Humans ; Ovarian Neoplasms/drug therapy* ; Folate Receptor 1/metabolism* ; Female ; Immunohistochemistry/standards* ; Consensus ; Biomarkers, Tumor/metabolism* ; Fallopian Tube Neoplasms/pathology*

PURPOSE: 14-3-3ζ regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζ is associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3-3ζ expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζ expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζ expression, and 14-3-3ζ overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζ overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζ expression group, but not reached in the low 14-3-3ζ expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζ by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION: 14-3-3ζ overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζ could be a therapeutic option that enhances the antitumor activity of cisplatin.
14-3-3 Proteins/metabolism ; Adult ; Aged ; Cell Line, Tumor ; Cisplatin/therapeutic use ; Disease-Free Survival ; Down-Regulation ; Female ; Gene Knockdown Techniques ; Gene Silencing ; Humans ; Immunohistochemistry ; Middle Aged ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Prognosis ; Young Adult

Development of ovarian cancer involves the co-evolution of neoplastic cells together with the adjacent microenvironment. Steps of malignant progression including primary tumor outgrowth, therapeutic resistance, and distant metastasis are not determined solely by genetic alterations in ovarian cancer cells, but considerably shaped by the fitness advantage conferred by benign components in the ovarian stroma. As the dynamic cancer topography varies drastically during disease progression, heterologous cell types within the tumor microenvironment (TME) can actively determine the pathological track of ovarian cancer. Resembling many other solid tumor types, ovarian malignancy is nurtured by a TME whose dark side may have been overlooked, rather than overestimated. Further, harnessing breakthrough and targeting cures in human ovarian cancer requires insightful understanding of the merits and drawbacks of current treatment modalities, which mainly target transformed cells. Thus, designing novel and precise strategies that both eliminate cancer cells and manipulate the TME is increasingly recognized as a rational avenue to improve therapeutic outcome and prevent disease deterioration of ovarian cancer patients.
Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Female ; Humans ; Ovarian Neoplasms ; drug therapy ; pathology ; Tumor Microenvironment ; drug effects

PURPOSE: This study aimed to investigate whether Mullerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis. MATERIALS AND METHODS: OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway. RESULTS: The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time-dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway. CONCLUSION: These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.
Anti-Mullerian Hormone/*pharmacology ; Apoptosis/*drug effects ; Calcitriol/*pharmacology ; Caspase 3/metabolism ; Caspase 9/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Cell Survival/drug effects ; DNA Fragmentation/*drug effects ; Enzyme-Linked Immunosorbent Assay ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Growth Inhibitors/metabolism/pharmacology ; Humans ; Ovarian Neoplasms/*drug therapy/metabolism/*pathology ; Receptors, Peptide ; Receptors, Transforming Growth Factor beta ; Signal Transduction/*drug effects

OBJECTIVE: Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. METHODS: We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged < or =40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. RESULTS: A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. CONCLUSION: FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Female ; *Fertility Preservation ; Humans ; Laparoscopy ; Live Birth ; Neoplasm Recurrence, Local/blood/diagnosis/*therapy ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial/drug therapy/*pathology/*surgery ; *Organ Sparing Treatments ; Ovarian Neoplasms/drug therapy/*pathology/*surgery ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Term Birth ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the effect of a Chinese medicine, Xiaoaiping, in combination with cisplatin on the proliferation, invasion and apoptosis in human ovarian cancer HO-8910PM cells in vitro and vivo.

METHODSCCK-8 assay was used to detect the inhibitoty effect of Xiaoaiping alone or in combination with cisplatin on the proliferation of human ovarian cancer HO-8910PM cells. Flow cytometry was used to detect the apoptosis and cell cycle distribution. Transwell migration test was used to assay the effect of drugs on the cell invasive capability. Changes of the tumor volume in nude mice were observed to evaluate the antitumor effects in vivo.

