256. CD20-Targeted Virus Eliminates Primary Mantel Cell Lymphoma Xenografts by Amplifying Locally the Therapeutic Effects of Fludarabine and Cyclophosphamide

Genetic ablation as well as pharmacological inhibition of sirtuin 2 (SIRT2), an NAD+-dependent protein deacylase, have therapeutic effects in various cancers and neurodegenerative diseases. Previously, we described the discovery of a dual SIRT1/SIRT2 inhibitor called cambinol (IC50 56 and 59 µM, respectively), which showed cytotoxic activity against cancer cells in vitro and a marked anti-proliferative effect in a Burkitt lymphoma mouse xenograft model. A number of recent studies have shown a protective effect of SIRT1 and SIRT3 in neurodegenerative and metabolic diseases as well as in certain cancers prompting us to initiate a medicinal chemistry effort to develop cambinol-based SIRT2-specific inhibitors devoid of SIRT1 or SIRT3 modulating activity. Here we describe potent cambinol-based SIRT2 inhibitors, several of which show potency of ~600 nM with >300 to >800-fold selectivity over SIRT1 and 3, respectively. In vitro, these inhibitors are found to be toxic to lymphoma and epithelial cancer cell lines. In particular, compounds 55 (IC50 SIRT2 0.25 µM and <25% inhibition at 50 µM against SIRT1 and SIRT3) and 56 (IC50 SIRT2 0.78 µM and <25% inhibition at 50 µM against SIRT1 and SIRT3) showed apoptotic as well as strong anti-proliferative properties against B-cell lymphoma cells.

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Chemotherapy combined with radiotherapy for successful treatment of angioimmunoblastic T-cell lymphoma: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-020-02489-4 ◽

2020 ◽

Vol 14 (1) ◽

Author(s):

Yudi Xiong ◽

Lei Yang ◽

Jing Dai ◽

Fuxiang Zhou ◽

Yunfeng Zhou

Keyword(s):

Radiation Therapy ◽

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Therapeutic Effects ◽

Case Presentation ◽

Angioimmunoblastic T Cell Lymphoma ◽

Computed Tomographic ◽

First Line Therapy ◽

Axillary Region

Abstract Background The incidence of angioimmunoblastic T-cell lymphoma is rare worldwide, and it has a poor prognosis. There is no proven or standard first-line therapy that works for the majority of patients with angioimmunoblastic T-cell lymphoma because of the rarity of this disease. The treatment and management are challenging for clinicians. Case presentation This report presents the diagnosis and treatment of a 65-year-old Chinese man who presented with cough and lymph node swellings in the left axillary region. The patient was diagnosed with angioimmunoblastic T-cell lymphoma. He underwent eight cycles of chemotherapy with CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone) followed by TOMO radiotherapy (helical tomotherapy, a kind of radiotherapy for cancer treatment using spiral computed tomographic scanning). After treatment, the therapeutic effects were evaluated by magnetic resonance imaging and computed tomography about every 3 months. The patient recovered well with no sign of tumor recurrence and no obvious severe treatment-related adverse effects. Conclusion This treatment experience indicates an essential role for the combination of radiation therapy with CHOP, which may have a better prognosis than treatments without radiation therapy. But challenges warrant further validation in prospective studies.

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Staphylococcus warneri meningitis in a patient with Strongyloides stercoralis hyperinfection and lymphoma: first report of a case

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652010000300011 ◽

2010 ◽

Vol 52 (3) ◽

pp. 169-170 ◽

Cited By ~ 12

Author(s):

Renzo Nino Incani ◽

Marcos Hernández ◽

Jackeline Cortez ◽

María Elena González ◽

Yaimir Dorel Salazar

Keyword(s):

