• Journal of Digestive Cancer Research
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• 제3권2호
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• pp.89-94
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• 2015

The role of adjuvant chemotherapy in patients with stage II colon cancer remains a controversial issue. Adjuvant chemotherapy aims to eliminate any micrometastatic disease that may have been missed, at the time of surgery. Although one prospective study showed a small but statistically significant benefit with respect to the overall survival for those who received adjuvant chemotherapy, multiple pooled data did not demonstrate any benefit of this therapy in patients with stage II colon cancer. Current national and international guidelines for the adjuvant treatment of stage II colon dose not advise routine implementation of adjuvant chemotherapy, but rather recommend selective use of this therapy for patients with high risk of recurrence. High risk features for recurrence include T4 disease, poorly differentiated histology, presence of lymphovascular invasion, presence of perineural invasion, inadequate retrieval of lymph nodes, bowel obstruction, localized perforation, or positive margins. More recently, prediction tools using gene expression cancer profiles are proposed to identify patients who are most likely to have recurrence and therefore may benefit from postoperative chemotherapy in stage II colon cancer. These novel methods together with conventional prognosticators, will allow us to implement more optimized personalizing adjuvant therapy in these patients.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2000년도 International Symposium on Bioinformatics
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• pp.74-82
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• 2000

Prostate cancer initially responds and regresses in response to androgen depletion therapy, but most human prostate cancers will eventually recur, and re-grow as an androgen independent tumor. Once these tumors become hormone refractory, they usually are incurable leading to death for the patient. Little is known about the molecular details of how prostate cancer cells regress following androgen ablation and which genes are involved in the androgen independent growth following the development of resistance to therapy. Such knowledge would reveal putative drug targets useful in the rational therapeutic design to prevent therapy resistance and control androgen independent growth. The application of genome scale technologies have permitted new insights into the molecular mechanisms associated with these processes. Specifically, we have applied functional genomics using high density cDNA microarray analysis for parallel gene expression analysis of prostate cancer in an experimental xenograft system during androgen withdrawal therapy, and following therapy resistance, The large amount of expression data generated posed a formidable bioinformatics challenge. A novel template based gene clustering algorithm was developed and applied to the data to discover the genes that respond to androgen ablation. The data show restoration of expression of androgen dependent genes in the recurrent tumors and other signaling genes. Together, the discovered genes appear to be involved in prostate cancer cell growth and therapy resistance in this system. We have also developed and applied tissue microarray (TMA) technology for high throughput molecular analysis of hundreds to thousands of clinical specimens simultaneously. TMA analysis was used for rapid clinical translation of candidate genes discovered by cDNA microarray analysis to determine their clinical utility as diagnostic, prognostic, and therapeutic targets. Finally, we have developed a bioinformatic approach to combine pharmacogenomic data on the efficacy and specificity of various drugs to target the discovered prostate cancer growth associated candidate genes in an attempt to improve current therapeutics.

• 한국정보통신학회논문지
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• 제22권9호
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• pp.1237-1242
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• 2018

광 역학 치료법은 그 효과가 특정 위치의 암세포에 국한되어있어 주변의 정상 세포에 큰 영향을 미치지 않기 때문에 다양한 부작용이 존재하는 현재의 암 치료법의 대안으로 제안되어 왔다. 이러한 광 역학 치료에는 광감응제를 선택적으로 자극시키기 위해 레이저를 이용하고 있으나, 고가의 치료비용과 높은 발열현상으로 사용에 제한적이다. 그러나 다양한 파장의 빛을 발할 수 있는 소형 발광 다이오드가 저가로 개발됨에 따라 대체가 가능하며, 이는 광 역학 치료 장비의 소형화 및 저가의 치료 장비 개발에 큰 영향을 미치고 있다. 현재 활발하게 연구되는 광 역학 치료법은 다양한 광감응제를 이용하여 암세포의 사멸을 유도하는데 목적이 있으나, 특정한 파장을 중심으로 진행된 연구는 상대적으로 미비한 실정이다. 따라서 본 논문에서는 저렴하며, 발열현상이 작고, 다양한 파장대의 광원지원이 가능한 발광 다이오드를 사용하고 이를 아두이노로 제어하여 새로운 저가의 암세포 증식 억제 모듈을 개발함으로써, 그 효과를 정량적으로 분석하고 새로운 항암치료법을 제시하고자 한다.

• Molecules and Cells
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• 제45권9호
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• pp.631-639
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• 2022

Breast cancer is the leading cause of cancer-related death in women worldwide, despite medical and technological advancements. The RhoBTB family consists of three isoforms: RhoBTB1, RhoBTB2, and RhoBTB3. RhoBTB1 and RhoBTB2 have been proposed as tumor suppressors in breast cancer. However, the roles of RhoBTB3 proteins are unknown in breast cancer. Bioinformatics analysis, including Oncomine, cBioportal, was used to evaluate the potential functions and prognostic values of RhoBTB3 and Col1a1 in breast cancer. qRT-PCR analysis and immunoblotting assay were performed to investigate relevant expression. Functional experiments including proliferation assay, invasion assay, and flow cytometry assay were conducted to determine the role of RhoBTB3 and Col1a1 in breast cancer cells. RhoBTB3 mRNA levels were significantly up-regulated in breast cancer tissues as compared to in adjacent normal tissues. Moreover, RhoBTB3 expression was found to be associated with Col1a1 expression. Decreasing RhoBTB3 expression may lead to decreases in the proliferative and invasive properties of breast cancer cells. Further, Col1a1 knockdown in breast cancer cells limited the proliferative and invasive ability of cancer cells. Knockdown of RhoBTB3 may exert inhibit the proliferation, migration, and metastasis of breast cancer cells by repressing the expression of Col1a1, providing a novel therapeutic strategy for treating breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5345-5351
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• 2012

