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

Protease inhibitors are an important new class of agents for the treatment of human immunodeficiency virus (HIV) infection. The purpose of our trial was to determine the feasibility of combining the protease inhibitor saquinavir with a 96-hour continuous intravenous infusion of cyclophosphamide (800 mg/M2), doxorubicin (50 mg/M2, and etoposide (240 mg/M2) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma associated with HIV infection. The effect of saquinavir on CDE-induced myelosuppression, CD4 lymphopenia, and non-hematologic toxicity was also sought. Twelve patients with HIV-related lymphoma received CDE every 28 or more days. All patients received saquinavir (600mg PO TID), filgrastim and Pneumocystis carinii and fungal prophylaxis. Patients also received either stavudine (n = 2) or both stavudine and didanosine (n = 10). Toxicity was analyzed using the NCI Common Toxicity Criteria for each cycle and the data were compared with the data from our prior study of CDE plus didanosine. An interim analysis was performed after accrual of the first 12 patients in order to assess toxicity. Severe (grade 3 or 4) mucositis occurred in eight of 12 patients (67%) treated with CDE plus saquinavir compared with three of 25 patients (12%) in our prior study treated with CDE without saquinavir (P < 0.001). In logistic regression analysis, saquinavir use was the only factor associated with a significantly greater risk of severe mucositis (relative risk 7.9; P = 0.03). Saquinavir use was not associated with a significant difference in the incidence of febrile neutropenia, prolonged neutropenia, chemotherapy dose reduction, or in the degree of myelosuppression. The decrease in CD4 lymphocytes for patients treated with saquinavir (absolute decrease of 23/microL, or a 26% decrease from baseline) was significantly less than for patients treated without saquinavir in the prior study (absolute decrease of 91/microL, or 42% decrease from baseline; P = 0.05). Four of 10 patients (40%) treated with saquinavir had an increase in CD4 lymphocytes of > or = 10/microL compared with none of 25 patients (0%) treated without saquinavir (P < 0.001). Combination of the protease inhibitor saquinavir with infusional CDE in patients with HIV-associated lymphoma was associated with a significant increase in the incidence of severe mucositis. This finding suggests that saquinavir may alter the metabolism of one of more of the cytotoxic agents in the CDE regimen, and underscores the need for careful investigation regarding the use of the protease inhibitors in patients receiving chemotherapy.
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PMID:Saquinavir enhances the mucosal toxicity of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma. 964 31

P-glycoprotein is a product of the multidrug resistance (MDR-1) gene. In non-Hodgkin's lymphoma, less than 20% of untreated de novo lymphomas express MDR-1 compared with approximately 50% after failure of chemotherapy. We wished to study the expression of MDR-1 in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Tissue biopsies from 50 patients with newly diagnosed AIDS-NHL were studied by immunohistochemical analysis using C494, a monoclonal antibody specific for the MDR-1 isoform of P-gp. MDR-1 expression was correlated with patient demographics, lymphoma characteristics, response to chemotherapy, and survival. Forty-six males and four females with a median age of 38 years (range 26-63) were studied. A prior AIDS-defining opportunistic infection was reported in 35 patients (70%). The median CD4+ lymphocyte count was 69/mm(3) (range 0-920). Thirty-two patients (63%) had received prior anti-HIV therapy, including a protease inhibitor in five (10%). Pathologic types consisted of diffuse large cell in 13 (26%), immunoblastic in 13 (26%), small non-cleaved in 22 (44%), and high grade not otherwise specified in two (4%). The majority of patients (76%) had stage III/IV disease. Pre-treatment lymphoma tissues from 33 patients (66%) stained positively for MDR-1. MDR-1 positive patients had a significantly lower complete remission rate compared to MDR-1 negative patients (33 versus 65%, P=0.042). Duration of complete response was significantly longer in MDR-1 negative patients compared with MDR-1 positive patients (not reached versus 9.9 months, P=0.003). Strategies to overcome MDR-1 expression may be important for initial treatment in patients with AIDS-NHL.
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PMID:Multidrug resistance (MDR-1) expression in AIDS-related lymphomas. 1175 62

