OBJECTIVE: Human papillomavirus (HPV) is strongly implicated as a causative agent in the etiology of cervical cancer. Of its gene products, E6 and E7 oncoproteins play major roles by inactivation of cellular p53 and pRb tumor suppressor proteins, respectively. However, it has been recently suggested that p53 and/or pRb-independent functions of E6 and E7 are involved in cervical carcinogenesis. The purpose of this study is to identify novel a cellular target, p73, of E6 and to determine how E6 inactivates p73 function, METHODS: The interaction between E6 and p73 were identified by the yeast two-hybrid assay in vivo and the GST pull-down assay in vitro. The function of the interaction was determined by transient transfections using p21 promoter-CAT reporter plasmid. The molecular mechanism underlying the functional significance of the interaction was further assessed by in vivo and in vitro protein degradation assays, and gel mobility shift assays. RESULTS: Yeast two-hybrid and GST pull-down assays indicate a physical interaction between p73 and either HPV-16 or HPV-11 E6 proteins in vivo and in vitro, respectively. Transactivation domain (amino acid residues 1-49) is found to be absolutely required for this interaction. Transient co-expression of E6 significantly inhibits the p73-mediated activation of p21WAF1 promoter in a p53-defective C33A cell line. Using Ga14-p73 fusion protein, we demonstrate that E6 inhibition of p73 transactivation function is independent of sequence-specific DNA binding, which is confirmed by direct electrophoretic mobility shift assay. Moreover, E6 inhibits p73 function by interfering with the activity of the amino-terminal activation domain. The protein degradation assays in vivo and in vitro indicate that p73, unlike p53, is not susceptible to E6-dependent proteolysis. CONCLUSION: Throughout this study, we identified p73 as a novel cellular target of HPV-E6 protein and found that E6 binds p73 through the amino-terminal transactivation domain, and inhibits its transactivation function independent of the protein degradation and DNA binding. These overall results, consequently, suggest that in addition to the inactivation of p53, the functional interference of p73 by HPV-E6 may, at least in part, contribute to E6-mediated cellular transformation.
Carcinogenesis ; Cell Line ; DNA ; Electrophoretic Mobility Shift Assay ; Human papillomavirus 11 ; Human papillomavirus 16 ; Humans ; Oncogene Proteins ; Plasmids ; Proteolysis ; Transcriptional Activation ; Transfection ; Tumor Suppressor Proteins ; Two-Hybrid System Techniques ; Uterine Cervical Neoplasms ; Yeasts

The sentinel lymph node is defined as the first node of a regional lymphatic basin that receives the lymphatic drainage from a tumor, thus representing an elective site of lymph node metastasis. According to the sentinel lymph node hypothesis, histologically negative sentinel lymph nodes can guarantee the histological negativity of the remaining regional lymph nodes. These assumptions suggest that the sentinel node can be a suitable marker of regional lymph node status. Thus sentinel node biopsy may be a reasonable alternative to unnecessary pelvic lymph nodes dissection and a suitable method for limited control of early stage cervical cancer. To improve the sentinel node detection in surgical procedures, we investigated lymphatic mapping of sentinel lymph nodes with isosulfan blue dye (lymphazur 1%) and technetium-99m colloid albumin. We have made it a rule to inject 5 ml of isosulfan blue dye in the peritumoral area of cervix. It is reported that isosulfan blue dye has been safe and easily used in the detection of sentinel lymph node in melanoma, breast cancer and vulvar cancer. We experienced a case of anaphylactic reactions to isosulfan blue dye in cervical cancer patient, so we report it with a brief review of literature.
Anaphylaxis* ; Biopsy ; Breast Neoplasms ; Cervix Uteri ; Colloids ; Drainage ; Female ; Humans ; Lymph Nodes ; Melanoma ; Neoplasm Metastasis ; Uterine Cervical Neoplasms* ; Vulvar Neoplasms

