Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
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The incidence of non-Hodgkin's lymphoma (NHL) has increased by over 50% in the United States since 1973. There is epidemiologic evidence that some of this increase is the result of AIDS-related lymphoma and that this component is increasing. Prolonged survival in the setting of a variety of immunodeficiency states is associated with an increased incidence of NHL. The development of antiretroviral therapy and improved therapy for the complications of AIDS has resulted in prolonged survival of patients with AIDS. As these patients survive longer with profound immunodeficiency, they have an increased cumulative risk of developing NHL. This may result in even more AIDS-related NHL in the future than predicted from current epidemiological studies. An increased understanding of the pathogenesis of AIDS-related NHL may lead to means of preventing their occurrence. Also, therapies that may prevent immunodeficiency from developing in HIV-infected patients may reduce the likelihood of NHL developing. Current efforts at treating these lymphomas are aimed at preventing the myelosuppression and immunosuppression associated with current regimens, lymphoma relapses within the central nervous system, and the opportunistic infections associated with treatment of these tumors. Ultimately, the best means of preventing the development of these lymphomas is by preventing infection with HIV.
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PMID:The occurrence of opportunistic non-Hodgkin's lymphomas in the setting of infection with the human immunodeficiency virus. 164 22

To investigate the range of pathology shown by acquired immune deficiency syndrome (AIDS)-related lymphomas arising in an epidemiologically well-defined group of patients, all cases of lymphoma recognized in Danish human immunodeficiency virus (HIV)-infected individuals up to the end of 1988 were studied. Twenty-seven cases (26 high-grade non-Hodgkin's lymphoma [NHL], 1 Hodgkin's disease) were found, to give a cumulative incidence rate of 8% among Danish AIDS patients. Morphologically most NHL patients were classified into two groups: 1) high-grade tumors with a predominant population of immunoblasts, either monomorphic or more often polymorphic with plasmacytic differentiation; 2) Burkitt-type. Of 26 NHLs, 22 had a B-cell paraffin-section immunophenotype and 4 were non-B, non-T. Epstein-Barr virus (EBV) DNA was demonstrated in tumor cells of 12 of 24 cases (50%) using in situ nucleic acid hybridization with a 35S-labeled probe in paraffin sections. Epstein-Barr virus DNA was found in 65% of group 1 and 20% of group 2 tumors. This study suggests the existence of two main groups of AIDS-related lymphoma with different pathogeneses. First there are immunoblast-rich lesions, which usually are associated with EBV and morphologically resemble lymphomas described in immunosuppressed organ-transplantation patients. Second there are Burkitt-type tumors in which EBV sequences are less common and that may be pathogenetically analogous to sporadic Burkitt's lymphoma.
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PMID:AIDS-related lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization. 184 63

Tumour cell karyotypes from patients with Burkitt lymphoma (BL) or Burkitt's type leukemia (ALL3) were studied for correlation with survival, bone marrow and cerebral spinal fluid involvement (CSF), human immunodeficiency virus (HIV) serology, and for recurrent cytogenetic abnormalities. The records of 22 patients with BL from our institution and of 148 cases of BL and ALL3 reported in the literature with karyotypes were evaluated for clinical and cytological features. Overall survival was only 28 per cent and 88 per cent of deaths occurred within the first nine months after diagnosis. Those who survived at least 18 months were unlikely to relapse. Age and gender did not significantly affect survival. Patients presenting with advanced Ann Arbor stage, bone marrow or CSF involvement had lower survival rates. The association of translocations involving chromosome band 8q24 with this disease is confirmed. Sixty-two per cent of karyotypes had t(8;14)(q24;q32) translocations; the recognized variant translocations t(8;22)(q24;q11) and t(2;8)(p12;q24) affected 12 per cent and 9 per cent respectively. Seventeen per cent had abnormal karyotypes but no classic translocation. Patients with variant translocations had the poorest survival rates, and those with the classic t(8;14)(q24;q32) did the best. Despite a small sample size, the variant translocation t(8;22)(q24;q11) appeared to occur at an increased frequency in the patients with AIDS. In the entire group, recurrent involvement of chromosome regions 1q2, 6q11-14 and 17p1 suggests that alteration of genes at these loci, B Cell Growth Factor (BCGF) at 1q2 and p53 on 17p, may contribute to the development and progression of this tumour. Similarly, the frequent trisomies of chromosomes 7, 8, 12 and 18 may indicate an effect on tumour cell growth due to increased gene dosage. Trisomy 12 was found in eight tumours, five from patients with AIDS, suggesting that chromosome 12 has a site or gene whose allelic dosage is selected for in AIDS related lymphoma cells. Cytogenetic studies of adult Burkitt lymphoma and leukemia suggest several likely loci for gene alterations that in conjunction with myc translocations can lead to tumorigenesis.
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PMID:Chromosomal abnormalities in adult non-endemic Burkitt's lymphoma and leukemia: 22 new reports and a review of 148 cases from the literature. 186 43

