3-Deoxysappanchalcone Inhibits Cell Growth of Gefitinib-Resistant Lung Cancer Cells by Simultaneous Targeting of EGFR and MET Kinases

The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anticancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-(L)-Methionine

S-methyl-(L)-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of −3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

Comparison of the Efficacy and Safety Profiles of a Pelubi Sustained Release Tab Versus a Pelubi Tab in Patients with Chronic Back Pain: A Randomized, Double-Blind, Multi-Institution Phase III Study

STUDY DESIGN: A randomized, double-blind, multi-institution, phase III study. OBJECTIVES: To evaluate the efficacy and safety of the Pelubi Sustained Release (SR) Tab in patients with chronic back pain, in comparison with the Pelubi Tab, whose efficacy has already been approved, a phase 3 clinical trial was conducted. SUMMARY OF LITERATURE REVIEW: The Pelubi Tab Has shown clinical efficacy in patients with back pain. MATERIALS AND METHODS: From April 11, 2014 to July 24, 2014, 166 chronic back pain patients were recruited as subjects through a multi-institution, double-blind, random sample. We compared the experimental and control groups' clinical efficacy, which was estimated by the 100-mm Pain Visual Analog Scale (VAS) after 28 days of medication. We also compared the treatment efficacy of both drugs by using a variation of the Oswestry Disability Index (ODI) and Physician Global Assessment (PGA), with the total usage of relief medicine. The side effects and clinical pathology were also noted. RESULTS: Neither group showed a significant difference in 100-mm Pain VAS or ODI variation (p=0.1702, p=0.9041). There was no statistically significant difference between the experimental group and the control group in PGA or total usage of relief medicine. The ODI and PGA variation were not worse in the experimental group than the control group. The two groups showed no significant differences in side effects (p=0.9708). CONCLUSIONS: This study found that the Pelubi SR Tab applied to back pain patients was not inferior to the Pelubi Tab and did not show any significant difference in terms of safety. The Pelubi SR Tab can be used with the same expectation of safety as the Pelubi Tab.

A Case of Medullomyoblastoma of Cerebellopontine Angle Mimicking Acoustic Neuroma

Medulloblastoma is a common malignant central nervous system neoplasm found mainly in children. One the contrary, medulloblastoma of the cerebellopontine angle, the location of the tumor is very unusual. This is the the first case of the medullomyoblastoma, a rare form of medulloblastoma, occurring in the cerebellopontine angle. A 15-year-old boy experienced a sudden hearing loss in the left ear. Conservative medical treatment failed, and temporal MR imaging revealed a heterogeneously enhancing mass at the left cerebellopontine angle cistern and in the internal auditory canal; therefore, the lesion was regarded as a typical acoustic neuroma. Few days before surgery, an ipsilateral facial palsy developed, and a follow-up MR imaging showed a rapid growth of the previous lesion. The extended translabyrinthine approach permitted surgical removal. And under pathological diagnosis of malignancy, radiation therapy and series of chemotherapy was performed.

Treatment of Frontal Sinus-Supraorbital Cell Mucocele: Endoscopic Surgery with Trephination & Transillumination Technique: Case Report / 대한이비인후과학회지

Mucoceles of the paranasal sinuses are chronic expanding lesions containing inspissated mucus, which occurs when sinus ostium is obstructed. A variety of conservative and radical surgical procedures have been introduced, with each approach having advantages as well as disadvantages. Diseased frontal sinus mucosa and bone were commonly ablated by radical frontal sinus surgery such as osteoplastic flap surgery in the past. During the last decade, endoscopic sinus surgery has become the major choice for the treatment of paranasal sinus mucoceles, and the technique of endoscopic sinus marsupialization has been considered non-invasive and successful. But the technique has limitation in cases with small frontal recess or mucocele in the lateral portion of the frontal sinus which is not accessible via the nose, and hypertrophic mucosa obstructing the entire sinus. A 52-year-old man was presented with a supraorbital cell mucocele located in the lateral side of frontal sinus mucocele, which could not be treated by endoscopic surgery alone. Endoscopic surgery with sinus marsupialization, trephination and transillumination technique was introduced. We report this case with a review of related literatures.

A Case of Myxolipoma in Parapharyngeal Space: First Report of a Case / 대한이비인후과학회지

Myxolipomas, or myxoid lipomas, are unusual histologic types of lipoma in which components of the tumor are replaced by mucoid substances. Lipomas of the parapharyngeal space are extremely rare with only a few cases having been reported. The presence of myxolipoma in the parapharyngeal space has not yet been reported in the literature. We present the first report of a 14-year-old female with myxolipoma in the left parapharyngeal space which was excised via a transcervical approach.

