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Abstract Rapid outbreak of coronavirus disease 2019 (Covid-19) raised major concern regarding medical resource constraints. We constructed and validated a scoring system for early prediction of progression to severe pneumonia in patients with Covid-19. A total of 561 patients from a Covid-19 designated hospital in Daegu, South Korea were randomly divided into two cohorts: development cohort (N = 421) and validation cohort (N = 140). We used multivariate logistic regression to identify four independent risk predictors for progression to severe pneumonia and constructed a risk scoring system by giving each factor a number of scores corresponding to its regression coefficient. We calculated risk scores for each patient and defined two groups: low risk (0 to 8 points) and high risk (9 to 20 points). In the development cohort, the sensitivity and specificity were 83.8% and 78.9%. In the validation cohort, the sensitivity and specificity were 70.8% and 79.3%, respectively. The C-statistics was 0.884 (95% CI 0.833–0.934) in the development cohort and 0.828 (95% CI 0.733–0.923) in the validation cohort. This risk scoring system is useful to identify high-risk group for progression to severe pneumonia in Covid-19 patients and can prevent unnecessary overuse of medical care in limited-resource settings.

Objectives: Two Coronavirus Disease 2019 (COVID-19) outbreaks simultaneously occurred at a church and a long-term care facility in Daegu, South Korea. This study aimed to investigate the epidemiological characteristics of COVID-19 and factors related to severe outcomes. Methods: We enrolled all inpatients diagnosed with COVID-19 between February 21 and April 2, 2020, in Daegu Dongsan Hospital. We analyzed their clinical and demographic data, laboratory parameters, radiological findings, symptoms, and treatment outcomes. Results: Of 694 patients, severe cases accounted for 19.7% (137 patients). No severe case was observed among patients aged ≤19 years. Hypertension was the most common comorbidity (27%), and cough was the most common symptom (59%). Asymptomatic patients accounted for 14.4% of cases. Lymphopenia, lactate dehydrogenase, C-reactive protein, and albumin were associated with severe outcomes. The first outbreak was mostly associated with younger age groups, and asymptomatic patients mostly showed mild progression. In the second outbreak involving a long-term care facility, both the number of severe patients and the mortality rate were higher. Conclusions: The overall mortality in Daegu was low, which might have resulted from large scale mass screening to detect patients and starting appropriate treatment, including hospitalization for severe cases, and quarantine for asymptomatic patients.

ObjectiveThe aims of this study were to introduce surgical guidelines, and to evaluate the feasibility and safety of a robotic single-site staging (RSSS) operation for early-stage endometrial cancer.MethodsPatients with a preoperative diagnosis of endometrial cancer (International Federation of Gynecology and Obstetrics stages IA to IB) from endometrial curettage and preoperative imaging studies were selected at Dongsan Medical Center from March 2014 to November 2015. All surgical procedures, including hysterectomy, salpingo-oophorectomy, bilateral pelvic node dissection, and cytology aspiration, were performed by robotic single-site instruments (da Vinci Si® surgical system; Intuitive Surgical, Sunnyvale, CA, USA).ResultsA total of 15 women with early-stage endometrial cancer underwent the RSSS operation. The median patient age and body mass index were 53 years (range, 37–70 years) and 25.4 kg/m2 (range, 18.3–46.4 kg/m2). The median docking time, console time, and total operative time were 8 minutes (range, 4–15 minutes), 75 minutes (range, 55–115 minutes), and 155 minutes (range, 125–190 minutes), respectively. The median retrieval of both pelvic lymph nodes was 9 (range, 6–15). There were no conversions to laparoscopy or laparotomy.ConclusionThe RSSS operation is feasible and safe in patients with early-stage endometrial cancer. In this study, operative times were reasonable, and the surgical procedure was well-tolerated by the patients. Further evaluation of patients with early-stage endometrial cancer should be performed in large-scale comparative studies using the laparoendoscopic, single-site staging operation to confirm the safety and benefits of the RSSS operation for early-stage endometrial cancer.

Background: Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a rare tumor belonging to a group of smooth muscle tumors that possess both benign and malignant features, complicating the diagnosis.Case report.We present the case of a 41-year-old primiparous woman who complained of heavy menstrual bleeding and severe pressure symptoms in the lower abdomen for 3 months. Magnetic resonance imaging revealed a large intramural myoma measuring 35 × 25 cm in the lower uterine corpus. A laparotomy including total hysterectomy was performed. Grossly, the uterine mass measured 38.5 × 35.4 × 20.4 cm in the largest diameter and weighed 18.3 kg. Pathological analysis revealed a uterine mass diagnosed as a smooth muscle tumor of uncertain malignant potential. The patient was normally discharged 7 days after surgery and decided to follow up without further treatment. At the time of this report, the patient had been followed up as an outpatient for 18 months without recurrence. Conclusion: Giant uterine STUMP is extremely rare and difficult to diagnose on physical examination and imaging findings alone. It is important to consider the possibility of an underlying malignancy when performing a preoperative examination and to perform frozen biopsy if malignancy is suspected. During follow-up, patients should undergo consultation with a gynecologic oncologist and should be surveilled closely because of the possibility of recurrence or metastasis.

Metastasis is responsible for 90% of human cancer mortality, yet it remains a challenge to model human cancer metastasis in vivo. Here we describe mouse models of high-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), the most common and deadliest human ovarian cancer type. Mice genetically engineered to harbor Dicer1 and Pten inactivation and mutant p53 robustly replicate the peritoneal metastases of human HGSC with complete penetrance. Arising from the fallopian tube, tumors spread to the ovary and metastasize throughout the pelvic and peritoneal cavities, invariably inducing hemorrhagic ascites. Widespread and abundant peritoneal metastases ultimately cause mouse deaths (100%). Besides the phenotypic and histopathological similarities, mouse HGSCs also display marked chromosomal instability, impaired DNA repair, and chemosensitivity. Faithfully recapitulating the clinical metastases as well as molecular and genomic features of human HGSC, this murine model will be valuable for elucidating the mechanisms underlying the development and progression of metastatic ovarian cancer and also for evaluating potential therapies.

Uterine fibroids (leiomyomas or myomas), benign monoclonal tumors, are the most common benign tumors in women. Heavy or prolonged menstrual bleeding, abnormal uterine bleeding, resultant anemia, pelvic pain, infertility, and/or recurrent pregnancy loss are generally associated with uterine fibroids. Although curative treatment of this tumor relies on surgical therapies, medical treatments are considered the first-line treatment to preserve fertility and avoid or delay surgery. The aim of this review is to provide available and emerging medical treatment options for symptomatic uterine fibroids. Literature review and consensus of expert opinion. Many uterine fibroids are asymptomatic and require no intervention, although it is advisable to follow-up patients to document stability in size and growth. Fibroid-associated symptoms include heavy menstrual bleeding and pain or pelvic discomfort. The association between infertility and fibroids increases with age. Treatment options for symptomatic uterine fibroids — include medical, surgical, and radiologically guided interventions. Various medical therapies are now available for women with uterine fibroids, although each therapy has its own advantages and disadvantages. Currently, gonadotrophin-releasing hormone (GnRH) agonists and selective progesterone receptor modulators (SPRMs) are the most effective medical therapies, with the most evidence to support their reduction of fibroid volume and symptomatic improvement in menstrual bleeding. The choice of treatment depends on the patient's personal treatment goals, as well as efficacy and need for repeated interventions.

