Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of the human tumor necrosis factor alpha (TNF-alpha) gene is one of the earliest events that occurs after stimulation of B or T cells via their antigen receptors. Antibody directed at surface immunoglobulin (anti-Ig) on B cells has previously been shown to induce a rapid burst of TNF-alpha gene transcription, which can be blocked by the immunosuppressants cyclosporin A (CsA) and FK506. Here, TNF-alpha gene transcription is shown also to be highly and rapidly induced in human B cells after stimulation via the CD40 and interleukin 4 pathways, which similarly is inhibited by CsA and a panel of CsA or FK506 analogues that block calcineurin phosphatase activity. Endogenous TNF-alpha produced after stimulation was involved in B-cell proliferation since anti-TNF-alpha monoclonal antibody inhibited both anti-Ig- and anti-CD40-induced B-cell proliferative responses. Moreover, addition of TNF-alpha during stimulation resulted in augmentation of B-cell proliferation, which was also inhibited by anti-TNF-alpha monoclonal antibody. Although lymphotoxin alpha (LT-alpha) mRNA is induced by both pathways, it is not blocked by CsA, whereas LT-beta mRNA is constitutively expressed in B cells. Thus, TNF-alpha is a necessary autocrine growth factor for human B cells stimulated via two independent CsA-sensitive pathways and plays a role similar to that of interleukin 2 in T-cell proliferation. The autocrine nature of TNF-alpha in activated B cells implies a potential role for this cytokine in infection-related polyclonal B-cell expansion and in B-cell malignancies.
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PMID:Tumor necrosis factor alpha is an autocrine growth factor for normal human B cells. 751 25

Post-transplant lymphoproliferative disorder (PTLD) is a recognized severe complication arising in allograft recipients treated with immunosuppressive drugs. Although not common, PTLD is one of the most frequent tumours among graft recipients, comprising 15-25% of neoplasms, compared with 5% in the general population. The introduction of cyclosporin A (CyA) in the early 1980's and the very potent new immunosuppressants such as anti-CD3 monoclonal OKT3 and FK506 have been associated with a significant rise in the incidence of PTLD and with their earlier presentation. The incidence of this malignancy varies with the organ transplanted (1-2% of renal transplant recipients) and with the nature and severity of the accompanying immunosuppressive regimen. While the precise etiology of PTLD is still unclear, significant advances have been made recently in the understanding of its pathogenesis. Most PTLD tumour cells present an activated B-cell phenotype and an unrestricted pattern of latent EBV gene products. It is generally accepted that Epstein-Barr virus (EBV) infection or reactivation and intensive anti-T lymphocyte regimens play a major role in the genesis of PTLD. They include a spectrum of EBV-related disorders ranging from lymphoid hyperplasia to frank malignant non-Hodgkin's lymphoma. Although different therapeutic attempts have been proposed, optimal treatment remains elusive. The mortality rate for monoclonal lymphomas was reported to be as high as 80%. Infusion of anti-B monoclonal antibodies seems to be a promising modality. Different preventive approaches have been proposed, including EBV sero-negative donor/recipient matching and careful monitoring of EBV infection. Cautious use of anti-rejection treatment in combination with prophylactic antiviral therapy is recommended.
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PMID:Incidence and consequences of post-transplantation lymphoproliferative disorders. 923 21

Leukoencephalopathy syndromes encompass a variety of neurologic abnormalities that affect cerebral white matter. Known etiologies include malignant hypertension, eclampsia, renal failure, CNS infection, and drug therapy with cyclosporine, tacrolimus (FK506) and interferon-alpha. Symptoms vary according to sites of involvement; they include altered mentation, visual disturbances, focal neurologic signs, and seizures. Characteristic radiologic findings are hypodense areas without contrast enhancement on CT and an increased T2 signal on MRI. The hypodense areas are often symmetric. The clinical symptoms and neuroimaging abnormalities are often reversible with treatment of the underlying condition or removal of the offending drug. We describe a patient with non-Hodgkin's lymphoma treated with conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy and high-dose steroids who developed a rapidly progressive fatal leukoencephalopathy. Her neurologic symptoms and findings on CT are consistent with reported cases of leukoencephalopathy; however, in this instance, the syndrome was not reversible and was ultimately fatal. None of the previously described etiologies could be demonstrated in association with the patient's illness. There are no prior reports of fatal leukoencephalopathy in adult patients treated with standard-dose CHOP. We believe the concurrent immunosuppression from chemotherapy and high-dose steroids resulted in this patient's fatal complication.
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PMID:Fatal leukoencephalopathy in a patient with non-Hodgkin's lymphoma treated with CHOP chemotherapy and high-dose steroids. 951 35

Nasal natural killer (NK)/T cell lymphoma is a rare entity of non-Hodgkin's lymphoma which mostly occurs in East Asian countries. The advanced disease above clinical stage III is often refractory to the radiation and chemotherapies, remission is transient even if achieved, and median survival is about 12 months. Thus the prognosis of advanced NK/T cell lymphoma is generally poor, however, the promising results of allogeneic hematopoietic stem cell transplantation for advanced NK/T cell lymphoma have been recently reported. In most of these cases, stem cell sources were human leukocyte antigen (HLA) matched donors and alternative sources were seldom used. We report here a case of a 36-year-old woman who was diagnosed as having an extranodal NK/T cell lymphoma, nasal type. The patient achieved a complete remission after 2 cycles of chemotherapy including Carboplatin, Etoposide, Ifosfamide, and Dexamethasone, but 3-months later relapsed during the search for HLA-matched unrelated donors. She received unrelated cord blood transplantation (CBT) in the second remission achieved by a regimen containing L-asparaginase. The conditioning regimen was 12 Gy of total body irradiation, high-dose cytarabin and cyclophosphamide. FK506 and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. GVHD involving the intestine and the oral mucosa was observed, but improved without additional immunosuppressive therapies. The patient remains in remission 33 months after CBT. Cord blood thus could be an appropriate stem cell source for patients with advanced NK/T lymphoma who have no HLA matched donors.
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PMID:Successful treatment of advanced extranodal NK/T cell lymphoma with unrelated cord blood transplantation. 1740 80