Correlation Between Serum Magnesium, Ionized Calcium and Plasma Renin Activity in Hypertensives

BACKGROUND AND OBJECTIVES: Previous studies reported that sodium and potassium play an important role in the pathogenesis of hypertension. Recently attention has been directed towards a possible role of the divalent cations such as calcium, and magnesium. Plasma renin activity is also known to be related to divalent cations heterogeneously. This study investigated the relationships between serum magnesium and ionized calcium and plasma renin activity. MATERIALS AND METHODS: The subjects consisted of 27 essential hypertensive patients and 25 normotensive controls. Criteria for hypertensive group in this study were systolic blood pressure> or =140mmHg or a diastolic blood pressure > or =90mmHg (JNC-VI, 1997). Inclusion criteria were normal urinalysis, no history of systemic illness, no intake of antihypertensive drugs, and no recent intake of any other medication. We took magnesium-loading test for a reliable method of assessing possible magnesium deficiency. RESULTS: There was no significant difference between two groups in serum Magnesium concentration and other electrolytes and plasma renin activity. There was significantly higher rate in hypertensives than in normotensives in magnesium retention(hypertensive vs. normotensive: 63.56+/-12.21% vs. 38.43+/-11.53%, P<0.001). There was significant differences in ionized calcium between high-renin and low-or normo-renin hypertensives(P<0.001). Plasma renin activity was correlated positively with serum ionized calcium in hypertensives(r=.8147; P<0.001). CONCLUSION: These results suggest that plasma renin activity is a factor that can influence on serum ionized calcium in high-renin hypertensives.

Correlation Between Serum Magnesium, Ionized Calcium and Plasma Renin Activity in Hypertensives

BACKGROUND AND OBJECTIVES: Previous studies reported that sodium and potassium play an important role in the pathogenesis of hypertension. Recently attention has been directed towards a possible role of the divalent cations such as calcium, and magnesium. Plasma renin activity is also known to be related to divalent cations heterogeneously. This study investigated the relationships between serum magnesium and ionized calcium and plasma renin activity. MATERIALS AND METHODS: The subjects consisted of 27 essential hypertensive patients and 25 normotensive controls. Criteria for hypertensive group in this study were systolic blood pressure> or =140mmHg or a diastolic blood pressure > or =90mmHg (JNC-VI, 1997). Inclusion criteria were normal urinalysis, no history of systemic illness, no intake of antihypertensive drugs, and no recent intake of any other medication. We took magnesium-loading test for a reliable method of assessing possible magnesium deficiency. RESULTS: There was no significant difference between two groups in serum Magnesium concentration and other electrolytes and plasma renin activity. There was significantly higher rate in hypertensives than in normotensives in magnesium retention(hypertensive vs. normotensive: 63.56+/-12.21% vs. 38.43+/-11.53%, P<0.001). There was significant differences in ionized calcium between high-renin and low-or normo-renin hypertensives(P<0.001). Plasma renin activity was correlated positively with serum ionized calcium in hypertensives(r=.8147; P<0.001). CONCLUSION: These results suggest that plasma renin activity is a factor that can influence on serum ionized calcium in high-renin hypertensives.

Prevalence and Risk Factors of Hepatitis C Virus Infection in Chronic Hamodialysis Patients(multi-center study) / 대한내과학회지

OBJECTIVES: The aim of this study was to evaluate the prevalence and risk factors of hepatitis C virus(HCV) infection in patients on chronic hemodialysis. METHODS: We measured antibody to HCV using second generation enzyme immunoassay(ELISA) test or radioimmunoassay(RIA) and hepatitis B surface antigen, serum values of AST, ALT in 224 patients of six urban hemodialysis units. We also investigated some clinicai parameters such as age, sex, duration and frequency of hemodialysis, the amount of blood transfusion, and hemodialysis of infected patients on separate machines. RESULTS: 1) 33 of 224 patients(14.7%) were positive for HCV antibody. 2) The prevalence of HCV antibody were most significantly correlated with duration of hemodialysis and less significantly with frequency of hemodialysis, amount of blood transfusion but not correlated with age, sex and level of liver enzyme. 3) The prevalence of HCV antibody was significantly higher in a center which did not separate dialysis machine for HCV antibody positive patients than centers which did. CONCLUSION: Th prevalence of HCV antibody was most signficantly correlated with duration of hemodialysis. We suggest that environmental factor of hemodialysis unit may play major role in HCV infection of hemodialysis patients. So the importance of separate dialysis machine from HCV antibody positive patients should be emphasized.

The difference of bone marrow pressure between the subchondral and neck area in ostenecrosis of the femoral head / 대한정형외과학회잡지

No abstract available.

Bone Marrow Pressure Study in Ostoenecrosis of the Femoral Head / 대한정형외과학회잡지

Authors measured the bone marrow pressure(B.M.P.) of 59 femoral heads in cases of either suspicious or diagnosed osteonecrosis and obtained the significant relationship between increased B.M.P. and the osteonecrosis. Increased bone marrow pressure provided both predictive and early diagnostic importance in even the preclinical stage of evolution of the disease, which subsequently had core biopsy proved osteonecrosis of femoral head. The results obstained were as follows; 1. Roentgenographically apperent osteonecrosis showed abnormal B.M.P. pattern, which were proved by the core biopsy. 2. In 21 cases of preclinical osteonecrosis, which did not show roentgenographic changes of osteonecrosis, measured B.M.P. parterns indicated as early stage of osteonecrosis in core biopsy at all. 3. The incidence of abnormal pressure pattern I was 51% and that of pattern II was 30%. 4. Enneking radiological staging did not correlate with the results of B.M.P. 5. The measurement of B.M.P. is relatively easy and simple method without any remarkable risk. The results of this study had great meaning in emphasizing the contribution of the bone marrow pressure measurement dianosing the preclinical stage of osteonecrosis, which had no roentgenographical changes and diagnostic symptoms.