Abstract Background We aimed to evaluate the potential benefits of the Leadership and Coaching for Health (LEACH) program on physical activity (PA), dietary habits, and distress management in cancer survivors. Methods We randomly assigned 248 cancer survivors with an allocation ratio of two-to-one to the LEACH program (LP) group, coached by long-term survivors, or the usual care (UC) group. At baseline, 3, 6, and 12 months, we used PA scores, the intake of vegetables and fruits (VF), and the Post Traumatic Growth Inventory (PTGI) as primary outcomes and, for secondary outcomes, the Ten Rules for Highly Effective Health Behavior adhered to and quality of life (QOL), the Hospital Anxiety and Depression Scale (HADS), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results For primary outcomes, the two groups did not significantly differ in PA scores or VF intake but differed marginally in PTGI. For secondary outcomes, the LP group showed a significantly greater improvement in the HADS anxiety score, the social functioning score, and the appetite loss and financial difficulties scores of the EORTC QLQ-C30 scales from baseline to 3 months. From baseline to 12 months, the LP group showed a significantly greater decrease in the EORTC QLQ-C30 fatigue score and a significantly greater increase in the number of the Ten Rules for Highly Effective Health Behavior. Conclusion Our findings indicate that the LEACH program, coached by long-term survivors, can provide effective management of the QOL of cancer survivors but not of their PA or dietary habits. Trial registration Clinical trial information can be found for the following: NCT01527409 (the date when the trial was registered: February 2012).

A 73-year-old woman was referred to the pulmonology department for abnormal findings on chest computed tomography. She had undergone a laparoscopic staging operation including a hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic node and para-aortic node dissection, and concurrent chemo-radiation therapy for endometrial serous carcinoma stage IIIc cancer 15 months earlier. A follow-up chest computed tomography after the chemotherapy showed that the right lower lobe bronchus was obstructed, and it was necessary to differentiate a primary lung malignancy from a metastasis and secretion. A positron emission tomography revealed an intense hypermetabolic nodule in the right lower lobe bronchus and diffuse hypometabolism of the right lower lobe lung. Bronchoscopy revealed a tumor mass obstructing the right lower lobe bronchus, and an endobronchial biopsy confirmed a metastatic serous carcinoma from the endometrium. We described an endobronchial metastasis from an endometrial carcinoma with various diagnostic images and histology. To the best of our knowledge, this is the first report of an endobronchial metastasis from an endometrial carcinoma in Korea.

Summary: Background: In an interim analysis of this phase 2 trial, adding the GX-188E vaccine to pembrolizumab resulted in manageable toxicity with antitumor activities in patients with recurrent or advanced cervical cancer. Here, we report the final safety and efficacy results after a long-term follow-up at the study's completion. Methods: This open-label, single-arm, phase II trial was conducted in nine hospitals in South Korea (ClinicalTrials.gov identifier, NCT03444376). Eligible patients were aged ≥18 years with recurrent or advanced inoperable cervical cancer, Eastern Cooperative Oncology Group Performance status of 0 or 1, and positivity for HPV 16/18, who failed the available standard-of-care therapy. Patients received intramuscular 2 mg GX-188E at weeks 1, 2, 4, 7, 13, 19, and 46 and intravenous 200 mg pembrolizumab every 3 weeks for up to 2 years or until disease progression. The primary endpoint was the objective response rate (ORR) within 24 weeks. Findings: Between June 19, 2018, and December 24, 2021, 65 patients were enrolled and received at least one dose of the study treatment. Sixty patients received combination treatment with GX-188E and pembrolizumab and underwent efficacy analysis. After a median follow-up of 14.72 months, the confirmed ORR was 35.0% (95% CI, 23.1–48.4). Five patients (8.3%) had a complete response, and 16 (26.7%) had a partial response. In addition, patients with PD-L1-positive and PD-L1-negative tumors had an ORR of 38.9% (95% CI, 23.1–56.5) and 29.2% (95% CI, 12.6–51.1), respectively. The median duration of response of all the patients was 12.3 months (95% CI, 5.3–not reached [NR]). For those with PD-L1-positive tumors, it was 12.3 months (95% CI, 3.5–NR), and for those with PD-L1-negative tumors, it was NR (95% CI, 2.4–NR). The median progression-free survival of the 60 patients was 4.4 months (95% CI, 2.1–8.3), and the median overall survival was 23.8 months (95% CI, 14.0–NR). 22 (33.8%) of 65 patients had treatment-related adverse events (TRAEs) of any grade and four (6.2%) had grade 3–4 TRAEs. No treatment-related deaths occurred. Interpretation: The GX-188E vaccine combined with pembrolizumab in recurrent or advanced HPV-positive cervical cancer was safe and showed a promising overall survival and clinical response rate. This combination therapy might provide a new potential treatment option for patients with recurrent or advanced cervical cancer. Funding: National Cancer Center Onco-Innovation Unit, Korea.

Abstract In this study, we examined the difference in the vaginal microbiota of women infected with human papillomavirus (HPV), according to menopausal status. A total of 75 cervicovaginal swab samples from 38 pre- and 37 postmenopausal women with HPV infection were obtained from the Korean HPV cohort. Vaginal microbiota analysis, including microbial diversity and specific bacterial abundances, was performed using 16S rRNA gene sequencing. The mean age of the pre- and postmenopausal women were 29.5 and 55.8 years, respectively (p

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m2), 4--6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). Methods: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women. In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. Results: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (-98.61%; 95% confidence interval=-99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. Conclusion: The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads. [ABSTRACT FROM AUTHOR]

