Purpose: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. Materials and Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. Results: A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). Conclusion This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

Purpose: We aimed to develop a prognostic model to assist palliative care referral at least 3 months before death in advanced cancer patients treated at an outpatient medical oncology clinic. Materials and Methods: In this prospective cohort study, a total of 200 patients were enrolled at a tertiary cancer center in South Korea. The major eligibility criterion was an expected survival of less than a year as estimated by their oncologists. We analyzed the influences of known prognostic factors along with chemotherapy status, mid-arm circumference, and triceps skinfold thickness on survival time. Results: The mean age of the patients was 64.5 years, 36% were female, and the median survival time was 7.6 months. In the multivariate analysis, we found 6 significant factors related to poor survival: a poor Eastern Cooperative Oncology Group (ECOG) performance status (≥2), not undergoing chemotherapy, anorexia, a low lymphocyte level (<12%), a high lactate dehydrogenase (LDH) level (≥300 IU/L), and a low mid-arm circumference (<23 cm). We developed a prognostic model (score, 0-8.0) to predict 3-month survival based on the multivariate analysis. Patients who scored ≥4.0 points had a short survival of less than 3 months (p<0.001). The discriminating ability of the prognostic model using the area under the receiver operating characteristic curve (AUC) was 0.88. Conclusion The prognostic model using ECOG performance status, chemotherapy status, anorexia, lymphocytes, LDH, and mid-arm circumference can predict 3-month survival in medical oncology outpatients. It can alert oncologists to refer patients to palliative care specialists before it is too late.

BACKGROUND: In order to produce and isolate the exosome derived from the cell of interests, a serum free environment (starvation) has been essential for excluding the unknown effect from serum-derived exosomes. Recently, serum-free culture media have been developed as a substitute for serum supplemented media so that MSC proliferates with maintaining the original characteristics of the cells in a serum free condition. Due to the different properties of the exosomes representing the states and characteristics of the origin cells, a study is needed to compare the properties of the cell-derived exosomes according to the cell culture media. METHODS: To compare the cell culture condition on exosomes, human umbilical cord mesenchymal stem cells (UCMSCs) were cultured with two different media, serum containing media, 10% FBS supplemented DMEM (NM) and serum-free chemically defined media, CellCor TM CD MSC (CDM). To remove FBS-derived exosomes from UCMSC cultured with NM, the medium was replaced with FBS-free DMEM for starvation during exosome isolation. The production yield and expression levels of angiogenic and pro-inflammatory factors were compared. And, the subpopulations of exosome were classified depending on the surface properties and loaded cytokines. Finally, the wound healing and angiogenic effects have been evaluated using in vitro assays. RESULTS: The UCMSC-derived exosomes under two different cell culture media could be classified into subpopulations according to the surface composition and loaded cytokines. Especially, exosome derived from UCMSC cultured with CDM showed higher expression levels of cytokines related to regenerative bioactivities which resulted in enhanced wound healing and angiogenesis. CONCLUSION CDM has the advantages to maintain cell proliferation even during the period of exosome isolations and eliminate unknown side effects caused by serumderived exosomes. Additionally, exosomes derived from UCMSC cultured with CDM show better wound healing and angiogenic effects due to a lot of regeneration-related cytokines and less pro-inflammatory cytokines compared to with NM.

BACKGROUND: In order to produce and isolate the exosome derived from the cell of interests, a serum free environment (starvation) has been essential for excluding the unknown effect from serum-derived exosomes. Recently, serum-free culture media have been developed as a substitute for serum supplemented media so that MSC proliferates with maintaining the original characteristics of the cells in a serum free condition. Due to the different properties of the exosomes representing the states and characteristics of the origin cells, a study is needed to compare the properties of the cell-derived exosomes according to the cell culture media. METHODS: To compare the cell culture condition on exosomes, human umbilical cord mesenchymal stem cells (UCMSCs) were cultured with two different media, serum containing media, 10% FBS supplemented DMEM (NM) and serum-free chemically defined media, CellCor TM CD MSC (CDM). To remove FBS-derived exosomes from UCMSC cultured with NM, the medium was replaced with FBS-free DMEM for starvation during exosome isolation. The production yield and expression levels of angiogenic and pro-inflammatory factors were compared. And, the subpopulations of exosome were classified depending on the surface properties and loaded cytokines. Finally, the wound healing and angiogenic effects have been evaluated using in vitro assays. RESULTS: The UCMSC-derived exosomes under two different cell culture media could be classified into subpopulations according to the surface composition and loaded cytokines. Especially, exosome derived from UCMSC cultured with CDM showed higher expression levels of cytokines related to regenerative bioactivities which resulted in enhanced wound healing and angiogenesis. CONCLUSION CDM has the advantages to maintain cell proliferation even during the period of exosome isolations and eliminate unknown side effects caused by serumderived exosomes. Additionally, exosomes derived from UCMSC cultured with CDM show better wound healing and angiogenic effects due to a lot of regeneration-related cytokines and less pro-inflammatory cytokines compared to with NM.

