The classification and localization of odontogenic lesions from panoramic radiographs is a challenging task due to the positional biases and class imbalances of the lesions. To address these challenges, a novel neural network, DOLNet, is proposed that uses mutually influencing hierarchical attention across different image scales to jointly learn the global representation of the entire jaw and the local discrepancy between normal tissue and lesions. The proposed approach uses local attention to learn representations within a patch. From the patch-level representations, we generate inter-patch, i.e., global, attention maps to represent the positional prior of lesions in the whole image. Global attention enables the reciprocal calibration of path-level representations by considering non-local information from other patches, thereby improving the generation of whole-image-level representation. To address class imbalances, we propose an effective data augmentation technique that involves merging lesion crops with normal images, thereby synthesizing new abnormal cases for effective model training. Our approach outperforms recent studies, enhancing the classification performance by up to 42.4% and 44.2% in recall and F1 scores, respectively, and ensuring robust lesion localization with respect to lesion size variations and positional biases. Our approach further outperforms human expert clinicians in classification by 10.7 % and 10.8 % in recall and F1 score, respectively.

Introduction/Background To demonstrate that blockade of inhibitory immune checkpoint, PD-1 pathway, is able to enhance the antitumor effects generated by therapeutic HPV vaccine, we tested the therapeutic HPV vaccines and in combination with programmed death- ligand 1 (PD-1) blockade in C57BL/6 mice with bearing the HPV16 E6/E7 transformed syngeneic tumor model, TC-1. Methodology HPV16 E6E7-expressing TC-1 tumor was established in female C57BL/6 mice by injection of 1 × 105 of TC-1 cells subcutaneously. 3 days (estimate, needs to modify based on the tumor growth) later, two groups (5 mice/group) of mice were treated with 10 mg/kg of anti-mouse PD-1 monoclonal antibody (clone 29F.1A12) via intraperitoneal injection. When the tumor size demonstrated smaller from anti-PD-1 antibody treated mice than untreated mice, two groups (one group of untreated and one group of anti-PD-1 antibody treated) of TC-1 tumor-bearing mice were vaccinated with DDV regimen (pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine, TA-HPV). Results Priming twice with an HPV DNA vaccine followed by a single TA-HPV booster immunization induced HPV-E6/E7 cell-mediated immunity and resulted in the clearance of small tumors and an overall survival benefit in mice with larger established tumors. When immunotherapy was combined with PD-1 immune checkpoint blockade, an increased level of anti-tumor activity against large tumors was observed in addition to an improvement in survival. Tumor microenvironment analysis in DDV and PD-1 blockade treated mice generated a comparable boost to E7-specific CD8+ T cell responses. Conclusion Our results provide rationale for future clinical testing of HPV DNA vaccine prime, TA-HPV vaccinia vaccine boost immunization regimen with PD-1 blockade for the control of HPV-associated diseases Disclosures None

Introduction/Background S6 kinase is a protein kinase that is involved in signal transduction. S6 kinase is thought to play an important role in the compensatory adaptive response of various cancers against anti-cancer drug. We examined whether inhibition of phospho-S6 can increase the treatment effect of carboplatin in ovarian cancer. Methodology We used a western blot analysis to pS6 expression after carboplatin treatment and addition of BX795 which is pS6 inhibitor on ovarian cancer cells. We used a cell viability assay to examine whether addition of BX795 to carboplatin increase the therapeutic effect of carboplatin on ovarian cancer cells. C57BL/6 mice were injected intraperitoneally with ID8 mouse ovarian cancer cells. Thirty days after the injection of ID8 cells, mice were treated with PBS (control group), carboplatin, BX795, and carboplatin + BX795. All of drugs were subcutaneously injected into the nuchal region of the mice. For each mouse, body weight, waist length, and ascites amount were measured. Results Carboplatin induced the upregulation of pS6 in ovarian cancer cells. BX795 as inhibitor induced the downregulation of pS6 with concentration dependent pattern on cancer cells. Combination of carboplatin and BX795 induced stronger inhibition of pS6 in ovarian cancer cells compared with carboplatin only. Compared to carboplatin only, additional treatment of BX795 to carboplatin brought the bigger decrease of viability on ovarian cancer cells. However, there was no significant difference between PBL, carboplatin, BX795, and carboplatin + BX795 treatment groups on mean body weight, mean waist length, and mean ascites amount at the sacrifice day. Conclusion Addition inhibition of pS6 by BX795 increased the therapeutic efficacy of carboplatin on ovarian cancer cells. However, increase of therapeutic effect of carboplatin was not showed on mouse model. Disclosures There was no funding for this research. The Authors declare no conflicts of interest.

