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1.
Article in English | WPRIM | ID: wpr-925930

ABSTRACT

Background@#Tenofovir disoproxil fumarate (TDF, Viread® ) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. @*Methods@#The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. @*Results@#A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was −5.13 ± 1.40 in the DA-2802 group and −4.97 ± 1.40 log 10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. @*Conclusion@#DA-2802 is considered an effective and safe treatment for patients with CHB.

2.
Article in English | WPRIM | ID: wpr-925757

ABSTRACT

Background/Aims@#We compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) treated by surgical resection (SR) and radiofrequency ablation (RFA). @*Methods@#We retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2–3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment. @*Results@#The median follow-up period was 64.8 months (interquartile range, 0.1–162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P<0.001), but not in those with HCC of ≤2 cm (P=0.234). The weighted Cox proportional hazards model with IPW provided adjusted hazard ratios (95% confidence interval) for OS, and the RFS after RFA versus SR were 0.698 (0.396–1.232) (P=0.215) and 1.698 (1.777–2.448) (P=0.005), respectively. @*Conclusions@#SR was similar for OS compared to RFA, but was better for RFS in patients with CTP class-A and single small (≤3 cm) HCC. The RFS was determined by the presence or absence of cirrhosis. Hence, SR rather than RFA should be considered in patients without cirrhosis to prolong the RFS, although there is no OS difference.

3.
Article in English | WPRIM | ID: wpr-924864

ABSTRACT

Background@#The aim of this study was to evaluate clinical outcomes of sodium tetradecyl sulphate (STS) sclerotherapy for conservative treatment of lateral malleolar bursitis of the ankle. @*Methods@#We reviewed data from 20 consecutive patients (20 ankles) who underwent STS sclerotherapy between August 2018 and June 2019. After aspiration of fluid from the lateral malleolar bursal sac, 2 mL (20 mg) STS was injected into the sac. Clinical outcomes and side effects and complications were evaluated at 2 weeks, 3 months, 1 year, and 2 years after sclerotherapy. Responses to treatment were assessed according to degree of fluctuation, shrinkage of the bursal sac, and soft-tissue swelling. The 36-item short form survey (SF-36) was completed for each patient before and after therapy. @*Results@#Complete response was observed in 17 patients (85%), and partial response was observed in 3 patients (15%) after STS sclerotherapy. SF-36 physical component scores improved from 62.2 (interquartile range, 5.2) before therapy to 70.0 (interquartile range, 7.9) at last follow-up (p < 0.05). One patient (5%) experienced transient hyperpigmentation at the injection site. No major complications occurred. @*Conclusions@#STS sclerotherapy was an effective and safe treatment for patients with lateral malleolar bursitis of the ankle.

4.
Article in English | WPRIM | ID: wpr-937344

ABSTRACT

Chronic hepatitis B (CHB) seriously threatens human health. About 820,000 deaths annually are due to related complications such as hepatitis B and hepatocellular carcinoma (HCC). Recently, the use of oral antiviral agents has significantly improved the prognosis of patients with CHB infection and reduced the risk of HCC. However, hepatitis B virus still remains a major factor in the development of HCC, raising many concerns. Therefore, numerous studies have been conducted to assess the risk of HCC in patients with CHB infection and many models have been proposed to predict the risk of developing HCC. However, as each study has different models for predicting HCC development that can be applied depending on the use of antiviral agents or the type of antiviral agents, it is necessary to properly understand characteristics of each model when using it for the evaluation of HCC in patients with CHB infection. In addition, because different variables such as host factor, viral activity, and cirrhosis are used to evaluate the risk of HCC development, it is necessary to assess the risk by carefully verifying which variables are used. Recently, studies have also evaluated the risk of HCC using risk prediction models through transient elastography and artificial intelligence (AI) system. These HCC risk predication models are also noteworthy. In this review, we aimed to compare HCC risk prediction models in patients with CHB infection reported to date to confirm variables used and specificity between each model to determine an appropriate HCC risk prediction method.

