Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study explored the use of interleukin 2 (IL-2) and interferon gamma (IFN-gamma) gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor used is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology, and responds to treatment in a manner similar to its human counterpart. Using retroviral vectors, the human IL-2 and mouse IFN-gamma genes were introduced and expressed in MBT-2 cells. The tumor-forming capacity of the cytokine gene-modified MBT-2 cells was significantly impaired, since no tumors formed in mice injected intradermally with either IL-2- or IFN-gamma-secreting cells, using cell doses far exceeding the minimal tumorigenic dose of parental MBT-2 cells. Furthermore, mice that rejected the IL-2- or IFN-gamma-secreting tumor cells became highly resistant to a subsequent challenge with parental MBT-2 cells, but not to 38C13 cells, a B cell lymphoma of the same genetic background. To approximate the conditions as closely as possible to the conditions prevailing in the cancer patient, inactivated cytokine-secreting cells were used to treat animals bearing tumors established by orthotopic implantation of MBT-2 cells into the bladder wall of the animal. Treatment of mice carrying a significant tumor burden with IL-2-secreting MBT-2 cells had a significant inhibitory effect on tumor progression with extended survival. Moreover, in 60% of the mice the tumor regressed completely and the animals remained alive and free of detectable tumor for the duration of the observation period. Treatment of tumor-bearing animals with IL-2-secreting MBT-2 cells was superior to the use of cisplatin, a chemotherapeutic agent used in the treatment of bladder cancer. The therapeutic effect of IFN-gamma-secreting cells was minimal and treatment with unmodified MBT-2 cells had no effect on tumor growth or survival, showing that the parental MBT-2 cells were nonimmunogenic in this experimental setting. Most importantly, mice that exhibited complete tumor regression after treatment with IL-2-secreting MBT-2 cells became resistant to a subsequent challenge with a highly tumorigenic dose of parental MBT-2 cells, indicating that long-term immunological memory was established in the "cured" mice.
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PMID:Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells. 845 7

The clinicopathological features of 10 patients with primary mediastinal large B-cell lymphoma (PMLBCL) are described. The patients were aged 19 to 63 years, with a median age of 25.5 years. There were 5 men and 5 women. All patients presented with chest symptoms, and 6 presented with superior vena cava syndrome. Nine patients had bulky mediastinal tumors. The disease was confined within the thorax and contiguous lymph nodes, although multiple liver tumors were observed in 1 patient. Laboratory findings included high lactate dehydrogenase levels and elevated C-reactive protein levels. The soluble interleukin 2-receptor level was high in 6 patients tested. A comparative study of PMLBCL and nodular sclerosis-type Hodgkin's disease (NS-HD) with a mediastinal mass revealed substantial overlap in clinical features. Histopathological examination of biopsy specimens of PMLBCL revealed clusters of CD20+ large cells; however, CD30+ Hodgkin/Reed-Sternberg-like cells were occasionally seen, raising the potential to misdiagnose PMLBCL as NS-HD. The patients with PMLBCL were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), biweekly CHOP, or MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin) regimen, and 6 received consolidation radiotherapy to the involved field. With the exception of 1 patient who was primarily refractory to therapy, 9 patients (90%) achieved complete response and 7 (70%) remain in continuous remission with a mean follow-up of 24 months.
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PMID:Primary mediastinal large B-cell lymphoma: a comparative study with nodular sclerosis-type Hodgkin's disease. 1159 19

