HOXA­AS3 induces tumor progression through the epithelial­mesenchymal transition pathway in epithelial ovarian cancer.

HOXA cluster antisense RNA 3 (HOXA­AS3) is considered to be involved in several malignancies, however, its biological function in the progression of epithelial ovarian cancer (EOC) remains unclear. The present study compared the expression of HOXA­AS3 in ovarian cancer and normal ovarian tissues and analyzed the association between the expression of HOXA­AS3 and the survival outcomes of patients with ovarian cancer. RNA interference was used to suppress HOXA­AS3 expression in ovarian cancer cell lines in order to demonstrate the function of HOXA­AS3 in ovarian cancer progression. The associations between HOXA­AS3 and epithelial­mesenchymal transition (EMT) markers were explored to verify the mechanism of action of HOXA­AS3 in ovarian cancer. The results of the present study revealed that ovarian cancer tissues exhibited higher HOXA­AS3 expression than normal ovarian tissues. Clinical data indicated that HOXA­AS3 was a significant predictor of progression­free survival and overall survival. Patients with high HOXA­AS3 expression had a poorer prognosis than patients with low HOXA­AS3 expression. In vitro experiments using HOXA­AS3­knockdown ovarian cancer cell lines demonstrated that HOXA­AS3 knockdown inhibited cell proliferation and migration. HOXA­AS3 was a potent inducer and modulator of the expression of EMT pathway­related markers and interacted with both the mRNA and protein forms of HOXA3. Collectively, the findings of the present study demonstrated that HOXA­AS3 expression is associated with ovarian cancer progression and thus, may be employed as a prognostic marker and therapeutic target in EOC.

Prognostic Significance of Clinical Factors Including BRCA Mutation in Epithelial Ovarian, Peritoneal, Fallopian Tube Cancer.

BACKGROUND/AIM: We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. PATIENTS AND METHODS: We included patients who had been diagnosed with and treated for epithelial ovarian, peritoneal, or fallopian tube cancer and had undergone germline BRCA testing in six hospitals between January 2012 and December 2019. RESULTS: Of the 378 identified patients, 76 (20.1%) carried a BRCA1/2 mutation. Progression-free survival (PFS) and overall survival (OS) did not differ between patients with and without BRCA1/2 mutation. Multivariate analysis for 18 months after the primary treatment showed higher PFS in the BRCA1/2 mutation group (p=0.024). Subgroup analysis in patients with high-grade serous carcinoma showed that BRCA1/2 mutation was an independent favorable prognostic factor for PFS (p=0.035). Subgroup analysis of patients with stage III or IV disease demonstrated an independent gain in PFS in patients with BRCA1/2 mutation (p=0.015). Neoadjuvant chemotherapy as a primary treatment was related to poor PFS (p<0.001) and reduced OS (p=0.005). CONCLUSION: Having a germline BRCA1/2 mutation improved short-term PFS in patients with epithelial ovarian, peritoneal, or fallopian tube cancer. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.

Informed consent forms for gynecologic cancer surgery: recommendations from the Korean Society of Gynecologic Oncology.

The sociomedical environment is changing. In the traditional physician-patient relationship, the physician was authoritative and the patient was obedient. The contractual relationship featured patient consent to the physician's decision. Today, the physician must explain fully the planned medical treatment, and any alternative, to the patient, who has the right to choose her treatment after considering the benefits and side-effects. The Korean Society of Gynecologic Oncology (KSGO) thus decided to standardize the surgical consent forms to meet the legal requirements of modern medicine, improve patient understanding of the surgical details, and protect medical staff from legal disputes. To determine the format and content, subcommittees for each cancer type collected and reviewed all relevant articles and the current consent forms of domestic medical institutions. After several meetings, 16 basic items to be included for each type of gynecologic cancer were selected. Also, to help patients understand the surgical details, figures were included. The revised forms were legally reviewed in terms of the appropriateness of the format and content. We also developed English versions to provide adequate information for foreign patients. We hope that these efforts will promote trust between patients and physicians, and contribute to effective treatment by laying a foundation of mutual respect.

