- Expression of Cancer-Related Genes in Epstein Barr Virus-Infected Burkitt's Lymphoma Cell Line Treated with Mitomycin C.
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Woo Bom Yeom, Seol Hee Park, Min Kyung Kim, Chul Hwan Kim, In Sun Kim, Dale Lee
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Korean J Pathol. 2001;35(4):271-277.
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 Abstract
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- BACKGROUND
Infection of Epstein Barr virus (EBV) into B cells drives the infected cells into the cell cycle and frequently results in lymphoblastoid cells. Mitomycin C inhibits DNA synthesis of epithelial cells as well as lymphoid cells by cross-linking with DNA. Many of the cancer cells have various pathways for escaping the responsiveness to the negative growth-regulatory effects of mitomycin C and gaining the immortalized property. The auther performed a cell culture of an EBV infected Jijoye lymphoma cell line, and compared the cell cycle and cancer related genes between the mitomycin treated- and non-treated group.
METHODS
DNA and RNA were extracted from the Jijoye cells; and EBV nuclear antigen (EBNA)-1, 2 and latent membrane protein (LMP) of EBV and p53 and p21 mRNA analyse was performed.
RESULTS
Mitomycin C blocked G2/M phase, however, mitomycin did not affect the expression of EBNA-1, 2 and LMP.
Mitomycin C also increased the p21 mRNA expression without p53 mRNA increase.
CONCLUSIONS
Mitomycin C induces B cell apoptosis by blocking the G2/M phase and by increasing p21 mRNA independent to p53, which reveals the presence of an alternative pathway of p21 induction by mitomycin C in EBV positive lymphoma cells
- Detection of Epstein-Barr virus in the inflammatory and neoplastic uterine cervical lesions.
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Hye Jin Jeong, Eung Seok Lee, Zhen Hua Lin, Seol Hee Park, In Sun Kim, Jae Sung Kang
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Korean J Cytopathol. 2001;12(2):73-80.
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- The prevalence of Epstein-Barr virus(EBV) in the uterine cervix was investigated to define the possible etiologic role in cervical carcinogenesis. The viral genotyping and LMP-1 30bp deletion were also studied. The materials included 169 uterine cervical swabs(152 within normal limits, 12 atypical squamous cells of uncertain significance, 3 low grade intraepithelial lesions, and 2 high grade squamous intraepithelial lesion) and 104 uterine cervical tissues obtained from hysterectomy specimens(32 carcinoma in situ, 9 microinvasive squamous cell carcinomas, 37 invasive squamous cell carcinomas, 7 adenocarcinomas, 7 adenosquamous carcinomas, and 12 cervicitis). EBV detected by PCR for EBNA-1 was positive in 52(56.5%) of 92 invasive and noninvasive cervical carcinomas, and 80(48.8%) of 164 inflammatory or normal cervices. The viruses detected in carcinomas were all type A, and LMP-1 30bp deletion form was more frequent in premalignant and malignant cervical lesions than in nonneoplastic cervices. From the above results, it may be concluded that EBV is one of common viruses detected in uterine cervix of Korean women, and type A virus and LMP-1 30bp deletion form may have a role in cervical carcinogenesis.
- Histopathologic Findings, and p53 and K-ras Mutational Analysis in Biopsy Specimens Using Fluorescence Bronchoscopy.
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Young Sik Kim, Seol Hee Park, Myung Hee Jung, Eun Chang Choi, I Yong Park, Han Kyeom Kim, Insun Kim
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Korean J Pathol. 2000;34(8):550-558.
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- A fluorescence bronchoscope system has been developed for detecting early lung cancer including dysplasia and carcinoma in situ. To determine the histologic findings and genetic alterations of the lung tissues, which were biopsied by the fluorescence bronchoscope, we analyzed 104 specimens from 62 heavy smokers for their histopathology, cell proliferation index, and genetic mutations of p53 and K-ras. We used immunohistochemistry for MIB-1 and p53, and PCR-SSCP and direct DNA sequencing for p53 and K-ras. The histology was variable from reactive conditions to invasive cancers, and consisted of basal cell hyperplasia (26.9%), dysplasia (4.8%), carcinoma in situ (1.9%), squamous cell carcinoma (7.7%), adenocarcinoma (4.8%), and small cell carcinoma (10.6%). The cellular proliferation index of the lesions increased as their aggressiveness increased. p53 and K-ras mutations were detected in 33.7% and 14.4% of all tissues, respectively. In dysplasia, p53 and K-ras mutations were observed in 3 of 5 and in 2 of 5 tissues, respectively. However, these genetic alterations were not found in carcinoma in situ. Interestingly, 28.6% of basal cell hyperplasia showed p53 mutations. In conclusion, these data suggest that the biopsy specimens using fluorescence bronchoscopy show variable histologic findings, ranging from reactive conditions to invasive cancers. In addition, some of the dysplastic lesions are related to p53 and K-ras mutations, although these genetic alterations are also seen in basal cell hyperplasia.
- Detection and Subtyping of Epstein-Barr Virus in Gastrointestinal Adenocarcinomas and Malignant Lymphomas.
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Young Sik Kim, Seol Hee Park, In sun Kim
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Korean J Pathol. 1997;31(9):847-861.
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- Epstein-Barr virus (EBV) has been linked to a spectrum of neoplastic conditions, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, lymphoepithelioma-like carcinomas and malignant lymphomas in immunocompromised state. To determine the prevalence and the subtype of EBV in gatrointestinal malignancies, fifty cases of adenocarcinomas and seventeen cases of malignant lymphomas were analyzed by EBERs in situ hybridization and polymerase chain reaction using primers for EBNA-1, EBNA-2A and EBNA-2B, on the paraffin sections. In addition, immunohistochemical stain for p53 protein was performed to investigate the potential role of EBV infection on tumor suppressor gene, p53, during tumorigenesis. EBER was detected in 6 of 26 gastric adenocarcinomas, 2 of 24 colon adenocarcinomas, and 8 of 17 malignant lymphomas. EBER was more prevalent in malignant lymphoma arising in the intestine (6/6) than in the stomach (2/11), and was detected in both B and T cell phenotypes. EBNA-1 was positive in 11 of 16 EBER positive cases and the subtyping was possible in 8; both type 1 and 2 were detected in gastric cancers, whereas only type 2 was found in intestinal neoplasms. In adenocarcinomas the high rate of p53 protein overexpression was found in both EBER positive (8/8) and negative cases (32/42), whereas the positive rate was higher in EBER positive cases (7/8) than in EBER negative cases (4/9) of malignant lymphomas. From the results, it can be concluded that EBV infection and the p53 tumor suppressor gene are independently associated in a significant portion of the gastrointestinal malignancies, but the mechanism of action remains to be elucidated.
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