• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7687-7692
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• 2014

Aim: To observe the effects of a novel all-trans retinoid acid (ATRA) derivative, N-(3-trifluoromethyl-phenyl)-retinamide (ATPR), on lung adenocarcinoma A549 cells and to explore the potential mechanism of ATPR inhibiting of A549 cell migration. Materials and Methods: The cytotoxicity of ATRA and ATPR on A549 cells was assessed using MTT assay. Wound healing assays were used to analyze the influences of ATRA, ATPR, ML-7 (a highly selective inhibitor of myosin light chain kinase (MLCK)), PMA (an activator of MAPKs) and PD98059 (a selective inhibitor of ERK1/2) on the migration of A549 cells. Expression of MLCK and phosphorylation of myosin light chain (MLC) were assessed by Western blotting. Results: ATRA and ATPR inhibited the proliferation of A549 cells in a dose- and time-dependent manner, and the effect of ATPR was much more remarkable compared with ATRA. Relative migration rate and migration distance of A549 cells both decreased significantly after treatment with ATPR or ML-7. The effect on cell migration of PD98059 combining ATPR treatment was more notable than that of ATPR alone. Moreover, compared with control groups, the expression levels of MLCK and phosphorylated MLC in A549 cells were both clearly reduced in ATRA and ATPR groups. Conclusions: ATPR could suppress the migration and invasion of A549 cells, and the mechanism might be concerned with down-regulating the expression of MLCK in the ERK-MAPK signaling pathway, pointing to therapeutic prospects in lung cancer.

• Tuberculosis and Respiratory Diseases
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• 제65권2호
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• pp.142-146
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• 2008

소세포폐암은 비교적 초기 항암치료에 대한 반응이 우수하지만 빠르게 진행하는 것으로 알려져 있다. Topotecan은 topoisomerase I inhibitor로 소세포폐암에서 이차치료제로 사용된다. Topotecan의 흔한 부작용으로는 빈혈, 혈소판감소증, 호중구감소증과 같은 혈액학적 부작용이 있으나, topotecan에 의한 폐독성은 잘 알려져 있지 않다. 저자들은 일차치료에 불응하여 이차치료제로 topotecan을 투여 받던 소세포폐암 환자에서 3주기 topotecan 투약중에 발생한 급성호흡곤란증후군을 경험하여 보고한다. 환자는 호흡곤란을 호소하면서 호흡부전에 빠졌으며, 흉부전산화단층촬영에서 약제에 의한 폐손상을 시사하는 미만성 간유리음영을 보였다. 환자는 급성호흡곤란증후군으로 사망하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8435-8440
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• 2014

Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent. Methods: Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis. Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, p<0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival. Conclusion: Both pro- and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE.

• 대한유전성대사질환학회지
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• 제17권1호
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• pp.24-30
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• 2017

Gorham-Stout disease (GSD)는 골용해와 함께 혈관 및 림프조직의 비정상적인 증식으로 골조직 파괴가 유발되는 매우 드문 질환이다. 아직까지 GSD의 정확한 병인 및 기전은 밝혀지지 않았다. 악성종양이나 신경병증, 감염과의 연관성은 불명확하며, 골조직이 있는 신체 어디에서든 기형적 혈관-림프관 증식이 발생할 수 있다. GSD 중 약 20%에서 유미흉을 동반하는데, 림프관 형성이상이나 가슴 림프관 손상에 의해 이차적으로 발생한다. 급격한 호흡부전으로 이어질 수 있어 불량한 예후인자로 알려져 있지만, 질환 자체의 희귀성 때문에 현재까지 확립된 표준치료법은 없다. 본 증례는 유미흉을 동반한 생명을 위협하는 GSD 환자에서 적극적인 외과적 중재술 후 mTOR inhibitor 및 beat-blocker 복합요법을 적용하여 치료에 성공한 보고이다. 환자는 가슴림프관 결찰술 및 흉막유착술을 시행 받았으나, 일시적 증상호전 이후로 유미흉 및 호흡곤란의 재악화 반복되었다. 양측 흉막유착제거 및 폐쇄 흉강삽관술과 함께, beta-blocker와 mTOR inbititor 경구투약을 시작했다. 약물투약 1개월 후 유미흉 재발없이 호흡 안정적으로 유지되어 산소 보조치료 없이 퇴원하였다. 현재 11개월째 지속적으로 약물 투약 중으로, 약물 부작용 및 추가적인 입원치료 없이 정상적인 일상생활을 유지하고 있다. 추후 유미흉을 동반한 GSD 환자의 치료에서, 적극적인 외과적 중재술과 함께 경구 mTOR inhibitor 및 beta-blocker 복합요법을 고려해 볼 수 있겠다.