Informed consent forms for gynecologic cancer surgery: recommendations from the Korean Society of Gynecologic Oncology.

The sociomedical environment is changing. In the traditional physician-patient relationship, the physician was authoritative and the patient was obedient. The contractual relationship featured patient consent to the physician's decision. Today, the physician must explain fully the planned medical treatment, and any alternative, to the patient, who has the right to choose her treatment after considering the benefits and side-effects. The Korean Society of Gynecologic Oncology thus decided to standardize the surgical consent forms to meet the legal requirements of modern medicine, improve patient understanding of the surgical details, and protect medical staff from legal disputes. To determine the format and content, subcommittees for each cancer type collected and reviewed all relevant articles and the current consent forms of domestic medical institutions. After several meetings, 16 basic items to be included for each type of gynecologic cancer were selected. Also, to help patients understand the surgical details, figures were included. The revised forms were legally reviewed in terms of the appropriateness of the format and content. We also developed English versions to provide adequate information for foreign patients. We hope that these efforts will promote trust between patients and physicians, and contribute to effective treatment by laying a foundation of mutual respect.

Long Non-coding RNA LOC285194 Promotes Epithelial Ovarian Cancer Progression via the Apoptosis Signaling Pathway.

BACKGROUND/AIM: To explore the molecular mechanism and clinical significance of a newly identified lncRNA LOC285194 in epithelial ovarian cancer (EOC). MATERIALS AND METHODS: LOC285194 transcript levels were analyzed in EOC cells compared to normal cells. Small interfering RNAs were used to suppress LOC285194 expression. Levels of apoptosis-related proteins were determined by western blot. LOC285194 expression in ovarian cancer and non-tumor tissues were compared with clinicopathologic and survival data. RESULTS: Knockdown of LOC285194 decreased cell migration and proliferation, enhanced reactive oxygen species production and resulted in increased levels of proteins of the extrinsic apoptotic signaling pathway. LOC285194 expression level was higher in ovarian cancer tissues compared to control. Overall survival was significantly shorter in patients with high LOC285194 expression. Lymph node metastasis and high LOC285194 expression were significant prognostic factors of mortality (HR=4.614 and 5.880; p=0.026 and p=0.002, respectively). CONCLUSION: LOC285194 can promote the progression of EOC via an anti-apoptotic mechanism. It may serve as a novel biomarker for predicting prognosis of EOC.

Dental Management of Congenital Granular Cell Lesion and Neonatal Teeth: A Case Report.

Congenital granular cell lesion (CGCL) is a rare benign oral cavity tumor in infants. Neonatal teeth are also rare dental anomalies that appear during the first month of life. This report describes a case of eruption of neonatal teeth after surgical excision of CGCL. Surprisingly, residual neonatal teeth erupted after extraction of the neonatal teeth. If neonatal teeth are mobile, they should be carefully extracted with curettage of the underlying tissues of the dental papilla; failure to curette the socket might result in eruption of odontogenic remnants. If neonatal teeth were exfoliated, parents should be informed of the need for regular checkups with a dentist due to possibility of development of residual neonatal teeth.

Knockdown of E2F4 suppresses the growth of ovarian cancer cells through the cell cycle pathway.

Ovarian cancer remains one of the major causes of death from gynecologic cancer in developed countries. The E2F family has been shown to have a central role in the control of cell proliferation, differentiation, and cell cycle progression in various types of cancer. Despite advances in cancer research, the carcinogenic role of E2F transcription factor 4 (E2F4) in ovarian cancer remains unclear. In this study, we investigated the underlying molecular mechanism of E2F4 in human ovarian cancer cells (OCC). E2F4 expression was demonstrated by quantitative real time polymerase chain reaction (qRT-PCR) in OCC. The alterations of expression values were determined using 2(-ΔΔCt) method. The effects of suppressing E2F4 on cell proliferation, migration, and differentiation were evaluated by cell proliferation assay, colony formation assay and wound healing assay in vitro. Overexpression of E2F4 was found at both mRNA and protein levels in OCC. Small interfering RNA was used to suppress E2F4 expression. Depletion of E2F4 inhibited cell proliferation and suppressed the cell migration and colony formation ability compared to controls. The expression of cell cycle machinery including cyclin A, cyclin D and cyclin dependent kinase 2 (CDK2) was increased after E2F4 knockdown. E2F4 modulates ovarian cancer cell proliferation and migration through cell cycle components including cyclin A, cyclin D, and CDK2. Our findings indicate that E2F4 may serve as a valuable candidate and therapeutic target for ovarian cancer treatment in regard to cell cycle control.

