Propranolol Inhibits the Proliferation of Human Glioblastoma Cell Lines through Notch1 and Hes1 Signaling System.

OBJECTIVE: The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. METHODS: We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. RESULTS: Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. CONCLUSION: These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.

Impact of metformin on survival outcome in ovarian cancer: a nationwide population-based cohort study.

OBJECTIVE: Investigation of new drugs (INDs) is a tremendously inefficient process in terms of time and cost. Drug repositioning is another method used to investigate potential new agents in well-known drugs. This study assessed the survival impact of metformin medication on ovarian cancer. METHODS: A national sample cohort of the Korean National Health Insurance Service Data was analyzed. Cox proportional hazards regression was used to analyzing hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for underlying diseases and medications as confounding factors for overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 866 eligible patients were included from among 1,025,340 cohort participants. Among them, 101 (11.7%) were metformin users. No difference in OS was observed between non-users and users. No difference in OS was observed according to age and Charlson Comorbidity Index. Long-term metformin use (≥720 days) was associated with better OS (adjusted HR=0.244; 95% CI=0.090-0.664; p=0.006). A multivariate Cox proportional hazards model showed that long-term metformin use was an independent favorable prognostic factor for OS (HR=0.193; 95% CI=0.070-0.528; p=0.001) but not for CSS (HR=0.599; 95% CI=0.178-2.017; p=0.408). CONCLUSION: Long-term metformin use reduced all-cause mortality, but not CSS in ovarian cancer. Whether metformin itself reduces deaths because of ovarian cancer requires further investigation.

Classification of cervical neoplasms on colposcopic photography using deep learning.

Colposcopy is widely used to detect cervical cancers, but experienced physicians who are needed for an accurate diagnosis are lacking in developing countries. Artificial intelligence (AI) has been recently used in computer-aided diagnosis showing remarkable promise. In this study, we developed and validated deep learning models to automatically classify cervical neoplasms on colposcopic photographs. Pre-trained convolutional neural networks were fine-tuned for two grading systems: the cervical intraepithelial neoplasia (CIN) system and the lower anogenital squamous terminology (LAST) system. The multi-class classification accuracies of the networks for the CIN system in the test dataset were 48.6 ± 1.3% by Inception-Resnet-v2 and 51.7 ± 5.2% by Resnet-152. The accuracies for the LAST system were 71.8 ± 1.8% and 74.7 ± 1.8%, respectively. The area under the curve (AUC) for discriminating high-risk lesions from low-risk lesions by Resnet-152 was 0.781 ± 0.020 for the CIN system and 0.708 ± 0.024 for the LAST system. The lesions requiring biopsy were also detected efficiently (AUC, 0.947 ± 0.030 by Resnet-152), and presented meaningfully on attention maps. These results may indicate the potential of the application of AI for automated reading of colposcopic photographs.

Impact of beta blockers on survival outcomes in ovarian cancer: a nationwide population-based cohort study.

OBJECTIVE: The impact of beta blockers (BBs) on survival outcomes in ovarian cancer was investigated. METHODS: By using Korean National Health Insurance Service Data, Cox proportional hazards regression was performed to analyze hazard ratios (HRs) with 95% confidence intervals (CIs) adjusting for confounding factors. RESULTS: Among 866 eligible patients, 206 (23.8%) were BB users and 660 (76.2%) were non-users. Among the 206 BB users, 151 (73.3%) were non-selective beta blocker (NSBB) users and 105 (51.0%) were selective beta blocker (SBB) users. BB use in patients aged ≥60 years, longer duration use (≥1 year), in patients with Charlson Comorbidity Index (CCI) ≥3, and in cardiovascular disease including hypertension was associated with better survival outcome. These findings were observed in both NSBB and SBB. When duration of medication was analyzed based on number of days, NSBB (≥180 days) was associated with improved overall survival (OS) with a relatively shorter period of use compared to SBB (≥720 days). In multivariate Cox proportional hazards model, longer duration of BB medication (≥1 year) was an independent favorable prognostic factor for both OS and disease-specific survival in ovarian cancer patients. CONCLUSION: In our nationwide population-based cohort study, BB use was associated with better survival outcomes in ovarian cancer in cases of long term duration of use, in older patients, and in cardiovascular and/or other underlying disease (CCI ≥3).

