Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that is associated with a variety of malignancies. In vivo infection of B lymphocytes is initially associated with the broad expression of immunodominant viral latency genes and proliferation of infected cells. Ultimately, a viral reservoir is established in resting B cells with restricted expression of viral latency genes and no expression of immunodominant viral genes. Among the tumours associated with EBV that are relevant to a consideration of EBV in HIV-associated malignancies are posttransplant lymphoproliferative disease, Burkitt's lymphoma (BL) and Hodgkin's disease (HD). BL carries whereas EBV in only a minority of cases whereas HD in patients infected with HIV is virtually always EBV-associated. EBV-directed T cell therapies have proven effective in posttransplant lymphomas in bone marrow transplantation patients. In patients with HIV infection, primary central nervous system (CNS) and immunoblastic lymphomas show similarities with posttransplant lymphoproliferative disease. EBV detection studies in cerebrospinal fluid are useful diagnostically in primary CNS lymphoma. T cell therapies may be useful in the treatment of EBV-associated lymphomas. Thus, a better understanding of the relationship between EBV and these tumours will not only help to clarify their pathogenesis, but may facilitate the development of new diagnostic and therapeutic strategies.
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PMID:Epstein-Barr virus associated lymphoproliferations in the AIDS setting. 1142 53

In the era of highly active antiretroviral therapy (HAART), systemic non-Hodgkin lymphoma (NHL) represented the most frequent cancer associated to HIV infection. In contrast to Kaposi's sarcoma and primary central nervous system lymphoma (PCNSL) which incidence have been declining after introduction of HAART, systemic NHL-HIV has relatively stable remained. Systemic HIV related NHL are markedly heterogeneous both histologically and clinically and this clinicophatological heterogenity reflects variability in the molecular lesions associated to these lymphomas and immunological status of these patients. The introduction of HAART has substantially modified the approach to HIV related lymphomas. The results of recent monoinstitutional study of Aviano Cancer's Institute on 235 patients have suggested that HAART would otherwise allow a long life expectancy with longer disease free survival and overall survival. In fact the reduced of morbidity of AIDS patients bought by HAART justified the use of aggressive antineoplastic therapies.
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PMID:[Systemic HIV-non-Hodgkin lymphoma in the era of HAART. Natural history]. 1176 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 had a dramatic impact on the morbidity and mortality of individuals living with human immunodeficiency virus (HIV). In addition to contributing to declines in the incidence of several opportunistic infections, HAART is affecting the incidences of several acquired immunodeficiency syndrome (AIDS)-defining malignancies. The incidence of Kaposi's sarcoma (KS) and primary central nervous system lymphoma (PCNSL) has dropped precipitously since the introduction of HAART in 1995. Systemic non-Hodgkin's lymphoma (NHL) appears to be declining in incidence as well, but to a lesser degree than KS and PCNSL. On the contrary, the incidence of invasive cervical carcinoma has not significantly changed in the HAART era. The impact of HAART on the epidemiology of other HIV-associated malignancies, including Hodgkin's disease and anal carcinoma, remains unclear. Data regarding the impact of HAART on the natural history and treatment outcomes of HIV-associated malignancies are limited. The possibility of direct and indirect roles of HIV in HIV-related carcinogenesis suggests that antiretroviral therapy may be an important component of the treatment strategy for several HIV-related malignancies. Patients with HIV-NHL treated with HAART in addition to chemotherapy experience fewer intercurrent opportunistic infections. Furthermore, the simultaneous administration of HAART and chemotherapy does not appear to significantly increase toxicity. Whether the combination of HAART and standard therapy results in improved survival remains uncertain. This two-part article, which will conclude in the May 2002 issue, analyzes the impact of HAARTon the incidence, clinical course, and outcomes of each of the AIDS-related malignancies.
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PMID:AIDS malignancies in the era of highly active antiretroviral therapy. 1201 34

