Cancer Research and Treatment

Original Articles

Cell-Specific Growth Inhibition of Human Cervical Cancer Cell by Recombinant Adenovirus p53 in vitro and in vivo: Su Mi Bae, Yong Wook Kim, Joo Hee Yoon, Jin Young Yoo, Young Seok Seo, Sang Lyun Nam, Joon Mo Lee, Sung Eun Namkoong, Chong Kook Kim, Yong Wan Kim, Woong Shick Ahn; Cancer Res Treat. 2003;35(3):181-190. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.181

PURPOSE
Despite the significance of the p53 adenoviral vector in cancer gene therapy, an advanced strategy for the development of preferential tumor cell-specific delivery and the long-term persistent gene expression control of p53 are required. In this study, the time-course expression patterns of p53 and E6, on cervical cancer cells, were investigated to obtain a molecular level understanding of the cell-dependent tumor growth suppression effects of a recombinant adenovirus expressing p53, both in vitro and in vivo. MATERIALS AND METHODS: The expressions of p53 and E6 in CaSki, SiHa, HeLa, HeLaS3, C33A and HT3 cervical cancer cell lines were examined. After infection with AdCMVp53, the cell growth inhibition was studied via cell count, MTT and Neutral red assays. After transfecting the AdCMVp53 and AdCMVLacZ into the cancer cells-xenografted nude mice, the anti-tumor effects were investigated for one month. RESULTS: The p53 protein levels were more notably expressed in the CaSki and HeLa than in the SiHa and HeLaS3 On day 6, the p53 was only detected in the HeLaS3. In contrast, the p53 expression was highly maintained in the C33A and HT3. The E6 mRNA levels gradually decreased in only the CaSki and HeLa. The growth suppression effects also showed cell-dependent patterns, which were consistent with the reciprocal expression patterns of p53 and E6. After transfection of the AdCMVp53, into the CaSki- and SiHa-xenografted nude mice, the tumor size was remarkably decreased in the SiHa cells as compared to that in the AdCMVLacZ transfected mice, indicating cell-specific growth inhibition patterns.
CONCLUSION
The adenovirus-mediated p53 gene transfection was very effective both in vitro and in vivo. Also, the anti-tumor effects were accomplished via the differential role of p53-specific apoptotic cell death, which was dependent on the cervical cancer cell line.

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Immunization with Adenoviral Vectors Carrying Recombinant IL-12 and E7 Enhanced the Antitumor Immunity against Human Papillomavirus 16-associated Tumor
Eun-Kyung Park, Young-Wook Kim, Joon-Mo Lee, Sung-Eun NamKoong, Do-Gang Kim, Heung-Jae Chun, Byoung-Don Han, Su-Mi Bae, Hyun-Sun Jin, Jeong-Im Sin, Woong-Shick Ahn
Cancer Research and Treatment.2005; 37(1): 63. CrossRef

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Polymorphisms of p53, p21 and IRF-1 and Cervical Cancer Susceptibility in Korean Women: Sung Jong Lee, Sung Eun Namkoong, Won Chul Lee, Jae Woong Sul, Sun Ha Jee, Youn Kyoung You, Jong Eun Lee, Jong Sup Park; Cancer Res Treat. 2002;34(5):357-364. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.357

Abstract PDF

PURPOSE
The aim of this study was to identify gene- gene and gene-environmental factor on cervical carcinogenesis in Korean women.
MATERIALS AND METHODS
We evaluated 185 women patients who had cervical cancer with 345 normal control healthy women. The single nucleotide polymorphisms (SNPs) of the p53 codon 72, the p21 codon 31 and the IRF-1 intron 6 were evaluated from extracted DNA of peripheral blood with an automatic DNA sequencer. The difference of each SNP, gene-gene and gene-environmental interaction between normal controls and patients, were evaluated in an adjusted environmental background.
RESULTS
With regard to environmental factors, the cervical cancer increased in the women with a lower level of education, a younger age at first sexual intercourse and with the increased number of children borne. The women who had p53 (Arg/Arg), IRF-1 (T/T) and an education of less than 6 years showed a 14.7 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and an education of more than 15 years. The women who had p53 (Arg/Arg), p21 (Ser/Ser) and more than 3 children showed a 6.4 fold increased risk of cervical cancer than those women who had p53 (~Pro), p21 (~Arg) and had borne no child. The women who had p53 (Arg/Arg), IRF-1 (T/T) and had experience of first sexual intercourse before the age of 22-years showed a 5.5 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and had experience of first sexual intercourse after the age of 26-years.
CONCLUSION
We found that the level of education, the age at first intercourse, and the number of children borne, were independent risk factors in cervical carcinogenesis. The specific combination of p53, p21 and IRF-1 gene-gene and gene-environmental interactions were significantly noted in the cervical carcinogenesis of Korean women.

