• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1845-1849
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• 2014

Background: There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. Materials and Methods: A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 $mg/m^2$ (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 $mg/m^2$ i.v. on day every 3 weeks (group B). Results: Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46). Conclusions: The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3447-3450
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• 2015

Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients and its correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-three elderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors (control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of Chinese People's Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carried out in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and the factors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results: The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC) and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the control group, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-${\pi}$ (GST-${\pi}$) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than in control group (P<0.05), while that of DNA topoisomerase $II{\alpha}$ ($TopoII{\alpha}$) expression lower than in the control group (P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlation with GST-${\pi}$ and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with $TopoII{\alpha}$ (r=-0.328, P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively (r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in the observation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) and eADM in tumor cells (r=-0.723, P=0.000; r=-0.570, P=0.000; r=-0.919, P=0.000; r=-0.781, P=0.000), but with hydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=-0.915, P=0.000; r=-0.890, P=0.000; r=-0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may be related to high COX-2 expression.

• 생명과학회지
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• 제27권11호
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• pp.1290-1298
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• 2017

인체의 장내에 존재하는 장내 미생물은 서로 공생 또는 길항 관계를 유지하며 우리 몸의 면역 방어 기전에 중요한 요소로 작용한다. 본 연구는 항암제가 위암 환자의 장내 미생물 생태계에 미치는 영향을 조사 하였다. 항암치료를 받는 환자의 분변에서 genomic DNA를 추출하고, 16S rDNA 유전자에 대한 denaturing gradient gel electrophoresis (DGGE)를 수행하였다. 분석된 균주는 개체간의 차이가 있었으나, 대부분 사람의 장내에 살고 있는 normal flora로 동정되었다. 모든 분변에 존재하는 5 개 밴드의 서열 분석 결과에 의하면 Faecalibacterium prausnitzii, Morganella morganii 및 Uncultured bacterium sp.가 나타났고, 항암제 처리 후 Sphingomonas paucimobilis, Lactobacillus gasseri, Parabacteroides distasonis 및 Enterobacter sp.가 증가하였다. 이 연구에서 probiotic으로 알려진 Bifidobacterium과 Lactobacillus를 특이적 PCR primer를 이용하여 동정한 결과, 항암제 투여로 인해 Bifidobacterium과 Lactobacillus의 개체군이 현저하게 줄어들어 diarrhea와 같은 부작용의 원인을 예상하게 하며, 장내 생태계의 주요 박테리아 집단에도 중요한 영향을 미치는 것을 알 수 있었다. 이러한 결과는 항암제 투여와 같이 시간의 흐름에 따른 균총의 변화를 시각적으로 모니터링하기 위하여 PCR-DGGE 분석법이 유용하다는 것을 나타낸다.

• Journal of Gastric Cancer
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• 제15권4호
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• pp.223-230
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• 2015

Purpose: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. Materials and Methods: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. Results: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. Conclusions: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.

• Radiation Oncology Journal
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• 제38권2호
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• pp.119-128
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• 2020

Purpose: Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods: In this clinical trial we recruited patients with rectal adenocarcinoma located from 5 cm to 15 cm above the anal verge. Patients in group I (short-course) received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/㎡ from day 1-5 twice daily and oxaliplatin 50 mg/㎡ on day 1 once daily). Patients in group II (long-course) received a total dose of 50-50.4 Gy/25-28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/㎡ twice daily. Both groups underwent consolidation chemotherapy followed by delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results: In this preliminary report on complications and pathological response, 66 patients were randomized into two study groups. Mean duration of radiotherapy in the group II (long-course) was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the shortcourse and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment-related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group except one grade 4 hematologic toxicity that was seen in group II. Within one month of surgery, no significant difference was seen regarding grade ≥3 postoperative complications (p = 0.333). Conclusion: For patients with rectal cancer located at least 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy.