Background: Distinguishing ovarian cancer from other gynecological malignancies is crucial for patient survival yet hindered by non-specific symptoms and limited understanding of ovarian cancer pathogenesis. Accumulating evidence suggests a link between ovarian cancer and deregulated lipid metabolism. Most studies have small sample sizes, especially for early-stage cases, and lack racial/ethnic diversity, necessitating more inclusive research for improved ovarian cancer diagnosis and prevention. Methods: Here, we profiled the serum lipidome of 208 ovarian cancer, including 93 early-stage patients with ovarian cancer and 117 nonovarian cancer (other gynecological malignancies) patients of Korean descent. Serum samples were analyzed with a high-coverage liquid chromatography high-resolution mass spectrometry platform, and lipidome alterations were investigated via statistical and machine learning (ML) approaches. Results: We found that lipidome alterations unique to ovarian cancer were present in Korean women as early as when the cancer is localized, and those changes increase in magnitude as the diseases progresses. Analysis of relative lipid abundances revealed specific patterns for various lipid classes, with most classes showing decreased abundance in ovarian cancer in comparison with other gynecological diseases. ML methods selected a panel of 17 lipids that discriminated ovarian cancer from nonovarian cancer cases with an AUC value of 0.85 for an independent test set. Conclusions: This study provides a systemic analysis of lipidome alterations in human ovarian cancer, specifically in Korean women. [ABSTRACT FROM AUTHOR]

We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in a prospective analysis of 47 serial blood samples collected at multiple time-points from 13 ovarian cancer patients. CTCs were isolated from whole blood using the FAST disc and were classified as epithelial cell adhesion molecule (EpCAM)/cytokeratin+, CD45−, and 4′,6-diamidino-2-phenylindole (DAPI)+. Mean CTC count at baseline was 20.2; 84.62% of patients had more than one CTC at baseline and had decreased CTCs counts after surgery and chemotherapy. The CTC counts in eight patients with complete responses were

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥ 3LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. Currently, twenty-five domestic institutions and five foreign institutions from China, India, Malaysia and Vietnam have confirmed their participation in this clinical trial. [ABSTRACT FROM AUTHOR]

Objective: Distinguishing uterine sarcomas from leiomyomas preoperatively poses a significant challenge. This study aims to analyze patient characteristics in cases where uterine sarcoma was suspected prior to surgery. Methods: A retrospective review of medical records (2018-2023) was conducted, focusing on patients who underwent pelvis magnetic resonance imaging (MRI) for uterine masses with suspected sarcoma or due to clinical indications of the disease. Analyzed factors included age, preoperative imaging (particularly pelvis MRI), and preoperative and postoperative diagnoses. Results: Out of the 95 patients meeting inclusion criteria, 52 were suspected of sarcoma via pelvis MRI for uterine mass, while 43 underwent MRI due to clinical suspicion. Postoperative diagnoses revealed 15 malignant cases, including endometrial stromal sarcoma (n=6), leiomyosarcoma (n=3), poorly differentiated sarcoma (n=1), endometrial cancer (n=2), and lymphoma (n=3). During the same period, 21 patients were diagnosed with uterine sarcoma postoperatively. Misdiagnoses as leiomyoma were common in younger patients, with an age difference observed between those suspected (50.1 years) and not suspected (44.9 years) of sarcoma preoperatively. Single, large tumors (>5 cm) were significant predictors of sarcoma (p<0.05). MRI proved the most effective in diagnosing sarcoma, with 60% accuracy, compared to a 76.4% misdiagnosis rate when solely relying on ultrasonography. Six patients required re-staging surgery due to incomplete initial staging following myomectomy, revealing peritoneal seeding in two leiomyosarcoma cases. Conclusion: Uterine sarcomas, often misdiagnosed as leiomyomas, tended to be in younger patients with smaller (<5 cm) or multiple tumors, primarily evaluated using only ultrasonography. Comprehensive assessments, including MRI, are recommended for accurate differentiation of uterine sarcomas in women with uterine mass. [ABSTRACT FROM AUTHOR]

Objective: A simultaneous detection of germline and somatic mutations in ovarian cancer (OC) using tumor materials is considered to be cost-effective for BRCA1/2 testing. However, there are limited studies of the analytical performances according to various sample types. The aim of this study is to propose a strategy for routine BRCA1/2 next-generation sequencing (NGS) screening based on analytical performance according to different sample types. Methods: We compared BRCA1/2 NGS screening assay using buffy coat, fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) from 130 samples. Results: The rate of repeated tests in a total of buffy coat, FF and FFPE was 0%, 8%, and 34%, respectively. The accuracy of BRCA1/2 NGS testing was 100.0%, 99.9% and 99.9% in buffy coat, FFPE and FF, respectively. However, due to the presence of variant allele frequency (VAF) shifted heterozygous variants, tumor materials (FFPE and FF) showed lower sensitivity (95.5%-99.0%) than buffy coat (100%). Furthermore, FFPE showed 51.4% of the positive predictive value (PPV) on account of sequence artifacts. When performed in the post-filtration process, PPV was increased by approximately 20% in FFPE. Buffy coat showed 100% of sensitivity, specificity and accuracy in BRCA1/2 NGS test. Conclusions: On the comparison of the analytical performance according to different sample types, the buffy coat was not affected by sequencing artifacts and VAF shifted variants. Therefore, the blood test should be given priority in detecting germline BRCA1/2 mutation, and tumor materials could be suitable to detect somatic mutations in OC patients without identifying germline BRCA1/2 mutation. [ABSTRACT FROM AUTHOR]

Objectives: Since 2007, human papillomavirus (HPV) vaccines have been administered for the prevention of cervical cancer in Korea. We investigated the status of HPV vaccination among HPV-infected adult women with abnormal cervical cytology before the introduction of National Immunization Program. Methods: From 2010 to 2016, HPV-positive women (age, 20-60 years) with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) were enrolled from five hospitals across Korea. Their HPV genotype, epidemiologic, and clinical data, including HPV vaccination history, were obtained. We compared the epidemiological characteristics and prevalence of HPV-16/18 genotypes between vaccinated and unvaccinated women. Results: Among the 1,300 women, approximately 26% had a history of vaccination. Vaccinated patients were significantly younger, unmarried, and had a higher education level than unvaccinated women. For HPV-vaccinated individuals by vaccine dose, there was a significant younger age at vaccination initiation (p=0.025), longer duration from HPV vaccination to Pap test date (p=0.001), and lower proportion of HPV-16/18 (p=0.028) in the women with three doses. There was a significantly lower prevalence of HPV-16/18 genotypes in women who were vaccinated at least 12 months prior than in unvaccinated women (adjusted prevalence ratio [aPR]=0.51; 95% confidence interval [CI]=0.29-0.88). For women with LSIL, the prevalence of the HPV-16/18 genotypes was significantly lower in women who were vaccinated more than 12 months prior than in unvaccinated women (aPR=0.35; 95% CI=0.13-0.96). Conclusion: This study highlighted the status of HPV vaccination and the prevalence of HPV- 16/18 genotypes among HPV-infected women with abnormal cervical cytology according to HPV vaccination. It provides preliminary information regarding the status of HPV vaccination among Korean adult women. [ABSTRACT FROM AUTHOR]