Secondhand smoke exposure, diabetes, and high BMI are risk factors for uterine cervical cancer: a cross-sectional study from the Korea national health and nutrition examination survey (2010-2018).

BACKGROUND: Human papilloma virus infection and tobacco smoking are the major risk factors for cervical cancer. There are limited studies searching other risk factors for cervical cancer and the results are not consistent. This study investigated the relations between cervical cancer and possible risk factors, including secondhand cigarette smoke exposure, diabetes, body mass index (BMI), and work schedule. METHODS: In this cross-sectional study, 29,557 women completed a cervical cancer questionnaire and were selected using 2010-2018 data from the Korea National Health and Nutrition Examination Survey. Details in secondhand smoke exposure, diabetes, BMI, and work schedule were assessed with participants' health interviews and health-related surveys. RESULTS: Two hundred sixty-two women (0.89%) in the sample were diagnosed with cervical cancer. Domestic secondhand smoke exposure, diabetes, and high BMI significantly increased cervical cancer risk. Respective odds ratios and 95% confidence intervals were: 1.547 (1.042-2.297), 2.156 (1.535-3.027), and 1.036 (1.006-1.067). Weekly work hours, and work schedule were not significantly related to cervical cancer incidence. CONCLUSION: Among Korean women, passive exposure to cigarette smoke at home, diabetes, and high BMI increase risk for cervical cancer.

Risk Factors for Early Childhood Caries: An Umbrella Review.

Purpose: The purpose of this umbrella review was to summarize and evaluate the available evidence concerning risk factors for early childhood caries (ECC). Methods: Literature searches were performed until July 2020 in Medline, Web of Science, and EMBASE databases. Systematic reviews were selected, and their methodological qualities were assessed using the AMSTAR 2 tool (16 items). Results: A total of 977 articles for possible inclusion were identified, and 15 studies were finally selected for qualitative analysis. In these 15 studies, the risk of bias varied from critically low to high. The included studies reported risk factors for ECC such as dietary factors, mutans streptococci, low maternal education, maternal age, low family income and parental education level, low social class, enamel defects, obesity, the presence of dentinal caries, presence of Candida albicans, moderate to late preterm birth, and prenatal maternal cigarette smoking. Conclusions: The potential risk factors for early childhood caries are enamel defects, high levels of mutans streptococci, the presence of dentinal caries, increased consumption of soda, daily intake of sugary snacks, and obesity. In the future, longitudinal studies are needed to explore the potential relationship between these risk factors and ECC.

Low serum T3 levels are associated with false-positive results when using the risk of ovarian malignancy algorithm (ROMA) in women with benign ovarian disease.

OBJECTIVE: We investigated factors that could cause false-positive results when using the risk of ovarian malignancy algorithm (ROMA) for assessing ovarian cancer risk. MATERIALS AND METHODS: ROMA scores were calculated from patients followed surgery to remove a pelvic mass. We compared a false-positive group with a true-negative group of ROMA scores. RESULTS: We analyzed 324 patients using medical records. There were 22 with an epithelial ovarian cancer (EOC), 15 with a borderline ovarian tumor, and 287 with benign disease. Twenty-nine (10.1%) of the patients with benign disease showed high-risk ROMA score (false positive) and 13/37 (35%) patients with EOC, or borderline ovarian tumor showed low ROMA scores (false negatives). The median serum triiodothyronine (T3) level of the false-positive ROMA group in patients with benign disease was lower than in the true-negative ROMA group (p < 0.001) and the estimated glomerular filtration rate (eGFR) was also lower (p = 0.001) in the false-positive ROMA group. Median serum T3 levels in the true-positive ROMA group among patients with EOC, or borderline ovarian tumor were lower than in the false-negative ROMA group (p = 0.043). CONCLUSION: Median serum T3 level and eGFR in the false-positive ROMA group in patients with benign ovarian disease were lower than in the true-negative group.