• Radiation Oncology Journal
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• 제36권3호
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• pp.218-226
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• 2018

Purpose: Standard treatment for locally advanced rectal cancer consists of neoadjuvant radiochemotherapy with concomitant fluoropyrimidine or oxaliplatin and surgery with curative intent. Pathological complete response has shown to be predictive for better outcome and survival; nevertheless there are no biological or genetic factors predictive for response to treatment. We explored the correlation between the single nucleotide polymorphisms (SNPs) GSTP1 (A313G) and XRCC1 (G28152A), and the pathological complete response and survival after neoadjuvant radiochemotherapy in locally advanced rectal cancer patients. Materials and Methods: Genotypes GSTP1 (A313G) and XRCC1 (G28152A) were determined by pyrosequencing technology in 80 patients affected by locally advanced rectal cancer. Results: The overall rate of pathological complete response in our study population was 18.75%. Patients homozygous AA for GSTP1 (A313G) presented a rate of pathological complete response of 26.6% as compared to 8.5% of the AG+GG population (p = 0.04). The heterozygous comparison (AA vs. AG) showed a significant difference in the rate of pathological complete response (26.6% vs. 6.8%; p = 0.034). GSTP1 AA+AG patients presented a 5- and 8-year cancer-specific survival longer than GSTP1 GG patients (87.7% and 83.3% vs. 44.4% and 44.4%, respectively) (p = 0.014). Overall survival showed only a trend toward significance in favor of the haplotypes GSTP1 AA+AG. No significant correlations were found for XRCC1 (G28152A). Conclusion: Our results suggest that GSTP1 (A313G) may predict a higher rate of pathological complete response after neoadjuvant radiochemotherapy and a better outcome, and should be considered in a more extensive analysis with the aim of personalization of radiation treatment.

• Journal of Yeungnam Medical Science
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• 제39권2호
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• pp.141-149
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• 2022

Background: The present study evaluated the clinical implications of adjuvant chemotherapy according to the mismatch repair (MMR) status and clinicopathologic features of patients with intermediate- and high-risk stage II colon cancer (CC). Methods: This study retrospectively reviewed 5,774 patients who were diagnosed with CC and underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The patients were enrolled according to the following criteria: (1) pathologically diagnosed with primary CC; (2) stage II CC classified based on the 7th edition of the American Joint Committee on Cancer staging system; (3) intermediate- and high-risk features; and (4) available test results for MMR status. A total of 286 patients met these criteria and were included in the study. Results: Among the 286 patients, 54 (18.9%) were identified as microsatellite instability-high (MSI-H) or deficient MMR (dMMR). Although all the patients identified as MSI-H/dMMR showed better survival outcomes, T4 tumors and adjuvant chemotherapy were identified as independent prognostic factors for survival. For the intermediate-risk patients identified as MSI-low (MSI-L)/microsatellite stable (MSS) or proficient MMR (pMMR), adjuvant chemotherapy exhibited a significantly better disease-free survival (DFS) but had no impact on overall survival (OS). Oxaliplatin-containing regimens showed no association with DFS or OS. Adjuvant chemotherapy was not associated with DFS in intermediate-risk patients identified as MSI-H/dMMR. Conclusion: The current study found that the use of adjuvant chemotherapy was correlated with better DFS in MSI-L/MSS or pMMR intermediate-risk stage II CC patients.

• Journal of Digestive Cancer Research
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• 제3권1호
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• pp.30-34
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• 2015

전이성 위암에서 1차 항암화학요법은 생존 기간을 연장시키고 삶의 질을 향상시키므로 환자의 전신 상태가 양호하다면 표준 요법으로 시행되어야 하며, 국내에서는 fluoropyrimidine과 platinum의 병합 요법이 가장 흔하게 사용된다. 또한 1차 치료에 실패한 위암 환자에서 2차 항암화학요법은 표준 치료이며, 환자의 전신 상태에 따라 그 시행을 적극적으로 고려해야 한다. HER2 양성 위암에서는 trastuzumab 포함 복합 항암화학요법을 시행해야 하며, 진행성 위암으로 진단 시 먼저 HER2/neu 과발현 여부를 확인하는 것이 매우 중요하다. 최근 혈관 신생 성장인자와 관련된 ramucirumab의 항암효과에 대한 임상 결과가 보고되었고, 현재 진행성 위암 환자를 대상으로 C-MET, PI3K, FGFR 및 immune checkpoint 등과 연관된 여러 새로운 표적 치료제에 대한 임상 연구가 활발히 진행되고 있으므로 이들 연구 결과가 임상 현장에 적용될 경우 향후 환자들의 생존과 삶의 질을 향상시키며, 더 나아가 환자 개개인의 분자적, 유전적 특성에 맞는 치료를 할 수 있을 것으로 전망되는 바이다. 저자들은 전신 상태가 비교적 양호하고 고령이 아닌 55세의 남자 환자가 T3N3M0 (Stage IIA)의 진행성 위암을 진단받고 수술적 치료 후 추적 관찰 도중에 간에 다발성의 전이성 병변들이 새롭게 확인되어 고식적인 항암화학요법의 실제 임상에서의 적용을 보고하고자 본 증례를 문헌 고찰과 함께 보고하는 바이다.

