Clinical Effects of a Home Care Pilot Program for Patients with Type 1 Diabetes Mellitus: A Retrospective Cohort Study

Background@#Given the importance of continuous self-care for people with type 1 diabetes mellitus (T1DM), the Ministry of Health and Welfare of Korea launched a pilot program for chronic disease management. Herein, we applied a home care pilot program to people with T1DM to investigate its effects. @*Methods@#This retrospective cohort study was conducted at a single tertiary hospital (January 2019 to October 2021). A multidisciplinary team comprising doctors, nurses, and clinical nutritionists provided specialized education and periodically assessed patients’ health status through phone calls or text messages. A linear mixed model adjusting for age, sex, and body mass index was used to analyze the glycemic control changes before and after implementing the program between the intervention and control groups. @*Results@#Among 408 people with T1DM, 196 were enrolled in the intervention group and 212 in the control group. The reduction in glycosylated hemoglobin (HbA1c) after the program was significantly greater in the intervention group than in the control group (estimated marginal mean, –0.57% vs. –0.23%, P=0.008); the same trend was confirmed for glycoalbumin (GA) (–3.2% vs. –0.39%, P<0.001). More patients achieved the target values of HbA1c (<7.0%) and GA (<20%) in the intervention group than in the control group at the 9-month follow-up (34.5% vs. 19.6% and 46.7% vs. 28.0%, respectively). @*Conclusion@#The home care program for T1DM was clinically effective in improving glycemic control and may provide an efficient care option for people with T1DM, and positive outcomes are expected to expand the program to include more patients.

The Childbirth Experience and Life Satisfaction among Women with Disabilities

Purpose@#The aim of this study was to show the association between the childbirth experience and life satisfaction among women with disabilities and estimate the moderating effect of family strengths and social support. @*Methods@#The target sample included disabled married women aged 20-49 years. We used the Disability and Life Dynamics Panel 2018. The total number of participants was 220. Three groups were defined based on the childbirth experience: women who had never given birth (13.6%), those who gave birth before the onset of disability (73.2%), and those who gave birth after the onset of disability (13.2%). We identified differences in general characteristics, family strengths, social support, and life satisfaction across the 3 groups and examined the moderating effect of family strengths and social support for the childbirth experience and life satisfaction. @*Results@#Women who gave birth after the onset of disability were in better health, exhibiting longer disability retention periods. The multiple regression analysis revealed that among women who gave birth after the onset of disability, life satisfaction was significantly higher than that of women without the childbirth experience because of the moderating effect of family strengths. However, social support had no significant effect on the childbirth experience and life satisfaction. @*Conclusion@#We empirically analyzed the status of childbirth before and after the onset of disability using representative survey data. The findings indicate a positive moderating effect of family strengths on the level of life satisfaction among women with disabilities.

Complications Including Capsular Contracture in Direct-to-Implant Breast Reconstruction With Textured Anatomical Versus Smooth Round Implants: A Single Center Retrospective Analysis / 한국유방암학회지

Purpose@#Implant-based breast reconstruction is the most common reconstruction method used after mastectomy in breast cancer patients. Many studies have compared the smooth round implants and textured anatomical implants. This study aimed to compare the complications, including capsular contracture, between these two implants used in direct-toimplant (DTI) breast reconstruction. @*Methods@#This retrospective chart review was performed using a prospectively maintained database from a single center. We identified patients who underwent mastectomy with DTI single-stage breast reconstruction at our hospital between August 2011 and June 2021. The overall complications, including capsular contracture, postoperative infection, seroma, hematoma, implant rupture, implant exposure, rippling, implant malposition, and nipple necrosis, were analyzed. @*Results@#In total, 340 breasts of 323 patients were reconstructed by the DTI approach using either textured anatomical (n = 203) or smooth round (n = 137) implants. The incidence of overall complications and capsular contracture was significantly lower with smooth round implants than with textured anatomical implants. Multivariate analysis showed that smooth round implants were associated with a reduced risk of overall complications (odds ratio [OR], 0.465; 95% confidence interval [CI], 0.265–0.813) and capsular contracture (OR, 0.475; 95% CI, 0.235–0.962). Particularly, smooth round implants were associated with a decreased risk of overall complications in patients not receiving adjuvant chemotherapy and a decreased risk of capsular contracture in patients with body mass index < 25 kg/m2 and in those not receiving adjuvant radiotherapy. @*Conclusion@#Smooth round implants demonstrated a decreased risk of overall complications and capsular contracture when compared with textured anatomical implants. These results may be utilized in counseling patients regarding the advantages and disadvantages of smooth round implants in DTI breast reconstruction.