RESULTSCCK-8 assay Xiaoaiping alone or combined with cisplatin could inhibit the proliferation of HO-8910PM cells with a dose-dependent manner. The inhibition rates of Xiaoaiping combined with cisplatin were (53.4±3.0)%, significantly increased than those with single drug (P<0.05). Flow cytometry showed that G0/G1 fraction was increased respectively from (64.2±1.6)% to (74.1±1.6)% and (68.6±1.6)%. The percentages of apoptotic cells were increased from (2.2±1.6)% to (16.1±1.6)%, (35.6±1.6)% after treated with Xiaoaiping, Cisplatin and combination drugs (P<0.05 for all). Transwell chamber with matrigel assay showed that number of cells penetrating through membrane in HO-8910PM cells was (89.2±20.7)/HPF in the drug combination group, significantly less than that in the control group(187.2±24.6)/HPF, Xiaoaiping(141.8±13.7 )/HPF or cisplatin group (155.8±19.4)/HPF (P<0.01 for all). The inhibition rate of drug combination group in the nude mouse transplanted tumors, compared with that of single Xiaoaiping and cisplatin group, was increased significantly (59.0% vs. 23.4% and 34.2%), (P<0.01 for both).

CONCLUSIONThe results of our in vitro and vivo experiments indicate that Xiaoaiping can inhibit cell proliferation, increase G0/G1 arrest, promote apoptosis, inhibit cell migration of human ovarian cancer HO-8910 PM cells, and can synergistically enhance the antitumor activity of cisplatine.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Mice, Nude ; Neoplasm Invasiveness ; Ovarian Neoplasms ; drug therapy ; pathology

OBJECTIVETo study the antitumor effects and associated mechanisms of extract of the Smilax china L. rhizome (SCR) on ovarian cancer cells.

METHODSOvarian cancer cells A2780 were treated with different concentrations of SCR extract (SCRE), and compared with controls. Effects on cell growth were evaluated by cell counting kit-8 (CCK-8) assay; proliferation effects by EdU incorporation assay; cell cycle by propidium iodide staining; apoptosis by annexin V-fluorescein isothiocyanate/propidium iodide; cellular distribution of nuclear factor-κB (NF-κB) by immunofluorescence; protein levels of NF-κB, caspase-3, poly-adenosine diphosphate (ADP)-ribose polymerase (PARP), Bcl-2-associated X protein (Bax), cellular inhibitor of apoptosis (cIAP)-1, anti-X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma-extra large (Bcl-XL), B-cell lymphoma-2 (Bcl-2) and AKT by Western blotting; and effects of SCRE combined with cisplatin or adriamycin on A2780 cells by CCK-8 assay.

RESULTSSCRE suppressed A2780 cell proliferation in a dose-dependent manner (P<0.05,P<0.01), arrested cells in G2/M phase and induced apoptosis by activating caspase-3, PARP and Bax. SCRE treatment also correlated with inhibition of NF-κB and downregulation of Bcl-2, Bcl-XL, cIAP-1, XIAP and AKT. SCRE can promote chemosensitivity to cisplatin and adriamycin in A2780 cells (P<0.01).

CONCLUSIONSCR effectively inhibits NF-κB, induces apoptosis and reduces chemoresistance to cisplatin and adriamycin in ovarian cancer cells, which might be its molecular basis for treating ovarian cancer.

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Female ; Humans ; NF-kappa B ; antagonists & inhibitors ; Ovarian Neoplasms ; drug therapy ; pathology ; Plant Extracts ; pharmacology ; Smilax

Gastric metastasis from ovarian carcinoma is extremely rare and the prognosis for patients is poor. We report a case of multimodal treatment improving the survival time of a patient with gastric metastasis from ovarian cancer. A 73-year-old woman with known serous ovarian cancer was admitted to the hospital due to epigastric pain and dyspepsia. On esophagogastroduodenoscopy, a protruding mass was noted at the gastric antrum. She underwent distal gastrectomy with Billroth I anastomosis and lymph node dissection, including the para-aortic lymph nodes. The final pathology revealed gastric metastasis from ovarian serous adenocarcinoma. In this case, after cytoreductive surgery, chemotherapy was performed each time a recurrence was diagnosed, and remission was accomplished. She survived for 108 months after the first diagnosis of the metastatic tumor in the stomach. Multimodal treatment of metastatic lesions since the first diagnosis allowed the patient to survive longer than those in previous reports.
Adenocarcinoma ; Aged ; Combined Modality Therapy* ; Diagnosis ; Drug Therapy ; Dyspepsia ; Endoscopy, Digestive System ; Female ; Gastrectomy ; Gastroenterostomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Metastasis* ; Ovarian Neoplasms* ; Pathology ; Prognosis ; Pyloric Antrum ; Recurrence ; Stomach

