• Asian Pacific Journal of Cancer Prevention
• /
• 제16권1호
• /
• pp.175-179
• /
• 2015

Rad51, a key factor in the homologous recombination pathway for the DNA double-strand break repair, plays a vital role in genesis of non-small-cell lung cancer (NSCLC). In recent years, more and more studies indicate that high expression of Rad51 is of great relevance to resistance of NSCLC to chemotherapeutic agents and ionizing radiation. However, the underlying molecular mechanisms are poorly understood. In this study, we investigated the role of single Rad51 on cell viability in vitro. Our results show that depletion of endogenous Rad51 is sufficient to inhibit the growth of the A549 lung cancer cell line, by accumulating cells in G1 phase and inducing cell death. We conclude that independent Rad51 expression is critical to the survival of A549 cells and can be an independent prognostic factor in NSCLC patients.

• Reproductive and Developmental Biology
• /
• 제29권2호
• /
• pp.101-108
• /
• 2005

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a well-known inducer of apoptotic cell death in many tumor cells. 1RAIL is expressed in human placenta, and cytotrophoblast cells express 1RAIL receptors. However, the role of TRAIL in human placentas and cytotrophoblast cells is not. well understood. In this study a trophoblast cell line, JEG-3, was used as a model system to examine the effect of TRAIL. on key intracellular signaling pathways involved in the control of trophoblastic cell apoptosis and survival JEG-3 cells expressed receptors for 1RAIL, death receptor (DR) 4, DR5, decoy receptor (OcR) 1 and DeR2. Recombinant human TRAIL (rhTRAIL) did not have a cytotoxic effect determined by MIT assay and did not induce apoptotic cell death determined by poly-(ADP-ribose) polymerase cleavage assay. rhTRAIL induced a rapid and transient nuclear translocation of nuclear $factor-{\kappa}B(NF-{\kappa}B)$ determined by immunoblotting using nuclear protein extracts. rhTRAIL rapidly activated extracellular signal-regulated protein kinase (ERK) 1/2 as determined by immnoblotting for phospho-ERK1/2. However, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) and Akt (protein kinase B) were not activated by rhTRAIL. The ability of 1RAIL to induce $NF-{\kappa}B$ and ERK1/2 suggests that interaction between TRAIL and its receptors may play an important role in trophoblast cell function during pregnancy.

• 한방안이비인후피부과학회지
• /
• 제19권3호통권31호
• /
• pp.22-33
• /
• 2006

Objective : Angiogenesis induced by hypoxia and inflammation are an essential process of solid tumors and psoriasis. We researched the HIF-1 ${\alpha}$ (hypoxia inducible factor 1 alpha), VEGF(Vascular Endothelial Growth Factor), survival related PI3K-Akt, and inflammation related COX-2 protein expressions to get the information of the mechanism and effects of Rehmannia glutinosa in HepG2 and HaCaT cell lines. Method : To investigate the roles of the Rehmannia glutinosa extract, we performed MTS assay and western blots using HaCaT cells and HepG2 cells. HaCaT cells and HepG2 cells were treated with $50{\mu}g/ml$ and $100{\mu}g/ml$ Rehmannia glutinosa extracts. After 4hrs, HaCaT cells were treated with IGF-II protein for 24hrs and HepG2 cells were treated with $CoCl_2$. Results : 1. We could ohserve that the reduction of the protein level of HIT-1 ${\alpha}$ induced by IGF-II in HaCaT cells. 2. We Could ohserve that the decreased PI3K-Akt and COX-2 expression level by Rehmannia glutinosa extracts treated in HaCaT cells independently ith ERK1/2. 3. We could observe that the reduction of the protein level of HIF-1 ${\alpha}$ induced by $CoCl_2$ in HepG2 cells. Conclusion : These results suggest that Rehmannia glutinosa extracts contributes to the anti-survival pathway and anti-inflammatory activities. Also, we could assume that Rehmannia glutinosa act as anti-inflanmmatory or anti-hypoxia agents via reduction of COX-2 and HIF-1 ${\alpha}$.

• Tuberculosis and Respiratory Diseases
• /
• 제75권4호
• /
• pp.140-149
• /
• 2013

Background: Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-${\beta}1$ initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain. Methods: We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009. Results: In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018). Conclusion: According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권4호
• /
• pp.1457-1461
• /
• 2012

Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

• Tuberculosis and Respiratory Diseases
• /
• 제79권4호
• /
• pp.248-256
• /
• 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.

• Archives of Plastic Surgery
• /
• 제44권5호
• /
• pp.370-377
• /
• 2017

Background Composite grafts are frequently used for facial reconstruction. However, the unpredictability of the results and difficulties with large defects are disadvantages. Adipose-derived stem cells (ADSCs) express several cytokines, and increase the survival of random flaps and fat grafts owing to their angiogenic potential. Methods This study investigated composite graft survival after ADSC injection. Circular chondrocutaneous composite tissues, 2 cm in diameter, from 15 New Zealand white rabbits were used. Thirty ears were randomly divided into 3 groups. In the experimental groups (1 and 2), ADSCs were subcutaneously injected 7 days and immediately before the operation, respectively. Similarly, phosphate-buffered saline was injected in the control group just before surgery in the same manner as in group 2. In all groups, chondrocutaneous composite tissue was elevated, rotated 90 degrees, and repaired in its original position. Skin flow was assessed using laser Doppler 1, 3, 6, 9, and 12 days after surgery. At 1 and 12 days after surgery, the viable area was assessed using digital photography; the rabbits were euthanized, and immunohistochemical staining for CD31 was performed to assess neovascularization. Results The survival of composite grafts increased significantly with the injection of ADSCs (P<0.05). ADSC injection significantly improved neovascularization based on anti-CD31 immunohistochemical analysis and vascular endothelial growth factor expression (P<0.05) in both group 1 and group 2 compared to the control group. No statistically significant differences in graft survival, anti-CD31 neovascularization, or microcirculation were found between groups 1 and 2. Conclusions Treatment with ADSCs improved the composite graft survival, as confirmed by the survival area and histological evaluation. The differences according to the injection timing were not significant.

