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Treatment with sodium butyrate and rapamycin inhibit growth of human cervical cancer cells.

Yong Jun JEON ; Chi Heum CHO ; So Jin SHIN ; Sang Hoon KWON ; Soon Do CHA

Korean Journal of Gynecologic Oncology.2007;18(3):165-171.

OBJECTIVE: To evaluate whether mTOR inhibition by rapamycin can enhance the inhibitory effect of sodium butyrate, a histone deacetylase (HDAC) inhibitor on human cervical cancer cell line HeLa. METHODS: Cervical cancer cells (HeLa) were treated with sodium butyrate alone or in combination with rapamycin. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTS) assay and flow cytometry was performed to ascertain the effects of sodium butyrate and combinations of sodium butyrate with rapamycin. Expression of cell cycle related proteins were evaluated by Western blot analysis. RESULTS: As proven previously rapamycin, the mTOR inhibitor was effective in reducing the cell growth of cervical cancer cell line HeLa. Rapamycin and sodium butyrate induced growth inhibition in a dose dependent manner, with 100 nM/L rapamycin and 10 mM/L sodium butyrate blocked 78% cell growth. FACS analysis data substantiated the competence of rapamycin in inducing G1 arrest of mammalian cells, and this ability was greatly enhanced by the combination of sodium butyrate and rapamycin. The percentage of sub G1 fraction of cells was remarkably increased by the combination of sodium butyrate and rapamycin. Sodium butyrate in combination with rapamycin showed the increased expression of CDK inhibitors p21, p27, and dephosphorylation of Rb whereas the expression levels of cyclin A, cyclin D1 and cyclin B1 were reduced. CONCLUSION: The findings implicate that rapamycin could enhance the anti-cancer effect of sodium butyrate. Further in depth studies and in vitro studies would throw more light on the growth inhibitory mechanism and its potential use as therapeutic drugs of butyric acid and rapamycin.
Blotting, Western ; Butyric Acid* ; Cell Cycle ; Cell Line ; Cell Survival ; Cyclin A ; Cyclin B1 ; Cyclin D1 ; Flow Cytometry ; HeLa Cells ; Histone Deacetylases ; Humans* ; Mental Competency ; Sirolimus* ; Sodium* ; Uterine Cervical Neoplasms*

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Three cases of squamous cell carcinoma arising in mature cystic teratoma of the ovary.

Jeong Suk KIM ; Yoon Young CHOI ; Sang Hoon JEONG ; Mi Jin KIM ; Doo Jin LEE ; Sung Ho LEE

Korean Journal of Gynecologic Oncology.2005;16(4):371-377.

Benign mature cystic teratoma is a very common ovarian lesion. It commonly occurs during a woman's reproductive years and most often is benign. In approximately 1% to 3% of cases, however, it can undergo a malignant transformation with a very poor prognosis. The frequency of malignant degeneration of dermoid is related to age, with the highest in-cidence in the postmenopausal years. Squamous cell carcinoma accounts for 70-88% of all malignant tumors arising in the mature cystic teratom-as followed by the much rarer adenocarcinomas and carcinoids. Preoperative diagnosis is difficult due to the rarity of this tumor and its similarity to mature cystic teratoma. We experienced 3 cases of squamous cell carcinoma arising in mature cystic teratoma and report our cases with a brief review of the literature.
Adenocarcinoma ; Carcinoid Tumor ; Carcinoma, Squamous Cell* ; Dermoid Cyst ; Diagnosis ; Female ; Ovary* ; Prognosis ; Teratoma*

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A case of diffuse large B-cell lymphoma of the uterus and ovary.

Sang Hoon LEE ; Kyung Jin MIN ; Keum Joon CHO ; Soon Cheol HONG ; Sang Wook YOO ; Nam Hee WON ; Kyu Wan LEE

Korean Journal of Gynecologic Oncology.2005;16(4):366-370.