Nerve Growth Factor Stimulates Glioblastoma Proliferation through Notch1 Receptor Signaling.

OBJECTIVE: Notch receptors are heterodimeric transmembrane proteins that regulate cell fate, such as differentiation, proliferation, and apoptosis. Dysregulated Notch pathway signaling has been observed in glioblastomas, as well as in other human malignancies. Nerve growth factor (NGF) is essential for cell growth and differentiation in the nervous system. Recent reports suggest that NGF stimulates glioblastoma proliferation. However, the relationship between NGF and Notch1 in glioblastomas remains unknown. Therefore, we investigated expression of Notch1 in a glioblastoma cell line (U87-MG), and examined the relationship between NGF and Notch1 signaling. METHODS: We evaluated expression of Notch1 in human glioblastomas and normal brain tissues by immunohistochemical staining. The effect of NGF on glioblastoma cell line (U87-MG) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. To evaluate the relationship between NGF and Notch1 signaling, Notch1 and Hes1 expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To confirm the effects of NGF on Notch1 signaling, Notch1 and Hes1 small interfering RNAs (siRNAs) were used. RESULTS: In immunohistochemistry, Notch1 expression was higher in glioblastoma than in normal brain tissue. MTT assay showed that NGF stimulates U87-MG cells in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated that Notch1 and Hes1 expression were increased by NGF in a dose-dependent manner. After transfection with Notch1 and Hes1 siRNAs, there was no significant difference between controls and 100 nM NGF-ß, which means that U87-MG cell proliferation was suppressed by Notch1 and Hes1 siRNAs. CONCLUSION: These results indicate that NGF stimulates glioblastoma cell proliferation via Notch1 signaling through Hes 1.

Effects of magnetic field therapy after taping application on pain and function of patients with knee osteoarthritis.

[Purpose] The purpose of study was to investigate the effect of taping applied before magnetic field therapy. [Subjects and Methods] Thirty patients who diagnosed with knee arthritis by a specialist in the rehabilitation department were divided into three groups using the random allocation method. The control group received 15 min general physiotherapy. For the experimental group 1, non-elastic taping was applied to the medial side of the knee after general physiotherapy, followed by a 15 min magnetic field therapy. For the experimental group 2, elastic taping was applied to the medial side of the knee after general physiotherapy, followed by a 15 min magnetic field therapy. This study used visual analog scale to evaluate pain. This study used Western Ontario and McMaster Universities to evaluate the knee function. [Results] Experimental group 1 and experimental group 2 showed a significant difference visual analog scale and Western Ontario and McMaster Universities from the control group. However, no significant difference was observed between experimental group 1 and experimental group 2. [Conclusion] Choosing the applicable taping method according to the condition of the patients and applying it to therapy is necessary to reduce pain and improve the function of the patients with knee osteoarthritis.

The effects of abdominal interferential current therapy on waist circumference and visceral fat distance in obese women.

[Purpose] The purpose of this study was to investigate the effects of interferential current therapy on the waist circumference and visceral fat length in obese women. [Subjects and Methods] In this study, we selected 30 patients whose body mass index was over 25 kg/m2. The subjects were randomly assigned to receive interferential current therapy three times a week for four weeks (n=15) and transcutaneous electrical nerve stimulation three times a week for four weeks (n=15). Waist circumference was measured in cm using a tape measure with the participant in an upright posture, and the length of visceral fat was measured using a high-resolution, B-mode ultrasound machine. [Results] There was a statistically significant difference between the group of waist circumference and visceral fat length. The change of waist circumference and visceral fat length was larger the experimental group than the control group. [Conclusion] These results can be used as a basis for reducing the risk factors that increase mortality due to diseases and can prevent cardiovascular and other adult diseases caused by obesity.

Effects of proprioceptive sense-based Kinesio taping on walking imbalance.

