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ABSTRACT: PRKCDBP is a putative tumor suppressor located at 11p15.4, where frequent genomic loss has been observed in human cancers. We explored the possible association between an intra-exonic single nucleotide polymorphism (SNP), rs1051992, that results in a Leu to Pro substitution, and risk for endometrial carcinogenesis. We assessed the genotype of rs1051992 in endometrial cancer tissues from 147 patients and normal endometrial tissue from 191 healthy individuals by restriction endonuclease PvuII-based genotyping. Allele frequencies in the cancer specimens were compared with those in the healthy controls. We also evaluated the association between polymorphisms at this locus and histopathological features of endometrial cancer.
Cancer Investigation 09/2012; 30(9):642-5. · 1.85 Impact Factor
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ABSTRACT: Aim: Non-endometrioid endometrial cancer is a clinically and pathologically distinct subtype of endometrial cancer. The aim of this study was to determine whether systematic pelvic lymphadenectomy improves overall survival compared to no lymphadenectomy in non-endometrioid endometrial cancer. Material and Methods: The authors retrospectively reviewed the medical records and pathological findings of 112 patients who underwent surgical staging for non-endometrioid endometrial cancer from 2000 to 2006 in Korea. Results: Systematic pelvic lymphadenectomy was performed in 71 patients. Pelvic lymph node metastases were identified in 31% and 14.6% patients who underwent systematic pelvic lymphadenectomy and no lymphadenectomy, respectively. After adjusting for risk factors, there was no significant difference in overall survival (odds ratio = 0.69; 95% confidence interval, 0.29-1.67) between patients who did or did not undergo systematic pelvic lymphadenectomy. On multivariate analysis, patients with lymph node metastasis had higher risk of death (odds ratio = 3.11; 95% confidence interval, 0.97-10.00) than the patients with no lymph node metastasis. Conclusion: Although systematic pelvic lymphadenectomy did not affect overall survival in patients with the non-endometrioid subtype, it has the potential benefit of providing prognostic information and acting as a guide for further adjuvant treatment.
Journal of Obstetrics and Gynaecology Research 05/2012; · 0.94 Impact Factor
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ABSTRACT: The aim of this study was to explore the association between 2-deoxy-2-F18-fluoro-D-glucose uptake and the expressions of glucose transporter type 1 (GLUT-1) and hexokinase II (HK-II) in the lymph nodes of patients with cervical cancer.
This prospective study included 20 women with International Federation of Gynecology and Obstetrics stage IB to stage IIA cervical cancer who underwent positron emission tomography (PET)-computed tomography (CT) (PET/CT) before surgical treatment. In 333 dissected lymph nodes (LNs) obtained, we examined the size, tumor involvement, and expressions of GLUT-1 and HK-II. These characteristics were compared with PET/CT and pathological findings.
Pathological analysis found that 21% (70) of the 333 surgically dissected LNs were metastatic. Positron emission tomography/CT detected metastasis with 22.8% sensitivity and 98.5% specificity. The levels of GLUT-1 and HK-II expression in false-positive LNs were higher than those in pathologically confirmed negative nodes (P = 0.015 and P = 0.001, respectively). In metastatic LNs, PET/CT-positive nodes were significantly different from PET/CT-negative nodes in mean size (P = 0.043), tumor involvement (P = 0.008), and proportion of GLUT-1-positive tumor cells (P = 0.042).
Our results indicate that overexpression of GLUT-1 and HK-II may be related to 2-deoxy-2-F18-fluoro-D-glucose uptake in false-positive tissues on PET/CT. In metastatic lymph nodes, the ability of PET/CT to detect cancer may depend on tumor involvement, lymph node size, and GLUT-1 expression.
International Journal of Gynecological Cancer 03/2012; 22(4):654-8. · 1.65 Impact Factor
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ABSTRACT: We performed an age-matched case-control study to compare the clinical and pathology outcomes between histologically diagnosed primary malignant mixed műllerian tumour (MMMT) of the uterus and endometrial carcinoma.
Thirty-two women were treated for primary MMMT at seven tertiary medical centres in Korea from 2000 to 2006. For each woman with MMMT, four women with endometrioid and two with non-endometrioid endometrial carcinoma were selected as age-matched controls for analysis. Medical records were retrospectively reviewed to obtain outcome data.
