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Microenvironment lymphoma

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https://www.readbyqxmd.com/read/28202459/il-4-cxcl12-loop-is-a-key-regulator-of-lymphoid-stroma-function-in-follicular-lymphoma
#1
Shubham Pandey, Frédéric Mourcin, Tony Marchand, Saba Nayar, Marion Guirriec, Céline Pangault, Céline Monvoisin, Patricia Amé-Thomas, Fabien Guilloton, Joelle Dulong, Mark Coles, Thierry Fest, Anja Mottok, Francesca Barone, Karin Tarte
Follicular lymphoma (FL) is the most frequent indolent lymphoma and is characterized by the accumulation of germinal center-derived malignant B cells engaged in a bidirectional crosstalk with their supportive microenvironment in invaded lymph nodes (LN) and bone marrow (BM). T follicular helper cells (TFH) and infiltrating stromal cells have been shown to favor FL B-cell growth but the mechanisms of their protumoral effect and how LN/BM microenvironment is converted into a lymphoma-permissive cell niche remain poorly understood...
February 15, 2017: Blood
https://www.readbyqxmd.com/read/28195314/reversal-of-tumor-acidosis-by-systemic-buffering-reactivates-nk-cells-to-express-ifn-%C3%AE-and-induces-nk-cell-dependent-lymphoma-control-without-other-immunotherapies
#2
Johann Pötzl, David Roser, Lorenz Bankel, Nadine Hömberg, Albert Geishauser, Christoph D Brenner, Michael Weigand, Martin Röcken, Ralph Mocikat
Like other immune cells, natural killer (NK) cells show impaired effector functions in the microenvironment of tumors, but little is known on the underlying mechanisms. Since lactate acidosis, a hallmark of malignant tissue, was shown to contribute to suppression of effective antitumor immune responses, we investigated the impact of tissue pH and lactate concentration on NK-cell functions in an aggressive model of endogenously arising B-cell lymphoma. The progressive loss of IFN-γ production by NK cells observed during development of this disease could be ascribed to decreased pH values and lactate accumulation in the microenvironment of growing tumors...
February 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28177577/lymph-node-stiffness-mimicking-hydrogels-regulate-human-b-cell-lymphoma-growth-and-cell-surface-receptor-expression-in-a-molecular-subtype-specific-manner
#3
Fnu Apoorva, Ye F Tian, Timothy M Pierpont, David M Bassen, Leandro Cerchietti, Jonathan T Butcher, Robert S Weiss, Ankur Singh
Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma, with multiple molecular subtypes. The activated B cell-like DLBCL subtype accounts for roughly one-third of all the cases and has an inferior prognosis. There is a need to develop better class of therapeutics that could target molecular pathways in resistant DLBCLs; however this requires DLBCLs to be studied in representative tumor microenvironments. The pathogenesis and progression of lymphoma has been mostly studied from the point of view of genetic alterations and intracellular pathway dysregulation...
February 8, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28166836/intracellular-ph-responsive-and-rituximab-conjugated-mesoporous-silica-nanoparticles-for-targeted-drug-delivery-to-lymphoma-b-cells
#4
Shoubing Zhou, Dan Wu, Xiaodong Yin, Xiaoxiao Jin, Xiu Zhang, Shiya Zheng, Cailian Wang, Yanwen Liu
BACKGROUND: One of the main problems in B cell lymphoma treatment is severe adverse effects and low therapeutic efficacy resulting from systemic chemotherapy. A pH-sensitive controlled drug release system based on mesoporous silica nanoparticles was constructed for targeted drug delivery to tumor cells to reduce systemic toxicity and improve the therapeutic efficacy. METHODS: In this study, the doxorubicin (DOX) was filled into the mesopores of the functional MSNs (DMSNs)...
