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https://www.readbyqxmd.com/read/28214651/a-review-on-the-evolution-of-pd-1-pd-l1-immunotherapy-for-bladder-cancer-the-future-is-now
#1
REVIEW
Joaquin Bellmunt, Thomas Powles, Nicholas J Vogelzang
The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated...
February 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28212535/integration-of-the-cancer-related-inflammatory-response-as-a-stratifying-biomarker-of-survival-in-hepatocellular-carcinoma-treated-with-sorafenib
#2
Jessica Howell, David J Pinato, Ramya Ramaswami, Tadaaki Arizumi, Carlotta Ferrari, Antonello Gibbin, Michela E Burlone, Giulia Guaschino, Pierluigi Toniutto, James Black, Laura Sellers, Masatoshi Kudo, Mario Pirisi, Rohini Sharma
BACKGROUND AND AIMS: Response to sorafenib is highly variable in hepatocellular carcinoma (HCC). Baseline inflammatory parameters and treatment toxicities may improve survival prediction in patients on sorafenib therapy. RESULTS: 442 patients with advanced stage HCC on sorafenib were recruited (follow-up 5096 person-months at risk). 88% had BCLC stage B or greater HCC and 72.3% had Child-Pugh A cirrhosis. On Cox multivariate regression, previously-treated HCC (HR 0...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209992/from-basic-apoptosis-discoveries-to-advanced-selective-bcl-2-family-inhibitors
#3
REVIEW
Avi Ashkenazi, Wayne J Fairbrother, Joel D Leverson, Andrew J Souers
Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-XL dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209123/relationships-between-longitudinal-neutrophil-to-lymphocyte-ratios-body-weight-changes-and-overall-survival-in-patients-with-non-small-cell-lung-cancer
#4
B A Derman, J N Macklis, M S Azeem, S Sayidine, S Basu, M Batus, F Esmail, J A Borgia, P Bonomi, M J Fidler
BACKGROUND: There is emerging evidence showing a significant relationship between overall survival (OS) in non-small cell lung cancer NSCLC patients and weight change during chemotherapy or chemoradiation. A high neutrophil/lymphocyte ratio (NLR) at baseline and at follow-up is associated with shorter survival in cancer patients and may be a surrogate for ongoing inflammation, implicated in cancer cachexia and tumor progression. The objective of this study is to explore potential relationships between OS, serial weights, and serial NLRs in advanced NSCLC patients receiving chemotherapy...
February 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28199334/childhood-hematologic-cancer-and-residential-proximity-to-oil-and-gas-development
#5
Lisa M McKenzie, William B Allshouse, Tim E Byers, Edward J Bedrick, Berrin Serdar, John L Adgate
BACKGROUND: Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. METHODS: Participants were 0-24 years old, living in rural Colorado, and diagnosed with cancer between 2001-2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16...