• Tuberculosis and Respiratory Diseases
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• 제61권2호
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• pp.137-142
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• 2006

연구배경: 8주 이상 지속되는 만성 기침의 원인 중 하나인 위식도역류질환는 환자의 약 75%가 증상이 없으며, 진단을 위한 24시간 식도 pH감시가 침습적이고 검사가 어려워 진단 및 치료에 어려움이 있다. 따라서 만성 기침환자 중 후비루증후군 및 기관지 천식이 아닌 환자를 대상으로 양자펌프억제제를 투여하고 치료효과를 관찰하였다. 방법 및 대상: 기침증상이 8주 이상인 만성기침 환자 중 X-ray 소견상 이상이 없고 메타콜린 기관지유발시험상 음성이며, 후비루증후군 치료에 반응이 없었던 40명을 대상으로 하였다. 8주 이상 양자펌프억제제를 투여하였으며 50%이상 기침이 감소한 경우를 부분 반응군, 기침이 거의 소실된 경우를 완전 반응군으로 분류하였다. 결 과: 대상자 40명중 29명만이 4주 이상 추적되었으며 이중 26명만이 8주까지 추적 관찰되었다. 29명중 남자가 9명, 여자가 20명이었으며 평균나이는 51세였다. 대상자들에서 기침 이외의 증상은 객담이 12%, 콧물이나 비폐색 등의 코 증상이 있는 환자는 10%, 속쓰림, 소화불량 등의 소화기 증상을 호소하는 환자는 13.4%였다. 29명중 4주간 투여 후 증상의 호전이 없는 환자가 3명(10.3%), 50% 이상의 증상호전을 보이는 환자가 22명(75.9%), 그리고 증상이 거의 소실된 환자가 4명(13.8%)로 약 90%정도의 환자가 기침의 증상호전이 있었다. 8주 투여 후 호전이 없는 환자가 2명(7.4%), 50% 이상 증상호전이 있는 환자가 8명(29.6%), 증상이 거의 소실된 환자가 16명(63.0%)이었다. 결 론: 8주이상의 만성기침 환자에서 8주 이상 양자펌프억제제 투여 후 92.6%환자가 증상호전이 있었으며 이중 63%는 거의 소실되었다. 하지만 본 연구는 위약을 통한 대조군이 없는 관계로 그 결과의 해석에 어려움이 있다. 앞으로 좀더 많은 환자를 대상으로 하는 이중맹검시험이 필요할 것으로 생각된다.

• 대한한방내과학회지
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• 제28권2호
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• pp.399-407
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• 2007

Angioedema is a localized transient swelling of sudden onset that can occur in the face, lips, tongue, hand, feet, respiratory system and gastrointestinal system. Angioedema is classified as allergy, hereditary, idiopathic or induced by medication as like aspirin, nonsteroidal anti-inflammatory agents, opiates, antibiotics, and angiotensin-converting enzyme. Angiotensin-converting enzyme inhibitors are widely prescribed for hypertension and heart failure. This drug is commonly associated with angioedema which may be potentially life threatening. We experienced a case of angioedema induced by ACE inhibitor (angiotensin-converting enzyme inhibitor) in a 74-year-old patient who took ACE inhibitor to control hypertension during hospitalization. We thought the angioedema in the face had relation to myenzhong (面腫, mienjong) in oriental medicine. Weiling-tang (Wiryung-tang) was effective for angioedema in the face. As a result the symptoms disappeared rapidly. After 6 days, the patient's symptoms had notably improved.