Malignant lymphoma of uterus and ovary is a very rare disease. Under the impression of ovarian malignancy, subtotal abdominal hysterectomy with bilateral salpingo-ophorectomy was done due to severe pelvic adhesion. Histopathologic and immunohistochemical study demonstrated the tumor to be diffuse large B-cell lymphoma of the ovary with involvement of the uterus. So, we have experienced a case of malignant lymphoma of the uterus and ovary in Department of Obstetrics and Gynecology and Pathology, College of Medicine Korea University and discribed our case with a brief review of literature.
B-Lymphocytes* ; Female ; Gynecology ; Hysterectomy ; Korea ; Lymphoma ; Lymphoma, B-Cell* ; Obstetrics ; Ovary* ; Pathology ; Rare Diseases ; Uterus*

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Malignant lymphoma originated from uterine cervix and extended to endometrium: A case report.

Won Moo LEE ; Jung Eun LEE ; Jeong Hye HWANG

Korean Journal of Gynecologic Oncology.2005;16(4):361-365.

Primary malignant lymphoma arising from the female genital tract is extremely rare. Most genital lymphomas arise in the Corpus and cervix of uterus and vagina. Patients usually present with bleeding, abdominal or pelvic discomfort but very infrequently the tumors are discovered as a result of a routine examination. We present a case of non-Hodgkin's malignant lymphoma originated from uterine cervix and extended to endometrium, and review the relevant literature.
Cervix Uteri* ; Endometrium* ; Female ; Hemorrhage ; Humans ; Lymphoma* ; Uterus ; Vagina

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A clinical study of 15 cases of primary carcinoma of the fallopian tube.

Hyun Jung LEE ; Keum Jung LEE ; Min Ji KIM ; Back Kyung SEO ; Young YU ; Kyung Taek LIM ; Seok Ju SEONG ; Tae Jin KIM ; Chong Taik PARK ; Jae Uk SHIM ; Ki Heon LEE

Korean Journal of Gynecologic Oncology.2005;16(4):354-360.

OBJECTIVE: The aim of the study is to determine the clinical characteristics and management of primary fallopian tube malignancies together with the results there unto that had been diagnosed and treated in Samsung Cheil Hospital oncology department retrospectively. METHODS: The fifteen cases of fallopian tube malignancies, of a total of 3495 gynecologic malignancies (0.043%) that has been diagnosed in or referred to our hospital between January 1993 and December 2004 were evaluated retrospectively. We investigate the clinicopathologic findings and analyze the survival period for 15 patients with primary fallpian tube malignancies who were surgically operated. RESULTS: The mean age of patients is 53.47 years. Most frequent application symptoms of the cases are pelvic mass (46.7%) and abnormal uterine bleeding (40%). The staging laparotomy was done in 12 patients. According to FIGO staging, seven of the cases are stage I, six of the cases are stage III, and one of the cases is borderline malignancy. Adjuvant chemotherapy was applied 13 cases and adjuvant radiotherapy was applied one case. Mean follow up period of the cases is 27.8 months. CONCLUSION: Primary fallopian tube malignancies are very rare malignancies. Diagnosis can be made generally peri or postoperatively. More extensive clinical research must be performed in order to have definite etiologic diagnostic management modalities and prognostic markers.
Chemotherapy, Adjuvant ; Diagnosis ; Fallopian Tubes* ; Female ; Follow-Up Studies ; Humans ; Laparotomy ; Radiotherapy, Adjuvant ; Retrospective Studies ; Uterine Hemorrhage

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Effects of cell growth inhibition on the combination of cisplatin with green tea extracts.

Hyun Kyung KIM ; Young Haw KANG ; Sun Young KWAK ; Guo Hua DING ; Su Mi BAE ; Eun Kyung PARK ; Yong Seok LEE ; Jung KIM ; Yong Wook KIM ; Duck Yeong RO ; Joon Mo LEE ; Sung Eun NAMKOONG ; Hong Seok CHANG ; Heung Jae CHUN ; Dae Seog LIM ; Woong Shick AHN

Korean Journal of Gynecologic Oncology.2005;16(4):347-353.

