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https://www.readbyqxmd.com/read/28105157/prognostic-impact-of-the-tumor-infiltrating-regulatory-t-cell-foxp3-activated-cytotoxic-t-lymphocyte-granzyme-b-ratio-on-resected-left-sided-pancreatic-cancer
#1
Ho Kyoung Hwang, Hyoung-Il Kim, Se Hoon Kim, Junjeong Choi, Chang Moo Kang, Kyung Sik Kim, Woo Jung Lee
Among the subsets of tumor-infiltrating lymphocytes (TILs), activated cytotoxic T lymphocytes (granzyme B(+)) have an antitumor effect, while regulatory T lymphocytes [forkhead box P3 (Foxp3)(+)] suppress the antitumor immune response. The aim of the present study was to investigate the possible associations between TIL subsets and survival outcomes in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). From January 2000 to December 2008, 30 patients who underwent curative distal pancreatectomy without neoadjuvant chemoradiotherapy due to left-sided PDAC were enrolled in the present study...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100392/replication-study-the-cd47-signal-regulatory-protein-alpha-sirpa-interaction-is-a-therapeutic-target-for-human-solid-tumors
#2
Stephen K Horrigan
In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Chroscinski et al., 2015) that described how we intended to replicate selected experiments from the paper "The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors "(Willingham et al., 2012). Here we report the results of those experiments. We found that treatment of immune competent mice bearing orthotopic breast tumors with anti-mouse CD47 antibodies resulted in short-term anemia compared to controls, consistent with the previously described function of CD47 in normal phagocytosis of aging red blood cells and results reported in the original study (Table S4; Willingham et al...
January 19, 2017: ELife
https://www.readbyqxmd.com/read/28099502/clinical-and-immune-effects-of-lenalidomide-in-combination-with-gemcitabine-in-patients-with-advanced-pancreatic-cancer
#3
Gustav J Ullenhag, Fariba Mozaffari, Mats Broberg, Håkan Mellstedt, Maria Liljefors
PURPOSE: To assess the immunomodulatory and clinical effects of lenalidomide with standard treatment of gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with advanced pancreatic cancer were treated in first line with lenalidomide orally for 21 days of a 28 days cycle and the standard regimen for gemcitabine. In Part I, which we previously have reported, the dose of lenalidomide was defined (n = 12). In Part II, every other consecutive patient was treated with either lenalidomide (Group A, n = 11) or gemcitabine (Group B, n = 10) during cycle 1...
2017: PloS One
https://www.readbyqxmd.com/read/28098136/exome-and-genome-sequencing-of-nasopharynx-cancer-identifies-nf-%C3%AE%C2%BAb-pathway-activating-mutations
#4
Yvonne Y Li, Grace T Y Chung, Vivian W Y Lui, Ka-Fai To, Brigette B Y Ma, Chit Chow, John K S Woo, Kevin Y Yip, Jeongsun Seo, Edwin P Hui, Michael K F Mak, Maria Rusan, Nicole G Chau, Yvonne Y Y Or, Marcus H N Law, Peggy P Y Law, Zoey W Y Liu, Hoi-Lam Ngan, Pok-Man Hau, Krista R Verhoeft, Peony H Y Poon, Seong-Keun Yoo, Jong-Yeon Shin, Sau-Dan Lee, Samantha W M Lun, Lin Jia, Anthony W H Chan, Jason Y K Chan, Paul B S Lai, Choi-Yi Fung, Suet-Ting Hung, Lin Wang, Ann Margaret V Chang, Simion I Chiosea, Matthew L Hedberg, Sai-Wah Tsao, Andrew C van Hasselt, Anthony T C Chan, Jennifer R Grandis, Peter S Hammerman, Kwok-Wai Lo
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#5
Natalie J Miller, Candice D Church, Lichun Dong, David Crispin, Matthew P Fitzgibbon, Kristina Lachance, Lichen Jing, Michi Shinohara, Ioannis Gavvovidis, Gerald Willimsky, Martin McIntosh, Thomas Blankenstein, David M Koelle, Paul Nghiem
Tumor-infiltrating CD8(+) T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8(+) T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer(+) CD8(+) T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28089635/venetoclax-plus-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukaemia-a-phase-1b-study
#6
John F Seymour, Shuo Ma, Danielle M Brander, Michael Y Choi, Jacqueline Barrientos, Matthew S Davids, Mary Ann Anderson, Anne W Beaven, Steven T Rosen, Constantine S Tam, Betty Prine, Suresh K Agarwal, Wijith Munasinghe, Ming Zhu, L Leanne Lash, Monali Desai, Elisa Cerri, Maria Verdugo, Su Young Kim, Rod A Humerickhouse, Gary B Gordon, Thomas J Kipps, Andrew W Roberts
BACKGROUND: Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab. METHODS: Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial...
