• Gut and Liver
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• 제12권6호
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• pp.623-632
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• 2018

Intestinal Behçet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behçet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor-${\alpha}$, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behçet's disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti-tumor necrosis factor-${\alpha}$ for the treatment of intestinal Behçet's disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behçet's disease. This review also discusses safety issues associated with anti-tumor necrosis factor-${\alpha}$, including vulnerability to infections and malignancy.

• 통합자연과학논문집
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• 제4권1호
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• pp.23-30
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• 2011

Multidrug resistance (MDR) is one of the main obstacles in the chemotherapy of cancer. MDR is associated with the over expression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. First-generation agents were limited by unacceptable toxicity, whereas second-generation agents had better tolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.

• Clinical and Experimental Pediatrics
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• 제64권6호
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• pp.269-279
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• 2021

Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) is an ancient prokaryotic defense system that precisely cuts foreign genomic DNA under the control of a small number of guide RNAs. The CRISPR-Cas9 system facilitates efficient double-stranded DNA cleavage that has been recently adopted for genome editing to create or correct inherited genetic mutations causing disease. Congenital heart disease (CHD) is generally caused by genetic mutations such as base substitutions, deletions, and insertions, which result in diverse developmental defects and remains a leading cause of birth defects. Pediatric CHD patients exhibit a spectrum of cardiac abnormalities such as septal defects, valvular defects, and abnormal chamber development. CHD onset occurs during the prenatal period and often results in early lethality during childhood. Because CRISPR-Cas9-based genome editing technology has gained considerable attention for its potential to prevent and treat diseases, we will review the CRISPR-Cas9 system as a genome editing tool and focus on its therapeutic application for CHD.

• Journal of Breast Cancer
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• 제21권4호
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• pp.343-353
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• 2018

Cancer is the leading cause of death worldwide. In developed as well as developing countries, breast cancer is the most common cancer found among women. Currently, treatment of breast cancer consists mainly of surgery, chemotherapy, hormone therapy, and radiotherapy. In recent years, because of increased understanding of the therapeutic potential of immunotherapy in cancer prevention, cancer vaccines have gained importance. Here, we review various immunotherapeutic breast cancer vaccines including peptide-based vaccines, whole tumor cell vaccines, gene-based vaccines, and dendritic cell vaccines. We also discuss novel nanotechnology-based approaches to improving breast cancer vaccine efficiency.

• Integrative Medicine Research
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• 제3권2호
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• pp.99-102
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• 2014

A 37-year-old female patient with chronic and stubborn abdominal pain had been hospitalized five times in three Western hospitals, but no effects were observed. No abnormalities were found in blood tests, gastrointestinal endoscopy, sonogram, and computed tomography of the abdomen, except mild paralytic ileus. The patient decided to rely on Korean medicine as an inpatient. She was diagnosed with functional abdominal pain syndrome, and her symptom differentiation was the "Yang deficiency of spleen and kidney." A herbal drug, Hwangikyeji-tang, along with moxibustion and acupuncture, was given to the patient. Abdominal pain and related symptoms were reduced radically within 16 days of treatment. This report shows a therapeutic potential of Korean medicine-based treatment for functional abdominal pain syndrome.

• BMB Reports
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• 제52권2호
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• pp.111-112
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• 2019

Although many studies have reported that the breakdown of the blood-brain barrier (BBB) represents one of the major pathological changes in aging, the mechanism underlying this process remains relatively unexplored. In this study, we described that acid sphingomyelinase (ASM) derived from endothelial cells plays a critical role in BBB disruption in aging. ASM levels were elevated in the brain endothelium and plasma of aged humans and mice, resulting in BBB leakage through an increase in caveolae-mediated transcytosis. Moreover, ASM caused damage to the caveolae-cytoskeleton via protein phosphatase 1-mediated ezrin/radixin/moesin dephosphorylation in primary mouse brain endothelial cells. Mice overexpressing brain endothelial cell-specific ASM exhibited acceleration of BBB impairment and neuronal dysfunction. However, genetic inhibition and endothelial specific knock-down of ASM in mice improved BBB disruption and neurocognitive impairment during aging. Results of this study revealed a novel role of ASM in the regulation of BBB integrity and neuronal function in aging, thus highlighting the potential of ASM as a new therapeutic target for anti-aging.

