assays, and by analyzing cell cycle distribution and protein expression, with a focus on DNA damage response (DDR) activation...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454356/harnessing-antitumor-immunity-employment-of-tumor-recall-antigens-to-optimize-the-inflammatory-response-to-cancer
#3
Kimberly A Silverio, Shyam A Patel
The advent of immunotherapy for cancer has contributed to the era of personalized medicine for cancer. The various immunotherapy-based treatments that have been explored thus far include monoclonal antibody therapy, tumor vaccines, immune checkpoint blockade and adoptive T cell transfer, among others. The groundwork for all these immunotherapeutic modalities rests within the tumor microenvironment, specifically the immune factors that influence the tumor-drug interface. Prior to therapeutic design, the tumor microenvironmental interactions and the current barriers to successful treatment must first be understood...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453695/genetic-variants-of-dna-repair-related-genes-predict-efficacy-of-tas-102-in-patients-with-refractory-metastatic-colorectal-cancer
#4
M Suenaga, M Schirripa, S Cao, W Zhang, D Yang, S Murgioni, D Rossini, F Marmorino, A Mennitto, Y Ning, S Okazaki, M D Berger, Y Miyamoto, R Gopez, A Barzi, T Yamaguchi, F Loupakis, H-J Lenz
Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28449524/a-mighty-oak-in-the-rapidly-expanding-field-of-checkpoint-inhibition-for-nsclc
#5
EDITORIAL
Petros Christopoulos, Michael Thomas
No abstract text is available yet for this article.
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28448802/ddk-promotes-tumor-chemoresistance-and-survival-via-multiple-pathways
#6
Nanda Kumar Sasi, Arjun Bhutkar, Nathan J Lanning, Jeffrey P MacKeigan, Michael Weinreich
DBF4-dependent kinase (DDK) is a two-subunit kinase required for initiating DNA replication at individual origins and is composed of CDC7 kinase and its regulatory subunit DBF4. Both subunits are highly expressed in many diverse tumor cell lines and primary tumors, and this is correlated with poor prognosis. Inhibiting DDK causes apoptosis of tumor cells, but not normal cells, through a largely unknown mechanism. Firstly, to understand why DDK is often overexpressed in tumors, we identified gene expression signatures that correlate with DDK high- and DDK low-expressing lung adenocarcinomas...
April 24, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28448494/integrin-%C3%AE-1-activation-induces-an-anti-melanoma-host-response
#7
Laila Ritsma, Ipsita Dey-Guha, Nilesh Talele, Xavier Sole, Salony, Joeeta Chowdhury, Kenneth N Ross, Sridhar Ramaswamy
TGF-β is a cytokine thought to function as a tumor promoter in advanced malignancies. In this setting, TGF-β increases cancer cell proliferation, survival, and migration, and orchestrates complex, pro-tumorigenic changes in the tumor microenvironment. Here, we find that in melanoma, integrin β1-mediated TGF-β activation may also produce tumor suppression via an altered host response. In the A375 human melanoma cell nu/nu xenograft model, we demonstrate that cell surface integrin β1-activation increases TGF-β activity, resulting in stromal activation, neo-angiogenesis and, unexpectedly for this nude mouse model, increase in the number of intra-tumoral CD8+ T lymphocytes within the tumor microenvironment...
2017: PloS One
https://www.readbyqxmd.com/read/28448462/targeting-the-atr-chk1-axis-in-cancer-therapy
#8
REVIEW
Stuart Rundle, Alice Bradbury, Yvette Drew, Nicola J Curtin
Targeting the DNA damage response (DDR) is a new therapeutic approach in cancer that shows great promise for tumour selectivity. Key components of the DDR are the ataxia telangiectasia mutated and Rad3 related (ATR) and checkpoint kinase 1 (CHK1) kinases. This review article describes the role of ATR and its major downstream target, CHK1, in the DDR and why cancer cells are particularly reliant on the ATR-CHK1 pathway, providing the rationale for targeting these kinases, and validation of this hypothesis by genetic manipulation...
April 27, 2017: Cancers
https://www.readbyqxmd.com/read/28447739/neural-precursor-cell-expressed-developmentally-downregulated-8%C3%A2-activating-enzyme-inhibitor-mln4924-sensitizes-colorectal-cancer-cells-to-oxaliplatin-by-inducing-dna-damage-g2-cell-cycle-arrest-and-apoptosis
#9
Wanwei Zheng, Zhongguang Luo, Jun Zhang, Pei Min, Wenshuai Li, Diannan Xu, Ziqiang Zhang, Panpan Xiong, Hong Liang, Jie Liu
Oxaliplatin-based chemotherapy is a primary treatment for patients with metastatic colorectal cancer (CRC); however, its efficacy is limited. Therefore, novel therapeutic agents are urgently required. MLN4924 is a first‑in‑class inhibitor of neural precursor cell expressed, developmentally downregulated 8 (NEDD8)‑activating enzyme E1, and has entered various phase‑I/II clinical trials for cancer therapy due to its significant anticancer efficacy. The aim of the present study was to examine the synergistic effect and underlying mechanisms of MLN4924 and oxaliplatin combined treatment for CRC...
