Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV-1 infection would initially predispose to neoplastic transformation in terms of a progressive lymphocytic proliferation followed by the onset of an immunodeficiency state. Both virion genomic integration and also active host cell proliferation would perhaps participate in the establishment of an often multifocal primary CNS lymphoma of AIDS type. Repeated opportunistic infections in AIDS patients tend to especially involve the central nervous system to also carry an increased risk of neoplastic transformation of the reactive B lymphocytes reaching the brain. A microenvironmental set of circumstances in patients with AIDS would predispose to non-Hodgkin's lymphoma largely in terms of an HIV-1 infection that progresses concurrently with evolving cell replication, immunodeficiency, and repeated opportunistic infections as caused by several different potential pathogens. Epstein-Barr virus infection in particular appears closely related to Hodgkin's disease that develops in some AIDS patients. A viral role in the development of lymphomas and of Kaposi sarcoma in HIV-infected individuals would account for neoplastic aggressiveness and for a particular predilection for primary CNS lymphoma. Such a role perhaps implicates viral integration within the genome of host cells that are actively proliferating or else infected by multiple viral pathogens such as EBV, HIV-1, CMV, and Herpes virus.
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PMID:Viral participation in cellular and microenvironmental transformation and amplification towards malignancy in AIDS patients. 1505 Jan 13

Polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) for detection of Epstein-Barr virus (EBV) DNA has been proposed as a minimally invasive method for establishing the diagnosis of human immunodeficiency virus-related primary central nervous system lymphoma (PCNSL). In a review of the operational characteristics of this test in our clinical practice, the positive predictive value of CSF PCR for EBV for establishing the diagnosis of PCNSL was only 29%. Of 7 patients with CSF PCR positive for EBV, 2 had PCNSL, and 5 received alternative diagnoses (specificity, 79.1%).
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PMID:Predictive value of polymerase chain reaction of cerebrospinal fluid for detection of Epstein-Barr virus to establish the diagnosis of HIV-related primary central nervous system lymphoma. 1549 20

We investigated the prevalence and prognostic role of CpG island methylation of the reduced folate carrier (RFC) gene promoter region in primary central nervous system lymphoma (PCNSL) in immunocompetent patients. Genomic DNA from 40 PCNSL was used for methylation-specific polymerase chain reaction and bisulphite genomic sequencing of the RFC promoter region. Human immunodeficiency virus-negative systemic diffuse large B-cell lymphomas (DLBCL) were used as controls (n = 50). The impact on outcome of RFC promoter methylation was assessed in 37 PCNSL patients treated with high-dose methotrexate (HD-MTX)-based chemotherapy +/- radiotherapy. RFC promoter methylation occurred in 12 of 40 (30%) PCNSL and in four of 50 (8%) DLBCL (P = 0.01). Of 37 PCNSL treated with HD-MTX-based chemotherapy, methylation occurred in nine cases (24%, M-PCNSL), while 28 cases (76%, U-PCNSL) were negative. Three M-PCNSL (33%) and 15 U-PCNSL (54%) achieved complete remission (CR) after primary chemotherapy. Logistic regression confirmed the independent association between CR rate and International Extranodal Lymphoma Study Group score (P = 0.03), RFC promoter methylation (P = 0.07) and use of cytarabine (P = 0.08). The 3-year failure-free survival (FFS) and overall survival for M-PCNSL and U-PCNSL was 0% vs. 31 +/- 9% (P = 0.34) and 0% vs. 31 +/- 9% (P = 0.35) respectively. This is the first study to assess the methylation status of the RFC promoter in human tumour samples. RFC methylation is more common in PCNSL compared with systemic DLBCL, and is associated with a lower CR rate to HD-MTX-based chemotherapy. If confirmed in prospective trials on PCNSL treated with HD-MTX alone, these data may suggest the necessity for alternative strategies in M-PCNSL considering the increased risk of MTX resistance by tumour cells.
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PMID:Aberrant methylation in the promoter region of the reduced folate carrier gene is a potential mechanism of resistance to methotrexate in primary central nervous system lymphomas. 1532 16

