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Aim: To evaluate prognostic factors in Korean patients with endometrial cancer. Methods: A retrospective analysis was conducted on 248 patients who were staged surgically at the Samsung Medical Center between 1995 and 2004. Survival data were analyzed using Kaplan Mcicr estimates, and multivariate analysis was performed using the Cox regression method. Results: The median age was 51 years (range 21-75), which was younger than in previous studies in Western patients, and the age of 50 years was the cutoff to predict survival. More than half (55.6%) were normal weight or underweight (BMI <25). Multivariate analysis revealed that age, Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage, and histopathology were independent predictors of disease-free survival, and FIGO stage and p53 mutation were independent prognostic factors for disease-specific survival (DSS). The 5-year DSS for patients with stage I, II, III and IV disease was 95.6,93.8,69.8 and 50%, respectively. The 5-year DSS rate for patients with a p53 mutation was 84.4%, compared with 97.1% for patients without. Conclusions: Korean patients with endometrial cancer were younger and had a lower BMI than previously reported. Furthermore, age greater than 50 years was predictive of a poor outcome. Age, FIGO stage, histopathology and a p53 mutation were independent prognostic factors for survival. [ABSTRACT FROM AUTHOR]

Clinical observation of skin metastasis in ovarian cancer cases is relatively uncommon. And distant metastatic skin lesions including the extremities are much rarer still as most metastatic skin lesions are located in the skin in the abdominal wall adjacent to where the primary ovarian tumors exist. We report the case of a 60-year-old woman who presented skin lesions on both lower extremities as a consequence of the metastasis of serous papillary adenocarcinoma of the ovary. She presented with erythematous and painful cutaneous nodules on both upper legs and in the inguinal area 42 months after initial diagnosis of ovarian cancer. Skin biopsy revealed metastasis of adenocarcinoma in the dermis. She was treated with surgical excision and systemic chemotherapy. Literature review has suggested that a combined modality approach including surgical excision and chemotherapy may be useful in the management of skin metastases due to ovarian cancer. [ABSTRACT FROM AUTHOR]

Thymosinβ10 (Tβ10) regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ10 diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.Tβ10, that can overexpress the Tβ10 gene in cancer cells. This was accomplished by replacing the native Tβ10 gene promoter with the human TERT promoter in Ad.TERT.Tβ10. We investigated the cancer suppression activity of Tβ10 and found that Ad.TERT.Tβ10 strikingly induced cancer-specific expression of Tβ10 as well as apoptosis in a co-culture model of human primary ovarian cancer cells and normal fibroblasts. Additionally, Ad.TERT.Tβ10 decreased mitochondrial membrane potential and increased reactive oxygen species (ROS) production. These effects were amplified by co-treatment with anticancer drugs, such as paclitaxel and cisplatin. These findings indicate that the rise in ROS production due to actin disruption by Tβ10 overexpression increases apoptosis of human ovarian cancer cells. Indeed, the cancer-specific overexpression of Tβ10 by Ad.TERT.Tβ10 could be a valuable anticancer therapeutic for the treatment of ovarian cancer without toxicity to normal cells. [ABSTRACT FROM AUTHOR]

The article evaluates the toxicity and efficacy of belotecan combined with carboplatin in patients with recurrent epithelial ovarian cancer (EOC). The researchers found grades 3 and 4 hematologic toxicities such as neutropenia, anemia, and thrombocytopenia. Findings also revealed that hematologic toxicity was the most common side effect of belotecan and carboplatin therapy.

