Altered excretion of modified nucleosides and beta-aminoisobutyric acid in subjects with acquired immunodeficiency syndrome or at risk for acquired immunodeficiency syndrome.

Urinary excretion of modified nucleosides and beta-aminoisobutyric acid, subsequently referred to as markers, was determined in populations of patients with acquired immunodeficiency syndrome (AIDS) or at risk for development of AIDS. Our results show that asymptomatic adult male homosexuals excreted elevated amounts of markers as compared to male heterosexuals. This aberrant excretion was more pronounced in asymptomatic adult male homosexuals with antibodies to HTLV-III. Significantly greater excretion of 1-methylinosine, N4-acetylcytidine, and N2-methylguanosine was observed in asymptomatic adult male homosexuals with antibodies to HTLV-III than in asymptomatic male homosexuals without antibodies to HTLV-III. Increased amounts of markers were also excreted by subjects with the generalized or chronic lymphadenopathy syndrome, AIDS related complex (ARC), or AIDS. In these subjects, the most pronounced differences between groups were between subjects with chronic lymphadenopathy syndrome and those with ARC; subjects with ARC excreted greater amounts of seven of the ten urinary markers. There were few differences between subjects with ARC and those with AIDS, Kaposi's sarcoma, or AIDS with opportunistic infections. This observation may be useful for identifying subjects who are at risk of developing AIDS. A prospective study to test this hypothesis is under way.

Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin.

OBJECTIVES: Elucidation of the mechanisms of the previously shown growth-inhibitory action of human chorionic gonadotropin (hCG) on Kaposi's sarcoma (KS) cells and the role of the luteinizing hormone/hCG receptor (hCGR). DESIGN AND METHODS: Analysis of KS tissues and cultured spindle-type KS cells for the presence of the hCGR using 125I-hCG binding and reverse transcriptase-polymerase chain reaction; analysis of several hCG preparations (urinary, recombinant, isolated alpha and beta subunits); analysis of apoptosis mechanisms by several assays including using z-Val-Ala-Asp-fluoromethylketone (zVAD-FMK), a known apoptosis-inhibitory drug. RESULTS: First, we found that some urinary preparations of hCG (e.g., CG-10, Steris Profasi) were indeed KS-killing but others (such as Pregnyl, Choragon, Serono Profasi) were not. Secondly, recombinant subunits (alpha as well as beta) of hCG were KS cell-killing but recombinant intact hCG was not. Thirdly, the hCGR message and protein were undetectable in KS. Fourthly, CG10-induced cell death occurred by apoptosis and KS cells could be rescued by preincubation with zVAD-FMK. Finally, we also found that normal peripheral blood lymphocytes (PBL) were killed by CG-10. CONCLUSION: It is proposed that the action of subunits or subunit fragments of hCG, mediated by a putative orphan receptor (as opposed to the hCGR) and executed by interleukin-1-converting enzyme (ICE)-like protease(s), constitutes a novel apoptosis mechanism effective towards KS cells, but PBLs and possibly other cells as well. These results provide a basis for testing in vitro the therapeutic efficacy of hCG preparations which, in turn, should improve current clinical trials with 'hCG' in patients who have KS.

New information gathering study for KS.

AIDS: New studies are being launched to learn more about Kaposi's sarcoma (KS), a skin cancer common in AIDS patients that may be caused by a sexually-transmitted virus. A New York study is currently comparing skin biopsies from KS lesions, both from AIDS patients and those not infected with HIV, and is evaluating urine samples, to determine whether angiogenesis causes lesions to grow. Biopsies are being taken only from lesions not treated by anticancer therapy. HIV negative men with healthy skin are serving as controls.^ieng

Urinary proteins with pro-apoptotic and antitumor activity.

Analysis of the protein composition of urine has been the subject of much research that has captured the interest of scientific groups over the years. A number of factors have been isolated from urine that possess anti-neoplastic activities as seen both in vitro and in vivo studies. The urine from pregnant women and commercial preparations of crude clinical grade human chorionic gonadotropin contain factors (HAF for hCG associated factor) with anti-Kaposi's sarcoma activity. Also found in urine with activity are eosinophil-derived neurotoxin (EDN), anti-neoplastic urinary protein (ANUP), inhibin, activin A, and angiostatin. The anti-cancer activity of urinary proteins is associated with apoptosis of endothelial cells and of tumor-associated endothelial cells. A better understanding of the biological functions of these various urinary proteins, and of others that remain to be discovered, should provide insights into novel cell regulatory systems operating during pregnancy.

[Polyamines in malignant lymphoma of the skin and in Kaposi's sarcoma]. / Poliaminy pri zlokachestvennykh limfomakh kozhi i sarkome Kaposhi.

High-pressure liquid chromatography was used to detect polyamines, the markers of lymphoproliferative diseases of the skin and of Kaposi's sarcoma. The urine polyamine detection may become one of the diagnostic tests in these conditions, but its findings should be confirmed by clinical and histologic data. Measurements of the urine polyamines may be helpful in assessment of the treatment efficacy.

Urinary neopterin and immunological features in patients with Kaposi's sarcoma.

We studied neopterin excretion levels and immunological features of 20 patients affected by Kaposi's sarcoma (KS), compared to 30 normal controls. Eighteen patients had the classic form of Kaposi's sarcoma (CKS), while two patients were anti-human immunodeficiency virus (HIV) seropositive and affected by the epidemic form associated with the acquired immunodeficiency syndrome (AIDS). In CKS patients, a trend of an increase of neopterin levels with more advanced stages appeared from our data whereas a significant reduction in CD3+ and CD4+ lymphocytes subsets was observed already at early stages (P less than 0.01). CD8+ cells did not show significant variations. A significant increase in serum IgA immunoglobulins (P less than 0.05) was also observed. Comparative analysis of the two patients affected by AIDS/KS showed the profound deficit in T-cell immunity but also the prognostic value of neopterin monitoring. Furthermore these findings seem to confirm Kaposi's sarcoma as an 'opportunistic neoplasia' and indicate neopterin as a useful prognostic marker.

[The effectiveness of treating patients with malignant skin lymphoma and Kaposi's sarcoma studied via polyamines]. / Izuchenie éffektivnosti lecheniia bol'nykh zlokachestvennymi limfomami kozhi i sarkomoi Kaposhi s pomoshch'iu poliaminov.

Lymphoproliferative diseases of the skin and Kaposi's sarcoma were found to involve high excretion of polyamines. Therapy with reaferon combined with prospidine and indomethacin improved the clinical course of the process and was associated with a decrease of polyamine excretion. Measurement of the urine polyamines may be used for the assessment of the treatment efficacy in malignant lymphomas of the skin and in Kaposi's sarcoma.