PURPOSE: Gonadotropin-releasing hormone (Gn-RH) can cause regression of hormonedependent human tumors, including uterine endometrial and ovarian carcinomas. These effects were thought to be mediated through the inhibition of gonadotropic and steroid hormone from the hypothalamus. But, in addition to its classic hypophysiotropic action, Gn-RH might play a role as a modulator of activity in the brain and many peripheral organs. It has been reported that this analog has a direct inhibitory effect on the tumor and that the specific binding sites for Gn-RH were demonstrated in certain tumors responsive to Gn-RH. In support of a possible clinical use of Gn-RH analogs in the treatment of the endometrial and ovarian carcinomas, we tried to find out whether Gn-RH receptors are present on hormone dependent tumors. MATERIALS AND METHODS: We have studied endometrial and ovarian tumor specimens and established uterine endometrial and ovarian carcinoma cell lines for the presence of Gn-RH receptor by the detection of its messenger ribonucleic acid (mRNA). We also compared the results obtained from tumor tissue specimens with the results from their corresponding normal tissues. Gn-RH receptor mRNA was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RH receptor sequence. RESULTS: Gn-RH receptor mRNA was detected in all normal endometrium and abnormally proliferative endometrium presenting dysfunctional bleeding, but not all in endometrial carcinomas (83%). Tumor stage and histologic grading had no relationship with receptor positivity. And, Gn-RH receptor mRNA was detected in less than 40% in normal myometrium and myomas. Gn-RH receptor expression was detected in same frequencies (86%) in normal ovarian tissues and ovarian carcinomas. Receptors were detected in a high proportion of the specimens from epithelial carcinomas (92%) and stromal tumors (100%) of the ovary. But, Gn-RH receptor was not detected in germ-cell derived tumors of the ovary. Established endometrial carcinoma (CUME-1) and epithelial ovarian carcinoma (CUMO-2) cell lines also demonstrated Gn-RH receptor mRNA, respectively. CONCLUSIONS: The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of hormone-dependent normal tissues and their respective tumors, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in endometrial and ovarian malignancies.
Animals ; Binding Sites ; Brain ; Cell Line ; DNA Primers ; Endometrial Neoplasms ; Endometrium ; Female ; Gonadotropin-Releasing Hormone* ; Hemorrhage ; Humans* ; Hypothalamus ; Mice ; Myoma ; Myometrium ; Ovary ; Receptors, LHRH* ; RNA ; RNA, Messenger

PURPOSE: This study was designed to find out whether protein kinase C (PKC) may affect telomerase activity in human ovarian cancers. MATERIALS AND METHODS: To determine whether PKC modulators influence PKC activities, NIH: OVCAR-3 and CUMO-2, cells were treated with PKC inhibitors, G 6976 and bisindolyl maleimide I, and PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA). Telomerase acti vity was determined by telomeric repeat amplification protocol (TRAP). Analysis of the expres sion of each telomerase subunits, human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT), was performed by RT-PCR. We also examined the alternative splicing of hTERT. RESULTS: G 6976 and bisindolylmaleimide I inhibited PKC activity. Telomerase activities appeared to be affected in a time-dependent manner by these two PKC inhibitors. PKC activities were increased in parallel with telomerase activity by TPA at the low dose (10 nM), but their activities were down-regulated at the high dose (1 micrometer). RT-PCR demonstrated the presence of hTR and hTERT mRNA before and after the treatment of PKC modulators, respectively, and showed the presence of one alternatively spliced transcript and full-length hTERT transcripts. CONCLUSION: These results showed that telomerase activity was affected by PKC and suggested PKC modulation may serve as an useful tool in the regulation of telomerase activity.
Alternative Splicing ; Cell Line* ; Humans* ; Ovarian Neoplasms* ; Protein Kinase C* ; Protein Kinases* ; RNA ; RNA, Messenger ; Telomerase* ; Tetradecanoylphorbol Acetate

Background: This study was conducted to identify the level of gender sensitivity and gender equality consciousness among dental hygiene students and to confirm the necessity of gender equality programs in the curriculum. Methods: A self-report questionnaire was conducted with some dental hygiene students using the Gender Sensitivity tool and Korean Gender Egalitarianism Scale for Adolescents (KGES-A). Results: First, the gender equality consciousness of the students who took women’s studies was high in the areas of educational life and socio-cultural life, and that of the subjects of grandparent families and Catholic was found to be high in the domestic life area. Second, the gender sensitivity of the subjects who took women’s studies was found to be high in all sub-areas. In addition, the gender sensitivity of females was higher in the areas of sexual identity, non-violence, and self-reflection than that of males. That of 4-year college students was higher in the areas of sexual identity, openness to gender roles, and non-violence than that of 3-year college students. In addition, the gender sensitivity of Catholic students was high in the areas of sexual identity and openness to gender roles. Third, gender equality consciousness was found to have an effect depending on whether subjects took women’s studies, family type, family type, and religion, and gender sensitivity was found to have an effect depending on whether subjects took women’s studies or gender. Conclusion Since dental hygienist is a profession that targets humans, education that can instill equal awareness and values of humans is important. To inspire gender sensitivity and gender equality consciousness in a prospective professional, it is necessary to conduct programs and education related to gender intelligence within dental hygiene curriculum.