The incidence of MMMT was 2.57% (32/1244). In comparison with women with endometrioid endometrial cancer, those with MMMT were characterised by large tumour size, higher incidence of adnexal involvement and lymph node metastases, leading to advanced disease stage. Despite the frequent use of adjuvant treatment, the 5-year survival rate of women with MMMT was significantly poorer than those with endometrioid endometrial cancer. However, women with MMMT were not significantly different from those with non-endometrioid endometrial cancer in terms of important pathologic variables, apart from larger tumour size. In addition, the 5-year survival rate of women MMMT was poorer than that those with non-endometrioid endometrial cancer, but the difference was not statistically significant.
Malignant mixed műllerian tumour is characterised by a high incidence of lymph node metastases and advanced stage at diagnosis, leading to poorer overall survival than other subtypes of endometrial carcinoma. Clinical trials for MMMT are critical for improving treatment strategies.
Australian and New Zealand Journal of Obstetrics and Gynaecology 12/2011; 52(1):44-8. · 1.24 Impact Factor
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ABSTRACT: The objective of this study was to assess whether para-aortic lymphadenectomy has therapeutic efficacy for patients with early-stage endometrioid uterine cancer who underwent systematic pelvic lymphadenectomy.
The authors retrospectively reviewed the medical records and pathological findings of 547 patients with histologically proven FIGO stage I-II endometrioid uterine cancer, based on comprehensive surgical staging, including pelvic with or without para-aortic lymphadenectomy.
Among 547 patients, 330 patients had systematic pelvic lymphadenectomy only, and 217 had systematic pelvic with para-aortic lymphadenectomy. There were no significant differences in histopathological factors in the high-risk group, even though deep myometrial invasion (p = 0.02) and lymphvascular space invasion (p = 0.01) were more common in patients who underwent systematic pelvic with para-aortic lymphadenectomy in all study populations. Within a median follow-up of 31 (range, 5-120) months, there was no significant difference in overall survival between the pelvic lymphadenectomy only and pelvic with para-aortic lymphadenectomy groups in all populations (p = 0.77), even in high-risk patients (p = 0.82). Upon multivariate analysis, patients with lymphvascular space invasion had significantly worse overall survival (odds ratio (OR) = 7.38; 95% confidence interval (CI) = 1.86-29.23; p = 0.004).
Although a prospective, randomized study needs to be performed for confirmation, our data suggest that the therapeutic benefit of para-aortic lymphadenectomy is uncertain in stage I and II endometrioid uterine corpus cancer, even in patients at high-risk for recurrence.
Annals of Surgical Oncology 12/2010; 18(5):1425-30. · 4.17 Impact Factor
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ABSTRACT: We evaluated associations between folate, vitamin B12, and the methylenetetrahydrofolate reductase (MTHFR) gene, and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer.
This multicenter case-control study enrolled 927 Korean women (440 controls, 165 patients with CIN 1, 167 patients with CIN 2/3, and 155 patients with cervical cancer, aged 20-75 years).
Patients with cervical cancer had significantly lower median serum folate and vitamin B12 concentrations vs. controls. Higher serum folate was significantly associated with lower cervical cancer risk (p for linear trend = 0.0058) with a trend for a lower CIN risk after multivariate adjustment. Low folate and the MTHFR 677 C > T variant were associated with a higher risk for CIN2/3 and cervical cancer vs. wild-type or heterozygous genotypes with high folate [OR, 2.39 (1.18-4.85) and 3.19 (1.43-7.13)]. Low vitamin B12 and the MTHFR 677 C > T variant also were associated with a higher risk for CIN 2/3 and cervical cancers [OR, 2.52 (1.17-5.42) and 2.40 (1-5.73)] vs. wild-type or heterozygous status with high vitamin levels.
Serum folate concentration is inversely associated with the risk of cervical cancer, and the MTHFR variant genotype may increase CIN and cervical cancer risk in women with low folate or vitamin B12 status.
Cancer Causes and Control 11/2010; 22(1):63-72. · 2.88 Impact Factor
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ABSTRACT: To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis.