The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for non-Hodgkin's lymphoma is more complex with a reduced incidence of primary central nervous system lymphoma, but a relative stability in the number of patients developing systemic NHL. AIDS-related NHL appears not to be markedly decreased by the introduction of HAART and it is the greatest therapeutic challenge in the area of AIDS oncology. The emphasis has now shifted to cure while maintaining vigilance regarding the unique vulnerability of HIV-infected hosts. Furthermore, also for the prolongation of the survival expectancy of these patients, other non-AIDS-defining tumors, such as Hodgkin's disease, anal, head and neck, lung and testicular cancer, and melanoma have been recently reported with increased frequency in patients with HIV infection.
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PMID:AIDS-related tumors: integrating antiviral and anticancer therapy. 1188 Feb 6

The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for non-Hodgkin's lymphoma is more complex with a reduced incidence of primary central nervous system lymphoma, but a relatively stability in the number of patients developing systemic NHL. AIDS related NHL appears not to be markedly decreased by the introduction of HAART and it is the greatest therapeutic challenge in the area of AIDS oncology. The emphasis has now shifted to cure while maintaining vigilance regarding the unique vulnerability of HIV-infected hosts. Furthermore, also for the prolongation of the survival expectancy of these patients, other non AIDS-defining tumors, such as Hodgkin's disease, anal and head and neck, lung and testicular cancer, and melanoma have been recently reported with increased frequency in patients with HIV infection.
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PMID:Therapeutic approaches to AIDS-related malignancies. 1452 90

In people infected with the human immunodeficiency virus (HIV) both the CD4 T-cell count and the viral load are used to monitor disease progression to acquired immunodeficiency syndrome (AIDS). CD4 counts of <500/mm(3) are associated with opportunistic infections and certain malignancies, so-called 'AIDS-defining' conditions. Highly active antiretroviral therapy, using combinations of reverse transcriptase inhibitors and/or protease inhibitors, can improve considerably the prognosis of people who are HIV-positive, but such therapy is not yet widely available in many developing countries. People with AIDS are predisposed to urinary tract infection (UTI) by uncommon bacteria and pathogens, e.g. fungi, parasites and viruses, which may affect any urogenital organ; treatment should be culture-specific and long-term, because there is a tendency to recurrence, infection with multiple organisms and resistant isolates. Voiding dysfunction in patients with AIDS is usually a result of neurological complications caused by opportunistic infections, and has a poor prognosis. Of patients with AIDS, 30-50% develop a cancer, especially Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL). KS may involve any urogenital organ, but is usually part of systemic disease. Small lesions on the external genitalia can be treated with laser, cryotherapy or surgical excision, larger lesions with radiotherapy, and disseminated or visceral KS with multidrug chemotherapy. NHL may involve the kidneys, testes and retroperitoneal lymph nodes, thus obstructing the ureters, which may require ureteric stenting or percutaneous nephrostomy. NHL can be treated with radiotherapy and combination chemotherapy. Urolithiasis in patients with AIDS may be caused by indinavir, a protease inhibitor, but the more common types of stones may also occur. Fluid-electrolyte and acid-base disturbances are common in patients with advanced AIDS, secondary to vomiting, diarrhoea, malnutrition or septicaemia. HIV-associated nephropathy occurs in 10-30% of patients, and often leads to renal failure. Testicular atrophy is common, leading to infertility, erectile dysfunction (ED) and decreased libido. Treatment for ED must include counselling about strategies to reduce the transmission of HIV. The risk of HIV transmission after parenteral exposure to blood from an HIV-positive patient is relatively low (0.2-0.4%); the urologist can reduce the risk of transmission during surgery by adopting certain precautions. After occupational exposure to HIV, chemoprophylaxis with antiretroviral medication can significantly reduce the probability of HIV transmission.
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PMID:The urological management of the patient with acquired immunodeficiency syndrome. 1692 74

