• Journal of Life Science
• /
• v.27 no.2
• /
• pp.149-154
• /
• 2017

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

• Journal of Life Science
• /
• v.27 no.5
• /
• pp.509-516
• /
• 2017

Perilla frutescens (L.) Britton var. sprouts (PFS) is a plant of the labiatae family. The purpose of this work was to assess the preventive effects of PFS ethanolic extracts (PFSEs) on cytokine-induced ${\beta}$-cell damage. Cytokines, which are released by the infiltration of inflammatory cells around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. The combination of interleukin-$1{\beta}$ (IL-1), interferon-${\gamma}$ (IFN-${\gamma}$), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) induced formation of reactive oxygen species (ROS). Accumulation of intracellular ROS led to ${\beta}$-cell dysfunction and apoptosis. PFSEs possess antioxidant activity and thus lead to downregulation of ROS generation. Cytokines decrease cell viability, stimulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and induce the production of nitric oxide (NO). PFSEs prevented cytokine-induced cell viability in a dose-dependent manner. Incubation with PFSE resulted in significant reduction in cytokine-induced NO production that correlated with reduced levels of the iNOS and COX-2 protein expression. Furthermore, PFSE significantly decreased the activation of nuclear factor ${\kappa}B$ (NF-${\kappa}B$) by inhibition of $I{\kappa}B{\alpha}$ phosphorylation in RINm5F cells. In summary, our results suggest that the protective effects of PFSE might serve to counteract cytokine-induced ${\beta}$-cell destruction. Findings indicate that consumption of Perilla frutescens (L.) Britton var. sprouts alleviates hyperglycemia-mediated oxidative stress and pro-inflammatory cytokine-induced ${\beta}$-cell damage and thus has beneficial anti-diabetic effects.

• Radiation Oncology Journal
• /
• v.24 no.3
• /
• pp.164-170
• /
• 2006

[ $\underline{Purpose}$ ]: This study identified the result of postoperative radiation therapy and the prognostic factors to affect survival rates in cancer patients. $\underline{Materials\;and\;Methods}$: One hundred and thirty three patients with cervical cancer who were treated with postoperative radiation therapy following surgery at our institution between June 1985 and November 2002 were retrospectively analyzed. One hundred and thirteen patients had stage IB disease, and 20 patients had stage IIA disease. Histological examination revealed 118 squamous cell carcinoma patients and 15 adenocarcinoma patients. Sixty seven patients were noted to have stromal invasion greater than 10 mm, and 45 patients were noted to have stromal Invasion 10 mm or less. Positive lymphovascular invasion was found in 24 patients, and positive pelvic lymph nodes were noted in 39 patients. Positive vaginal resection margin was documented in 8 patients. All of the patients were treated with external beam radiation therapy to encompass whole pelvis and primary surgical tumor bed. Intracavitary radiation therapy was added to 19 patients who had positive or close surgical margins. $\underline{Results}$: Actuarial overall and disease-free survival rates for entire group of the patients were 88% and 84% at 5 years, respectively. Five-year disease-free survival rates for patients with stromal invasion greater than 10 mm and 10 mm or less were 76% and 97%, respectively (p<0.05). Also there was a significantly lower survival in patients with positive pelvic lymph nodes compared with patients with negative pelvic lymph nodes (p<0.05). However, lymphovascular invasion, positive vaginal resection margins were not statistically significant prognostic factors. Addition of neoadjuvant chemotherapy or type of surgery did not affect disease-free survival. $\underline{Conclusion}$: Postoperative radiation therapy appears to achieve satisfactory local control with limited morbidity in cervical cancer patients with high pathologic risk factors. Distant metastasis was a dominant failure pattern to affect survival in cervical cancer patients after radical surgery and radiation and more effective systemic treatment should be investigated in these high-risk patients.

• Radiation Oncology Journal
• /
• v.25 no.3
• /
• pp.177-184
• /
• 2007

Purpose: To evaluate the palliative effect of endobronchial brachytherapy (EBB) for patients with lung cancer that previously received external beam radiotherapy (EBRT). Materials and Methods: From July 1992 to May 2003, 29 patients with a recurrent or persistent lung cancer were treated with palliative EBB at our institute. EBB consisted of three fractions (once a week) of a dose of 5 Gy using the high dose-rate remote afterloader. Symptomatic improvement was assessed subjectively, and patients were divided into two groups according to whether symptoms were improved or not. Factors such as age, performance status, duration from EBRT to EBB and the location of the tumor were compared between the improved and unimproved groups of patients. Results: Overall symptomatic improvement was found in 27 out of 52 symptoms (52%). Improvement as to the type of symptoms was seen in 41 %, 50%, 82% and 33% of patients with cough, dyspnea, hemoptysis, and obstructive pneumonia respectively. The rate of improvement of hemoptysis was more than that of cough (p<0.05). The median time to symptom relapse was 5 months. The improved patient group (n=17, 59%) had a better performance status and longer duration from EBRT to EBB than the unimproved patient group (p<0.05). Lesions located in the distal trachea and/or main bronchus were found more frequently in the improved group of patients than in the unimproved group of patients, but the difference was not statistically significant (p=0.06). Fatal complications developed in two patients (7%), which were a hemoptysis and bronchopleural fistula respectively. Conclusion: Symptom improvement was found in 60% of patients after EBB and improvement was maintained for 5 months. Palliative EBB, even when EBRT was given previously, can be effective for a patient that has an endobronchial symptom, such as hemoptysis, and for a patient with good performance and a long duration from previous EBRT to EBB.

