Cancer detection and prevention. Supplement : official publication of the International Society for Preventive Oncology, Inc最新文献

An increased incidence of lymphoid neoplasias is associated with the states of immune deficiency both congenital and acquired. Thirty-five cases of lymphoma in males at high risk for AIDS were diagnosed in one community hospital in New York City within the past 2 years. The mean age of these patients was 39.6 years; 34 were homosexual, and one was an intravenous drug abuser. There were four Hodgkin and 31 non-Hodgkin lymphomas of various histologic types but almost all of high-grade categories. The proportion of extranodal lymphomas, the involvement of the gastrointestinal tract, central nervous system, bone marrow, and myocardium were significantly higher than in the lymphomas of the general population. The phenotypes were B-cell and non-B-non-T-cell types without any T-cell lymphomas. All patients had reversed helper-suppressor T-cell ratios, and all those tested had circulating HTLV-III and antilymphocyte antibodies. Nine patients have had previous lymph node biopsies showing the lesions of AIDS-related lymphadenopathies that were often directly associated with lymphoma. A variety of severe opportunistic infections and Kaposi sarcoma affected these patients. All lymphomas associated with immune deficiency were highly aggressive, involved multiple organs, and responded poorly to treatment resulting in early deaths.

Vaccinia melanoma oncolysates (VMO) were tested in a Southeastern Cancer Study Group (SECSG)-sponsored phase I/II multiinstitutional trial. Forty-eight patients with stage I or II disease were placed on study at six different dose levels of VMO and two different dose schedules, immediate or delayed. Patients' sera, obtained before treatment and every 3 months following initiation of treatment, were tested for antimelanoma antibodies using a Staphylococcus protein A (SpA) assay. Pretreatment sera were negative in 46 of 47 patients, and only two of 19 patients on delayed treatment developed reactivity by 6 months. However, 13 of 23 on immediate treatment developed reactivity, including eight of eight at the higher doses (1.5 and 2.0 mg). Neither anti-HLA antibody tested by a standard microcytotoxicity assay nor circulating immune complexes measured by both Clq and conglutinin binding assays were produced as a result of the immunization. The demonstration of immunogenicity of VMO at the 2 mg dose and immediate schedule supported the rationale for the use of this dose and schedule for the ongoing second phase Ia/Ib trial and for the future phase III randomized prospective study.

Phytohemagglutinin (PHA)- induced Interleukin-2 (IL-2) production by peripheral blood mononuclear cells was studied in 28 untreated patients with Hodgkin Disease (HD). A group of 28 patients were also investigated for the expression of Tac antigen in the resting stage of lymphocytes and after activation with PHA and mixed leukocyte culture (using anti-Tac monoclonal antibody). The blastogenic response to PHA and IL-2 production by lymphocytes of HD patients was significantly lower than that of normal lymphocytes. Production of IL-2 appeared to be severely affected in 14 of 28 HD patients who also showed PHA response less than the normal range. The Tac antigen expression was found to be lower in PHA-stimulated but not alloantigen-stimulated lymphocytes from the HD patients. No correlation was observed between the levels of IL-2 production, Tac antigen expression, and blastogenic response to PHA or allogeneic cells and the stage of disease when tested in the same patients.

Patients affected by AIDS related-complex (ARC) showed several immunological abnormalities that could lead to a disregulation of immunosurveillance against viral latent infections. We report Epstein-Barr virus (EBV) reactivation was found in seven of eight ARC patients and in two of seven affected by persistent generalized lymphoadenopathy. These patients showed either elevated levels of circulating EBV-positive transformed cells and/or depressed EBV-specific T cell cytotoxicity as assessed by the regression assay. Natural killer cell activity was found to be decreased and correlated with evidence of circulating EBV-infected cells and with impaired EBV-specific immune control. Our data demonstrate that loss of control of EBV latency in the infected host by specific immune mechanisms increases the risk for EBV reactivation and emergence of clones with unlimited growth potential. A role of EBV as a cofactor in the development of ARC is suggested.

Lymph nodes of patients with lymphadenopathy syndrome (LAS) are characterized by two main histological patterns: hyperplastic reactive (H) and regressive (R). In both conditions, the paracortex (PC) is markedly activated with presence of selectively Ia-1+ high endothelial venules. Using a monoclonal antibody for p24, the major core protein of HTLV3, we have immunohistochemically determined the distribution of p24+ cells in lymph nodes from 23 LAS patients' HTLV3-ab serologically positive. p24+ cells were demonstrated in 11 cases. Control nodes were negative. p24+ cells included high endothelial cells of PC postcapillary venules, large perivenular cells, large mono- or binucleated cells in PC and in GC, and few lymphocytelike cells. Our preliminary observations indicate that the majority of p24+ cells are high endothelial and accessory cells that may act either as virus reservoir or as antigen-presenting cells to T4 lymphocytes and to GC B cells. In addition, the positivity of high endothelial cells for p24 might help to explain their selective Ia-1+.

