bcl-2 prevents cell death from a wide variety of stimuli and provides survival of cells with accumulated genetic alterations and c-myc can promote both cell proliferation and cell death through the transcriptional regulation of target genes. Although several studies have been reported on the expression of bcl-2 or c-myc separately, little has been known about the role of coexpression of bcl-2 and c-myc to cell proliferation and apoptosis, as well as the frequency of these coexpression in cervical cancer specimens. In this study, we have examined the expression of bcl-2 and c-myc in cervical cancer specimens and cervical intraepithelial neoplasia(CIN) to determine the role of coexpression of bcl-2 and c-myc during progression into cervical cancer. Proteins and transcripts of bcl-2 and c-myc were evaluated by immunohistochemistry in 60 clinical specimens(20 cervical cancer, 30 CIN, and 10 normal cervix). In addtion, we evaluated kinetic indices of cell proliferation and apoptosis simultaneously. The cell proliferation index was determined by detection of the Ki- 67 in immunohistochemistry. Apoptotic index was determined by the detection of apoptotic cells with TUNEL staining. Medical records including pathologic reports were reviewed. Overexpression of bcl-2 and c-myc was identified in 7(35%) and 10(50%) of 20 cervical cancer specimens respectively, but none in normal cervix and CIN samples. In addition, coexpression of bcl-2 and c-myc was found in 5(25%) of 20 cervical cancer specimens. The cell proliferation index increased with progression from normal to CIN and invasive cancer(normal cervix, 10.2; CIN 1, 24.1; CIN 2/3 59.7; cervical cancer, 71.2; p <0.01). The apoptotic index also increased with grade of lesions(normal cervix, 0; CIN 1, 0.33; CIN 2/3, 1.85; cervical cancer, 3.89; p <0.01) and showed a significant correlation with proliferation index(r=0.7451, p=0.0002). However, there was no significant difference in apoptotic index between bcl-2 positive and bcl-2 negative group in cervical cancer(p=0.4765). In addition, there was also no significant difference in cell proliferation between c-myc positive and c-myc negative group(p=0.6891). Furthermore, there was no significant difference in cell proliferation and apoptosis between bcl-2 and c-myc positive group and others in cervical cancer(p=0.6311 and p=0.7600 respectively). The well-known clinicopathologic parameters, including tumor diameter, FIGO clinical stage, lymph node metastasis, did not correlate with simultanuos positive immunoreactivity for bcl-2 and c-myc proteins in cervical cancer. In conclusion, the cell proliferation and apoptosis increase with increasing lesion grade of cervical neoplasia and apoptosis correlates with cell proliferation. In addition, overexpression of bcl-2 and/or c-myc may be genetic alteration found only in cervical cancer and may not play a role in the development and progression of CIN. However, neither bcl-2 nor c-myc immunoreactivity correlated with the proliferation index or apoptotic index. These results suggest that other factors may also play a role in controlling the cell proliferation and apoptosis of cervical cancer.
Apoptosis* ; Cell Death ; Cell Proliferation ; Cervical Intraepithelial Neoplasia* ; Cervix Uteri ; Female ; Immunohistochemistry ; In Situ Nick-End Labeling ; Lymph Nodes ; Medical Records ; Neoplasm Metastasis ; Proto-Oncogene Proteins c-myc ; Uterine Cervical Neoplasms

OBJECTIVE: This study was performed to evaluate the radiosensitizing effect of combined administration of 13-cis-retinoic acid (cRA) and interferon-alpha-2a (INF) in normal cervical keratinocyte and cervical cancer cell lines. METHODS: cRA, INF and radiotherapy was applied to cervical cancer cell lines (HT-3 and HeLa cells) to obtain optimum dose 20% cytotoxicity in MTT assay from each treatment. The dose was determined as 1.8 Gy for radiation, 10uM for cRA, and 1,000 U/ml for INF. Primary cultured cervical keratinocyte (PCCK), HT-3 and HeLa cells were treated with cRA and INF alone or in combination and compared with untreated control cells. Finally, radiotherapy was added to the cRA and INF treatment. RESULTS: The treatment of cRA and INF-alpha reduced significantly the mean number of colony of HT-3 cells from 250 (SD, 19) to 143 (SD, 32). In contrast, PCCK and HeLa cells exhibited less than 15% reduction of colony formation with the treatment of cRA and INF-alpha. Irradiation of HT-3 cells reduced the colony formation significantly (from 63.6% to 18.4%, p=0.002) after treatment of cRA and INF-alpha. However, PCCK and HeLa cells showed 13.2% (from 70.0 to 56.8%, p=0.807) and 8.4% (from 60.8% to 52.4%, p=0.816) reduction of their colonies respectively. CONCLUSION: These results suggested that the treatment of cRA and INF-alpha showed significant radiosensitizing effect in HPV-negative HT-3 cells but not in the normal cervical cells or HPV-positive HeLa cervical cancer cells.
Cell Line* ; HeLa Cells ; Humans ; Isotretinoin* ; Keratinocytes* ; Radiation-Sensitizing Agents* ; Radiotherapy ; Uterine Cervical Neoplasms*