In our efforts to understand the systemic features of tumors, the importance of animal models is increasing due to the recent growth in the development of immunotherapy and targeted therapies. This has resulted in increased attention towards tumor animal models using C57BL/6N, which are mainly used in immunological studies. In this study, the C57BL/6NKorl stock and two other commercial stocks (C57BL/6NA and C57BL/N6B) are evaluated by comparing the occurrence of tumors using the syngeneic model; furthermore, we compare the response to anti-cancer drugs in the syngeneic model by evaluating survival, growth of tumors, proliferation and molecular biology analysis. In the syngeneic model using LLC (Lewis lung carcinoma) cells, the survival of mice and growth of the tumor showed a better response in the C57BL/6NKorl stock, and was dependent on the cell concentration of the dosing tumor, as compared to the other C57BL/6N stocks. However, the Ki-67 staining showed only little difference in cell proliferation within the tumor tissue each mouse stocks. Comparing the sensitivity to anti-cancer drug by examining changes in growth, volume and weight revealed that cisplatin treatment for tumor-bearing C57BL/6NKorl was more dependent on concentration. The Ki-67 staining, however, showed no difference among the C57BL/6N stocks after cisplatin treatment. The expressions of p27 and p53 tumor suppressor proteins, caspase-3 and Bax showed dose-dependent increase after exposure to cisplatin, whereas the expression of Bcl-2 was reduced in a dose-dependent manner. Furthermore, the expressions of MMP-2 and VEGF involved in metastasis, as well as inflammatory genes IL-1β, IL-6 and IL-10, showed dose-dependent decrease in tumor tissue after cisplatin exposure. Differences observed among the C57BL/6N stocks were not significant. Taken together, our studies reveal that C57BL/6NKorl has the potential of being a useful biological resource established in Korea, as it does not differ from the two commercially available C57BL/6N stocks when considering response to tumor generation and sensitivity to anti-cancer drugs using the syngeneic tumor model.
Animals ; Caspase 3 ; Cell Proliferation ; Cisplatin ; Immunotherapy ; Interleukin-10 ; Interleukin-6 ; Korea ; Lung ; Mice ; Models, Animal ; Molecular Biology ; Neoplasm Metastasis ; Tumor Suppressor Protein p53 ; Vascular Endothelial Growth Factor A

The cysts of Sarcocystis grueneri were detected and characterized from the cardiac muscles of the Korean water deer (Hydropotes inermis argyropus). Of the 38 heart muscle samples examined by light microscopy, 10 were found infected with the cysts of Sarcocystis sp. The cysts appeared oval to spherical shape and measured 110–380 μm in length and 90–170 μm in width. A phylogenetic tree of the 18S rRNA sequences (1.5 kb) revealed a close relationship of the infected cysts to genus Sarcocystis. The 18S rRNA sequence of the infected cysts showed 100% identity to S. grueneri and 97% to S. capracanis. Here, we first report the S. grueneri infections in the Korean water deer.
Deer ; Microscopy ; Myocardium ; Sarcocystis ; Trees ; Water

