Preclinical investigation of patient-derived cervical cancer organoids for precision medicine / 부인종양

Objective@#Advanced cervical cancer is still difficult to treat and in the case of recurrent cancer, it is desirable to utilize personalized treatment rather than uniform treatment because the type of recurrence is different for each individual. Therefore, this study aimed to establish a patient-derived organoid (PDO) platform to determine the effects of chemotherapy, radiation therapy, and targeted therapy in cervical cancer. @*Methods@#We established organoids from 4 patients with various types of cervical cancer. The histopathological and gene profiles of these organoid models were compared to determine their characteristics and the maintenance of the patient phenotype. Each type of organoid was also subjected to anticancer drug screening and radiation therapy to evaluate its sensitivity. @*Results@#We established PDOs to recapitulate the main elements of the original patient tumors, including the DNA copy number and mutational profile. We selected 7 drugs that showed growth inhibition in cervical cancer organoids out of 171 using an Food and Drug Administration -approved drug library. Moreover, adenocarcinoma and large-cell neuroendocrine carcinoma showed resistance to radiation therapy. whereas squamous cell carcinoma and villoglandular carcinoma showed a significant response to radiotherapy. @*Conclusion@#Our results showed that patient-derived cervical cancer organoids can be used as a platform for drug and radiation sensitivity testing. These findings suggest that patient-derived cervical cancer organoids could be used as a personalized medicine platform and may provide the best treatment options for patients with various subtypes of cervical cancer.

Improving the Outcomes of Complex Lesions of the Femoropopliteal Artery Using Atherectomy and Drug Coated Balloon

no abstract available.

Simultaneous Occurrence of ImmuneMediated Thrombocytopenia and Myocarditis After mRNA-1273COVID-19 Vaccination: A Case Report

With the global spread of severe acute respiratory syndrome coronavirus 2, several vaccines were developed; messenger RNA (mRNA) vaccines have recently been widely used worldwide. However, the incidence of myocarditis following mRNA vaccination is increasing;although the cause of myocarditis has not yet been clearly identified, it is presumed to be caused by a problem in the innate immune system. Immune-mediated thrombocytopenia (ITP) after vaccination is rare but has been reported and is also assumed to occur by the same mechanism. We report the first case of simultaneous myocarditis and ITP after mRNA vaccination. A 38-year-old woman presented with chest pain, mild dyspnea, and sweating after vaccination with mRNA-1273 vaccine (Moderna) 4 days prior to admission.Upon admission to the emergency department, cardiac enzymes were elevated; blood test performed 5 months ago showed normal platelet count, but severe thrombocytopenia was observed upon admission. After administration of intravenous immunoglobulin, the platelet count improved; subsequently, myocarditis was observed on endomyocardial biopsy. Thus, myocarditis and ITP were judged to have occurred simultaneously due to the expression of the innate immune system markers after mRNA vaccination. The patient was discharged on day 6 of admission.

The clinical and microbiological effects of non-surgical periodontal treatments in necrotizing periodontal disease: case report

Necrotizing periodontal disease caused by plaque bacteria is showed clinical findings including pseudo-membrane, interproximal necrosis of the affected area, pain on palpation and gingiva bleeding. Microbiological examination is showed that patients have fusospirochetal bacteria. Two patients who were provisionally diagnosed as necrotizing periodontal disease received nonsurgical periodontal treatments in conjunction with dressing using 3% hydrogen peroxide and local antibiotic delivery. Before and 3 - 5 days after initial treatment, the levels of periodontal bacteria in gingival crevicular fluid obtained using quantitative PCR were compared. After treatment, patients recovered normal gingiva. The number of periodontal diseases related bacterial species decreased from seven or eight to one. As a result, periodontium of patients with necrotizing periodontal disease was recovered to normal periodontium by nonsurgical periodontal treatments.

