• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10439-10444
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• 2015

Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

• 대한영상의학회지
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• 제82권4호
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• pp.876-888
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• 2021

목적 항암 치료를 진행하는 위암 간전이 환자에서 종양의 길이를 이용한 반응 평가와 비교하여 종양의 부피를 이용한 반응 평가가 환자의 생존율을 더 잘 예측할 수 있는지 알아보는 연구이다. 대상과 방법 항암 치료를 진행하는 위암 간전이 환자 43명을 연구에 포함하였다. 간전이 종양의 부피를 정량적으로 계산한 기준과 Response Evaluation Criteria in Solid Tumors 기준을 비교하였다. 카플란-마이어, 콕스비례위험 모형을 사용하여 일변량분석과 다변량분석을 통해 환자 생존율 및 연관된 인자를 알아보았다. 결과 저자들은 간전이 종양의 부피를 정량적으로 계산한 기준을 이용했을 때, 질환 반응군(23.6개월; 95% 신뢰구간, 8.63~38.57)과 질환 비반응군(7.6개월; 95% 신뢰구간, 3.78~11.42)간 생존율에 통계학적 유의한 차이를 확인하였다(p = 0.039). 질환 안정군과 질환 진행군을 부피를 이용한 반응 평가와 길이를 이용한 반응 평가로 구분할 경우 양군은 생존기간과 위험비에서 의미 있는 차이를 보였으나 두 반응 평가 방법 간 차이는 없었다(카플란-마이어 모형: p = 0.006; 콕스비례위험 모형: 위험비, 2.437, p = 0.008). 결론 항암 치료를 진행하는 위암 간전이 환자들에서 간전이의 부피 반응 평가는 환자들의 생존율을 예측하는 데 도움을 줄 수 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.775-781
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• 2015

Background: RB1 (retinoblastoma 1) was reportedly one of the major determinative factors for sensitivity to taxanes in previous studies. In this study, we investigated the influence of RB1 single nucleotide polymorphisms (SNPs) on the efficacy of platinum-taxane regimens in advanced NSCLC patients. Materials and Methods: 234 cases of patients with advanced NSCLC who were treated with first-line platinum-taxane agents were enrolled in this study. Genomic DNA was extracted from patients' peripheral blood samples using a QIAamp DNA Maxi Kit, and genotyped by iSelect HD Bead-Chip. Results: Regression analyses were conducted through the univariate and multivariate Cox proportional hazards model in the 234 patients. The results showed that of the eight RB1 tagSNPs, only rs4151510 was a positive predictive factor for the advanced NSCLC patients treated with platinum taxanes regimen. The patients with G/G genotype of RB rs4151510 had longer overall survival (OS) than the non-G/G genotype (p=0.018). The histology was also correlated with OS in the whole advanced NSCLC patients. Three tagSNPs of RB1, rs4151510, rs4151465, rs9568036 were significantly associated with OS in the advanced NSCLC patients with squamous cell histology using Kaplan-Meier overall survival analysis stratified by histology. Conclusions: RB1 genomic variants were correlated with the efficacy of platinum-taxanes regimen. RB rs4151510 is an independent factor of the prognosis of NSCLC patients receiving platinum-taxane chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4153-4158
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• 2014

Background: This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III ${\beta}$-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy. Materials and Methods: We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatin-based first-line treatment were analyzed. Results: These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05). Conclusions: A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6149-6154
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• 2015

Background: There is no suggested molecular indicator for the determination of which patients will benefit from anti-angiogenetic treatment in metastatic colorectal cancers. Materials and Methods: In this study, VEGF and $HIF-1{\alpha}$ expression and their clinical significance were studied in tumor tissues of patients with colorectal cancer receiving bevacizumab-based treatment. VEGF and $HIF-1{\alpha}$ were assessed by immunohistochemistry in the primary tumors of 53 metastatic colorectal cancer patients receiving chemotherapy in combination with first line bevacizumab. Results: The clinical benefit rate in the low-VEGF expression group was 38%, while it was 62% in the high expression group. While the median progression-free survival (PFS) was 10 months in the high-VEGF expression group, it was 8 months in the low-VEGF expression group (p = 0.009). The median overall survival (OS) was found to be 26 months vs 15 months. Thus, when VEGF was strongly expressed it was in favor of that group and the difference was statistically significant (p = 0.03). High VEGF expression rate was an independent factor that correlated with OS or PFS (p=0.016 and 0.009, respectively). Conclusions: The data showed that VEGF may have predictive value for determining the treatment of CRC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8715-8718
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• 2014