[Purpose] The aim of this study was to determine how application of Kinesio tape to the upper and lower limbs affects walking through stimulation of the proprioceptive sense. [Subjects and Methods] Twelve patients diagnosed with hemiplegia due to stroke were selected as the subjects of the study. To ascertain the effects of Kinesio taping on walking, all subjects performed a straight line walking test three times while barefoot. In terms of the actual taping application, elastic Kinesio tape was used on the hemiplegic side in all subjects. [Results] The results of testing showed a significant difference in the values between before and after taping. In terms of left and right deviation according to the site of the taping application, there were statistically significant differences among the groups. [Conclusion] In conclusion, application of Kinesio taping for central nerve injury was confirmed to be effective in reducing walking deviation.

Effects of Kinesio taping and Mcconnell taping on balance and walking speed of hemiplegia patients.

[Purpose] The aim of this study was to evaluate the overlap effect of the PNF following the application of Kinesio taping and the McConnell taping, and also the impact of the taping application method on the balance and walking speed of the patients with stroke. [Subjects and Methods] Thirty-six patients who were diagnosed with hemiplegia due to stroke were selected as subjects of this study. They were randomly and evenly divided into experiment group 1 (Kinesio taping group), experiment group 2 (McConnell taping group), and the control group; each group had 12 patients. [Results] The Berg balance scale (BBS) was used to evaluate balance, and the ability in this study. A 10 m walking test (10MWT) was performed to measure the walking speed. Experiment group 1 showed a statistically significant improvement in balance and walking speed compared to experiment group 2, and the control group in week 4 and week 8. [Conclusion] Application of Kinesio taping had a more beneficial effect on the balance and walking speed than joint-fixation taping of the patients with stroke.

The effects of self-mobilization techniques for the sciatic nerves on physical functions and health of low back pain patients with lower limb radiating pain.

[Purpose] This study aimed to examine the effects of self-mobilization techniques for the sciatic nerves on the quality of life in patients with chronic low back pain in the lower limbs accompanied by radiating pain. [Subjects and Methods] The subjects were divided into two groups: a group receiving of lumbar segmental stabilization exercise training including sciatic nerve mobilization techniques, which included 8 males and 7 females, and a group receiving lumbar segmental stabilization exercise training, which included 8 males and 7 females. [Results] There were statistically significant differences in comparison of measurement results between the groups before and after the intervention. [Conclusion] Application of mobilization techniques for the sciatic nerves may promote healing of the soft tissues by stimulating the functions of the nervous system to improve nervous system adaptability and decrease sensitivity, helping to alleviate the symptoms.

The effects of stabilization exercise with an oral assistive device on pain and functionality of low back pain patients.

[Purpose] This study examined low back pain patients' decrease in pain and improvement in functionality after performance of a lumbar stabilization exercise using an oral assistive device, which can replace a lumbar assistive device. [Subjects and Methods] The experimental group (n=12) conducted a stabilization exercise using an oral assistive device after conventional physical therapy. The control group (n=12) received conventional physical therapy. In order to objectively measure pain in this study, a visual analogue scale (VAS) was used. In order to evaluate the subjects' functional aspects while living with low back pain, the Oswestry Disability Index (ODI) was used. [Results] There were statistically significant improvements in the comparison of the VAS and ODI of the experimental group and the control group. The experimental group's VAS and ODI significantly improved after the intervention compared to the control group. [Conclusion] The stabilization exercise using the assistive device after conventional physical therapy in the rehabilitation of low back pain patients reduced subjects' pain and increased their functional activities.

Comparison of HE4, CA125, and Risk of Ovarian Malignancy Algorithm in the Prediction of Ovarian Cancer in Korean Women.

This study is a multi-center clinical study, which aimed to compare CA125, HE4, and risk of ovarian malignancy algorithm (ROMA) in predicting epithelial ovarian cancer of Korean women with a pelvic mass. Prospectively, serum from 90 Korean women with ovarian mass was obtained prior to surgery. For control group, serum from 79 normal populations without ovarian mass was also obtained. The HE4 and CA125 data were registered and evaluated separately and ROMA was calculated for each sample. Total 67 benign tumors and 23 ovarian cancers were evaluated. Median serum levels of HE4 and CA125, and ROMA score were significantly higher in patients with ovarian cancer than those with benign ovarian tumor and normal population (P < 0.001). In ROC curve analysis for women with a pelvic mass, area under the curve (AUC) for HE4 and ROMA was higher than CA125. Statistical differences in each study compared to CA125 were marginal (P compared to CA125; 0.082 for HE4 and 0.069 for ROMA). Sub-analysis revealed that AUC for HE4 and ROMA was higher than AUC for CA125 in post-menopausal women with a pelvic mass, but there were no statistically significant differences (P compared to CA125; 0.160 for HE4 and 0.127 for ROMA). Our data suggested that both HE4 and ROMA score showed better performance than CA125 for the detection of ovarian cancer in women with a pelvic mass. HE4 and ROMA can be a useful independent diagnostic marker for epithelial ovarian cancer in Korean women.

