Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

BACKGROUND: The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). METHODS: Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4. RESULTS: Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = −0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775–0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500–0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected. CONCLUSION: TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV.

PURPOSE: Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. MATERIALS AND METHODS: This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS). RESULTS: This study initially planned to enroll 394 patients, but prematurely ended due to low recruitment rate. Overall, 127 patients were included in the analyses: 64 in the lansoprazole group and 63 in the placebo group. During the median follow-up of 6.4 months, tumor bleeding rates were 7.8% and 9.5%, in the lansoprazole and placebo groups, respectively, with the cumulative bleeding incidence not statistically different between the groups (P=0.515, Gray's test). However, during the initial 4 months, 4 placebo-treated patients developed tumor bleeding, whereas there were no bleeding events in the lansoprazole-treated patients (P=0.041, Gray's test). There was no difference in the proportion of patients who required transfusion between the groups. The OS between the lansoprazole (11.7 months) and the placebo (11.0 months) groups was not statistically different (P=0.610). Study drug-related serious adverse event or bleeding-related death did not occur. CONCLUSIONS: Treating patients with inoperable gastric cancer with lansoprazole did not significantly reduce the incidence of tumor bleeding. However, further studies are needed to evaluate whether lansoprazole can prevent tumor bleeding during earlier phases of chemotherapy (ClinicalTrial.gov, identifier No. NCT02150447).
Drug Therapy ; Follow-Up Studies ; Hemorrhage* ; Humans ; Incidence ; Lansoprazole ; Primary Prevention ; Prospective Studies ; Proton Pump Inhibitors ; Proton Pumps* ; Protons* ; Stomach Neoplasms*

PURPOSE: Hollow fiber assays offer an early in vivo method of anticancer drug screening. The assays have been optimized for human cancers originating from the lung, breast, colon, ovary, and brain, but not from the stomach and liver. The current study focused on optimization of hollow fiber assays for gastric and hepatocellular carcinoma cell lines. MATERIALS AND METHODS: Gastric (SNU-16, SNU-484, SNU-668) and hepatocellular (HepG2, SK-Hep-1, Hep3B) carcinoma cell lines in hollow fibers were transplanted subcutaneously and intraperitoneally into mice, which were subsequently treated with a standard anticancer agent, paclitaxel. The hollow fiber activity of paclitaxel in each cell line was compared with the xenograft activity. RESULTS: Using optimized inoculation densities and schedules, treatment with paclitaxel was effective in gastric carcinoma cell lines, SNU-16 and SNU-484, but not in SNU-668. In the hollow fiber assays, paclitaxel was effective in hepatocellular carcinoma cell lines, HepG2 and SK-Hep-1, but not in Hep3B. Consistent with the results of the hollow fiber assay, SNU-16 and SNU-484, but not SNU-668, showed tumor regression, and HepG2 and SK-Hep-1, but not Hep3B, showed effective tumor responses following treatment with paclitaxel in xenograft models. When EW7197, a novel compound, and flavopiridol were tested in SNU-16 cells under optimized conditions, the hollow fiber activity showed good correlation with the xenograft activity of each compound. CONCLUSION: Our protocols may be useful for screening candidate small molecules that may exhibit activity against stomach and liver cancers, both of which are common in Korea.
Animals ; Appointments and Schedules ; Brain ; Breast ; Carcinoma, Hepatocellular ; Cell Line ; Colon ; Drug Evaluation, Preclinical ; Female ; Heterografts ; Humans ; Korea ; Liver ; Liver Neoplasms* ; Lung ; Mass Screening ; Mice ; Ovary ; Paclitaxel ; Stomach Neoplasms ; Stomach*

A 25-yr-old woman presented with a right pleural effusion. Destruction of 9th through 12th ribs, adjacent vertebral bodies, and transverse processes was noted on plain radiograph and a large low-attenuated, irregular shaped mass lesion with peripheral rim enhancement, destroying vertebral body and transverse process, was revealed on the computed tomographic scan. Magnetic resonance imaging showed high signal on T1- weighted image and iso- and low signal on T2-weighted image for the mass lesion replacing the vertebral bony cortex and marrow space. An open rib biopsy revealed the histopathological changes of Gorham's disease (essential osteolysis), even though only bloody fluid filling the empty space and rib and vertebral transverse process destruction were grossly observed on operation. Even though there was no definite response to radiotherapy and pleurodesis, the patient showed stable condition up to 20 months after diagnosis.
Adult ; Chylothorax/complications/*pathology/radiotherapy ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Osteolysis, Essential/complications/*pathology/*radiotherapy ; Pleurodesis ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome

PURPOSE: To evaluate antitumor response, time to progression, and toxicities of oxaliplatin, 5- fluorouracil (5-FU), and leucovorin (LV) continuous infusion in patients with metastatic colorectal cancer who progressed during or after treatment with a 5-FU-containing regimen. MATERIALS AND METHODS: Forty-eight patients with metastatic colorectal cancer, who progressed while receiving or after discontinuing palliative chemotherapy with 5- FU-based regimen, were enrolled in this study. Treatment consisted of oxaliplatin (85 mg/m2 on day 1) as a 2-hour infusion followed by bolus 5-FU (400 mg/m2 on day 1), and 5-FU 48-hour infusion 2.4~3 g/m2 concurrently with LV 48-hour infusion 150 mg/m2, without mixing. Cycles were repeated at 2-week intervals. The dose of 5-FU was modified, depending on the hematologic toxicity profile. RESULTS: The objective response rate was 28% for 43 assessable patients (95% confidence interval, 14% to 42%), including one complete remission (2%). Seventeen additional patients (39%) had stable disease, and fourteen (33%) progressed. The median time to progression was 5.9 months and the median overall survival was 13.2 months from the start of the chemotherapy. From the 297 cycles analyzed, hematologic toxicities per course were: leukopenia; grade I 26.6%, grade II 3.4%, and grade III 0.3%, thrombocytopenia; grade I 10.8%, grade II 3.0%, grade III 1.0%, and grade IV 0.3%. The most frequent nonhematologic adverse reactions were nausea/vomiting and peripheral neuropathy, which were rated as WHO grade II in 13 patients (49%) and 11 patients (22%), respectively. CONCLUSION: This phase II study of oxaliplatin, 5-FU, and LV continuous infusion showed enhanced antitumor activity in patients with 5-FU-pretreated metastatic colorectal cancer. Overall toxicity was acceptable; neurotoxicity and bone marrow suppression constituted the dose-limiting side effects.
Bone Marrow ; Colorectal Neoplasms* ; Drug Therapy ; Fluorouracil* ; Humans ; Leucovorin* ; Leukopenia ; Peripheral Nervous System Diseases ; Thrombocytopenia

BACKGROUND: The aim of this study is to determine prognostic factors of breast cancer in Korean patients who underwent curative mastectomy. METHODS: Medical records of 181 patients who underwent curative mastectomy were reviewed. Relapse-free survival and overall survival were documented for each patient. Factors influencing survival were analyzed using Cox proportional hazard model. RESULTS: Overall 5-year survival rate was 82.0%, and 8-year survival rate was 74.7%. Multivariate analysis indicated that multiple axillary lymph node involvement (> or =4), postmenopausal status, and negative estrogen receptor were independent adverse prognostic factors. The adjusted relative risks of multiple axillary lymph node involvement (> or =4), postmenopausal status, and negative estrogen receptor were estimated 2.60 (95% Confidence Interval (CI): 1.28-5.30), 2.64 (95% CI: 1.46-4.79), and 2.27 (95% CI: 1.19-4.35), respectively. CONCLUSION: Multiple axillary lymph node involvement (> or =4), postmenopausal status, and negative estrogen receptor were independent adverse prognostic factors in Korean breast cancer patients after curative mastectomy.
Breast Neoplasms* ; Breast* ; Estrogens ; Humans ; Lymph Nodes ; Mastectomy ; Medical Records ; Multivariate Analysis ; Proportional Hazards Models ; Survival Rate