5.
Yonsei Medical Journal ; : 650-659, 2021.
Article in English | WPRIM | ID: wpr-904235

ABSTRACT

Purpose@#Our previous work demonstrated that miRNA-495 targets SOX9 to inhibit chondrogenesis of mesenchymal stem cells.In this study, we aimed to investigate whether miRNA-495-mediated SOX9 regulation could be a novel therapeutic target for osteoarthritis (OA) using an in vitro cell culture model. @*Materials and Methods@#An in vitro model mimicking the OA environment was established using TC28a2 normal human chondrocyte cells. Interleukin-1β (IL-1β, 10 ng/mL) was utilized to induce inflammation-related changes in TC28a2 cells. Safranin O staining and glycosaminoglycan assay were used to detect changes in proteoglycans among TC28a2 cells. Expression levels of COX-2, ADAMTS5, MMP13, SOX9, CCL4, and COL2A1 were examined by qRT-PCR and/or Western blotting. Immunohistochemistry was performed to detect SOX9 and CCL4 proteins in human cartilage tissues obtained from patients with OA. @*Results@#miRNA-495 was upregulated in IL-1β-treated TC28a2 cells and chondrocytes from damaged cartilage tissues of patients with OA. Anti-miR-495 abolished the effect of IL-1β in TC28a2 cells and rescued the protein levels of SOX9 and COL2A1, which were reduced by IL-1β. SOX9 was downregulated in the damaged cartilage tissues of patients with OA, and knockdown of SOX9 abolished the effect of anti-miR-495 on IL-1β-treated TC28a2 cells. @*Conclusion@#We demonstrated that inhibition of miRNA-495 alleviates IL-1β-induced inflammatory responses in chondrocytes by rescuing SOX9 expression. Accordingly, miRNA-495 could be a potential novel target for OA therapy, and the application of anti-miR-495 to chondrocytes could be a therapeutic strategy for treating OA.

6.
Article in English | WPRIM | ID: wpr-903755

ABSTRACT

Objective@#The aim of this study was to compare the differences in mandibular posterior anatomic limit (MPAL) distances stratified by vertical patterns in patients with skeletal Class III malocclusion by using cone-beam computed tomography (CBCT). @*Methods@#CBCT images of 48 patients with skeletal Class III malocclusion (mean age, 22.8 ± 3.1 years) categorized according to the vertical patterns (hypodivergent, normodivergent, and hyperdivergent; n = 16 per group) were analyzed. While parallel to the posterior occlusal line, the shortest linear distances from the distal root of the mandibular second molar to the inner cortex of the mandibular body were measured at depths of 4, 6, and 8 mm from the cementoenamel junction. MPAL distances were compared between the three groups, and their correlations were analyzed. @*Results@#The mean ages, sex distribution, asymmetry, and crowding in the three groups showed no significant differences. MPAL distance was significantly longer in male (3.8 ± 2.6 mm) than in female (1.8 ± 1.2 mm) at the 8-mm root level. At all root levels, MPAL distances were significantly different in the hypodivergent and hyperdivergent groups (p < 0.001) and between the normodivergent and hyperdivergent groups (p < 0.01). MPAL distances were the shortest in the hyperdivergent group. The mandibular plane angle highly correlated with MPAL distances at all root levels (p < 0.01). @*Conclusions@#MPAL distances were the shortest in patients with hyperdivergent patterns and showed a decreasing tendency as the mandibular plane angle increased. MPAL distances were significantly shorter (~3.16 mm) at the 8-mm root level.

