OBJECTIVE: Flavopiridol that inhibits cyclin-dependent kinase, can cause cell cycle arrest, induce apoptosis in human tumor cell lines. In the present study, we investigated apoptotic effects of flavopiridol and the underlying molecular mechanisms in human ovarian cancer cell lines. METHODS: We used TOV-21G and TOV-112D cell lines. The cell viability was tested by MTT assay and apoptosis was assessed by TUNEL assay and annexin-V binding. Western blot was used to examine apoptosis related protein levels. MAP kinase activity was analyzed by non-radioactive MAP kinase assay kit. RESULTS: Treatment of TOV-21G and TOV-112D cells with flavopiridol (50 nM to 1000 nM) led to a dose- and time-dependent inhibition of cell growth and survival. Dose-related induction of apoptosis was also observed in these cell lines. Flavopiridol (500 nM) induced striking decreases in the levels of the antiapoptic proteins Mcl-1, Bcl-X(L), and XIAP in both cell lines. In contrast, expression of Bax, Bcl-2, and AIF was not significantly influenced by flavopiridol. Although flavopiridol resulted in accumulation of p53 in both cells, flavopiridol mediated apoptosis was p53 independent because it occurred to the same degree in TOV-112D cells in which p53 was inactivated by mutation. Flavopiridol treatment resulted in enhanced cleavage of pro-caspase 9 and activation of caspase 3. Apoptosis was associated with suppression of ERK activity. CONCLUSION: Although the precise mechanisms of flavopiridol mediated cytotoxicity have not been fully defined, these data suggest that flavopiridol has activity against ovarian cancers in vitro and is worthy of continued clinical development in the treatment of ovarian cancer.
Apoptosis ; Blotting, Western ; Caspase 3 ; Cell Cycle Checkpoints ; Cell Line ; Cell Line, Tumor ; Cell Survival ; Flavonoids ; Humans ; In Situ Nick-End Labeling ; Ovarian Neoplasms ; Phosphotransferases ; Piperidines ; Proteins ; Strikes, Employee

OBJECTIVE: The aim of this study was to determine the role of survivin, caspase 3, p53 and Ki-67 expression in the carcinogenesis of cervical carcinoma and aggressiveness of cervical intraepithelial neoplasia (CIN). METHODS: The pathology specimens of 94 patients with a diagnosis of Low grade CIN (31 cases), High grade CINL (32 cases) and squamous cell carcinoma (31 cases) were evaluated immunohistochemically for the expression of survivin, caspase 3, p53 and Ki-67 in paraffin sections. RESULTS: Survivin, p53 and Ki-67 expressions were progressively increased in accordance with the increasing degree of malignancy, but caspase 3 immunoreactivity was higher in high grade CIN than in low grade CIN and invasive cervical cancers. There was no significant difference between Ki-67 index and survivin, caspase 3 and p53 expression with the increasing degree of malignancy. The Ki-67 index was closely related to p53 overexpression in invasive cervical carcinoma group. CONCLUSION: A sequential increase of survivin, p53, and Ki-67 was observed in paralleling the progression of grade of CIN and cervical cancer. In addition, caspase 3 expression increased proportionally to the low-grade CIN to high grade CIN.
Carcinoma, Squamous Cell ; Caspase 3 ; Cervical Intraepithelial Neoplasia ; Humans ; Paraffin ; Uterine Cervical Neoplasms

OBJECTIVE: Cancer metastasis is a complex process involving a sequential series of multi-step genetic events, which produces an imbalance between stimulatory and inhibitory genes for metastasis. Presently, we examined the expression of metastatic tumor antigen 1 (MTA1) and nonmetastatic protein 23 homologue H1 (nm23-H1) proteins in metastasized epithelial ovarian cancer cells. METHODS: Fifty-one primary epithelial ovarian tumors and corresponding lymph nodes (LNs) were examined immunohistochemically for expression of MTA1 and nm23-H1. Expression of these proteins was statistically evaluated. RESULTS: The frequency of MTA1 expression was 30.3% (10/33) in stage III/IV LNs but was absent (0/18) in stage I/II LNs (p=0.01). MTA1 expression was observed in 50% (6/12) of metastasizing LNs but in only 10.3% (4/39) of non-metastasizing LNs (p=0.01). In contrast with MTA1, nm23-H1 expression was evident in 16 of 18 (88.9%) stage I/II ovarian cancer tissue samples but only in 20 of 33 (60.6%) stage III/IV tissues (p=0.05), and nm23-H1 production was also observed in 75.6% (34/45) of ovarian cancer tissue with residual tumors under 2 cm in diameter, but in 2/6 (33.3%) of cancer tissue with residual tumors exceeding 2 cm in diameter (p=0.03). CONCLUSION: The degree of expression and imbalance of MTA1 and nm23H1 are correlated with ovarian cancer LN metastasis.
Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Metastasis ; Neoplasm, Residual ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Proteins