Metastatic cancers of the stomach are rare. Metastatic diseases of the stomach can occur with melanoma and other primary tumors of the breast, lung, ovary, liver, colon, and testis; however, breast cancer is the most common. Other rare malignant tumors that can involve the stomach include Kaposi's sarcoma, myenteric schwannoma, glomus tumor, small cell carcinoma, and parietal cell carcinoma. On the other hand, solitary fibrous tumors of the pleura are rare soft tissue sarcomas, and most are benign; however, 13 to 36% may be malignant. Metastases may occur in extrathoracic sites, such as the liver, central nervous system, spleen, adrenal gland, and bone. We herein report a case of a 75-year-old man with previously diagnosed brain and liver metastases. He developed a stomach metastasis from a malignant solitary fibrous tumor and presented with gastrointestinal bleeding symptoms.
Adrenal Glands ; Aged ; Brain ; Breast ; Breast Neoplasms ; Carcinoma, Small Cell ; Central Nervous System ; Colon ; Endoscopy ; Female ; Gastrointestinal Hemorrhage ; Glomus Tumor ; Hand ; Hemorrhage ; Humans ; Liver ; Lung ; Melanoma ; Neoplasm Metastasis ; Neurilemmoma ; Ovary ; Pleura ; Sarcoma ; Sarcoma, Kaposi ; Solitary Fibrous Tumors ; Spleen ; Stomach

The aim of this project was to use 3D scanning data collected at incident scenes and various evidence to 1) develop surveying methods based on 3D data consisting of overall and detailed scene evidence, captured by long-range and micros-canner, which can be shared by personnel working in different fields such as forensic medicine, video analysis, physical analysis, traffic engineering, and fire investigation; 2) create digital storage for human skeletons and set the foundation for virtual anthropology; and 3) improve the credibility of 3D evidence by virtual remodeling and simulation of incident scenes and evidence to provide a basis for advanced and high-tech scientific investigation. Two complete skeletons of male and female were scanned using 3D micro-scanner. Each bone was successfully reproduced and assembled in virtual space. In addition, recreating evidence scheduled for invasive examination by creating RP (rapid prototype) was possible. These outcomes could play an important role in setting up the new field of virtual anthropology. Case-specific surveying methods were developed through analysis of 3D scanning data collected by long-range surface scanners at the scenes of vehicular accidents, falls, shootings, and violent crimes. A technique and recording method was also developed for detecting forged seals by micro-scanning the pressure exerted on the seal. Appraisal methods developed in this project could be utilized to secure 3D data of human skeletal remains and incident scenes, create a standard for application, and increase objectivity, reproducibility, and accuracy of scanning methods. We plan to develop case-specific 3D data analysis techniques to improve the credibility of analysis at the NFS and to establish a 3D data collection and analysis team.
Crime ; Data Collection ; Female ; Fires ; Forensic Medicine ; Forensic Sciences ; Humans ; Male ; Skeleton ; Statistics as Topic

Retroperitoneal fibrosis is a disease characterized by proliferation of fibro-inflammatory tissue, which mainly encloses the abdominal aorta, iliac arteries and (enlarges to the retroperitoneum to surrounds) ureters. Two leading pathogenesis are an exacerbated local inflammatory reaction to aortic atherosclerosis and a manifestation of systemic autoimmune disease. Because of insidious disease course, most cases are diagnosed late when bilateral urinary obstruction caused oliguria and symptoms related to uremia. In this case, the patient complained left flank pain which might have been caused by left ureter stone, but through abdominal CT scan, the patient was diagnosed as left unilateral retroperitoneal fibrosis. Abdominal CT scan showed encircling mass around abdominal aorta and left ureter with hydronephrosis. The patient had no underlying disease and didn't take any medication; she was diagnosed as idiopathic unilateral retroperitoneal fibrosis and started prednisolone, 40 mg daily. Three months have passed since the therapy was started; most fibrous tissue was disappeared, hydronephrosis was resolved and flank pain was relieved.
Aorta, Abdominal ; Atherosclerosis ; Autoimmune Diseases ; Flank Pain ; Humans ; Hydronephrosis ; Iliac Artery ; Oliguria ; Prednisolone ; Retroperitoneal Fibrosis ; Uremia ; Ureter

Portal vein thrombosis (PVT) is a rare form of venous thrombosis that affects the hepatic portal vein flow, which can lead to portal hypertension. Treatment of PVT includes anticoagulants, thrombolysis, insertion of shunts, bypass surgery, and liver transplantation. Single anticoagulation therapy is not regarded as a curative treatment but can be associated with a reduction in new thrombotic episodes. We experienced a case of acute total occlusion of PVT provoked by protein C and S deficiency syndrome. PVT was completely recanalized with oral anticoagulant therapy following low molecular weight heparin therapy.
Anticoagulants ; Heparin, Low-Molecular-Weight ; Hypertension, Portal ; Liver Transplantation ; Portal Vein ; Protein C ; Protein C Deficiency ; Protein S Deficiency ; Thrombosis ; Venous Thrombosis