7.
Article in English | WPRIM | ID: wpr-900794

ABSTRACT

Over the last two decades, bisphosphonate has widely been applied in the treatment of osteoporosis.We reviewed the various adverse effects, current trials involving diverse bone metabolic diseases, andthe future direction of bisphosphonate. Acute phase reaction, hypocalcemia, ocular inflammation, and gastrointestinal disturbances are the well-known short-term side-effects of bisphosphonate. Long term side-effects include osteonecrosis of the jaws and atypical femur fracture. In the modern clinical setting, bisphosphonate is widely used in treatments for osteoporosis, osteopenia, osteoarthritis, rheumatoid arthritis, and metastatic bone cancer. Further studies are underway for expanding the application as a bone-targeting agent in bone-related diseases. Bisphosphonate remains useful and invaluable as the 1st line medication for osteoporosis. Considering the numerous clinical situations, including time to medication after fracture, duration of drug usage, and individual drug holiday, an optimal and proper use of bisphosphonate needs to be achieved. In the current scenario, bisphosphonate will retain a strong position due to good efficacy and effectiveness for osteoporosis treatment, and the precise ap-plication to various bone diseases. We anticipate a key role of bisphosphonate for future applicationin the treatment of metabolic bone diseases. Further studies and advancement are highly anticipated, considering the high potential of bisphosphonate for various uses.

8.
Journal of Liver Cancer ; : 34-44, 2021.
Article in English | WPRIM | ID: wpr-900270

ABSTRACT

Background@#/objective: Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) is rarely observed in patients without liver cirrhosis (LC). We evaluated the incidence and clinical feature of HCV-associated HCC patients with or without LC. @*Methods@#The medical records of 1,516 patients diagnosed as having primary HCC at our hospital between January 2005 and December 2017 were retrospectively reviewed. Of these, 154 (10.2%) HCV-associated HCC patients were analyzed. LC was diagnosed histologically or clinically. @*Results@#Seventeen (11.0%) of the 154 patients had non-cirrhotic HCC, and all were of Child-Turcotte-Pugh (CTP) class A, Among the 17 patients, 88.2% were male, all had nodular type HCC, and only 2 (11.8%) were under HCC surveillance. Median overall survival (OS) of HCV-associated HCC patients with and without LC was 15 months and 37 months, respectively. Cumulative OS rates were not different between non-cirrhotic patients and cirrhotic patients with CTP class A (P=0.229). Cumulative OS rates were significantly higher in non-cirrhotic patients than in cirrhotic patients of CTP class B (P<0.001) or C (P<0.001). Multivariate analyses showed serum AST (hazard ratio [HR] 1.01, P=0.003) and AFP levels (HR 1.01, P=0.016), antiviral therapy (HR 0.25, P=0.022), and LC of CTP class B (HR, 5.24, P=0.006) or C (HR 21.79, P<0.001) were significantly associated with prognosis in HCV-associated HCC patients. @*Conclusions@#HCC in a non-cirrhotic liver was found in 11% of HCV-associated HCC patients. OSs of HCV-associated HCC patients were better in those of CTP A, regardless of LC than in those with LC of CTP class B or C.

9.
Article in English | WPRIM | ID: wpr-897944

ABSTRACT

Background@#Many researchers have questioned whether shoulder kinematics such as the glenohumeral position and scapular kinematics would be different in different age groups. However, studies comparing shoulder kinematics between different age groups have been rare. The aim of this study was to analyze and compare the three-dimensional (3D) glenohumeral position, scapular kinematics, and scapulohumeral rhythm (SHR) during scapular plane arm abduction between a normal young male group and a normal older male group. @*Methods@#Twenty normal men (10 young and 10 older) were enrolled in this controlled laboratory study. Fluoroscopic images were obtained using a single plane X-ray system. Bilateral computed tomography scans were taken to create a 3D model. A 3D-2D registration technique was used to determine the 3D position and orientation of the bones of the shoulder. @*Results@#During scapular plane arm abduction, there were significant differences in scapular kinematics between the groups. The older male group showed more upward rotation, posterior tilt, and external rotation than the young male group. On the other hand, the glenohumeral position such as superior inferior translation, anterior posterior translation, and external rotation of the humeral head did not show significant difference between the groups. The mean value of SHR for the overall arm elevation range from start to maximum elevation angle for the older group and young group was 2.298 ± 0.964 and 2.622 ± 0.931, respectively, showing a significant difference between the two groups (p = 0.035). @*Conclusions@#Scapular kinematics and SHR were significantly different between the older male group and the young male group. Our study could provide reference values of shoulder kinematics for older men aged 55–65 years.