Dual inhibition of FOXM1 and its compensatory signaling pathway decreased the survival of ovarian cancer cells.

The present study aimed to analyze the compensatory signaling pathways induced by forkhead domain inhibitor­6 (FDI­6), which is a forkhead box protein M1 (FOXM1) inhibitor, in ovarian cancer cells and evaluate the effectiveness of simultaneous inhibition of FOXM1 and the compensatory signaling pathway in decreasing the survival of ovarian cancer cells. The present study identified the proteins involved in the compensatory mechanism activated by FDI­6 in HeyA8 ovarian cancer cells using western blot analysis and a reverse­phase protein array. In addition, a cell viability assay was performed to determine the effects of FDI­6 and the compensatory signaling pathway on cancer cell viability. All experiments were performed in three­dimensional cell cultures. The present study observed that FDI­6 stimulated the upregulation of N­Ras, phosphoprotein kinase Cδ (p­PKCδ) (S664) and HER3 in HeyA8 cells. Tipifarnib as an N­Ras inhibitor, rottlerin as a p­PKCδ (S664) inhibitor and sapitinib as a HER3 inhibitor were selected. The combination of FDI­6 with tipifarnib attenuated the upregulation of N­Ras induced by FDI­6 and the combination of FDI­6 with sapitinib also attenuated HER3 downstream signaling pathway in HeyA8 cells, as shown by on western blot analysis. Rottlerin downregulated p­PKCδ (S664) by inhibiting the activity of a Src­related tyrosine kinase that transfers a phosphate group to PKCδ. Compared with FDI­6 alone, the addition of tipifarnib or rottlerin to FDI­6 was significantly more effective in reducing the growth of HeyA8 cells. However, the combination of FDI­6 and sapitinib did not induce a significant decrease in survival of HeyA8 cells. In conclusion, the addition of tipifarnib or rottlerin to inhibit N­Ras or p­PKCδ (S664), respectively, inhibited the compensatory signaling pathway response induced by FDI­6 in HeyA8 cells. These inhibitors increased the efficacy of FDI­6, which inhibits FOXM1, in reducing ovarian cancer cell viability.

Comparative Survival Outcome of Robot-Assisted Staging Surgery Using Three Robotic Arms versus Open Surgery for Endometrial Cancer.

PURPOSE: There is lack of data on direct comparison of survival outcomes between open surgery and robot-assisted staging surgery (RSS) using three robotic arms for endometrial cancer. The purpose of this study was to compare the overall survival (OS) and disease-free survival (DFS) between open surgery and RSS using three robotic arms for endometrial cancer. MATERIALS AND METHODS: Consecutive women with endometrial cancer who underwent surgery between May 2006 and May 2018 were identified. Robotic procedures were performed using the da Vinci robotic system, and the robotic approach consisted of three robotic arms including a camera arm. Propensity score matching, as well as univariate and multivariate Cox regression of OS and DFS were performed according to clinicopathologic data and surgical method. RESULTS: The study cohort included 423 unselected patients with endometrial cancer, of whom 218 underwent open surgery and 205 underwent RSS using three robotic arms. Propensity score-matched cohorts of 146 women in each surgical group showed no significant differences in survival: 5-year OS of 91% vs. 92% and DFS of 86% vs. 89% in the open and robotic cohorts, respectively (hazard ratio, 1.02; 95% confidence interval, 0.82-1.67). In the univariate analysis with OS as the endpoint, surgical method, age, stage, type II histology, grade, and lymph node metastasis were independently associated with survival. Surgical stage, grade, and type II histology were found to be significant independent predictors for OS in the multivariate analysis. CONCLUSION: RSS using three robotic arms and laparotomy for endometrial carcinoma had comparable survival outcomes.