March 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447210/mitf-suppression-by-ch5552074-inhibits-cell-growth-in-melanoma-cells
#10
Satoshi Aida, Yukiko Sonobe, Munehiro Yuhki, Kiyoaki Sakata, Toshihiko Fujii, Hiroshi Sakamoto, Takakazu Mizuno
PURPOSE: Although treatment of melanoma with BRAF inhibitors and immune checkpoint inhibitors achieves a high response rate, a subset of melanoma patients with intrinsic and acquired resistance are insensitive to these therapeutics, so to improve melanoma therapy other target molecules need to be found. Here, we screened our chemical library to identify an anti-melanoma agent and examined its action mechanisms to show cell growth inhibition activity. METHODS: We screened a chemical library against multiple skin cancer cell lines and conducted ingenuity pathway analysis (IPA) to investigate the mechanisms of CH5552074 activity...
April 26, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28447005/future-directions-in-esophageal-cancer-therapy
#11
Ori Wald, Brandon Smaglo, Henry Mok, Shawn S Groth
Resection techniques for esophageal carcinoma continue to evolve, from endoscopic mucosal resection or endoscopic submucosal dissection for early stage disease to standard and robot-assisted minimally invasive esophagectomy as part of multimodal therapy for locally advanced disease. Though currently limited to assessing conduit perfusion and sentinel lymph nodes, embedded technology in the robotic surgical platform will likely play an expanded role during esophagectomy in the future. The use of targeted therapies, checkpoint inhibitors, engineered immune cell therapy, and cancer vaccines show promise in the treatment of systemic disease...
March 2017: Annals of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/28446908/association-of-ctla-4-gene-variants-with-response-to-therapy-and-long-term-survival-in-metastatic-melanoma-patients-treated-with-ipilimumab-an-italian-melanoma-intergroup-study
#12
Paola Queirolo, Beatrice Dozin, Anna Morabito, Barbara Banelli, Patrizia Piccioli, Cristiana Fava, Claudio Leo, Roberta Carosio, Stefania Laurent, Vincenzo Fontana, Pier Francesco Ferrucci, Chiara Martinoli, Emilia Cocorocchio, Angelo Battaglia, Paolo A Ascierto, Mariaelena Capone, Ester Simeone, Federica De Galitiis, Elena Pagani, Gian Carlo Antonini Cappellini, Paolo Marchetti, Michele Guida, Stefania Tommasi, Mario Mandalà, Barbara Merelli, Pietro Quaglino, Paolo Fava, Massimo Guidoboni, Massimo Romani, Francesco Spagnolo, Maria Pia Pistillo
Ipilimumab (IPI) blocks CTLA-4 immune checkpoint resulting in T cell activation and enhanced antitumor immunity. IPI improves overall survival (OS) in 22% of patients with metastatic melanoma (MM). We investigated the association of CTLA-4 single nucleotide variants (SNVs) with best overall response (BOR) to IPI and OS in a cohort of 173 MM patients. Patients were genotyped for six CTLA-4 SNVs (-1661A>G, -1577G>A, -658C>T, -319C>T, +49A>G, and CT60G>A). We assessed the association between SNVs and BOR through multinomial logistic regression (MLR) and the prognostic effect of SNVs on OS through Kaplan-Meier method...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28446466/landscape-of-combination-immunotherapy-and-targeted-therapy-to-improve-cancer-management
#13
Leandro M Colli, Mitchell J Machiela, Han Zhang, Timothy Myers, Lea Jessop, Olivier Delattre, Kai Yu, Stephen J Chanock
Cancer treatments composed of immune checkpoint inhibitors and oncogene-targeted drugs might improve cancer management, but there has been little investigation of their combined potential as yet. To estimate the fraction of cancer cases that might benefit from such combination therapy, we conducted an exploratory study of cancer genomic data sets to determine the proportion with somatic mutation profiles amenable to either immunotherapy or targeted therapy. We surveyed 13,349 genomic profiles from public databases for cases with specific mutations targeted by current agents or a burden of exome-wide non-synonymous mutations (NsM) that exceeds a proposed threshold for response to checkpoint inhibitors...