2017: PloS One
https://www.readbyqxmd.com/read/28197391/high-nkg2a-expression-contributes-to-nk-cell-exhaustion-and-predicts-a-poor-prognosis-of-patients-with-liver-cancer
#6
Cheng Sun, Jing Xu, Qiang Huang, Mei Huang, Hao Wen, Chuanshan Zhang, Jinyu Wang, Jiaxi Song, Meijuan Zheng, Haoyu Sun, Haiming Wei, Weihua Xiao, Rui Sun, Zhigang Tian
Background and Aims: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported. Methods: In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197375/tumor-infiltrating-lymphocyte-composition-organization-and-pd-1-pd-l1-expression-are-linked-in-breast-cancer
#7
Laurence Buisseret, Soizic Garaud, Alexandre de Wind, Gert Van den Eynden, Anais Boisson, Cinzia Solinas, Chunyan Gu-Trantien, Céline Naveaux, Jean-Nicolas Lodewyckx, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Denis Larsimont, Martine Piccart-Gebhart, John Stagg, Christos Sotiriou, Karen Willard-Gallo
The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed in some patients, and critical features of the infiltrate remains unresolved. This study examined TIL density, composition and organization together with PD-1 and PD-L1 expression in freshly collected and paraffin-embedded tissues from 125 patients with invasive primary BC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28186092/epstein-barr-virus-particles-induce-centrosome-amplification-and-chromosomal-instability
#8
Anatoliy Shumilov, Ming-Han Tsai, Yvonne T Schlosser, Anne-Sophie Kratz, Katharina Bernhardt, Susanne Fink, Tuba Mizani, Xiaochen Lin, Anna Jauch, Josef Mautner, Annette Kopp-Schneider, Regina Feederle, Ingrid Hoffmann, Henri-Jacques Delecluse
Infections with Epstein-Barr virus (EBV) are associated with cancer development, and EBV lytic replication (the process that generates virus progeny) is a strong risk factor for some cancer types. Here we report that EBV infection of B-lymphocytes (in vitro and in a mouse model) leads to an increased rate of centrosome amplification, associated with chromosomal instability. This effect can be reproduced with virus-like particles devoid of EBV DNA, but not with defective virus-like particles that cannot infect host cells...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28184943/analysis-of-chromosomal-radiosensitivity-of-healthy-brca2-mutation-carriers-and-non-carriers-in-brca-families-with-the-g2-micronucleus-assay
#9
Annelot Baert, Julie Depuydt, Tom Van Maerken, Bruce Poppe, Fransiska Malfait, Tim Van Damme, Sylvia De Nobele, Gianpaolo Perletti, Kim De Leeneer, Kathleen B M Claes, Anne Vral
Breast cancer risk drastically increases in individuals with a heterozygous germline BRCA1 or BRCA2 mutation, while it is estimated to equal the population risk for relatives without the familial mutation (non-carriers). The aim of the present study was to use a G2 phase-specific micronucleus assay to investigate whether lymphocytes of healthy BRCA2 mutation carriers are characterized by increased radiosensitivity compared to controls without a family history of breast/ovarian cancer and how this relates to healthy non-carrier relatives...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28179379/rag1-2-induces-genomic-insertions-by-mobilizing-dna-into-rag1-2-independent-breaks
#10
Philipp C Rommel, Thiago Y Oliveira, Michel C Nussenzweig, Davide F Robbiani
The RAG recombinase (RAG1/2) plays an essential role in adaptive immunity by mediating V(D)J recombination in developing lymphocytes. In contrast, aberrant RAG1/2 activity promotes lymphocyte malignancies by causing chromosomal translocations and DNA deletions at cancer genes. RAG1/2 can also induce genomic DNA insertions by transposition and trans-V(D)J recombination, but only few such putative events have been documented in vivo. We used next-generation sequencing techniques to examine chromosomal rearrangements in primary murine B cells and discovered that RAG1/2 causes aberrant insertions by releasing cleaved antibody gene fragments that subsequently reintegrate into DNA breaks induced on a heterologous chromosome...
February 8, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28178623/t-cell-leukemia-lymphoma-1a-predicts-the-clinical-outcome-for-patients-with-stage-ii-iii-colorectal-cancer
#11
Hao Li, Xuebing Yan, Liguo Liu, Linsheng Huang, Mingming Yin, Cheng Pan, Peng Zhang, Huanlong Qin
T-cell leukemia/lymphoma-1A (TCL1A) as a stem cell marker is abundantly expressed in embryonic stem cells and has been identified as an oncogene in various hematological malignancies such as chronic lymphocytic leukemia and B-cell lymphoma. However, with regard to its role in solid tumors, few studies are available and less are for colorectal cancer (CRC). In this study, we aim to investigate the expression and clinical significance of TCL1A in a cohort of 278 stage II/III CRC patients. As a result, we find TCL1A expression is higher in CRC tissues than that in adjacent normal tissues, and significantly correlated with tumor differentiation, TNM stage and Ki-67 positive rate...