• Journal of Radiation Protection and Research
• /
• v.27 no.3
• /
• pp.147-154
• /
• 2002

Purpose : Measurement of transmission dose is useful for in vivo dosimetry of QA purpose. The objective of this study is to develope an algorithm for estimation of tumor dose using measured transmission dose for open radiation field. Materials and Methods : Transmission dose was measured with various field size (FS), phantom thickness (Tp), and phantom chamber distance (PCD) with a acrylic phantom for 6 MV and 10 MV X-ray. Source to chamber distance (SCD) was set to 150 cm. Measurement was conducted with a 0.6 co Farmer type ion chamber. Using measured data and regression analysis, an algorithm was developed lot estimation of expected reading of transmission dose. Accuracy of the algorithm was tested with flat solid phantom with various settings. Results : The algorithm consisted of quadratic function of log(A/P) (where A/P is area-perimeter ratio) and tertiary function of PCD. The algorithm could estimate dose with very high accuracy for open square field, with errors within ${\pm}0.5%$. For elongated radiation field, the errors were limited to ${\pm}1.0%$. Conclusion : The developed algorithm can accurately estimate the transmission dose in open radiation fields with various treatment settings.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.4
• /
• pp.766-775
• /
• 1998

Background : The prognosis of patients with lung cancer is still poor. Lung cancer exhibits a variable clinical outcome, even in those patients with same stage. Numerous reports suggest that oncogene expression might playa role in explaining the variability of response and survival But many of these reports are still under debate. So we studied the clinical relevance of oncogene expression in Korean lung cancer patients. Immunohistochemistry of p53, erbB-2, CEA expression was performed. Method: From March, 1992 until March, 1997, 120 patients with lung cancer were reviewed. p53, erbB-2, and CEA expression were detected on paraffin-embedded tumor blocks with the use of monoclonal antibodies. The survival and response has correlated with the expressibility of p53, erbB-2, and CEA oncoprotein Results: Overall, the expression rates of p53, erbB-2, and CEA were 33.7%, 59.3%, and 32.6% respectively. Expression rates were not correlated to cell type or stage. Compared with response to chemotherapy, no correlation was found. The expression of p53, erbB-2, or CEA was not correlated with 2-year survival. With simultaneous applications of p53, erbB-2, and CEA, patients with 2 or more expressions also did not show poor response to chemotherapy. Conclusion: We conclude the p53, erbB-2, and CEA expression are clinically less useful in predicting response to chemotherapy or survival.

• Tuberculosis and Respiratory Diseases
• /
• v.55 no.4
• /
• pp.378-387
• /
• 2003

Background : Promoter methylation of tumor suppressor genes is one of the key epigenetic changes in many human cancers. The aim of this study was to evaluate the promoter methylation status of the Death-associated protein(DAP) kinase gene, which played an important role in lung cancer, in the serum DNA of primary lung cancer patients. Methods : This study investigated the aberrant methylation of DAP kinase in the serum of 65 primary lung cancer patients by methylation-specific PCR (MSP). Results : Methylation in the serum was detected in 29 of 65(44.6%) for DAP kinase. There was no statistical association between methylation of DAP kinase and age, smoking history, histologic type, or stage. Methylation of DAP kinase was found more frequently in men (p=0.044). Conclusions : This study suggests that the aberrant methylation of the DAP kinase promoter is readily detectable in the serum DNA of lung cancer patients using MSP analysis.

• Tuberculosis and Respiratory Diseases
• /
• v.42 no.4
• /
• pp.502-512
• /
• 1995