Risk factors of head and neck cancer mortality compared with those of all-cause and all-cancer mortalities.

This study aimed to clarify the risk factors of head and neck cancer (HNC) mortality, relative to those of all-cause and all-cancer mortalities, using the Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data set. Data from 238 HNC deaths, 14,769 all-cancer deaths, and 38,086 all-cause deaths were extracted during a median follow-up period of 9.5 years. Baseline characteristics were assessed via chi-square tests, t tests, and multivariable logistic regression. HNC mortality was found to be positively associated with male sex, past and current smoking habits, moderate-to-heavy alcohol consumption, and being underweight. In addition, serum gamma-glutamyltransferase level was found to be significantly elevated in cases of HNC mortality. In contrast, obesity, a history of diabetes, and fasting blood glucose levels were found to be inversely associated with overall HNC mortality. Among the HNC subtypes, mortality due to laryngeal cancer was most strongly associated with past and heavy cigarette smoking, and mortality due to oro-/hypopharyngeal cancer was most strongly associated with heavy alcohol consumption. The present study demonstrates that this nationwide, population-based NHIS-HEALS data set can provide useful information for health research and policy development.

Abdominal wall mass suspected of endometriosis: clinical and pathologic features.

OBJECTIVE: To evaluate the clinical and pathological characteristics of lower anterior abdominal wall masses suspicious for endometriosis. METHODS: A retrospective review of 38 patients who underwent surgery for a lower anterior abdominal wall mass suspicious for endometriosis was performed. Those with skin and intraperitoneal masses, lipomas, hernias, and metastatic malignant masses were excluded. Patient age, body mass index, delivery history, dysmenorrhea, and mass size and location were analyzed. RESULTS: Thirty-seven (97.3%) patients had a relevant surgical history, including 35 (92.1%) with a history of cesarean section (C/S). Among the three patients with no history of C/S, 1 underwent total abdominal and another total laparoscopic hysterectomy, and 1 had no previous surgical history. The mean (±standard deviation) size of the abdominal masses was 3.2±1.2 cm. One patient developed a recurrent mass after excision of abdominal wall endometriosis. Trocar site endometrioma was found in one patient following total laparoscopic hysterectomy. According to the final pathology reports, endometriosis was found in 35 (92.1%) of patients. The remaining 3 patients (7.9%) had malignancy: adenocarcinoma, squamous cell carcinoma, and extra-gastrointestinal stromal tumor. Before surgery, only 3 patients (7.9%) underwent fine-needle aspiration biopsy of the masses, which were all postoperatively confirmed to be pathologically benign. CONCLUSION: Although most abdominal wall masses in the present sample were endometriosis occurring at the scar site from a previous operation, 7.9% of patients ultimately exhibited malignancy. Therefore, all patients with suspected anterior wall endometriosis should undergo preoperative biopsy to identify the few that will have an alternative diagnosis.

Factors Associated with Molar-Incisor Hypomineralization: A Population-Based Case-Control Study.

Purpose: The purpose of this case-control study was to investigate the relationship between molar-incisor hypomineralization (MIH) and pre-, peri-, and postnatal conditions of children and mothers in South Korea. Methods: The Korean Academy of Pediatric Dentistry con- ducted this study to examine factors associated with MIH among six- to 13-year-olds. The European Academy of Pediatric Dentistry criteria and self-administered questionnaires associated with MIH were used. Results: In multivariable logistic regression analysis, the odds ratio (OR) of MIH for children whose mothers used health supplements during pregnancy was 0.65 (P=0.009). Also, children with more than three hours of out- door activities per day tended to have a lower MIH (P=0.03) than did those with zero hours of outdoor activity. Additionally, the OR of MIH for children whose mothers smoked during pregnancy was 2.37 (P=0.019) and the MIH found to be 1.33 times more frequent in children with respiratory infections during the first three years of life (P=0.048). Conclusions: Maternal smoking during pregnancy and child's pediatric respiratory infection suffered within three years after birth are factors associated with the MIH among Korean children. Further study is needed because the prevalence of MIH in children whose mothers taking health supplements (vitamins or folic acid or iron) during pregnancy is low.