Major clinical research advances in gynecologic cancer in 2007 are as follows. Human papillomavirus (HPV) vaccines were shown to be effective in preventing cervical intraepithelial neoplasia (CIN). In treating cervical cancer, the intensity-modulated radiotherapy (IMRT) was suggested to be less toxic than the conventional radiotherapy was. Minimally invasive surgery, especially robot surgery is expected to be more popular in future. Adjuvant radiotherapy did not increase the survival rate in early endometrial cancer. Adjuvant chemoradiation was demonstrated to be superior to adjuvant radiation in the treatment of early endometrial cancer. Hormone therapy in endometrial cancer was effective but has high recurrence rate. Pelvic/abdominal pain, increased abdominal size/bloating, difficulty eating/feeling full, urinary frequency/urgency could be the symptoms of ovarian cancer. Serial CA-125 measurement or combining ultrasonography and CA-125 could be effective screening strategies of ovarian cancer. Molecules interfering vascular-endothelial growth factor (VEGF) were shown to be effective in the treatment of ovarian cancer.
Cervical Intraepithelial Neoplasia ; Endometrial Neoplasms ; Female ; Gynecology ; Humans ; Mass Screening ; Ovarian Neoplasms ; Radiotherapy, Adjuvant ; Radiotherapy, Intensity-Modulated ; Recurrence ; Survival Rate ; Urogenital Neoplasms ; Uterine Cervical Neoplasms ; Vaccines

Ascites following radical hysterectomy with retroperitoneal lymphadenectomy for invasive cervical cancer has been reported previously. Most of these reports described chylous ascites. The chylous ascitic fluid is milky; further, chylous ascites leads to nutritional problems. Authors present the case of a patient who developed serous ascites following radical hysterectomy with bilateral pelvic lymphadenectomy. The amount of ascites was approximately 18,000 ml over 52 days. The patient had no nutritional problems or complications. Although the etiology could not be determined, Authors surmise that the ascites may have been due to massive drainage from injured lymphatic channels below the cisterna chyli. Authors could not found any literatures which described massive serous ascites following surgery in gynecologic malignancy and reports this case with review of literatures.
Adenocarcinoma ; Ascites ; Ascitic Fluid ; Chylous Ascites ; Drainage ; Humans ; Hysterectomy ; Lymph Node Excision ; Thoracic Duct ; Uterine Cervical Neoplasms

Endometrial stromal sarcoma (ESS) that arises from extrauterine endometriosis is a rare form of malignancy. We report the case of a 37-year-old ESS patient with extrauterine endometriosis who was treated with ifosfamide/cisplatin chemotherapy. A woman presented with epigastric pain and abdominal distension. Computed tomography imaging revealed a profuse amount of ascites, including a 12.4x12.3 cm sized posterior cul-de-sac mass composed of solid and cystic components. Cytoreductive surgery was performed to remove the mass and the histopathologic findings indicated ESS associated with extrauterine endometriosis. Six cycles of combination chemotherapy [ifosfamide (5 g/m(2)) with mesna (1 g/m(2)) and cisplatin (50 mg/m(2)) (IP)] were administered. After a six-month of disease-free interval, recurrent ESS developed in the pelvic cavity and in both lung fields. Megace medication decreased tumor marker CA-125 for six weeks. However, the patient expired sixteen months after the cytoreductive surgery. ESS associated with extrauterine endometriosis showed response to IP chemotherapy and megace.
Adult ; Ascites ; Cisplatin ; Drug Therapy, Combination ; Endometriosis ; Female ; Humans ; Lung ; Megestrol Acetate ; Mesna ; Sarcoma, Endometrial Stromal

Malignant fibrous histiocytoma (MFH) is the most frequent malignant soft tissue tumor in adults. A primary MFH occurs most commonly in the extremities and the trunk, but rarely in the pelvic cavity. We report a case of malignant fibrous histiocytoma of the unknown origin in the pelvic cavity with a review of the literature. The neoplasm occurred in the pelvic cavity of 53-year-old female who complained of enlarging nontender mass in the lower abdomen. The final diagnosis was based on the pathological report of the surgical specimen.
Abdomen ; Adult ; Extremities ; Female ; Histiocytoma, Malignant Fibrous ; Humans ; Middle Aged ; Pelvic Neoplasms