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Distinctive cell cycle regulatory protein profiles by adenovirus delivery of p53 in human papillomavirus-associated cancer cells
H.-S. JIN, S.-M. BAE, Y.-W. KIM, J.-M. LEE, S.-E. NAMKOONG, B.-D. HAN, Y.-J. LEE, C.-K. KIM, H.-J. CHUN, W.-S. AHN
International Journal of Gynecological Cancer.2006; 16(2): 698. CrossRef
Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells
Yong-Seok Lee, Su-Mi Bae, Sun-Young Kwak, Dong-Chun Park, Yong-Wook Kim, Soo-Young Hur, Eun-Kyung Park, Byoung-Don Han, Young-Joo Lee, Chong-Kook Kim, Do Kang Kim, Woong-Shick Ahn
Cancer Research and Treatment.2006; 38(3): 168. CrossRef
Cellular process classification of human papillomavirus-16-positive SiHa cervical carcinoma cell using Gene Ontology
W. S. Ahn, M.-J. Seo, S. M. Bae, J. M. Lee, S. E. Namkoong, C. K. Kim, Y.-W. Kim
International Journal of Gynecological Cancer.2005; 15(1): 94. CrossRef

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Clinical Analysis of PTEN, p53 and Her-2/neu Expressions in Thyroid Cancers: Jeong Soo Kim, Ja Seong Bae, Kee Hwan Kim, Chang Hyeok Ahn, Se Jeong Oh, Hae Myung Jeon, Keun Woo Lim, Chung Soo Chun; Cancer Res Treat. 2001;33(5):433-437. Published online October 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.5.433

Abstract PDF

PURPOSE
The dual-specificity phosphatase PTEN/ MMAC1/TEP1 has recently been identified as the tumor suppressor gene most frequently mutated and/or deleted in human tumors. However, PTEN mutations have rarely been detected in sporadic thyroid cancers. Therefore, this study investigated the PTEN expression of thyroid cancer and the relationship between PTEN, clinical status and other biologic factors such as HER-2/neu and p53.
MATERIALS AND METHODS
The study samples consisted of 62 thyroid cancer specimens and 24 benign thyroid tumor specimens from patients who were operated on the Department of Surgery, Uijongbu St. Mary's hospital during the 5 years from January 1995 until January 2000. All tumors were studied by immunohistochemical staining using monoclonal antibodies against PTEN, HER-2/neu and p53. The results were analyzed statistically.
RESULTS
PTEN protein was found to be under-expressed more frequently in thyroid cancers (29%) than in benign thyroid tumors (4.2%). The reduction in PTEN expression in thyroid cancers was not significantly related with the recorded clinical factors such as size, age, lymph node metastasis and p53, except for HER-2 which was found to be significantly related (p=0.001). HER-2 over- expression was noted in thyroid cancer (83.8%) more frequently than in benign tumors (16.7%).
CONCLUSION
This study has demonstrated that the under-expression of PTEN protein and the over-expression of HER-2 protein may play a role in the carcinogenesis and development of thyroid cancer.