Retrospective study.
Medical center.
Twenty-two epithelial ovarian cancer and six normal ovary tissues.
Mutation and altered expression of hSRBC gene.
hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing.
Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50% (two of four) of cancer cell lines and 41% (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2'-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7%) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level.
Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.
Acta Obstetricia Et Gynecologica Scandinavica 05/2010; 89(5):629-35. · 1.77 Impact Factor
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ABSTRACT: Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NAC-VBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity.
Journal of Korean medical science 02/2010; 25(2):240-4. · 0.84 Impact Factor
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ABSTRACT: Manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, plays a key role in protecting cells from oxidative stress. Furthermore, the MnSOD rs4880 polymorphism is associated with enzyme activity. The authors evaluated the interaction between MnSOD genotypes and cervical carcinogenesis risk and the modulating effects of serum antioxidant nutrient status (beta-carotene, lycopene, zeaxanthin/lutein, retinol, alpha-tocopherol and gamma-tocopherol).
Cases and controls for this study were recruited between June 2006 and July 2007 (263 controls, 84 cervical intraepithelial neoplasia (CIN), 94 CIN 2/3, and 99 cases of cervical cancer). The MnSOD polymorphism at rs4880T/C was examined using SNaPshot assays. Serum antioxidant vitamin concentrations were measured by reverse-phase gradient high-pressure liquid chromatography. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated after adjusting for age, menopause, parity, oral contraceptive use, smoking and alcohol consumption.
No association was found between the MnSOD rs4880 polymorphism and cervical cancer. However, genotypes significantly modified the risk of cervical cancer in association with the serum statuses of micronutrients (P(interaction)<0.05 for beta-carotene, lycopene, zeaxanthin/lutein, alpha-tocopherol, and gamma-tocopherol). Decreased CIN1 risk in association with the MnSOD rs4880 variant genotype was also observed particularly for subjects with higher beta-carotene and gamma-tocopherol levels. Similar results were observed for lycopene and alpha-tocopherol in relation to the risk of CIN2/3.
Our findings suggest that a higher antioxidant micronutrients status may decrease the risk of CIN and cervical cancer and modify the effect of the MnSOD polymorphism on disease risk.
Gynecologic Oncology 09/2009; 115(2):272-6. · 3.89 Impact Factor
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Seo-Yun Tong,
Jong-Min Lee,
Eun-Seop Song,
Kwang-Beom Lee,
Mi-Kyung Kim,
Young Mi Yun,
Jae-Kwan Lee,
Sung-Kyong Son,
Jung-Pil Lee,
Jae-Hoon Kim,
Soo-Young Hur,
Yong-Il Kwon
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ABSTRACT: The purpose of the study was to investigate the association between cervical cancer risk and single-nucleotide polymorphisms (SNPs) in three one-carbon metabolism genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) in Korean women. Twelve SNPs were identified in MTHFR, MTR, and MTRR in the 927 case-control samples, which included 165 cervical intraepithelial neoplasia 1 (CIN1), 167 cervical intraepithelial neoplasia 2 and 3 (CIN2/3), 155 cervical cancer patients, and 440 normal controls. The frequencies of the genotypes and haplotypes were assessed in the controls, CINs, and cervical cancers. Individual carriers of the variant allele C of MTHFR A1298C (rs1801131) had a 0.64-fold [95% confidence interval (CI): 0.42-0.98] decreased risk for CIN2/3 compared with common homozygotes. However, no significant association was found between most other variants and cervical cancer risk. The results also identified an increased CIN1 risk in carriers with at least one copy of haplotype 3 in the MTHFR gene (odds ratio, 1.88; 95% CI: 1.03-3.42). In conclusion, there was no significant association between most SNPs in MTHFR, MTR, or MTRR and the risk of CIN and cervical cancer in Korean women. In addition, there was no significant association of MTHFR haplotypes with risk of CIN2/3 and cervical cancer.
