A framework for nationwide COVID-19 vaccine safety research in the Republic of Korea: the COVID-19 Vaccine Safety Research Committee

With the introduction of coronavirus disease 2019 (COVID-19) vaccines, the Korea Disease Control and Prevention Agency (KDCA) commissioned the National Academy of Medicine of Korea to gather experts to independently assess post-vaccination adverse events. Accordingly, the COVID-19 Vaccine Safety Research Committee (CoVaSC) was launched in November 2021 to perform safety studies and establish evidence for policy guidance. The CoVaSC established 3 committees for epidemiology, clinical research, and communication. The CoVaSC mainly utilizes pseudonymized data linking KDCA’s COVID-19 vaccination data and the National Health Insurance Service’s claims data. The CoVaSC’s 5-step research process involves defining the target diseases and organizing ad-hoc committees, developing research protocols, performing analyses, assessing causal relationships, and announcing research findings and utilizing them to guide compensation policies. As of 2022, the CoVaSC completed this research process for 15 adverse events. The CoVaSC launched the COVID-19 Vaccine Safety Research Center in September 2022 and has been reorganized into 4 divisions to promote research including international collaborative studies, long-/short-term follow-up studies, and education programs. Through these enhancements, the CoVaSC will continue to swiftly provide scientific evidence for COVID-19 vaccine research and compensation and may serve as a model for preparing for future epidemics of new diseases.

Long-term outcomes of photodynamic therapy for a positive resection margin after conization for cervical intraepithelial neoplasia grade 3.

BACKGROUND: Positive resection margins after conization or loop electrosurgical excision procedure (conization/LEEP) are associated with increased risks of recurrence or residual cervical intraepithelial neoplasia (CIN). Herein, we investigated the long-term outcomes of photodynamic therapy (PDT) for incomplete excision of CIN3. METHODS: We retrospectively reviewed the medical charts of 73 patients treated with PDT between 2000 and 2011. Patients who underwent conization/LEEP before PDT within 6 months were included. The primary outcomes were the complete response (CR) rate after 1 year and human papillomavirus (HPV) eradication rate at 6 months after PDT. RESULTS: A total of 34 patients with positive resection margins were finally enrolled. The median patient age was 33 years. Carcinoma in situ was diagnosed in 25 patients and CIN3 in 7 patients. The CR rate was 97.1% after 1 year. Except for one case of a persistent disease, there was no recurrence or newly developed disease during the median follow-up of 84 months (range, 12-224 months). The HPV eradication rate of PDT following conization/LEEP after 6 months was 96.9% (31/32). Photosensitivity was identified in five patients and cervical stenosis in one patient. CONCLUSIONS: In conclusion, PDT could be an effective therapeutic option for patients with a positive resection margin after conization/LEEP for CIN3. It could reduce the residual or recurrence rate of CIN lesions with tolerable adverse events.

Machine Learning Approach for Active Vaccine Safety Monitoring

Background@#Vaccine safety surveillance is important because it is related to vaccine hesitancy, which affects vaccination rate. To increase confidence in vaccination, the active monitoring of vaccine adverse events is important. For effective active surveillance, we developed and verified a machine learning-based active surveillance system using national claim data. @*Methods@#We used two databases, one from the Korea Disease Control and Prevention Agency, which contains flu vaccination records for the elderly, and another from the National Health Insurance Service, which contains the claim data of vaccinated people. We developed a casecrossover design based machine learning model to predict the health outcome of interest events (anaphylaxis and agranulocytosis) using a random forest. Feature importance values were evaluated to determine candidate associations with each outcome. We investigated the relationship of the features to each event via a literature review, comparison with the Side Effect Resource, and using the Local Interpretable Model-agnostic Explanation method. @*Results@#The trained model predicted each health outcome of interest with a high accuracy (approximately 70%). We found literature supporting our results, and most of the important drug-related features were listed in the Side Effect Resource database as inducing the health outcome of interest. For anaphylaxis, flu vaccination ranked high in our feature importance analysis and had a positive association in Local Interpretable Model-Agnostic Explanation analysis. Although the feature importance of vaccination was lower for agranulocytosis, it also had a positive relationship in the Local Interpretable Model-Agnostic Explanation analysis. @*Conclusion@#We developed a machine learning-based active surveillance system for detecting possible factors that can induce adverse events using health claim and vaccination databases. The results of the study demonstrated a potentially useful application of two linked national health record databases. Our model can contribute to the establishment of a system for conducting active surveillance on vaccination.