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Links between Breast and Thyroid Cancer: Hormones, Genetic Susceptibility and Medical Interventions
Man Lu, Hanqing Liu, Bilian Zheng, Shengrong Sun, Chuang Chen
Cancers.2022; 14(20): 5117. CrossRef
Recommendations on Surveillance for Differentiated Thyroid Carcinoma in Children with PTEN Hamartoma Tumor Syndrome
L.A. Jonker, C.A. Lebbink, M.C.J. Jongmans, R.A.J. Nievelstein, J.H.M. Merks, E.J.M. Nieveen van Dijkum, T.P. Links, N. Hoogerbrugge, A.S.P. van Trotsenburg, H.M. van Santen
European Thyroid Journal.2020; 9(5): 234. CrossRef
Activity of Green Tea Polyphenol Epigallocatechin-3-gallate Against Ovarian Carcinoma Cell Lines
Yong Wook Kim, Su Mi Bae, Joon Mo Lee, Sung Eun Namkoong, Sei Jun Han, Byoung Rai Lee, Insu P. Lee, Sang Hee Kim, Young Joo Lee, Chong Kook Kim, Yong-Wan Kim, Woong Shick Ahn
Cancer Research and Treatment.2004; 36(5): 315. CrossRef

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E-Cadherin Expression and p53 Alterations in Soft Tissue Sarcomas: A Possible Role in Epithelial Differentiation: Jin Young Yoo, Seok Jin Kang, Woong Shick Ahn, Byung Kee Kim; Cancer Res Treat. 2001;33(4):343-349. Published online August 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.4.343

Abstract PDF

PURPOSE
We investigated the expressions of E- Cadherin and p53 in soft tissue tumors to determine their significance in sarcoma development and/or progression and to assess their potential correlation with epithelial features.
MATERIALS AND METHODS
A total of 79 soft tissue sarcomas, including 10 tumors comprising epithelial components, were studied immunohistochemically in paraffin-embedded tissue sections. Further analysis was performed on 61 tumors by the application of a polymerase chain reaction technique and a direct sequence analysis procedure applied to exons 5 through 8 in the p53 gene.
RESULTS
E-Cadherin was expressed at the cell-cell boundaries in 8 (10%) tumors: 5 of grade 2 and 3 of grade 3. Of these, six (being 60% of the total of 10 tumors containing epithelial elements) contained and two did not contain histologic evidence of epithelial differentiation. Overexpression of p53 was detected in 26 (33%) samples, 7 of which demonstrated mutations in the p53 gene. No association was established between E-Cadherin immunoreactivities and p53 abnormalities. Tumor grade was found to be strongly correlated with p53 alterations (p=0.01) but not with E-Cadherin expression (p=0.09).
CONCLUSION
These data confirm a role for altered p53 in the pathogenesis of soft tissue sarcomas and suggest a possible role for E-Cadherin in the maintenance of epithelial architecture in these tumors regardless of p53 status.

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Meloxicam Modulates Oxidative Stress Status, Inhibits Prostaglandin E2, and Abrogates Apoptosis in Carbon Tetrachloride–Induced Rat Hepatic Injury
Mohamed Edfawy, Memy H. Hassan, Ahmed Mansour, Abdel-Aziz Hamed, Hebat Allah A. Amin
International Journal of Toxicology.2012; 31(3): 276. CrossRef
Antioxidant and antiapoptotic effects of capsaicin against carbon tetrachloride-induced hepatotoxicity in rats
Memy H Hassan, Mohamed Edfawy, Ahmed Mansour, Abdel-Aziz Hamed
Toxicology and Industrial Health.2012; 28(5): 428. CrossRef
Expression of c-kit and p53 in Non-small Cell Lung Cancers
Jinyoung Yoo, Chi Hong Kim, So Hyang Song, Byoung Yong Shim, Youn Ju Jeong, Meyung Im Ahn, Sung Whan Kim, Deog Gon Cho, Min Seop Jo, Kyu Do Cho, Hong Joo Cho, Hoon-Kyo Kim
Cancer Research and Treatment.2004; 36(3): 167. CrossRef
Expression of Caspase-3 and c-myc in Non-Small Cell Lung Cancer
Jin young Yoo, Chi Hong Kim, So Hyang Song, Byoung Yong Shim, Youn Ju Jeong, Meyung Im Ahn, Suji Kim, Deog Gon Cho, Min Seop Jo, Kyu Do Cho, Hong Joo Cho, Seok Jin Kang, Hoon Kyo Kim
Cancer Research and Treatment.2004; 36(5): 303. CrossRef
The Expression of c-myc, bcl-2 and p53 Proteins in Adenocarcinomas of Lung
Jinyoung Yoo, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Chang Suk Kang
Cancer Research and Treatment.2004; 36(2): 146. CrossRef

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Expression of Cell Cycle Regulatory and Apoptosis-related Proteins in Etoposide-treated Human Skin Fibroblast: Jae We Cho, Min Ho Suh; J Korean Cancer Assoc. 2001;33(1):77-83.