10.
Article in English | WPRIM | ID: wpr-897659

ABSTRACT

Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

11.
Article in English | WPRIM | ID: wpr-897654

ABSTRACT

There is some dissatisfaction with the term “nonalcoholic fatty liver disease (NAFLD),” which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.

12.
Article in English | WPRIM | ID: wpr-893090

ABSTRACT

Over the last two decades, bisphosphonate has widely been applied in the treatment of osteoporosis.We reviewed the various adverse effects, current trials involving diverse bone metabolic diseases, andthe future direction of bisphosphonate. Acute phase reaction, hypocalcemia, ocular inflammation, and gastrointestinal disturbances are the well-known short-term side-effects of bisphosphonate. Long term side-effects include osteonecrosis of the jaws and atypical femur fracture. In the modern clinical setting, bisphosphonate is widely used in treatments for osteoporosis, osteopenia, osteoarthritis, rheumatoid arthritis, and metastatic bone cancer. Further studies are underway for expanding the application as a bone-targeting agent in bone-related diseases. Bisphosphonate remains useful and invaluable as the 1st line medication for osteoporosis. Considering the numerous clinical situations, including time to medication after fracture, duration of drug usage, and individual drug holiday, an optimal and proper use of bisphosphonate needs to be achieved. In the current scenario, bisphosphonate will retain a strong position due to good efficacy and effectiveness for osteoporosis treatment, and the precise ap-plication to various bone diseases. We anticipate a key role of bisphosphonate for future applicationin the treatment of metabolic bone diseases. Further studies and advancement are highly anticipated, considering the high potential of bisphosphonate for various uses.

13.
Journal of Liver Cancer ; : 34-44, 2021.
Article in English | WPRIM | ID: wpr-892566

ABSTRACT

Background@#/objective: Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) is rarely observed in patients without liver cirrhosis (LC). We evaluated the incidence and clinical feature of HCV-associated HCC patients with or without LC. @*Methods@#The medical records of 1,516 patients diagnosed as having primary HCC at our hospital between January 2005 and December 2017 were retrospectively reviewed. Of these, 154 (10.2%) HCV-associated HCC patients were analyzed. LC was diagnosed histologically or clinically. @*Results@#Seventeen (11.0%) of the 154 patients had non-cirrhotic HCC, and all were of Child-Turcotte-Pugh (CTP) class A, Among the 17 patients, 88.2% were male, all had nodular type HCC, and only 2 (11.8%) were under HCC surveillance. Median overall survival (OS) of HCV-associated HCC patients with and without LC was 15 months and 37 months, respectively. Cumulative OS rates were not different between non-cirrhotic patients and cirrhotic patients with CTP class A (P=0.229). Cumulative OS rates were significantly higher in non-cirrhotic patients than in cirrhotic patients of CTP class B (P<0.001) or C (P<0.001). Multivariate analyses showed serum AST (hazard ratio [HR] 1.01, P=0.003) and AFP levels (HR 1.01, P=0.016), antiviral therapy (HR 0.25, P=0.022), and LC of CTP class B (HR, 5.24, P=0.006) or C (HR 21.79, P<0.001) were significantly associated with prognosis in HCV-associated HCC patients. @*Conclusions@#HCC in a non-cirrhotic liver was found in 11% of HCV-associated HCC patients. OSs of HCV-associated HCC patients were better in those of CTP A, regardless of LC than in those with LC of CTP class B or C.