Machine Learning Approach for Active Vaccine Safety Monitoring

Background@#Vaccine safety surveillance is important because it is related to vaccine hesitancy, which affects vaccination rate. To increase confidence in vaccination, the active monitoring of vaccine adverse events is important. For effective active surveillance, we developed and verified a machine learning-based active surveillance system using national claim data. @*Methods@#We used two databases, one from the Korea Disease Control and Prevention Agency, which contains flu vaccination records for the elderly, and another from the National Health Insurance Service, which contains the claim data of vaccinated people. We developed a casecrossover design based machine learning model to predict the health outcome of interest events (anaphylaxis and agranulocytosis) using a random forest. Feature importance values were evaluated to determine candidate associations with each outcome. We investigated the relationship of the features to each event via a literature review, comparison with the Side Effect Resource, and using the Local Interpretable Model-agnostic Explanation method. @*Results@#The trained model predicted each health outcome of interest with a high accuracy (approximately 70%). We found literature supporting our results, and most of the important drug-related features were listed in the Side Effect Resource database as inducing the health outcome of interest. For anaphylaxis, flu vaccination ranked high in our feature importance analysis and had a positive association in Local Interpretable Model-Agnostic Explanation analysis. Although the feature importance of vaccination was lower for agranulocytosis, it also had a positive relationship in the Local Interpretable Model-Agnostic Explanation analysis. @*Conclusion@#We developed a machine learning-based active surveillance system for detecting possible factors that can induce adverse events using health claim and vaccination databases. The results of the study demonstrated a potentially useful application of two linked national health record databases. Our model can contribute to the establishment of a system for conducting active surveillance on vaccination.

Methods for Systematic Identification of Membrane Proteins for Specific Capture of Cancer-Derived Extracellular Vesicles.

Analysis of cancer-derived extracellular vesicles (EVs) in biofluids potentially provides a source of disease biomarkers. At present there is no procedure to systematically identify which antigens should be targeted to differentiate cancer-derived from normal host cell-derived EVs. Here, we propose a computational framework that integrates information about membrane proteins in tumors and normal tissues from databases: UniProt, The Cancer Genome Atlas, the Genotype-Tissue Expression Project, and the Human Protein Atlas. We developed two methods to assess capture of EVs from specific cell types. (1) We used palmitoylated fluorescent protein (palmtdTomato) to label tumor-derived EVs. Beads displaying antibodies of interest were incubated with conditioned medium from palmtdTomato-expressing cells. Bound EVs were quantified using flow cytometry. (2) We also showed that membrane-bound Gaussia luciferase allows the detection of cancer-derived EVs in blood of tumor-bearing animals. Our analytical and validation platform should be applicable to identify antigens on EVs from any tumor type.

Big data differential analysis of microglial cell responses in neurodegenerative diseases / 대한해부학회지

Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models.

Intraperitoneal (IP) chemotherapy for ovarian cancer treatment prolongs overall survival by 16 months compared to intravenous chemotherapy but is not widely practiced due to catheter-related complications and complexity of administration. An implantable, nonresorbable IP microdevice was used to release chemotherapeutic agent at a constant rate of approximately 1.3 µg/h in vitro and 1.0 µg/h in vivo. Studies conducted in two orthotopic murine models bearing human xenografts (SKOV3 and UCI101) demonstrate that continuous dosing reduces tumor burden to the same extent as weekly IP bolus drug injections. Treatment-induced toxicity was quantified via body weight loss and complete blood count. The microdevice resulted in significantly less toxicity than IP bolus injections, despite administration of higher cumulative doses (total area under the concentration-time curve of 3049 ng day/mL with the microdevice vs. 2118 ng-day/mL with IP bolus injections). This preclinical study supports the concept that reduced toxicity with similar efficacy outcomes can be achieved by continuous dosing in ovarian cancer patients currently treated with IP therapy.

Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes.