Renal Tubular Damage Marker, Urinary N-acetyl-β-D-Glucosaminidase, as a Predictive Marker of Hepatic Fibrosis in Type 2 Diabetes Mellitus

Background@#Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-β-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM. @*Methods@#A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured. @*Results@#Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (β=1.58, P<0.01). @*Conclusion@#The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future.

Sodium Glucose Cotransporter-2 Inhibitors as an Add-on Therapy to Metformin Plus Dipeptidyl Peptidase-4 Inhibitor in Patients with Type 2 Diabetes

Purpose@#To date, no study has compared the effects of adding sodium glucose cotransporter-2 (SGLT-2) inhibitors to the combination of metformin plus dipeptidyl peptidase-4 (DPP-4) inhibitors to the effects of adding other conventional anti-diabetic drugs (ADDs) to the dual therapy. We aimed to compare the effect of adding SGLT-2 inhibitors with that of adding sulfonylurea (SU) in type 2 diabetes (T2D) patients inadequately controlled with metformin plus DPP-4 inhibitors. @*Materials and Methods@#This study was designed to evaluate the non-inferiority of SGLT-2 inhibitor to SU as an add-on therapy to the dual combination of metformin plus DPP-4 inhibitors. A total of 292 T2D patients who started SU or SGLT-2 inhibitors as an add-on therapy to metformin plus DPP-4 inhibitors due to uncontrolled hyperglycemia, defined as glycated hemoglobin (HbA1c) ≥7%, were recruited. After propensity score matching, 90 pairs of patients remained, and 12-week changes in HbA1c levels were reviewed to assess glycemic effectiveness. Data from these patients were analyzed retrospectively. @*Results@#After 12 weeks of triple therapy, both groups showed significant changes in HbA1c levels, with a mean of -0.9% in each group. The inter-group difference was 0.01% [95% confidence interval (CI): -0.26–0.27], and the upper limit of the 95% CI was within the limit for non-inferiority (0.40%). There were no inter-group differences in the changes of liver enzyme levels and kidney function. @*Conclusion@#Adding SGLT-2 inhibitors is not inferior to adding SU as a third-line ADD to metformin plus DPP-4 inhibitor combination therapy.

A Literature Review of Issues and Tasks by Period of Revision of Regulations Related to Convalescent Rehabilitation Wards in Japan: Focusing on Quality Evaluation

Purpose@#Japan established the convalescent rehabilitation wards, corresponding to Korea's rehabilitation medical institutions, in 2000 and developed it into the present system through continuous revisions. This study sought to analyze the issues and tasks faced by Japan segregated by the period of revision of convalescent rehabilitation ward-related medical fee regulations, through a literature review and further aimed to explore the direction of development of domestic rehabilitation medical institutions. @*Methods@#Ten revisions of the medical fee regulations were classified into three stages based on quality evaluation: (1) the quantitative expansion stage (2000–2006); (2) quality evaluation introduction stage (2008–2014); and (3) quality evaluation maturity stage (2016– 2020). @*Results@#The following issues and tasks emerged: (1) For the quantitative expansion stage; insufficient rehabilitation within the ward, insufficient after-hour rehabilitation, insufficient connection with acute-stage hospitals and maintenance facilities, and the low ratio of specialists. (2) For the quality evaluation introduction stage; disparity in the manpower between institutions, the necessity of a 365-day rehabilitation system, avoidance of critical patients, and the problem that an increase in the amount of rehabilitation did not lead to a qualitative improvement. 3) For the quality evaluation maturity stage; cream-skimming issues in selecting patients, inappropriate evaluation of rehabilitation effects, and the necessity of follow-up measures after discharge. @*Conclusion@#It is worth referring to the established regulations in Japan, and concurrently it is necessary to strengthen the evaluation of the structures, processes, and results when operating and evaluating rehabilitation medical institutions in Korea taking into account the side effects that could be identified in Japan.