Development of chemoresistance is a persistent problem during the treatment of local and disseminated disease. Elucidation of the mechanism involved in multiple drug resistance has been a major goal of cancer molecular biology. Here, we review the recent work that has identified several gene families associated with drug resistance including genes of membrane transporter, DNA damage, apoptosis, and survival signaling. These genes may be cooperatively regulated as part of gene expression program that confers drug resistance through multiple pathways. We describe various complex gene expression programs for drug resistance. Thus the altered expression of a single gene may not be predictive of response to therapy. Nevertheless, understanding of the mechanism involved in multiple drug resistance in addition to the identification of critical genes, most relevant to the development of clinical drug resistance, is important to the development of novel drugs which can evade the current resistance mechanism of the cancer cells.
Apoptosis ; DNA Damage ; DNA Repair ; Drug Resistance* ; Drug Resistance, Multiple ; Drug Therapy* ; Gene Expression ; Humans ; Membranes ; Methylation ; Molecular Biology

Infection with one of 15 types of high-risk human papillomavirus (HPV) is the cause of cervical cancer. Worldwide, 70% of cervical cancer is caused by either HPV type 16 or 18. The current HPV vaccine is composed of virus-like particles (VLPs) of the L1 capsid protein as well as adjuvant. Quadrivalent HPV vaccine contains L1 VLPs from HPV types 6, 11, 16, and 18, and the bivalent vaccine contains HPV 16 and 18 L1 VLPs. HPV vaccines have demonstrated almost 100% efficacy in preventing HPV 16- or 18- associated cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in large-scale randomized studies. The HPV vaccine was confirmed to be safe by the WHO Global Advisory Committee for Vaccine Safety after reviewing information from clinical trials and post-marketing surveillance of two HPV vaccines. Local injection site reactions were the most commonly observed side effect, and these resolved spontaneously. A three-dose schedule is recommended prior to sexual contact and potential exposure to HPV, but a two-dose schedule is also recommended for adolescent girls aged 9 to 13 years. Recently, cervical cancer screening and HPV vaccination to prevent cervical cancer and HPV-related disease have become major public health issues. The effects of HPV vaccination, such as a rapid decrease in HPV prevalence, genital warts, and cervical precancerous lesions, have been observed in several countries in which HPV vaccination coverage is very high. At this point, cost-effectiveness analysis should be performed in Korea with the view to include HPV vaccination in the national immunization program to increase the coverage of HPV vaccination. In the future, we can eradicate cervical cancer through the universal HPV prophylactic vaccine and therapeutic HPV vaccine, together with cervical cancer screening.
Adolescent ; Advisory Committees ; Appointments and Schedules ; Capsid Proteins ; Cervical Intraepithelial Neoplasia ; Condylomata Acuminata ; Female ; Human papillomavirus 16 ; Humans ; Immunization Programs ; Korea ; Mass Screening ; Papillomavirus Vaccines ; Prevalence ; Public Health ; Uterine Cervical Neoplasms ; Vaccination*

No abstract available.
Antigens, Neoplasm ; Carcinoma, Squamous Cell ; Serpins ; Uterine Cervical Neoplasms

Endometrial cancer is a third common female malignancy in Korea, affecting approximately 714 women per year. Despite the publication of several prospective randomized trials, there continues to be controversy regarding the use of adjuvant therapy in endometrial cancer management. It is clear that most women with earlystage, low-risk disease will do well without adjuvant therapy. Intermediate-risk patients are at risk for local regional relapse, and radiotherapy has been shown to effectively reduce this risk without significantly impacting overall survival. The absence of a clear impact on survival has resulted in a lack of consensus regarding the use of radiotherapy in intermediate-risk patients. At the same time, the patterns of failure in intermediate-risk patients have resulted in differing recommendations regarding appropriate radiotherapy targets. High-risk patients are at risk for both local and distant failure, and chemotherapy has been shown to improve outcome in these patients. High-risk patients are also at risk for local failure, and targeted radiotherapy may be appropriate. In this article, we discuss the controversies surrounding the use of adjuvant radiotherapy in endometrial cancer using an evidence-based approach and along the National Comprehensive Cancer Network 2005 practice guideline.
Consensus ; Drug Therapy ; Endometrial Neoplasms* ; Female ; Humans ; Korea ; Prognosis ; Publications ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence

No abstract available.
Female ; Ovarian Hyperstimulation Syndrome*

OBJECTIVES: To investigate clinicopathologic findings of patients with small cell carcinoma of uterine cervix, and to evaluate the recurrence pattern and prognosis of patients with small cell carcinoma of the uterine cervix. Methods: From Jan. 1990, to Dec. 1997, 23 patients with small cell carcinoma of the uterine cervix were registered and followed-up at Korea Cancer Center Hospital. Clinical characteristics, survival of these patients were studied retrospectively. RESULTS: Among the 23 cases of small cell carcinoma of uterine cervix, 17 cases(74%) were of the neuroendocrine type (NE group), and 6 cases(26.0%) of the squamous cell type (SCC group). The median age, FIGO stage, and treatment modality were not significant difference between two groups. Pelvic lymph node metastases were found 53% in NE group, and 33% in SCC group, but there were not significant difference between two groups(p>0.05). Three patients showed distant metastases in NE group(bone 18%, bladder 9%), but there was no distant metastasis in SCC group. The 3 year survival rate was 50.0% in SCC group and 32.1% in NE group, but there were not statistical significance(p>0.05). Six patients showed recurrence after treatment (4/17 cases in NE group, 2/6 cases in SCC group). Recurrence sites were liver (3/6, 50%), and lung (2/6, 33%), brain (2/6, 33%), retroperitoneum (1/6, 17%), and axillae lymph node (1/6, 17%). CONCLUSION: This study showed neuroendocrine small cell carcinoma may have more aggressive than squamous small cell carcinoma, but there were not significant difference in prognosis between the two groups. Because of limitation of number of patients, further large scaled multicenter studies are needed.
Axilla ; Brain ; Carcinoma, Small Cell* ; Cervix Uteri* ; Female ; Humans ; Korea ; Liver ; Lung ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Retrospective Studies ; Survival Rate ; Urinary Bladder ; Uterine Cervical Neoplasms

OBJECTIVES: This non-randomized retrospective study was to investigate the clinical characteristics and to evaluate the actual 5-year survival rate of the patients with invasive cancer of the cervix. METHODS: 489 evaluable patients with invasive cancer of the cervix were treated at Korea Cancer Center Hospital from January to December 1992. In this retrospective study, we studied the clinico-pathologic characteristics(age, FIGO stage, histologic type, nodal metastasis) and treatment modalities by the review of medical records. Especially, the survival was confirmed by the support of the police and government office. RESULTS: The most common subsets of patients were found in the group of FIGO stage IIb(32.5%) and age between 51 and 60(33%). Surgery was the main treatment in stage Ib/IIa(65%) and radiation in stage IIb or more(97%). Nodal metastasis were surgically identified in 6% of stage Ib, 29% of stage IIa and 36% of stage IIb. Overall actual 5-year survival rate was 72.2%; stage Ia(100%), Ib(94%), IIa(82%), IIb(63%), IIIa(36%), IIIb(47%), and IV(0%). The five-year survival rate according to LN status in surgically confirmed FIGO stage Ib-II patients were 91.9% in negative patients and 73.1% in positive patients respectively. Five-year survival rate was significantly different according to stage(P < 0.02) and nodal metastasis(p < 0.01). However, age and histologic type did not show any significant differences in survival. CONCLUSION: Overall actual five-year survival rate of 489 evaluable patients with invasive cancer of the cervix who were treated at Korea Cancer Center Hospital from January to December 1992 was 72.2%. Five-year survival rate was different according to stage and nodal metastasis.
Humans ; Korea ; Medical Records ; Neoplasm Metastasis ; Police ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms*

Angiosarcoma is rare malignant neoplasms, which account for less than 1% of all sarcomas. They have a wide distribution in various body organs and tissues: approximately a third of cases occur in the skin and a quarter in soft tissues. Angiosarcoma rarely involves the female reproductive system. We present a case of a 37-yaer-old woman who had primary angiosarcoma of the left breast; With metastases to the spleen and ovary.
Breast ; Female ; Hemangiosarcoma* ; Humans ; Neoplasm Metastasis ; Ovary* ; Sarcoma ; Skin ; Spleen