February 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28161850/potential-anti-proliferative-and-immunomodulatory-effects-of-marine-microalgal-exopolysaccharide-on-various-human-cancer-cells-and-lymphocytes-in-vitro
#12
Geon-Tae Park, Ryeo-Eun Go, Hae-Miru Lee, Geum-A Lee, Cho-Won Kim, Jeong-Woo Seo, Won-Kyung Hong, Kyung-Chul Choi, Kyung-A Hwang
Marine microalgal exopolysaccharides (EPSs) have drawn great attention due to their biotechnological potentials such as anti-viral, anti-oxidant, anti-lipidemic, anti-proliferative, and immunomodulatory activities, etc. In the present study, the EPS derived from microalgae Thraustochytriidae sp.-derived mutant GA was investigated for its anti-proliferation and immunomodulation. Anti-cancer efficacy of the microalgal EPS was examined for the alterations in cell proliferation and cell cycle-related gene expression that occur in three types of human cancer cell lines, BG-1 ovarian, MCF-7 breast, and SW-620 colon cancer cell lines, by its treatment...
February 4, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28160756/receptor-tyrosine-kinase-like-orphan-receptor-1-ror-1-an-emerging-target-for-diagnosis-and-therapy-of-chronic-lymphocytic-leukemia
#13
REVIEW
Leili Aghebati-Maleki, Mahdi Shabani, Behzad Baradaran, Morteza Motallebnezhad, Jafar Majidi, Mehdi Yousefi
Chronic lymphocytic leukemia (CLL) is characterized by reposition of malignant B cells in the blood, bone marrow, spleen and lymph nodes. It remains the most common leukemia in the Western world. Within the recent years, major breakthroughs have been made to prolong the survival and improve the health of patients. Despite these advances, CLL is still recognized as a disease without definitive cure. New treatment approaches, based on unique targets and novel drugs, are highly desired for CLL therapy. The Identification and subsequent targeting of molecules that are overexpressed uniquely in malignant cells not normal ones play critical roles in the success of anticancer therapeutic strategies...
February 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28155861/preoperative-adjuvant-transarterial-chemoembolization-cannot-improve-the-long-term-outcome-of-radical-therapies-for-hepatocellular-carcinoma
#14
Lei Jianyong, Zhong Jinjing, Yan Lunan, Zhu Jingqiang, Wang Wentao, Zeng Yong, Li Bo, Wen Tianfu, Yang Jiaying
Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28153581/delivery-of-tlr7-agonist-to-monocytes-and-dendritic-cells-by-dcir-targeted-liposomes-induces-robust-production-of-anti-cancer-cytokines
#15
Thomas C B Klauber, Janne M Laursen, Daniel Zucker, Susanne Brix, Simon S Jensen, Thomas L Andresen
: Tumor immune escape is today recognized as an important cancer hallmark and is therefore a major focus area in cancer therapy. Monocytes and dendritic cells (DCs), which are central to creating a robust anti-tumor immune response and establishing an anti-tumorigenic microenvironment, are directly targeted by the tumor escape mechanisms to develop immunosuppressive phenotypes. Providing activated monocytes and DCs to the tumor tissue is therefore an attractive way to break the tumor-derived immune suppression and reinstate cancer immune surveillance...