Non-Laboratory-Based Simple Screening Model for Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Developed Using Multi-Center Cohorts

Background@#Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is a risk factor that accelerates NAFLD progression, leading to fibrosis and cirrhosis. Thus, here we aimed to develop a simple model to predict the presence of NAFLD based on clinical parameters of patients with T2DM. @*Methods@#A total of 698 patients with T2DM who visited five medical centers were included. NAFLD was evaluated using transient elastography. Univariate logistic regression analyses were performed to identify potential contributors to NAFLD, followed by multivariable logistic regression analyses to create the final prediction model for NAFLD. @*Results@#Two NAFLD prediction models were developed, with and without serum biomarker use. The non-laboratory model comprised six variables: age, sex, waist circumference, body mass index (BMI), dyslipidemia, and smoking status. For a cutoff value of ≥60, the prediction accuracy was 0.780 (95% confidence interval [CI], 0.743 to 0.817). The second comprehensive model showed an improved discrimination ability of up to 0.815 (95% CI, 0.782 to 0.847) and comprised seven variables: age, sex, waist circumference, BMI, glycated hemoglobin, triglyceride, and alanine aminotransferase to aspartate aminotransferase ratio. Our non-laboratory model showed non-inferiority in the prediction of NAFLD versus previously established models, including serum parameters. @*Conclusion@#The new models are simple and user-friendly screening methods that can identify individuals with T2DM who are at high-risk for NAFLD. Additional studies are warranted to validate these new models as useful predictive tools for NAFLD in clinicalpractice.

Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction. Among available oral antidiabetic agents, only the thiazolidinediones (TZDs) primarily target insulin resistance. TZDs improve insulin sensitivity by activating peroxisome proliferator-activated receptor γ. Rosiglitazone and pioglitazone have been used widely for T2DM treatment due to their potent glycemic efficacy and low risk of hypoglycemia. However, their use has decreased because of side effects and safety issues, such as cardiovascular concerns and bladder cancer. Lobeglitazone (Chong Kun Dang Pharmaceutical Corporation), a novel TZD, was developed to meet the demands for an effective and safe TZD. Lobeglitazone shows similar glycemic efficacy to pioglitazone, with a lower effective dose, and favorable safety results. It also showed pleiotropic effects in preclinical and clinical studies. In this article, we summarize the pharmacologic, pharmacokinetic, and clinical characteristics of lobeglitazone.

Non-Laboratory-Based Simple Screening Model for Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Developed Using Multi-Center Cohorts

Background@#Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is a risk factor that accelerates NAFLD progression, leading to fibrosis and cirrhosis. Thus, here we aimed to develop a simple model to predict the presence of NAFLD based on clinical parameters of patients with T2DM. @*Methods@#A total of 698 patients with T2DM who visited five medical centers were included. NAFLD was evaluated using transient elastography. Univariate logistic regression analyses were performed to identify potential contributors to NAFLD, followed by multivariable logistic regression analyses to create the final prediction model for NAFLD. @*Results@#Two NAFLD prediction models were developed, with and without serum biomarker use. The non-laboratory model comprised six variables: age, sex, waist circumference, body mass index (BMI), dyslipidemia, and smoking status. For a cutoff value of ≥60, the prediction accuracy was 0.780 (95% confidence interval [CI], 0.743 to 0.817). The second comprehensive model showed an improved discrimination ability of up to 0.815 (95% CI, 0.782 to 0.847) and comprised seven variables: age, sex, waist circumference, BMI, glycated hemoglobin, triglyceride, and alanine aminotransferase to aspartate aminotransferase ratio. Our non-laboratory model showed non-inferiority in the prediction of NAFLD versus previously established models, including serum parameters. @*Conclusion@#The new models are simple and user-friendly screening methods that can identify individuals with T2DM who are at high-risk for NAFLD. Additional studies are warranted to validate these new models as useful predictive tools for NAFLD in clinicalpractice.

Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction. Among available oral antidiabetic agents, only the thiazolidinediones (TZDs) primarily target insulin resistance. TZDs improve insulin sensitivity by activating peroxisome proliferator-activated receptor γ. Rosiglitazone and pioglitazone have been used widely for T2DM treatment due to their potent glycemic efficacy and low risk of hypoglycemia. However, their use has decreased because of side effects and safety issues, such as cardiovascular concerns and bladder cancer. Lobeglitazone (Chong Kun Dang Pharmaceutical Corporation), a novel TZD, was developed to meet the demands for an effective and safe TZD. Lobeglitazone shows similar glycemic efficacy to pioglitazone, with a lower effective dose, and favorable safety results. It also showed pleiotropic effects in preclinical and clinical studies. In this article, we summarize the pharmacologic, pharmacokinetic, and clinical characteristics of lobeglitazone.

Focal Acral Hyperkeratosis / 이화의대지

no abstract available

The Effect of Having a Usual Source of Care on Patient-Centered Communication among Persons with Disabilities / 보건행정학회지

Background@#This study examined the effect of having a usual source of care on the degree of patient-centered communication among persons with disability. The role of the usual source of care has been emphasized to improve patient experience, especially for patients with complex health conditions. @*Methods@#This study used the 2017–2018 Korean Health Panel data, and the final study observations were 22,475 (20,806 people without disability and 1,669 people with disability). We applied generalized estimating equation model to show the effect of having a usual source of care on patient-centered communication, and subgroup analysis considering the types and severity of disabilities. @*Results@#Persons who have disabilities, compared with ones without it, significantly had more usual sources of care (32.4% vs. 24.6%). By type of disability, persons with mental (51.4%), internal organ (43.8%), visual (37%), and physical disabilities (31.6%) had more usual sources of care than hearing/speech (26.6%), and developmental disabilities (18.6%). The average score of patient-centered communication was higher among who had a usual sources of care (3.2 vs. 2.7), and the regression analysis showed that having a usual sources of care was positively associated with higher patient-centered communication score (β=0.476, p<0.05). However, the positive effects of usual sources of care was not observed among persons with severe hearing/speech, developmental, and mental disabilities. @*Conclusion@#This study showed that role of patient-centered communication was limited in persons with severe hearing/speech disabilities, developmental, and mental disabilities. The education programs and supports are needed to improve communication skills between medical staff and persons with specific types of disabilities.

Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway

Background@#Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism. @*Methods@#Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks. @*Results@#The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue. @*Conclusion@#SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors

BACKGROUND: We investigated the predictive markers for the therapeutic efficacy and the best combination of sodium-glucose co-transporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and ipragliflozin) therapy in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 804 patients with T2DM who had taken SGLT2 inhibitor as monotherapy or an add-on therapy were analyzed. Multivariate regression analyses were performed to identify the predictors of SGLT2 inhibitor response including the classes of baseline anti-diabetic medications. RESULTS: After adjusting for age, sex, baseline body mass index (BMI), diabetes duration, duration of SGLT2 inhibitor use, initial glycosylated hemoglobin (HbA1c) level, estimated glomerular filtration rate (eGFR), and other anti-diabetic agent usage, multivariate analysis revealed that shorter diabetes duration, higher initial HbA1c and eGFR were associated with better glycemic response. However, baseline BMI was inversely correlated with glycemic status; lean subjects with well-controlled diabetes and obese subjects with inadequately controlled diabetes received more benefit from SGLT2 inhibitor treatment. In addition, dipeptidyl peptidase 4 (DPP4) inhibitor use was related to a greater reduction in HbA1c in patients with higher baseline HbA1c ≥7%. Sulfonylurea users experienced a larger change from baseline HbA1c but the significance was lost after adjustment for covariates and metformin and thiazolidinedione use did not affect the glycemic outcome. CONCLUSION: A better response to SGLT2 inhibitors is expected in Korean T2DM patients who have higher baseline HbA1c and eGFR with a shorter diabetes duration. Moreover, the add-on of an SGLT2 inhibitor to a DPP4 inhibitor is likely to show the greatest glycemic response.

Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35–56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

Higher glucagon-to-insulin ratio is associated with elevated glycated hemoglobin levels in type 2 diabetes patients

BACKGROUND/AIMS@#The importance of α-cell dysfunction in the pathogenesis of type 2 diabetes has re-emerged recently. However, data on whether relative glucagon excess is present in clinical settings are scarce. We aimed to investigate associations between glucagon-to-insulin ratio and various metabolic parameters.@*METHODS@#A total of 451 patients with type 2 diabetes naïve to insulin treatment were recruited. Using glucagon-to-insulin ratio, we divided subjects into quartiles according to both fasting and postprandial glucagon-to-insulin ratios.@*RESULTS@#The mean age of the subjects was 58 years, with a mean body mass index of 25 kg/m² The patients in the highest quartile of glucagon-to-insulin ratio had higher glycated hemoglobin (HbA1c) levels. HbA1c levels were positively correlated with both fasting and postprandial glucagon-to-insulin ratios. Subjects in the highest quartile of postprandial glucagon-to-insulin ratio were more likely to exhibit uncontrolled hyperglycemia, even after adjusting for confounding factors (odds ratio, 2.730; 95% confidence interval, 1.236 to 6.028; p for trend < 0.01).@*CONCLUSIONS@#Hyperglucagonemia relative to insulin could contribute to uncontrolled hyperglycemia in type 2 diabetes patients.

Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal Tubulopathy in Subjects with Early Diabetic Kidney Disease

BACKGROUND: The aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR). METHODS: We classified 1,061 participants with T2DM into two groups according to uNAG level—normal vs. high (>5.8 U/g creatinine)—and measured their biochemical parameters. RESULTS: Subjects with high uNAG level had significantly higher levels of fasting and stimulated glucose, glycated albumin (GA), and glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment of β-cell compared with subjects with normal uNAG level. Multiple linear regression analyses showed that uNAG was significantly associated with GA (standardized β coefficient [β]=0.213, P=0.016), but not with HbA1c (β=−0.137, P=0.096) or stimulated glucose (β=0.095, P=0.140) after adjusting confounding factors. In receiver operating characteristic analysis, the value of the area under the curve (AUC) for renal tubular injury of GA was significantly higher (AUC=0.634; 95% confidence interval [CI], 0.646 to 0.899) than those for HbA1c (AUC=0.598; 95% CI, 0.553 to 0.640), stimulated glucose (AUC=0.594; 95% CI, 0.552 to 0.636), or fasting glucose (AUC=0.558; 95% CI, 0.515 to 0.600). The optimal GA cutoff point for renal tubular damage was 17.55% (sensitivity 59%, specificity 62%). CONCLUSION: GA is a more useful glycation index than HbA1c for reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and normal eGFR.