The introduction of highly active antiretroviral therapy (HAART) has had a dramatic impact on the morbidity and mortality of individuals living with human immunodeficiency virus (HIV). In addition to contributing to dramatic declines in the incidence of several opportunistic infections, HAART is affecting the incidences of several acquired immunodeficiency syndrome (AIDS)-defining malignancies. The incidence of Kaposi's sarcoma (KS) and primary central nervous system lymphoma (PCNSL) has dropped precipitously since the introduction of HAART in 1995. Systemic non-Hodgkin's lymphoma (NHL) appears to be declining in incidence as well, but to a lesser degree than KS and PCNSL. On the contrary, the incidence of invasive cervical carcinoma has not significantly changed in the HAART era. The impact of HAART on the epidemiology of other HIV-associated malignancies, including Hodgkin's disease and anal carcinoma, remains unclear. Data regarding the impact of HAART on the natural history and treatment outcomes of HIV-associated malignancies are limited. The possibility of direct and indirect roles of HIV in HIV-related carcinogenesis suggests that antiretroviral therapy may be an important component of the treatment strategy for several HIV-related malignancies. Patients with HIV-NHL treated with HAART in addition to chemotherapy experience fewer intercurrent opportunistic infections. Furthermore, the simultaneous administration of HAART and chemotherapy does not appear to significantly increase toxicity. Whether the combination of HAART and standard therapy results in improved survival remains uncertain. This two-part article, which began in the April 2002 issue, analyzes the impact of HAART on the incidence, clinical course, and outcomes of each of the AIDS-related malignancies.
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PMID:AIDS malignancies in the era of highly active antiretroviral therapy. 1210 91

Most lymphomas that involve the central nervous system are B-cell neoplasms that express the cell surface molecule CD20. After intravenous administration, rituximab can be reproducibly measured in the cerebrospinal fluid (CSF) in patients with primary central nervous system lymphoma; however, the CSF levels of rituximab are approximately 0.1% of serum levels associated with therapeutic activity in patients with systemic non-Hodgkin lymphoma. Because lymphomatous meningitis is a frequent complication of non-Hodgkin lymphoma, we have conducted an analysis of the safety and pharmacokinetics of direct intrathecal administration of rituximab using cynomolgus monkeys. No significant acute or delayed toxicity, neurologic or otherwise, was detected. Pharmacokinetic analysis suggests that drug clearance from the CSF is biphasic, with a terminal half-life of 4.96 hours. A phase 1 study to investigate the safety and pharmacokinetics of intrathecal rituximab in patients with recurrent lymphomatous meningitis will be implemented based on these findings.
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PMID:Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. 1239 4

Primary central nervous system lymphoma (PCNSL) is a rare but often rapidly fatal form of non-Hodgkin B-cell lymphoma that arises within the central nervous system (CNS) and has a low propensity to metastasize. We performed immunohistochemistry on formalin-fixed, paraffin-embedded brain biopsy specimens from 24 patients with PCNSL to investigate the expression of B cell-attracting chemokine 1 (BCA-1, CXCL13), a lymphoid chemokine involved in B-cell compartmental homing within secondary lymphoid organs and recently implicated in the pathogenesis of inflammatory and malignant lymphocyte-mediated diseases. Whereas BCA-1 was not detected in normal human brain, all 24 brain biopsy specimens containing PCNSL were positive for BCA-1. Double immunostaining on selected specimens localized BCA-1 to malignant B lymphocytes and vascular endothelium. In contrast, 2 chemokines implicated particularly in T-cell movement, secondary lymphoid tissue chemokine (SLC, CCL21) and Epstein-Barr virus-induced molecule 1 ligand chemokine (ELC, CCL19), were expressed only by occasional stromal cells in 2 and 4 of the 24 specimens, respectively. Tumor cells stained positively for CXCR5, the primary receptor for BCA-1. In situ hybridization verified the expression of BCA-1 mRNA by malignant B cells, but not vascular endothelium, within the tumor mass, suggesting that vascular endothelial BCA-1 expression may be consequent to transcytosis. In PCNSL, expression of BCA-1 by malignant lymphocytes and vascular endothelium may influence tumor development and localization to CNS.
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PMID:Expression of B-cell-attracting chemokine 1 (CXCL13) by malignant lymphocytes and vascular endothelium in primary central nervous system lymphoma. 1239 12

