• Journal of Life Science
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• v.21 no.8
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• pp.1134-1141
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• 2011

Transmembrane protein 21 (TMP21) is a member of the p24 cargo protein family and has been shown to modulate ${\alpha}$-secretase-mediated A${\beta}$ production which was specifically observed in the brains of subjects with Alzheimer's disease (AD). In order to investigate whether TMP21 could affect nerve growth factor (NGF) receptor signaling pathway, the alteration of NGF receptors and their downstream proteins were detected in TMP21 over-expressed cells. CMV/hTMP21 vector used in this study was successfully expressed into TMP21 proteins in B35 cells after lipofectamin transfection. Expressed TMP21 proteins induced the down-regulation of ${\gamma}$-secretase complex components including Presenlin-1 (PS-1), PS-2, Nicastrin (NST), Pen-2 and APH-1. Also, the expression level of NGF receptor $p75^{NTR}$ and RhoA were significantly higher in CMV/hTMP21 transfectants than vehicle transfectants, while their levels returned to vehicle levels after NGF treatment. However, the phosphorylation of NGF receptor TrkA was dramtically decreased in NGF No-treated CMV/hTMP21 transfectants compared with vehicle transfectants, and increased in NGF treated CMV/hTMP21 transfectants. In TrkA downstream signaling pathway, the phosphorylation level of ERK was also decreased in CMV/hTMP21 transfectants, while the phosphorylation of Akt was increased in the same transfectants. Furthermore, NGF treatment induced the increase of phosphorylation level of Akt and ERK in CMV/hTMP21 transfectants. Therefore, these results suggested that over-expression of TMP21may simultaneously induce the up-regulation of $p75^{NTR}$/RhoA expression and the down-regulation of TrkA/ERK phosphorylation through the inhibition of ${\gamma}$-secretase activity.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.208-218
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• 1999

Background: Lung cancer-associated hypercalcemia is one of the most disabling and life-threatening paraneoplastic disorders. Humoral hypercalcemia is responsible for most lung cancer-associated hypercalcemia. Patients with hypercalcemia are usually in the advanced stage with obvious bulky tumor and carry a poor prognosis. Materials and Methods: Total 29 patients satisfied the following criteria: histologically proven primary lung cancer, corrected calcium level ${\geq}$ 10.5 mg/dL, and symptoms which could possibly be attributed to hypercalcemia. In this retrospective study, we evaluated the various clinical aspects of hypercalcemia, in relation to cancer stage, histologic cell type, mass size, bone metastasis, performance status, and other possible characteristics. Results: Total 29 lung cancer patients with hypercalcemia were studied, and most of them had squamous cell carcinoma in their histologic finding. The incidence of hypercalcemia was significantly higher between 50 and 69 years of age, and in the advancement of cancer stage. Although serum calcium level showed positive correlation with mass size, performance status, and bone metastasis, it was not significant statistically. Altered consciousness was significantly more frequent in the patients with higher serum calcium level. There were no differences in effectiveness among therapeutic regimens. Hypercalcemia was more frequently in the later stage of disease than during the initial diagnosis of lung cancer. Most of the patients died within 1 month after development of hypercalcemia. Conclusion: We concluded that hypercalcemia in lung cancer is related to extremely poor prognosis, and may be one of the causes of death and should be treated aggressively to prevent sudden deterioration or death.

• Journal of Chest Surgery
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• v.41 no.4
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• pp.447-456
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• 2008