14.
Article in English | WPRIM | ID: wpr-890240

ABSTRACT

Background@#Many researchers have questioned whether shoulder kinematics such as the glenohumeral position and scapular kinematics would be different in different age groups. However, studies comparing shoulder kinematics between different age groups have been rare. The aim of this study was to analyze and compare the three-dimensional (3D) glenohumeral position, scapular kinematics, and scapulohumeral rhythm (SHR) during scapular plane arm abduction between a normal young male group and a normal older male group. @*Methods@#Twenty normal men (10 young and 10 older) were enrolled in this controlled laboratory study. Fluoroscopic images were obtained using a single plane X-ray system. Bilateral computed tomography scans were taken to create a 3D model. A 3D-2D registration technique was used to determine the 3D position and orientation of the bones of the shoulder. @*Results@#During scapular plane arm abduction, there were significant differences in scapular kinematics between the groups. The older male group showed more upward rotation, posterior tilt, and external rotation than the young male group. On the other hand, the glenohumeral position such as superior inferior translation, anterior posterior translation, and external rotation of the humeral head did not show significant difference between the groups. The mean value of SHR for the overall arm elevation range from start to maximum elevation angle for the older group and young group was 2.298 ± 0.964 and 2.622 ± 0.931, respectively, showing a significant difference between the two groups (p = 0.035). @*Conclusions@#Scapular kinematics and SHR were significantly different between the older male group and the young male group. Our study could provide reference values of shoulder kinematics for older men aged 55–65 years.

15.
Article in English | WPRIM | ID: wpr-889955

ABSTRACT

Background/Aims@#Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. @*Methods@#Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). @*Results@#Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. @*Conclusions@#BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

16.
Article in English | WPRIM | ID: wpr-889950

ABSTRACT

There is some dissatisfaction with the term “nonalcoholic fatty liver disease (NAFLD),” which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.

17.
Article in English | WPRIM | ID: wpr-914646

ABSTRACT

Cancer stem cells (CSCs) are a small subset of cancer cells with stem cell-like properties, self-renewal potential, and differentiation capacity into multiple cell types. Critical genetic alterations or aberrantly activated signaling pathways associated with drug resistance and recurrence have been observed in multiple types of CSCs. In this context, CSCs are considered to be responsible for tumor initiation, growth, progression, therapeutic resistance, and metastasis. Therefore, to effectively eradicate CSCs, tremendous efforts have been devoted to identify specific target molecules that play a critical role in regulating their distinct functions and to develop novel therapeutics, such as proteins, monoclonal antibodies, selective small molecule inhibitors, and small antisense RNA (asRNA) drugs. Similar to other CSC types, oral CSCs can be characterized by certain pluripotency-associated markers, and oral CSCs can also survive and form 3D tumor spheres in suspension culture conditions. These oral CSC-targeting therapeutics selectively suppress specific surface markers or key signaling components and subsequently inhibit the stem-like properties of oral CSCs. A large number of new therapeutic candidates have been tested, and some products are currently in the pre-clinical or clinical development phase. In the present study, we review new oral CSC-targeted therapeutic strategies and discuss the various specific CSC surface markers and key signaling components involved in the stem-like properties, growth, drug resistance, and tumorigenicity of oral CSCs.

18.
Gut and Liver ; : 895-903, 2021.
Article in English | WPRIM | ID: wpr-914355

ABSTRACT

Background/Aims@#Glecaprevir/pibrentasvir (G/P) is the first pan-genotypic direct-acting antiviral combination therapy approved in Korea. An integrated analysis of five phase II and III trials was conducted to evaluate the efficacy and safety of G/P in Korean patients with chronic hepatitis C virus (HCV) infection. @*Methods@#The study analyzed pooled data on Korean patients with HCV infection enrolled in the ENDURANCE 1 and 2, SURVEYOR II part 4 and VOYAGE I and II trials, which evaluated the efficacy and safety of 8 or 12 weeks of G/P treatment. The patients were either treatment-naïve or had received sofosbuvir or interferon-based treatment. Efficacy was evaluated by assessing the rate of sustained virologic response at 12 weeks posttreatment (SVR12). Safety was evaluated by monitoring adverse events (AEs) and laboratory assessments. @*Results@#The analysis included 265 patients; 179 (67.5%) were HCV treatment-naïve, and most patients were either subgenotype 1B (48.7%) or 2A (44.5%). In the intention-to-treat population, 262 patients (98.9%) achieved SVR12. Three patients did not achieve SVR12: one had virologic failure and two had non-virologic failures. Most AEs were grade 1/2; eight patients (3.0%) expe-rienced at least one grade ≥3 AE. No serious AEs related to G/P treatment were reported, and grade ≥3 hepatic laboratory abnormalities were rare (0.8%). @*Conclusions@#G/P therapy was highly efficacious and well tolerated in Korean patients with HCV infection, with most patients achieving SVR12. The safety profile was comparable to that observed in a pooled analysis of a global pan-genotypic population of patients with HCV infection who received G/P.

