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ABSTRACT: Abstract Background. Several researchers have determined the tumor length to be an important prognostic indictor of esophageal cancer (EC). However, controversy exists concerning the optimal cut-off points for tumor length to predict overall survival. The aim of this study was to determine the prognostic value of tumor length and propose the optimum cut-off point for tumor length in predicting survival difference in elderly patients with esophageal squamous cell carcinoma (ESCC). Methods. From January 2001 to December 2009, a retrospective analysis of 132 consecutive patients older than 70 years with ESCC was conducted. A receiver-operating characteristic (ROC) curve for survival prediction was plotted to verify the optimum cut-off point for tumor length. Univariate and multivariate analyses were performed to evaluate prognostic parameters for survival. Results. A ROC curve for survival prediction was plotted to verify the optimum cut-off point for tumor length, which was 4.0 cm. Patients with tumor length ≤4.0 cm had significantly better 5-year survival rate than patients with a tumor length >4.0 cm (60.7% versus 31.6%, P = 0.007). Multivariate analyses showed that tumor length (>4.0 cm versus ≤4.0 cm, P = 0.036), differentiation (poor versus well/moderate, P = 0.032), N staging (N1-3 versus N0, P = 0.018), and T grade (T3-4 versus T1-2, P = 0.002) were independent prognostic factors. Conclusion. Tumor length is a predictive factor for long-term survival in elderly patients with ESCC, especially in T3-4 grade or nodal-negative patients. We conclude that 4.0 cm may be the optimum cut-off point for tumor length in predicting survival in elderly patients with ESCC.
Upsala journal of medical sciences 04/2013; · 0.73 Impact Factor
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ABSTRACT: The sensitivity of lung cancer to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has been found to be associated with mutations in the tyrosine kinase domain of EGFR. However, not all mutations are sensitive to gefitinib. While CpG island methylation in the promoter region of the EGFR gene and transcriptional silencing are common in solid tumors, the role of the EGFR gene promoter methylation in affecting resistance to TKIs in non-small cell lung cancer (NSCLC) remains unknown. In this study, we examined the correlation between EGFR gene promoter methylation and the therapeutic effect of gefitinib in NSCLC cells. Three NSCLC cell lines with different EGFR mutation statuses and levels of sensitivity to EGFR-TKIs were used in this study: H1650 (del E746-A750), H1299 (wild-type EGFR) and PC-9 (del E746-A750). Cells were treated with gefitinib or 5-aza-2'-deoxy cytidine (5-aza-CdR), a methylation inhibitor, alone or in combination. Subsequently, the methylation status of the EGFR gene promoter was examined by methylation-specific PCR (MSP). Cell survival and apoptosis assays were performed using the Cell Counting Kit-8 (CCK-8) and flow cytometry. In addition, western blot analysis and quantitative real-time PCR were used to examine the expression levels of EGFR protein and mRNA. Our study showed that the promoter region of the EGFR gene in PC-9 cells was unmethylated, and that the cells were sensitive to gefitinib. By contrast, the promoter region of the EGFR gene in the H1650 and H1299 cells was methylated, and the cells were resistant to gefitinib. Of note, the combination treatment with 5-aza-CdR and gefitinib further enhanced the growth inhibitory effects and led to the induction of apoptosis, while a significant reduction in the expression of EGFR protein and mRNA was observed in the H1650 and H1299 cells. These results suggest that blockade of DNA methylation may enhance the antitumor effects of EGFR-TKIs and gefitinib in NSCLC cells. Thus, EGFR gene promoter methylation may be a potential mechanism for acquired resistance to gefitinib.