Background: Caspase-3 is a cysteine protease that plays a major role in the process of apoptotic cell death. The dysregulated expression of c-myc contributes to the tumorigenesis in a variety of human cancers. The aim of this study was to investigate the expressions of caspase-3 and c-myc and their significances as prognosis markers in patients with completely resected non-small cell lung cancer (NSCLC). Material and Method: A total 130 consecutive patients who had undergone complete resection without pre-operative radio-therapy or chemotherapy between May 1996 and December 2003 for NSCLC were retrospectively reviewed. The median follow-up period of the patients was 50 months (range: $3{\sim}128$ months). The expressions of caspase-3 and c-myc were immuno-histochemically examined, and these were correlated with the clinico-pathologic data. Result: The prevalence of caspase-3 and c-myc expressions in the patients was 68% (88/130) and 59% (77/130), respectively. Significant association was found between the frequency of the expressions of caspase-3 and c-myc (p=0.025). The caspase-3 and c-myc expressions were not significantly associated with the prognosis in all the patients. However, according to stages, a positive caspase-3 expression was significantly correlated with a favorable prognosis for patients with stage IIIa disease (median survival period: 35 months vs. 10 months, p=0.021). Multivariate analysis showed the pathologic stage to be significantly correlated with a good prognosis in all the patients (p=0.024), and with a positive caspase-3 expression, well differentiated tumor and negative neuronal invasion in the patients with stage llla disease (p=0.005, p=0.003, p=0.004, respectively). Conclusion: Caspase-3 and c-myc were frequently expressed in NSCLC, suggesting its possible involvement in tumor development. The caspase-3 expression, as determined with performing immunohistochemical staining, may be a favorable prognostic indicator in patients with completely resected NSCLC an advanced stage (IIIa).

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.113-123
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• 1996

It has been well known that polyamines ensure the stability of chromatin structure and the fidelity of DNA transcription. This study was carried out to evaluate the effect of polyamines on the apoptosis of mouse thymocytes induced by dexamethasone and polyamine synthesis inhibitors. 1) In the histological death findings of thymocytes double-stained with acridine orange and ethidium bromide, the apoptotic and the necrotic fractions (AF; NF) in the control group were $9.4{\pm}4.2%$ and $4.5{\pm}5.3%$, respectively. Dexamethasone $(3\;{\times}\;10^{-8}\;M:\;DX)$ in creased AF upto $52.0{\pm}8.1%$ and did not change NF, but A23187 $(5\;{\times}\;10^{-7}\;M:\;A2)$ increased AF and NF upto $45.0{\pm}8.9%$ and $20.5{\pm}10.6%$, respectively. 2) The thymocyte viability was significantly reduced by DX, DHEA $(1\;{\times}\;10^{-4}\;M)$, A2, DFMO $(1\;{\times}\;10^{-4}\;M)$, and $MGBG\;(1\;{\times}\;10^{-4}\;M)$, respectively. It was, however, little affected by $aminoguanidine\;(1\;{\times}\;10^{-4}\;M:\;AG)$, $putrescine\;(1\;{\times}\;10^{-5}\;M:\;PT)$, $spermidine\;(1\;{\times}\;10^{-5}\;M:\;SD)$, and $spermine\;(1\;{\times}\;10^{-5}\;M:\;SM)$. 3) The genomic DNA of mouse thymocyte was markedly fragmented by DX and A2, respectively, and to a lesser extent, by DHEA, but was little affected by MGBG, DFMO, AG, and each of polyamines. 4) The DX induced reduction of thymocyte viability was moderately attenuated by DHEA, but little affected by DFMO, MGBC, and AG. However, SM significantly attenuated the viability reduction induced by A2 as well as DX. 5) The thymocyte viability reduction by MGBG and DFMO was significantly attenuated by only SM among three polyamines applied in this study. 6) The thymocyte viability redution by combined treatments of DX with DFMO and MGBG, respectively, was significantly attenuated by SM, and moderately by PT. But the viability reduction by combined treatment of DX with AG or DHEA was not affected by polyamines. These results suggest that polyamines, particularly spermine, might play the inhibitory role in thymocyte apoptosis and the inhibitory effect can be ascribed in part to the increase of polyamine uptake by thymocytes pretreated with DFMO and MGBG.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.5
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• pp.429-435
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• 2009