Radiotherapy is an important part of modern cancer management for many malignancies, and enhancing the radiosensitivity of tumor cells is critical for effective cancer therapies. The Notch signaling pathway plays a key role in regulation of numerous fundamental cellular processes. Further, there is accumulating evidence that dysregulated Notch activity is involved in the genesis of many human cancers. As such, Notch inhibitors are attractive therapeutic agents, although as for other anticancer agents, they exhibit significant and potential side effects. Thus, Notch inhibitors may be best used in combination with other agents or therapy. Herein, we describe evidence supporting the use of Notch inhibitors as novel and potent radiosensitizers in cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.101-105
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• 2014

Background and Purpose: Human epididymis protein 4 (HE4) has been suggested to be a novel biomarker of epithelial ovarian cancer (EOC). The present study aimed to evaluate and compare HE4 with the commonly used marker, carbohydrate antigen 125 (CA125), in prediction and therapy-monitoring of EOC. Patients and Methods: Serum HE4 concentrations from 123 ovarian cancer patients and 174 controls were measured by Roche electrochemiluminescent immunoassay (ECLIA). Risk of ovarian malignancy algorithm (ROMA) values were calculated and assessed. In addition, the prospects of HE4 detection for therapy-monitoring were evaluated in EOC patients. Results: The ROMA score could classify patients into high- and low-risk groups with malignancy. Indeed, lower serum HE4 was significantly associated with successful surgical therapy. Specifically, 38 patients with EOC exhibited a greater decline of HE4 compared with CA125. In contrast, elevation of HE4 better predicted recurrence (of 46, 11 patients developed recurrence, and with it increased HE4 serum concentrations) and a poor prognosis than CA125. Conclusions: This study suggests that serum HE4 levels are closely associated with outcome of surgical therapy and disease prognosis in Chinese EOC patients.

• Tuberculosis and Respiratory Diseases
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• 제72권4호
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• pp.343-351
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• 2012

Background: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit this pathway are currently under development for lung cancer treatment. In the present study, we have tested whether dual inhibition of PI3K/Akt/mTOR signaling can lead to enahnced antitumor effects. We have also examined the role of autophagy during this process. Methods: We analyzed the combination effect of the mTOR inhibitor, temsirolimus, and the Akt inhibitor, GSK690693, on the survival of NCI-H460 and A549 non-small cell lung cancer cells. Cell proliferation was determined by MTT assay and apoptosis induction was evaluated by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Autophagy induction was also evaluated by acridine orange staining. Changes of apoptosis or autophagy-related proteins were evaluated by western blot analysis. Results: Combination treatment with temsirolimus and GSK690693 caused synergistically increased cell death in NCI-H460 and A549 cells. This was attributable to increased induction of apoptosis. Caspase 3 activation and poly(ADP-ribose) polymerase cleavage accompanied these findings. Autophagy also increased and inhibition of autophagy resulted in increased cell death, suggesting its cytoprotective role during this process. Conclusion: Taken together, our results suggest that the combination of temsirolimus and GSK690693 could be a novel strategy for lung cancer therapy. Inhibition of autophagy could also be a promising method of enhancing the combination effect of these drugs.

• Korean Circulation Journal
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• 제53권3호
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• pp.168-169
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• 2023

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5371-5374
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• 2013

Objective: Photodynamic therapy (PDT) is an emerging therapeutic procedure suitable for the treatment of cervical cancer. However, the side effects of PDT are severe, including skin ulceration, so we designed an experiment to examine the effects of multiple low-dose photodynamic therapy of 5, 10, 15, 20-tetrakis(1-methylpyridinium-4-yl) porphyrin (Tmpyp4) on tumour growth by utilizing a model in nude mice implanted with Hela cervical cancer cells. Materials and Methods: Female BALB/c nude mice (aged 5-6 weeks, weighing 18-20 g) were used. Hela cervical cancer cells were injected subcutaneously ($1{\times}10^7cells/200{\mu}L$). Ten days after injection, the mice were divided into three groups (n=6), the A group of controls without any treatment, the B group receiving a single-treatment with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation (blue laser, $108J/cm^2$), and the C group given three-treatments with Tmpyp4 (10 mg/kg, intratumor injection) and irradiation at intervals of two days. After starting treatment, tumours were measured every two days, to assess growth. At 2 weeks after the last treatment of C group, tumour tissue and organs were collected from each mouse to evaluate tumor histology and organ damage. Results: Tumour growth in C group was significantly inhibited compared with A and B groups (P<0.05), without any injury to the skin and internal organs. Conclusion: Our novel findings demonstrated that multiple low-dose photodynamic therapy of Tmpyp4 could inhibit cervical cancer growth significantly with no apparent side effects.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.151-156
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• 1999

Despite the impressive antitumor activity of cisplatin, two major limitations of the drug, that is severe side effects and drug-resistance of cancer cells, make its use difficult of r cancer therapy. These limitations have resulted in a greate deal of effort having been expended into structural modifications of cisplatin. In this study, we tested two novel cisplatin analogues, (CPA)2 Pt[DOLYM] (COMP-I) and (DACH)Pt[DOLYM] (CoMP-II), for the mode of cytotoxic action against human tumor cells comparing with cisplatin and carboplatin in vitro. These two novel analogues had considerable cytotoxic activities against five kinds of human solid tumor cells, and especially COMP-II was more effective on HCT15 colon cancer cells than other compounds. In addition, COMP-II had cytostatic activity at low concentrations (10~0.3${\mu}g/ml$), but other compounds revealed little effect on tumor growth at the low concentration.