• 대한두경부종양학회:학술대회논문집
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• 2005.11a
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• pp.230-231
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• 2005

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.1-10
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• 2020

Objective: The aim of the study was to perform a meta-analysis of randomized clinical trials to compare the clinical efficacy and safety between combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with aromatase inhibitors (AIs) and AIs alone in patients with hormone receptor+/human epidermal growth factor receptor type2-(HR+/HER2-) advanced breast cancer. Methods: Published clinical studies were identified through electronic database searches until February 2019. Literature qualities were assessed by the Scottish Intercollegiate Guidelines Network Checklist. Key endpoints of efficacy were progression-free survival (PFS), objective response rate (ORR), and clinical benefit (CB). Endpoints of safety were adverse events (AEs) (neutropenia, leukopenia, any grade 3/4 AEs, and serious AEs) and on-treatment death. Meta-analysis was performed using the RevMan 5.3 software. Results: The selected five studies were evaluated as "good" in quality assessment. Compared to AIs alone, the combination therapy significantly improved PFS (pooled hazard ratio=0.55; 95% confidence interval (CI) 0.49-0.62), ORR (odds ratio=1.78; 95% CI=1.49-2.13), and CB (odds ratio=1.86; 95% CI=1.51-2.28). The prevalence of AEs was significantly higher in the combination group than in the AIs alone group. On-treatment death was greater in the combination group than in the AIs alone group, although insignificant. Conclusion: The combination therapy of CDK4/6 inhibitors with AIs was more effective for the treatment of HR+/HER2- advanced breast cancer, but less safe than AIs alone. The combination therapy should be effectively managed through patient monitoring, and further studies are needed to reduce AEs in the combination therapy of CDK4/6 inhibitors with AIs.

• PNF and Movement
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• v.5 no.2
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• pp.37-46
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• 2007

Purpose : The purpose of this study was to examine the effects of combination of isotonic and rhythmic stabilization in proprioceptive neuromuscular facilitation on trunk stability and balance in elderly people with chronic low back pain. Subjects : Thirty-two elderly people ($73.78{\pm}8.49$ years of age) who had complaints of CLBP were randomly assigned to 2 groups: experimental group and control group. Methods : Subject trained with combination of isotonic and rhythmic stabilization in proprioceptive neuromuscular facilitation for 4weeks with aim of improving trunk stability and balance. Weight distribution, trunk muscle balance, static balance ability and dynamic balance ability were measured before, at the end of training. Results : Data were analyzed using two-way ANOVA. After the exercise programs, there were significant differences in the weight distribution, trunk muscle balance and dynamic balance ability between the experimental and control group. However there was no significant difference in the one leg stance test(p<.05). Conclusion : This study suggest that PNF programs may be appropriate for improving trunk stability and balance in elderly people with CLBP.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.307-313
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• 1994

Purpose : Maxillary sinus cancers usually are locally advanced and involve the structures around sinus. It is uncommon for this cancer to spread to the regional lymph-nodes. For this reason, local control is of paramount important for cure. A policy of combined treatment is generally accepted as the most effective means of enhancing cure rartes. This paper reports our experience of a retrospective study of 31 Patients treated with radiation therapy alone and combination therapy of surgery and radiation. Materials and Methods: Between July 1974 and January 1992, 47 Patients with maxillary sinus cancers underwent either radiation therpay alone or combination therapy of surgery and radiation. Of these, only 31 patients were eligible for analysis. The distribution of clinical stage by the AJCC system was $26\%$(8/31) for T2 and $74\%$(23/31) for T3 and T4. Eight patients had palpable lymphadenopathy at diagnosis. Primary site was treated by Cobalt-60 radiation therapy using through a $45^{\circ}$ wedge-pair technique. Elective neck irradiation was not routinely given. Of these 8 patients, the six who had clinically involved nodes were treated with definite radiation therapy. The other two patients had received radical neck dissection. The twenty-two patients were treated with radiation alone and 9 patients were treated with combination radiation therapy, The RT alone patients with RT dose less than 60 Gy were 9 and those above 60 Gy were 13. Results : The overall 5 year survival rate was $23.8\%$. The 5 year survival rate by T-stage was $60.5\%$ and $7.9\%$ for T2 and T3,4, respectively. Statistical significance was found by T-stage(p<0.005). The 5 year survival rate by N-stage was $30\%$ for N (-) and $8.3\%$ for N(+), but statistically no significant difference was seen(p${\geq}$0.1). The 5 year survival rate for RT alone and combination RT was $22.5\%$ and $27.4\%$, respectively. The primary local control rate was $65\%$ (20/31). Conclusion : This study did not show significant difference in survival between RT alone and combination RT. There is still much controversy with regard to which treatment is optimum. Improved RT technique and development of multimodality treatment are essential to improve the local control and the survival rate in patients with advanced maxillary sinus cancer.

