Targeting progesterone signaling prevents metastatic ovarian cancer.

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

In vivo modeling of metastatic human high-grade serous ovarian cancer in mice.

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.

A multicentre, randomised, open-label, parallel-group Phase 2b study of belotecan versus topotecan for recurrent ovarian cancer.

BACKGROUND: This Phase 2b study compared the efficacy and toxicity of belotecan and topotecan in recurrent ovarian cancer. METHODS: Patients with platinum-sensitive recurrent or platinum-resistant recurrent ovarian cancer (PRROC) were randomised 1:1 to receive belotecan 0.5 mg/m2 or topotecan 1.5 mg/m2 for five consecutive days every 3 weeks. The primary endpoint was overall response rate (ORR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: A total of 140 (belotecan, n = 71; topotecan, n = 69) and 130 patients (belotecan, n = 66; topotecan, n = 64) were included in the intention-to-treat (ITT) and per-protocol (PP) populations. ORR did not differ significantly between the belotecan and topotecan groups (ITT, 29.6% versus 26.1%; PP, 30.3% versus 25%). Although PFS did not differ between the groups, belotecan was associated with improved OS compared with topotecan in the PP population (39.7 versus 26.6 months; P = 0.034). In particular, belotecan showed longer OS in PRROC and non-high-grade serous carcinoma (non-HGSC; PP, adjusted hazard ratios, 0.499 and 0.187; 95% confidence intervals 0.255-0.977 and 0.039-0.895). Furthermore, there were no differences in toxicities between the two groups. CONCLUSIONS: Belotecan was not inferior to topotecan in terms of overall response for recurrent ovarian cancer. CLINICAL TRIAL REGISTRATION: NCT01630018.

Lessons from a COVID-19 hospital, Republic of Korea.

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.

NAA10 as a New Prognostic Marker for Cancer Progression.

N-α-acetyltransferase 10 (NAA10) is an acetyltransferase that acetylates both N-terminal amino acid and internal lysine residues of proteins. NAA10 is a crucial player to regulate cell proliferation, migration, differentiation, apoptosis, and autophagy. Recently, mounting evidence presented the overexpression of NAA10 in various types of cancer, including liver, bone, lung, breast, colon, and prostate cancers, and demonstrated a correlation of overexpressed NAA10 with vascular invasion and metastasis, thereby affecting overall survival rates of cancer patients and recurrence of diseases. This evidence all points NAA10 toward a promising biomarker for cancer prognosis. Here we summarize the current knowledge regarding the biological functions of NAA10 in cancer progression and provide the potential usage of NAA10 as a prognostic marker for cancer progression.

A randomized controlled trial of physical activity, dietary habit, and distress management with the Leadership and Coaching for Health (LEACH) program for disease-free cancer survivors.

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).

Efficacy and safety of aprepitant for the prevention of chemotherapy-induced nausea and vomiting during the first cycle of moderately emetogenic chemotherapy in Korean patients with a broad range of tumor types.

PURPOSE: This study evaluated the efficacy and safety of a 3-day aprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) during the first cycle of non-anthracycline plus cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) based on government guidelines in Korean patients. METHODS: This multicenter, randomized, double-blind, phase IV trial (NCT01636947) enrolled adult South Korean patients with a broad range of tumor types who were scheduled to receive a single dose of ≥1 MEC agent. Patients were randomized to a 3-day regimen of aprepitant (aprepitant regimen) or placebo (control regimen) on top of ondansetron plus dexamethasone. The primary and key secondary efficacy endpoints were the proportions of subjects who achieved no vomiting and complete response (CR) during the overall phase. RESULTS: Of the 494 randomized subjects, 480 were included in the modified intent-to-treat population. Response rates for no vomiting and CR in the overall phase were numerically higher for the aprepitant regimen compared with the control regimen groups, but failed to reach statistical significance (no vomiting 77.2 vs 72.0%; p = 0.191; CR 73.4 vs 70.4%; p = 0.458). Both the aprepitant and control regimens were generally well tolerated. CONCLUSION: A 3-day aprepitant regimen was numerically better but not statistically superior to a control regimen with respect to the achievement of no vomiting or CR during the overall phase in a non-AC MEC Korean population based on government reimbursement guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT01636947 ( https://clinicaltrials.Gov/ct2/show/NCT01636947 ).

Health-Related Quality of Life and Sociodemographic Characteristics as Prognostic Indicators of Long-term Survival in Disease-Free Cervical Cancer Survivors.