February 6, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28138030/the-tlr3-agonist-inhibit-drug-efflux-and-sequentially-consolidates-low-dose-cisplatin-based-chemoimmunotherapy-while-reducing-side-effects
#5
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, XiaoFeng Huang, Jianjian Ji, Qingang Hu, Hui Wang, Yanhong Ni, Yayi Hou
The traditional maximum dose density chemotherapy renders the tumor patients not only the tumor remission but the chemotherapy resistance and more adverse side effects. According to the widely positive expression of Toll-like receptor (TLR)-3 in oral squamous cell carcinoma (OSCC) patients (n=166), we here provided an alternative strategy involved the orderly treatment of TLR3 agonist polyinosine-polycytidylic acid (PIC) and low-dose cisplatin. The optimal dose of cisplatin, the novel role of PIC and the side effects of the combined chemotherapy were determined in vitro and in distinct human tumor models in vivo...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28107044/quercetin-attenuates-cell-survival-inflammation-and-angiogenesis-via-modulation-of-akt-signaling-in-murine-t-cell-lymphoma
#6
Akhilendra Kumar Maurya, Manjula Vinayak
AKT signaling is important to maintaining normal physiology. Hyperactivation of AKT signaling is frequent in cancer, which maintains a high oxidative state in a tumor microenvironment that is needed for tumor adaptation. Therefore, antioxidants are proposed to exhibit anticancer properties by interfering with the tumor microenvironment. Quercetin is an ubiquitous bioactive antioxidant rich in vegetables and beverages. The present study aimed to analyze cancer preventive property of quercetin in ascite cells of Dalton's lymphoma-bearing mice...
January 20, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28088788/dual-syk-jak-inhibition-overcomes-ibrutinib-resistance-in-chronic-lymphocytic-leukemia-cerdulatinib-but-not-ibrutinib-induces-apoptosis-of-tumor-cells-protected-by-the-microenvironment
#7
Ailin Guo, Pin Lu, Greg Coffey, Pamela Conley, Anjali Pandey, Y Lynn Wang
Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. However, the drug, to a large extent, does not cause cell death directly and does not eradicate CLL malignant clones. Inability to eradicate CLL has fostered resistance generation. Once patients become resistant, they do poorly with a median survival of 3-4 months. Novel therapeutic strategies are needed to prevent resistance, improve treatment outcome and ultimately cure the disease. Herein, we explore dual targeting of the BCR and JAK-STAT pathways with a novel single agent, cerdulatinib, which selectively inhibits both SYK (a BCR component) and JAK kinases...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28062796/integrated-cellular-and-plasma-proteomics-of-contrasting-b-cell-cancers-reveals-common-unique-and-systemic-signatures
#8
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/28059091/identification-of-distinct-subgroups-of-ebv-positive-post-transplant-diffuse-large-b-cell-lymphoma
#9
Julie Morscio, Julio Finalet Ferreiro, Sara Vander Borght, Emilie Bittoun, Olivier Gheysens, Daan Dierickx, Gregor Verhoef, Iwona Wlodarska, Thomas Tousseyn
Post-transplantation lymphoproliferative disorder is an aggressive complication of transplantation, most frequently of diffuse large B-cell lymphoma morphology and associated with Epstein-Barr virus (EBV) infection/reactivation. In this study the microenvironment of EBV(+) (n=23) and EBV(-) (n=9) post-transplant non-germinal center B-cell diffuse large B-cell lymphoma was characterized. Of EBV(+) cases somatic hypermutation analysis, gene expression profiling, and extensive phenotyping were performed. Our results demonstrated variable cytotoxic T-cell infiltration and significantly increased CD163(+) M2 macrophage infiltration in EBV(+) compared with EBV(-) post-transplant diffuse large B-cell lymphoma...
January 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28056186/tampering-with-cancer-chemoresistance-by-targeting-the-tgm2-il6-autophagy-regulatory-network
#10
Han Zhang, Nami McCarty
Macroautophagy/autophagy is a well-established process involved in maintaining cellular homeostasis, but its role in cancer is complex and even controversial. Many studies have reported a correlative relationship between increased autophagy and evolving cancer cells under stress conditions such as nutrient or oxygen deprivation; however, there has been a lack of a plausible mechanistic link to properly target the autophagy process in the context of this microenvironment. We recently unveiled a positive regulatory loop involving TGM2 (transglutaminase 2)-NFKB/NF-κB signaling, IL6 and autophagy in cancer using mantle cell lymphoma (MCL) as a model system...
