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Serum miR-19a Predicts Resistance to FOLFOX Chemotherapy in Advanced Colorectal Cancer Cases

  • Chen, Qi;Xia, Hong-Wei;Ge, Xiao-Jun;Zhang, Yu-Chen;Tang, Qiu-Lin;Bi, Feng
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권12호
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    • pp.7421-7426
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    • 2013
  • Background: Colorectal cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death. FOLFOX is the most common regimen used in the first-line chemotherapy in advanced colorectal cancer, but only half of the patients respond to this regimen and we have almost no clue in predicting resistance in such first-line application. Methods: To explore the potential molecular biomarkers predicting the resistance of FOLFOX regimen as the first-line treatment in advanced colorectal cancer, we screened microRNAs in serum samples from drug-responsive and drug-resistant patients by microarrays. Then differential microRNA expression was further validated in an independent population by reverse transcription and quantitative real-time PCR. Results: 62 microRNAs expressing differentially with fold-change >2 were screened out by microarray analysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144) were chosen for further validation in an independent population (N=72). Our results indicated serum miR-19a to be significantly up-regulated in resistance-phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of serum miR-19a to discriminate the resistant patients from the response ones was 66.7%, and the specificity was 63.9% when the AUC was 0.679. We additionally observed serum miR-19a had a complementary value for cancer embryonic antigen (CEA). Stratified analysis further revealed that serum miR-19a predicted both intrinsic and acquired drug resistance. Conclusions: Our findings confirmed aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.

Potential Predictors of Sensitivity to Pemetrexed as First-line Chemotherapy for Patients with Advanced Non-Squamous NSCLCs

  • Lu, Yan-Yan;Huang, Xin-En;Xu, Lin;Liu, De-Gan;Cao, Jie;Wu, Xue-Yan;Liu, Jin;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권3호
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    • pp.2005-2008
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    • 2013
  • Background: Pemetrexed (PEM) is effective in first-line treatment for patients with non-squamous non-small cell lung cancer (NSCLC). However there are currently no definitive determinants to certify which patients could benefit from PEM. To improve the efficacy of PEM combined with platinum as first-line therapy for advanced non-squamous NSCLC, we conducted this retrospective study to detect potential determinants of this regimen. Methods: We recruited 109 patients with advanced non-squamous NSCLC who received PEM with a platinum as first-line therapy from June 2006 to February 2013 in Jiangsu Cancer Hospital. Multiple variables (age, sex, smoking, degree of cell differentiation, hemoglobin, platinum drugs combined, positions of metastasis) were selected. Logistic regression analysis was used to analyse relationships between these variables and tumor response. Result: In univariate analysis, we found that age and platinum significantly influenced the results of PEM therapy (P<0.05). In multivariable analysis, no factors were independently significant. Conclusion: Our analysis did not suggest that the age, sex, metastasis of liver or other organs, hemoglobin, smoking history and pathological differentiation are associated with the response of PEM. We should conduct further analyses with larger sample size to reconfirm this issue.

Prognostic Factors in First-Line Chemotherapy Treated Metastatic Gastric Cancer Patients: A Retrospective Study

  • Inal, Ali;Kaplan, M. Ali;Kucukoner, Mehmet;Urakci, Zuhat;Guven, Mehmet;Nas, Necip;Yunce, Muharrem;Isikdogan, Abdurrahman
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.3869-3872
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    • 2012
  • Background: The majority of patients with gastric cancer in developing countries present with advanced disease. Systemic chemotherapy therefore has limited impact on overall survival. Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyze prognostic factors for survival in advanced gastric cancer patients undergoing first-line palliative chemotherapy. Methods: We retrospectively reviewed 107 locally advanced or metastatic gastric cancer patients who were treated with docetaxel and cisplatin plus fluorouracil (DCF) as first-line treatment between June 2007 and August 2011. Twenty-eight potential prognostic variables were chosen for univariate and multivariate analyses. Results: Among the 28 variables of univariate analysis, nine variables were identified to have prognostic significance: performance status, histology, location of primary tumor, lung metastasis, peritoneum metastasis, ascites, hemoglobin, albumin, weight loss and bone metastasis. Multivariate analysis by Cox proportional hazard model, including nine prognostic significance factors evident in univariate analysis, revealed weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level to be independent variables. Conclusion: Performance status, weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level were identified as important prognostic factors in advanced gastric cancer patients. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.

