• Tuberculosis and Respiratory Diseases
• /
• 제76권3호
• /
• pp.105-113
• /
• 2014

From January 2012 up until March 2013, many articles with huge clinical importance in asthma were published based on large numbered clinical trials or meta-analysis. The main subjects of these studies were the new therapeutic plan based on the asthma phenotype or efficacy along with the safety issues regarding the current treatment guidelines. For efficacy and safety issues, inhaled corticosteroid tapering strategy or continued long-acting beta agonists use was the major concern. As new therapeutic trials, monoclonal antibodies or macrolide antibiotics based on inflammatory phenotypes have been under investigation, with promising preliminary results. There were other issues on the disease susceptibility or genetic background of asthma, particularly for the "severe asthma" phenotype. In the era of genome and pharmacogenetics, there have been extensive studies to identify susceptible candidate genes based on the results of genome wide association studies (GWAS). However, for severe asthma, which is where most of the mortality or medical costs develop, it is very unclear. Moreover, there have been some efforts to find important genetic information in order to predict the possible disease progression, but with few significant results up until now. In conclusion, there are new on-going aspects in the phenotypic classification of asthma and therapeutic strategy according to the phenotypic variations. With more pharmacogenomic information and clear identification of the "severe asthma" group even before disease progression from GWAS data, more adequate and individualized therapeutic strategy could be realized in the future.

• BMB Reports
• /
• 제50권7호
• /
• pp.345-354
• /
• 2017

Autophagy, a catabolic process necessary for the maintenance of intracellular homeostasis, has recently been the focus of numerous human diseases and conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, the continued presence of autophagy is essential for cell survival and dysfunctional autophagy is thought to speed up the progression of neurodegeneration. The actual molecular mechanism behind the progression of dysfunctional autophagy is not yet fully understood. Emerging evidence suggests that basal autophagy is necessary for the removal of misfolded, aggregated proteins and damaged cellular organelles through lysosomal mediated degradation. Physiologically, neurodegenerative disorders are related to the accumulation of amyloid ${\beta}$ peptide and ${\alpha}-synuclein$ protein aggregation, as seen in patients with Alzheimer's disease and Parkinson's disease, respectively. Even though autophagy could impact several facets of human biology and disease, it generally functions as a clearance for toxic proteins in the brain, which contributes novel insight into the pathophysiological understanding of neurodegenerative disorders. In particular, several studies demonstrate that natural compounds or small molecule autophagy enhancer stimuli are essential in the clearance of amyloid ${\beta}$ and ${\alpha}-synuclein$ deposits. Therefore, this review briefly deliberates on the recent implications of autophagy in neurodegenerative disorder control, and emphasizes the opportunities and potential therapeutic application of applied autophagy.

• BMB Reports
• /
• 제51권1호
• /
• pp.5-13
• /
• 2018

Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affects the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins. So far, many important and NDD-related substrates of TG2 have been identified, including $amlyoid-{\beta}$, tau, ${\alpha}-synuclein$, mutant huntingtin, and ALS-linked trans-activation response (TAR) DNA-binding protein 43. Recently, the formation of toxic inclusions mediated by several TG2 substrates were efficiently inhibited by TG2 inhibitors. Therefore, the development of highly specific TG2 inhibitors would be an important tool in alleviating the progression of TG2-related brain disorders. In this review, the authors discuss recent advances in TG2 biochemistry, several mechanisms of molecular regulation and pleotropic signaling functions, and the presumed role of TG2 in the progression of many NDDs.

• Molecules and Cells
• /
• 제25권1호
• /
• pp.1-6
• /
• 2008

Osteoarthritis (OA), one of the most common skeletal disorders characterized by cartilage degradation and osteophyte formation in joints, is induced by accumulated mechanical stress; however, little is known about the underlying molecular mechanism. Several experimental OA models in mice by producing instability in the knee joints have been developed to apply approaches from mouse genetics. Although proteinases like matrix metalloproteinases and aggrecanases have now been proven to be the principal initiators of OA progression, clinical trials of proteinase inhibitors have not been successful for the treatment, turning the interest of researchers to the upstream signals of proteinase induction. These signals include undegraded and fragmented matrix proteins like type II collagen or fibronection that affects chondrocytes through distinct receptors. Another signal is proinflammatory factors that are produced by chondrocytes and synovial cells; however, recent studies that used mouse OA models in knockout mice did not support that these factors have a role in the central contribution to OA development. Our mouse genetic approaches found that the induction of a transcriptional activator Runx2 in chondrocytes under mechanical stress contributes to the pathogenesis of OA through chondrocyte hypertrophy. In addition, chondrocyte apoptosis has recently been identified as being involved in OA progression. We hereby propose that these endochondral ossification signals may be important for the OA progression, suggesting that the related molecules can clinically be therapeutic targets of this disease.