OBJECTIVE: The chemotherapeutic agent cisplatin (cis-diamminedichloroplatinum (II)) is particularly effective against cervical cancer. The purpose of this study is to elucidate combination effect of cisplatin and green tea extracts on the growth inhibition of TC-1 cell. METHODS: To observe the anti-proliferative effects, we treated different doses of cisplatin (0.1, 0.5, 2.5 uM), GTP (1, 5, 25 ug/ml) and EGCG (25, 50, 100 uM). to TC-1 cells. Also, we treated 0.5 uM of cisplatin and different doses of GTP (1 and 5 ug/ml) or EGCG (25 and 50 uM). Cell viability was scored by use of MTT assay. In addition, E6 gene expression patterns in TC-1 cell were investigated by using RT-PCR. RESULTS: Cell growth inhibition in a dose dependent was observed at the different concentration of ciaplatin, GTP and EGCG. Also, in the groups treated by 0.5 uM of cisplatin and GTP (1 and 5 ug/ml) or EGCG (25 and 50 uM), the inhibition of cell growth showed with 12.2%, 6.9% and 63.4%, 72.2% as compared to the group treated by cisplatin only. In RT-PCR, down regulation of E6 was shown. CONCLUSION: Additive effect of the combination of cisplatin with GTP or EGCG on the inhibition of cell growth was observed. This effect suggests the possibility lowering the concentration of chemotherapeutic drugs, which alleviate the side effect of drugs.
Cell Survival ; Cisplatin* ; Down-Regulation ; Gene Expression ; Guanosine Triphosphate ; Tea* ; Uterine Cervical Neoplasms

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Differential protein expression of etoposide-treated CaSki cervical carcinoma cells.

Seung Baek LEE ; Jun Sang BAE ; Jung Jin KIM ; Seo Yun TONG ; Eun Kyoung YIM ; Keun Ho LEE ; Chan Joo KIM ; Soo Jong UM ; Jong Sup PARK

Korean Journal of Gynecologic Oncology.2005;16(4):333-346.

OBJECTIVE: This study was designed to examine the pharmaco-dynamic pattern of proteomic expression in cervical carcinoma cells (CaSki cell line; HPV-16 positive) after in vitro treatment by the etoposide. METHODS: We analyzed proteomic profiling in cervical carcinoma cells after etoposide treatment using two-dimensional gel electrophoresis (2-DE) with MALDI-TOF-MS used for protein identification. Then, we tested the several experimental methods for verification and functional identification, including MTT assay, PI staining, DNA fragmentation assay, FDA, FACS and Western blot analysis. RESULTS: Etoposide inhibited the CaSki cervical cancer cell growth in a dose-dependent manner and the optimal concentration of etoposide is 2micrometer(IC50) in the CaSki cervical cancer cells. The etoposide induced apoptosis, as determined by DNA fragmentation assay, FACS, and Western blot. The etoposide increased the protein expression of Fas (Apo-1/CD95), p53, pRb and caspase-3, but decreased the level of Bcl-2 and caspase-3 precursor and subsequently triggered the mitochondrial apoptotic pathway (release of cytochrome c and activation of caspase-9). To this end, we analyzed CaSki cancer cells using 2-DE. Eight proteins (XAP-5, HXC-36, serine/threonine protein phosphatase 2B catalytic subunit, G2/mitotic-specific cyclin B1, T-box transcription factor TBX20, diacylglycerol kinase, amiloride-sensitive amine oxidase, HEF-like protein, ras-related protein Rab-20) were down-regulated and nine proteins (RNA 3'-terminal phosphate cyclase-like protein, late endosomal/lysosomal Mp1 interacting protein, glia maturation factor, replication protein A 14 kDa subunit, mago sashi protein homolog, 14 kDa phosphohistidine phosphatase, protein C14 or f48, cyclin-dependent kinase 4 inhibitior A, retinoic acid-binding protein II) were up-regulated in etoposide-treated CaSki cells when compared with non-treated cells. CONCLUSION: Our results clearly indicate that etoposide induced cell death by apoptosis. These findings may provide insights into the mechanisms underlying the apparent anti-tumoral effects of etoposide.
Apoptosis ; Blotting, Western ; Calcineurin ; Caspase 3 ; Catalytic Domain ; Cell Death ; Cell Line ; Cyclin B1 ; Cyclin-Dependent Kinase 4 ; Cytochromes c ; Diacylglycerol Kinase ; DNA Fragmentation ; Electrophoresis, Gel, Two-Dimensional ; Etoposide ; Glia Maturation Factor ; Human papillomavirus 16 ; Oxidoreductases ; Proteomics ; Replication Protein A ; Transcription Factors ; Uterine Cervical Neoplasms