In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.
Biomedical Research/*trends ; Endometrial Neoplasms/drug therapy/pathology/surgery ; Female ; Genital Neoplasms, Female/diagnosis/*therapy ; Humans ; Ovarian Neoplasms/drug therapy/pathology/surgery ; Uterine Cervical Neoplasms/drug therapy/pathology/surgery

OBJECTIVETo investigate the effect of estrogen (E2), progesterone(P4), and paclitaxel (taxol) on the growth of primary human ovarian cancer cells in vitro and the expression of Drosha.

METHODSHuman ovarian cancer cells were treated with estrogen, progesterone or in combination with paclitaxel in vitro. The inhibition rate of ovarian cancer cells was assessed by methyl thiazolyl tetrazolium (MTT) assay. Apoptosis rate and cell cycle were determined by FACS analysis. The relative abundence of Drosha expression was detected by real-time quantitative PCR (qRT-PCR) and Western blotting.

RESULTSThe inhibition rate of the estrogen group, progesterone group, paclitaxel group, E2(+)Taxol group, P4(+)Taxol group was (31.53 ± 8.21)%, (25.22 ± 15.50)%, (46.71 ± 4.25)%, (69.46 ± 3.71)%, and (47.35 ± 39.02)%, respectively, significantly higher than that of the control group (0%, P<0.05 for all). Relative to the ER (-) in ovarian cancer cells,Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+) Taxol group,and P4(+)Taxol group was 1.62 ± 0.10,1.60 ± 0.10,1.75 ± 0.16,1.95 ± 0.20, and 1.53 ± 0.06, respectively, significantly higher than that of the control group (1.00, P<0.05 for all). Relative to the ER (+)in ovarian cancer cells,the Drosha mRNA expression level of estrogen group, progesterone group, paclitaxel group, E2(+)taxol group, and P4(+)Taxol group was 1.03 ± 0.14, 1.60 ± 0.09, 1.75 ± 0.16, 1.60 ± 0.10, 1.53 ± 0.06, respectively except estrogen group, significantly higher than that of the control group (1.00, P<0.05). Relative to the ER (-) in ovarian cancer cells, the Drosha protein expression levels of the control group, estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) Taxol group were 0.25 ± 0.05, 0.87 ± 0.30, 0.85 ± 0.38, 1.30 ± 0.21, 1.75 ± 0.83, 1.62 ± 0.82, respectively, with a significant difference between the experimental groups and the control group (P<0.05). Relative to the ER(+)ovarian cancer cells, the Drosha protein expression levels in the estrogen group, progesterone group, paclitaxel group, E2(+) taxol group, and P4(+) taxol group, were 0.28 ± 0.16, 0.85 ± 0.38, 1.30 ± 0.21, 0.94 ± 0.18, and 1.62 ± 0.82, respectively except estrogen group, significantly higher than that of the control group (0.25 ± 0.05, P<0.05 for all).

CONCLUSIONSEstrogen and progesterone in combination with paclitaxel can inhibit the growth of human ovarian cancer cells in vitro, and affect the cell apoptosis rate. Estrogen and taxol can alter the cell cycle. Estrogen and progesterone combined with paclitaxel show tumor suppressing or sensitizing effect through upregulated Drosha expression, and are associated with the estrogen receptor expression.

Antineoplastic Agents, Phytogenic ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; Cell Cycle ; Cell Growth Processes ; drug effects ; Cell Line, Tumor ; Coloring Agents ; Drug Therapy, Combination ; Estrogens ; pharmacology ; Female ; Humans ; In Vitro Techniques ; Ovarian Neoplasms ; chemistry ; drug therapy ; metabolism ; pathology ; Paclitaxel ; pharmacology ; Progesterone ; pharmacology ; RNA, Messenger ; metabolism ; Receptors, Estrogen ; metabolism ; Ribonuclease III ; genetics ; metabolism ; Tetrazolium Salts ; Thiazoles ; Up-Regulation