Diagnostic Accuracy of the Risk of Ovarian Malignancy Algorithm in Clinical Practice at a Single Hospital in Korea.

BACKGROUND: The risk of ovarian malignancy algorithm (ROMA) is used for assessing ovarian cancer risk in women with a pelvic mass. Its diagnostic accuracy is variable. We investigated whether the clinically acceptable minimal sensitivity of >80.0% could be obtained with the suggested cutoff of 7.4%/25.3% for pre/postmenopausal women and with adjusted cutoffs set to a specificity of ≥75.0% or a sensitivity of 95.0%, in a hospital with a lower ovarian cancer (OC) prevalence than previously reported. METHODS: ROMA scores were calculated from measurements of human epididymis protein 4 and cancer antigen 125 in blood specimens from 443 patients with a pelvic mass. The ROMA-based risk group was compared against biopsy (N=309) or clinical follow-up with imaging (N=134) results. The ROMA sensitivity and specificity for predicting epithelial OC (EOC) and borderline ovarian tumor (BOT) were calculated for the suggested and adjusted cutoff values. RESULTS: When targeting BOT and EOC, the prevalence was 7.4% and sensitivity and specificity at the suggested cutoff were 63.6% and 90.7%, respectively. Sensitivity was 81.8% at the 4.65%/13.71% cutoff set to a specificity of 75.0%. When targeting only EOC, the prevalence was 4.1% and sensitivity and specificity at the suggested cutoff were 77.8% and 89.4%, respectively. Sensitivity was 88.9% at the 4.78%/14.35% cutoff set to a specificity of 75.0%. CONCLUSIONS: The sensitivity of ROMA was lower than expected when using the suggested cutoff. When using the adjusted cutoff, its sensitivity reached 80.0%.

Decompression for Unerupted Primary Mandibular Second Molars Associated with Physical Barriers: Case Reports.

Primary impaction of primary teeth might be due to genetic predisposition or physical disturbance including odontoma, supernumerary tooth, and crowded tooth. Among them, calcific deposit or odontoma is commonly associated with primary dentition. Early diagnosis and treatment is the key to prevent complications. However, results of treatment may vary depending on the condition of unerupted tooth. Here we report two clinical cases of unerupted primary mandibular second molars with physical barriers such as compound odontoma and calcific deposit focusing on diagnostic means and the importance of early treatment of these lesions.

Relationship between alcohol consumption and age at menopause: The Korea National Health and Nutrition Examination Survey.

OBJECTIVE: We used data from the 2011-2014 Korean National Health and Nutrition Examination Surveys (KNHANES) to investigate whether the age at menopause is related to alcohol consumption in South Korean women. MATERIALS AND METHODS: This was a cross-sectional study of the data for 940 women who became menopausal within the 3 years preceding the KNHANES. RESULTS: The numbers of nondrinkers, mild to moderate drinkers, and heavy drinkers in this group were 345 (34.7%), 573 (62.2%), and 22 (3%). Body mass index (BMI), smoking, and exercise were adjusted in model 1 and age was additionally adjusted in model 2. The mean ages at menopause were 51.6 ± 0.2, 50.8 ± 0.1, and 50.4 ± 0.5 years (p = 0.0025) in model 1 and 51.7 ± 0.2, 51.1 ± 0.1, and 50.1 ± 0.5 years (p = 0.0018) in model 2 for nondrinkers, mild to moderate drinkers, and heavy drinkers, respectively. BMI, smoking, exercise, educational level, income, duration of menopause, age at menarche, age at first delivery, and gravidity were adjusted in model 3, and the respective mean ages at menopause were 51.3 ± 0.2, 50.7 ± 0.2, and 50.1 ± 0.8 years (p = 0.0402). The population was classified into groups using the Alcohol Use Disorders Identification Test (AUDIT) scores of <5 (n = 778), <10 (n = 108), and ≥10 score (n = 54). The mean ages at menopause according to AUDIT score were 51.3 ± 0.1, 50.5 ± 0.3, and 50.4 ± 0.4 years (p = 0.0222, model 1), 51.4 ± 0.1, 50.8 ± 0.3, and 50.8 ± 0.3 years (p = 0.0261, model 2), and 51.1 ± 0.1, 50.6 ± 0.4, and 49.5 ± 0.6 years (p = 0.0241, model 3) respectively. CONCLUSION: In Korean women, alcohol consumption was associated with younger age at menopause. A higher AUDIT score was also related to younger age at menopause.

