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Abnormal FHIT gene transcript and c-myc and c-erbB2 amplification in breast cancer.

100%

Kowara R., Gołębiowski F., Chrzan P., Skokowski J., Karmolinski A., Pawełczyk T.

2002

vol. 49

issue 2

341-350

Searching for ways to improve the characterization of breast cancer we examined the relationship between the status of the FHIT gene transcript and amplification of c-myc and the c-erbB2 oncogene. Abnormal FHIT transcript was detected in 32 of 79 cancers examined. The presence of Fhit protein estimated by Western blots was evident only in cancers exhibiting a normal-sized FHIT transcript. This indicates that abnormal FHIT transcripts observed in our study did not encode any Fhit protein or the amount of such protein was very low. There was no association between the presence of aberrant FHIT gene transcript with age, tumor size, estrogen and progesterone receptor status, local metastases and histological grading. However, the abnormalities in FHIT gene transcripts were observed with different frequency depending on the histopathological type of the tumor. The aberrant FHIT transcript was detected in 60% of lobular cancers and only in 28% of ductal cancers. Analyzing the occurrence of c-myc and c-erbB2 amplification and the presence of aberrant FHIT gene transcripts we found that the aberrant FHIT transcript more frequently occurred in tissues with c-myc amplification. There was a significant (P <0.05) correlation between the occurrence of the aberrant FHIT gene transcript with accompanying c-myc amplification and positive lymph node status. However, in order to evaluate the predictive value of these findings in breast cancer, an extended clinical follow up will be necessary.

Celecoxib - A Selective Cyclooxygenase-2 Inhibitor Exhibits Dose - Dependent Chemopreventive Activity on an Animal Model of Colorectal Cancer*

86%

Spychalski M., Dziki Ł., Buczyński J., Kulig A., Sporny S., Dziki A.

Polish Journal of Surgery

2008

vol. 80

issue 5

248-255

Colorectal cancer (CRC) is still one of the unresolved issues in medicine. Despite constant improvements in diagnosis and treatment, the prognosis for CRC is unsatisfactory. In recent years, much attention has been paid to experiments concerning chemoprevention of CRC.The aim of the study was evaluation of the effectiveness of celecoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor of chemically-induced CRC carcinogenesis in Fisher F344 rats.Material and methods. Forty-five four-week old male F344 rats were randomized into four groups. In Groups 1, 2, and 3, we induced the CRC carcinogenesis through two subcutaneous injections of Azoxymethane in doses of 20 mg/kg. Rats from groups 1 and 2 were treated with celecoxib in doses of 10 and 30 mg/kg from the start of the experiment. Group 4 was a negative control. The experiment ended in the 26th week. We assessed the following parameters: the number of Aberrant Crypt Foci (premalignant lesions in colons) and the immunoexpression indexes: COX-2, Vascular Endothelial Growth Factor (VEGF), and c-myc.Results. Celecoxib reduced the ACF number. The ACF reduction was dose-dependent. The median ACF number per field of vision was as follows for each of the groups: 1.7, 0.75, 3.2, and 0.2. Celecoxib, irrespective of the dose, reduced the VEGF immunoexpression index. We did not observe a reduction of COX-2 or c-myc immunoexpression in the celecoxib groups.Conclusions. In this experiment, we proved that celecoxib possessed chemopreventive activity. Carcinogenesis inhibition by selective COX-2 inhibitor was dose-dependent. We demonstrated that celecoxib hidners angiogenesis, expressed as VEGF immunoexpression. We indirectly confirmed the hypothesis of a celecoxib COX-2 independent pathway mechanism of action.

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1 Acta Biochimica Polonica

1 Polish Journal of Surgery

1 2008

1 2002

1 Buczyński J.

1 Chrzan P.

1 Dziki A.

1 Dziki Ł.

1 Gołębiowski F.

1 Karmolinski A.

1 Kowara R.

1 Kulig A.

1 Pawełczyk T.

1 Skokowski J.

1 Sporny S.

1 Spychalski M.

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Abnormal FHIT gene transcript and c-myc and c-erbB2 amplification in breast cancer.

Celecoxib - A Selective Cyclooxygenase-2 Inhibitor Exhibits Dose - Dependent Chemopreventive Activity on an Animal Model of Colorectal Cancer*