In an attempt to determine factors predictive of survival in patients seropositive for human immunodeficiency virus (HIV) with acquired immune deficiency syndrome (AIDS)-related lymphoma, the authors studied 60 such patients, all of whom were treated with curative intent. Eleven patients presented with lymphoma primary to the brain (P-CNS); the remaining 49 had systemic AIDS-related lymphoma. Patients with P-CNS lymphoma had more severe underlying HIV-related disease than did patients with systemic lymphoma as evidenced by a higher incidence of AIDS before the diagnosis of lymphoma (73% versus 37%; P = 0.04), and lower median number of CD-4-positive lymphocytes in peripheral blood at diagnosis of lymphoma (30/dl versus 189/dl; P = 0.005). Median survival of such patients was 2.5 months versus 6.0 months for patients with systemic lymphoma (P = 0.04). Forty patients with systemic AIDS-related lymphoma have died; three factors were strongly associated with shorter survival: (1) Karnofsky performance status (KPS) of less than 70% (multivariate relative survival risk [RSR] = 3.1); (2) history of AIDS before the diagnosis of lymphoma (multivariate RSR = 3.0 for opportunistic infection plus Kaposi's sarcoma); and (3) bone marrow involvement (RSR = 3.1)). All three factors (KPS of less than 70%, prior AIDS diagnosis, and marrow involvement) were associated with early demise attributed to AIDS, whereas death attributed to lymphoma per se was associated with only two factors (KPS of less than 70% and marrow involvement). In the absence of all three risk factors, a "good prognosis" group of 17 patients was defined, with a median survival of 11.3 months; the median survival of the remaining patients ("poor prognosis") was 4.0 months (P = 0.0002). Attainment of complete response to therapy (CR) was strongly related to prolonged survival in the patients in the good prognosis group (17.8 months in patients with CR versus 5.0 months in those with less than CR); however, such meaningful prolongation of survival was not seen in patients with poor prognosis who attained CR (6.3 months versus 3.4 months). The patients with poor prognosis may be unable to tolerate the insult of multiagent chemotherapy, experiencing low CR rates (25%) and death caused by lymphoma and AIDS. However, patients in either prognostic category who attained CR remained at risk for dying of AIDS while the lymphoma was in remission. Thus, it is apparent that meaningful prolongation of survival in the patient with AIDS-related lymphoma will require not only effective antineoplastic intervention, but also control of the underlying HIV infection. In addition, future therapeutic trials should stratify patients based upon the prognostic factors defined here in an attempt to clarify the results obtained.
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PMID:Human immunodeficiency virus-related lymphoma. Prognostic factors predictive of survival. 768 56

The multifactorial etiology of Kaposi's sarcoma (KS), which is seen primarily in men, includes genetic predisposition and immunosuppression. Recently, the KS seen in association with human immunodeficiency virus (HIV) infection has been shown to be mediated by the production of certain growth factors. HIV per se may also play an etiologic role via its tat gene. Therapeutic options include irradiation for local or cosmetic control, interferon-alpha, combinations of antiretroviral agents and interferon-alpha, and chemotherapy. The use of antineoplastic agents, either individually or in combination, in cases of advanced disease has been somewhat successful, but resultant immunosuppression and neutropenia may predispose patients to further infection, thereby adversely affecting survival. AIDS-related lymphoma, a late manifestation of HIV infection, often presents with widespread extranodal disease; the median survival time in all series has been approximately 6 months. Two-thirds of patients may have central nervous system involvement at some time in the course of illness. Intensive chemotherapeutic regimens are associated with an increased likelihood of opportunistic infection and do not prolong survival. Combinations of antineoplastic agents given at low doses for short periods may be associated with long-term remissions.
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PMID:Therapeutic approaches to neoplasms in AIDS. 223 35

A case of nonHodgkin's lymphoma of the perianal region in a patient with AIDS is reported. The unusual features of AIDS-related lymphoma and the possible role of immunodeficiency increasing susceptibility to oncogenic viruses are discussed.
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PMID:Perianal lymphoma as a manifestation of the acquired immune deficiency syndrome. Report of a case. 279 89

Non-Hodgkin's lymphomas with particular clinicopathologic features occur with a high incidence in homosexual men affected by AIDS. More frequently than in the general population, these lymphomas have an extranodal location including the gastrointestinal tract. We have recently observed four cases of AIDS-associated lymphomas whose primary location is in the lower rectum and anus. The patients were 27 to 44 years of age, had greatly depressed helper-suppressor T-cell ratios, and antibodies to human immunodeficiency virus (HIV). All four presented with anorectal symptoms and originally had surgery for anorectal fistulas or tumor masses. When staged, three patients had no other organ involvement, the fourth only had lymphoma in an axillary lymph node, and all four had large tumor masses confined within the rectum. In terms of histology, the lymphomas were of undifferentiated or of large cell type and of B-cell phenotype. Lymphomas with primary or major location in the rectum are a rare occurrence in the general population, and until recently, are rare even among the lymphomas associated with the immune deficiency syndrome. At the Lenox Hill Hospital in New York City, no rectal lymphoma among the 58 cases of AIDS-related lymphoma diagnosed during the past 4 years was recorded until 10 months ago. The recognition of the new feature in presentation, a neoplasm associated with AIDS, is obviously important for its early diagnosis and treatment. Its unusual occurrence at the suspected portal of entry of the HIV infection is of interest because it may provide new clues to the association between AIDS and neoplasia.
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PMID:Primary anorectal lymphoma. A new manifestation of the acquired immune deficiency syndrome (AIDS). 295 43