• Journal of Digestive Cancer Research
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• 제6권1호
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• pp.25-31
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• 2018

Background: In Korea, stomach cancer is the second most common malignancy and the third leading cause of cancer-related deaths. the time of diagnosis is very important for treatment so early detection and surgery are currently considered the mainstay of treatment, when diagnosed advanced with tumor extension through the gastric wall and direct extension into other organs, with metastatic involvement. Recently, new drugs, drug combinations, and multimodal approaches have been used to treat this disease and In cancers over expressing or amplifying HER2, the combination of cisplatin-fluoropyrimidine-trastuzumab is considered to be the treatment of reference. but At present, the choice of treatment schedule for HER2-negative tumors is based on the medical institution's preferences and adverse effects profile. The aim of this study was to evaluate the effectiveness and safety of using FOLFOX regimen as a first-line therapy or a salvage therapy in the patients with HER2-negative advanced or metastatic gastric cancer. Methods: We retrospective reviewed the patient medical record from March 2012 to July 2017. This study evaluated 113 patients. Sixty-eight patients were treated with the FOLFOX regimen for the first time (first-line group) and 45 patients were treated with the FOLFOX regimen as a second (35 patients) or third (10 patients) chemotherapy (salvage group). Results: In the first-line group, the response rate was 54.9%. In the salvage therapy group, the response rate was 24.4% and The difference was statistically significant (p=0.205). The median TTP of the first-line group was 10.7 months (95% confidence interval [95% CI], 7.8-13.7 months) and that of salvage line group was 6.1 months (95% CI, 3.8-8.4 months). The median OS of the first-line group was 15.8 months (95% CI, 12.7-18.9 months) and that of the salvage therapy group was 10.2 months (95% CI, 8.2-11.9 months). drug toxicity was similar andtolerable between two groups. Conclusion: In patients with unresctable metastatic gastric cancer, after failing to respond to first-line therapy, most patients have no alternative other than second-line therapy because the disease is highly progressive. if the performance status of the patient is good enough to be eligible to treatments beyond best supportive care. FOLFOX regimen can be a considerable therapeutic option for salvage treatment.

• Journal of Gastric Cancer
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• 제8권1호
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• pp.40-46
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• 2008

목적: 재발했거나 수술이 불가능한 진행성 위암 환자에 있어서 FOIFOX 항암치료의 반응성 및 독성에 대한 초기경험을 조사, 정리하고자 하였다. 대상 및 방법: 2006년 4월부터 2007년 8월까지 근치적 위암 절제술 후 재발한 환자 35명과 수술 불가능한 위암으로 처음 진단된 환자 43명을 대상으로 modified FOIFOX-6 항암 치료를 진행하였으며, 그 결과를 후향적으로 분석하였다. 결과: 총 78명의 환자를 대상으로 평균 7.1회의 항암치료를 시행하였으며 RECIST 기준에 의한 부분 관해가 11명(14.1%)의 환자에서 관찰되었으며 안정 상태는 35명(44.9%)이었고 진행성 병변은 32명(44%)이었다. 진행성 병변이 나타나는데 걸리는 시간의 중앙값은 6개월이었으며 생존기간의 평균값은 13개월이었다. 독성 평가에서 1, 2등급의 빈혈이 가장 많은 41명의 환자에서 나타났으며 1, 2등급의 혈소판 감소증은 14명의 환자에서 나타났고 20명의 환자에서 1, 2등급의 말초신경독성을 보였다. 13명의 환자에서 진행성 병변에 의해 FOIFOX에서 S1-cisplatin으로 항암제의 교체가 있었으나 평균 1.76회 밖에 진행할 수 없었다. 결론: 59%의 환자에서 안정 상태 이상의 반응을 보였으며 어떠한 3, 4등급의 독성반응도 관찰되지 않았으므로, 수술 불가능하거나 재발한 위암 환자에서 FOLFOX 항암치료는 비교적 무난한 독성과 유리한 생존을 보이는 적절한 1차적 약제 선택으로 생각된다.