Clinical Outcomes of U-blade Gamma3 Nails Used to Treat Patients with Trochanteric Fractures: Retrospective Multicenter Study / 대한고관절학회지

PURPOSE: This study was performed to assess the radiologic and clinical results of U-blade Gamma3 nail use for the treatment of trochanteric fractures. MATERIALS AND METHODS: Between September 2015 and May 2018, all patients aged 65 years and older who underwent surgery with U-blade Gamma3 nails were analyzed. A total of 129 patients were selected based on having at least six months of follow-up. Image evaluations included bone quality (T-score), fracture classification on plain radiograph (AO/OTA), computed tomography configuration, union period, position of lag screw, anatomical reduction, tip apex distance (TAD), sliding extent of lag screw, change of neck shaft angle, and complications leading to reoperations were analyzed. Functional outcome were assessed using the Koval grade (ambulatory ability) at the final follow-up. RESULTS: The mean time to union was 19.7 (range, 6–36) weeks. The screw position was centric (93 cases; 72.1%) and anatomical reduction was achieved in 74 cases (57.4%). The mean TAD was 20.3 (range, 12.3–38.1) mm. The mean sliding length of the lag screws was 3.8 (range, 0.1–12.6) mm. The mean change of neck shaft angle was 3.4° (range, 0–12.8°). Reoperations were required in two cases (1.6%) due to the cutting out of the lag screw (n=1) and metal failure with U-blade bending (n=1). Finally, Koval grades for 49.8% of patients reached preoperative status. CONCLUSION: Overall, use of the U-blade Gamma3 nail led to favorable clinical results, suggesting that this system may be a good option for the treatment of trochanteric fractures.

Cripto Enhances Proliferation and Survival of Mesenchymal Stem Cells by Up-Regulating JAK2/STAT3 Pathway in a GRP78-Dependent Manner

Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1. Notably, treatment with an anti-GRP78 antibody blocked these effects. In addition, pretreatment with STAT3 short interfering RNA (siRNA) inhibited the increase in p-JAK2, c-Myc, cyclin D1, and BCL3 levels caused by Cripto and attenuated the pro-survival action of Cripto on MSCs. We also found that incubation with Cripto protected MSCs from apoptosis caused by hypoxia or H₂O₂ exposure, and the level of caspase-3 decreased by the Cripto-induced expression of B-cell lymphoma 3-encoded protein (BCL3). These effects were sensitive to down-regulation of BCL3 expression by BCL3 siRNA. Finally, we showed that Cripto enhanced expression levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). In summary, our results demonstrated that Cripto activated a novel biochemical cascade that potentiated MSC proliferation and survival. This cascade relied on phosphorylation of JAK2 and STAT3 and was regulated by GRP78. Our findings may facilitate clinical applications of MSCs, as these cells may benefit from positive effects of Cripto on their survival and biological properties.

Berberine Suppresses Fibronectin Expression through Inhibition of c-Jun Phosphorylation in Breast Cancer Cells / 한국유방암학회지

PURPOSE: The exact mechanism regulating fibronectin (FN) expression in breast cancer cells has not been fully elucidated. In this study, we investigated the pharmacological mechanism of berberine (BBR) with respect to FN expression in triple-negative breast cancer (TNBC) cells. METHODS: The clinical significance of FN mRNA expression was analyzed using the Kaplan-Meier plotter database (http://kmplot.com/breast). FN mRNA and protein expression levels were analyzed by real-time polymerase chain reaction and western blotting, respectively. RESULTS: Using publicly available clinical data, we observed that high FN expression was associated with poor prognosis in patients with breast cancer. FN mRNA and protein expression was increased in TNBC cells compared with non-TNBC cells. As expected, recombinant human FN significantly induced cell spreading and adhesion in MDA-MB231 TNBC cells. We also investigated the regulatory mechanism underlying FN expression. Basal levels of FN mRNA and protein expression were downregulated by a specific activator protein-1 (AP-1) inhibitor, SR11302. Interestingly, FN expression in TNBC cells was dose-dependently decreased by BBR treatment. The level of c-Jun phosphorylation was also decreased by BBR treatment. CONCLUSION: Our findings demonstrate that FN expression is regulated via an AP-1–dependent mechanism, and that BBR suppresses FN expression in TNBC cells through inhibition of AP-1 activity.