Abstract PDF: PURPOSE
This study was designed to investigate effect of the etoposide on expression of cell cycle regulatory proteins and apoptosis-related proteins in human skin fibroblast (HSF).
MATERIALS AND METHODS
HSF cells were treated with etoposide. After treatment, expression patterns of cell cycle regulatory proteins and apoptosis-related proteins were analyzed by using Immunoprecipitation-Western blot method and RT-PCR.
RESULTS
Immediately after etoposide treatment, E2F-1 was up- regulated following MDM2 down-regulation. After E2F-1 up-regulation, p53 and p21WAF1 level was markedly increased without or with mRNA up-regulation, respectively. Consistent with these results, cell cycles arrested in mainly G1 phase 24 hr after etoposide treatment. However, HSF cells progressed into apoptosis 72 hr after etoposide treatment. In this process, caspase-3 activation and Bax up-regulation were observed.
CONCLUSION
In early response of etoposide treatment, E2F-1 plays an important role in p53 accumulation through MDM2 down- regulation. The increased p53 induce an increase of p21WAF1 level through p21WAF1 mRNA up-regulation. However, after long term treatment of etoposide, HSF cells resulted in apoptotic cell death through caspase-3 activation and Bax up-regulation.

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p53 Gene Mutation by Direct DNA Sequencing Predicts Poor Survival in Patients with Stomach Cancer: Tae Won Kim, Kyoo Hyung Lee, Je Hwan Lee, Yoon Koo Kang, Jung Shin Lee, Sang Hee Kim, Sang Won Im, Ji Sun Kim, Joon Kim, Woo Kun Kim; J Korean Cancer Assoc. 2000;32(5):835-843.

Abstract PDF: No abstract available.

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Relationship of HPV Detection and p53 Expression in Urinary Bladder Cancer: Keun Hong Kee, Hyang Mee Shin, Young Chul Kim; J Korean Cancer Assoc. 2000;32(1):129-135.

Abstract PDF: PURPOSE
The purpose of this study was to investigate the relationship between aberrant p53 expression and the presence of human papillomavirus DNA in transitional cell carcinomas of the urinary bladder.
MATERIALS AND METHODS
This study analyzed 30 paraffin-embedded transitional cell carcinoma of the urinary bladder, including 10 cases of grade I, 10 cases of grade II, and 10 cases of grade III, for the presence of DNA-HPV and abnormal accumulation of p53. We used immunohistochemical staining for p53 protein and in situ hybridization for HPV DNA, respectively.
RESULTS
Overall positive rate of HPV DNA type 16 and type 18 was 60.0% and 53.3%, respectively. Nuclear accumulation of p53 was found in 13 cases (43.3%) of all transitional cell carcinomas. In HPV DNA type 16 positive cases, the p53 was positive in 8 cases and negative in 10 cases. In HPV DNA type 16 negative cases, the p53 was positive in 5 cases and negative in 7 cases. In HPV DNA type 18 positive cases, the p53 was positive in 7 cases and negative in 9 cases. In HPV DNA type 16 negative cases, the p53 was positive in 6 cases and negative in 8 cases.
CONCLUSION
This results suggest that HPV infection and p53 gene accumulation may contribute to the significant role in the carcinogenesis of the utinary bladder. In additon, HPV infection and p53 accumulation may be related to tumor progression and higher grade.

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Detection of Human Papillomavirus DNA and p53 , p21 Gene Expression in CIN3 and Uterine Cervical Cancer: Jae Hyung Na, Ho Sun Choi; J Korean Cancer Assoc. 2000;32(1):100-109.