OBJECTIVE: To identify clinical prognostic factor improving survival of recurrent epithelial ovarian cancer (EOC) patients treated with secondary cytoreductive surgery (SCS). METHODS: The indications of SCS were as follows; 1) complete response (CR) after primary cytoreductive surgery and adjuvant chemotherapy, 2) disease-free survival (DFS) (> or =6 months). Clinical data of 17 patients including age, DFS, peritoneal seeding identified during SCS, the number of recurrent tumors (> or =1 cm), serum CA-125 levels and maximal diameter of residual tumor after SCS were reviewed retrospectively between January 1990 and March 2007. Survival analyses were performed using Kaplan-Meier method with log-rank test and univariate Cox's regression analysis. RESULTS: Mean age of them was 51.7 years. No peritoneal seeding identified during SCS was a prognostic factor improving progression-free survival after SCS (PFS-SCS) (30 vs. 6 months, p<.01 hazard ratio 0.099, 95% confidence interval 0.011-0.929, p=.043). Furthermore, serum CA-125 level (< or =37 U/ml) after SCS was a significant prognostic factors improving overall survival (51 vs. 19 months, p=.033; hazard ratio 0.212, 95% confidence interval 0.045-0.983, p=.045). CONCLUSION: Serum CA-125 levels with normal value after SCS and no peritoneal seeding may be associated with the improvement of survival in recurrent epithelial ovarian cancer patients treated with SCS.
Chemotherapy, Adjuvant ; Disease-Free Survival ; Humans ; Neoplasm, Residual ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Reference Values ; Retrospective Studies ; Seeds

OBJECTIVE: Paclitaxel is one of the most effective antineoplastic drugs. HPV-related cervical lesions have only managed with invasive procedure. Topical drug administration with temperature sensitive copolymer gels are useful approaches to clinical situation. In this study, we evaluated the activity of multiblock copolymers of PEG/PLA (poly(L-lactic acid)/polyethylene glycol) gels with paclitaxel (PTX) formulation administered by topical treatment to mice bearing human cervical cancer cell lines (HeLa). METHODS: We have synthesized gels of PEG/PLLA (poly(L-lactic acid)/polyethylene glycol) multiblock copolymers containing Paclitaxel which have temperature-sensitivecharacteristics. This Paclitaxel-containg copolymers has the sol-gel-sol transition temperature at body temperature. The efficacy of PTX in PEG/PLA mutiblock copolymer micelle were conducted in HeLa-tumor bearing Balb/c Nu/Nu athymic mice at an equivalent paclitaxel dose of 10 mg/kg with 48 hr interval. The inhibition of tumor growth was evaluated after 8 days of treatment. Tumors were harvested at day 10 and stained with hematoxylin and eosine to measure tumor. RESULTS: PTX-containing PEG/PLA mutiblock copolymer significantly decreased tumor growth at day 8, as measured by tumor size; ie, PEG/PLA mutiblock copolymer only goup ; 1.43+/-0.26 m versus intraperitoneal treatment of Paclitaxel : 0.75+/-0.07 mm and topical treatment of PTX-containing PEG/PLA copolymer containing Paclitaxel : 0.28 mm (Min; 0.1 mm-Maxu0.8 mm). CONCLUSION: This demonstration that PTX-containing PEG/PLA mutiblock copolymer have a useful topical drug deliversy system carrying temperature sensitive characetersitics in HPV-related cervical lesions.
Administration, Topical ; Animals ; Antineoplastic Agents ; Body Temperature ; Cell Line ; Eosine Yellowish-(YS) ; Gels ; Hematoxylin ; Humans ; Lifting ; Mice ; Mice, Nude ; Models, Animal ; Paclitaxel ; Polymers ; Transition Temperature ; Ursidae ; Uterine Cervical Neoplasms

OBJECTIVE: Homeostasis of the extracellular matrix (ECM) is maintained by the action of a specific system of proteolytic enzymes known as matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP). The MMP/TIMP system regulates the composition and turnover of ECM to control the site and extent of connective tissue remodeling. In pathologic conditions, MMP play a key role in degradation of basement membrane and extracellular matrix, and is responsible for cancer invasion, progression and metastasis. The aim of this study is to evaluate the correlation between expressions of MMP/TIMP and clinicopathologic factors in endometrial cancer. METHODS: Expressions of MMP-2, MMP-9, TIMP-1, and TIMP-2 were assessed by immunohistochemistry in a total of 55 endometrial cancers and were analyzed by the correlation between expressions of MMP/TIMP and clinicopathologic factors in endometrial cancer. RESULTS: Expression rates of MMP-2,-9, TIMP-1, and TIMP-2 were 71.7%, 54.9%, 41.2%, and 76.5% respectively. Expression of MMP-2 was correlated with the group of positive lymph node metastasis in endometrial cancer (p=0.04). Specially, coexpression of MMP-2 and TIMP-2 was significantly more frequent in the group of positive lymph node metastasis (p<0.01) and the group of positive peritoneal CONCLUSION: The expressions of MMP and TIMP were not a significant difference in survival analysis, but this study was recognized that the coexpression MMP-2 and TIMP-2 is correlated with lymph node metastasis and positive peritoneal cytology.
Basement Membrane ; Connective Tissue ; Endometrial Neoplasms ; Extracellular Matrix ; Female ; Homeostasis ; Immunohistochemistry ; Lymph Nodes ; Matrix Metalloproteinases ; Metalloproteases ; Neoplasm Metastasis ; Peptide Hydrolases ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2