Objective: Persistent infection of HPV increases the chance of carcinoma in situ of cervix through stages of cervical intraepithelial neoplasia (CIN) 1, 2, and 3, and finally progresses into cervical cancer. We aimed to explore the safety and efficacy of BLS-M07 which is orally administered agent expressing human papillomavirus (HPV) 16 E7 antigen on the surface of Lactobacillus casei in patients with CIN 3. Methods: Patients with CIN 3 were recruited in our clinical trial. Reid Colposcopic Index (RCI) grading and serum HPV16 E7 specific antibody production were used to evaluate efficacy of BLS-M07. In phase 1, BLS-M07 was administered orally, 5 times a week, on weeks 1, 2, 4, and 8 with dosages of 500 mg, 1,000 mg, and 1,500 mg. In phase 2a, patients were treated with 1,000 mg. The primary endpoints were the safety and the pathologic regression on colposcopic biopsy. Results: Nineteen patients were enrolled in the CIN 3 cohort. In phase 1, no patients experienced dose limiting toxicity. No grade 3 or 4 treatment-related adverse events or deaths were observed. At 16 weeks after treatment, RCI grading was improved and serum HPV16 E7 specific antibody production increased (p<0.05). Six of 8 (75%) patients with CIN 3 were cured in phase 2a. Conclusions: Oral immunization with BLS-M07 increases production of serum HPV16 E7 specific antibody which induces protective humoral immunity. The safety of this oral vaccine was proved and could be a competitive non-surgical therapeutic agent of CIN 3. [ABSTRACT FROM AUTHOR]

Objective: Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer, which progresses from precursor lesions with no symptom if left untreated. We compared the risk of cervical dysplasia among HPV-positive Korean women based on HPV types and infection patterns. Methods: We observed participants of a 5-year multicenter prospective cohort study, comprising HPV-positive women with either atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion of the cervix at their enrollment. Follow-ups, comprising cytology and HPV DNA testing results, were included in the final analysis. Incidence was calculated for each infection pattern (persistent infection, incidental infection, and clearance). To investigate cervical dysplasia risk, we used Cox proportional hazard models adjusted for variables that were significantly different among infection patterns. From April 2010 to September 2017, 71 of 1,027 subjects developed cervical dysplasia more severe than high-grade squamous intraepithelial lesion of the cervix. Results: Of these 71 subjects, persistent infection, incidental infection, and clearance were noted in 30, 39, and 2 individuals, respectively. Based on changes in DNA results during follow-up, cumulative incidence was 27.2%, 10.4%, and 0.5% for persistent infection, incidental infection, and clearance, respectively. Compared to clearance, the adjusted hazard ratios for cervical dysplasia were 51.6 and 24.1 for persistent and incidental infections, respectively (p<0.001). Conclusion: Individuals persistently infected with the same HPV types during the follow-up period had the highest risk of severe cervical dysplasia. Hence, it is necessary to monitor HPV types and infection patterns to prevent severe cervical precancerous lesions. [ABSTRACT FROM AUTHOR]

Objective: We performed small-scale mutation and large genomic rearrangement (LGR) analysis of BRCA1/2 in ovarian cancer patients to determine the prevalence and the characteristics of the mutations. Methods: All ovarian cancer patients who visited a single institution between September 2015 and April 2017 were included. Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-range polymerase chain reaction (PCR) were performed to comprehensively study BRCA1/2. The genetic risk models BRCAPRO, Myriad, and BOADICEA were used to evaluate the mutation analysis. Results: In total, 131 patients were enrolled. Of the 131 patients, Sanger sequencing identified 16 different BRCA1/2 small-scale mutations in 20 patients (15.3%). Two novel nonsense mutations were detected in 2 patients with a serous borderline tumor and a large-cell neuroendocrine carcinoma. MLPA analysis of BRCA1/2 in Sanger-negative patients revealed 2 LGRs. The LGRs accounted for 14.3% of all identified BRCA1 mutations, and the prevalence of LGRs identified in this study was 1.8% in 111 Sanger-negative patients. The genetic risk models showed statistically significant differences between mutation carriers and non-carriers. The 2 patients with LGRs had at least one blood relative with breast or ovarian cancer. Conclusion: Twenty-two (16.8%) of the unselected ovarian cancer patients had BRCA1/2 mutations that were detected through comprehensive BRCA1/2 genetic testing. Ovarian cancer patients with Sanger-negative results should be considered for LGR detection if they have one blood relative with breast or ovarian cancer. The detection of more BRCA1/2 mutations in patients is important for efforts to provide targeted therapy to ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Purpose Genexol-PM is a biodegradable cremophor EL-free polymeric micelle formulation of paclitaxel. Here, we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment. Materials and Methods In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 with 5 area under the curve carboplatin every 3 weeks (6 cycles). The primary endpoint was the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR). Results Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00±0.00 mg/m2 Genexol-PM or 174.24±3.81 mg/m2 Genexol. Median followup was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (noninferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p= 0.148). Peripheral neuropathy of ≥ grade 3 occurred in one patient receiving Genexol. All toxicities were manageable. Conclusion Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the in vitro effect of a heat shock protein (Hsp)90 inhibitor, SY-016, on the paclitaxel (PTX)-resistant human ovarian cancer cell line OVCAR-3PTX, and explore its mechanism of apoptosis. In the present study, SY-016 was used in combination with PTX to determine its effect on the cell proliferation and apoptosis of OVCAR-3PTX cells. The drug-resistant tumor cells were established in vitro by stepwise sequential exposure to increasing concentrations of PTX. The cell viability and cell cycle distribution were measured by MTT assay and flow cytometric analysis, respectively. The induction of apoptosis was measured by caspase-3 activity, DNA fragmentation and western blot analyses. The cell viability significantly decreased following treatment with PTX and SY-016 as compared with either drug alone. The DNA fragmentation assay revealed an induction of apoptosis. The results from the flow cytometric analysis revealed an increase in the percentage of cells in the G2/M phase. Downregulation of B-cell lymphoma (Bcl)-2, X-linked inhibitor of apoptosis protein, survivin, Akt, nuclear factor-κB and cyclin-dependent kinase 4, as well as upregulation of Bcl-2-associated X protein, were observed. SY-016 may contribute to the induction of apoptosis in OVCAR-3PTX cells. These results suggest that SY-016 in combination with PTX may be a beneficial chemotherapeutic strategy, particularly in patients with tumors refractory to PTX. [ABSTRACT FROM AUTHOR]