Highly sensitive detection of small, deep tumors for early diagnosis and surgical interventions remains a challenge for conventional imaging modalities. Second-window near-infrared light (NIR2, 950-1,400 nm) is promising for in vivo fluorescence imaging due to deep tissue penetration and low tissue autofluorescence. With their intrinsic fluorescence in the NIR2 regime and lack of photobleaching, single-walled carbon nanotubes (SWNTs) are potentially attractive contrast agents to detect tumors. Here, targeted M13 virus-stabilized SWNTs are used to visualize deep, disseminated tumors in vivo. This targeted nanoprobe, which uses M13 to stably display both tumor-targeting peptides and an SWNT imaging probe, demonstrates excellent tumor-to-background uptake and exhibits higher signal-to-noise performance compared with visible and near-infrared (NIR1) dyes for delineating tumor nodules. Detection and excision of tumors by a gynecological surgeon improved with SWNT image guidance and led to the identification of submillimeter tumors. Collectively, these findings demonstrate the promise of targeted SWNT nanoprobes for noninvasive disease monitoring and guided surgery.

Clinical Neuroanatomy and Neurotransmitter-Mediated Regulation of Penile Erection / 대한배뇨장애요실금학회지

Erectile dysfunction (ED) has an adverse impact on men's quality of life. Penile erection, which is regulated by nerves that are innervated into the erectile tissue, can be affected by functional or anatomical trauma of the perineal region, including specific structures of the penis, causing ED. Penile erection is neurologically controlled by the autonomic nervous system. Therefore, it is of utmost importance to understand the neurogenic structure of the erectile tissue and the types of neurotransmitters involved in the penile erection process. Here, we highlight the basic clinical anatomy and erectile function of the penis. Understanding the clinical connotation of the relationship between penile erectile structure and function may provide fresh insights for identifying the main mechanisms involved in ED and help develop surgical techniques for the treatment of ED.

G protein-coupled receptor, family C, group 5 (GPRC5B) downregulation in spinal cord neurons is involved in neuropathic pain / 대한마취과학회지

BACKGROUND: G protein-coupled receptor, family C, group 5 (GPRC5B), a retinoic acid-inducible orphan G-protein-coupled receptor (GPCR), is a member of the group C metabotropic glutamate receptor family proteins presumably related in non-canonical Wnt signaling. In this study, we investigated altered GPRC5B expression in the dorsal horn of the spinal cord after spinal nerve injury and its involvement in the development of neuropathic pain. METHODS: After induction of anesthesia by intraperitoneal injection of pentobarbital (35 mg /kg), the left L5 spinal nerve at the level of 2 mm distal to the L5 DRG was tightly ligated with silk and cut just distal to the ligature. Seven days after nerve injury, animals were perfused with 4% paraformaldehyde, and the spinal cords were extracted and post-fixed at 4degrees C overnight. To identify the expression of GPRC5B and analyze the involvement of GPRC5B in neuropathic pain, immunofluorescence was performed using several markers for neurons and glial cells in spinal cord tissue. RESULTS: After L5 spinal nerve ligation (SNL), the expression of GPRC5B was decreased in the ipsilateral part, as compared to the contralateral part, of the spinal dorsal horn. SNL induced the downregulation of GPRC5B in NeuN-positive neurons in the spinal dorsal horn. However, CNPase-positive oligodendrocytes, OX42-positive microglia, and GFAP-positive astrocytes were not immunolabeled with GPRC5B antibody in the spinal dorsal horn. CONCLUSIONS: These results imply that L5 SNL-induced GPRC5B downregulation may affect microglial activation in the spinal dorsal horn and be involved in neuropathic pain.

Robustness of chemometrics-based feature selection methods in early cancer detection and biomarker discovery.

In omics studies aimed at the early detection and diagnosis of cancer, bioinformatics tools play a significant role when analyzing high dimensional, complex datasets, as well as when identifying a small set of biomarkers. However, in many cases, there are ambiguities in the robustness and the consistency of the discovered biomarker sets, since the feature selection methods often lead to irreproducible results. To address this, both the stability and the classification power of several chemometrics-based feature selection algorithms were evaluated using the Monte Carlo sampling technique, aiming at finding the most suitable feature selection methods for early cancer detection and biomarker discovery. To this end, two data sets were analyzed, which comprised of MALDI-TOF-MS and LC/TOF-MS spectra measured on serum samples in order to diagnose ovarian cancer. Using these datasets, the stability and the classification power of multiple feature subsets found by different feature selection methods were quantified by varying either the number of selected features, or the number of samples in the training set, with special emphasis placed on the property of stability. The results show that high consistency does not necessarily guarantee high predictive power. In addition, differences in the stability, as well as agreement in feature lists between several feature selection methods, depend on several factors, such as the number of available samples, feature sizes, quality of the information in the dataset, etc. Among the tested methods, only the variable importance in projection (VIP)-based method shows complementary properties, providing both highly consistent and accurate subsets of features. In addition, successive projection analysis (SPA) was excellent with regards to maintaining high stability over a wide range of experimental conditions. The stability of several feature selection methods is highly variable, stressing the importance of making the proper choice among feature selection methods. Therefore, rather than evaluating the selected features using only classification accuracy, stability measurements should be examined as well to improve the reliability of biomarker discovery.