Cell Lymphoma ◽

Gastrointestinal Symptoms ◽

Strongyloides Stercoralis ◽

Staphylococcus Warneri ◽

Hyperinfection Syndrome ◽

History Of ◽

Cerebrospinal Fluid Culture ◽

Mantel Cell Lymphoma ◽

First Time ◽

Fluid Culture

A case of meningitis due to Staphylococcus warneri in a patient with a hyperinfection with Strongyloides stercoralis possibly associated with rituximab treatment for mantel cell lymphoma is reported for the first time in the literature. The patient was a 59-year-old woman, with a 3-year history of an apparently well controlled lymphoma after treatment with chemotherapy-immunotherapy and then immunotherapy alone, and diagnosis of strongyloidiasis. Meningitis was diagnosed by cerebrospinal fluid culture and tested with an automated plate system. The patient was successfully treated with vancomycin; although fever and productive cough persisted. Severe gastrointestinal symptoms and pneumonia developed three weeks later. Hyperinfection syndrome by S. stercoralis was diagnosed, with abundant larvae in feces and expectoration.

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A good response of refractory mantel cell lymphoma to haploidentical CAR T cell therapy after failure of autologous CAR T cell therapy

Journal for ImmunoTherapy of Cancer ◽

10.1186/s40425-019-0529-9 ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 5

Author(s):

Tongjuan Li ◽

Yuanyuan Zhang ◽

Dan Peng ◽

Xia Mao ◽

Xiaoxi Zhou ◽

...

Keyword(s):

T Cell ◽

Cell Therapy ◽

Cell Lymphoma ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T ◽

Mantel Cell Lymphoma

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Endoscopic features of mantel cell lymphoma involving the gastrointestinal tract

Gastrointestinal Endoscopy ◽

10.1016/s0016-5107(01)80436-3 ◽

2001 ◽

Vol 53 (5) ◽

pp. AB182

Keyword(s):

Gastrointestinal Tract ◽

Cell Lymphoma ◽

Mantel Cell Lymphoma

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3-Methyladenine but not antioxidants to overcome BACH2-mediated bortezomib resistance in mantle cell lymphoma

Cancer Cell International ◽

10.1186/s12935-021-01980-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Min Feng ◽

Jia Wang ◽

Ming Sun ◽

Guilan Li ◽

BingXiang Li ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Molecular Mechanisms ◽

Nuclear Translocation ◽

Cell Lymphoma ◽

Heme Oxygenase 1 ◽

Therapeutic Effects ◽

Major Drawback ◽

Dual Inhibitor ◽

Mantle Cell ◽

Resistant Cells

Abstract Background Bortezomib (BTZ) is an inhibitor of the proteasome that has been used to treat patients with mantle cell lymphoma (MCL), but the resistance to BTZ in clinical cases remains a major drawback. BACH2 is a lymphoid-specific transcription repressor recognized as a tumor suppressor in MCL. Reduced BACH2 levels contribute to BTZ resistance; however, the molecular events underlying BACH2-mediated BTZ resistance are largely unclear. Methods We silenced BACH2 in MCL cells using a lentiviral shRNA-mediated knockdown system. Bioinformatic, real-time RT-PCR, immunoblotting and a series of functional assays were performed to describe the molecular mechanisms underlying BTZ resistance in MCL. The therapeutic effects of chemicals were evaluated on numerous cellular and molecular processes in resistant MCL cell lines and xenografts. Results In resistant cells, BTZ-triggered mild oxidative stress induced a strong activation of PI3K-AKT signaling, which further blocked nuclear translocation of BACH2. Defective nuclear translocation of BACH2 or silencing BACH2 removed its transcriptional repression on HMOX1, leading to upregulation of heme oxygenase-1 (HO-1). Increased HO-1 further maintained reactive oxygen species (ROS) within a minimal tumor-promoting level and enhanced cytoprotective autophagy. Interestingly, although mild increase in ROS exhibited a pro-tumorigenic effect on resistant cells, simply blocking ROS by antioxidants did not lead to cell death but aggravated BTZ resistance via stabilizing BACH1, the other member of BACH family. Instead, 3-methyladenine (3-MA), a dual inhibitor to suppress PI3K signaling and autophagosome formation, sensitized resistant MCL cells to BTZ, both in vitro and in vivo. Conclusion Our results dissected the interconnected molecular network in resistant MCL cells in which 3-MA represents an effective therapeutic strategy to overcome BTZ resistance. Notably, BACH1 and BACH2, albeit from the same family, are likely to play opposite roles in pathogenesis and progression of MCL.