Clinical Observation and Prognostic Analysis of Pemetrexed plus Platinum as First-line Treatment in Patients with Advanced Non-small Cell Lung Cancer

  • Wang, Ji-Ying;Cai, Yong
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권11호
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    • pp.6267-6271
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    • 2013
  • Objective: To determine clinical efficacy, safety and prognostic factors of pemetrexed plus platinum as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Clinical characteristics, short-term efficacy, survival and adverse reactions of 47 advanced non-squamous NSCLC patients who had received pemetrexed plus platinum as first-line treatment in Shanghai Pulmonary Hospital from January 2009 to June 2011 were retrospectively analyzed. The Chi-squared test was applied to statistically analyze the overall response rate (ORR), disease control rate (DCR) and toxicity reactions in both groups, while survival data wereanalyzed by Kaplan-Meier and logrank methods, and the COX proportional hazards model was adopted for a series of multi-factor analyses. Results: Only two patients were lost to follow-up. The ORR, DCR, medium progression-free survival time (PFS) and medium overall survival (OS) were 31.9%, 74.5%, 5 months and 15.2 months, while 1- and 2-year survival rates were 63.8% (30/47) and 19.2% (9/47), respectively. Single-factor analysis showed that tumor pathological patterns and efficacy were in association with medium PFS (P<0.05), whereas tumor pathological patterns, smoking history and efficacy were closely connected with medium OS (P<0.05). Multi-factor analyses demonstrated that pathological patterns and efficacy were independent factors influencing OS (P<0.05). The rate of toxicity reactions in degree III/IV was low, including hematologic toxicity marked by decline in white blood cell count and decrease in the platelet count (PLT), and non-hematologic toxicity manifested by gastrointestinal reactions, such as nausea and vomiting. Conclusions: Pemetrexed plus platinum as first-line treatment has excellent efficacy and slight adverse reactions with favorable drug-tolerance in patients with advanced non-squamous NSCLC.

Factors Prognostic for Survival in Japanese Patients Treated with Sunitinib as First-line Therapy for Metastatic Clear Cell Renal Cell Cancer

  • Kawai, Y;Osawa, T;Kobayashi, K;Inoue, R;Yamamoto, Y;Matsumoto, H;Nagao, K;Hara, T;Sakano, S;Nagamori, S;Matsuyama, H
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권14호
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    • pp.5687-5690
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    • 2015
  • Background: Factors predictive of survival have been identified in Western patients with metastatic clear cell renal cell carcinoma (mCCRCC) treated with sunitinib. Less is known, however, about factors predictive of survival in Japanese patients. This study evaluated factors prognostic of survival in Japanese patients with mCCRCC treated with first-line sunitinib. Materials and Methods: This retrospective study evaluated 46 consecutive Japanese mCCRCC patients treated with sunitinib as first line therapy. Clinical and biochemical markers associated with progression-free survival (PFS) were analyzed, with prognostic factors selected by uniand multivariate Cox regression analyses. Results: Univariate analysis showed that factors significantly associated with poor PFS included Memorial Sloan-Kettering Cancer Center poor risk scores, International Metastatic RCC Database Consortium poor risk and high (>0.5 mg/dl) serum C-reactive protein (CRP) concentrations (p<0.001 each). Multivariate analysis showed that high serum CRP was independently associated with poorer PFS (p=0.040). Six month disease control rate (complete response, partial response and stable disease) in response to sunitinib was significantly higher in patients with normal (${\leq}0.5mg/dl$) than elevated baseline CRP (p<0.001). Conclusions: CRP is a significant independent predictor of PFS for Japanese patients with mCCRCC treated with first-line sunitinib. Pretreatment CRP concentration may be a useful biomarker predicting response to sunitinib treatment.

Metastatic Pancreatic Carcinoma and Experience with FOLFIRINOX - a Cross Sectional Analysis From a Developing Country

  • Zahir, Muhammad Nauman;Jabbar, Adnan Abdul
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권14호
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    • pp.6001-6006
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    • 2015
  • Background: Pancreatic cancer is the fourth leading cause of cancer related death with median survival ranging from 3 to 6 months for metastatic disease. Palliative chemotherapy has been the backbone of treatment in advanced stage and has evolved over time. Data pertaining to the disease are scarce from our part of the world where treatment poses a significant challenge due to lack of resources. Materials and Methods: A retrospective chart review was performed for all patients presenting with stage IV pancreatic carcinoma at a tertiary care hospital in Karachi, Pakistan between January 2008 and December 2012. Data were collected using a pre-designed, coded questionnaire looking at patient characteristics, treatment given and outcome. Results: 101 patients were found to be eligible. Mean age was $56.7{\pm}12.8years$, the male to female ratio was 2:1 and most patients had a good performance status. More than half of the tumors were located in the head (57%, n=58) and almost all were adenocarcinomas (95%, n=96). Some 58% (n=59) received first line chemotherapy of which 49% (n=29) received gemcitabine-based regimens and 39% (n=23) received FOLFIRINOX. The median progression free survival for gemcitabine based treatment was 2.9 months (IQR=1.6-5.6) as opposed to 7.3 months (IQR=4.5-9.2) for FOLFIRINOX (P=0.02). Median overall survival was 4.9 months (IQR=2.3-9.5) for first line gemcitabine based treatment and 10.5 months (IQR=7.0-13.2) for first line FOLFIRINOX therapy (P=0.002). Patients on FOLFIRINOX had better survival across all subgroups. Inpatient admissions and dose reductions were more frequent with FOLFIRINOX but the difference between the two regimens was not statistically significant. FOLFIRINOX could be successfully administered as outpatient therapy to a number of patients. Conclusions: FOLFIRINOX remains a suitable first line option in patients with metastatic pancreatic cancer with good performance status even in a resource-poor country where diagnostic and supportive care facilities may be less than optimal and cost is a limitation.