January 30, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28138560/leukemia-cell-proliferation-and-death-in-chronic-lymphocytic-leukemia-patients-on-therapy-with-the-btk-inhibitor-ibrutinib
#16
Jan A Burger, Kelvin W Li, Michael J Keating, Mariela Sivina, Ahmed M Amer, Naveen Garg, Alessandra Ferrajoli, Xuelin Huang, Hagop Kantarjian, William G Wierda, Susan O'Brien, Marc K Hellerstein, Scott M Turner, Claire L Emson, Shih-Shih Chen, Xiao-Jie Yan, Dominik Wodarz, Nicholas Chiorazzi
BACKGROUND. Ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL) that inhibits Bruton's tyrosine kinase (BTK), a kinase involved in B cell receptor signaling. METHODS. We used stable isotopic labeling with deuterated water ((2)H2O) to measure directly the effects of ibrutinib on leukemia cell proliferation and death in 30 patients with CLL. RESULTS. The measured average CLL cell proliferation ("birth") rate before ibrutinib therapy was 0.39% of the clone per day (range 0...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28125674/characterisation-of-immune-and-neuroinflammatory-changes-associated-with-chemotherapy-induced-peripheral-neuropathy
#17
Preet G S Makker, Samuel S Duffy, Justin G Lees, Chamini J Perera, Ryan S Tonkin, Oleg Butovsky, Susanna B Park, David Goldstein, Gila Moalem-Taylor
Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain is a debilitating adverse effect of cancer treatment. Current understanding of the mechanisms underpinning CIPN is limited and there are no effective treatment strategies. In this study, we treated male C57BL/6J mice with 4 cycles of either Paclitaxel (PTX) or Oxaliplatin (OXA) over a week and tested pain hypersensitivity and changes in peripheral immune responses and neuroinflammation on days 7 and 13 post 1st injection. We found that both PTX and OXA caused significant mechanical allodynia...
2017: PloS One
https://www.readbyqxmd.com/read/28119186/phytosterols-isolated-from-clinacanthus-nutans-induce-immunosuppressive-activity-in-murine-cells
#18
Cheng-Foh Le, Thina Hareesh Kailaivasan, Sek-Chuen Chow, Zunoliza Abdullah, Sui-Kiong Ling, Chee-Mun Fang
Clinacanthus nutans (Burm. f.) Lindau is a traditional medicinal plant belonging to the Acanthaceae family. Its therapeutic potentials have been increasingly documented particularly the antiviral activity against Herpes Simplex Virus (HSV), anti-cancer, anti-oxidant, anti-inflammatory and immunomodulatory activities. However, majority of these studies used crude or fractionated extracts and not much is known about individual compounds from these extracts and their biological activities. In the present study, we have isolated four compounds (CN1, CN2, CN3 and CN4) from the hexane fractions of C...
January 21, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28110394/chimeric-antigen-receptor-car-t-cells-lessons-learned-from-targeting-of-cd19-in-b-cell-malignancies
#19
Kevin A Hay, Cameron J Turtle
Adoptive immunotherapy with chimeric antigen receptor-modified (CAR)-T cells is a rapidly growing therapeutic approach to treating patients with refractory cancer, with over 100 clinical trials in various malignancies in progress. The enthusiasm for CAR-T cells has been driven by the clinical success of CD19-targeted CAR-T cell therapy in B-cell acute lymphoblastic leukemia, and the promising data in B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Despite the success of targeting CD19 with CAR-T cells in early clinical studies, many challenges remain to improve outcomes, reduce toxicity, and determine the appropriate settings for CAR-T cell immunotherapy...
January 21, 2017: Drugs
https://www.readbyqxmd.com/read/28108506/biomarker-dynamics-in-b-cell-lymphoma-a-longitudinal-prospective-study-of-plasma-samples-up-to-25-years-before-diagnosis
#20
Florentin Späth, Carl Wibom, Esmeralda J M Krop, Ann-Sofie Johansson, Ingvar A Bergdahl, Roel Vermeulen, Beatrice Melin
The B-cell activation markers CXCL13, sCD23, sCD27, and sCD30 are associated with future lymphoma risk. However, a lack of information about the individual dynamics of marker-disease association hampers interpretation. In this study, we identified 170 individuals who had donated two pre-diagnostic blood samples before B-cell lymphoma diagnosis, along with 170 matched cancer-free controls from the Northern Sweden Health and Disease Study. Lymphoma risk associations were investigated by subtype and marker levels measured at baseline, at the time of the repeated sample, and with the rate of change in the marker level...
January 20, 2017: Cancer Research
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