Mechanism Underlying NaF-Induced Apoptosis in Human Oral Squamous Cell Carcinoma

Few studies have evaluated the apoptosis-inducing efficacy of NaF on cancer cells in vitro but there has been no previous investigation of the apoptotic effects of NaF on human oral squamous cell carcinoma cells. In this study, we have investigated the mechanisms underlying the apoptotic response to NaF treatment in the YD9 human squamous cell carcinoma cell line. The viability of YD9 cells and their growth inhibition were assessed by MTT and clonogenic assays, respectively. Hoechst staining, DNA electrophoresis and TUNEL staining were conducted to detect apoptosis. YD9 cells were treated with NaF, and western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, and MMP and proteasome activity assays were performed sequentially. The NaF treatment resulted in a time- and dose-dependent decrease in YD9 cell viability, a dose-dependent inhibition of cell growth, and the induction of apoptotic cell death. The apoptotic response of these cells was manifested by nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, a significant shift of the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-3, PARP, Lamin A/C and DFF45 (ICAD). Furthermore, NaF treatment resulted in the downregulation of G1 cell cyclerelated proteins, and upregulation of p53 and the Cdk inhibitor p27KIP1. Taken collectively, our present findings demonstrate that NaF strongly inhibits YD9 cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via mitochondrial and caspase pathways.

Mechanism Underlying NaF-Induced Apoptosis in Human Oral Squamous Cell Carcinoma

Few studies have evaluated the apoptosis-inducing efficacy of NaF on cancer cells in vitro but there has been no previous investigation of the apoptotic effects of NaF on human oral squamous cell carcinoma cells. In this study, we have investigated the mechanisms underlying the apoptotic response to NaF treatment in the YD9 human squamous cell carcinoma cell line. The viability of YD9 cells and their growth inhibition were assessed by MTT and clonogenic assays, respectively. Hoechst staining, DNA electrophoresis and TUNEL staining were conducted to detect apoptosis. YD9 cells were treated with NaF, and western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, and MMP and proteasome activity assays were performed sequentially. The NaF treatment resulted in a time- and dose-dependent decrease in YD9 cell viability, a dose-dependent inhibition of cell growth, and the induction of apoptotic cell death. The apoptotic response of these cells was manifested by nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, a significant shift of the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-3, PARP, Lamin A/C and DFF45 (ICAD). Furthermore, NaF treatment resulted in the downregulation of G1 cell cyclerelated proteins, and upregulation of p53 and the Cdk inhibitor p27KIP1. Taken collectively, our present findings demonstrate that NaF strongly inhibits YD9 cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via mitochondrial and caspase pathways.

Ovarian cancer: markers of response.

OBJECTIVES: Despite improved knowledge regarding the etiology of ovarian cancer, as well as application of aggressive surgery and chemotherapy, there has been only a modest change in the mortality statistics over the last 30 years. Given these results and the evolution of targeted therapies, there is an increasing need for prognostic and predictive factors to stratify patients for individualized care. Many laboratories have also investigated the specific individual biomarkers correlating them with clinicopathologic characteristics. Unfortunately, the vast majorities of these biomarkers have not proved clinically valuable. In this article, we review published genomic signatures including data generated in our laboratory for their relevance. METHODS: Multiple published expression profiling articles were selected for review and discussion. Genomic studies were separated from those with dichotomized survival data and unsupervised analysis to identify discreet subsets of tumors and studies that generated activated pathways. RESULTS: The identification of prognostic and predictive individual biomarkers has been common. Few of these have been validated. Genomic profiles have been obtained that distinguish short- from long-term survivors. The relevance of these studies to the large number of patients within the extremes remains unclear. Unsupervised clustering studies of ovarian cancers have identified potential subsets of tumors that reflect different clinical behavior. These studies will require large numbers of independent samples for validation. Another approach has been to identify genes that correlate with patient survival as a continuous variable. These genes are then placed into biologic context using pathway analysis. These pathways provide potential therapeutic targets, and those patients whose tumors express these targets may be most effectively treated by using inhibitors specific for the pathway. CONCLUSIONS: There is a major need for prognostic and predictive biomarkers for ovarian cancer. With the development of new genomic technologies, there is an opportunity to identify gene expression signatures that can be used to stratify patients according to their ultimate survival and response to chemotherapy. Large independent sets and robust statistical techniques will be required to fully exploit this approach.