Oncology Reports 02/2013; · 1.84 Impact Factor
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ABSTRACT: Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 01/2013; · 1.08 Impact Factor
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ABSTRACT: Abstract Background. The risk factors for No. 12p and No. 12b lymph node (LN) metastases in advanced gastric cancer (GC) remain controversial. The aim of this study was to investigate the risk factors for No. 12p and No. 12b LN metastases in advanced GC. Methods. From January 1999 to December 2005, a retrospective analysis of 163 patients with advanced GC who underwent D2 lymphadenectomy in addition to No. 12p and No. 12b LN dissections was conducted. Potential clinicopathological factors that could influence No. 12p and No. 12b LN metastases were statistically analyzed. Results. There were 15 cases (9.2%) with No. 12p LN metastases and 5 cases (3.1%) with synchronous No. 12b LN metastases. A logistic regression analysis revealed that the Borrmann type (III/IV versus I/II, P = 0.029), localization (lesser/circular versus greater, P = 0.025), and depth of invasion (pT4 versus pT2/pT3, P = 0.009) were associated with 11.1-, 3.8-, and 5.6-fold increases, respectively, for risk of No. 12p and No. 12b LN metastases. A logistic regression analysis also showed that No. 5 (P = 0.006) and No. 12a (P = 0.004) LN metastases were associated with 6.9- and 11.3-fold increases, respectively, for risk of No. 12p and No. 12b LN metastases. In addition, significant differences in 5-year survival of patients with and without No. 12p and No. 12b LN metastases were observed (13.3% versus 35.1%, P = 0.022). Conclusion. We conclude that Borrmann type, localization, and depth of invasion are significant variables for identifying patients with No. 12p and No. 12b LN metastases. Individuals with No. 5 or No. 12a LN metastases should be on high alert for the possibility of additional metastases to the No. 12p and No. 12b LNs.
Upsala journal of medical sciences 10/2012; · 0.73 Impact Factor
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ABSTRACT: Both environmental and genetic factors participate in the pathogenesis of lung cancer. The aim of this study was to explore the association between CHRNA3 polymorphisms of the nicotinic acetylcholine receptor gene and lung cancer risk in a hospital-based, case-controlled study. Single nucleotide polymorphisms (SNPs) in CHRNA3 rs3743073 (A>G) were determined using the TaqMan-MGB probe technique in 600 lung cancer cases and 600 normal controls. The differences in genotype and allele frequency were compared between groups and their association with lung cancer. The genotype frequency of rs3743073 (A>G) demonstrated Hardy-Weinberg equilibrium (P<0.05). The genotype and allele frequencies were significantly different between the cancer and control groups (P<0.05). Compared with patients with the TT genotype, lung cancer incidence was increased in patients with the TG and GG genotypes (OR=1.68; 95% CI, 1.30-2.19; P<0.05; OR=1.30; 95% CI, 1.05-1.61; P<0.05, respectively). Patients with rs3743073G variant alleles (TG and GG) were at greater risk (OR=0.65; 95% CI, 0.50-0.84; P<0.05) of developing lung cancer. Increased risk associated with rs3743073G variant alleles was observed in male smokers over the age of 60 (P<0.05). In this cohort, the CHRNA3 gene rs3743073G variant genotype significantly increased lung cancer risk, especially in male smokers over the age of 60.
Molecular Medicine Reports 09/2012; 6(6):1389-92. · 0.42 Impact Factor
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ABSTRACT: To investigate the expression of HER-2/neu mRNA and RECK mRNA in breast carcinoma tissue and relationship with progression of breast carcinoma.
92 cases of breast carcinoma tissue and homologous paraneoplastic breast tissue were selected, expressive level of HER-2/neu mRNA and RECK mRNA were detected with RT-PCR, expressive difference of HER-2/neu mRNA and RECK mRNA were contrasted between breast carcinoma tissue and homologous paraneoplastic breast tissue, along with different TNM stage breast carcinoma tissue and differentiate breast carcinoma.
The level of HER-2/neu mRNA was higher and RECK mRNA was lower in breast carcinoma tissue than homologous paraneoplastic breast tissue, the expressive level of HER-2/neu mRNA and RECK mRNA was remarkably different along with different TNM stage breast carcinoma tissue and differentiate breast carcinoma, there was a negative correlation between expressive level of HER-2/neu mRNA and RECK mRNA in breast carcinoma tissue.