Tumor size and lymph node status determined by imaging are reliable factors for predicting advanced cervical cancer prognosis.

The aim of the present study was to investigate the prognostic role of a number of clinical factors in advanced cervical cancer patients. Patients (n=157) with stage IIA-IIB cervical cancer treated at four Hallym Medical Centers in South Korea (Hallym University Sacred Heart Hospital; Kangnam Sacred Heart Hospital; Chuncheon Sacred Heart Hospital; and Kangdong Sacred Heart Hospital) between 2006 and 2010 were retrospectively enrolled. Univariate analysis identified significant predictive values in the following eight factors: i) Cancer stage (P<0.0001); ii) tumor size (≤4 vs. 4-6 cm, P=0.0147; and ≤4 vs. >6 cm, P<0.0001); iii) serum squamous cell carcinoma antigen level (≤2 vs. >15 ng/ml; P=0.0291); iv) lower third vaginal involvement (P<0.0001); v) hydronephrosis (P=0.0003); vi) bladder/rectum involvement (P=0.0015); vii) pelvic (P=0.0017) or para-aortic (P=0.0019) lymph node (LN) metastasis detected by imaging vs. no metastasis; and viii) pelvic LN metastasis identified by pathological analysis (P=0.0289). Furthermore, multivariate analysis determined that tumor size (≤4 vs. 4-6 cm, P=0.0371; and ≤4 vs. >6 cm, P=0.0024) and pelvic LN metastasis determined by imaging vs. no metastasis (P=0.0499) were independent predictive variables. Therefore, tumor size and pelvic LN metastasis measured by imaging were independent predictive factors for the prognosis of advanced cervical cancer. These factors may provide more clinically significant prognostic information compared with the currently used International Federation of Gynecology and Obstetrics staging system.

Effects of a Task-specific Exercise Program on Balance, Mobility, and Muscle Strength in the Elderly.

[Purpose] The aim of this study was to investigate the effects of a task-specific exercise program based on motor learning on balance ability and strength of the lower extremity in the elderly with/without falling experiences. [Subjects and Methods] Individuals who had experiences of falling over 2 times within the past 6 months were included in the falling group. The task-specific exercise program consisted of 3 stages (weeks 1-2, 3-4, and 5-6) and was conducted according to the level of difficulty in this study. [Results] The scores of the Korean version of the Activities-Specific Balance Confidence Scale and Performance-Oriented Mobility Assessment were significantly changed in both the falling group and non-falling group after the task-specific exercise program. In comparisons between the falling group and non-falling group, there were also significant differences in the Korean version of the Activities-Specific Balance Confidence Scale and muscle strength of the semitendinosus and gastrocnemius. [Conclusion] The task-specific exercise program has a positive effect on balance ability and muscle strength related to falls in the elderly.

Effects of thoracic mobilization and manipulation on function and mental state in chronic lower back pain.

[Purpose] The aim of this study was to evaluate the changes in function and mental state after thoracic mobilization and manipulation in patients with chronic lower back pain (LBP). [Subjects and Methods] Thirty-six subjects were randomly divided into mobilization group (group A), manipulation group (group B) and control group (group C). The Oswestry disability index (ODI) was used to measure the functional impairment of patients with LBP. A multiple spinal diagnosis was used to measure the range of motion (ROM) of vertebra segments. The Fear-avoidance beliefs questionnaire (FABQ) was used to investigate the mental state of LBP patients. [Results] Group A and group B were significantly different from group C in terms of the ODI. Between groups, there was no difference in ROM during trunk flexion. Group A and group B were also significantly different from the control group in extension ROM. The FABQ of group B was significantly different from that of group A. [Conclusion] Application of mobilization or manipulation to thoracic lumbar vertebrae has a positive effect on function, mental state, and ROM in patients with lower back pain.