HOXA cluster antisense RNA 3 (HOXA-AS3) 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 HOXA-AS3 in ovarian cancer and normal ovarian tissues and analyzed the association between the expression of HOXA-AS3 and the survival outcomes of patients with ovarian cancer. RNA interference was used to suppress HOXA-AS3 expression in ovarian cancer cell lines in order to demonstrate the function of HOXA-AS3 in ovarian cancer progression. The associations between HOXA-AS3 and epithelial-mesenchymal transition (EMT) markers were explored to verify the mechanism of action of HOXA-AS3 in ovarian cancer. The results of the present study revealed that ovarian cancer tissues exhibited higher HOXA-AS3 expression than normal ovarian tissues. Clinical data indicated that HOXA-AS3 was a significant predictor of progression-free survival and overall survival. Patients with high HOXA-AS3 expression had a poorer prognosis than patients with low HOXA-AS3 expression. In vitro experiments using HOXA-AS3-knockdown ovarian cancer cell lines demonstrated that HOXA-AS3 knockdown inhibited cell proliferation and migration. HOXA-AS3 was a potent inducer and modulator of the expression of EMT pathway-related markers and interacted with both the mRNA and protein forms of HOXA3. Collectively, the findings of the present study demonstrated that HOXA-AS3 expression is associated with ovarian cancer progression and thus, may be employed as a prognostic marker and therapeutic target in EOC.

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.

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.

Objectives We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer (EOPFTC) with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. Methods Based on the data collected from Clinical Data Warehouse of Catholic university of Korea, we investigated patients who had been diagnosed and treated for EOPFTC, and undergone germline BRCA test in 6 hospitals between January 2012 and December 2019. Results In total, 378 patients were identified and 76 (20.1%) women carried BRCA 1/2 mutation. There was no significant difference in progression-free survival (PFS; p = 0.562) and overall survival (p = 0.677) between BRCA 1/2 mutation and wild-type groups. In multivariate analysis, however, PFS of BRCA 1/2 mutation group for 18 month from primary treatment was significantly superior to wild-type group (p = 0.024). In subgroup analysis for high grade serous carcinoma patients, BRCA 1/2 mutation was an independent favorable prognostic factor for PFS (p = 0.035). Subgroup analysis for stage III to IV disease also demonstrated an independent PFS gain in patients with BRCA 1/2 mutation (p = 0.015). Neoadjuvant chemotherapy as primary treatment was related with poor PFS (p < 0.001) and reduced OS (p = 0.005). Conclusions Germline BRCA 1/2 mutation improved short-term PFS in patients with EOPFTC. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.

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.

The present study aimed to analyze the compensatory signaling pathways induced by forkhead domain inhibitor‑6 (FDI‑6), 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 FDI‑6 in HeyA8 ovarian cancer cells using western blot analysis and a reverse‑phase protein array. In addition, a cell viability assay was performed to determine the effects of FDI‑6 and the compensatory signaling pathway on cancer cell viability. All experiments were performed in three‑dimensional cell cultures. The present study observed that FDI‑6 stimulated the upregulation of N‑Ras, phosphoprotein kinase Cδ (p‑PKCδ) (S664) and HER3 in HeyA8 cells. Tipifarnib as an N‑Ras inhibitor, rottlerin as a p‑PKCδ (S664) inhibitor and sapitinib as a HER3 inhibitor were selected. The combination of FDI‑6 with tipifarnib attenuated the upregulation of N‑Ras induced by FDI‑6 and the combination of FDI‑6 with sapitinib also attenuated HER3 downstream signaling pathway in HeyA8 cells, as shown by on western blot analysis. Rottlerin downregulated p‑PKCδ (S664) by inhibiting the activity of a Src‑related tyrosine kinase that transfers a phosphate group to PKCδ. Compared with FDI‑6 alone, the addition of tipifarnib or rottlerin to FDI‑6 was significantly more effective in reducing the growth of HeyA8 cells. However, the combination of FDI‑6 and sapitinib did not induce a significant decrease in survival of HeyA8 cells. In conclusion, the addition of tipifarnib or rottlerin to inhibit N‑Ras or p‑PKCδ (S664), respectively, inhibited the compensatory signaling pathway response induced by FDI‑6 in HeyA8 cells. These inhibitors increased the efficacy of FDI‑6, which inhibits FOXM1, in reducing ovarian cancer cell viability.