April 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28446055/investigational-drugs-for-nasopharyngeal-carcinoma
#14
Brigette B Y Ma, Edwin P Hui, Anthony T C Chan
Nasopharyngeal carcinoma (NPC) is endemic to Southern China and Asia and is etiologically associated with the Epstein Barr virus (EBV). Whole exome and genome sequencing (WES, WGS) studies of NPC have reported several actionable therapeutic targets, and that the mutational load of NPC maybe comparable to that of squamous head and neck cancer. These unique biological characteristics have been exploited as potential targets and a wide range of investigational drugs are being investigated in clinical trials. Area covered: This review focused on the latest clinical development of the most promising classes of investigational agents in the treatment of advanced NPC...
April 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28446053/immunotherapy-for-the-treatment-of-breast-cancer
#15
Mariela A Moreno Ayala, Maria Florencia Gottardo, Antonela S Asad, Camila Zuccato, Alejandro Nicola, Adriana Seilicovich, Marianela Candolfi
Introduction Breast cancer is the most common cancer as well as the highest cause of death by cancer in women worldwide. Although routine treatment improves the outcome of early stage breast cancer patients, there is no effective therapy for the disseminated disease. Immunotherapy has emerged as a powerful therapeutic strategy for the treatment of many cancers. Although traditionally conceived as a non-immunogenic tumor, breast cancer is now considered a potential target for immunotherapy. Areas covered In this review, the authors discuss different immunotherapeutic strategies that are currently being tested for the treatment of breast cancer: These strategies include: (i) the blockade of immunological checkpoints, (ii) antitumor vaccines, (iii) adoptive T-cell transfer therapy, and (iv) adoptive immunotherapy with monoclonal antibodies...
April 27, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28445951/pd-l1-expression-in-perihilar-and-intrahepatic-cholangiocarcinoma
#16
Jacqueline Fontugne, Jérémy Augustin, Anaïs Pujals, Philippe Compagnon, Benoit Rousseau, Alain Luciani, Christophe Tournigand, Daniel Cherqui, Daniel Azoulay, Jean-Michel Pawlotsky, Julien Calderaro
Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444424/the-experience-of-immune-checkpoint-inhibitors-in-chinese-patients-with-metastatic-melanoma-a-retrospective-case-series
#17
Xizhi Wen, Ya Ding, Jingjing Li, Jingjing Zhao, Ruiqing Peng, Dandan Li, Baoyan Zhu, Yao Wang, Xing Zhang, Xiaoshi Zhang
Melanomas in Chinese patients show relatively higher rates of acral and mucosal types than in other populations. However, the efficacy of checkpoint inhibitor therapies against these melanoma subtypes is not well defined. We analyzed 52 patients treated with ipilimumab, pembrolizumab, or a combination of both to evaluate the efficacy and safety of checkpoint inhibitors in Chinese patients with advanced melanoma, particularly those with acral and mucosal types. The objective response rates (ORRs) were 0, 25, and 20% for ipilimumab, pembrolizumab, and pembrolizumab plus ipilimumab, respectively...
April 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28444111/pattern-recognition-receptors-immune-targets-to-enhance-cancer-immunotherapy
#18
T Shekarian, S Valsesia-Wittmann, J Brody, M C Michallet, S Depil, C Caux, A Marabelle
Durable tumor responses and significant levels of disease control rates have been described in more than 20 advanced/metastatic cancer types with B7-family immune checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies. These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab and atezolizumab are currently revolutionizing the way we envision the future of cancer care. However these clinical benefits are not observed in all cancer types and in every patient. Therefore, our clinical challenge is to identify therapeutic strategies which could overcome the primary and secondary resistances to these novel cancer immunotherapies...
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28443099/a-century-of-radiation-therapy-and-adaptive-immunity
#19
REVIEW
Dörthe Schaue
The coming of age for immunotherapy (IT) as a genuine treatment option for cancer patients through the development of new and effective agents, in particular immune checkpoint inhibitors, has led to a huge renaissance of an old idea, namely to harness the power of the immune system to that of radiation therapy (RT). It is not an overstatement to say that the combination of RT with IT has provided a new conceptual platform that has re-energized the field of radiation oncology as a whole. One only has to look at the immense rise in sessions at professional conferences and in grant applications dealing with this topic to see its emergence as a force, while the number of published reviews on the topic is staggering...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28442918/targeting-the-pd-1-pathway-in-pediatric-solid-tumors-and-brain-tumors
#20
REVIEW
Lars M Wagner, Val R Adams
While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1) pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies...
2017: OncoTargets and Therapy
keyword
keyword
26597
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"