Expression of Ceramide Galactosyltransferase (UGT8) in Primary and Metastatic Lung Tissues of Non-Small-Cell Lung Cancer.

Ceramide galactosyltransferase (UGT8) is an enzyme that regulates the synthesis of sphingolipids of the myelin sheath in nervous systems. The protein raises an increasing research interest as a potential marker of cancer progression in various organs. In the present study we seek to determine whether UGT8 could play a role of a therapeutic marker in non-small cell lung carcinoma (NSCLC). We addressed the issue by examining the intensity of UGT8 expression in tissue specimens of primary and corresponding metastatic lung tumors in 19 NSCLC patients undergoing surgery. The methodology was one of immunohistochemical tissue staining using light microscopy. The findings were that the majority of both lung primary and metastatic tumor tissues were positive in UGT8 signals. The cytoplasmic expression of UGT8 was found in 68.4 % of cases of primary tumors and 82.2 % of metastases, with a positive correlation between the UGT8 expression in both tumor tissues. The normal tissue adjacent to tumors showed no positive UGT8 staining. However, we failed to find any appreciable difference in UGT8 expression depending on the clinical stage of NSCLC or lymph node involvement. Nor was there any association between UGT8 expression in tumor tissues and patients' survival time. We conclude that it is unlikely that therapeutic targeting of UGT8 could inhibit cell proliferation and invasion of NSCLC. UGT8, although enhanced in NSCLC tissues, does not meet the criteria of a lung tumor marker. Thus, UGT8 cannot be considered as having diagnostic or therapeutic utility in NSCLC. The pathophysiological meaning of enhanced expression of UGT8 in lung cancer remains to be explored in further studies.

A clinically relevant, syngeneic model of spontaneous, highly metastatic B16 mouse melanoma.

We report a syngeneic model of spontaneous metastatic B16-F10 mouse melanoma in C57/BL6 mice with a very high metastatic frequency that mimics clinical metastatic melanoma. The B16 melanoma cells were injected between the skin and cartilage on the dorsal side of the ear. The model generated lymphatic and visceral metastases in all of the tested animals. In mice with large primary tumors, tumor weight correlated with the tumor growth time and also with the number of metastases in lymph nodes and organs. The dorsal ear space between the skin and cartilage enables both lymphatic and hematogenous metastatic spread. The model should be useful to study the mechanism of melanoma metastasis and to develop therapy for this currently untreatable disease.

Apoptotic markers p53, Bcl-2 and Bax in primary lung cancer.

BACKGROUND: Apoptosis is the fundamental process necessary for eliminating damaged or unwanted cells. Alterations in the apoptotic pathway appear to be key events in cancer development and progression. The aim of the study was to determine the p53, Bcl-2 and Bax expressions in lung cancer, taking into account histological heterogeneity and the adjacent bronchial resection margin. MATERIALS AND METHODS: Tissue specimens from 60 histopathologically verified lung cancer specimens and 12 bronchial stumps were evaluated. The presence of the studied markers was revealed by immunocytochemistry on paraffin-embedded tissue. RESULTS: The percentage of p53- and Bax-positive lung cancers was comparable (51.6% for both proteins), while Bcl-2 immunoreactivity was observed in fewer (31.6%) cases. There was no p53 accumulation in bronchial stumps, while Bcl-2 and Bax staining formed a repeatable specific pattern in bronchial epithelium. The differences in apoptotic marker expression between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) were revealed, especially regarding p53 and Bax expression (60% vs. 10%, p = 0.005 and 58% vs. 20%, p = 0.04, respectively). Taking into account the histological structure of NSCLC, Bax expression appeared to be more frequent in adenocarcinoma than in squamous cell lung cancers (88% vs. 42%, p = 0.004). No interrelationship between the studied proteins in lung cancer tissue was revealed. CONCLUSION: The expression of p53, Bcl-2 and Bax was altered in lung cancer tissue compared to histologically normal bronchial epithelium. The difference between apoptotic marker expression in NSCLC and SCLC could reflect the different pathogenesis of these two lung pathologies.