Humanizing NOD/SCID/IL-2Rγnull (NSG) mice using busulfan and retro-orbital injection of umbilical cord blood-derived CD34+ cells

BACKGROUND: Humanized mouse models are still under development, and various protocols exist to improve human cell engraftment and function. METHODS: Fourteen NOD/SCID/IL-2Rγnull (NSG) mice (4‒5 wk old) were conditioned with busulfan and injected with human umbilical cord blood (hUCB)-derived CD34+ hematopoietic stem cells (HSC) via retro-orbital sinuses. The bone marrow (BM), spleen, and peripheral blood (PB) were analyzed 8 and 12 weeks after HSC transplantation. RESULTS: Most of the NSG mice tolerated the regimen well. The percentage of hCD45+ and CD19+ cells rose significantly in a time-dependent manner. The median percentage of hCD45+cells in the BM was 55.5% at week 8, and 67.2% at week 12. The median percentage of hCD45+ cells in the spleen at weeks 8 and 12 was 42% and 51%, respectively. The median percentage of hCD19+ cells in BM at weeks 8 and 12 was 21.5% and 39%, respectively (P=0.04). Similarly, the median percentage of hCD19+ cells in the spleen at weeks 8 and 12 was 10% and 24%, respectively (P=0.04). The percentage of hCD19+ B cells in PB was 23% at week 12. At week 8, hCD3+ T cells were barely detectable, while hCD7+ was detected in the BM and spleen. The percentage of hCD3+ T cells was 2‒3% at week 12 in the BM, spleen, and PB of humanized NSG mice. CONCLUSION: We adopted a simplified protocol for establishing humanized NSG mice. We observed a higher engraftment rate of human CD45+ cells than earlier studies without any significant toxicity. And human CD45+ cell engraftment at week 8 was comparable to that of week 12.

Metformin displays in vitro and in vivo antitumor effect against osteosarcoma / 소아과

PURPOSE: Patients with unresectable, relapsed, or refractory osteosarcoma need a novel therapeutic agent. Metformin is a biguanide derivative used in the treatment of type II diabetes, and is recently gaining attention in cancer research. METHODS: We evaluated the effect of metformin against human osteosarcoma. Four osteosarcoma cell lines (KHOS/NP, HOS, MG-63, U-2 OS) were treated with metformin and cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were evaluated using flow cytometric analysis, and migration and wound healing assay were performed. Fourteen female Balb/c-nude mice received KHOS/NP cell grafts in their thigh, and were allowed access to metformin containing water (2 mg/mL) ad libitum. Tumor volume was measured every 3–4 days for a period of 4 weeks. RESULTS: Metformin had a significant antiproliferative effect on human osteosarcoma cells. In particular, metformin inhibited the proliferation and migration of KHOS/NP cells by activation of AMP-activated protein kinase and consequent inhibition of the mammalian target of rapamycin pathway. It also inhibited the proliferation of cisplatin-resistant KHOS/NP clone cells. Analysis of KHOS/NP xenograft Balb/c-nude models indicated that metformin displayed potent in vivo antitumor effects. CONCLUSION: Further studies are necessary to explore metformin's therapeutic potential and the possibilities for its use as an adjuvant agent for osteosarcoma.

Increasing the alpha 2, 6 Sialylation of Glycoproteins May Contribute to Metastatic Spread and Therapeutic Resistance in Colorectal Cancer

Abnormal glycosylation due to dysregulated glycosyltransferases and glycosidases is a key phenomenon of many malignancies, including colorectal cancer (CRC). In particular, increased ST6 Gal I (beta-galactoside alpha 2, 6 sialyltransferase) and subsequently elevated levels of cell-surface alpha 2, 6-linked sialic acids have been associated with metastasis and therapeutic failure in CRC. As many CRC patients experience metastasis to the liver or lung and fail to respond to curative therapies, intensive research efforts have sought to identify the molecular changes underlying CRC metastasis. ST6 Gal I has been shown to facilitate CRC metastasis, and we believe that additional investigations into the involvement of ST6 Gal I in CRC could facilitate the development of new diagnostic and therapeutic targets. This review summarizes how ST6 Gal I has been implicated in the altered expression of sialylated glycoproteins, which have been linked to CRC metastasis, radioresistance, and chemoresistance.