Cytotoxic T-lymphocyte responses to subcellular antigens are enhanced when antigens are presented on cell-sized silica microbeads called large multivalent immunogens (LMIs). LMIs prepared with tumour cell membrane fragments have induced partial remissions in humans with melanoma and renal cell carcinoma. The purpose of this phase I study was to evaluate the safety of LMIs, prepared with autologous lymphoma cell membranes, along with subcutaneous interleukin 2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) in dogs with untreated B-cell lymphoma. After lymph node excision and induction chemotherapy, five dogs were vaccinated with three weekly doses of LMI alone; five with LMI and subcutaneous IL-2 and five with LMI, IL-2 and GM-CSF. No significant toxicity was noted, treatment did not adversely affect disease-free interval and half of the dogs showed measurable delayed-type hypersensitivity reactions to intradermal challenge with LMI, suggesting specific cell-mediated immunity.
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PMID:Immunotherapy with autologous tumour antigen-coated microbeads (large multivalent immunogen), IL-2 and GM-CSF in dogs with spontaneous B-cell lymphoma. 2156 95

We report a case of follicular B-cell lymphoma (FL) treated successfully using clarithromycin (CAM). A 44-year-old man who presented with lymphadenopathy was diagnosed with FL after a histological examination of his biopsy specimens. He was administered chemotherapy with R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone) following which stable disease was achieved. However, the subsequent clinical course showed partial remission of FL and stable disease with tumor regrowth, each of which was treated with chemotherapeutic regimens. Since the patient was diagnosed with leukocytopenia, he could not undergo chemotherapy for the third regrowth; hence, he was administered CAM. His lymphadenopathy regressed and the levels of soluble interleukin 2-receptor decreased. This case shows that treatment using CAM may be effective in some cases of FL.
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PMID:A case of follicular B-cell lymphoma treated using clarithromycin. 2206 78

The protease activity of the paracaspase MALT1 is central to lymphocyte activation and lymphomagenesis, but how this activity is controlled remains unknown. Here we identify a monoubiquitination of MALT1 on Lys644 that activated the protease function of MALT1. Monoubiquitinated MALT1 had enhanced protease activity, whereas a ubiquitination-deficient MALT1 mutant with replacement of that lysine with arginine (MALT1(K644R)) had less protease activity, which correlated with impaired induction of interleukin 2 (IL-2) via the T cell antigen receptor in activated T cells. Expression of MALT1(K644R) diminished the survival of cells derived from diffuse large B cell lymphoma of the activated B cell-like subtype (ABC DLBCL), which require constitutive protease activity of MALT1 for survival. Thus, monoubiquitination of MALT1 is essential for its catalytic activation and is therefore a potential target for the treatment of ABC-DLBCL and for immunomodulation.
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PMID:The protease activity of the paracaspase MALT1 is controlled by monoubiquitination. 2341 15

The present study aimed to uncover the pharmacological function and underlying mechanism of puerarin as a potential treatment for COVID-19, using an in silico methodology, including network pharmacology and molecular docking. The pivotal targets of puerarin to treat COVID-19 were identified and included the epidermal growth factor receptor (EGFR), tumour necrosis factor (TNF), tumour protein p53 (TP53), caspase 3 (CASP3), RELA proto-oncogene (RELA), Fos proto-oncogene (FOS), caspase 8 (CASP8), prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin 2 (IL2), protein kinase CB (PRKCB), B cell lymphoma/leukaemia gene-2 (BCL2), protein kinase CA (PRKCA), nitric oxide synthase 3 (NOS3) and peroxisome proliferator-activated receptor gamma (PPARG). Functionally, the anti-COVID-19 action of puerarin was associated with the suppression of oxidative stress and inflammatory cascades, and cell apoptosis. The signalling pathways of puerarin to treat COVID-19 included modulation of the pathways of apoptosis, IL-17 signalling, mitogen-activated protein kinase (MAPK) signalling and TNF signalling. Molecular docking data illustrated the binding capacity of puerarin with COVID-19 and the effective anti-COVID-19 activity of puerarin. Taken together, our current network pharmacology-based findings revealed the pharmacological role of puerarin in the treatment of COVID-19. Furthermore, the bioinformatic findings elucidated that some of these pivotal targets might serve as potential molecular markers for detecting COVID-19.
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PMID:Anti-coronavirus disease 2019 (COVID-19) targets and mechanisms of puerarin. 3324 58


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