• BMB Reports
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• v.53 no.2
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• pp.88-93
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• 2020

Cisplatin is a widely used anti-cancer agent. However, the effectiveness of cisplatin has been limited by the commonly developed drug resistance. This study aimed to investigate the potential effects of endoplasmic reticulum (ER) stress to overcome drug resistance using the cisplatin-resistant A2780/CisR ovarian cancer cell model. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (named DPP23) is an ER stress inducer. We found that DPP23 triggered apoptosis in both parental cisplatin-sensitive A2780 and cisplatin-resistant A2780/CisR ovarian cancer cells due to activation of reactive oxygen species (ROS)-mediated unfolded protein response (UPR) pathway in the endoplasmic reticulum. This result suggests that ROS-mediated UPR activation is potential in overcoming drug resistance. DPP23 can be used as a target pharmacophore for the development of novel chemotherapeutic agents capable of overcoming drug resistance in cancer cells, particularly ovarian cancer cells.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.479-489
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• 2022

5-Fluorouracil (5-FU) remains to be an important chemotherapeutic drug for treating several cancers when targeted therapy is unavailable. Chemoresistance limits the clinical utility of 5-FU, and new strategies are required to overcome the resistance. Reactive oxygen species (ROS) and antioxidants are balanced differently in both normal and cancer cells. Modulating ROS can be one method of overcoming 5-FU resistance. This review summarizes selected compounds and endogenous cellular targets modulating ROS generation to overcome 5-FU resistance.

• Archives of Pharmacal Research
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• v.29 no.12
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• pp.1067-1073
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• 2006

Cisplatin, a platinum coordinated complex, is a widely used antineoplastic agent for the treatment of metastatic tumors of the testis, metastatic ovarian tumors, lung cancer, advanced bladder cancer and many other solid tumors. The cytotoxic action of the drug is often thought to be associated with its ability to bind DNA to form cisplatin-DNA adducts. The development of resistance to cisplatin during treatment is common and constitutes a major obstacle to the cure of sensitive tumors. Although to understand the clinically relevant mechanisms of resistance, many studies have been aimed at clarifying the biochemical/molecular alterations of cisplatin-resistance cells, these studies did not conclusively identify the basis of cellular resistance to cisplatin. In this review, cisplatin resistance was discussed in terms of the relevant transporters, such as copper transporters (CTRs), organic cation transporters (OCTs) and multi-drug resistance related transporters (MDRs). These transporters seem to be contributed to cisplatin resistance through the reduction of drug accumulation in the cell. Better understanding the mechanism of cisplatin resistance associated with transporters will provide the useful informations for overcoming the cisplatin resistance.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.248-256
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• 2016

Somatic mutations that lead to hyperactivation of epidermal growth factor receptor (EGFR) signaling are detected in approximately 50% of lung adenocarcinoma in people from the Far East population and tyrosine kinase inhibitors are now the standard first line treatment for advanced disease. They have led to a doubling of progression-free survival and an increase in overall survival by more than 2 years. However, emergence of resistant clones has become the primary cause for treatment failure, and has created a new challenge in the daily management of patients with EGFR mutations. Identification of mechanisms leading to inhibitor resistance has led to new therapeutic modalities, some of which have now been adapted for patients with unsuccessful tyrosine kinase inhibitor treatment. In this review, we describe mechanisms of tyrosine kinase inhibitor resistance and the available strategies to overcoming resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6831-6839
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• 2015

Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

• Proceedings of the Korean Institute of Interior Design Conference
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• 2007.11a
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• pp.198-201
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• 2007

Currently, both Korea and Japan have cooperated to get a foothold in economic major countries in the Asia through the various economic cooperation and the overcoming of cultural difference in cultural interchanges between two countries. However, in the present age, two countries are on the other road in historical view and conception; the final report over 3 year studies by the two countries' history study partnership commission shows the above views; while Korea has been in base of Japan colonialization's unjustification, Japan has been in base of its facts. The aboves have proved that Japan has not taken an honest self examination and conscience over the history. Accordingly, Japan resistance volunteer memorial is proposed as the educational place to carry down the martyr's holy patriotism in later ages and practice its spirit by learning the resistance volunteer resistance volunteer movement, which focused on resisting the Japan invasion and fighting the independence.

• BMB Reports
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• v.54 no.1
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• pp.70-88
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• 2021

Immunotherapy has revolutionized the landscape of cancer treatment and become a standard pillar of the treatment. The two main drivers, immune checkpoint inhibitors and chimeric antigen receptor T cells, contributed to this unprecedented success. However, despite the striking clinical improvements, most patients still suffer from disease progression because of the evolution of primary or acquired resistance. This mini-review summarizes new treatment options including novel targets and interesting combinational approaches to increase our understanding of the mechanisms of the action of and resistance to immunotherapy, to expand our knowledge of advances in biomarker and therapeutics development, and to help to find the most appropriate option or a way of overcoming the resistance for cancer patients.

• Physical Therapy Rehabilitation Science
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• v.8 no.2
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• pp.61-66
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• 2019

Objective: The purpose of this study was to investigate the effects of resistance applied in various directions on lower extremity muscle activity and balance during squat exercise performance. Design: Cross-sectional study. Methods: Forty-one adults (19 males and 22 females) agreed to the study purpose and procedures. All subjects randomly performed squat exercises with an intensity of overcoming 10% of body weight resistance pulled forward, backward and general squats with $60^{\circ}$ of knee joint flexion. Electromyography was used to measure muscle activity of the vastus medialis oblique (VMO), rectus femoris (RF), vastus lateralis oblique (VLO), biceps femoris (BF), and semitendinosus (ST) muscles. The Wii Balance Board was used to assess balance during the three-method squat operation. Each operation was measured three times for 10 seconds. Results: There were significant differences in muscle activities of the VMO, RF, VLO, ST and balance ability with the application of three directions of resistance (p<0.05). Post hoc comparisons revealed that squats performed with resistance pulled in the backward direction resulted in higher VMO, RF and VLO activity than with the resistance placed in a pulled forward direction (p<0.05). In the ST, resistance applied in the pulled forward direction showed greater muscle activity compared to the pulled backward direction (p<0.05). With balance, squats performed with resistance pulled in the forward direction showed greater muscle activity than with resistance applied in the pulled backward direction and during general squat performance (p<0.05). Conclusions: In this study, squat exercises performed with resistance applied in the direction of pulling backwards was found to be the most effective in improving quadriceps muscle strength and balance. It is effective to provide resistance that is placed in the forward when it is difficult to perform a general squat due to weakness of the quadriceps.

• Research in Plant Disease
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• v.27 no.4
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• pp.137-148
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• 2021

Plant RNA viruses are one of the most destructive pathogens that cause a significant loss in crop production worldwide. They have evolved with high genetic diversity and adaptability due to the short replication cycle and high mutation rate during genome replication, which are characteristics of RNA viruses. Plant RNA viruses exist as quasispecies with high genetic diversity; thereby, a rapid population transition with new fitness can occur due to selective pressure resulting from environmental changes. Plant resistance can act as selective pressure and affect the fitness of the virus, which may lead to the emergence of resistance-breaking variants. In this paper, we introduced the evolutionary perspectives of plant RNA viruses and the driving forces in their evolution. Based on this, we discussed the mechanism of the emergence of variant viruses that overcome plant resistance. In addition, strategies for deploying plant resistance to viral diseases and improving resistance durability were discussed.