• Molecules and Cells
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• 제42권3호
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• pp.200-209
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• 2019

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been used as promising tools for regenerative medicine, disease modeling, and drug screening. Traditional and common strategies for pluripotent stem cell (PSC) differentiation toward disease-relevant cell types depend on sequential treatment of signaling molecules identified based on knowledge of developmental biology. However, these strategies suffer from low purity, inefficiency, and time-consuming culture conditions. A growing body of recent research has shown efficient cell fate reprogramming by forced expression of single or multiple transcription factors. Here, we review transcription factor-directed differentiation methods of PSCs toward neural, muscle, liver, and pancreatic endocrine cells. Potential applications and limitations are also discussed in order to establish future directions of this technique for therapeutic purposes.

• Journal of Cancer Prevention
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• 제23권4호
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• pp.153-161
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• 2018

Imbalance of protein homeostasis (proteostasis) is known to cause cellular malfunction, cell death, and diseases. Elaborate regulation of protein synthesis and degradation is one of the important processes in maintaining normal cellular functions. Protein degradation pathways in eukaryotes are largely divided into proteasome-mediated degradation and lysosome-mediated degradation. Proteasome is a multisubunit complex that selectively degrades 80% to 90% of cellular proteins. Proteasome-mediated degradation can be divided into 26S proteasome (20S proteasome + 19S regulatory particle) and free 20S proteasome degradation. In 1980, it was discovered that during ubiquitination process, wherein ubiquitin binds to a substrate protein in an ATP-dependent manner, ubiquitin acts as a degrading signal to degrade the substrate protein via proteasome. Conversely, 20S proteasome degrades the substrate protein without using ATP or ubiquitin because it recognizes the oxidized and structurally modified hydrophobic patch of the substrate protein. To date, most studies have focused on protein degradation via 26S proteasome. This review describes the 26S/20S proteasomal pathway of protein degradation and discusses the potential of proteasome as therapeutic targets for cancer treatment as well as against diseases caused by abnormalities in the proteolytic system.

• Quantitative Bio-Science
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• 제37권2호
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• pp.113-124
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• 2018

Pim kinases are important targets for cancer therapies because they are mainly responsible for cancer metastasis and overall therapeutic treatment responses. Because of their unusual structural feature in the hinge region of the ATP-binding site, new binding motifs have been discovered and used for the development of Pim kinases inhibitors. The results of a screening of 5-membered heteroaromatic compounds and the effects of structural modifications on the inhibition of Pim kinases' activities showed the potential scaffold for Pim inhibitors. 1,3,4-Oxadiazole-2(3H)-thione was found as a new scaffold for Pim kinase inhibitors.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제30권2호
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• pp.50-56
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• 2019

Most patients with Tourette's disorder experience an uncomfortable sensory phenomenon called the premonitory urge immediately before experiencing tics. It has been suggested that premonitory urges are associated with comorbidities such as obsessive compulsive disorder, anxiety disorders, and attention-deficit/hyperactivity disorder, although these associations have been inconsistent. Most patients experience tics as a result of the premonitory urges, and after the tics occur, most patients report that the premonitory urges are temporarily relieved. As a consequence, several studies have assessed the premonitory urge and its potential therapeutic utility. Based on the concept that the premonitory urge induces tics, behavioral treatments such as Exposure and Response Prevention and Habit Reversal Therapy have been developed. However, it is still unclear whether habituation, the main mechanism of these therapies, is directly related to their effectiveness. Moreover, the observed effects of pharmacological treatments on premonitory urges have been inconsistent.