• Journal of Digestive Cancer Research
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• 제1권1호
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• pp.6-16
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• 2013

식생활의 서구화와 대장암 검진의 증가로 인하여 국내의 대장암 유병률은 지속적으로 증가하고 있으며, 최근 보고에 의하면 남자에서는 종양 발생률 2위, 여자에서는 종양 발생률의 3위를 차지하고 있다. 비록 대장내시경이 대장암의 진단과 선별검사에 아주 효과적인 방법이지만, 여전히 대장암의 20-25%는 이미 진단 당시에 전이를 동반하고 있는 것으로 되어 있다. 최근 10년 동안 이러한 전이성대장암의 고식적인 치료로 irinotecan과 oxaliplatin 등의 약제들의 개발과 이들의 다양한 조합에 관련된 연구들이 보고되어 왔으며, 분자생물학적인 발전에 힘입은 표적 치료제의 개발과 이에 대한 다양한 연구들은 향후에도 진행성대장암 환자들의 종양 반응률과 생존기간을 증가시킬 것으로 기대된다.

• Journal of Yeungnam Medical Science
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• 제23권2호
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• pp.143-151
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• 2006

In the past decade, the median duration of survival among patients with advanced colorectal cancer has increased from 12 months to about 18 months, primarily as a results of the introduction of irinotecan and oxaliplatin. Advances in the understanding of the molecular mechanisms underlying the development and progression of cancer have resulted in the discovery of new therapeutic interventions that target specific molecular abnormalities. Their specificity, and therefore their potential to bind preferentially and modify tumor-specific targets, sparing normal tissues and causing fewer side-effects compared to conventional cytotoxic agents, makes them an attractive therapeutic option. The future of this approach for the treatment of solid tumors is promising.

• Journal of Digestive Cancer Research
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• 제2권2호
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• pp.52-55
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• 2014

The incidence of colorectal cancer (CRC) has continuously increased and CRC is a major cause of cancer-related death. Systemic chemotherapy has resulted in a significant improvement in overall survival in metastatic CRC. The development of biologic agents for the treatment of CRC has additionally expanded the options for the treatment. Cetuximab is useful in KRAS wild type tumors in combination with chemotherapy for metastatic disease in both the first and second line settings. It is also used as monotherapy after failure of both irinotecan and oxaliplatin containing regimens. Panitumumab has similar indications, and is primarily used in patients intolerant to cetuximab due to hypersensitivity reactions. Bevacizumab is primarily used as first line and second line therapy in metastatic CRC. However, the optimal way and duration to combine these chemotherapeutic agents are not yet established.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2833-2838
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• 2015

Background: Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients with metastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewed our registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatin-based regimens as rechallenge third and fourth-line therapy. Materials and Methods: Patients who received irinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-line therapy. These patients were selected from the database of Turkish mCRC registry archives between October 2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overall survival (OS) by the Kaplan-Meire and Cox-regression methods. Results: Thirty-nine patients were enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up. In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line. Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.68 months). The factors effecting survival (PFS and OS) were only being PFS after first-line chemotherapy ${\geq}12months$ (p=0.007, 95% CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. Conclusions: This study indicates that rechallenge treatment could be a good option as a third or later line therapy in patients who had ${\geq}12months$ PFS onreceiving first line therapy.

• Journal of Gastric Cancer
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• 제7권3호
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• pp.160-166
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• 2007

목적: 진행성위암의 경우 근치적 수술 후 보조항암요법에도 불구하고 5년 생존율이 그리 높지 않은 것으로 보고되고 있다. 이에 항암제 감수성 검사를 기초로 한 항암요법은 최소한 환자들에게 효과가 없는 약제 투여를 막을 수 있는 기회를 제공할 수 있다는 측면에서는 고무적이라 할 수 있다. 본 연구에서는 보조항암요법의 효과를 높이기 위한 유효약제 선정을 위하여 항암제 감수성검사를 실시하였으며 그 결과를 분석하여 항암제 선택에 이용하고자 임상병리학적 요인에 따른 항암제 감수성을 비교하였다. 대상 및 방법: 2005년 8월부터 2006년 8월까지 영남대학교 병원 외과에서 위절제술을 받은 위암환자 81명의 위암절제조직을 이용하여 항암제 감수성 검사를 실시하였다. 검사방법은 ATP (Adenosine Triphosphate) based chemotherapy response assay였다. 항암제 감수성과 임상병리학적 요인과의 상관관계를 보기 위하여 성별, 연령, 종양표지자(CEA 치, CA19-9 치), 암의 위치, 진행암 형태, 조직학적 형태, 분화 유무, 침윤도, Lauren 분류, Ming 분류, 림프관 침윤 유무, 맥관 침윤 유무, 신경 침윤 유무, 림프절 전이 유무, 병리학적 병기를 선정 비교하였다. 결과: 위암 환자를 대상으로 한 항암제 감수성 순위를 보면 5-FU, Epirubicin, Irinotecan, Oxaliplatin 순이었으며 통계학적으로 유의했다(P=0.000). 성별, 연령, 종양표지자(CEA 치, CA19-9치), 암의 위치, 진행암 형태, 조직학적 형태, 분화 유무, 침윤도, Lauren 분류, Ming 분류, 림프관 침윤 유무, 맥관 침윤 유무, 신경 침윤 유무, 림프절 전이 유무, 병리학적 병기 모두에서 유의하게 감수성의 차이를 보였다. 결론: 위암절제조직에서 시행한 항암제 감수성 순위는 5-FU, Epirubicin, Irinotecan, Oxaliplatin의 순이었으며 위절제술을 받은 위암환자의 절제조직을 이용 항암제 감수성검사를 시행한 결과 약제별 임상병리학적 인자에 따라 감수성의 차이가 있으므로 획일적인 항암화학요법을 실시하는 것보다 항암제 감수성 검사를 통하여 감수성 높은 약제들을 조합하여 사용하는 것이 바람직할 것으로 보인다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6587-6590
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• 2014