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Chidamide triggers BTG1-mediated autophagy and reverses the chemotherapy resistance in the relapsed/refractory B-cell lymphoma

Cell Death and Disease ◽

10.1038/s41419-021-04187-5 ◽

2021 ◽

Vol 12 (10) ◽

Author(s):

Kai Xue ◽

Ji-Chuan Wu ◽

Xi-Ya Li ◽

Ran Li ◽

Qun-ling Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Growth Inhibition ◽

B Cell ◽

Target Genes ◽

Cell Lymphoma ◽

Chemotherapy Resistance ◽

B Cell Lymphoma ◽

Tumor Burden ◽

Therapeutic Effects ◽

Mechanistic Basis

AbstractRituximab/chemotherapy relapsed and refractory B cell lymphoma patients have a poor overall prognosis, and it is urgent to develop novel drugs for improving the therapy outcomes. Here, we examined the therapeutic effects of chidamide, a new histone deacetylase (HDAC) inhibitor, on the cell and mouse models of rituximab/chemotherapy resistant B-cell lymphoma. In Raji-4RH/RL-4RH cells, the rituximab/chemotherapy resistant B-cell lymphoma cell lines (RRCL), chidamide treatment induced growth inhibition and G0/G1 cell cycle arrest. The primary B-cell lymphoma cells from Rituximab/chemotherapy relapsed patients were sensitive to chidamide. Interestingly, chidamide triggered the cell death with the activation of autophagy in RRCLs, likely due to the lack of the pro-apoptotic proteins. Based on the RNA-seq and chromatin immunoprecipitation (ChIP) analysis, we identified BTG1 and FOXO1 as chidamide target genes, which control the autophagy and the cell cycle, respectively. Moreover, the combination of chidamide with the chemotherapy drug cisplatin increased growth inhibition on the RRCL in a synergistic manner, and significantly reduced the tumor burden of a mouse lymphoma model established with engraftment of RRCL. Taken together, these results provide a theoretic and mechanistic basis for further evaluation of the chidamide-based treatment in rituximab/chemotherapy relapsed and refractory B-cell lymphoma patients.

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Recent Advances in Chemotherapeutic Implications of Deguelin, A Plant Derived Retinoid

The Natural Products Journal ◽

10.2174/2210315510666200128125950 ◽

2020 ◽

Vol 10 ◽

Author(s):

Manzoor A Mir ◽

Umar Mehraj ◽

Bashir A Sheikh

Keyword(s):

B Cell ◽

Therapeutic Agent ◽

Cell Lymphoma ◽

Myeloid Cell ◽

Cancer Chemoprevention ◽

B Cell Lymphoma ◽

Signalling Pathway ◽

Therapeutic Effects ◽

Underlying Mechanisms ◽

And Migration

Deguelin, a plant retinoid has emerged to be a promising therapeutic agent in the treatment of different cancers. Recent studies demonstrate that deguelin has potential as an angiogenesis antagonist in malignant and endothelial cells by specifically targeting HGF-c-Met and VEGF-VEGFR pathways. It is reported to have profound therapeutic effects in pancreatic cancer by inactivation of the hedgehog (Hh) signalling pathway and suppresses the expression of matrix metalloproteinases such as MMP-2 and MMP-9. The basic underlying mechanisms for deguelin mediated anti-NSCLC effect were uncovered through its induction of elevated intracellular reactive oxygen species (ROS) levels and suppression of the PI3K /Akt-HK2 signalling pathway. Deguelin induces cell apoptosis by targeting various pathways most notably regulating expression of galectin-1 and binding directly to anti-apoptotic Bcl-2 (B-cell lymphoma 2), Bcl-xl (B-cell lymphoma-extralarge) and Mcl-1 (Myeloid Cell Leukemia Sequence 1) in the hydrophobic grooves thereby liberating BAD and BAX from binding with these proteins. These results derived from effect of Deguelin on various cancer cell lines have further elucidated its role as a novel anti-tumorigenic agent targeting angiogenesis, apoptosis, cell proliferation and migration for cancer chemoprevention. In this review, an attempt has been made to highlight the potential therapeutic effects of Deguelin in destroying the cancer cells by inhibiting various tumour promoting pathways and its uses as a therapeutic agent alone or in combination.