• Genomics & Informatics
• /
• 제12권4호
• /
• pp.156-164
• /
• 2014

Cancer is the most dreaded disease in human and also major health problem worldwide. Despite its high occurrence, the exact molecular mechanisms of the development and progression are not fully understood. The existing cancer therapy based on allopathic medicine is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a non-toxic and effective mode of treatment is needed to control cancer development and progression. Some medicinal plants offer a safe, effective and affordable remedy to control the cancer progression. Nimbolide, a limnoid derived from the neem (Azadirachta indica) leaves and flowers of neem, is widely used in traditional medical practices for treating various human diseases. Nimbolide exhibits several pharmacological effects among which its anticancer activity is the most promising. The previous studies carried out over the decades have shown that nimbolide inhibits cell proliferation and metastasis of cancer cells. This review highlights the current knowledge on the molecular targets that contribute to the observed anticancer activity of nimbolide related to induction of apoptosis and cell cycle arrest; and inhibition of signaling pathways related to cancer progression.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제15권1호
• /
• pp.19-22
• /
• 2012

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract and characterized by relapsing and remitting episodes, with progression over time to complications of stricture, fistulas, or abscesses. The etiology is unknown, although the common opinion is that the disease arises from a disordered immune response to the gut contents in genetically predisposed individuals. Infliximab is a mouse-human chimeric antibody against tumor necrosis factor ${\alpha}$, and has proven to be effective in active Crohn's disease for both induction and maintenance therapy. Despite the growing experience with infliximab in Crohn's disease, optimal treatment strategies still need to be determined. The purpose of this review is to summarize the current knowledge on the use of infliximab in Crohn's disease and to discuss the yet-unsolved issues.

• 대한핵의학회:학술대회논문집
• /
• 대한핵의학회 2002년도 춘계학술대회 및 총회
• /
• pp.32-36
• /
• 2002

Lymphoma is a group of neoplastic disease of lymphoid tissues, which can be classified into categories of Hodgkin's disease and non-Hodgkin's lymphoma(NHL). Prognosis of lymphoma depends on the extent of disease(staging) especially in Hodgkin's disease, but also depends on the histologic make up in non-Hodgkin's lymphoma. Although non-Hodgkin's lymphoma is a neoplastic transformation of lymphoid cell it is a collection of disease with merphologically and immunologically diverse make up. Consequently the classification of NHL has changed frequently and evolved according to the progress of immunologic and molecular knowledge added to the original morphologic classification. Lymphoma is a disorder sensitive to chemotherapy which often leads to cure of the disease even in advanced stage, while many other patients die from the progression of disease. Therefore, better understanding in newer classification and sensitive imaging technique, such as PET, in lymphoma will likely lead to the improvement of survival rate.

• 대한임상검사과학회지
• /
• 제51권1호
• /
• pp.26-33
• /
• 2019

최근 반려동물 시장의 급격한 성장으로 인해 동물용 질병 진단키트의 개발이 이루어지고 있다. 이에 동물 분자진단 개발을 위한 바이오마커의 도입으로 효용성을 재평가하고 있다. 좋은 바이오 마커는 정확하고 신뢰할 수 있어야 하고, 정상 상태와 질병 상태를 구별하고, 다른 질병을 구별해야 한다. 최근 보고된 유전마커나 세포유리 DNA, 순환종양세포, granzyme, 피부종양에 관한 종양마커의 개발이 활발히 이루어지고 있으며, 기타로는 브루셀라증, programmed death receptor-1, symmetric dimethylarginine, periostin, cysteinyl leukotrien이 활발히 도입되고 있다. 따라서 바이오마커는 위험 예측에 사용되거나 질병 진행의 스크리닝, 진단 및 모니터링에 사용된다. 관련 바이오 마커에 대한 가장 중요한 기준은 질병 특이성이며 많은 잠재적 바이오 마커가 실험실 및 시험 연구에서 출현했지만, 독립적인 실험이나 대규모 임상 연구에서 검증이 부족하다. 후보 바이오 마커는 질병과 연관성을 평가하고, 조기 발견, 질병 진행에 대한 바이오 마커의 유효성을 검증하여서 인간 및 동물에게 접목하게 된다. 향후 잘 구조화 된 바이오마커 기반 연구의 효용성을 재평가하고 동물 질병 진단에 도입되는 추세에 맞춰 현장검사에서 활용될 수 있는 키트의 개발에 대한 연구가 요구돼야 할 것으로 사료된다.