The incidence of primary central nervous system lymphoma (PCNSL) has been on the rise in the setting of immunodeficiency syndromes such as acquired immune deficiency syndrome (AIDS). Its diagnosis has been facilitated by the advent of a cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) PCR assay. The reported high sensitivity and specificity of this assay has made it the cornerstone of diagnosis of PCNSL, replacing more traditional methods such as an open CNS biopsy. Here, we have described a patient with a known history of C3 AIDS presenting with lower extremity weakness and eventual myelopathy who was later diagnosed as having intramedullary PCNSL after detection of EBV DNA in his CSF. After failing to respond to radiotherapy, he underwent a spinal cord biopsy revealing intramedullary tuberculoma. This case illustrates the risk of misdiagnosis with this assay and the importance of histological confirmation of a pathological lesion prior to implementation of therapy.
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PMID:Intramedullary tuberculoma mimicking primary CNS lymphoma. 1548 5

The impact of highly active antiretroviral therapy (HAART) on the incidence of non-Hodgkin's lymphoma was less obvious initially, although primary central nervous system lymphoma (PCNSL) has dropped precipitously since the introduction of HAART. The pathogenesis of acquired immunodeficiency syndrome-related lymphoma is multifactorial. Epstein-Barr virus plays a significant role in these diseases, especially Burkitt lymphoma and PCNSL. Data regarding the effect of HAART on the natural history and treatment outcomes of these malignancies are emerging. The possibility of direct and indirect roles of human immunodeficiency virus in the carcinogenesis suggests that antiretroviral therapy may be an important component of the treatment for these malignancies. The simultaneous administration of HAART and chemotherapy does not appear to significantly alter the toxicity profile, although the information with respect to the interaction of HAART and chemotherapy is limited. The use of biological agents, for example, monoclonal antibody against CD-20, is being explored to improve the clinical outcome of this disease.
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PMID:AIDS-related cancer in the era of highly active antiretroviral therapy (HAART): a model of the interplay of the immune system, virus, and cancer. "On the offensive--the Trojan Horse is being destroyed"--Part B: Malignant lymphoma. 1558 Oct 59

We experienced 8 cases of progressive multifocal leukoencephalopathy (PML) complicated by human immunodeficiency virus (HIV) type-1 infection from 1985 to 1999. These cases showed dementia, bradykinesia, dysarthria, hemiparesis, and so on. All of the cases were severely immunocompromised hosts, because none had more than 150/mm3 CD4 + lymphocytes; indeed, 5 of the cases were below 20/mm3. Other neurological complications except PML were primary CNS lymphoma, HIV encephalitis, and CMV encephalitis. The mean life durations was 7.6 months after the first symptom appeared, for all but one of the patients; the exceptional patient lived for 24 months after. Autopsy studies of the central nervous systems were performed for 7 cases, all of which showed extensive demyelinating lesions of the white matter, and in some cases these extended into the spinal cord. In contrast to Western countries, in Japan there have been few reports of AIDS-associated PML. Thus, this report was thought to be important here.
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PMID:[Clinical investigation of the 8 cases with AIDS (acquired immunodeficiency syndrome)-associated progressive multifocal leukoencephalopathy (PML)]. 1578 5

Applying nested-PCRs, we frequently detected DNA of Epstein-Barr virus and cytomegalovirus but not JC virus in cerebrospinal fluid samples from 140 human immunodeficiency virus-infected patients with central nervous system symptoms in northern Thailand. Despite the low incidence of primary central nervous system lymphoma or cytomegalovirus encephalitis among Thai AIDS patients, Epstein-Barr virus and cytomegalovirus infections in the central nervous system are common.
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PMID:Frequent detection of Epstein-Barr Virus and cytomegalovirus but not JC virus DNA in cerebrospinal fluid samples from human immunodeficiency virus-infected patients in northern Thailand. 1600 Apr 85