January 12, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28089238/ruxolitinib-for-symptom-control-in-patients-with-chronic-lymphocytic-leukaemia-a-single-group-phase-2-trial
#7
Preetesh Jain, Michael Keating, Sarah Renner, Charles Cleeland, Huang Xuelin, Graciela Nogueras Gonzalez, David Harris, Ping Li, Zhiming Liu, Ivo Veletic, Uri Rozovski, Nitin Jain, Phillip Thompson, Prithviraj Bose, Courtney DiNardo, Alessandra Ferrajoli, Susan O'Brien, Jan Burger, William Wierda, Srdan Verstovsek, Hagop Kantarjian, Zeev Estrov
BACKGROUND: Disease-related symptoms impair the quality of life of patients with chronic lymphocytic leukaemia (CLL) who do not require systemic therapy. Available therapies are not specifically aimed at symptom control. Because stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients with myelofibrosis, we postulated that ruxolitinib would improve disease-related symptoms in patients with CLL. We did a phase 2 trial of ruxolitinib to test this hypothesis...
January 11, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28078860/effects-of-two-different-anesthetic-methods-on-cellular-immunity-of-patients-after-liver-cancer-resection
#8
Y Xu, Y Sun, H Chen, Y Wang, G N Wang
This study aims to investigate the effects of epidural block in combination with general anesthesia and general anesthesia alone on the immune function of patients undergoing primary liver cancer resection. Twenty-four patients with liver cancer who received treatment in the Third Hospital of Harbin Medical University, Heilongjiang, China, were enrolled and randomly allocated into group A and group B, with 12 in each group. The data on the T lymphocyte subpopulation, pro-inflammatory cytokines and antiinflammatory cytokines were recorded before, immediately after and 24 h after liver cancer resection to compare differences and changes...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28077796/tumor-cell-migration-is-inhibited-by-a-novel-therapeutic-strategy-antagonizing-the-alpha-7-receptor
#9
Chris Pepper, Henry Tu, Paul Morrill, Sara Garcia-Rates, Chris Fegan, Susan Greenfield
A 14mer peptide (T14) derived from the C-terminus of acetylcholinesterase (AChE) selectively activates metastatic breast cancer cells via the alpha-7 nicotinic receptor (α7 nAChR). This naturally occurring peptide is also present in brain, is elevated in Alzheimer's disease, and is antagonised by a cyclized variant (NBP-14). Here we investigated the effects of NBP-14 in six different cancer cell lines, primary leukemia B-cells and normal B-cells. All cells tested expressed α7 nAChR, intracellular and extracellular T14...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076862/prognostic-value-of-the-pretreatment-advanced-lung-cancer-inflammation-index-ali-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop-chemotherapy
#10
Young Hoon Park, Hyeon Gyu Yi, Moon Hee Lee, Chul Soo Kim, Joo Han Lim
BACKGROUND: The Advanced Lung Cancer Inflammation Index (ALI, body mass index × albumin/neutrophil-to-lymphocyte ratio) has been demonstrated to be a prognostic factor of survival in some solid cancers. We retrospectively investigated the usefulness of the ALI to predict chemotherapy response and survival in 212 patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. METHODS: Patients were allocated to a low ALI group (n = 82, 38...
January 12, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28076843/pax-5-is-a-potent-regulator-of-e-cadherin-and-breast-cancer-malignant-processes
#11
Sami Benzina, Annie-Pier Beauregard, Roxann Guerrette, Stéphanie Jean, Mame Daro Faye, Mark Laflamme, Emmanuel Maïcas, Nicolas Crapoulet, Rodney J Ouellette, Gilles A Robichaud
Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the development and progression of lymphoid cancers and carcinoma. In contrast to B-cell cancer lesions, the specific expression signatures and roles of Pax-5 in breast cancer progression are relatively unknown. In the present study, we set out to profile Pax-5 expression in mammary tissues and elucidate the cellular and molecular roles of Pax-5 in breast cancer processes. Using immunohistology on mammary tissue arrays, Pax-5 was detected in a total of 298/306 (97...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28073846/extended-treatment-with-single-agent-ibrutinib-at-the-420-mg-dose-leads-to-durable-responses-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma
#12
Steven E Coutré, Richard R Furman, Ian W Flinn, Jan A Burger, Kristie Blum, Jeff Sharman, Jeffrey Jones, William Wierda, Weiqiang Zhao, Nyla A Heerema, Amy J Johnson, Anh Tran, Cathy Zhou, Elizabeth Bilotti, Danelle F James, John C Byrd, Susan O'Brien
PURPOSE: Ibrutinib, a first-in-class, once-daily, oral inhibitor of Bruton tyrosine kinase, promotes apoptosis, and inhibits B-cell proliferation, adhesion, and migration. Ibrutinib has demonstrated single-agent efficacy and acceptable tolerability at doses of 420 and 840 mg in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were treatment-naïve (TN) or had relapsed/refractory (R/R) CLL after ≥1 prior therapy in a phase Ib/II study (PCYC-1102). Subsequently, the ibrutinib 420 mg dose was approved in CLL...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28073773/long-term-survival-and-clinical-benefit-from-adoptive-t-cell-transfer-in-stage-iv-melanoma-patients-is-determined-by-a-four-parameter-tumor-immune-signature
#13
Sara M Melief, Valeria V Visconti, Marten Visser, Merel van Diepen, Ellen H W Kapiteijn, Joost H van den Berg, John B A G Haanen, Vincent T H B M Smit, Jan Oosting, Sjoerd H van der Burg, Els M E Verdegaal
The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28068240/does-unintentional-splenic-radiation-predict-outcomes-after-pancreatic-cancer-radiation-therapy
#14
Awalpreet S Chadha, Guan Liu, Hsiang-Chun Chen, Prajnan Das, Bruce D Minsky, Usama Mahmood, Marc E Delclos, Yelin Suh, Gabriel O Sawakuchi, Sam Beddar, Matthew H Katz, Jason B Fleming, Milind M Javle, Gauri R Varadhachary, Robert A Wolff, Christopher H Crane, Xuemei Wang, Howard Thames, Sunil Krishnan
PURPOSE: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT...