Objective: Cancer stem cells (CSCs) represent a subpopulation of undifferentiated tumorigenic cells thought to be responsible for tumor initiation, maintenance, drug resistance, and metastasis. The role of CSCs in drug resistance and relapse of cancers could significantly affect outcomes of ovarian cancer patient. Therefore, therapies that target CSCs could be a promising approach for ovarian cancer treatment. The antibiotic salinomycin has recently been shown to deplete CSCs. In this study, we evaluated the effect of salinomycin on ovarian cancer stem cells (OCSCs), both alone and in combination with paclitaxel (PTX). Methods: The CD44+CD117+CSCs were obtained from the ascitic fluid of patients with epithelial ovarian cancer by using an immune magnetic-activated cell sorting system. OCSCs were treated with PTX and salinomycin either singly or in combination. Cell viability and apoptosis assays were performed and spheroid-forming ability was measured. The expression of sex determining region Y-box 2 (SOX2) and octamer-binding transcription factor 3/4 (OCT3/4) mRNA was determined using reverse transcription polymerase chain reaction, and protein expression was observed using western blot analysis. Results: Treatment with salinomycin alone reduced the stemness marker expression and spheroid-forming ability of OCSCs. Treatment with PTX alone did not decrease the viability of OCSCs. Treatment with a combination of salinomycin decreased the viability of OCSCs and promoted cell apoptosis. The enhancement of combination treatment was achieved through the apoptosis as determined by annexin V/propidium iodide (PI) staining, caspase-3 activity, and DNA fragmentation assay. Conclusion: Based on our findings, combining salinomycin with other anti-cancer therapeutic agents holds promise as an ovarian cancer treatment approach that can target OCSCs. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the impact of high-risk human papillomaviruses (HPVs) other than HPV 16/18 on the natural course of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL). Materials and Methods: The study population was derived from the Korean HPV cohort (2010-2014). Women aged 20 to 60 who satisfied the criteria of having both HPV infection and abnormal cervical cytology of either ASC-US or LSIL were recruited from five institutions nationwide. Enrolled patients underwent cervical cytology and HPV DNA testing every 6 months. Results: A total of 1,158 patients were enrolled. The 10 most common HPV types were HPV 16 (12.3%), 58 (10.0%), 56 (8.8%), 53 (8.4%), 52 (7.7%), 39 (6.2%), 18 (6.0%), 51 (5.7%), 68 (5.1%), and 66 (4.6%). Among these patients, 636 women were positive for high-risk HPVs other than HPV 16 or 18, and 429 women were followed for more than 6 months. Cytology evaluations showed progression in 15.3% of women, no change in 22.6%, and regression in 62.1% of women at 12 months. In cases of HPV 58 single infection, a more highly significant progression rate, compared to other high-risk types, was observed at 6 months (relative risk [RR], 3.3; 95% confidence interval [CI], 2.04 to 5.30; p < 0.001) and 12 months (RR, 5.03; 95% CI, 2.56 to 9.91; p < 0.001). Conclusion: HPV genotypes numbered in the 50s were frequent in Korean women with ASC-US and LSIL. HPV 58 was the second most common type, with a high progression rate of cervical cytology. [ABSTRACT FROM AUTHOR]

Objectives: Health-related quality-of-life (HRQOL) issues of cancer patients are considered an important clinical outcome. We aimed to investigate the prognostic value of HRQOL on long-term survival outcomes in disease-free cervical cancer survivors (CCSs). Methods: The study sample consisted of 860 disease-free CCSs from 6 Korean cancer hospitals recruited for HRQOL survey during 2005 (median time from diagnosis, 5.9 years). Health-related quality-of-life measures included the European Organization for Research and Treatment of Cancer QLQ-C30 and its Cervical Cancer Module (CX24). Survival data were retrieved from the Korean Statistical Office after 6 years from the survey. Health-related quality-of-life domains along with sociodemographic and clinicopathologic variables were analyzed as prognostic factors for survival from the date of survey. Results: During the median follow-up period of 6.3 years after the survey, 30 (3.5%) patients died from all causes. Age, time since diagnosis, and physical activity were independent prognostic factors, which constituted the baseline model along with cancer stage. When HRQOL domains were tested separately against the baseline model, functional scales (physical, role, social, and emotional functioning), global health status, symptom scales (pain and appetite loss), and cervical cancer module items (body image, sexual inactivity, and sexual worry) were significantly associated with survival (P < 0.05). Conclusions: These findings suggest that, in addition to well-known prognostic factors, including age, time since diagnosis, and physical activity, HRQOL scores obtained from disease-free CCSs are associated with survival. [ABSTRACT FROM AUTHOR]

The incidence rate of cervical cancer in Korea is still higher than in other developed countries, notwithstanding the national mass-screening program. Furthermore, a new method has been introduced in cervical cancer screening. Therefore, the committee for cervical cancer screening in Korea updated the recommendation statement established in 2002. The new version of the guideline was developed by the committee using evidence-based methods. The committee reviewed the evidence for the benefits and harms of the Papanicolaou test, liquid-based cytology, and human papillomavirus (HPV) testing, and reached conclusions after deliberation. The committee recommends screening for cervical cancer with cytology (Papanicolaou test or liquid-based cytology) every three years in women older than 20 years of age (recommendation A). The cervical cytology combined with HPV test is optionally recommended after taking into consideration individual risk or preference (recommendation C). The current evidence for primary HPV screening is insufficient to assess the benefits and harms of cervical cancer screening (recommendation I). Cervical cancer screening can be terminated at the age of 74 years if more than three consecutive negative cytology reports have been confirmed within 10 years (recommendation D). [ABSTRACT FROM AUTHOR]

Objective: Little is known regarding cervical cancer survivors' employment status, which represents social integration of cancer survivors as a pivotal domain of long-term quality of life. The goal of this study was to assess the correlates of unemployment and evaluate the impact on the comprehensive quality of life in cervical cancer survivors. Methods: We enrolled 858 cervical cancer survivors from the gynecologic oncology departments of multi-centers in Korea. Factors associated with unemployment were identified using multivariate logistic regression analyses. We assessed different health-related quality of life domains with multivariate-adjusted least-square means between cervical cancer survivors who currently work and do not. Results: After diagnosis and treatment, the percentage of unemployed survivors increased from 50.6% to 72.8%. Lower income (adjusted odds ratio [aOR], 1.97; 95% confidence interval [CI], 1.38 to 2.81), medical aid (aOR, 1.58; 95% CI, 1.05 to 2.38), two or more comorbidities (aOR, 1.80; 95% CI, 1.12 to 2.90), current alcohol drinkers (aOR, 2.33; 95% CI, 1.54 to 3.52), and employed at the time of diagnosis (aOR, 10.72; 95% CI, 7.10 to 16.16) were significantly associated with unemployment. Non-working groups showed significant differences with respect to physical functioning, role functioning, depression, and existential well-being. Conclusion: The proportion of unemployed cervical cancer survivors seems to increase, with low-income status and the presence of medical aid negatively being associated with employment, in addition to other comorbidities and previous working status. Effort should be made to secure the financial status of cervical cancer survivors. [ABSTRACT FROM AUTHOR]