No abstract available.
Mass Screening* ; Uterine Cervical Neoplasms*

OBJECTIVE: The purpose of this study is to evaluate the clinical effect of V-Y advancement flap after vulvectomy in patients with vulvar cancer. Local and systemic morbidity, the degree of satisfaction after operation, length of hospital stay were evaluated. PATIENTS AND METHODS: From March 2001 to september 2002, five patients with invasive vulvar cancer were eligible for this study. All the patients underwent radical vulvectomy with groin lymph nodes dissection. All of them were reconstructed by the same surgeon using ischial fasciocutaneous V-Y flaps based on perforators from the inferior border of the gluteous maximus muscle. RESULTS: Flap survival was 100%. There were no major complication including wound infection, wound disruption, urinary tract infection, and seroma in the femoral triangle. Functional outcome was excellent in all patients. CONCLUSION: The V-Y advancement flap provides a straight-forward and simple safe reliable method as a common approach in radical vulvectomy.
Groin ; Humans ; Length of Stay ; Lymph Nodes ; Seroma ; Urinary Tract Infections ; Vulvar Neoplasms* ; Wound Infection ; Wounds and Injuries

OBJECTIVE: The aim of this study was to obtain information on the prognosis and treatment of the low grade endometrial stromal sarcoma. PATIENTS AND METHODS: Three patients with low grade endometrial stromal sarcoma treated in kangnam St. Mary's hospital between 1993 and 2002 were evaluated. The clinical stage, management and outcome were analyzed. RESULTS: Those patients with low grade endometrial stromal sarcoma had a long overall survival in the presence of receiving hormonal therapy after initial surgery. Two are alive with disease-free status, one has shown a partial response to hormonal treatment. CONCLUSION: Surgery is the primary treatment for low grade endometrial stromal sarcoma. High dose hormonal replacement as adjuvant therapy will be associated with a lengthened overall survival in patients with low grade endometrial stromal sarcoma.
Humans ; Prognosis ; Sarcoma, Endometrial Stromal*

OBJECTIVES: AGUS often reflects an immediate cervical cancer precursor such as a HSIL mimicking an endocervical glandular lesion. In this study, we attempted to assess the clinical significance of a cytologic diagnosis of atypical glandular cells of undetermined significance (AGUS) and determine the usefulness of the human papillomavirus (HPV) DNA testing as the triage strategies in evaluating AGUS. METHODS: Between 1994 and 1998, 67,730 Papanicolaou smears were evaluated at Kangnam and Uijongbu St Mary's Hospital. There were 87 (0.13%) cases of AGUS smears during that time. Colposcopy was performed on all women, and HPV DNA testing was performed on 11 persons. RESULTS: Mean age of these patients was 45.8 years. Histologic diagnosis of AGUS were kolocytosis and CIN-I in 6 (6.9%), CIS in one, endometrial hyperplasia in 2 (2.3%), endometrial adenocarcinoma in 7 (8.0%), cervical adenocarcinoma in 14 (16.1%) and cervical squamous cell carcinoma in 2 (2.3%) cases. Endometriosis was 8.9% under 46 years old and none in over 46. CIN was 8.9% and 7.2%, respectively. Cervical adenocarcinoma was 6.7% under 46 and 19.1% over 46. Endometrial cancer was 4.4% and 11.9%, respectively. The risk of cervical cancer and endometrial cancer was high in the AGUS with Adenocarcinoma ; Carcinoma, Squamous Cell ; Colposcopy ; Diagnosis ; DNA* ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Endometriosis ; Female ; Human Papillomavirus DNA Tests ; Humans ; Middle Aged ; Papanicolaou Test ; Triage ; Uterine Cervical Neoplasms

No abstract available.
Hysterectomy* ; Sexual Behavior*