Primary central nervous system lymphoma of non-Hodgkin's type are distinguished from systemic non-Hodgkin's lymphoma because of their different pathobiological behaviour. Predisposing factors are pharmacologically induced immunosuppression and those referring to diseases. We present the case of a patient who was sent to hospital in case of emergency due to pain of one half of the face. The symptoms corresponded essentially to neuralgia of the trigeminal nerve. During course other neurological symptoms showed up. The right diagnoses of a primary central nervous system lymphoma of non-hodgkin's type was finally made post mortem. The case especially reveals the difficulties of diagnosis - including negative and confusing MRI-findings - and the variety of differential diagnosis of this also in not immunosuppressed persons more and more frequent kind of tumor.
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PMID:[Neuralgia of the trigeminal nerve as first symptom of a primary central nervous system lymphoma of non-Hodgkin's type]. 1257 69

The pathogenesis of AIDS-related non-Hodgkin lymphomas (AIDS-NHLs) is associated with chromosomal translocations that deregulate the expression of various oncogenes. Recently, a novel mechanism of genetic lesion, termed aberrant hypermutation, has been identified in diffuse large B-cell lymphoma (DLBCL) of immunocompetent hosts. In these tumors, the somatic hypermutation (SHM) process that normally targets immunoglobulin V (IgV) genes in B cells appears to misfire and causes mutations in the 5' sequences of multiple proto-oncogenes, including PIM-1, PAX-5, RhoH/TTF, and c-MYC. To investigate whether aberrant hypermutation occurs also in AIDS-NHL, we studied the mutation profile of these 4 genes in various histologic subtypes. Mutations in 1 gene or more were detected in 19 of 39 (48.7%) AIDS-NHL cases (10 of 18 AIDS-diffuse large B-cell lymphoma; 4 of 11 AIDS-Burkitt lymphoma; 4 of 6 AIDS-primary effusion lymphoma; 1 of 4 AIDS-primary central nervous system lymphoma), with 9 of 39 (23.1%) cases carrying mutations in 2 or more genes. Overall, PIM-1 was mutated in 5 of 39 (12.8%), PAX-5 in 8 of 39 (20.5%), RhoH/TTF in 9 of 39 (23.1%), and c-MYC in 7 of 27 (25.9%) AIDS-NHL cases. Mutations were represented mainly by single base pair substitutions (n = 63) with rare deletions/insertions (n = 5) and displayed features typical of the IgV-associated SHM process. In addition, a number of mutations in PIM-1 and c-MYC were found to affect coding exons, leading to amino acid substitutions with likely functional consequences. Analysis of intraclonal heterogeneity documented that the aberrant hypermutation activity may be ongoing in at least some cases. These data indicate that aberrant hypermutation is associated with various subtypes of AIDS-NHL and may represent a major contributor to their pathogenesis.
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PMID:Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma. 1271 22

Human immunodeficiency virus (HIV)-associated malignancies include acquired immunodeficiency virus: Aids-defining malignancies, Kaposi's sarcoma, (KS), non-Hodgkin's lymphoma (NHL), and, since 1993, invasive cervical cancer (1CC), and non-Aids defining malignancies. Most cancers that are associated with HIV infection are driven by oncogenic viruses such as Epstein-Barr virus, human herpes virus 8 and human papillomavirus. Highly active antiretroviral therapy (HAART) is affecting the incidence of several Aids defining malignancies. The incidence of KS and primary central nervous system lymphoma (PCNSL) has dropped since the introduction of HAART in 1996. Systemic NHL appears to be declining in incidence as well, but to a lesser degree than KS and PCNLS. In contrast, the incidence of invasive cervical carcinoma has not changed in the HAART era. The impact of HAART on the epidemiology of other HIV-associated malignancies, including Hodgkin's disease and anal carcinoma, remains unclear.
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PMID:[Epidemiology of HIV-associated malignancies]. 1285 Jul 60


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