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The efficacy of HPV DNA chip test in the atypical squamous cell of undetermined significance.

Won Sik LEE ; Jong Taeg PARK ; Gi Heon LEE ; Seog Ju SEONG ; So Eun JUNG ; Nak Woo LEE ; Kyu Wan LEE

Korean Journal of Gynecologic Oncology.2005;16(4):323-332.

OBJECTIVE: This study was performed to investigate the efficacy of DNA chip method for detecting and genotyping of human papillomavirus (HPV) and screening of high-grade CIN (cervical intraepithelial neoplasia) or invasive cancer in the patients with atypical squamous cells of undetermined significance (ASC-US). METHODS: This study was based on 131 cases to be revealed ASC-US by Pap smear for the cervical cancer screening from July 2004 to Octorber 2004. They were evaluated by HPV DNA chip test, Cervical colposcopy and directed biopsy, and cone biopsy. The results of type 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 54, 56, 58, 59, 66 and 68 in HPV DNA chip test were categorized as high risk HPV. We evaluate the detection rate of the high-grade CIN and invasive cancer by HPV DNA chip test. RESULTS: The incidence of high risk HPV DNA was 51.1% (67/131). Twelve of 131 (9.2%) were diagnosed as high-grade CIN or CIS on histology. The detection rate of high risk HPV DNA in high-grade CIN and invasive cancer was 83.3% (10/12). The detection rate of high risk HPV DNA was 36.0% (31/86) in normal or reactive, and 83.3% (10/12) in CIN II or above on histology. Higher the grade of biopsy, more the detection rate of high risk HPV DNA by HPV DNA chip test. CONCLUSION: The use of HPV DNA chip test in patients with ASC-US may be useful in detection of high-grade CIN or invasive cancer.
Biopsy ; Cervix Uteri ; Colposcopy ; DNA* ; Female ; Humans ; Incidence ; Mass Screening ; Oligonucleotide Array Sequence Analysis* ; Uterine Cervical Neoplasms

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No association between genetic polymorphisms of the Interleukin-4 Receptor alpha gene and cervical cancer in Korean population.

Sang Eun LEE ; Jae Weon KIM ; Noh Hyun PARK ; Yong Sang SONG ; Soon Beom KANG ; Hyo Pyo LEE

Korean Journal of Gynecologic Oncology.2005;16(4):316-322.