February 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28067817/resveratrol-potential-therapeutic-interest-in-joint-disorders-a-critical-narrative-review
#15
REVIEW
Christelle Nguyen, Jean-François Savouret, Magdalena Widerak, Marie-Thérèse Corvol, François Rannou
Trans-resveratrol (t-Res) is a natural compound of a family of hydroxystilbenes found in a variety of spermatophyte plants. Because of its effects on lipids and arachidonic acid metabolisms, and its antioxidant activity, t-Res is considered as the major cardioprotective component of red wine, leading to the "French Paradox" health concept. In the past decade, research on the effects of resveratrol on human health has developed considerably in diverse fields such as cancer, neurodegenerative and cardiovascular diseases, and metabolic disorders...
January 6, 2017: Nutrients
https://www.readbyqxmd.com/read/28067179/cd20-based-immunotherapy-of-b-cell-derived-hematologic-malignancies
#16
Dariush Shanehbandi, Jafar Majidi, Tohid Kazemi, Behzad Baradaran, Leili Aghebati-Maleki
CD20 is a surface antigen which is expressed at certain stages of B-cell differentiation. Targeting the CD20-positive B-cells with therapeutic monoclonal antibodies (MAbs) has been an effectual strategy in the treatment of hematologic malignancies such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Initial success with Rituximab (RTX) has encouraged the creation and development of more effective CD20 based therapeutics. However, treatment with conventional MAbs has not been adequate to overcome the problems such as refractory/relapsed disease...
January 9, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28063304/splenic-irradiation-for-splenomegaly-a-systematic-review
#17
REVIEW
Nicholas G Zaorsky, Graeme R Williams, Stefan K Barta, Nestor F Esnaola, Patricia L Kropf, Shelly B Hayes, Joshua E Meyer
Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016...
December 22, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28062796/integrated-cellular-and-plasma-proteomics-of-contrasting-b-cell-cancers-reveals-common-unique-and-systemic-signatures
#18
Harvey E Johnston, Matthew J Carter, Kerry L Cox, Melanie Dunscombe, Antigoni Manousopoulou, Paul A Townsend, Spiro D Garbis, Mark S Cragg
Approximately 800,000 leukaemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukaemia (CLL), are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumour, frequently affecting children, whilst CLL typically presents as an indolent, slow-progressing leukaemia affecting the elderly. The B-cell-specific over-expression of the myc and tcl1 oncogenes in mice induce spontaneous malignancies modelling BL and CLL, respectively. Quantitative mass spectrometry proteomics and isobaric labelling were employed to examine the biology underpinning contrasting Eμ-myc and Eμ-TCL1 B-cell tumours...
January 4, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#19
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28051230/prognostic-nutritional-index-score-is-useful-to-predict-post-operative-mortality-and-morbidity-in-gastric-cancer
#20
Mehdi Khalfallah, Hichem Jerraya, Akram Sbai, Wejih Dougaz, Amel Changuel, Ramzi Nouira, Ibtissem Bouasker, Chadli Dziri
Background - The Prognostic Nutritional Index (PNI) score is based on the level of lymphocytes and albuminemia. The aim of this study was to validate the pre-operative PNI score for predicting post-operative mortality and morbidity of patients operated on for gastric cancer. Methods - This retrospective study collected data from patients operated on for a gastric cancer at the surgical unit B of Charles Nicolle's hospital in Tunis between January 1st, 2008 and December 31, 2012. The main outcome measure was post-operative death within 30 days...
July 2016: La Tunisie Médicale
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