Starting antiretroviral therapy (ART) with low CD4 counts raises the likelihood of certain cancers, but others increase with longer time on therapy, reflecting the rising risk associated with older age. Researchers in the USA looked at patterns of cancer incidence and timing after ART initiation (Yanik, et al. Clin Infect Dis. 2013;57:756-64). The analysis included medical records from 11,485 participants in eight U.S. HIV clinical cohorts who started ART between 1996 and 2011. Around 80% were male and they started treatment at a median age of 38 years. At the time of ART initiation, the median CD4 count was 202 cells/mm3. Nearly half started a protease inhibitor regimen. The authors looked at incidence rates for AIDS-defining cancers (Kaposi sarcoma [KS], non-Hodgkin's lymphoma, and cervical cancer) and non-AIDS cancers. They separately assessed cancers caused by viruses, such as hepatocellular carcinoma caused by hepatitis B or C, lymphoma related to Epstein-Barr virus, and cervical or anal cancer caused by human papillomavirus (HPV).
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PMID:Cancer in HIV patients. 2432 84

Abstract Hepatitis C virus (HCV) infection is a serious health problem worldwide that can lead to hepatocellular carcinoma or end-stage liver disease. Current treatment with pegylated interferon, ribavirin, and NS3/4A protease inhibitor would lead to a good prognosis in a large population of patients, but there is still no effective vaccine for HCV. HCV robustly infects hepatocytes in the liver. However, extrahepatic manifestations such as mixed cryoglobulinemia, a systemic immune complex-mediated disorder characterized by B-cell proliferation, which may evolve into overt B-cell non-Hodgkin's lymphoma, have been demonstrated. HCV-RNA is often found to be associated with peripheral blood lymphocytes, suggesting a possible interaction with peripheral blood mononuclear cells (PBMCs), especially B-cells with HCV. B-cell HCV infection was a matter of debate for a long time, and the new advance in HCV in vitro infectious systems suggest that exosome can transmit HCV genome to support "infection." We aimed to clarify the susceptibility of primary B-cells to HCV infection, and to study its functional effect. In this article, we found that the recombinant HCV J6JFH1 strain could infect human B-cells isolated from the peripheral blood of normal volunteers by the detection of both HCV-negative-strand RNA by reverse transcription polymerase chain reaction, and NS5A protein. We also show the blocking of HCV replication by type I interferon after B-cell HCV infection. Although HCV replication in B-lymphocytes showed lower efficiency, in comparison with hepatocyte line (Huh7) cells, our results clearly demonstrate that human B-lymphocytes without other non-B-cells can actually be infected with HCV, and that this interaction leads to the induction of B-cells' innate immune response, and change the response of these cells to apoptosis.
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PMID:The J6JFH1 strain of hepatitis C virus infects human B-cells with low replication efficacy. 2485 7

We report on the first well-tolerated and successful use of sofosbuvir-based therapy in a patient in whom chronic infection with hepatitis C had preceded the development of B-cell non-Hodgkin's lymphoma. The patient had previously failed numerous attempts to clear the hepatitis C virus with traditional antiviral schedules. We demonstrate that sofosbuvir-based therapy resulted in cure of hepatitis C in a patient who had relapsed during combination therapy with an NS5A inhibitor, an NS3 protease inhibitor and ribavirin, as well as treatment failures to multiple courses of interferon-based therapy. This report also suggests that eradication of hepatitis C virus may result in the short-term prevention of B-cell non-Hodgkin's lymphoma relapse. The findings from our case require further validation in future cohorts of patients.
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PMID:Sofosbuvir-based therapy cures hepatitis C virus infection after prior treatment failures in a patient with concurrent lymphoma. 2620 83