19.
Yonsei Medical Journal ; : 650-659, 2021.
Article in English | WPRIM | ID: wpr-896531

ABSTRACT

Purpose@#Our previous work demonstrated that miRNA-495 targets SOX9 to inhibit chondrogenesis of mesenchymal stem cells.In this study, we aimed to investigate whether miRNA-495-mediated SOX9 regulation could be a novel therapeutic target for osteoarthritis (OA) using an in vitro cell culture model. @*Materials and Methods@#An in vitro model mimicking the OA environment was established using TC28a2 normal human chondrocyte cells. Interleukin-1β (IL-1β, 10 ng/mL) was utilized to induce inflammation-related changes in TC28a2 cells. Safranin O staining and glycosaminoglycan assay were used to detect changes in proteoglycans among TC28a2 cells. Expression levels of COX-2, ADAMTS5, MMP13, SOX9, CCL4, and COL2A1 were examined by qRT-PCR and/or Western blotting. Immunohistochemistry was performed to detect SOX9 and CCL4 proteins in human cartilage tissues obtained from patients with OA. @*Results@#miRNA-495 was upregulated in IL-1β-treated TC28a2 cells and chondrocytes from damaged cartilage tissues of patients with OA. Anti-miR-495 abolished the effect of IL-1β in TC28a2 cells and rescued the protein levels of SOX9 and COL2A1, which were reduced by IL-1β. SOX9 was downregulated in the damaged cartilage tissues of patients with OA, and knockdown of SOX9 abolished the effect of anti-miR-495 on IL-1β-treated TC28a2 cells. @*Conclusion@#We demonstrated that inhibition of miRNA-495 alleviates IL-1β-induced inflammatory responses in chondrocytes by rescuing SOX9 expression. Accordingly, miRNA-495 could be a potential novel target for OA therapy, and the application of anti-miR-495 to chondrocytes could be a therapeutic strategy for treating OA.

20.
Article in English | WPRIM | ID: wpr-896051

ABSTRACT

Objective@#The aim of this study was to compare the differences in mandibular posterior anatomic limit (MPAL) distances stratified by vertical patterns in patients with skeletal Class III malocclusion by using cone-beam computed tomography (CBCT). @*Methods@#CBCT images of 48 patients with skeletal Class III malocclusion (mean age, 22.8 ± 3.1 years) categorized according to the vertical patterns (hypodivergent, normodivergent, and hyperdivergent; n = 16 per group) were analyzed. While parallel to the posterior occlusal line, the shortest linear distances from the distal root of the mandibular second molar to the inner cortex of the mandibular body were measured at depths of 4, 6, and 8 mm from the cementoenamel junction. MPAL distances were compared between the three groups, and their correlations were analyzed. @*Results@#The mean ages, sex distribution, asymmetry, and crowding in the three groups showed no significant differences. MPAL distance was significantly longer in male (3.8 ± 2.6 mm) than in female (1.8 ± 1.2 mm) at the 8-mm root level. At all root levels, MPAL distances were significantly different in the hypodivergent and hyperdivergent groups (p < 0.001) and between the normodivergent and hyperdivergent groups (p < 0.01). MPAL distances were the shortest in the hyperdivergent group. The mandibular plane angle highly correlated with MPAL distances at all root levels (p < 0.01). @*Conclusions@#MPAL distances were the shortest in patients with hyperdivergent patterns and showed a decreasing tendency as the mandibular plane angle increased. MPAL distances were significantly shorter (~3.16 mm) at the 8-mm root level.

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