The effect of muscle facilitation using kinesio taping on walking and balance of stroke patients.

[Purpose] The aim of this study was to evaluate the changes in function and balance after Kinesio Taping application in stroke patients. [Subjects and Methods] Thirty subjects were randomly divided into an experimental group and control group. The experimental group was applied taping before therapeutic exercise, and the control group received only therapeutic exercise. Functional gait was measured using the straight line walking test, and dynamic balance ability was measured using the Berg Balance Scale. Walking velocity was measured with the 10 m walking test. [Results] There were statistically significant differences between the results of the straight line walking and 10 m walking tests in the pre-post analysis for the experimental group. There were a statistically significant difference in the Berg Balance Scale and 10 m walking test between the two groups. [Conclusion] Application of taping to the paralyzed parts of a stroke patient has a positive effect on improvement of typical asymmetric gait and walking speed.

The expression and role of krüppel-like factor 4 in psoriasis.

BACKGROUND: Krüppel-like factor 4 (KLF4) is a transcription factor that regulates a diverse array of cellular processes, including development, differentiation, proliferation, and apoptosis. Although its function in keratinocytes has been widely studied, its exact role in psoriasis has not been elucidated. OBJECTIVE: We designed this study to investigate epidermal expression levels of KLF4 and the change in KLF4 expression after treatment in patients with psoriasis. METHODS: We compared the expression levels of KLF4 in the basal, suprabasal, and superficial epidermal layers, in psoriatic lesional, non-lesional, and normal skin, using an immunoreactivity intensity distribution index (IRIDI). In addition, we measured the change in KLF4 expression on the basis of the IRIDI and by reverse transcription polymerase chain reaction (RT-PCR) analysis after treatment. RESULTS: The combined IRIDI scores in psoriatic lesional skin were significantly higher than the scores in both non-lesional and normal skin. The psoriatic epidermis, particularly the suprabasal layer, showed a significantly increased IRIDI score compared to that of non-lesional and normal skin, which was significantly decreased after treatment. RT-PCR analysis exhibited a slight increase in KLF4 mRNA expression level after treatment; however, this increase was not significant. CONCLUSION: These data indicate that KLF4 could regulate epidermal proliferation and differentiation. Moreover, we believe that KLF4 may play an important role in the physiological reaction to counteract abnormal differentiation and proliferation of keratinocytes.

Laparoscopic reconstructive surgery is superior to vaginal reconstruction in the pelvic organ prolapse.

BACKGROUND: Our purpose was to provide the clinical advantages of the laparoscopic approach compare to the vaginal approach in correcting uterine and vaginal vault prolapse. METHODS: Between June 2007 and June 2011, 174 women were admitted to HUMC (Hallym University Medical Center) and underwent pelvic reconstructive surgery for prolapsed vaginal vault and uterus. Upon retrospective review of the medical records, 174 of the patients who had symptoms of pelvic organ prolapsed and Baden-Walker prolapse grade ≥ 2 were selected and divided into two groups as follows: vaginal approach group (n=120) and laparoscopic approach group (n=54). We compared the results of clinical outcome by analyzing Student's t-test and χ(2)-test or the Fisher exact test as appropriate. RESULTS: There were significant difference in success rates without reoperation for recurrence as 91.7% (vaginal approach group, n=110) vs 100% (laparoscopic approach group, n=54), p=0.032. Mean follow-up duration was 31.3 ± 7.6 months for vaginal approach group and 29.7 ± 9.7 months for laparoscopic approach group. The Foley catheter indwelling duration (4.7± 1.9 vs 3.4±2.1 days, p< 0.001) and the length of postoperative hospitalization (6.4 ± 2.1 vs 5.0 ± 1.9 days, p <0.001) were significantly longer in vaginal approach group, whereas the operative time was significantly longer (108.2 ± 38.6 vs 168.3 ± 69.7 minutes, p <0.001) in laparoscopic approach group. CONCLUSIONS: Our result suggest there is significantly lower recurrence rate requiring reoperation and less catheterization time but increased operative time for laparascopic sacrocolpopexy.