Objective: To further observe the efficacy and safety of pemetrexed, combined with Irinotecan or oxaliplatin or cisplatin in treating patients with advanced gastric cancer as second-line or third-line chemotherapy. Methods: From September 2013 to February 2014 we recruited 50 patients with advanced gastric cancer, with stage IV disease or postoperative recurrence, or unresectable. Then treated with pemetrexed based chemotherapy. After two cycles of treatment, efficacy and toxicity were evaluated. Results: Pemetrexed based chemotherapy was used as second-line in 33 patients, RR(CR+PR) is 41.2%. And achieved 36.4% when used as third-line. Overall response rate of 50 patients treated with Pemetrexed based treatment was 38% (CR+PR). Treatment related side effects were bone marrow suppression, vomiting, hepatic dysfunction and malaise.No treatment related death occurred. Conclusions: Treatment with pemetrexed based chemotherapy is active and is well tolerated in patients with advanced gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.973-978
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• 2016

Background: Between October 2012 and February 2015, 25 patients with metastatic colorectal cancer (mCRC) (mean age, $57.0{\pm}12.1years$) were granted access to aflibercept via the Aflibercept Named Patient Program at four centers. Materials and Methods: Here we reported the initial experience of aflibercept / FOLFIRI in combination. We evaluated treatment-related adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Results: The majority of the patients experienced gastrointestinal toxicity (grade 1-2), with diarrhea (52%), mucositis (52%), and nausea/vomiting (20%) being largely observed. Neutropenia (16%) and febrile neutropenia (8%) were common grade 3-4 hematological events. Aflibercept-related toxicity was managed as per practice guidelines. No grade 5 event was reported. Median PFS was 6.12 months (95% CI, 4.80-7.20) and OS was 12 months (95% CI, 9.80-14.18). The partial response (PR), stable disease (SD), and progressive disease (PD) rates were 25% (95% CI: 23.4-27.0), 37.5% (95% CI: 31.6-43.3), and 37.5% (95% CI: 22.5-52.5), respectively. Conclusions: Aflibercept/FOLFIRI can be administered safely in a second line setting to Malaysian patients with mCRC, as the AEs experienced were generally reversible and manageable. The safety and efficacy outcomes were consistent with those observed in Western populations.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2191-2194
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• 2014

Background: Fluorouracil-based regimens have been widely accepted and recommended in the guidelines for treating patients with early or advanced staged colon cancer, although results are controversial. Here we performed a systemic analysis to evaluate the impact of S-1 based regimens on response and survival of patients with colon cancer. Methods: Clinical studies evaluating the impact of S-1 based regimens on response and survival of patients with colon cancer were identified using a predefined search strategy. Summary response rates (RRs) to treatment were calculated. Results: Six clinical studies which including 227 patients with advanced colorectal cancer were considered eligible for inclusion. Two studies were conducted using combination of S-1 and Oxaliplatin, and four studies featured S-1 and irinotecan. Systemic analysis showed that, in all patients, pooled RRs was 43.17%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. No treatment related death occurred. Conclusion: This systemic analysis suggests that S-1 based regimens, both with oxaliplatin or irinotean are associated with acceptable response and toxicity in patients with colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1637-1641
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• 2016

Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

• Journal of Microbiology and Biotechnology
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• 제31권11호
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• pp.1576-1582
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• 2021

Bacterial β-glucuronidase in the intestine is involved in the conversion of 7-ethyl-10-hydroxycamptochecin glucuronide (derived from irinotecan) to 7-ethyl-10-hydroxycamptothecin, which causes intestinal bleeding and diarrhea (side effects of anti-cancer drugs). Twelve compounds (1-12) from Polygala tenuifolia were evaluated in terms of β-glucuronidase inhibition in vitro. 4-O-Benzoyl-3'-O-(O-methylsinapoyl) sucrose (C3) was highly inhibitory at low concentrations. C3 (an uncompetitive inhibitor) exhibited a k_i value of 13.4 μM; inhibitory activity increased as the substrate concentration rose. Molecular simulation revealed that C3 bound principally to the Gln158-Tyr160 enzyme loop. Thus, C3 will serve as a lead compound for development of new β-glucuronidase inhibitors.