Purpose: The purpose of this study was to assess the prognostic value of preoperative FDG-PET in colorectal cancer (CRC) patients with hepatic metastasis (HM). Materials and Methods: 24 CRC patients (M:F=14:10; age, $63{\pm}10$ yrs) with HM who had undergone preoperative FDG PET were included. Cure-intent surgery was performed in all the patients and HMs were controlled using resection (n=13), radio-frequency ablation (RFA) (n=7), and resection plus RFA (n=4). Potential prognostic markers tested were maxSUV of primary tumor, maxSUV of HM, maxSUV ratio of HM over primary tumor (M/P ratio), histologic grade, CEA level, venous/lymphatic/nerve invasion, T stage, N stage, no. of HM, no. of lymph node metastasis, and treatment modality of HM. Results: 14 CRC patients developed a recurrence with a median follow-up duration of 244 days, whereas 10 patients did not develop recurrence with a median follow-up duration of 504 days. M/P ratios but other potential prognostic markers were significantly higher in the recurrent patients ($0.72{\pm}0.14$) than recurrence-free patients ($0.54{\pm}0.23$) (p=0.038). M/P ratio only was found to predict recurrence by Cox multivariate analysis (hazard ratio 37.7, 95% confidence interval 2.01-706.1, p=0.016). The 11 patients with lower M/P ratio of <0.61 had significantly better disease-free survival rate than the 13 patients with higher M/P ratio (${\geq}0.61$) (p=0.026). Conclusion: maxSUV ratio of HM over primary tumor (M/P ratio) may be useful for prognosis prediction of CRC patients with HM. Higher FDG uptake of HM than that of primary tumor may indicate a more advanced status in stage IV CRC.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.331-338
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• 1999

Background: Nearly 10% of cancer patients will develop a second primary cancer within ten years after surgical removal of the primary tumor. The detection of risk factors for developing multiple primary tumors would be important This study was conducted to evaluate the clinical characteristics and abnormal p53 expression of lung cancer associated with multiple primary cancer(MPC). Method: Clinical characteristics and abnormal p53 expression were compared between 20 cases of lung cancer(NSCLC ; 16 cases, SCLC ; 4 cases) associated with MPC and 26 cases of primary non-small cell lung cancer. Result: MPC associated with lung cancer was gastric cancer(8), lung cancer(2), esophageal cancer(2), colon cancer(2), laryngeal cancer(1), bladder cancer(1), small bowel cancer(l), adrenal cancer(1), hepatocellular carcinoma(1), and breast cancer (1) in order. The clinical stage of primary NSCLC was relatively advanced, but NSCLC associated with MPC was even distribution at each stage. The detected incidences of abnormal p53 expressions were 62.5% in NSCLC associated with MPC and 76.9% in primary NSCLC(p>0.05). Conclusion: There was no difference in abnormal p53 expression between non-small cell carcinoma associated with multiple primary cancer and primary non-small cell carcinoma.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.11-19
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• 2011

Purpose: To evaluate the pathological and clinical effects of preoperative chemoradiation (CCRT) in cases of locally advanced rectal cancer and to determine the predictive factors for tumor downstaging. Materials and Methods: From March 2004 to August 2008, 33 patients with locally advanced rectal cancer were treated with preoperative CCRT. Twenty-eight patients (84.8%) were treated using a concomitant boost technique while five (15.2%) patients were treated using a cone down boost technique. All patients received 50.4 Gy of irradiation and concurrent chemotherapy with 5-fluorouracil. The median follow-up duration was 24.2 months (range, 9.8 to 64.7 months). Results: Thirty-one (93.9%) patients underwent surgery. Twenty-four patients (72.7%) underwent anal sphincter-preserving surgery. The 3-year disease free survival (DFS) and overall survival rates were 63.4% and 78.8%, respectively. Post-operative factors were more important for DFS. Pathologic N stage, margin status, and pathologic differentiation were significant prognostic factors (p=0.001, 0.029, 0.030). Tumor size and lymphovascular invasion were also associated with marginal significance (p=0.081, 0.073). However, only pre-treatment T stage was a significant pre-operative factor (p=0.018). The complete pathological response rate was 9.1 %. T-downstaging was observed in ten (30.3%) patients, whereas N-downstaging was found in 24 (72.7%) patients. Pre-treatment T stage and the interval between CCRT and operation were the predictive factors for downstaging in a univariate analysis (p=0.029, 0.027). Pre-treatment carcinoembryogenic antigen was also associated with marginal significance (p=0.068). Conclusion: The survival of rectal cancer patients can be better determined based on post-operative findings. Therefore, pre-operative CCRT for downstaging of the tumor seems to be important. Pre-treatment T stage and the interval between CCRT and operation can be used to predict downstaging.