Abstract PDF: PURPOSE
Though the etiology of this cancer has not been elucidated, it has been suggested that certain types of human papillomavirus (HPV) and alteration of the p53 gene are closely associated with uterine cervical cancer. The aim of the study was to investigate the role of high risk HPV, p53 and p21 gene in cervical intraepithelial neoplasia III (CIN3) and invasive squamous cell carcinoma.
MATERIALS AND METHODS
The presence of high-risk HPV DNA (16, 18, 31, 33, 35, 45, 51, 52, 56) were detected from cervical swab in 240 patients by hybrid capture method. Expression of p53 genes were studied in paraffin-embedded specimens by immunohisto- chemical staining and p53, p21 gene alteration by RT-PCR SSCP using fresh cervical tissues.
RESULTS
High risk HPV DNA were detected in 34%, 74.3% and 75.7% in control, CIN3 and invasive squamaus cell carcinoma respectively. In patients with high risk HPV DNA, type 16 were detected of 5.9%, 30.8%, 47.2% respectively. Relative concentration of HPV DNA to control was 16.3+-27.4 in CIN3 and 30.4+-40.8 in invasive squamous cell cancer. Of patients with high risk HPV DNA, p53 expression was found in 42.9% of CIN3 immunohistochemically, while patients with invasive squamous cell carcinoma was de- tected in 50%. In patients without high risk HPV DNA, p53 expression was detected in 17.1% in CIN3, 15.7% in invasive squamous cell carcinoma. But the mutation of p53 and p21 gene by RT-PCR SSCP were not observed in CIN3 and invasive squamous cell carcinoma.
CONCLUSION
These observations suggest that carcinogenesis of invasive squamous cell carcinoma from CIN3 may be concerned with high risk HPV concentration and may be occurred via another pathway without HPV and p53 or p21 mutation.

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Sequencing of p53 Gene Mutations in Primary Breast Cancer Tissues: Jeoung Won Bae, Bum Hwan Koo, Cheung Wung Whang, Seul Hee Park, In Sun Kim; J Korean Cancer Assoc. 1999;31(4):663-669.

Abstract PDF: PURPOSE
The etiology of breast cancer involves very complex factors such as genetic, hormonal, and dietary. The peak age of Korean breast cancer is much earlier, about ten years, than those of western countries. The role of p53 gene on the carcinogenesis has been studied since 1991. This study was designed for the evaluation of genetic factor by determining p53 gene mutations in Korean breast cancer.
MATERIALS AND METHODS
Mutation screening on p53 tumor suppressor gene was examined with PCR-SSCP and nucleotide sequencing technique from the genomic DNA extracted from the 27 fresh-frozen breast cancer tissues.
RESULTS
Mutations in p53 gene exon 5-7 were identified in 2 of 27 cases (7%). One had a missense mutation substituted gcg with ggg at codon 159, exon 5, and the other had a point mutation substituted tcc serine to tGc cysteine at codon 241, exon 7.
CONCLUSION
Point mutation of p53 gene in breast cancer seems to be the major defect found in Korean patients. It is necessary to perform further study in mutation of other exon 2, 4, 8, 9, and 11 of p53 gene to compare the genetic backgrounds of Korean breast cancer with those of westerns.

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p53 Mutation in Gastric Carcinoma Detected by PCR - SSCP and Direct - Sequencing: Sang Suk Lee, Sang Pyo Kim, Eun Joo Sohn, Mi Seon Hwang, Soo Sang Sohn; J Korean Cancer Assoc. 1998;30(6):1069-1077.

Abstract PDF: PURPOSE
p53 gene mutations, one of the most common alterations found in human tumors, has also been detected in gastric carcinoma, and shown to have a crucial and early role in gastric carcinogenesis of intestinal type and mainly associated with tumor progression in the cancer of diffuse type. We tried to investigate the frequency of p53 mutations in 27 gastric carcinomas.
MATERIALS AND METHODS
Fresh tumor tissue from a series of gastric carcinoma was screened for p53 mutations by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) with silver staining and confirmed by direct-sequencing in 27 cases of gastric carcinoma. Immunohistochemical method for p53 protein accumulation was also performed in the same cases.
RESULTS
Immunohistochemistry revealed 20 of 27 cases of gastric carcinoma, positive for p53. PCR-SSCP analysis of p53 exons 5-8 detected mobility shift in 4 out of 20 p53-positive tumors; three from exon 5 and the other from exon 7, respectively. DNA sequencing of exon 5 showed CGC to CAC point mutation in one of three cases; exon 7, ATC to AAC point mutation. It seemed that there was no correlation between genetic alterations of p53 gene detected by PCR-SSCP and expression of p53 protein by immunohistochemistry. CONCLUSIOAS: Our results suggest that mutations of the p53 gene are rare genetic events in carcinogenesis of gastric carcinomas. There was discrepancy between mutations screened by PCR-SSCP and overexpressions in immunohistochemical staining.