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.

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. (c) 2021 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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, 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, work schedule were assessed from participants’ health interviews and blood test results were used for fasting glucose level and hemoglobin A1c (HbA1c) level.Results: Two hundred sixty-two women (0.89%) in the sample were diagnosed with cervical cancer. Domestic secondhand smoke exposure, diabetes, high fasting glucose level, and high HbA1c significantly increased cervical cancer risk. The respective odd ratios and 95% confidence intervals were: 1.488 (1.002–2.207), 2.369 (1.713–3.274), 1.008 (1.005–1.009), and 1.304 (1.193–1.425). 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, elevated fasting glucose level, and high HbA1c level all increase risk for cervical cancer.

Objective: This study aims to evaluate circulating tumor cells isolated by high gradient magnetic separation of circulating endothelial cells (CECs) as a diagnostic tool for ovarian cancer.Methods: Thirty-six newly diagnosis with pelvic mass who were scheduled for surgery were included in this study.Blood samples were obtained from patients.CECs were identified with fluorescent microscopy by expert cytologists.The diagnostic performance of CECs was compared with the histopathological results.Results: Definite diagnosis showed that twenty-six patients were later diagnosed as having malignant ovarian cancer (69.4%), 5 cancerous patients (19.2%) had metastatic ovarian tumor from gastrointestinal origin, and 10 patients were diagnosed as benign ovarian tumor (30.6%).Serum from patients were extracted for CECs were found in 10 patients.CECs demonstrated modest diagnostic performance for malignant ovarian cancer with accuracy, sensitivity and specificity of 38.9%, 26.9%, and 70.0%, respectively.Conclusion: CECs has low sensitivity.However, the clinical value of CECs in borderline ovarian tumor cases must be further investigated.This technique needs more development to improve sensitivity for diagnostic for ovarian cancer.

ObjectiveTo evaluate the clinical and pathological characteristics of lower anterior abdominal wall masses suspicious for endometriosis.MethodsA 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.ResultsThirty-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.ConclusionAlthough 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.

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.

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.

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%.

Polyurethane (PU) is a versatile polymer used in a wide range of applications. Recently, imparting PU with self-healing properties has attracted much interest to improve the product durability. The self-healing mechanism conceivably occurs through the existence of dynamic reversible bonds over a specific temperature range. The present study investigates the self-healing properties of 1,4:3,6-dianhydrohexitol-based PUs prepared from a prepolymer of poly(tetra-methylene ether glycol) and 4,4-methylenebis(phenyl isocyanate) with different chain extenders (isosorbide or isomannide). PU with the conventional chain extender 1,4-butanediol was prepared for comparison. The urethane bonds in 1,4:3,6-dianhydrohexitol-based PUs were thermally reversible (as confirmed by the generation of isocyanate peaks observed by Fourier transform infrared spectroscopy) at mildly elevated temperatures and the PUs showed good mechanical properties. Especially the isosorbide-based polyurethane showed potential self-healing ability under mild heat treatment, as observed in reprocessing tests. It is inferred that isosorbide, bio-based bicyclic diol, can be employed as an efficient chain extender of polyurethane prepolymers to improve self-healing properties of polyurethane elastomers via reversible features of the urethane bonds.