Cancer Causes and Control 09/2009; 21(1):23-30. · 2.88 Impact Factor
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ABSTRACT: This cross-sectional study examined the distribution of HPV 58 sequence variation in Korean women for the first time. Among 1,750 Korean women, 53 women were positive for HPV 58 single infection, of whom 26 were without disease, 20 were with cervical intraepithelial neoplasia (CIN) 1, and 7 with CIN 2 or 3. Altogether, 36 different nucleotide sequence variations were identified with the L1, 20 within E2, 5 within E6, and 10 within E7. Further studies on variants of oncogenic HPVs are necessary, particularly for the purpose of developing more predictive HPV detection methods.
Journal of Microbiology and Biotechnology 09/2009; 19(9):1051-4. · 1.38 Impact Factor
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ABSTRACT: To define the molecular basis of TGF-beta1 function in cervical carcinogenesis, we explored the expression and mutational status of TGF-beta1, TGF-beta1 receptors, and Smads, the regulators of the TGF-beta1 signaling pathway, in human cervical cancers.
Expression of TGF-beta1, TGF-beta1 receptors, and Smads transcripts were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and sequence alteration was analyzed using RT-PCR-single-strand conformation polymorphism (SSCP) analysis. Genomic levels of TGF-beta1, TGF-beta1 receptors and Smads was also measured by quantitative genomic PCR.
Abnormal overexpression of TGF-beta1 and abnormal reduction of type II TGF-beta1 receptor were identified in 36% (18 of 50) and 20% (10 of 50) of cervical cancer tissues, respectively. 22% (11 of 50) in Smad2 and 14% (7 of 50) in Smad4 revealed tumor specific mRNA reduction less than a half of normal means. In addition, no evidence for sequence alterations of the gene was found by RT-PCR-SSCP analysis.
Our study demonstrates that disruption of TGF-beta/Smad signaling pathway exist in human cervical cancer, suggesting that abnormal expressions of the member of TGF-beta/Smad signaling pathway might contribute to the malignant progression of human cervical tumors via suppressing the tumor suppression function of TGF-beta1 1's tumor suppression function.
Journal of Gynecologic Oncology 07/2009; 20(2):117-21. · 1.49 Impact Factor
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ABSTRACT: Although primary cytoreductive surgery is well accepted as a cornerstone of the management for epithelial ovarian cancer, the benefits of secondary cytoreduction in recurrent ovarian cancer remain unclear. Furthermore, no consensus has been reached regarding treatment strategies for extraperitoneal metastasis.
A 29-year-old woman was admitted to our hospital due to suspected recurrent ovarian cancer. Four years previously, she had undergone primary debulking surgery which was followed by adjuvant chemotherapy consisting of paclitaxel (175 mg/m(2)) and carboplatin (area under the curve = 5) for 6 cycles due to an ovarian papillary serous adenocarcinoma stage IIIc. Preoperative evaluation revealed a palpable inguinal mass and multiple enlarged pelvic lymph nodes with a well-defined mediastinal mass on abdomino-pelvic and chest computed tomography. Secondary debulking combined with video-assisted thoracoscopic surgery (VATS) was performed. The patient had no discernable evidence of disease at her 18-month follow-up.
VATS may be a reasonable option for secondary debulking in selected patients with isolated mediastinal metastasis.
Onkologie 06/2009; 32(5):274-6. · 0.87 Impact Factor
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Jong-Min Lee, Seo-Yun Tong,
Kwang-Beom Lee,
Young-Tae Kim,
Young-Jae Kim,
Jae Weon Kim,
Seok-Mo Kim,
Chi-Heum Cho,
Ki-Tae Kim,
Young-Lae Cho,
Kyu-Chan Lee
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ABSTRACT: To evaluate whether concurrent chemoradiation therapy (CRT) improves overall survival as compared to radiation therapy (RT) alone in stage III cervical cancers.
A multicenter retrospective review.
Nine tertiary medical centers in Korea.
A total of 277 patients treated for stage III cervical cancer without para-aortic lymph node (PALN) metastasis based on clinical staging workup from 1996 to 2003.
Medical and histopathological record review.
Disease-specific overall survival.
CRT and RT alone were performed in 172 and 105 patients, respectively. There was no significant difference in disease-specific overall survival between the CRT and RT alone arms based on clinical staging workup, even though the CRT arm was characterized by younger age, more favorable performance status and lower pretreatment blood urea nitrogen level as compared to the RT alone arm. In the CRT arm, three patients succumbed to treatment-related death.