Background: One quarter to one third of patients with NSCLC present with primary tumors that although confined to the thorax are too extensive for surgical resection. Until resently standard treatment for these patients had been thoracic radiation, which produces tumor regression in most patients but few cures and dismal 5-year survival rate. The fact that death for most patients with stage III tumors is caused by distant metastases has promped a reevaluation of combined modality treatment approaches that include systemic chemotherapy. Therefore, we report the results observed in a study to evaluate the effect of multimodality treatment in locally advanced non-small cell lung cancer from 1/91 to 8/93 in CNUH. Method: We grouped the patients according to the treatment modalities and evaluated response rate, median survival and the effect of prognostic variables. Among 67 patients evaluated, twenty seven patients classified with group A, received cisplatin and etoposide containing combination chemotherapy alone, eighteen patients, classified with group B, received chemotherapy and radiotherapy, fifteen patients, group C, received neoadjuvant or adjuvant chemotherapy and surgery with/without radiation therapy, seven patients, group D, received only supportive care. Result: The major response rate for group A and B was 37% and 61% respectively. There was no statistically significant difference in response rate between A and B groups(p=0.97). The analysis of prognostic factors showed that differences of age, sex, pathology, blood type, smoking year, stage and ECOG performance did not related to improvement in survival. Median survival time was 8.6 months for group A, 13.4 months for group B, 19.2 months for group C, and 5.4 months for group D, respectively and there was statistically significant difference(p=0.003), suggesting that multimodality therapy was associated with signigicant improvement in survival. Subset survival analysis showed a significant therapeutic effect for earlier stage and good performance state(p=0.007, 0.009, respectively). A possible survival advantages were observed for major response groups. Conclusion: It was suggested that multimodality therapy for the management of patients who had stage III disease, has yielded good median survival and long survival for seleted patients. But, it is necessory to validate above result with further investigation in large scale and in prospective randomized trials.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.6
• /
• pp.1285-1295
• /
• 1997

Background : EGFR is one of the initial step in signal transduction pathway about multistep carcinogenesis. It is homologous to oncogene erbB-2 and is the receptor for EGF and TGF alpha. EGFR has important role in the growth and differentiation of tumor cells. So, EGFR in non-small cell lung cancer was examined to search for possible evidence as clinical prognostic factor. Methods : To investigate the role of EGFR in lung cancer, the author performed immunohistochemical stain of EGFR on 57 resected primary non-small cell lung cancer specimens. And the author analyzed the correlation between EGFR expression, clinical parameters, Sand $G_1$ phase fraction and survival. Results : 1) EGFR were detected in 56% of total 57 patients (according to histologic type, squamous cancer 50%, adenocarcinoma 63%, large cell cancer 75%) (according to TNM stage, stage I 64%, stage II 38%, stage III 55%) (according to cellular differentiation, well 50%, moderately 52%, poorly 65%). All differences were insignificant 2) Using the flow cytometric analysis, mean S-phase fraction of EGFR (+) and (-) group were 22.3(${\pm}10.5$)%. 18.0(${\pm}10.9$)% (p>0.05), mean $G_1$-phase fraction of EGFR (+) and (-) group were 68.4(${\pm}11.6$)%, 71.1(${\pm}12.8$)%, (p>0.05) 3) Two-year survival rate of EGFR (+) and (-) group were 53%, 84%, median survival time of EGFR (+) and (-) group were 26, 53 months. (p<0.05, Kaplan-Meier, generalized Wilcox) Conclusion : EGFR immunostaining may be a simple and useful method for survival prediction in non-small cell lung cancer.

• Journal of Life Science
• /
• v.17 no.10
• /
• pp.1447-1451
• /
• 2007

Through the screening of marine natural compounds that inhibit cancer cell proliferation, we previously reported that pectenotoxin-2 (PTX-2) isolated from marine sponges exhibits selective cytotoxicity against several cell lines in p53-deficient tumor cells compared to those with functional p53. However, the molecular mechanisms of its anti-proliferative action on malignant cell growth are not completely known. To further explore the mechanisms of its anti-cancer activity and to test whether the status of p53 in liver cancer cells correlates with their chemo-sensitivities to PTX-2, we used two well-known hepatocarcinoma cell lines, p53-deficient Hep3B and p53-wild type HepG2. We have demonstrated that PTX-2 markedly inhibits Hep3B cell growth and induces apoptosis whereas HepG2 cells are much more resistant to PTX-2 suggesting that PTX-2 seems to act by p53-independent cytotoxic mechanism. The apoptosis induced by PTX-2 in Hep3B cells was associated with the modulation of DNA fragmentation factor (DFF) family proteins, up-regulation of pro-apoptotic Bcl-2 family members such as Bax and Bcl-xS and activation of caspases (caspase-3, -8 and -9). Blockade of the caspase-3 activity by caspase-3 inhibitor, z-DEVD-fmk, prevented the PTX-2-induced growth inhibition in Hep3B cells. Moreover, treatment with PTX-2 also induced phosphorylation of AKT and extracellular-signal regulating kinase (ERK), but not c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MARK). Specific inhibitors of PI3K inhibitor (LY294002) and ERK1/2 inhibitor (PD98059) significantly blocks PTX-2-induced-anti-proliferative effects, whereas a JNK inhibitor (SP600125) and a p38 MAPK inhibitor (SB203580) have no significant effects demonstrating that the pro-apoptotic effect of PTX-2 mediated through activation of AKT and ERK signal pathway in Hep3B cells.