First-Line Mono-Chemotherapy in Frail Elderly Patients with Metastatic Colorectal Cancer

  • Varol, Umut;Dirican, Ahmet;Yildiz, Ibrahim;Oktay, Esin;Degirmenci, Mustafa;Alacacioglu, Ahmet;Barutca, Sabri;Karabulut, Bulent;Uslu, Ruchan
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권7호
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    • pp.3157-3161
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    • 2014
  • Background: Unlike for fit elderly metastatic colorectal cancer (mCRC) patients, general approaches to initial treatment for the frail older mCRC patients are not clear. Our aim was to evaluate the efficiency and safety of first-line single-agent treatment in one such group. Materials and Methods: We retrospectively evaluated mCRC patients aged 70 or older with an Eastern Cooperative Oncology Group performance score of 2. They had no prior treatment and underwent first-line single-agent capecitabine or other monotherapies until disease progression or unacceptable toxicity. Results: Thirty-six patients were included. Most (n:28, 77.8%) were treated with capecitabine. One patient achieved a complete response and 5 patients had a partial response for an overall response rate of 16.6%. Twelve patients (33.3%) remained stable. Median progression free survival was 5 months (confidence interval (CI), %; 3.59-6.40) and median overall survival was 10 months (95 CI%; 8.1-11.8). Grade 3-4 toxicity was found in 6 patients (16.6%). Febrile neutropenia was not observed and there were no toxicity-associated deaths. Conclusions: Capecitabine is a safe chemotherapeutic agent with moderate activity for first-line treatment of older metastatic colorectal cancer patients with limited performance status.

자기공명영상으로 분류한 소아 임파관종 주사 요법의 평가 (Evaluation of Intralesional Injection Therapy for Pediatric Lymphangiomas Classified with MRI)

  • 김인규;문석배;신현백;서정민;이석구
    • Advances in pediatric surgery
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    • 제15권2호
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    • pp.113-120
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    • 2009
  • Pediatric lymphangioma can occur at any site. However the neck is the most common site. There are two treatment modalities (surgical excision and intralesional injection) for lymphangiomas. But, the treatment guide line for lymphangioma has not been established, yet. The aim of this study is to establish the treatment guide line based on our experience with lymphangiomas. Medical records of 82 cases of lymphangioma were reviewed retrospectively. On MRI (magnetic resonance image) findings, lymphangiomas were divided into 4 groups by the proportion of the cyst bigger than 2 cm in diameter of the tumor; group A-proportion of cyst occupies more than 75%, group B-proportion of the cyst 50~75%, group C-25~50%, and D in less than 25%. All patients were treated with OK-432 intralesional injection as the initial treatment. The effective response rates of OK-432 in group A & B were 88.2% and 88.8%, respectively. Group C response was 38.0% and D only 20.0%. Twenty-three patients received surgical excision. The result of surgical excision was generally satisfactory. Surgical site infection occurred in 1 case and postoperative bleeding in 1 case. Theses results indicate that intralesional injection of OK-432 could be the first line therapy in group A & B. In group C, OK-432 would be better as the first line therapy than surgery. For the group D, surgical excision should be the first line of treatment.

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RSA 문제와 동등한 안전성을 갖는 온라인/오프라인 서명 기법 (On-Line/Off-Line Signature Schemes with Tight Security Reduction to the RSA Problem)

  • 최경용;박종환
    • 정보보호학회논문지
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    • 제28권2호
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    • pp.327-338
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    • 2018
  • 온라인/오프라인(On-line/off-line) 서명은 오프라인 단계에서 서명생성에 필요한 무거운 연산을 수행하고, 온라인 단계에서 간단한 연산만으로 최종 서명을 완성하는 기법이다. 이는 다수의 사용자에게 즉각적인 서명 응답을 해야 하는 응용환경에 적합하다. 본 논문에서는 RSA 문제에 기반한 새로운 온라인/오프라인 서명기법을 두 가지로 제안한다. 첫 번째 기법은 온라인 서명 시 고정된 밑수에서의 지수승이면 되고, 두 번째 기법은 해쉬연산과 같은 매우 간단한 계산만으로 온라인 서명을 완성할 수 있다. 두 서명의 안전성은 모두 RSA 문제로 환원되는데, 랜덤 오라클 모델에서 안전성 손실 없이 증명이 된다.

Analyses of Multiple Factors for Determination of "Selected Patients" Who Should Receive Rechallenge Treatment in Metastatic Colorectal Cancer: a Retrospective Study from Turkey

  • Ozaslan, Ersin;Duran, Ayse Ocak;Bozkurt, Oktay;Inanc, Mevlude;Ucar, Mahmut;Berk, Veli;Karaca, Halit;Elmali, Ferhan;Ozkan, Metin
    • 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.