Nutrition Knowledge and Eating Behaviors of Elementary School Children in Seoul / 대한지역사회영양학회지

This study was aimed to examine nutrition knowledge, dietary attitudes, and eating habits of elementary school students and to examine if their characteristics differ by gender. Subjects were 5th and 6th graders of an elementary school (n = 317) in Seoul, and the survey was done during July 2007. Mean height, weight, BMI of subjects was 148.1 cm. 41.7 kg, 19.0, and 14.3% of subjects were categorized as the overweight/obese group. Anthropometric data were not significantly different by gender. Mean score of nutrition knowledge was 14.9 out of 20 showing moderate knowledge levels, and girls scored higher on nutrition knowledge than boys (p < 0.05). Subjects showed knowledge deficit in areas such as nutrients, food groups and specific weight control information. The percentages of correct answers regarding meals for brain function were significantly higher in girls than in boys (p < 0.05). They got nutrition information mainly from mass media and family/relatives. The mean score of dietary attitudes was 41.2 (possible score: 10-50) indicating somewhat positive attitudes, and the score of eating behaviors was 34.8 (possible score: 15-45). Subjects showed problems in eating habits such as having unbalanced diets and snack foods. 82.6% of subjects had unbalanced meals, and these percentages were higher in girls (87.2%) than in boys (78.1%, p < 0.05). Vegetables and fish/shellfish were the most disliked foods. Specific eating behaviors, such as eating slowly, eating grains and having processed foods less frequently, were better in girls than in boys (p < 0.05). Results also showed that majority of subjects need to improve specific behaviors including having diverse foods, eating meals slowly, having meals at regular times, having adequate foods in each food groups, and eating sweets or salty foods less frequently. Only 52.7% of subjects perceived their body images as normal, and 56.4% had experience of weight control. Reasons for weight control were different by gender (p< 0.05). Based on these findings, nutrition education for school children should focus on modifying eating habits or eating behaviors, by suggesting practically applicable methods and providing nutrition information that is interesting and suitable to school-aged children.

Successful use of magnetic resonance-guided focused ultrasound surgery to relieve symptoms in a patient with symptomatic focal adenomyosis.

OBJECTIVE: To report a successful treatment of symptomatic adenomyosis using magnetic resonance-guided focused ultrasound surgery (MRgFUS). DESIGN: Case study. SETTING: General hospital. PATIENT(S): A 47-year-old premenopausal woman with focal symptomatic adenomyosis. INTERVENTION(S): MRgFUS. MAIN OUTCOME MEASURE(S): Score on the Uterine Fibroids Symptoms Quality of Life (UFS-QOL) questionnaire and the degree of menstrual pain. RESULT(S): Uterine Fibroids Symptoms reduced from 53 to 28 and the degree of menstrual pain reduced from 10 to 5. CONCLUSION(S): For adenomyosis patients who wish to preserve their uterus, MRgFUS may be a promising alternative to hysterectomy. Additional studies of the safety and efficacy of MRgFUS in this indication should be conducted.

Patient selection guidelines in MR-guided focused ultrasound surgery of uterine fibroids: a pictorial guide to relevant findings in screening pelvic MRI.

Uterine leiomyomas (fibroids), the most common benign tumor in women of childbearing age, can cause symptoms including dysmenorrhea, menorrhagia, urinary symptoms, pain and infertility. Hysterectomy is a common approach to treating uterine fibroids, and less invasive surgical approaches such as myomectomy and uterine artery embolization also have been shown to alleviate symptoms. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is the only totally non-invasive surgical approved method for treating uterine fibroids. In clinical trials, MRgFUS resulted in significant relief of uterine fibroid symptoms. The safe and effective use of MRgFUS is affected by fibroid type and location, position relative to adjacent anatomical structures and the presence of co-existent pelvic disease. Additionally, successful outcomes with MRgFUS have been correlated with the volume of fibroids ablated during the procedure. Thus, selection of patients in whom sufficient fibroid volumes can be treated safely using the MRgFUS system is critical for successful outcomes. The MR images in this pictorial essay provide examples of uterine fibroids for which MRgFUS should be considered and is designed to facilitate the selection of patients for whom MRgFUS is most likely to provide sustained symptom relief.