January 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28055963/emetine-elicits-apoptosis-of-intractable-b-cell-lymphoma-cells-with-myc-rearrangement-through-inhibition-of-glycolytic-metabolism
#11
Tomohiro Aoki, Kazuyuki Shimada, Akihiko Sakamoto, Keiki Sugimoto, Takanobu Morishita, Yuki Kojima, Satoko Shimada, Seiichi Kato, Chisako Iriyama, Shunsuke Kuno, Yasuhiko Harada, Akihiro Tomita, Fumihiko Hayakawa, Hitoshi Kiyoi
Despite improved clinical outcomes of diffuse large B-cell lymphoma, a certain proportion of patients still develop a primary refractory disease. To overcome these lymphomas that are intractable to existing treatment strategies, the tumor microenvironment has been identified as a potential therapeutic target. Here we describe our search for effective drugs for primary refractory lymphoma cells with MYC rearrangement. Through the drug screening of 3,440 known compounds, we identified a unique compound, emetine...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28054086/3d-microvascular-model-recapitulates-the-diffuse-large-b-cell-lymphoma-tumor-microenvironment-in-vitro
#12
Robert G Mannino, Adriana N Santiago-Miranda, Pallab Pradhan, Yongzhi Qiu, Joscelyn C Mejias, Sattva S Neelapu, Krishnendu Roy, Wilbur A Lam
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer that affects ∼22 000 people in the United States yearly. Understanding the complex cellular interactions of the tumor microenvironment is critical to the success and development of DLBCL treatment strategies. In vitro platforms that successfully model the complex tumor microenvironment without introducing the variability of in vivo systems are vital for understanding these interactions. To date, no such in vitro model exists that can accurately recapitulate the interactions that occur between immune cells, cancer cells, and endothelial cells in the tumor microenvironment of DLBCL...
January 31, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28038319/recruitment-of-tiam1-to-semaphorin-4d-activates-rac-and-enhances-proliferation-invasion-and-metastasis-in-oral-squamous-cell-carcinoma
#13
Hua Zhou, Maricel G Kann, Emily K Mallory, Ying-Hua Yang, Amr Bugshan, Nada O Binmadi, John R Basile
The semaphorins and the plexins are a family of large, cysteine-rich proteins originally identified as regulators of axon growth and lymphocyte activation that are now known to provide motility and positional information for a number of cell and tissue types. For example, our group and others have shown that some malignancies over express Semaphorin 4D (S4D), which acts through its receptor Plexin-B1 (PB1) on endothelial cells to attract blood vessels from the surrounding stroma for the purpose of supporting tumor growth...
February 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28018857/murine-models-of-splenic-marginal-zone-lymphoma-a-role-for-cav1
#14
REVIEW
Chelsey L Patten, Christine E Cutucache
Dozens of murine models of indolent and aggressive B-cell lymphomas have been generated to date. These include those manifesting chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), as well as xenografts of mantle cell lymphoma (MCL). These models have led to an improved understanding of disease etiology, B-cell biology, immunomodulation, and the importance of the tumor microenvironment. Despite these efforts in CLL, DLBCL, and MCL, considerably little progress toward a model of splenic marginal zone lymphoma (SMZL) has been accomplished...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/28017967/duvelisib-treatment-is-associated-with-altered-expression-of-apoptotic-regulators-that-helps-in-sensitization-of-chronic-lymphocytic-leukemia-cells-to-venetoclax-abt-199
#15
V M Patel, K Balakrishnan, M Douglas, T Tibbitts, E Y Xu, J L Kutok, M Ayers, A Sarkar, R Guerrieri, W G Wierda, S O'Brien, N Jain, H M Stern, V Gandhi
Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma (iNHL). In CLL, duvelisib monotherapy is associated with high iwCLL and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene-expression studies (RNA seq, Nanostring, Affymetrix array, and real time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28007011/mimicking-the-acute-myeloid-leukemia-niche-for-molecular-study-and-drug-screening
#16
Mohammad Houshmand, Masoud Soleimani, Amir Atashi, Giuseppe Saglio, Mohammad Abdollahi, Mahin Nikougoftar Zarif
Bone marrow niche is a major contributing factor in leukemia development and drug resistance in acute myeloid leukemia (AML) patients. Although mimicking leukemic bone marrow niche relies on two-dimensional (2D) culture conditions, it cannot recapitulate complex bone marrow structure that causes introduction of different three-dimensional (3D) scaffolds. Simultaneously, microfluidic platform by perfusing medium culture mimic interstitial fluid flow, along with 3D scaffold would help for mimicking bone marrow microenvironment...