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.

Multi-institution, Prospective, Randomized Trial to Compare the Success Rates of Single-port Versus Multiport Laparoscopic Hysterectomy for the Treatment of Uterine Myoma or Adenomyosis.

STUDY OBJECTIVE: To compare the operative outcomes of patients undergoing either single-port or multiport laparoscopic hysterectomy (LH). METHODS: Two hundred fifty-six women scheduled for LH for symptomatic myoma and/or adenomyosis from 8 tertiary teaching hospitals were randomized to single-port or multiport groups. Primary outcome was conversion and/or complication proportion of the planned procedure to determine whether the success proportion of the single-port approach was not inferior to that of the multiport approach. Secondary outcomes were postoperative pain and operative scar. RESULTS: Demographic parameters including age, body mass index, parity, and history of vaginal and cesarean delivery were comparable between the 2 groups. The primary outcome of a combined conversion and/or complication rate was similar between the single-port and multiport groups at 8% and 10.3%, respectively. Conversions were similar between the groups with 4% of single-port cases and .8% of multiport cases. Transfusions were the most frequent complication required in 4.0% of single-port cases and 7.9% of multiport cases, with no difference between the groups. Concerning secondary outcomes, postoperative pain score and patient and observer scar assessment were not different between the 2 groups. Although not a specific outcome measure, there was no difference between the groups in blood loss, operative time, and postoperative hospital stay. CONCLUSION: Single-port LH is not inferior to multiport LH in terms of conversion and/or complications rates, including transfusion. However, the single-port approach did not have any advantage over multiport LH with regard to pain or cosmetic outcomes. These findings were demonstrated by multi-institutional surgeons in Korea.

Lymph node status did not significantly improve the predictability of survival in patients with clinically early-stage endometrial cancer.

OBJECTIVE: The aim of this study was to determine whether knowledge of lymph node status improves survival prediction in clinically early-stage endometrial cancer. METHODS: The records of 661 patients with apparently uterine-confined disease were reviewed. The performance in predicting overall survival and cause-specific survival was compared between a multivariate prognostic model with nodal status and a model without nodal status by calculating Harrell concordance index. RESULTS: Among 661 patients with clinically early-stage endometrial cancer, the lymph node metastasis rate was 8.3% (55/661). Lymph node metastasis independently associated with cause-specific survival only when no stratification according to adjuvant treatment was applied (P = 0.035). After stratification according to adjuvant radiotherapy, lymph node status marginally associated with cause-specific survival (P = 0.073), whereas myometrial invasion retained its strong association with cause-specific survival (P < 0.001). However, there was no significant difference in the performance of the survival model using only uterine factors and the model using lymph node status and uterine factors (concordance index, 0.77 vs 0.77, respectively; P = 0.798). CONCLUSIONS: Knowledge of lymph node status did not significantly improve the performance of survival prediction in apparently uterine-confined endometrial cancer, although it was independently associated with survival. In the patients with clinically early-stage endometrial cancer, the accuracy of the prediction of survival was comparable between risk grouping without lymph node status and that including lymph node status.

A Web-based nomogram predicting para-aortic nodal metastasis in incompletely staged patients with endometrial cancer: a Korean Multicenter Study.

OBJECTIVE: The purpose of this study is to develop a Web-based nomogram for predicting the individualized risk of para-aortic nodal metastasis in incompletely staged patients with endometrial cancer. METHODS: From 8 institutions, the medical records of 397 patients who underwent pelvic and para-aortic lymphadenectomy as a surgical staging procedure were retrospectively reviewed. A multivariate logistic regression model was created and internally validated by rigorous bootstrap resampling methods. Finally, the model was transformed into a user-friendly Web-based nomogram (http://http://www.kgog.org/nomogram/empa001.html). RESULTS: The rate of para-aortic nodal metastasis was 14.4% (57/397 patients). Using a stepwise variable selection, 4 variables including deep myometrial invasion, non-endometrioid subtype, lymphovascular space invasion, and log-transformed CA-125 levels were finally adopted. After 1000 repetitions of bootstrapping, all of these 4 variables retained a significant association with para-aortic nodal metastasis in the multivariate analysis-deep myometrial invasion (P = 0.001), non-endometrioid histologic subtype (P = 0.034), lymphovascular space invasion (P = 0.003), and log-transformed serum CA-125 levels (P = 0.004). The model showed good discrimination (C statistics = 0.87; 95% confidence interval, 0.82-0.92) and accurate calibration (Hosmer-Lemeshow P = 0.74). CONCLUSIONS: This nomogram showed good performance in predicting para-aortic metastasis in patients with endometrial cancer. The tool may be useful in determining the extent of lymphadenectomy after incomplete surgery.