OBJECTIVE: Genetic variants of IL-4Ralpha polymorphisms of Ile50Val were known to upregulate receptor response to IL-4. IL-4 was found in cervical cancer cell lines and known to promote cervical carcinogenesis and the progression from cervical intraepithelial neoplasia to cervical cancer. So, we aim to explore whether the Ile50Val polymorphisms of Interleukin-4 receptor alpha (IL-4Ralpha) gene increase cervical cancer risk, which could serve as useful genetic markers for assessing the risk of the development and progression of cervical cancer in Korean population. METHODS: The blood samples of 228 cervical cancer patients who were diagnosed at Seoul National University Hospital from 1999 to 2002 and 204 subjects who had screened at the health care system of Seoul National University Hospital and confirmed as non-cancer controls, were obtained. PCR amplification and TagMan assay were used. We used the chi-square test to evaluate whether the distribution of genotypes varied significantly between cervical cancer and controls. Odds Ratio and 95% confidence intervals were calculated using logistic regression test after age adjusting. RESULTS: The distribution of homozygotes and heterozygotes closely approximated the expected values under Hardy-Weinberg equilibrium in cases and controls (p=0.33, chi-square=0.94; p=0.15, chi-square=2.04). In cervical cancer group, allele frequency of Ile was 46.1%, in comparison with 43.4% in control group which showed no significant difference statistically (p=0.52). Using subject with the Val/Val homozygote as a reference group, we found no association between the Ile/Val and Ile/Ile genotypes and the risk of cervical cancer with age adjusted regression analysis (aOR=1.09, 95% CI=0.70-1.72, p=0.7; aOR=1.21, 95% CI=0.67-2.19, p=0.52). Subanalyses of the cervical cancer according with clinical stage, histologic type, lymph node status and parametrial invasion status showed no statistically significant association with these polymorphisms. CONCLUSION: The polymorphisms of the IL-4Ralpha gene are neither associated with increasing risk of cervical cancer nor more vulnerable for cervical cancer progression in Korean population.
Carcinogenesis ; Cell Line ; Cervical Intraepithelial Neoplasia ; Delivery of Health Care ; Gene Frequency ; Genetic Markers ; Genotype ; Heterozygote ; Homozygote ; Humans ; Interleukin-4* ; Logistic Models ; Lymph Nodes ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism, Genetic* ; Seoul ; Uterine Cervical Neoplasms*

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FIGO stage IB clear cell carcinoma and adenocarcinoma of uterine cervix.

Jin Hee KIM ; Eun Sun CHOI ; Dae Yeon KIM ; Dae Sik SUH ; Jong Hyeok KIM ; Yong Man KIM ; Young Tak KIM ; Joo Hyun NAM ; Jung Eun MOK

Korean Journal of Gynecologic Oncology.2005;16(4):307-315.

OBJECTIVE: To compare the clinical features and prognosis of patients with clear cell carcinoma (CCA) and adenocarcinoma (ACA)of the uterine cervix. METHODS: We have performed retrospective clinical study on 5 patients diagnosed as CCA and 55 patients diagnosed as ACA from November 2000 to December 2004. Demographic data, pathologic findings, treatments and survival time were reviewed. RESULTS: The mean age of patients with CCA and ACA was 31.5 or 30.4 years respectively and all patients were FIGO stage IB. Among the 5 patients of CCA, 4 patients have underwent radical hysterectomy (RH) and one patient have treated with radiotherapy only. Among the 55 patients of ACA, 50 patients have underwent RH and pelvic lymph node dissection (PLND), paraaortic lymph node sampling (PALNS) and the other have underwent only bilateral salphingoophorectomy (BSO) and PLND. There are no significant difference on age, tumor size, depth of invasion, parametrial involvement, vaginal involvement and pelvic lymph node metastasis (p>0.05). The mean survival time of CCA and ACA was 42.5 and 43.2 months respectively (p=0.32). The recurrent rate of CCA and ACA are 25% and 5.45% (p=0.30) and the disease free survival of CCA and ACA are 18.7 months and 43.6 months respectively (p=0.054). CONCLUSION: There were no significant difference on clinical features and prognosis of FIGO stage Ib CCA and ACA. Large scaled prospective multicenter trials will be able to provide a decision for prognosis and proper therapy.
Adenocarcinoma* ; Cervix Uteri* ; Disease-Free Survival ; Female ; Humans ; Hysterectomy ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Radiotherapy ; Retrospective Studies ; Survival Rate

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