February 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28000533/prospects-to-improve-chimeric-antigen-receptor-t-cell-therapy-for-solid-tumors
#17
Chuan Jin, Di Yu, Magnus Essand
Adoptive transfer of patient-derived T-cells engineered with a chimeric antigen receptor (CAR) targeting the pan-B-cell marker CD19 has led to complete remission in patients with B-cell leukemias while response rates are more modest for B-cell lymphomas. This can be attributed to the fact that the semi-solid structure of lymphomas impedes T-cell infiltration and that the immune suppressive microenvironment within these tumors dampens the effect of CAR T-cells. These obstacles are even more pronounced for solid tumors where dense and often highly immunosuppressive structures are found...
December 2016: Immunotherapy
https://www.readbyqxmd.com/read/27999289/characterization-of-the-microenvironment-of-nodular-lymphocyte-predominant-hodgkin-lymphoma
#18
Lydia Visser, Rui Wu, Bea Rutgers, Arjan Diepstra, Anke van den Berg
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by a low percentage of neoplastic lymphocyte predominant (LP) cells in a background of lymphocytes. The goal of this study is to characterize the microenvironment in NLPHL. Ten NLPHL cases and seven reactive lymph nodes (RLN) were analyzed by flow cytometry for the main immune cells and multiple specific subpopulations. To discriminate between cells in or outside the tumor cell area, we used CD26. We observed significantly lower levels of CD20+ B-cells and CD56+ NK cells and higher levels of CD4+ T-cells in NLPHL in comparison to RLN...
December 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27993085/vaccine-strategies-for-the-treatment-of-lymphoma-preclinical-progress-and-clinical-trial-update
#19
Thomas U Marron, Lukas Ronner, Peter E Martin, Christopher R Flowers, Joshua D Brody
The clonal B-cell immunoglobulin idiotype found on the surface of lymphomas was the first targeted tumor-specific antigen, and combinations of idiotype with classical and novel adjuvants were shown to stimulate robust humoral and cellular responses, though clinical efficacy was more variable. Cellular and in situ vaccination to help target a wider array of tumor-specific antigens have also been able to stimulate tumor-specific cellular responses, though their clinical success has also been limited. Our growing understanding of the role of regulatory cells and the immunosuppressive tumor microenvironment, along with a wide variety of immunomodulatory agents developed as of late, offer promising adjuvants to potentiate the immune responses elicited by these vaccine protocols and to achieve durable remissions...
November 2016: Immunotherapy
https://www.readbyqxmd.com/read/27990323/impaired-functional-responses-in-follicular-lymphoma-cd8-tim-3-t-lymphocytes-following-tcr-engagement
#20
Pauline Gravelle, Catherine Do, Camille Franchet, Sabina Mueller, Lucie Oberic, Loïc Ysebaert, Luigi Maria Larocca, Stefan Hohaus, Marie-Noëlle Calmels, François-Xavier Frenois, Robert Kridel, Randy D Gascoyne, Guy Laurent, Pierre Brousset, Salvatore Valitutti, Camille Laurent
Upregulation of T cell immunoglobulin-3 (TIM-3) has been associated with negative regulation of the immune response in chronic infection and cancer, including lymphoma. Here, we investigated the possible correlation between TIM-3 expression by ex vivo cytotoxic T cells (CTL) from follicular lymphoma (FL) biopsies and their functional unresponsiveness that could limit the favorable impact of CTL on disease progression. We report a high percentage of CD8(+)TIM-3(+)T cells in lymph nodes of FL patients. When compared to their CD8(+)TIM-3(-) counterparts, CD8(+)TIM-3(+) T cells exhibited defective cytokine production following TCR engagement...
2016: Oncoimmunology
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