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bcl-2 and p53 Gene Expression in Colonic Adenoma and Carcinoma: Chang Young Lim, Jeong Won Kim, Il Han Song, Young Joo Jin, Im Whan Rho, Dong Kook Park, Jeong Hee Cho, Sung Bae Choi; J Korean Cancer Assoc. 1998;30(1):89-99.

Abstract PDF: PURPOSE
Recently, it is suggested that the inhibitian of apoptosis is associated with tumorigenesis of colon. Bcl-2 gene is an important inhibitory regulator of apoptosis, and bcl-2 acts antagonistly with the wild type p53 gene, one of the tumor suppressor genes, in apoptosis. To detnmine the role of bcl-2 and p53 gene in colonic tumorigenesis, we performed the study.
MATERIALS AND METHODS
We tested the tissue obtained by polypectomy and surgical resection by immunohistochemical staining for Bcl-2 and p53.
RESULTS
We found that in normal colonic tissue, the Bcl-2 was sparcely expressed, and the p53 was expressed sporadically. The rate of positivity of staining was below 5%. However, in colonic adenoma and colon cancer tissue, Bcl-2 and p53 were expressed more than in nonnal colonic tissue(p<0.05). (Scoring in Colonic adenoma: Bcl-2 6.2+/-1.1, p53 5.7+/-1.0; Scoring in Colonic carcinoma: Bcl-2 4.7+/-1.0, p53 8.3+/-0.9) CONCLUSION: Our results suggested that the bcl-2 and p53 play an important role in colonic tumorigenesis.

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A Study of Retrovirus-mediated p53 Gene Transduction Into Human Gastric Cancer Cell Lines: Joo Hang Kim, Yoo Sun Moon, Dong Hwan Shin, Jae Jin Song, Soo Jung Gong, Sun Young Rha, Soo Kyoung Kim, Sook Jung Jeong, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(5):754-764.

Abstract PDF: PURPOSE
The development of new therapeutic modalities such as gene therapy, which still requires further investigation, is clearly important to improve the prognosis of gastric cancer. This study was conducted to evaluate the effect on the growth and the tumorigenicity of retrovirus-mediated p53 gene transduction into gastric cancer cells.
MATERIALS AND METHODS
Human gastric cancer cell lines were cultured and their DNAs were analyzed to evaluate the p53 status with PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and DNA sequencing. Retroviral supernatants were obtained from each producer cell line, PA317/LNCX and PA317/LNC/p53, after construction of retroviral vector LNC/p53 containing human p53 cDNA and producer cell line PA 317/ LNC/p53. To investigate the effect of retrovirus-mediated p53 gene transduction in human gastric cancer cell lines, the in vitro growth rates and in vivo tumorigenicities of the N-87 cell line having mutant p53 and the YCC-S-2 cell line having wild-type p53 were compared before and after infection with LNC/p53 retrovirus. RESULTS: The following results were obtained: 1) The growth inhibition of N-87 cells after p53 transduction was signficant when compared to that of the parent N-87 cells. The growth of the p53 transduced YCC-S-2 cells and the parent YCC-S-2 cells was not different. 2) In nude mice, the growth of tumors formed by N-87 cells was modestly inhibited after retrovirus-mediated wild-type p53 gene transduction. However, the growth of tumors formed by YCC-S-2 cells was not inhibited by retrovirus-mediated p53 gene transduction. 3) The expression rate of p53 protein after p53-containing retroviral infection in the KATO-III cell lines, which have no p53 gene, was dose-dependent on the m.o.i. of retrovirus, although it was not more than 15% with the m.o.i. of 100 upon immunohistochemical analysis.
CONCLUSION
The growth inhibition by retrovirus-mediated p53 transduction in human gastric cancer cells was significant in a gastric cancer cell line having mutant p53 in vitro, and the growth of tumor masses formed by a gastric cancer cell line having mutant p53 was modestly inhibited after p53 transduction using retroviral vector in nude mice, although it was not statistically significant. Only modest inhibition of tumor growth using retrovirus-mediated p53 gene transduction in vivo is most likely to be due to low transduction efficiency.