PURPOSE: The clinicopathologic features and prognostic factors of gastrointestinal leiomyosarcoma have been a source of controversy. MATERIALS AND METHODS: A retrospective study was made of 91 incident cases of gastrointestinal leiomyosarcoma from 1979 to 1998 to identify clinicopathologic features and prognostic factors. RESULTS: The median age of study subjects was 56 years and 58.2% was male. Tumors consisted of 2 esophagus, 39 stomach, 38 small bowel, 12 large bowel leiomyosarcoma. Mean size of the tumors was 10.9 cm and 52.9% of them was larger than 10 cm. The tumors were classified as localized stage (42 cases), advanced stage (21 cases), and metastatic stage (28 cases). Again, the tumors were classified as low grade (48 cases) and high grade (18 cases). Median overall survival was 37.4 months and median disease-free survival was 28.2 months. In univariate analysis, the significant factors affecting the overall survival of patients with leiomyosarcoma were stage, size greater than 10 cm, performance status, and histologic grade. In multivariate analysis, stage, performance status, and histologic grade were independent factors affecting the overall survival. In univariate analysis, the significant factors affecting the disease-free survival were stage, performance status, and histologic grade. In multivariate analysis, histologic grade was the only independent factor affecting the disease-free survival. CONCLUSION: Stage, performance status, and histologic grade were independent factors affecting the overall survival. Histologic grade was independent factor affecting the disease-free survival.
Disease-Free Survival ; Esophagus ; Humans ; Korea* ; Leiomyosarcoma* ; Male ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Stomach

PURPOSE: The major aim of this study is to evaluate the pattems of recurrence of breast cancer and to determine risk factom influencing the pattem. MATERIALS AND METHODS: Medical records of 322 female patients who underwent mastectomy from 1989 till 1992 were reviewed. Recurrence pattem and the length of survival after the first relapse of each relapsed patient were identified. Factors influencing the pattem of recurrence and the length of survival after relapse were analyzed using Cox proportional hazards model. RESULTS: Locoregional relapse was identified in the first failure sites of sixteen patients (5-year relapse rate, 5.7%). Risk of locoregional relapse was associated with the number of positive axillary lymph nodes [adjusted Relative Risk (aRR), 31.28 (95% Confidence Interval (CI), 6.81-143.77)]. The 5-year estimates of the first relapse at bone, lung, pleura, liver, and brain were 15.4%, 6.9%, 1.9%, 3.1%, and 0.8%, respectively. The multivariate analysis indicated that distant metastasis was associated with the number of positive axillary lymph nodes [aRR, 3.14 (95% CI, 1.56-6.32)] and with the age of 35 years and younger [aRR, 1.95 (95% CI, 1.01-3.75)]. The statistical association of negative estrogen receptor (ER) with distant relapse was borderline [aRR, 1.89 (95% CI, 0.99-3.61)]. Factors independently affecting the survival of relapsed patients were the pattem of metastasis and the disease-free interval. CONCLUSION: Bone metastasis was the most frequent pattem of first relapse in Korean breast cancer patients. The number of positive axillary lymph nodes, younger age, and negative ER were independent risk factors for distant relapse in Korean female breast cancer patients.
Brain ; Breast Neoplasms* ; Breast* ; Estrogens ; Female* ; Humans ; Liver ; Lung ; Lymph Nodes ; Mastectomy ; Medical Records ; Multivariate Analysis ; Neoplasm Metastasis ; Pleura ; Proportional Hazards Models ; Recurrence* ; Risk Factors

PURPOSE: The major aim of this study is to evaluate the patterns of recurrence of the stomach cancer after curative resection. MATERIALS AND METHODS: Patterns of the fimt failure and survival after relapse of 136 female gastric cancer patients who had received curative resection were evaluated. Factors influencing survival after relapse were analyzed using Cox proportional hazard model. RESULTS: Peritoneal relapse was the most common pattern of the first failure, with 3-year estimate of overall peritoneal relapse being 13.0%. The 3-year estimates of overall local- regional relapse, liver metastasis, and extraabdominal relapse were 11.2%, 4.8%, and 3.8%, respectively. Patients younger than 45 years developed peritoneal relapse at a significantly higher rate than patients aged 45-65 years (p 0.037). The most significant factor affecting the survival of relapsed patients was whether resection was performed for recurrent disease without remaining gross residual disease. Patterns of relapse did not significantly affect survival, but patients whose recurrences were limited to local-regional area tended to survive longer than those with extraaMominal component (p=0.067). CONCLUSION: Peritoneal relapse was the most common pattem and significantly associated with younger age after curative resection af gastric cancer of Korean female patients.
Female* ; Humans ; Liver ; Neoplasm Metastasis ; Proportional Hazards Models ; Recurrence ; Stomach Neoplasms*