• Radiation Oncology Journal
• /
• 제19권4호
• /
• pp.312-318
• /
• 2001

목적 : 고위험 유방암 환자의 수술 후 방사선치료 후 국소 재발율, 생존율 및 예후인자를 후향적 분석하여 방사선치료의 역할을 규명하고자 하였다. 대상 및 방법 : 1984년부터 1995년까지 유방암으로 변형 근치적 유방절제술 후 종양의 크기가 4 cm 이상이거나, 4 cm 미만이나 액와 림프절의 전이가 있는 환자 중 방사선치료를 완료한 48명을 대상으로 하였다. 중앙 연령은 47세 ($31\~79$세)이었으며, 종양의 크기가 2 cm미만 1명, $2\~5\;cm$ 15명, 5 cm이상이 32명이었다. 액와림프절에 전이된 환자는 32명이었다. 흉벽과 국소림프절에 방사선치료받은 환자는 42명, 흉벽만 받은 환자는 6명이었으며 방사선량은 1일 1회(1.8 Gy)로 총 선량은 50.4 Gy이었다. 48명 중 18명$(38\%)$은 5-FU를 기본으로 하는 항암화학요법을 방사선치료 전 혹은 후에 투여하였다. 중앙 추적기간은 61개월이었다. 결과 : 국소 재발율은 $8\%$, 원격전이율은 $14\%$이었다. 전체환자의 5년 생존율은 $63\%$, 무병생존율은 $62\%$이었으며 중앙생존기간은 67개월이었다. 병기에 따른 5년 생존율은 IIB는 $70\%$, IIIA는 $58\%$이었으며, 생존율에 미치는 예후인자는 병기이었다(p=0.0076). 결론 : 고 위험군의 유방암 환자의 수술 후 방사선치료는 국소재발율은 감소시키고 생존율을 향상시킬 수 있으며, 생존율에 영향을 주는 인자는 병기이었다.

• Journal of Chest Surgery
• /
• 제50권2호
• /
• pp.86-93
• /
• 2017

Background: The influence of lifestyle diseases on postoperative complications and long-term survival in patients with non-small cell lung cancer (NSCLC) is unclear. The aim of this study was to determine whether lifestyle diseases were significant risk factors of perioperative and long-term surgical outcomes in elderly patients with stage I NSCLC. Methods: Between December 1995 and November 2013, 110 patients aged 65 years or older who underwent surgical resection of stage I NSCLC at Dong-A University Hospital were retrospectively studied. We assessed the presence of the following lifestyle diseases as risk factors for postoperative complications and long-term mortality: diabetes, hypertension, chronic obstructive pulmonary disease, stroke, and ischemic heart disease. Results: The mean age of the patients was 71 years (range, 65 to 82 years). Forty-six patients (41.8%) had hypertension, making it the most common lifestyle disease, followed by diabetes (n=23, 20.9%). The in-hospital mortality rate was 0.9% (n=1). The 3-year and 5-year survival rates were 78% and 64%, respectively. Postoperative complications developed in 32 patients (29.1%), including 7 (6.4%) with prolonged air leakage, 6 (5.5%) with atrial fibrillation, 5 (4.5%) with delirium and atelectasis, and 3 (2.7%) with acute kidney injury and pneumonia. Univariate and multivariate analyses showed that the presence of a lifestyle disease was the only independent risk factor for postoperative complications. In survival analysis, univariate analysis showed that age, smoking, body mass index, extent of resection, and pathologic stage were associated with impaired survival. Multivariate analysis revealed that resection type (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.08 to 4.49; p=0.030) and pathologic stage (HR, 1.89; 95% CI, 1.02 to 3.49; p=0.043) had independent adverse impacts on survival. Conclusion: This study demonstrated that the presence of a lifestyle disease was a significant prognostic factor for postoperative complications, but not of survival, in elderly patients with stage I NSCLC. Therefore, postoperative complications may be influenced by the presence of a lifestyle disease.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권2호
• /
• pp.411-420
• /
• 2015

Ki-67 has been widely used as an indicator of cell proliferation in gliomas. However, the role of Ki-67 as a prognostic marker is still undefined. Thus, we conducted a meta-analysis of the published literatures in order to clarify the impact of Ki-67 on survival in glioma cases. Eligible studies were identified in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, Science Direct and Wiley Online Library with the last search updated on August 31, 2014. The clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with Ki-67 expression at different time points were extracted. A total of 51 studies, covering 4,307 patients, were included in the current meta-analysis. The results showed that overexpression of Ki-67 can predict poor OS (HR=1.66, 95%CI: 1.53-1.80; Z=11.87; p=0.000) and poor PFS (HR=1.67, 95%CI: 1.47-1.91; Z=7.67; p=0.000) in gliomas. Moreover, subgroup analyses also indicated that high level of Ki-67 expression was related to poor OS and PFS in glioma patients regardless of region, pathology type, cut-off value and statistical method. In conclusion, the current meta-analysis revealed that Ki-67 expression might be a predicative factor for poor prognosis of glioma patients, emphasizing its importance as a predictor.