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Limited Cytotoxic Effect of Adenoviral-mediated p53 Gene Transfer in Variable Non-small Cell Lung Cancer (NSCLC) Cell Lines: Jhingook Kim, Sook Hyun Lee, Eun Sung Hwang, Jong Sik Kim, Kwhanmien Kim, Je Ho Lee; J Korean Cancer Assoc. 1997;29(4):565-575.

Abstract PDF: PURPOSE
Cancer gene therapeutic strategy using p53 tumor suppresser gene have been suggested to be effective in many solid tumors including non-small cell lung cancer (NSCLC). To test generalized applicability, we tested a number of non-small cell lung cancer cell lines for their sensitivity to adenoviral-mediated wild-type p53 gene transfer.
MATERIALS AND METHOD
Replication-incompetent recombinant adenovirus encoding wild- type p53 (Avp53) under the control of the human cytomegalovirus (CMV) promoter was constructed and the cytotoxic effectiveness was evaluated in various NSCLC cell lines. Because 20 moi (multiplicity of infection; number of active virus particle/cell number) of Avp53 showed highly-effective cytotoxicity in p53-deleted cell lines (NCI-H1299, and NCI-H358), same amount was used for other cell lines.
RESULTS
Variable degree of cytotoxicity were observed in cell line with p53 mutation, but almost no effect were observed in those with will-type p53. Neither the infectivity of adenovirus, which was observed by x-gal stain after adenoviral mediated lac Z gene, nor the expression of p53 protein in infected cell, which was observed by western blot, was not the useful marker to expect the cytotoxic effect of Avp53. However, in responsive cell lines with Avp53, prominent expression of p21 protein, which was observed by western blot, was noticed.
CONCLUSION
In conclusion, adenoviral-mediated wild-type p53 transfer may not be applicable to every patient with non-small cell lung cancer, especially when the tumor has wild-type p53 gene. Better method to predict the effectiveness before application and strategy to widen the applicable extent is needed.

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A Study on the Loss of Heterozygosity of the p53 Gene in Primary Uterine Cervical Carcinomas: Jin Woo Kim, Chun Geun Lee, Yeo Won Sohn, Hong Ki Min, Su Mi Han, Eun Young Cho, Kyung Sook Kim, Joon Mo Lee, Sung Eun Namkoong; J Korean Cancer Assoc. 1997;29(2):280-290.

Abstract PDF: PURPOSE
Allelic deletion of p53 tumor suppressor gene have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancers. But the loss of heterozygosity (LOH) data on chromosome 17p are rare and controversial with respect to cervical carcinomas. So, we tried to elucidate the frequency of p53 locus LOH in primary cervical carcinoma and compared the LOH data with clinicopathological parameters.
MATERIALS AND METHODS
In order to detect LOH within one of the well-known tumor suppressor gene, p53, three intragenic polymorphisms (exon 1, exon 4, and intron 6) and one microsatellite distal to the p53 gene (D17S5) were examined. Paired DNA samples from 55 primary uterine cervical carcinomas and normal bloods were studied for the chromosomal allelic loss of p53 gene locus by polymerase chain reaction (PCR), the presence of human papilloma virus (HPV), and the presence of p53 gene point mutation by PCR-single conformation polymorphism (SSCP) analysis. And the relationships between allelic losses of this gene and conventional clinicopathological parameters were evaluated.
RESULTS
We could increase the heterozygosity of the p53 gene up to 1 (100%). The observed allelic loss rate of the p53 locus in informative cases was 5.5% (3/55) and the observed allelic loss rate of the D17S5 locus in informative cases was 8.7% (4/46) . Only one of the four patients with LOH at the D17S5 locus showed a concomittant allelic loss of the p53 gene. The overall LOH incidence of the chromosomal region comprising 17p13.1 (p53) to 17p13.3 (D13S5) was 10.9% (6/55). All the samples contained at least one of the oncogenic HPV type 16 and/or 18 sequences. No shifted bands were observed in the PCR-SSCP analysis of the p53 gene. The LOH of the p53 gene was not related to other parameters including clinical stage, histological type, and degree of differentiation.
CONCLUSION
Concerning with the results above, we conclude that the allelic imbalance of the p53 gene itself is not implicated as a major contributing factor in the malignant transformation or the tumor progression in HPV-positive cervical cancers. Another putative tumor suppressor gene which has more important function than p53 gene in cervical carcinogenesis might exist between these two loci [p53 (17p13.1) and D17S5 (17p13.3)].