We have designed a five-year multicentre prospective cohort study in women who are both human papillomavirus (HPV)-positive with either atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) of cervix. This study aimed to analyze the risk of developing a high-grade squamous intraepithelial lesion (HSIL) from either ASCUS or LSIL in HPV-positive women, so called 'progression' rate, to investigate differences in the progression rates according to HPV type-specific infection, and to evaluate the various factors associated with the persistence or clearance of HPV infection in the Korean population. At present, the study protocol composed of cervical cytology, HPV DNA testing, and questionnaire have been conducted actively since the first participant was enrolled in 2010. This study is the first nationwide Korea HPV cohort study. Our data will provide valuable information about not only the ambiguous cytology results of ASCUS and LSIL but also the effect of the specific HPV type and other various factors on the progression to HSIL. Finally, the results of our study will be helpful and applicable to determine the primary cervical cancer prevention strategies. [ABSTRACT FROM AUTHOR]

We report 2 cases of minimal deviation adenocarcinoma of the cervix and tumorlets of sex cord tumor with annular tubules (SCTATs) of the ovaries, accompanied by Peutz-Jeghers syndrome. Case 1 is a 36-year-old woman and case 2 is a 35-year-old woman. Grossly, the cervix of both cases showed markedly barrel shaped enlargement with an infiltrating tumor. Microscopically, well-differentiated atypical glands were infiltrating into the entire thickness of the cervix. The ovarian masses in case 1 were diagnosed as metastatic carcinoma in mucinous cystadenoma with tumorlets of SCTATs of the ovaries. Multiple scattered tumorlets of SCTATs were also found in the ovary of case 2. By direct DNA sequencing analysis, a frame shift mutation of the STK11/LKB1 gene was identified in case 1. Case 1 represented the more aggressive clinical course, and although the patient received additional combined chemo-radiation therapy, she expired 1 year later. In general, mutation of the STK11/LKB1 gene is associated with poor clinical outcome in malignant tumors accompanied by Peutz-Jeghers syndrome. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify a standard for the evaluation of future models for prediction of lymph node metastasis in endometrial cancer through estimation of performance of well-known surgicopathological models. Methods: Using the medical records of 947 patients with endometrial cancer who underwent surgical management with lymphadenectomy, we retrospectively assessed the predictive performances of nodal metastasis of currently available models. Results: We evaluated three models included: 1) a model modified from the Gynecologic Oncology Group (GOG) pilot study; 2) one from the GOG-33 data; and 3) one from Mayo Clinic data. The three models showed similar negative predictive values ranging from 97.1% to 97.4%. Using Bayes' theorem, this can be translated into 2% of negative post-test probability when 10% of prevalence of lymph node metastasis was assumed. In addition, although the negative predictive value was similar among these models, the proportion that was classified as low-risk was significantly different between the studies (56.4%, 44.8%, and 30.5%, respectively; p<0.001). Conclusion: The current study suggests that a false negativity of 2% or less should be a goal for determining clinical usefulness of preoperative or intraoperative prediction models for low-risk of nodal metastasis. [ABSTRACT FROM AUTHOR]

Background: Whereas most studies have focused on euthanasia and physician-assisted suicide, few have dealt comprehensively with other critical interventions administered at the end of life. We surveyed cancer patients, family caregivers, oncologists and members of the general public to determine their attitudes toward such interventions. Methods: We administered a questionnaire to four groups about their attitudes toward five end-of-life interventions -- withdrawal of futile life-sustaining treatment, active pain control, withholding of life-sustaining measures, active euthanasia and physician-assisted suicide. We performed multivariable analyses to compare attitudes and to identify socio-demographic characteristics associated with the attitudes. Results: A total of 3840 individuals -- 1242 cancer patients, 1289 family caregivers and 303 oncologists from 17 hospitals, as well as 1006 members of the general Korean population -- participated in the survey. A large majority in each of the groups supported withdrawal of futile life-sustaining treatment (87.1%---94.0%) and use of active pain control (89.0%--98.4%). A smaller majority (60.8%--76.0%) supported withholding of life-sustaining treatment. About 50% of those in the patient and general population groups supported active euthanasia or physician-assisted suicide, as compared with less than 40% of the family caregivers and less than 10% of the oncologists. Higher income was significantly associated with approval of the withdrawal of futile life-sustaining treatment and the practice of active pain control. Older age, male sex and having no religion were significantly associated with approval of withholding of life-sustaining measures. Older age, male sex, having no religion and lower education level were significantly associated with approval of active euthanasia and physician-assisted suicide. Interpretation: Although the various participant groups shared the same attitude toward futile and ameliorative end-of-life care (the withdrawal of futile life-sustaining treatment and the use of active pain control), oncologists had a more negative attitude than those in the other groups toward the active ending of life (euthanasia and physician-assisted suicide). [ABSTRACT FROM AUTHOR]

The article presents a multicenter retrospective study of endometrioid epithelial ovarian cancer (EEOC) with concurrent endometriosis. The researchers examined 221 patients who were treated for the medical condition at four educational hospitals from 2000 to 2008. They found that the most common symptoms of the disease include palpable mass, pelvic pain as well as abdominal distension.

Objective. To evaluate whether concurrent chemoradiation therapy (CRT) improves overall survival as compared to radiation therapy (RT) alone in stage III cervical cancers. Design. A multicenter retrospective review. Setting. Nine tertiary medical centers in Korea. Population. A total of 277 patients treated for stage III cervical cancer without para-aortic lymph node (PALN) metastasis based on clinical staging workup from 1996 to 2003. Methods. Medical and histopathological record review. Main outcome measures. Disease-specific overall survival. Results. CRT and RT alone were performed in 172 and 105 patients, respectively. There was no significant difference in disease-specific overall survival between the CRT and RT alone arms based on clinical staging workup, even though the CRT arm was characterized by younger age, more favorable performance status and lower pretreatment blood urea nitrogen level as compared to the RT alone arm. In the CRT arm, three patients succumbed to treatment-related death. Conclusion. CRT does not improve the overall survival rate in stage III cervical cancer as compared to RT alone based on clinical staging workup for PALN status. Special care needs to be taken regarding optimal dose and duration of RT, use of brachytherapy, anemia control and accurate pretreatment staging workup to improve survival outcome in patients with stage III cervical cancer. [ABSTRACT FROM AUTHOR]