Erratum: Validation of a Web-Based Tool to Predict the Ipsilateral Breast Tumor Recurrence (IBTR! 2.0) after Breast-Conserving Therapy for Korean Patients / 한국유방암학회지

This article was published with a misspelled the date of acceptance. The date of acceptance should be corrected as “March 7, 2013”.

Breast Cancer Screening Knowledge and Perceived Health Beliefs among Immigrant Women in Korea / 한국유방암학회지

PURPOSE: Recently, through international marriage, immigrant women have rapidly increased throughout Korea. This study was performed to identify health beliefs and practices related to breast cancer screening in immigrant women in Korea. METHODS: A cross-sectional survey was carried out between March and July 2012, and study population included immigrant females from six other Asian countries (Cambodia, China, Japan, Mongolia, Vietnam, and the Philippines). We surveyed 197 women and categorized them into four groups according to home countries. The questionnaire consisted of 55 items, including demographic and socioeconomic factors, breast cancer-related knowledge regarding risk factors and symptoms, beliefs and attitudes towards health and breast cancer, perceived susceptibility, barriers, and benefits of screening. RESULTS: Japanese participants were significantly older and had resided in Korea for more years than other country-of-origin groups (all p<0.001), and showed higher screening rates without statistical significance (p=0.392). In multivariate analysis, country of origin showed a significant correlation with knowledge (p=0.001), positive beliefs (p=0.002), and perceived benefits (p=0.025) of breast cancer screening. The group with the lowest household income showed a significantly lower score of perceived benefits (p=0.022). Through analysis to identify factors affecting participation in screening mammography, we found that education level (p=0.009), occupation status (p=0.006), and Korean language fluency (p=0.002) were independent predictors for screening behavior. CONCLUSION: This study identified conditions related to breast cancer screening knowledge, perception, and behavior of immigrant women in Korea. The results reflect the need for increased social aids to remove barriers to medical services and more educational programs to facilitate higher rates of screening.

The Role of the CDH1 Promoter Hypermethylation in the Axillary Lymph Node Metastasis and Prognosis / 한국유방암학회지

PURPOSE: Hypermethylation of the tumor suppressor genes is frequently observed in the tumor development and progression. However, the correlation between the hypermethylation of the tumor suppressor genes, CDH1 and the axillary lymph node (ALN) metastasis is not fully elucidated. To verify the role of the CDH1 promoter hypermethylation in the ALN metastasis and prognosis, we compared the methylation status of the CDH1 genes in the primary lesion and the paired metastatic ALNs. METHODS: We selected a total of 122 paraffin-embedded specimens of the primary and paired metastatic lymph node from 61 breast cancer patients and analyzed the frequency of hypermethylation in the primary and metastatic lymph node using the methylation-specific polymerase chain reaction. In addition, the methylation status of CDH1 was analyzed with the clinicopathologic characteristics, the disease-free survival and disease-specific survival. RESULTS: The hypermethylation of CDH1 gene was identified in 54 (88.5%) of the 61 patients who had axillary metastasis. The hypermethylation status of the CDH1 gene was significantly increased in the metastatic ALNs compared with that in the primary tumors (60.7% vs. 45.9%, p<0.001). The hypermethylation status of the CDH1 genes in the metastatic ALNs was associated with a poor histologic grade (p=0.041) and the patients who had methylated tumor in the primary lesion showed worse disease-free survival than the patients who did not have methylated tumor (p=0.046). CONCLUSION: This study suggests that hypermethylation of the CDH1 gene may play a pivotal role in the metastasis of the axillary lymph node and the breast cancer recurrence.