Background: ABVD (doxorubicin, bleomycin, vinblastine (Vb) and dacarbazine) is the standard regimen in Hodgkin's lymphoma (HL).Vincristine (O) is a mitotic spindle agent like Vb. We aimed to evaluate the efficacy and safety of O as a part of ABOD in HL. Materials and Methods: Patients who had ABOD were enrolled. Stage I-II HL were evaluated for unfavorable risk factors according to NCCN. National Cancer Institute Common Toxicity Criteria was used for toxicity. Results: Seventy-nine HL patients in our center between 2003 and 2007 were evaluated retrospectively. Median follow-up was 54 months. Most of the patients were male in their third decade. Median ABOD cycles were 6 (2-8). Primary refractory disease rate was 17.7% whereas it was 5.1% for early relapse and 5.1% for late relapse disease. Response rates were as 82.3% for complete response, 11.4% for partial response, 5.1% for stable disease and 1.3% for progressive disease. Half of relapsed patients had autologous stem cell transplantation. Estimated 5-year failure-free survival was 71% and significantly longer in early stage patients without risk factors, bulky disease or radiotherapy (RT) (p=0.05, p<0.0001, p=0.02; respectively). Estimated 5-year overall survival was 74% and significantly longer in those who had no RT (p=0.001). Dose modification rate was 5.1% and chemotherapy delay rate was 19%. There were no toxicity-related deaths. Conclusions: ABOD seems to be effective with managable toxicity in HL, even in those with poor prognostic factors.

• IMMUNE NETWORK
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• 제20권1호
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• pp.10.1-10.14
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• 2020

Immune checkpoint inhibitors (ICIs) have shown remarkable benefit in the treatment of patients with non-small-cell lung cancer (NSCLC) and have emerged as an effective treatment option even in the first-line setting. ICIs can block inhibitory pathways that restrain the immune response against cancer, restoring and sustaining antitumor immunity. Currently, there are 4 PD-1/PD-L1 blocking agents available in clinics, and immunotherapy-based regimen alone or in combination with chemotherapy is now preferred option. Combination trials assessing combination of ICIs with chemotherapy, targeted therapy and other immunotherapy are ongoing. Controversies remain regarding the use of ICIs in targetable oncogene-addicted subpopulations, but their initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the choice. For the majority of patients without targetable driver oncogenes, deciding between therapeutic options can be difficult due to lack of direct cross-comparison studies. There are continuous efforts to find predictive biomarkers to find those who respond better to ICIs. PD-L1 protein expressions by immunohistochemistry and tumor mutational burden have emerged as most well-validated biomarkers in multiple clinical trials. However, there still is a need to improve patient selection, and to establish the most effective concurrent or sequential combination therapies in different NSCLC clinical settings. In this review, we will introduce currently used ICIs in NSCLC and analyze most recent trials, and finally discuss how, when and for whom ICIs can be used to provide promising avenues for lung cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2415-2418
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• 2012

Objective: To investigate the efficacy and safety of voriconazole in treating Chinese patients with hematological malignancies and invasive aspergillosis. Methods: From March 2007 to April 2012, patients with diagnoses confirmed by CT, GM test and/or PCR assays, were recruited into this study. Aspergillosis of all patients were treated with voriconazole 6 mg/kg intravenous infusion (iv) every 12 h for 1 day, followed by 4 mg/kg IV every 12 h for 10-15 days; Then, switch to oral administration that was 200mg every 12h for 4-12 weeks. Efficacy and safety were evaluated according to Practice Guideline of Infectious Diseases Society of America. Results: The overall response rate of 38 patients after voriconazole treatment was 81.6%. The median time to pyretolysis was 4.5 days. Treatment related side effects were mild and found in only 15.8% of cases. No treatment related deaths occurred. Conclusions: Voriconazole can considered to be a safe and effective front-line therapy to treat patients with hematological malignancies and invasive aspergillosis. Alternatively it could be used as a remedial treatment when other antifungal therapies are ineffective.

• Tuberculosis and Respiratory Diseases
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• 제61권2호
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• pp.143-149
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• 2006

연구배경: Toptisomerase I 억제제인 irinotecan 과 소세포폐암 치료의 근간인 cisplatin의 복합화학용법을 확장기 소세포폐암 환자에게 1차 치료법으로 실시하여 반응률, 생존율 및 부작용을 확인하였다. 방 법: 2002년 6월부터 2005년 2월까지 확진된 확장기 소세포폐암 환자 39명에게 irinotecan $60mg/m^2$, 제 1, 8, 15일째 cisplatin $60mg/m^2$ 제1일째에 28일 간격으로 4회 투여하였다. 결 과: 반응률은 77%(완전반응 8%), 중앙생존기간은 14.8개월, 1-및 2-년 생존율은 60.9%, 27.6%였으며, 중앙 무진행생존기간은 8.4개월, 6-및 12-개월 무진행생존율은 75.0%, 18.8%였다. WHO grade 3 이상의 부작용은 백혈구 감소증 23%, 설사 26%였으나, 심한 설사때문에 2명은 치료방법을 바꾸었고, 1명은 사망하였다. 결 론: Irinotecan과 cisplatin 복합화학요법은 확장기 소세포폐암 환자의 1차 치료법으로 유용하며, 부작용으로서 설사에 대해서는 치명적일수 있으므로 심각한 주의가 요망된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8661-8666
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• 2014

Background: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. Materials and Methods: Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel $60mg/m^2$ plus cisplatin $60mg/m^2$ (day 1) combined with capecitabine $1650mg/m^2$ (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. Results: The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. Conclusions: DCX regimen offers prominent anti-tumor activity and considered to be effective first-line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.