CRT does not improve the overall survival rate in stage III cervical cancer as compared to RT alone based on clinical staging workup for PALN status. Special care needs to be taken regarding optimal dose and duration of RT, use of brachytherapy, anemia control and accurate pretreatment staging workup to improve survival outcome in patients with stage III cervical cancer.
Acta Obstetricia Et Gynecologica Scandinavica 05/2009; 88(6):707-12. · 1.77 Impact Factor
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ABSTRACT: Approximately 5-30% of the ovarian cancers are metastatic malignancies. The prevalence of metastatic ovarian tumors varies with the incidence rates and spread patterns of primary malignancies. We evaluated the prevalence, pre- and postoperative characteristics of metastatic ovarian cancer in Korean women. We reviewed the records for 821 ovarian malignancies with pathological consultation from 1996-2006 and recorded patient demographical, radiological, histopathological, and survival data. The study included 112 cases of histologically confirmed metastatic ovarian cancer. Metastatic ovarian cancer accounted for 13.6% of all ovarian malignancy, primarily arising from the gastrointestinal tract. The preoperative detection rate with imaging was 75%, and none of the radiological or serological features were useful for differential diagnosis. In multivariate analysis for prognostic variables, the only significant factor was the primary tumor site (p=0.004). Furthermore, extensive resection increased survival for some patients. The differential diagnosis of metastatic ovarian cancer can be problematic, so multiple diagnostic approaches are necessary. The extent of cytoreductive surgery for this type of tumor must be decided on a case-by-case basis.
Journal of Korean medical science 03/2009; 24(1):114-9. · 0.84 Impact Factor
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ABSTRACT: Previously, we used proteome analysis to identify transforming acidic coiled coil (TACC) 3 as a protein that is down-regulated upon paclitaxel treatment in cervical cancer cells. TACC3 mRNA and protein levels decreased after paclitaxel treatment in a time- and dose-dependent manner, and the transactivation of TACC3 promoter was dramatically diminished by paclitaxel. Importantly, paclitaxel treatment and knockdown of TACC3 by siRNA led to a synergistic enhancement of significant G2/M phase arrest and apoptosis in HeLa cells. In contrast to TACC3-deficient cells, paclitaxel treatment of mTACC3-overexpressing cells failed to induce G2/M phase arrest, cell growth inhibition, and apoptotic cell death. We studied the associated gene in mTACC overexpressed cells using microarray. From these results, numerous genes have been identified as being associated with tumor progression (Ppia, TMSB10, Annexin A2, rab31, prostaglandin E2-EP2, UHRF1), chemoresistance (Akt, Plk-1, MAP kinase) and metastasis (MMP9, PECAM-1) in mTACC3 overexpressed HeLa cells. Thus, TACC3 is thought to be the critical molecule in mediating the anticancer mechanisms of paclitaxel in p53 inactivated cells by inducing G2/M arrest and apoptosis. And our data suggested that the overexpression of TACC3 may be associated with the mechanisms of chemoresistance, tumor progression, cell proliferation and metastasis.
Oncology Reports 03/2009; 21(2):549-57. · 1.84 Impact Factor
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ABSTRACT: The abnormal expression of fragile histidine triad (FHIT) gene has been frequently reported in a variety of epithelial malignancies including cervical carcinoma. Furthermore, in a recent study it was proposed that transcriptional inactivation of FHIT, as a consequence of aberrant 5'-CpG island methylation, plays an important role in the carcinogenesis of human cervical carcinoma. The authors sought to determine whether abnormal FHIT transcription occurs in human cervical carcinoma, and if so, whether this abnormal expression is associated with aberrant 5'-CpG island methylation. In addition, the clinical significance of FHIT inactivation was investigated in Korean women with cervical cancer.
To examine for abnormal transcripts of the FHIT gene, quantitative RT-PCR, genomic DNA-PCR and nonisotopic RT-PCR-SSCP analysis were performed using the standard method. The methylation status was determined by methylation specific PCR and bisulfite DNA sequencing.