Interleukin-10 (IL-10) is an acid-sensitive protein of 35 kD that has pleiotropic effects including inhibition of cytotoxic T-cell response, induction of major histocompatibility complex type II in B lymphocytes, induction of B-cell growth and differentiation, and autocrine growth factor activity in monocytes. We and others have shown that IL-10 is produced spontaneously by blood mononuclear cells from human immunodeficiency virus-seropositive patients. In an attempt to ascertain the potential role of IL-10 in acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, we evaluated the expression of human IL-10 in both tumor-derived B-cell lines and primary tumor cells. Expression of human IL-10 (hIL-10) mRNA and protein was detected in four of five cell lines examined. An IL-10 antisense oligonucleotide inhibited IL-10 mRNA expression and IL-10 protein production. The proliferation of all B-cell lines was inhibited by an antisense oligonucleotide in a dose-dependent manner that was abrogated by the addition of recombinant hIL-10 protein. No effect of antisense oligonucleotide was observed in the B-cell line not producing hIL-10. Evaluation of primary tumor cells from patients with AIDS-lymphoma cells showed similar production and response to IL-10. These data suggest an autocrine growth mechanism for IL-10 in AIDS-related lymphoma cells and that IL-10 may be important in its pathogenesis.
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PMID:Interleukin-10 is an autocrine growth factor for acquired immunodeficiency syndrome-related B-cell lymphoma. 749 1

The number of cases HIV-associated non-Hodgkin's lymphoma continues to increase as the AIDS epidemic grows. Approximately 3% of AIDS-defining illnesses are non-Hodgkin's lymphoma. The number of non-Hodgkin's lymphoma cases may actually be higher because many cases go unreported. There is also evidence that increasing numbers of patients who are surviving longer on antiretroviral therapy are developing non-Hodgkin's lymphoma. A majority of HIV-related lymphomas are large cell, either high-grade immunoblastic or aggressive intermediate grade, diffuse cleaved, or small noncleaved (Burkitt's-like). HIV-related non-Hodgkin's lymphomas behave aggressively. They are predominantly extranodal and often show unusual patterns of organ involvement. They are typically stage III or IV at the time of diagnosis. Current treatment strategies involve the use of combination chemotherapy regimens with or without antiretroviral therapy. Current studies are evaluating the efficacy of low-dose chemotherapy regimens versus standard-dose regimens with granulocyte-macrophage colony-stimulating factor support. New strategies for treating AIDS-associated non-Hodgkin's lymphoma will incorporate our current knowledge of AIDS-related lymphoma pathogenesis. Factors that reflect a patient's state of immunodeficiency seem to be the most important prognostic features determining clinical outcome after treatment. Patients with good prognostic features may benefit the most from aggressive treatment regimens. AIDS-related primary central nervous system lymphomas continue to comprise approximately 15% of AIDS-related non-Hodgkin's lymphoma cases. Treatment is limited. Although whole-brain radiation therapy can result in an improved neurologic status, the median survival remains 3 to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical aspects of HIV-related lymphoma. 821 98

The incidence of three malignancies has increased in conjunction with the epidemic of human immunodeficiency virus (HIV) disease, and they are currently considered acquired immunodeficiency syndrome (AIDS)-defining conditions. These are Kaposi's sarcoma, associated with AIDS since the onset of the epidemic in 1981; intermediate or high-grade B-cell lymphoma, which became AIDS-defining in 1985; and cervical carcinoma in HIV-infected women, formally recognized as an AIDS-defining diagnosis on January 1, 1993. Approximately 40% of all patients with AIDS have developed cancer during the course of HIV infection. Further, as survival has improved in HIV disease, the incidence of these malignancies has increased. It is thus expected that greater numbers of patients with AIDS-related lymphoma and cervical cancer will be diagnosed in the years ahead. The epidemiologic factors associated with neoplastic disease differ among patients with the three AIDS-related malignancies. The pathogenesis of neoplastic disease also differs. The specific etiologic steps in the development of AIDS-related Kaposi's sarcoma and lymphoma are currently unknown. However, a great deal of information has already been acquired, which may have bearing on the pathogenesis of malignant disease in general, as well as the elucidation of future therapeutic modalities. The specific epidemiologic, etiologic, and clinical characteristics of the AIDS-related malignancies will be described herein. It is hoped that this review will serve to outline our current understanding of this area, to introduce the questions and controversies which are apparent in the field, and to mention those areas in which future research might be focused.
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PMID:AIDS-related malignancies: the emerging epidemic. 835 Mar 62


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