Apoptotic Effect of Co-Treatment with a Natural Product, Chios Gum Mastic, and a Proteasome Inhibitor, Lactacystin, on Human Osteosarcoma Cells / 대한해부학회지

Chios gum mastic (CGM) is a resinous exudate obtained from the stem and the main leaves of Pistacia lenticulus tree native to Mediterranean areas. Recently, it was reported that CGM induced apoptosis in a few cancer cells in vitro. Since recent studies indicated the synergistic interactions between the apoptotic stimulus and a proteasome inhibitor, the ubiquintin-proteasome pathway has become an attractive target in cancer therapy. And to date, there has been no report of the synergistic apoptotic effect between CGM and a proteasome inhibitor to become an attractive target in cancer therapy. Therefore, this study was undertaken to investigate the synergistic apoptotic effect of co-treatment with a natural product, CGM, and a proteasome inhibitor, lactacystin, on human osteosarcoma (HOS) cells. To investigate whether the co-treatment of CGM and lactacystin compared with each single treatment efficiently induced apoptosis on HOS cells, MTT assay, DNA electrophoresis, Hoechst staining, DNA hypoploidy assay, Westen blot analysis, immunofluorescent staining, proteasome activity and mitochondrial membrane potential (MMP) change were performed. In this study, HOS cells co-treated with CGM and lactacystin showed several lines of apoptotic manifestation such as nuclear condensation, DNA fragmentation, the reduction of MMP and proteasome activity, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-7, caspase-3, PARP and DFF45 (ICAD) whereas each single treated HOS cells hardly showed. We presented data indicating that the co-treatment of CGM and lactacystin induced potentially apoptosis whereas each single treatment did slightly. Moreover, the co-treatment of CGM and lactacystin potentiated the inhibition of proteasome activity. Therefore, our data provide the possibility that combination therapy of CGM and lactacystin could be considered as a novel therapeutic strategy for human osteosarcoma.

Apoptotic Effect of Co-Treatment with a Natural Product, Chios Gum Mastic, and a Synthetic Chenodeoxycholic Acid Derivative, HS-1200, on Human Osteosarcoma Cells / 체질인류학회지

Chios gum mastic (CGM) is a resinous exudate obtained from the stem and the main leaves of Pistacia lenticulus tree native to Mediterranean areas. Recently it reported that CGM induced apoptosis in a few cancer cells in vitro. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with a natural product, CGM and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. To investigate whether the co-treatment of CGM and HS-1200 compared with each single treatment efficiently reduced the viability of HOS cells, MTT assay was conducted. Induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and DNA hypoploidy, Westen blot analysis and immunofluorescent staining were performed to study the alterations of the expression level and translocation of apoptosis-related proteins in co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) change were also assayed. In this study, HOS cells co-treated with CGM and HS-1200 showed several lines of apoptotic manifestation whereas each single treated HOS cells did not. Although the single treatment of 40 microgram/mL CGM or 25 micrometer HS-1200 for 24 h did not induce apoptosis, the cotreatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of CGM and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

Management of high-risk hydatidiform mole and persistent gestational trophoblastic neoplasia: the Korean experience.

OBJECTIVE: To test the efficacy of a new scoring system to differentiate high-risk hydatidiform mole (H-mole) and initiate early selective postmolar chemotherapy. STUDY DESIGN: According to Kim's scoring system, 262 patients were identified as high-risk H-mole patients. Fifty (19.1%) received early chemotherapy, and the rest constituted the control group. Salvage therapy with etoposide, methotrexate, actinomycin D/etoposide, cisplatin (EMA/EP) and taxol, cisplatin/taxol, etoposide (TP/TE) was applied in 21 cases of ultra-high-risk GTT. RESULTS: None of the 50 cases in the early chemotherapy group progressed to persistent GTT. However, 58.9% in the control group developed GTT with 8.0% drug resistance. Of those receiving salvage therapy in the 21 ultra-high-risk GTT cases resistant to EMA/CO, 10 of 14 (71%) receiving EMA/EP and 4 of 7 (57.1%) receiving TP/TE achieved remission. CONCLUSION: Early postmolar chemotherapy for high-risk H-mole is effective in preventing progression to persistent GTT and treatment failure. Ultra-high-risk GTT should be approached with multimodal treatment, including EMA/EP and TP/TE regimens.