• Journal of Cardiovascular Imaging
• /
• 제26권4호
• /
• pp.229-237
• /
• 2018

BACKGROUND: Statins are thought to have little effect on the progression of aortic stenosis, but the data on their role in patients with aortic valve sclerosis (AVS) are limited and inconsistent. METHODS: We retrospectively analyzed 541 consecutive patients (214 men, age: $70{\pm}11$ years) with AVS. Each patient underwent two or more electrocardiography examinations at least 6 months apart at Kangwon National University Hospital from August 2010 to August 2015. AVS is defined as irregular thickening of the leaflets, focal increases in echogenicity and minimal elevation of the peak aortic valve velocity (> 1.5 and < 2 m/s). The progression rate of AVS was expressed as the increase in peak velocity per year (m/s/yr). RESULTS: The mean follow-up duration was $24.9{\pm}13.3$ months in the statin-treated group and $24.1{\pm}12.4$ months in the non-statin-treated group (p = 0.460). There were no differences between the statin-treated and non-statin-treated groups in mean age, gender or smoking status. Relative to the non-statin-treated group, a higher number of patients in the statin-treated group had hypertension, diabetes, ischemic heart disease, and stroke. The progression rate of AVS did not differ between the statin-treated and non-statin-treated groups ($0.012{\pm}0.340m/s/yr$ vs. $0.014{\pm}0.245m/s/yr$, p = 0.956). Multivariate analysis showed initial peak aortic jet velocity was significantly associated with AVS progression (${\beta}=0.153$, p = 0.009). CONCLUSIONS: Our study demonstrated that statins had no effect on the progression of AVS. However, well-designed studies are needed to define the prognosis and management of AVS.

• 대한두경부종양학회지
• /
• 제16권1호
• /
• pp.58-63
• /
• 2000

Objectives: To demonstrate effective diagnostic method and proper management of recurrent thyroid cancer through to compare treatment and surveillance of $I^{131}$ scanning detected recurrence and clinically detected recurrence. Material and Methods: We retrospectively analyzed clinical information about 46 patients who has recurrent thyroid cancer of 298 patients who have been primarily operated due to thyroid cancer in PMC at the over 10 years between 1986 and 1995. We examine incidence of recurrence due to pathologic types, site of recurrence, disease free interval, detection method of recurrence, and also treatment and progression of recurrence. A patients in which the clinical examination was entirely negative and the $I^{131}$ scan demonstrated either a new area of $I^{131}$ uptake or an increased area of concentration, compared to the previous scan, was designated as a recurrence detected by $I^{131}$ scan only. Recurrences that were obviously by physical examination or chest x-ray, etc were considered clinically detected recurrence, regardless of the the results of the thyroid scan. Results: Mean of disease tree interval(DFI) is 36months. When mean DFI of $I^{131}$ scan detected recurrence is 28months, whereas mean DFI of clinically detected recurrence is 47months. In statiscal analysis, p-value is 0.043 as significantly. In progression of recurrent patient, NED is 28case, AWD is Sease, DOD is 13case. Among the 13case, scan detected recurrence is lease of 20 patients(5%), whereas clinically detected recurrence is l2case of 26 patient(46%). In statiscal analysis, p-value is 0.003 as significantly. Conclusion: Early detection of the recurrent thyroid cancer by $I^{131}$ scanning leads to good progress compare with detection by clinical examination. NED: No Evidence of Disease AWD : Alive With Disease DOD : Dead Of Disease DOC: Dead of Other Cause