Background: The objective of the study was to compare the perioperative outcomes, including the operative time, length of hospital stay, and postoperative pain, of a single-port-access laparoscopic-assisted vaginal hysterectomy (SPA-LAVH) and conventional LAVH. Methods: This is a retrospective case–control study. A single surgeon performed 43 SPA-LAVH (cases) between May 2008 and February 2009, and 43 conventional LAVH between September 2005 and April 2008 (controls). Data of the SPA-LAVH cases were collected prospectively into our data registry and we reviewed the data of controls on chart. Results: The demographic parameters, except a history of vaginal delivery, were comparable between the two groups. The SPA group was associated with a history of fewer vaginal deliveries (SPA, 63%; conventional, 84%; p = 0.03). The two groups were comparable with respect to indications for surgery, failed cases from planned procedures, cases requiring additional procedures, and cases needing transfusion. The operative time, estimated blood loss (EBL), drop in hemoglobin preoperatively to postoperative day 1, and postoperative hospital stay were comparable between both groups. SPA-LAVH was associated with reduced postoperative pain. The VAS-based pain scores 24 h (SPA, 2.5 ± 0.7; conventional, 3.5 ± 0.8; p < 0.01) and 36 h after surgery (SPA, 1.7 ± 1.2; conventional, 2.9 ± 1.1; p < 0.01) were lower in the SPA group. There were no complications, including reoperation, adjacent organ damage, and any postoperative morbidity, in both groups. In addition, we have encountered no umbilical complications to date using SPA. Conclusions: Our study demonstrated that SPA-LAVH has comparable operative outcomes to conventional LAVH and the postoperative pain was decreased significantly in the SPA group 24 and 36 h after surgery. [ABSTRACT FROM AUTHOR]

Aim: To better predict treatment responses for managing bulky cervical carcinoma with neoadjuvant chemotherapy (NAC). Methods: The expression of p-STAT3 was analyzed by immunohistochemistry using paraffin-embedded pretreatment cervical biopsy tissues. The study included 29 patients with bulky IB to IIA cervical squamous cell carcinoma treated with NAC. Results: Twenty (69.0%) of 29 patients were scored as p-STAT3-positive. Pathological response to chemotherapy (complete response or residual tumor with less than 3 mm stromal invasion) was observed in eight patients (27.6%). The p-STAT3-positive patients had a longer disease-free survival compared to p-STAT3-negative patients ( P = 0.03), though they had more frequent clinical nodal involvement ( P = 0.046). Conclusion: Pretreatment assessment of p-STAT3 expression may provide additional information for the identification of patients with cervical cancer who have a favorable prognosis. [ABSTRACT FROM AUTHOR]

SUMOylation of transcription factors often attenuates transcription activity. This regulation of protein activity allows more diversity in the control of gene expression. Interferon regulatory factor-1 (IRF-1) was originally identified as a regulator of IFN-α/β. and its expression is induced by viral infection or IFN stimulation. Accumulating evidence supports the theory that IRF-1 functions as a tumor suppressor and represses the transformed phenotype. Here we report that the level of SUMOylated IRF-1 is elevated in tumors. Site-directed mutagenesis experiments disclose that the SUMOylation sites of IRF-1 are identical to the major ubiquitination sites. Consequently. SUMOylated IRF-1 displays enhanced resis- tance to degradation. SUMOylation of IRF-1 attenuates its tran- scription activity, and SUMOylated IRF-1 inhibits apoptosis by repression of its transcriptional activity. These data support a mechanism whereby SUMOylation of IRF-1 inactivates its tumor suppressor function, which facilitates resistance to the immune response. [ABSTRACT FROM AUTHOR]

Celecoxib, a selective cyclooxygenase 2 inhibitor, is known to have anti-inflammatory activity and to induce apoptosis in various types of cancer cells. Here, we examined the molecular mechanism of celecoxib-induced apoptosis in cervical cancer cell lines (HeLa, CaSki and C33A). Screening of a microarray cDNA-chip containing 225 different genes revealed that growth arrest and DNA damage inducible gene (GADD153), a transcription factor involved in apoptosis, showed the strongest differential expression following celecoxib treatment in all three cervical cancer cell lines. Notably, siRNA-induced silencing of GADD153 suppressed celecoxib-induced apoptosis in all the three cell lines, and exogenous expression of GADD153 triggered apoptosis in cervical cancer cells in the absence of other apoptotic stimuli. A luciferase reporter gene assay and mRNA stability tests revealed that expression of GADD153 was regulated at both the transcriptional and post-transcriptional levels following celecoxib treatment. The region between −649 and −249, containing an intact C/EBP-ATF binding site, was required for the basal activity and celecoxib-induced stimulation of GADD153 promoter activity. Also, mRNA stability test showed that celecoxib prolonged the half-life of GADD153 mRNA. In terms of signaling pathway, addition of the NF-κB inhibitor, N-tosyl-l phenylalanyl-chloromethyl ketone (TPCK), had no effect on GADD153 expression levels. Celecoxib treatment induced Bak expression, whereas cell treated with siGADD153 or TPCK showed lower levels of celecoxib-induced Bak up-regulation. These novel findings collectively suggest that GADD153 may play a key role in celecoxib-induced apoptosis in cervical cancer cells by regulating the expression of proapoptotic proteins such as Bak. [ABSTRACT FROM AUTHOR]