• Development and Reproduction
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• v.24 no.2
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• pp.113-123
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• 2020

Metformin has been widely used as an antidiabetic drug, and reported to inhibit cell proliferation in many cancers including non-small cell lung cancer (NSCLC). In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure. Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. The present study tested the combination therapy of metformin and trametinib by monitoring the alterations of regulatory effector proteins of cell signaling pathways and the effect of the combination on cell viability in NCI-H2087 NSCLC cells with NRAS and BRAF mutations. We show that metformin alone blocks PI3K/AKT/mTOR signaling pathway but induces the activation and phosphorylation of ERK. The combination therapy synergistically decreased cell viability in treatment with low doses of two drugs, while it gave antagonistic effect with high doses. These findings suggest that the efficacy of metformin and trametinib combination therapy may depend on the alteration of ERK activity induced by metformin and specific cellular context of cancer cells.

• YAKHAK HOEJI
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• v.59 no.6
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• pp.259-265
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• 2015

In recent, there are increasing reports about pharmacological activities of Crataegi Fructus which has been used for many centuries as medicinal and food sources in East Asia. However, its antifungal efficacy needs to be investigated. Thus, in the current study, we determined synergistic antifungal activity of the Crataegi Fructus extract (CFE) when combined with fluconazole (FLC) against disseminated candidiasis due to Candida albicans. This fungus is one of the most problematic fungal pathogens. Data resulting from a microdilution susceptibility test showed that CFE had a dose-dependent antifungal activity. When the extract was combined with FLC, the activity was synergistic. For example, the antifungal activity by the combination of CFE at $20{\mu}g/ml$ plus FLC at $0.1{\mu}g/ml$ was 4 times more effective than antifungal activity by FLC alone at the same concentration (P<0.05). In the murine model of disseminated candidiasis, the combination therapy potentiated resistance of mice, resulting in 80% of C. albicans-infected animals surviving the entire period of 40 days observation, whereas mice given CFE alone or FLC alone all died with 17 and 23 days, respectively, although they survived longer than the untreated control animals (P<0.05). The CFE's antifungal activity seemed to be related to the blockage of hyphal production of C. albicans yeast cells. In summary, CFE has a synergistic antifungal activity, which can be produced by combining CFE with FLC. Thus, our data strongly indicate that CFE may be a potential candidate as an antifungal agent for combination therapy.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.1-15
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• 2023

Autophagy is a process of eliminating damaged or unnecessary proteins and organelles, thereby maintaining intracellular homeostasis. Deregulation of autophagy is associated with several diseases including cancer. Contradictory dual roles of autophagy have been well established in cancer. Cytoprotective mechanism of autophagy has been extensively investigated for overcoming resistance to cancer therapies including radiotherapy, targeted therapy, immunotherapy, and chemotherapy. Selective autophagy inhibitors that directly target autophagic process have been developed for cancer treatment. Efficacies of autophagy inhibitors have been tested in various pre-clinical cancer animal models. Combination therapies of autophagy inhibitors with chemotherapeutics are being evaluated in clinal trials. In this review, we will focus on genetical and pharmacological perturbations of autophagy-related proteins in different steps of autophagic process and their therapeutic benefits. We will also summarize combination therapies of autophagy inhibitors with chemotherapies and their outcomes in pre-clinical and clinical studies. Understanding of current knowledge of development, progress, and application of cytoprotective autophagy inhibitors in combination therapies will open new possibilities for overcoming drug resistance and improving clinical outcomes.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.4
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• pp.251-259
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• 2013

