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

We investigated whether epigenetic rather than mutational events might be involved in the induction of immunogenicity by the triazene derivative 1-(p-chlorophenyl)-3,3-dimethyltriazene (DM-Cl). To this purpose, we assessed the DNA methylation pattern of murine lymphoma cells xenogenized by DM-Cl and compared it with the changes induced by the DNA hypomethylating agent 5-azacytidine (5-Aza), which is also capable of affecting tumor cell immunogenicity. Both agents were found to increase the immunogenic potential of the treated tumor but according to different modalities. In particular, the novel immunogenicity conferred by 5-Aza treatment correlated well with the extent of hypomethylation induced, as opposed to what was observed for tumor xenogenization by DM-Cl.

Modulation of H-2Kb antigens on cells of a subline of the murine Lewis lung carcinoma was induced in vitro by a monoclonal antibody with specificity for H-2Kb antigens. High antibody concentrations resulted in a more spherical morphology of the cells, in a discrete loss of all antibody-antigen complexes within 4-6 hr, and in a corresponding maximal decrease in the total cellular antigen content 6-8 hr after antibody exposure. Restoration was complete within 2 hr after removal of the complexed antigen and occurred without any visible cap formation.

A highly metastatic murine tumor line (ESb) and a plastic-adherent variant derived from it (ESb-M) were compared for expression of cell surface glycoproteins. Previous studies had shown that ESb-M cells were very similar to ESb cells in terms of cell surface marker expression and invasive capacity in vitro, but studies in vivo revealed that they exerted a decreased metastatic capacity. Syngeneic animals inoculated SC with ESb-M cells developed larger primary tumors and survived much longer than animals inoculated similarly with ESb cells. When using the lectin soybean agglutinin (SBA), distinct differences were observed in the glycosylation of a 220 kDa and a 80 kDa cell surface glycoprotein. Further differences in expression of cell membrane proteins were detected by means of variant-specific monoclonal antibodies. These specific ligands reacted with 65-75 kDa membrane glycoproteins, which were more prominent in ESb-M cells than in ESb cells. Apart from these differences, the two cell lines showed very similar profiles of membrane glycoproteins and lectin staining. Whether the structural differences seen in cell surface proteins can explain the changes in functional behavior (metastatic behavior and plastic-adhesive properties) of the cells remains to be investigated.

Cultures of rat palatal epithelium grown on collagen rafts were treated with different doses of the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Sections from biopsies taken 1, 6, 24, and 48 hr after the addition of TPA were examined for the localization of staining by blood group antigen H antibody and antikeratin antibody AE1. In contrast to control cultures, where antigen H was seen exclusively at the cell membranes of the second and third cell layer, several antigen H-positive cells, some appearing in groups, were found in the basal cell layer of TPA-treated specimens. Staining for keratins with the AE1 antikeratin antibody showed no staining of basal cells but only suprabasal cells in controls, whereas several cells of the basal cell layer of TPA-treated cultures stained positively with this antibody. The results support the theory that TPA, by forcing a part of the basal cell population to terminal differentiation, strongly affects the composition of the basal cell population.

There are a number of strategies that have been used for the development of monoclonal antibodies which recognise tumour associated antigens. These include the use of whole tumour cells or membrane components as the immunogen, and the use of differentiation antigens, for example the human milk fat globule. The monoclonal antibody HMFG-2 was developed using the latter strategy and has been shown to react with a large molecular weight mucin-like molecule which appears to be highly immunogenic in the mouse. The HMFG-2 antibody is proving to be extremely useful in the localisation of ovarian tumours and is being used in a number of clinics. This antibody and its antigen have a number of characteristics which have contributed to its success in imaging ovarian carcinomas, including the repetitive nature of the antigenic epitope and the antibody's affinity.

This study followed 184 drug abusers. Examined in all of them were urinary neopterin levels, HBV, SGOT, and Luestest. Seventy-three percent of IV drug addicts showed elevated neopterin levels reflecting activated cellular immunity. Statistically, no correlation of neopterin levels with, eg, excessive alcohol consumption, duration of drug abuse, or studied laboratory parameters was found. Individuals using cocaine revealed higher neopterin levels than those not doing so. Twenty-one of twenty-two patients with no parenteral drug use had normal neopterin excretion. In 34 drug detoxification patients, we examined in addition: T-lymphocyte subsets (T4/T8 ratio) and serum neopterin levels. Thirty-eight of ninety-four parenteral drug addicts presented with anti-LAV/HTLV-III antibodies (ELISA + Western blot + IFT). Our data demonstrate an activated cellular immune status in parenteral drug addicts that cannot be attributed to LAV/HTLV-III infection in all cases. The development of AIDS seems to depend not only on the exposure to LAV/HTLV-III but also on activated cellular immunity, which is easily assessed by neopterin measurement.

Urinary neopterin levels are raised with a high incidence in all risk groups for AIDS. Neopterin elevations reflect activated cellular immunity in risk group members, in some cases independently of LAV/HTLV-III infection. Moreover, we are able to show that in patients receiving multiple blood transfusions at least a transient challenge of cell-mediated immunity occurs, which is indicated in part by increasing neopterin levels. We conclude that neopterin levels are a reliable index for assessment of susceptibility for AIDS when infection with LAV/HTLV-III occurs. Activated status of cell-mediated immunity might predispose infected persons to an overwhelming infection and secondary spreading of LAV/HTLV-III, thus leading to the development of full-blown AIDS or ARC. As a consequence of these observations, T-cell-stimulatory actions and agents should intentionally be avoided. Treatment of AIDS patients with immunosuppressants should be examined. The success of therapeutic regimens should be monitored by measurement of neopterin levels.

The monoclonal islet cell antibody HISL-19 generated after immunization of BALB/c mice with human pancreatic islet cell preparations, demonstrated specific immunoreactivity for neuroendocrine (Merkel) cells of the skin as shown by successive and simultaneous localization of neuron-specific enolase and the antigen detected by mab HISL-19 in the same cells of the bovine epidermis. Following these observations, we tested nine neuroendocrine carcinomas of the skin that were believed to be of Merkel cell origin for their immunoreactivity with mab HISL-19 using an indirect immunoperoxidase technique on formalin-fixed and paraplast-embedded tissues. In contrast to malignant lymphomas, poorly differentiated squamous cell carcinomas, and malignant melanomas, all nine neuroendocrine carcinomas reacted strongly with mab HISL-19, indicating its potential as a useful immunohistochemical probe for the distinction of neuroendocrine carcinomas of the skin from other cutaneous neoplasms with similar histological appearance.

Although no case of lymphoproliferative syndrome occurred among our first 680 transplant patients, 13 cases developed in a subsequent series of 170 patients. This severe condition involved a proliferation of B cells and/or plasma cells that invaded a number of organs, resulting in the deaths of eight patients. Early tapering off of immunosuppressive therapy enabled five patients to recover without loss of the transplant. The factors likely to be involved in the occurrence of malignant lymphoproliferation are immunosuppressive drugs, and introduction of allogeneic EBV-infected cells or reactivation of EBV.