Infection with the human immunodeficiency virus (HIV) is associated with an increased risk of systemic non-Hodgkin's lymphoma, Hodgkin's disease, and primary central nervous system lymphoma (PCNSL). Systemic lymphoma usually involves extranodal sites (80%-90%) and is usually of intermediate-grade (diffuse large-cell or immunoblastic( or high-grade (diffuse small noncleaved) histology. Approximately one third to one half of patients are cured with the cytotoxic treatment regimens that are used in immunocompetent patients with lymphoma. Careful attention must be paid to appropriate treatment of HIV infection and to primary and secondary infection prophylaxis. Colony-stimulating factors are commonly used in conjunction with cytotoxic therapy because of the high risk of febrile neutropenia. Patients with HIV-associated Hodgkin's disease also frequently have extranodal involvement and mixed cellularity histology, features associated with an adverse prognosis in immunocompetent patients. Treatment regimens used to treat Hodgkin's disease in immunocompetent patients have been used with some success, although the prognosis is not favorable in HIV-infected patients with PCNSL is generally poor because such patients typically present with advanced immunodeficiency (CD4 <50/microL), and the lymphoma often relapses after transient initial response to whole brain irradiation. There are anecdotal reports of responses to therapy directed against Epstein-Barr virus (ie, high-dose zidovudine, gancyclovir, and interleukin-2).
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PMID:Human immunodeficiency virus-associated lymphoma. 1622 26

Primary central nervous system lymphoma has been traditionally described in patients with immunodeficiency syndromes; however, there is an increasing number of immunocompetent patients with this type of tumor that have been reported recently. In this paper we have retrospectively analyzed 22 immunocompetent patients with a confirmed diagnosis of primary lymphoma of the brain. The mean age in this group was 65 years with a similar male/female ratio. The time of evolution of the clinical course was 80.4 days and it was mainly characterized by headache and focal neurological deficit. In four patients multiple lesions were observed, while the remaining presented single lesions mainly located in the periventricular area of the cerebral hemispheres. All patients were initially administered steroids and a stereotactic biopsy was performed. The majority of tumors were histologically classified as diffuse large cells and all of them showed a positive reaction to B-cells antigens on immunohistochemistry. All patients were treated with radiotherapy and in 10 of them, chemotherapy with methotrexate was also indicated. The mean survival rate was II months among patients treated with radiotherapy alone and increased to 36 months when chemotherapy was added.
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PMID:[Primary central nervous system lymphoma in immunocompetent patients]. 1638

Before the introduction of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-related primary central nervous system lymphoma (PCNSL) represented one of the most prevalent causes of focal brain lesions in HIV-infected people. The prognosis of PCNSL was very poor, with median survival time not exceeding 2 months. Brain biopsy was the method of choice for the definitive diagnosis, but it was and remains an invasive procedure with morbidity and mortality as well as considerable costs in terms of patients' management and quality of life. The strict association between AIDS-PCNSL and Epstein-Barr virus led to the suggestion that EBV DNA in cerebrospinal spinal fluid (CSF) might serve as a diagnostic marker, reducing the time required for diagnosis and allowing a minimally invasive approach. The clinical usefulness of this methodology has been largely demonstrated through clinical practice. After the introduction of HAART in clinical practice, a survival benefit has been observed for most persons with acquired immunodeficiency syndrome (AIDS)-associated opportunistic infections and cancers. In particular, for patients with non-Hodgkin lymphoma, a higher likelihood of response to chemotherapy as well as a longer survival has been found as a consequence of the use of combined antiretroviral therapy. Although larger studies did not show significant changes in survival of HIV-infected patients with PCNSL in the era of HAART, small case series and anecdotal reports showed the benefit of HAART in the treatment of PCNSL. Nevertheless, these patients' survival still remains very poor and it could be hypothesized that, other than specific cancer prognostic determinants and severe immunodeficiency, viral pathogenesis as well as EBV-specific immunologic dysfunction may be responsible.
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PMID:Changing pattern of primary cerebral lymphoma in the highly active antiretroviral therapy era. 1654 Apr 54


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