We previously reported that BRCA1 interacts with aryl hydrocarbon receptor nuclear translocator (ARNT) and that this interaction affects TCDD-induced CYP1A1 gene expression (Kang et al., J Biol Chem 281:14654–14662, 2006). In this study we continue this investigation and begin to define the significance of this interaction for the regulation of stress-induced transcription. Immunoprecipitations (IPs), western blot (WB) analysis, GST pull-down assays and promoter reporter assays were used to investigate whether the aryl hydrocarbon receptor (AhR) can regulate transcription that is dependent on the activation domain 1 (AD1) domain of BRCA1. We show that AhR, a transcription factor, can bind specifically to AD1 in the C-terminal region of BRCA1 and affect BRCA1’s ability to regulate transcription activity. We found that xenobiotics that positively and negatively affect AhR’s activity as a transcription factor (e.g., dioxin and α-naphthoflavone, respectively), have similar effects on AhR’s ability to affect AD1-domain-dependent transcription. These physical and functional AhR–AD1 interactions may require the coiled-coil motif in AD1 because point-mutations in this motif reduce these interactions. Xenobiotic-activated AhR can function in two ways, as a component of the AhR/ARNT transcription factor and a regulator of AD1-dependent transcription. Consequently, BRCA1 has two distinct mechanisms for sensing xenobiotics and regulating AhR-dependent stress responses to these xenobiotics. We speculate that the normal functioning of this interaction could play a role in BRCA1’s tumor suppressing ability. [ABSTRACT FROM AUTHOR]

Isoliquiritigenin(ISL), a calchone flavonoid, has cancer-preventing properties and is often used in Chinese medicine. In the present study, the authors use ISL to determine its effect on cell proliferation and cell cycle progression in primary cultured human uterine leiomyoma cells. Cell viability and cell proliferation assays were conducted. Flow cytometry, annexin V apoptosis assay, and DNA fragmentation assay were performed to determine the effect of ISL on cell cycle and apoptosis. The expression of cell cycle regulatory--related proteins urns evaluated by Western blot. The cell viability and proliferation of uterine leiomyoma cells were significantly reduced by ISL treatment in a dose-dependent manner. Flow cytometry results showed that ISL induced subG1 and G2/M arrest. DNA fragmentation assay and annexin V apoptosis assays revealed apoptosis induction. ISL-induced growth inhibition in uterine leiomyoma cells was associated with increased p21Cip1/Waf1 expression in a p53-dependent manner. Activation of caspase-3 and downregulation of Bcl-2, cdk 2/4, and E2F, with a concomitant increase in dephosphorylation of Rb and poly--ADP-ribose polymerase cleavage, were observed. This study demonstrates that ISL inhibits cell proliferation by initiating apoptosis in human uterine leiomyoma cells coupled with increased cell cycle arrest. These results indicate that ISL could prove to be a promising chemopreventive and therapeutic agent against human uterine leiomyoma. [ABSTRACT FROM AUTHOR]

Observations from the authors' laboratory suggest a physiological role for increased cyclin G1 protein levels in human uterine leiomyoma. The hypothesis of the present study is that the strategic modulation of cyclin G1 by antisense technology will inhibit the survival of in vitro-grown uterine leiomyoma cells. Cultured uterine leiomyoma cells were transfected with cyclin G1 ribbon-type antisense oligonucleotide (cyclin G1 RiAS) to effectively reduce cyclin G1 expression. Cell viability, in situ terminal deoxyuridine nick end-labeling (TUNEL) assay, flow cytometry, DNA fragmentation, and expression of cell cycle regulatory-related proteins were evaluated by Western blot. Antisense oligonucleotides compromised uterine leiomyoma cell viability and inducted apoptosis in a caspase-independent mechanism. In situ TUNEL and DNA fragmentation revealed apoptosis induction, and fluorescent-activated cell sorting analysis showed increased sub-Gl-phase cells. Furthermore, abrogation of cyclin G1 enhanced p53 accumulation, phosphorylation of p53 at Ser-15 residue, and increased expression of cyclin-dependent kinase inhibitors p21 and p27. These data imply that cyclin G1 expression is assodated with growth promotion and the potential utility and novelty of using ribbon-type antisense oligonucleotides as a gene therapy strategy to treat human uterine leiomyoma. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the prevalence of comorbidities in cervical cancer survivors compared with the general population and to identify risk factors and impact on their quality of life (QoL). Methods: 860 female cervical cancer survivors enrolled at six tertiary hospitals and 994 women from the general population were surveyed on current comorbidities and QoL (EORTC QLQ-C30 and QLQ-CX24). Results: Compared with the general female population, the cervical cancer survivors reported higher prevalence of comorbidities (0.93 ± 2.91 vs. 0.37 ± 0.67, p < 0.01), significantly more heart disease (adjusted odds ratio (aOR), 2.64; 95% confidence interval (CI), 1.38–5.07), liver disease (aOR, 3.29; 95% CI, 1.54–7.02), hypertension (aOR, 1.72; 95% CI, 1.30–2.27), gastrointestinal disease (aOR, 1.79; 95% CI, 1.37–2.33) and musculoskeletal disease (aOR, 1.94; 95% CI, 1.45–2.59). Heart and renal disease significantly influenced QoL in many subscales. Patients with diabetes or cerebrovascular disease had an increased likelihood of sexual problems. Conclusions: The cervical cancer survivors had more comorbidities than the general population, and that in turn affected their QoL. Vigilant follow-up of comorbidities should be incorporated into in the care of cancer survivors. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article details a study which investigated the long-term quality of life (QOL) and sexual function in cervical cancer survivors. More than 800 women with a history of cervical cancer who had been treated at any of 6 hospitals from 1983 through 2004 and 494 control subjects were selected randomly from a representative sample of Korean women. The authors found that cervical cancer survivors had clinically significant worse problems with social functioning, constipation, diarrhea and difficulties with their finances than control subjects.

This study investigated the acute effects of a peroxisome proliferator-activated receptor (PPAR)-γ ligand, ciglitizone, on cell proliferation and intracellular Ca2+ signaling in human normal myometrium and uterine leiomyoma. Changes in intracellular Ca2+ concentration ([Ca2+]i) were measured with fura-2 AM, and cellular viabilities were determined by viable cell count and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction assay. Ciglitizone (100 µM) induced greater inhibition of cell proliferation in uterine leiomyoma than in myometrium. Ciglitizone also dose-dependently increased [Ca2+]i in both myometrium and uterine leiomyoma; these [Ca2+]i increases were inhibited by PPAR-γ antagonists and raloxifene. Ciglitizone-induced [Ca2+]i increase showed only an initial peak in normal myometrial cells, whereas in uterine leiomyoma there was a second sustained [Ca2+]i increase as well. The initial [Ca2+]i increase in both myometrium and uterine leiomyoma resulted from the release of Ca2+ by the sarcoplasmic reticulum via activation of ryanodine receptors. The second [Ca2+]i increase was observed only in uterine leiomyoma because of a Ca2+ influx via an activation of store-operated Ca2+ channels (SOCCs). Cell proliferation was inhibited and secondary [Ca2+]i increase in uterine leiomyoma was attenuated by cotreatment of ciglitizone with a SOCC blocker, lanthanum. The results suggest that ciglitizone inhibits cell proliferation and increases [Ca2+]i through the activation of SOCCs, especially in human uterine leiomyoma. [ABSTRACT FROM AUTHOR]