1p36.22 region containing PGD gene is frequently gained in human cervical cancer.

AIM: To identify commonly occurring DNA copy number alterations in Korean cervical cancers. METHODS: DNA copy number alteration was screened by whole-genome array comparative genomic hybridization (CGH) analysis. For the array CGH discovery, genomic DNA from five cervical cancers and 10 normal cervical tissues were examined. For the independent validation of the most significant chromosomal alteration (1p36.22, PGD gene), 40 formalin-fixed paraffin-embedded cervical tissue samples were collected; 10 of them were used for quantitative polymerase chain reaction and the other 30 samples were used for immunohistochemical analysis. Chromosomal segments differently distributed between cancers and normal controls were determined to be recurrently altered regions (RAR). RESULTS: A total of 13 RAR (11 RAR losses and two RAR gains) were defined in this study. Of the 13 cervical cancer-specific RAR, RAR gain in the 1p36.22 locus where the PGD gene is located was the most commonly detected in cancers (P = 0.004). In the quantitative polymerase chain reaction replication, copy number gain of the PGD gene was consistently identified in cervical cancers but not in the normal tissues (P = 0.02). In immunohistochemical analysis, PGD expression was significantly higher in cervical cancers than normal tissues (P = 0.02). CONCLUSION: Our results will be helpful to understand cervical carcinogenesis, and the PGD gene can be a useful biomarker of cervical cancer.

Comparison of Long-Term Outcomes in Early-Stage Endometrial Cancer: Robotic Single-Site vs. Multiport Laparoscopic Surgery.

The purpose of this study was to establish the noninferiority of robotic single-site (RSS) surgery compared with multiport laparoscopic (MPL) surgery in surgical outcomes and overall survival for early endometrial cancer. This study was conducted retrospectively in a single center and included 421 patients who underwent either RSS (n = 146) or MPL (n = 275) surgery between 2014 and 2022. In terms of perioperative outcomes, the RSS group had a longer operating time than the MPL surgery group (mean (standard deviation [SD]) RSS 97.55 [29.79] vs. MPL 85.56 [26.13], p < 0.001). However, no significant differences in estimated blood loss or perioperative complications were found between the groups (p = 0.196 and p = 0.080, respectively). The patients in the RSS group were discharged earlier than those in the MPL group (mean [SD]): 4.06 [3.24] vs. 9.39 [4.76], p < 0.001). Regarding oncologic outcomes, no significant differences in the type of therapy, disease stage, tumor grade, histopathological type, or lymphovascular invasion were found between the groups. No statistically significant differences were found in the disease-free (p = 0.27) and overall survival rates (p = 0.5) either. In conclusion, this study suggests that RSS and MPL surgery are both safe and effective options for staging operations in patients with early-stage endometrial cancer.

Serum Lipidome Profiling Reveals a Distinct Signature of Ovarian Cancer in Korean Women.

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. IMPACT: Here, we show the potential of circulating lipids in distinguishing ovarian cancer from nonovarian cancer conditions.

A phase 1/2a, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet in healthy women and patients with cervical intraepithelial neoplasia 2.

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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02139267.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Prevalence and type distribution of human papillomavirus in cervical adenocarcinoma in Korean women.

BACKGROUND: An increase in incidence of cervical adenocarcinoma (CADC) has been reported in many countries, including Korea. However, few studies describe human papillomavirus (HPV) type distribution among CADC in Asia. OBJECTIVE AND METHODS: This was a retrospective, hospital-based observational study between 2005 and 2010 to estimate the overall prevalence and distribution of HPV types among CDAC in Korean women. The study used hematoxylin & eosin and immunohistochemical staining (for the two biomarkers p16 and progesterone receptor [PR]) to diagnose and subtype CADC samples. HPV DNA was amplified by polymerase chain reaction (PCR) and HPV genotypes were identified using reverse hybridization. RESULTS: Of 196 cases submitted, 89.3% of the cases were confirmed as CADC. The mean age at diagnosis was 47.1 (standard deviation [SD] 11.9) years. No statistically significant differences in mean age at diagnosis by histological subtype were found. HPV DNA was detected in 90.3% (177/196) of CADC. HPV-18 was the most prevalent type (54.2%), followed by HPV-16 (44.1%) and HPV-45 (3.4%). Infection with any high-risk HPV type was identified in 97.7% of HPV-DNA-positive CADC. The biomarker p16 was positive in 92% of CADC cases and PR was positive in 19.6% of CADC. CONCLUSION: HPV DNA was found in the large majority of CADC in Korean women, with HPV-18 being the most common type followed by HPV-16 and HPV-45. This study is among the first in Asia to specifically report HPV type distribution in CADC. This information will help inform policy decisions concerning HPV vaccination for the prevention of CADC.