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells.

OBJECTIVE: To identify the proteins involved the compensatory adaptive response to paclitaxel in ovarian cancer cells and to determine whether inhibition of the compensatory adaptive response increases the efficacy of paclitaxel in decreasing the viability of cancer cells. METHODS: We used a reverse-phase protein array and western blot analysis to identify the proteins involved in the compensatory mechanism induced by paclitaxel in HeyA8 and SKOV3 ovarian cancer cells. We used a cell viability assay to examine whether inhibition of the proteins involved in the compensatory adaptive response influenced the effects of paclitaxel on cancer cell viability. All experiments were performed in three-dimensional cell cultures. RESULTS: Paclitaxel induced the upregulation of pS6 (S240/S244) and pS6 (S235/S236) in HeyA8 and SKOV3 cells, and pPRAS40 (T246) in HeyA8 cells. BX795 and CCT128930 were chosen as inhibitors of pS6 (S240/S244), pS6 (S235/S236), and pPRAS40 (T246). BX795 and CCT128930 decreased pS6 (S240/S244) and pS6 (S235/S236) expression in HeyA8 and SKOV3 cells. However, pPRAS40 (T246) expression was inhibited only by BX795 and not by CCT128930 in HeyA8 cells. Compared with paclitaxel alone, addition of BX795 or CCT128930 to paclitaxel was more effective in decreasing the viability of HeyA8 and SKOV3 cells. CONCLUSION: Addition of BX795 or CCT128930 to inhibit pS6 (S240/S244) or pS6 (S235/S236) restricted the compensatory adaptive response to paclitaxel in HeyA8 and SKOV3 cells. These inhibitors increased the efficacy of paclitaxel in reducing cancer cell viability.

Does diabetes mellitus have an impact on the prognosis for patients with cervical cancer?

OBJECTIVE: To evaluate the impact of comorbid diabetes mellitus (DM) on prognoses among patients with cervical cancer. METHODS: We analyzed cervical cancer outcomes in patients who treated in two hospitals retrospectively. Patients were divided into those with DM and those without. Clinicopathologic parameters, disease-free survival (DFS), and overall survival (OS) rates were evaluated. RESULTS: Of the 494 patients, 50 had DM. These were more likely to be older than those in the non-DM group and their body mass index (BMI) was higher. They showed higher levels of tumor markers and had more combined diseases. They were less likely to have had surgical treatment. Among these patients, 12 (24%) experienced a recurrence (hazard ratio, HR, 1.484; 95% confidence interval, CI, 0.746-2.951). Differences in DFS did not show statistical significance. In the OS analysis, 11 (22%) in the DM group and 62 (14%) in the non-DM group died (HR, 1.239; 95% CI, 0.606-2.533). No statistically significant differences were also observed for cancer-specific death (HR, 1.246; 95% CI, 0.567-2.737). Those with DM and an adenocarcinoma tended to have an increased risk of dying compared with the non-DM patients with an adenocarcinoma (HR, 3.673; 95% CI, 0.990-13.625), but this difference was not statistically significant (p=0.0518). CONCLUSION: Diabetes mellitus did not have an impact on the prognosis for patients with cervical cancers. In those with an adenocarcinoma, patients with diabetes tended to have an increased risk of dying compared with the non-DM group, but this difference was not statistically significant.