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Therapeutic Antibody Targeting of CD47 Synergizes with Rituximab to Completely Eradicate Human B-Cell Lymphoma Xenografts.

Blood ◽

10.1182/blood.v114.22.2716.2716 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2716-2716

Author(s):

Mark P. Chao ◽

Ash A Alizadeh ◽

Chad Z. Tang ◽

June Helen Myklebust ◽

Bindu Varghese ◽

...

Keyword(s):

Stem Cells ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Fc Receptor ◽

Therapeutic Antibody ◽

Therapeutic Effects ◽

Term Survival ◽

Human B Cell

Abstract Abstract 2716 Poster Board II-692 The anti-CD20 antibody, rituximab, is standard therapy for many CD20 positive B-cell lymphomas, significantly improving long-term survival in combination with chemotherapy. However, rituximab alone is not curative in many non-Hodgkin lymphoma (NHL) patients with observation of primary and acquired resistance, arguing for a need for additional targeted therapies. We identified the cell surface protein CD47 as a potential therapeutic antibody target in human NHL. A major function of CD47 is to inhibit phagocytosis through binding its receptor SIRPα, on phagocytes. We hypothesize that NHL cells over-express CD47 to evade immune phagocytosis and that blockade of CD47 signaling with a monoclonal antibody can eliminate NHL cells by enabling phagocytic engulfment. We have previously shown that an anti-CD47 antibody enables phagocytosis of acute myeloid leukemia (AML) stem cells and eliminates AML in vivo. Here we investigate the therapeutic potential of an anti-CD47 antibody alone and in combination with rituximab for the treatment of NHL. We predict that the combination of anti-CD47 antibody and rituximab will result in synergistic elimination of NHL cells by both blocking an inhibitory signal and delivering a positive signal for phagocytosis. We found that CD47 protein is highly expressed on primary human B-cell NHL cells compared to normal peripheral blood B-cells. Higher CD47 gene expression independently predicted a worse clinical outcome in several cohorts of NHL patients including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and chronic lymphocytic leukemia. Blocking anti-CD47 antibodies preferentially enabled phagocytosis of NHL cells but not normal cell counterparts in vitro. Using isobologram analyses, the combination of anti-CD47 antibody and rituximab resulted in synergistic phagocytosis of NHL cells at higher levels compared to either anti-CD47 antibody or rituximab alone. In addition, anti-CD47 antibody and rituximab mediated their therapeutic effects through Fc-receptor-independent and Fc-receptor-dependent effector mechanisms, respectively. In vivo, anti-CD47 antibody treatment of NHL-engrafted mice reduced lymphoma burden and prolonged survival compared to IgG control. Furthermore, combination treatment with anti-CD47 antibody and rituximab led to elimination of lymphoma and cure of NHL-engrafted mice. These in vivo results were observed in both a disseminated and localized human NHL cell line mouse model as well as in primary human DLBCL mouse xenotransplants. Together, these data provide the rationale for utilizing an anti-CD47 antibody either alone or in combination with rituximab in treating human NHL. Disclosures: Weissman: U.S. Patent Application 11/528,890 entitled “Methods for Diagnosing and Evaluating Treatment of Blood Disorders.”: Patents & Royalties; Stem Cells Inc.: Cofounder and director; Cellerant Inc.: cofounder; Amgen: Equity Ownership.

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