The site-dependent growth characteristics of a human xenotransplanted basaloid squamous cell carcinoma.

PURPOSE: To improve our understanding of the aggressive behaviour of basaloid squamous cell carcinoma (BSCC) certain biological features related to malignancy were compared in the basaloid and in the squamous cell population of this tumour. METHODS: Growth rate, cell population kinetics parameters, ploidy and collagenase activity were measured in BSCC xeno-transplanted subcutaneously or into oral submucosa. RESULTS: The basaloid component of BSCC showed a growth advantage in the subcutaneous location and formed a mainly aneuploid population (69.3%) without any sign of invasiveness. However the transplantation of this tumour into the oral submucosa resulted in the reappearance of the squamous carcinoma cell population containing diploid and aneuploid cells in equal proportion. The diploid cells in the tumour growing in the subcutis were in G1 phase, whereas 30% of the diploid and aneuploid cells growing in the oral submucosa were in the growing (S+G2) phases of the cell cycle. The mixed tumour cell population in the oral submucosa produced 92-kDa collagenase IV, indicating a potential to infiltrate surrounding tissues. CONCLUSIONS: The biological behaviour of a human oral carcinoma (BSCC) in a xenograft model depends on the site of the transplantation. The aggressive malignancy of BSCC may be associated with the capacity of the basaloid cell population to generate squamous cells that are able to produce the 92-kDa type of collagenases in an appropriate microenvironment.

The antiproliferative action of a melphalan hexapeptide with collagenase-cleavable site.

PURPOSE: The objective of the present study was to examine the relevance of collagenase in the antitumor action of a melphalan peptide (MHP) with a collagenase-cleavable sequence. The question was addressed as to whether collagenase may act as an activator or a target in the antiproliferative mechanism of MHP. METHODS: Melphalan was inserted into peptides representing the sequence Pro-Gln-Gly-Ile-Ala.Gly of the collagenase-cleavable site in collagens. Changes in growth and collagenase IV activities of HT-1080, HT-29, HT-168, and MCF-7 cell cultures were investigated. RESULTS: The present investigations provide data indicating that Pro-Gln-Gly-Ile-Mel-Gly (melphalan hexapeptide, MHP) is a substrate for both bacterial and 72-kDa type IV collagenases and that in this way it can generate Ile-Mel-Gly (melphalan tripeptide, MTP) of higher cytotoxic potency. Indeed, the formation of MTP was detected in the conditioned medium of HT-1080, a collagenase IV-producing human fibrosarcoma. In a comparison of equimolar concentrations of melphalan and its two peptide derivatives (MHP and MTP), superior antiproliferative action of MTP was seen in HT-29, HT-1080, and HT-168 tumor cell cultures. However, the relatively modest cytostatic actions of MHP were increased when bacterial collagenase was added to the cell cultures. After melphalan treatment, reduced levels of both 92 and 72-kDa type IV collagenases were seen in the HT-1080 cell cultures. However, the reduction of collagenase activity and the cell counts did not run parallel in the MTP- or MHP-treated cultures; indeed, collagenase activity related to cell numbers showed an elevated level. CONCLUSIONS: As the conversion of MHP to the more toxic MTP was detected in the presence of collagenases, it is possible that collagenase-directed activation of prodrugs may be a promising approach for the development of more selective cytostatic drugs against malignant tumors with high collagenase activities.

Establishment and characterization of a new transplantable pancreatic cancer xenograft (PZX-5) in immunosuppressed mice.

CONCLUSION: A new, stable, transplantable human pancreatic cancer xenograft (PZX-5) model has been established in CBA immunosuppressed mice. BACKGROUND: Numerous human pancreatic carcinomas have been successfully transplanted into athymic nude mice. However, artificially immunosuppressed animals have rarely been used as recipients. Because this model system proved to be reliable for hosting many human malignancies at our institute, successive xenotransplantations of a ductal adenocarcinoma have been carried out. METHOD: Immunosuppression of CBA/CA mice was achieved by thymectomy, whole-body irradiation and bone-marrow reconstruction. Tumor fragments were subcutaneously implanted from a well/moderately differentiated ductal pancreatic adenocarcinoma and serially transplanted for more than 20 mo. The xenografted tumors were characterized using morphological, immunohistochemical, biochemical, and flow cytometric methods. RESULTS: During the serial transplantations, the neoplasm maintained its original morphological-pathobiological characteristics. It produced a large amount of mucin and expressed carcinoembryonic antigen (CEA). Neither the mitotic activity nor the degree of differentiation was altered, and CEA was permanently detected. Flow cytometric DNA analysis revealed an aneuploid pattern (DNA index 1.45+/-0.03), which has remained within the same range during xenograftings. The doubling time in an in vitro system proved to be 18 h. The human character has been well preserved even 9 mo posttransplantation, as was evidenced by LDH-isoenzyme electrophoresis. The results indicate that the thymectomized--whole-body irradiated--bone-marrow reconstructed immunosuppressed mice are also appropriate hosts for pancreatic cancer xenografts.

The pathomorphology of a human xenotransplanted basaloid squamous cell carcinoma.

To elucidate some factors related to the malignant phenotype of an oral tumor with mixed cell population the question has been raised whether the biological behavior of the basaloid or the squamous cells show any difference in an immunosuppressed host organism. Basaloid squamous cell carcinoma (BSCC) surgically removed from sublingual location was xenotransplanted either subcutaneously or in the oral submucosa and the histology, ultrastructures, LDH isoenzyme pattern were investigated. The epithelial origin of the established tumor line (HTB-1) could be recognized according to the characteristic epithelial ultrastructures, while the type of the LDH isoenzymes proved its human origin. The squamous cell population dominating the parent surgical specimen of BSCC regressed during xenotransplantation in the subcutan location, on the contrary the basaloid cells grew and maintained the tumor. Interestingly the basaloid cells transplanted from the subcutis to the oral submucosa generated a squamous cell population with an infiltrative growth pattern. The xenografted BSCC offer a promising model to investigate the contribution of each cell populations in the malignant phenotype. The presented data indicate that the basaloid cells are responsible for maintaining the tumor cell population, but certain malignant features (i.e. infiltrative growth) is associated to the squamous cells which are generated from the basaloid cells only under specific circumstances. Thus this particular model system showed that different malignant features could be associated to the basaloid and to the squamous cell component.

[Additional roentgen-anatomical examination of OP (orthopantomography) pictures]. / OP-felvételek kiegészítö röntgenanatómiai vizsgálata.

The authors examined various anatomical details which appeared in the OP pictures with varying frequency and in various recognisable forms. They sought to help to a more perfect implementation and evaluation of techniques which are considered to be relatively new in our country.