• 대한임상검사과학회지
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• 제39권3호
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• pp.249-255
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• 2007

While respiratory burst enhances neutrophil glucose utilization, many neutrophil functions are critically influenced by extracellular matrix interaction and phosphoinositide-3-OH kinase (PI3K) signaling. We thus evaluated the role of RGD integrin occupancy and PI3K inhibition on respiratory burst and [18F]FDG uptake of stimulated neutrophils. Human neutrophils were stimulated by 100 ng/mL phorbol-myristate-acetate (PMA), and respiratory burst was measured by cumulative luminescence with lucigenin. [18F]FDG uptake and total hexokinase activity was measured 20 min after PMA stimulation in the presence or absence of soluble RGD peptides (200 g/mL) and/or the PI3K inhibitor wortmannin (200 nM). PMA induced a 71.70.9 fold increase in neutrophil oxygen intermediate generation. [18F]FDG uptake was increased to $194.6{\pm} 3.7%$ and hexokinase activity to $145.0{\pm}2.0%$ of basal levels (both p<0.0005). RGD peptides attenuated respiratory burst activation to $35.6{\pm}0.2%$ (p<0.005), but did not inhibit stimulated [18F]FDG uptake or hexokinase activity. In contrast, without affecting respiratory burst activation, wortmannin inhibited PMA stimulated [18F]FDG uptake to $66.9{\pm}1.6%$ and hexokinase activity to $81.0{\pm}4.2%$ (both P<0.0005), demonstrating its dependence on PI3K activity. Neither RGD nor wortmannin reversed the other's inhibitory effect on stimulated [18F]FDG uptake and hexokinase activity or respiratory burst, which suggests the involvement of distinct signaling pathways. Neutrophil [18F]FDG uptake is enhanced by PMA through a mechanism that requires PI3K activity but is independent of integrin receptor occupancy or respiratory burst activation.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Tuberculosis and Respiratory Diseases
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• 제62권2호
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• pp.144-148
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• 2007

저자 등은 gefitinib 투약 중 발생한 급성호흡곤란으로 사망한 2 예를 경험하였기에 이를 보고하는 바이다.

• Tuberculosis and Respiratory Diseases
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• 제68권5호
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• pp.273-279
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• 2010

Background: Pulmonary hypertension is considered as a poor prognosis factor in patients with chronic obstructive pulmonary disease (COPD). There has been reported brain natriuretic peptide (pro-BNP) is related with increased right ventricular (RV) workloads. However, there are few studies that evaluate the relationship between BNP and pulmonary arterial pressure (PAP), RV function and St. George Respiratory Questionnaire (SGRQ) score in patients with COPD, and the effects of angiotensin converting enzyme inhibitor (ACEI) on these parameters. Methods: Pulmonary function test, echocardiography, blood BNP, and SGRQ score were evaluated in stabilized moderate degree COPD patients ($FEV_1$/FVC< 70%, $50%{\leq}FEV_1$ < 80%) aged 45 years and over, without worsening of symptoms within recent 3 months. After treating with ramipril 10 mg for 3 months, the same evaluation was repeated. Results: Twenty-two patients were included in this study. BNP was significantly correlated with PAP (Pearson coefficient ${\rho}=0.51$, p=0.02), but not with RV ejection fraction (EF) and predicted $FEV_1%$. The values for predicted $FEV_1%$ showed significant correlation with SGRQ total score and activity score, but not with BNP or PAP. After ramipril treatment, PAP showed significant decrease ($42.8{\pm}8.1$ vs. $34.5{\pm}4.5mm$ Hg p=0.0003), tricuspid annular plane systolic excursion significant increase ($21.5{\pm}3.3$ vs. $22.7{\pm}3.1mm$ p=0.009). BNP showed a tendency to decrease without statistical significance ($40.8{\pm}59.6$ vs. $18.0{\pm}9.1pg/mL$ p=0.55). SGRQ scores showed no significant change. Conclusion: BNP showed significant correlation with resting PAP, which means BNP could be used as markers for pulmonary hypertension. Treatment with ACEI didn't show significant change in the level of BNP, while pulmonary hypertension and RV function were improved.