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https://www.readbyqxmd.com/read/28331288/development-of-venetoclax-for-therapy-of-lymphoid-malignancies
#1
REVIEW
Huayuan Zhu, Alexandru Almasan
B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#2
A K Gopal, M A Fanale, C H Moskowitz, A R Shustov, S Mitra, W Ye, A Younes, A J Moskowitz
Background: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28277849/targeting-indolent-non-hodgkin-lymphoma
#3
Lori A Leslie, Alan P Skarbnik, Coleen Bejot, Susan Stives, Tatyana A Feldman, Andre H Goy
Due to recent advancements in the understanding of the molecular pathogenesis of B-cell malignancies, there has been an explosion of innovative agents in development. The purpose of this review is to efficiently summarize novel therapies with activity in indolent non-Hodgkin lymphoma (iNHL) targeting surface antigens, signaling pathways, and the tumor microenvironment. Areas covered: A literature search was performed to identify preclinical data and clinical trials focused on the use of targeted therapies in iNHL subtypes including follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia...
March 15, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28273184/-how-can-we-treat-waldenstr%C3%A3-m-s-macroglobulinemia
#4
Anna Orsolya Mucsi, Zsolt Nagy
Waldenström's macroglobulinemia is a rare, low-grade non-Hodgkin lymphoma of B cell origin, most common in elderly male patients with a median age of 64 years at diagnosis. It accounts for approximately 2% of hematologic malignancies. The disease is incurable now with a median overall survival of 6.2 years. In the past decade growing evidence suggests the role of the complex signaling pathways and microenvironment as a potential target of the therapy in the lymphoproliferative disorders as well as Waldenström's macroglobulinemia...
March 8, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28267244/a-multicenter-phase-ii-study-of-nivolumab-in-japanese-patients-with-relapsed-or-refractory-classical-hodgkin-lymphoma
#5
Dai Maruyama, Kiyohiko Hatake, Tomohiro Kinoshita, Noriko Fukuhara, Ilseung Choi, Masafumi Taniwaki, Kiyoshi Ando, Yasuhito Terui, Yusuke Higuchi, Yasushi Onishi, Yasunobu Abe, Tsutomu Kobayashi, Yukari Shirasugi, Kensei Tobinai
Overexpression of programmed death-1 (PD-1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD-1-blocking antibody that inhibits the PD-1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR)...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28265553/overview-of-the-use-of-murine-models-in-leukemia-and-lymphoma-research
#6
REVIEW
Rebecca Kohnken, Pierluigi Porcu, Anjali Mishra
Murine models have been adopted as a significant and powerful tool in the study of cancer. The applications of murine models of cancer are numerous: mechanism discovery, oncogenesis, molecular genetics, microenvironment, metastasis, and therapeutic efficacy. Leukemias and lymphomas are a group of highly heterogeneous hematologic malignancies that affect people of all ages and ethnicities. Leukemia and lymphoma arise from hematopoietic and immune cells and usually spread widely throughout the body. The liquid nature of many of these malignancies, as well as the complex microenvironment from which they arise and their multifaceted genetic basis, has added to the difficulty in generating appropriate and translational models to study them...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28257957/the-cancer-immunity-cycle-as-rational-design-for-synthetic-cancer-drugs-novel-dc-vaccines-and-car-t-cells
#7
REVIEW
Mohanraj Ramachandran, Anna Dimberg, Magnus Essand
Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas...
February 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28231401/reappraisal-of-ebv-in-diffuse-large-b-cell-lymphoma-dlbcl-comparative-analysis-between-ebv-positive-and-negative-dlbcl-with-ebv-positive-bystander-cells
#8
Akiko Ohashi, Seiichi Kato, Akinao Okamoto, Yoko Inaguma, Akira Satou, Toyonori Tsuzuki, Nobuhiko Emi, Masataka Okamoto, Shigeo Nakamura
AIMS: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is defined as monoclonal EBV(+) B-cell proliferation affecting patients without any known immunosuppression. Non-neoplastic EBV(+) cells proliferating in or adjacent to EBV(-) DLBCL were reported recently, but their clinical significance is unclear. Thus, we investigated the prognostic impact of EBV(+) cells in DLBCL. METHODS AND RESULTS: We compared the clinico-pathological characteristics of 30 EBV(+) DLBCL patients and 29 and 604 EBV(-) DLBCL patients with and without EBV(+) bystander cells (median age of onset 71, 67, and 62 years, respectively)...
February 23, 2017: Histopathology
https://www.readbyqxmd.com/read/28202459/il-4-cxcl12-loop-is-a-key-regulator-of-lymphoid-stroma-function-in-follicular-lymphoma
#9
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
#10
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...
May 1, 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
#11
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
#12
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
#13
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
#14
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...
April 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
#15
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
#16
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
#17
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
#18
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...
March 4, 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
#19
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
#20
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
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