A low-taurine diet during fetal or early postnatal life causes abnormal pancreatic β-cell development. Tissue and plasma taurine concentrations can also be low in diabetic patients. We examined the effect of taurine on impaired glucose responses in diabetic rat β-cells adenovirally overexpressing uncoupling protein (UCP)2, which is upregulated in obesity-related type 2 diabetes. We found that taurine pretreatment restored the ATP-toADP (ATP/ADP) ratio and glucose-stimulated insulin secretion in UCP2-infected islets. ATP-sensitive K+ channel sensitivity to dihydroxyacetone, another insulin secretagogue, was similar in both UCP2-infected and control β-cells. In freshly isolated mitochondria from UCP2-overexpressing insulin-secreting (INS)-1 β-cells, methyl pyruvate-mediated mitochondrial Ca2+ increase was significantly ameliorated by taurine. A mitochondrial Ca2+ uniporter blocker, ruthenium red, inhibited the action of taurine. This study suggests that taurine enhances the glucose sensitivity of UCP2-overexpressing β-cells, probably by increasing mitochondrial Ca2+ influx through the Ca2+ uniporter, thereby enhancing mitochondrial metabolic function and increasing the ATP/ADP ratio. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to detect the expression of cyclin G1 in leiomyoma and to investigate the alteration of its expression compared with normal myometrial tissue that was obtained from the same patient. STUDY DESIGN: With the use of Northern blot analysis, Western blot analysis, and immunohistochemistry, we analyzed the expression of cyclin G1 in 24 patients who underwent hysterectomies. RESULTS: We found that messenger RNA levels of cyclin G1 were elevated in human leiomyomas compared with their adjacent normal myometrial tissues. Consistent with elevated messenger RNA levels, high levels of cyclin G1 protein expression were detected by immunoblot analysis in all leiomyoma samples. Immunohistochemistry revealed that cyclin G1 is located mainly in the nucleus in both normal myometrium and leiomyoma. However, higher levels of cyclin G1 were apparent in tumor regions compared with adjacent normal myometrial regions. In addition, we found the expression levels of other cyclins (A and E) and CDK2 were elevated in leiomyomas compared with normal myometrium. Because cyclin G1 is a transcriptional target of the p53 tumor suppressor, we examined the p53 status of all eight leiomyoma samples and found no p53 mutations. CONCLUSION: These results suggest that cyclin G1 is frequently overexpressed in uterine leiomyoma in a p53-independent manner and that this abnormality could be attributed to the severe proliferation of human uterine leiomyomas. [ABSTRACT FROM AUTHOR]

ObjectiveThis study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL).MethodsWe analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20–60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing.ResultsOf the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08–2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P

Objective To document the experiences of converting a general hospital to a coronavirus disease 2019 (COVID-19) designated hospital during an outbreak in Daegu, Republic of Korea. Methods The hospital management formed an emergency task force team, whose role was to organize the COVID-19 hospital. The task force used different collaborative channels to redistribute resources and expertise to the hospital. Leading doctors from the departments of infectious diseases, critical care and pulmonology developed standardized guidelines for treatment coherence. Nurses from the infection control team provided regular training on donning and doffing of personal protective equipment and basic safety measures. Findings Keimyung University Daegu Dongsan hospital became a red zone hospital for COVID-19 patients on 21 February 2020. As of 29 June 2020, 1048 COVID-19 patients had been admitted to the hospital, of which 22 patients died and five patients were still being treated in the recovery ward. A total of 906 health-care personnel worked in the designated hospital, of whom 402 were regular hospital staff and 504 were dispatched health-care workers. Of these health-care workers, only one dispatched nurse acquired COVID-19. On June 15, the hospital management and Daegu city government decided to reconvert the main building to a general hospital for non-COVID-19 patients, while keeping the additional negative pressure rooms available, in case of resurgence of the disease. Conclusion Centralized coordination in frontline hospital operation, staff management, and patient treatment and placement allowed for successful pooling and utilization of medical resources and manpower during the COVID-19 outbreak. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of this study was to investigate the short-term efficacy and safety of Poly-gamma-glutamic acid (γ-PGA) and the immunologic changes in patients with CIN 1.MethodsParticipants were randomly assigned to one of two groups and orally treated with placebo or 1,500 mg of γ-PGA for 4 weeks. The primary endpoint of the study was histologic regression rate of CIN 1 at 12 weeks between γ-PGA and control groups. The secondary endpoints were HPV clearance and change in immune responses.ResultFrom April 2013 to December 2015, 195 patients participated in the study. In the intention-to-treat analysis, 42 (42.4%) of the women who received γ-PGA experienced histologic remission versus 26 (27.1%) in the control group, with a statistically significant difference (p = 0.018). In the γ-PGA group, HPV clearance was found in 37 (43.5%) of 85 patients infected with high-risk HPV, showing a significant difference compared to the control group, in which 20 (26.7%) of 75 patients exhibited HPV clearance (p = 0.026). However, there was no significant difference between the two groups in the change of NK cell activity, major histocompatibility complex (MHC) class II CD8 count, and CD56 count.Conclusionγ-PGA showed a short-term therapeutic effect on CIN 1 and high-risk HPV infection. It is a non-invasive, promising oral medication for women with these conditions.Trial registrationClinical Trials NCT01826045.

Purpose A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m² was administered once weekly for 5 weeks during radiation therapy. Results Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study. [ABSTRACT FROM AUTHOR]

Background: Despite advances in treatment, ovarian cancer is the most lethal gynecologic malignancy. Therefore significant efforts are being made to develop novel strategies for the treatment of ovarian cancer. Salinomycin has been shown to be highly effective in the elimination of cancer stem cells both in vitro and in vivo. The present study focused on investigating important cell signaling molecules such as Akt and NF-κB during salinomycin-induced apoptosis in cisplatin resistant ovarian cancer cells (A2780cis). Methods: MTT assay was performed to determine cell viability. Flow cytometry and DNA fragmentation assay were performed to analyze the effect on cell cycle and apoptosis. The expression of apoptosis related proteins was evaluated by Western blot analysis. Results: The cell viability was significantly reduced by salinomycin treatment in a dose dependent manner. The flow cytometry result showed an increase in sub-G1 phase. Salinomycin inhibited the nuclear transportation of NF-kB, and downregulated Akt expression. Declined Bcl-2, activation of caspase-3 and increased PARP cleavage triggered apoptosis. Moreover, DNA fragmentation assay also revealed apoptotic induction. Conclusion: The result suggested that salinomycin-induced apoptosis in A2780cis was associated with inhibition of Akt/NF-κB. It may become a potential chemotherapeutic agent for the cisplatin resistant ovarian cancer therapy. [ABSTRACT FROM AUTHOR]