Regulatory role of osteopontin in malignant transformation of endometrial cancer.

Osteopontin (OPN) involves in the tumor-promoting or metastasis in human endometrial cancer. Depletion of OPN gene expression in endometrial cancer cells was significantly decreased in cell viability and the cells undergo apoptotic cell death. The status of OPN in THESC, RL95, Hec1A and Ishikawa cell lines were analyzed by RT-PCR and western blot. After OPN-siRNA transfection, mRNA and protein expression levels of OPN were determined in Hec1A and Ishikawa cells. Cell proliferation and cell cycle distribution were observed by MTT and flow cytometry analysis. DNA fragmentation assay was used to measure cell apoptosis. Cell migration was assessed by wound healing assay. Depletion of OPN gene expression in endometrial cancer cell lines (Hec1A and Ishikawa cells) reproducibly changed their ability of proliferation. Concomitant changes were seen in the expression of OPN binding cell surface receptors, cell cycle-regulatory genes, cell invasion and colony formation nature of the tumor cells. Decreased colonizing potential in the absence of OPN was reversed in the presence of recombinant OPN. Inhibition of anchorage-independent growth was observed in the presence of metabolic inhibitors of the PI3K, Src and integrin signaling cascades, which was ameliorated in the presence of exogenously added OPN. Our result showed the role of OPN in endometrial cancer, in particular on the malignancy-promoting aspects of OPN that may pave way for new approaches to the clinical management of endometrial cancer.

The attitudes of Korean cancer patients, family caregivers, oncologists, and members of the general public toward advance directives.

PURPOSE: The purpose of this study was to investigate Korean attitudes toward advance directives (ADs) among cancer patients, family caregivers, oncologists, and the general public. METHODS: A multicenter survey study explored the attitudes of participants to ADs, and hospice-palliative care (HPC) was conducted. A total of 1,242 cancer patients, 1,289 family caregivers, 303 oncologists, and 1,006 members of the general public participated in the survey. RESULTS: The majority of patients, family caregivers, oncologists, and general public agreed with the necessity of ADs. However, oncologists regard "when became terminal status" as an optimal timing for completion of ADs (52.2 %), while other groups regard earlier periods as it. More than 95 % oncologist answered that cardiopulmonary resuscitation and mechanical ventilator are necessity items for ADs form, while around 70 % of other groups answered so. Multivariate analysis revealed that several factors including agreement with terminal disclosures and a positive attitude toward HPC were independently associated with necessity of ADs. CONCLUSIONS: We found that attitudes toward ADs among cancer patients, family caregivers, oncologists, and the general public were significantly different. Our study also suggests that favorable attitudes toward comfort end-of-life care and HPC are keys that influence the perceived need for ADs.

The synergistic apoptotic interaction of Indole-3-Carbinol and Genistein with TRAIL on endometrial cancer cells.

Induction of apoptosis in target cells is a key mechanism by which chemotherapy promotes cell killing. The purpose of this study was to determine whether Indole-3-Carbinol (I3C) and Genistein in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce apoptosis in endometrial cancer cell (Ishikawa) and to assess apoptotic mechanism. The MTT assay and flow cytometry were performed to determine cell viability and cell cycle. The induction of apoptosis was measured by caspase-3 activity test, DNA fragmentation assay, annexin V binding assay and western blot analysis. There was no effect in cell growth inhibition and cell cycle progression alone or in two-combination. However, the treatment of I3C and Genistein followed by TRAIL showed significant cell death and marked increase in sub-G1 arrest. Three-combination treatment revealed elevated expression of DR4, DR5 and cleaved forms of caspase-3, caspase-8, PARP. The Flip was found down regulated. Moreover, increase in caspase-3 activity and DNA fragmentation indicated the induction of apoptosis. The results indicate that I3C and Genistein with TRAIL synergistically induced apoptosis via death receptor dependent pathway. Our findings might provide a new insight into the development of novel combination therapies against endometrial cancer.