Fifty male AIDS patients with Kaposi sarcoma and 50 matched controls were interviewed about occupation, exposure to pesticides, Vietnam service, smoking habits, etc. No difference in use of pesticides was seen. One case but no control had served in Vietnam and was thereby exposed to agent orange. Dioxins are known to be immunosuppressive in animals. No significant difference in exposure to dioxin-containing products was found between cases and controls, however. Of interest was the fact that four cases but no control were occupationally exposed to hair dyes, some of which have been reported to be carcinogenic.

AIDS has existed in subsaharan Africa at least since 1980. However, the genesis of this condition and its emergence as a health problem remain obscured by lack of data and by antibody data that are now questionable. In Africa, as elsewhere, AIDS is associated with an immunodeficiency associated with the LAV/HTLV-III retrovirus. The clinical manifestations vary somewhat because of the different range of opportunistic pathogens in that environment. Although the "classical," more indolent, endemic form of African Kaposi sarcoma is not associated with this virus or with immunodeficiency, a new, aggressive variety of Kaposi sarcoma in Africa appears to be. The origin of LAV/HTLV-III remains unclear, but the clinical syndrome of AIDS has emerged in Africa only in the past decade. A pattern of geographic spread can be recognized, in which AIDS was seen earliest in Kinshasa, Zaïre, and then emerged in Zambia, Rwanda, and Uganda. Recently, reports indicate spread into Tanzania and Kenya. Transmission appears to be primarily heterosexual, but the factors enhancing heterosexual spread in Africa to a greater extent than in the U.S. and Europe need to be further studied.

Seven of seven chimpanzees inoculated with LAV/HTLV-III and three of three chimpanzee-to-chimpanzee passages seroconverted for LAV/HTLV-III as tested by ELISA and immunoblotting. Serum IgG reactivity to gag-gene products emerged between 3 and 6 weeks after inoculation, p24gag reactivity always reaching maximum titers first. Serum IgG antibodies to env-related proteins occurred 11-21 weeks after inoculation. Throughout the observation period (greater than 36 weeks), IgG reactivity to gag, pol, and env gene products persisted. Matched serum and cerebrospinal fluid (CSF) from three LAV/HTLV-III-infected chimpanzees were available in the chronic phase of infection and titers of viral antibody and albumin and IgG content were determined. By calculation of antibody/albumin indices, evidence was obtained for intrathecal synthesis of IgG antibodies to LAV/HTLV-III in one animal.

The specificities of six monoclonal antibodies produced against plasminogen activator of the human Bowes melanoma cell line are described. They have been used to detect membrane-bound plasminogen activator on cultured human lymphoid cell lines and in neoplastic human lymphocytic and myeloid cells of leukemic patients. These studies indicate that only certain phenotypic subsets of the T-cell lineage derived from patients with chronic lymphocytic leukemia or with Szezary syndrome express plasminogen activator on their surface membrane.

T-cell colonies were generated from the peripheral blood and bone marrow of 61 patients with acquired immunodeficiency syndrome (AIDS), 54 patients with persistent lymphadenopathy syndrome (LAS), 14 clinically normal male homosexuals, and 17 healthy heterosexuals. Mononuclear cells were cultured in methylcellulose in the presence of IL2-containing conditioned medium. The number of T-cell forming cells (T-CFC) from healthy male homosexuals and AIDS and LAS patients was significantly (P less than 0.01) reduced compared to T-CFC from healthy heterosexuals. In AIDS patients, the low colony growth capacity of T-CFC was independent of the presence of either opportunistic infections or Kaposi sarcoma. Twelve LAS patients who subsequently developed AIDS showed the lowest capacity of peripheral blood and bone marrow T-CFC to proliferate. Pooled induced colonies from AIDS and LAS patients and normal homosexuals were composed of immature cells bearing the T3+, T4+, T6+, and T8+ surface phenotype, unlike colonies from normal heterosexuals, which displayed mature cells bearing the T3+, T4+, T6-, and T3+, T8+, T6- surface phenotype. Moreover, most T-CFC from primary colonies had lost their self-renewal capacity. In some AIDS and LAS patients but not healthy homosexuals peripheral blood and bone marrow T-CFC were capable of generating colonies with recombinant IL2 (rIL2) without any other mitogenic stimulation. The rIL2-induced colony growth was abrogated by a monoclonal antibody against the IL2 receptor. These results suggest that early impairment of T-CFC plays a predominant role in the pathogenesis of AIDS.