Celecoxib, a selective cyclooxygenase-2 inhibitor, is known to possess anti-inflammatory activity and also induces apoptosis in various types of cancer cells. Here, we examined the molecular mechanism of celecoxib-induced apoptosis in cervical cancer cell lines (HeLa, CaSki and C33A). Screening of a cDNA microarray chip containing 225 different genes revealed that GADD153 (growth arrest and DNA damage inducible gene), a transcription factor involved in apoptosis, showed the strongest differential expression following celecoxib treatment in all three cervical cancer cell lines. Notably, siRNA-induced silencing of GADD153 suppressed celecoxib-induced apoptosis in all three cell lines, and exogenous expression of GADD153 triggered apoptosis in cervical cancer cells in the absence of other apoptotic stimuli. A luciferase reporter gene assay and mRNA stability tests revealed that the expression of GADD153 was regulated at both the transcriptional and post-transcriptional levels following celecoxib treatment. The region between −649 and −249, containing an intact C/EBP-ATF binding site, is required for celecoxib-induced stimulation of GADD153 promoter activity. In terms of signaling pathway, addition of the NF-κB inhibitor, N-tosyl-l-phenylalanyl-chloromethyl ketone, had no effect on GADD153 expression levels. Celecoxib treatment induced Bak expression, whereas cell transfected with siGADD153 showed lower levels of celecoxib-induced Bak upregulation. These novel findings collectively suggest that GADD153 may play a key role in celecoxib-induced apoptosis in cervical cancer cells by regulating the expression of proapoptotic proteins such as Bak. [ABSTRACT FROM AUTHOR]

Purpose: Galectin-3 is expressed widely in epithelial and immune cells and the level of expression varies in many cancer cells relative to the normal tissues from which they arise. We investigated whether the expression of galectin-3 is associated with the progression of cervical neoplasia. Methods: Galectin-3 expression was evaluated in fresh frozen tissues of cervical carcinoma using real-time quantitative RT-PCR. In addition, galectin-3 expression was evaluated at the protein level by immunohistochemistry in 90 formalin-fixed paraffin-embedded cervical tissues, 10 normal cervical specimens, 20 low-grade squamous intraepithelial lesions (LSILs), 20 high-grade squamous intraepithelial lesions (HSILs), and 40 invasive squamous cell carcinomas (ISCCs). Results: Real-time quantitative RT-PCR revealed that galectin-3 expressions in tumor cells were significantly downregulated compared with corresponding normal tissue ( P=0.005). Moreover, immunohistochemistry showed that galectin-3 expression was strong in all normal cervical squamous epithelia and gradually decreased in accordance with the histopathologic grades in order LSIL > HSIL > ISCC ( P<0.001). Conclusions: These data constitute the first observation that the expression of galectin-3 is downregulated in cervical cancer tissues and suggest that the decreased expression of this galactoside-binding lectin is associated with the progression of cervical neoplasia. [ABSTRACT FROM AUTHOR]

Aim: This study was performed to evaluate the efficacy of neoadjuvant chemotherapy (NAC) with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who were inadequate for primary optimal surgery. Methods: Patients with histologically confirmed epithelial ovarian cancer at International Federation of Gynecology and Obstetrics stages IIIc/IV that was unresectable according to computed tomography findings were eligible for this study. Three cycles of paclitaxel plus cisplatin NAC were administered and the response was evaluated. Patients were then selected for interval debulking surgery or three cycles of additional chemotherapy with the same regimen according to the resectability and response. Interval debulking surgery followed by second-line chemotherapy was applied to patients with no response to NAC. During the same period, patients who did not agree to the protocol were treated by the conventional method of tumor debulking surgery followed by adjuvant chemotherapy, and served as the control group. A comparison of both groups of patients was carried out. Results: A total of 40 patients were involved in the study. All patients were evaluable. Eighteen patients underwent NAC and 22 patients were treated by conventional therapy. Optimal debulking was possible in 14 patients (77.8%) in the NAC group and in 10 patients (45.5%) in the conventional therapy group ( P = 0.04). The mean estimated blood loss was 620 cc (range: 300–1500 cc) in the NAC group and 1061 cc (range: 300–3500 cc) in the conventional therapy group ( P = 0.04). However, no significant differences were found in the disease-free and overall survival rates between the two groups ( P = 0.48 and P = 0.61, respectively). Conclusion: NAC provided a higher rate of optimum cytoreduction and equivalent survival with less invasive surgery and reduced morbidity compared with conventional therapy in patients with advanced epithelial ovarian cancer inadequate for primary optimum surgery. Therefore, NAC may be a valuable alternative treatment for these patients. [ABSTRACT FROM AUTHOR]