The purpose of this study is to observe the effect of Korean medicine treatment in combination with intra-articular bee venom injection and needle-embedding therapy on recurrent patellar dislocation in patient. The Patient, diagnosed as recurrent patellar dislocation, was treated by Korean medicine treatment in combination with intra-articular bee venom injection and needle-embedding therapy. Visual analogue scale (VAS), knee flexion range of motion (ROM), Korean Western Ontario and Mcmaster Universities arthritis index (K-WOMAC) were used to measure changes during treatment. After treatment, VAS, knee flexion ROM, K-WOMAC were improved significantly. The Korean medicine treatment in combination with intra-articular bee venom injection and needle-embedding therapy was proved to be helpful to improve the symptoms of the recurrent patellar dislocation.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.131-133
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• 2016

Background: Combination chemotherapy regimes are common treatments for cancer. The aim of this study was to evaluation the effect of individual chemotherapeutic agents in comparison with a first line chemotherapy regime treatment in the AGS gastric cancer cell line by MTT assay. Materials and Methods: In this experimental study, AGS cells were grown in RPMI-1640 supplemented with 10% fetal calf serum and 100 IU/ml penicillin, and $10{\mu}g/ml$ streptomycinin, under a humidified condition at $37^{\circ}C$ with 5% CO2. All cells were washed with PBS and detached with trypsin, centrifuged and 8000 cells re-plated on to 96- well plates. LD50 doses of Epirubicin, Cisplatin and 5-fluorouracil were added to each well in mono or triple therapy. Anti-proliferative activities were determined by MTT assay after 24, 48 or 72 h. Results: Results of MTT assays showed that there were no significant differences among 3 drugs in monotherapy (p=0.088), but there was significant difference between combination therapy with epirubicin (P=0.031) and 5FU (p=0.013) on cell survival at 24 h. After 48 and 72 hours, cell viability showed significant differences between the 3 drugs (p=0.048 and P=0.000 for 48 and 72 h, respectively) and there was significant difference between combination therapy with epirubicin (P=0.035 and P=0.002 for 48 and 72 h, respectively). Conclusions: The results showed no significant differences between these chemotherapy drugs each given alone, but combination therapy with 3 drugs had significant effects on cell viability in comparison with epirubicin alone.

• Journal of Yeungnam Medical Science
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• v.32 no.2
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• pp.85-89
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• 2015

Background: We examined the usefulness of urine osmolality, as a predictive factor in the treatment of monosymptomatic nocturnal enuresis (NE) with combination therapy of imipramine and desmopressin. Methods: From May 2014 to April 2015, 59 monosymptomatic NE patients participated in this study. Early morning urine osmolality was measured at 1 week and 1 day before combination therapy of imipramine and desmopressin, and at 1 week and 2 weeks after therapy. The response to combination therapy was evaluated at 3 months after treatment. The mean period of combination therapy was $6.4{\pm}4.2weeks$. Therapeutic response was classified as complete (0-1 wet night/week), partial (over 50% reduction of night) and non-responders (less than 50% reduction of night). Results: The cumulative rate of the complete and partial responders was 76.3%. Among the 3 groups, the statistically lowest value of pre-treatment urine osmolality was observed in the complete responder group (p<0.001). Urine osmolality increased in all groups after treatment, however, statistically the greatest difference between pre and post-treatment urine osmolality was observed in the complete responder group (p=0.024). No serious side effects were observed. Conclusion: Early morning urine osmolality and change of urine osmolality between pre and post-treatment have predictive values in the response to combined imipramine and desmopressin for treatment of monosymptomatic NE.