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Prognostic Significance of p53 Protein Expression in Colorectal Cancer: Kang Choon Lee, Dong Wook Choi, Nan Mo Moon, Yong Kyu Kim, Nam Sun Paik, Jong Inn Lee, Dae Yong Hwang, Ja June Jang; J Korean Cancer Assoc. 1994;26(6):878-885.

Abstract PDF: Molecular carcinogenesis model in colorectal cancer was proposed by Vogelstein in 19B9, that is, the accumulation of a series of genetic alterations results in malignant transformation from normal epithelium. Among them, p 53 gene mutation is known to take place in late stage, and is detected in more than 70% of colorectal cancers. Also, it was suggested that genetic alteration of p53 gene was related to worse prognosis in colorectal cancer patients. On the other hand, it is controversial still now whether p53 oncoprotein expression have relation with poor prognosis in colorectal cancers or not. So, we studied the p53 protein expression in l39 case of colorectal cancer patients who underwent curative surgical resection in Korean Cancer Center Hospital from Jan. 1984 to Dec. 1988 with immunohistochemical technique using Pab 1801, which is monoclonal antibody to p53 protein. We also analyzed the relevance between p53 protein expression and the conventional prognostic parameters. The positive rate of p53 protein expression was 43.9%. We didn't find any relevance between positive p53 protein expression and the conventional prognostic parameters except significantly lower expression rate in mucinous carcinoma(p=0.02). And, we could not detect any prognostic significance of p53 protein expression in resectable colorectal cancer patients. In conclusion, nuclear p53 protein expression by immunohistochemistry is considered to have no prognostic impact in resectable colorectal cancer patients. and we suggest that further study shou1d be going on including multiple genetic alteraions, and cytoplasmic p53 protein expression to detect the factors influencing on prognosis.

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The Association of p53 Mutation with Human Papillomavirus Type 16 , 18 Infection and its Clinical Significance: Chang Soo Park, Yong Sang Song, Chang Won Koh, Hye Won Jeon, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 1996;28(1):122-138.

Abstract PDF: Recent several studies have suggested that inactivation of p53 gene could occur by two theoretical mechanisms in cervical cancer. The E6 transforming protein of oncogenic human papillomavirus(HPV) binds to and promotes the degradation of p53 protein, or the mutation of the p53 gene could result in its inactivation without HPV infection. The purpose of this study were to investigate HPV infection and p53 mutation according to the status of lymph node metastasis and to analyse the relationship and role of HPV infection and p53 alteration in the advance and metastasis of cervical cancer. Paraffin embedded tissue sections were obtained from 30 patients with cervical cancer, each l5 patients with or without lymph node metastasis. The PCR and Southern blotting were used for the detection of HPV l6/18 DNA. Alteration of p53 activity was evaluated by immunohistochemistry using MAb DO7 and polymerase chain reaction with single stranded conformation polymorphism(PCR-SSCP). There was no significant difference in HPV infection between two groups, 73.3%(l l/15) in negative lymph node group and 80.0%(l2/15) in positive lymph node group. Although by immunohistochemistry p53 alterations were found more frequently in positive lymph node group(46.7%) than in negative lymph node group(20.0%), there was no significant difference between two groups. HPV negative cervical cancers had more p53 alterations(57.l%) than HPV positive cervical cancers(26.1%). However, there was no significant inverse relationship between HPV infection and p53 alteration. In conclusion, these data suggest that HPV infection and p53 alteration may play an important role independantly in the development of cervical cancer and p53 alteration may be associated with the advance and metastasis in some cases.

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