Evaluates the biological significance of phospholipase c β1 gene mutation in mouse sperm in the acrosome reaction, fertilization and embryo development. Reduction in acrosome reaction rate, fertilization rate and embryo development rate; Increase in the intracellular calcium concentration; Requisite of acrosomal exocytosis.

High quality gallium sulfide II (GaS) and gallium sulfide III () thin films on /Si substrates were simultaneously grown by using physical vapor deposition with GaS powder as a single precursor. By controlling the substrate temperature, we can selectively grow either GaS or Ga2S3 thin films on SiO2/Si substrates. Relatively high and low substrate temperature conditions resulted in Ga2S3 and GaS thin films, respectively. The synthesized thin films were characterized by x-ray diffraction, Raman spectroscopy, field emission scanning electron microscopy, atomic force microscopy, and x-ray photoelectron spectroscopy analyses. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of this study was to evaluate the clinicopathological features of minimal deviation adenocarcinoma (MDA) and to analyze its prognostic factors.MethodsWe retrospectively analyzed the medical records of 17 patients who were diagnosed with MDA at a single institution between January 2005 and December 2015.ResultsThe median age of the patients was 47.7 years (33–75 years). MDA was diagnosed in 7 patients (41.2%) before performing definitive surgery. Stage IB disease was diagnosed in 12 patients (70.6%) and advanced stage disease (stage II: 3, stage III: 2) in 5. MDA was incidentally diagnosed following hysterectomy for benign conditions in 6 patients. Adjuvant therapy was administered to 13 patients (76.5%). During median follow-up over 33.6 months (7–99 months), 11 patients (64.7%) showed no evidence of disease, 6 (35.3%) showed persistent or recurrent disease and 5 died of the disease. Peutz-Jeghers syndrome was not suspected in any patient, and no mutation was detected in the 3 patients who underwent genetic testing. Univariate analysis showed that advanced stage disease (P=0.016) and lymphovascular space invasion (P=0.002) demonstrated a statistically significant association with poor overall survival (OS) rates. Advanced stage disease continued to show a significant association with poor OS rates (hazard ratio, 2.92; 95% confidence interval, 1.097–7.746; P=0.032) even after multivariate analysis.ConclusionEarly diagnosis is important to manage MDA. Clinicians should consider MDA among the differential diagnoses in patients with a suspicious clinical presentation even with negative cervical screening tests.

Thymosin β-10 (TB10) is an actin monomer-sequestering peptide that consists of 43 amino acid residues and that tends to form a-helical structures. Previously, we showed that the overexpression of TB10 dramatically increases the frequency of apoptosis in human ovarian cancer cells. To identify the critical residues responsible for TB10-mediated apoptosis, we used a series of computational methods. First, a three-dimensional structure of human TB10 was constructed using the homology modeling method with the calf thymosin β-9 NMR structure as a template. Although the sequences of both of these structures are almost identical, 200-ps molecular dynamics simulation results showed that their secondary structures differ. Analyses of molecular dynamics snapshot structures suggested that the TB10 structure is conformationally more complicated than the TB9 structure. The conserved 17LKKTET22 motif region of TB10 was tested by Ala and Set scanning mutagenesis using computational and biochemical methods, and 12 mutants were transfected into cancer cell lines and tested for their effects on growth arrest. Of the 12 mutants examined, only the Thr20 to Ser20 mutation showed reduced growth arrest. These results strongly suggest that Thr20 is specifically required for actin sequestration by TB10 in ovarian cancer cells. These results may provide useful information for the development of a new ovarian cancer therapy. [ABSTRACT FROM AUTHOR]