Different expression of MAGE-A-antigens in foetal and adult keratinocyte cell lines.

MAGE-A-antigens are an immunologic marker for many cancers. The goal of this study was to compare the expression profiles of MAGE-A2, -A3, -A4, -A6 and -A10 in foetal and adult keratinocytes with an oral squamous cell carcinoma (OSCC) cell line. Expression of MAGE-A2, -A3, -A4, -A6 and -A10-antigens were detected with PCR in foetal and adult keratinocyte cell lines and in an OSCC cell line (pT4N1M0). Quantitative expression of the single MAGE-A-antigens was measured with rtq-PCR. The results were compared to the reference value of the adult keratinocyte cell line. MAGE-A-antigens were detected in all cell lines. Expression profiles of adult and foetal keratinocyte cell lines differed significantly. Expression profiles of foetal and carcinoma cell lines differed significantly also. MAGE-A-antigens were detected in foetal keratinocyte cell line and oral squamous cell carcinoma cell line but differ in their expression profiles. Up to now MAGE-A-antigens were not detected in foetal keratinocytes. Their role is still unknown.

A critical role for I kappaB kinase alpha in the development of human and mouse squamous cell carcinomas.

IKK (I kappaB kinase) alpha is essential for embryonic skin development in mice. Mice deficient in IKKalpha display markedly hyperplasic epidermis that lacks terminal differentiation, and they die because of this severely impaired skin. However, the function of IKKalpha in human skin diseases remains largely unknown. To shed light on the role of IKKalpha in human skin diseases, we examined IKKalpha expression and Ikkalpha mutations in human squamous cell carcinomas (SCCs). We found a marked reduction in IKKalpha expression in poorly differentiated human SCCs and identified Ikkalpha mutations in exon 15 of Ikkalpha in eight of nine human SCCs, implying that IKKalpha is involved in development of this human skin cancer. Furthermore, in a chemical carcinogen-induced skin carcinogenesis setting, mice overexpressing human IKKalpha in the epidermis under the control of a truncated loricrin promoter developed significantly fewer SCCs and metastases than did wild-type mice. The IKKalpha transgene altered the skin microenvironment conditions, leading to elevated terminal differentiation in the epidermis, reduced mitogenic activity in the epidermis, and decreased angiogenic activity in the skin stroma. Thus, overexpression of IKKalpha in the epidermis antagonized chemical carcinogen-induced mitogenic and angiogenic activities, repressing tumor progression and metastases.

[Tumoral degeneration occurring over a non-healing meningocele. Report of two cases]. / Degeneración tumoral en meningocele no intervenido. Descripción de dos casos.

A giant meningocelic sac has not been usually described in adult patients, due to the fact that it shows a low incidence and few newborn have survived to date though the malformation is benign. We report two cases of patients born with the described malformation and who were not operated at that time, so they reached adulthood with bigger sacs. They needed surgery to remove the sacs, for a different reason. The older one had a fistulous abcess but the LCR did not come out, and it did not improved by the application of topic and antibiotic treatment. The other patient showed a progressive growth of the malformation during the last year, skin hardening and pain. The histological study of the dried sacs proved the existence of a carcinomatous degeneration. In the patients we have treated, it seems that a chronic irritation of the LCR and the appearance of multipotent cells in the meningocele may favour the malignancy of the tissues surrounding the sac. This possible malignancy, already described in the bibliography, suggests a prompt elective surgical treatment of the patients with these congenital lesions as soon as possible.

Tyrosine-nitration of caspase 3 and cytochrome c does not suppress apoptosis induction in squamous cell carcinoma cells.

The influence of tyrosine nitration of cytochrome c and caspase 3 on apoptosis induction was investigated in an established squamous carcinoma cell line, OSC-4. The intracellular NO and O2(-) levels were increased up to about 110-120% and 140-180% of the control levels, respectively, after the treatment of OSC-4 cells with 5-FU (100 microg/ml), PLM (10 microg/ml), CDDP (10 microg/ml), or gamma-rays (20 Gy). The treatment of OSC-4 cells with ONOO(-) (1 mM) and the above anticancer agents induced tyrosine nitration of 14, 32 kDa protein among others and nitration of tyrosine residues of cytochrome c and caspase 3 was identified by the Western blotting of immunoprecipitates obtained by antibodies to these proapoptotic proteins. When cytochrome c and procaspase 3 were treated with ONOO(-), tyrosine nitration was increased in a ONOO(-)-dose dependent manner. Tyrosine nitration of cleaved (17 kDa) caspase 3, however, was not induced by ONOO(-). Procaspase 3 in the cytosol of HeLa cells was activated by the addition of ONOO(-)-treated as well as ONOO(-)-untreated cytochrome c. In addition, cleavage of ICAD and PARP were not suppressed in OSC-4 cells by pretreatment with ONOO(-). Activity of cleaved caspase 3 was not suppressed at low concentrations or by treatment with ONOO(-) or NO donors, SIN-1 and SNP. Furthermore, apoptosis of OSC-4 cells by the anticancer agents was not suppressed by ONOO(-). In conclusion, these results suggest that nitration of tyrosine residues of cytochrome c and procaspase 3 is induced by chemoradiotherapy but their nitration does not suppress cancer cell apoptosis.

Squamous cell carcinoma-like and pox lesions occurring simultaneously in chorioallantoic membranes of chicken embryos inoculated with materials from squamous cell carcinoma and pox lesions in broiler chickens.

The finding of closely associated squamous cell carcinoma (SCC)-like lesions and pox lesions in chorioallantoic membranes (CAMs) inoculated with skin and palate samples taken from broilers is described. The samples were obtained from two broilers coming from different flocks that were not vaccinated against fowl pox. Both birds presented skin lesions, which were diagnosed in one bird as fowl pox, and in the other as SCC. After inoculation of CAMs with fresh tissues from both birds, histologic examination revealed, in all CAMs, lesions that were characteristic of fowl pox together with lesions consistent with those seen in the skin of broilers affected with SCC. This finding was unexpected and may shed some light on the etiology of SCC.

Comparison of cancer cell surfaces of the lower reproductive tract by scanning electron microscopy.

The squamous cells of the cervix simulate those of the vagina and vulva both histologically and by scanning electron microscopy. However, in areas of the cervix undergoing active metaplasia, there are cells which share some of the characteristics demonstrated by scanning electron microscopy of both squamous and columnar epithelium. In these cells there is a wide range of characteristics of each cell type, suggesting a possible gradual transition from columnar to squamous epithelium. Furthermore, the cells of severe dysplasia and of intraepithelial and invasive squamous cancers of the cervix, though histologically similar to those of vaginal and vulvar cancers, are distinctly different when examined by scanning electron microscopy. These findings suggest that both metaplastic and neoplastic squamous cells are derived from the same progenitor columnar cells of the cervix, by orderly transition in the former and by atypical transformation in the latter. Second, the distinctiveness from the vaginal and vulvar cells indicates different embryonic stem cell lines.