The FHIT gene was down-regulated in 15 of 58 (25.9%) cervical carcinomas. FHIT promoter hypermethylation was detected in 15 of 15 (100%) abnormally expression in cervical carcinomas. Bisulfite DNA sequencing confirmed these findings and a significant correlation was found between CpG site hypermethylation and low FHIT expression. However, no significant correlation was found between reduced FHIT expression and clinicopathological characteristics.
In this study, FHIT inactivation in cervical cancer was found to be strongly correlated with 5'-CpG island hypermethylation rather than a genetic alteration. Furthermore, no significant relation was found between a lack of FHIT expression and the prognostic factors of cervical cancer in our Korean cohort.
Journal of Gynecologic Oncology 07/2008; 19(2):117-22. · 1.49 Impact Factor
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ABSTRACT: In this study, a histopathologic review of synchronous primary neoplasms including gynecologic malignancies is presented, and the possible correlation among discrete tumor subsets, natural history, and survival is evaluated.
Between the years 2000 and 2005, 20 patients suffering from synchronous primary cancers of gynecologic malignancy were identified. Clinical and pathologic information was obtained from medical records. Kaplan-Meier survival analyses were conducted.
Patients with synchronous primary malignancies constituted 0.63% of all genital malignancies. The most frequently observed synchronous neoplasm was ovarian cancer coexistent with endometrial cancer (40%). The mean age of patients suffering from synchronous ovarian and endometrial cancer was 45.2 years. All patients with synchronous primary genital malignancies underwent hysterectomy with bilateral salpingo-oophorectomy and/or adjuvant therapy. The mean duration of survival was 57 months (S.E.: 10.0; 95% confidence interval: 37-77).
Patients suffering from primary genital malignancies are sometimes co-afflicted with other primary cancers. Synchronous ovarian and endometrial cancer constitutes the most common of these cases, and is detected at a relatively early age, with generally favorable prognoses.
European Journal of Obstetrics & Gynecology and Reproductive Biology 02/2008; 136(1):78-82. · 1.97 Impact Factor
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ABSTRACT: We studied the in vitro mechanism of etoposide-induced cell death in cervical cancer cells. Etoposide is cytotoxic to these cells, causing cell death by both apoptosis and autophagy, which has recently been described as a possible mechanism for nonapoptotic cell death. Electron microscopy revealed that autophagosomes/autolysosomes exhibited an autophagic appearance in the presence of etoposide. When autophagy was blocked by inhibitors of autophagy, including 3-methyladenine, both the expression of beclin 1 protein and the antitumor effect of etoposide were suppressed. Benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a pan-caspase inhibitor, reduced etoposide-induced cytotoxicity in CaSki cells. Hence, autophagy and apoptosis likely occur concurrently in etoposide-treated cervical cancer cells.
DNA and Cell Biology 11/2007; 26(10):713-20. · 2.07 Impact Factor
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ABSTRACT: Human papillomaviruses (HPVs), which are associated with the majority of cervical cancers, encode a transforming protein, E6, which interacts with the p53 tumor suppressor protein. There is a wide effort focused on searching for the target of the involvement of p53-independent HPV 16 E6-interacting proteins. We identified Breast Cancer 1 Gene (BRCA1)-associated ring domain protein 1 (BARD1) as a binding partner of E6 and investigated its biological function in cervical cancer cells. In vivo co-immunoprecipitation assay was performed to determine whether E6-BARD1 interaction occurred. We then used a degradation assay to determine whether E6-mediated inactivation of BARD1 transactivation function was associated with BARD1 degradation. A mutation assay revealed the site of interaction of E6 with BARD1. The effect of BARD1 on p53 transcriptional activity was tested using BARD1 knockdown and overexpression systems. BARD1 was not degraded by E6, and, instead, formed a physical complex with E6. Moreover, the mutations of the metal motif zinc-finger region decreased the ability of E6 to interact with BARD1. Transient transfection of BARD1 increased the p53-mediated activation of p21(WAF1) promoter despite the presence of E6. Additionally, the existence of BARD1 inactivated the expression of E6 in cervical cancer cells. These findings suggest that BARD1 may regulate the transcriptional activities of p53 as tumor suppressors.
DNA and Cell Biology 11/2007; 26(10):753-61. · 2.07 Impact Factor