Expression of HER-2/neu mRNA and RECK mRNA was abnormal in breast carcinoma tissue, HER-2/neu mRNA and RECK mRNA regulate each other and mutual participate occurrence and progression of breast carcinoma.
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 08/2012; 26(4):279-81.
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Pei-Pei Xu,
Bao-An Chen, Ji-Feng Feng,
Lu Cheng,
Guo-Hua Xia,
Yu-Feng Li,
Jun Qian,
Jia-Hua Ding,
Zu-Hong Lu,
Xue-Mei Wang,
Ke Xu,
Margaret Schultz
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ABSTRACT: The cytosine arabinoside (Ara-C)-based chemotherapy is the major remedial measure for acute myeloid leukemia (AML). Deoxycytidine kinase (DCK) and cytidine deaminase (CDA) are the key enzymes in the metabolism of Ara-C. Many single nucleotide polymorphisms (SNPs) and haplotypes of DCK and CDA, which contribute to susceptibility to Ara-C, have been identified in Africans and Europeans. However, there has been no report about the relation among three SNPs in DCK (rs115543896, rs72552079, and rs111454937) and two SNPs in CDA (rs2072671 and rs60369023), and their clinical response to Ara-C for a Chinese population. In this study, we aimed to investigate whether these five SNPs are associated with the therapeutic outcomes of Ara-C-based chemotherapy regimens in patients with AML.
A total of 151 Chinese patients with AML were enrolled in our study. SNPs genotyping were performed using the MassARRAY system by means of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) method.
The results illustrated that DCKrs111454937 AA genotype was more frequent in patients with higher platelet count, and A allele frequency was significantly higher in the group £40 years, lower white blood cell (WBC) count patients group and the group with platelet counts > 60'10(9)/L. Meanwhile, both DCKrs72552079 TC (OR = 1.225, 95%CI = 1.225 - 9.851, P = 0.0192) and CDArs60369023 GA (OR = 9.851, 95%CI = 1.31 - 77.93, P = 0.0263) significantly improved Ara-C-based chemotherapy response. While DCKrs11554389 AA (OR = 0.147, 95%CI = 0.027 - 0.801, P = 0.0267) was associated with the decrease of Ara-C-based chemotherapy response.
It is evident that the DCK and CDA polymorphisms might be the important markers for the AML patients' therapy outcomes in a Chinese population.
Chinese medical journal 06/2012; 125(12):2137-43. · 0.86 Impact Factor
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Xiao-ping Zhang,
Zhi-bin Bai,
Bao-an Chen, Ji-feng Feng,
Feng Yan,
Zhi Jiang,
Yue-jiao Zhong,
Jian-zhong Wu,
Lu Chen,
Zu-hong Lu,
Na Tong,
Zheng-dong Zhang,
Pei-pei Xu,
Miao-xin Peng,
Wen-jing Zhang,
Shuai Wang
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ABSTRACT: Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.
Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment.
The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465).
These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.
Chinese medical journal 03/2012; 125(5):741-6. · 0.86 Impact Factor
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ABSTRACT: Although pulmonary small cell carcinoma (SCC) is seen frequently, SCC that originates from the extrapulmonary organs is extremely rare. We herein report a case of a SCC located in the lesser omentum. A 61-year-old male was admitted to our department due to intermittent epigastralgia for 2 months. Ultrasonography (US) revealed an irregular hypoechoic mass measuring about 58 mm × 50 mm × 45 mm under the left lobe of the liver. Magnetic resonance imaging (MRI) was performed to verify the irregular mass with T1- and T2- weighted images between the left lobe of liver and the stomach. At laparotomy, the well-circumscribed neoplasm was found in the lesser omentum, and the fundus of the neoplasm was located in the root of left gastric artery. Intraoperative microscopic evaluation of frozen sections revealed malignancy of the lesser omentum. Resection of the neoplasm was performed, and the combined resection of the vagal nerve was also performed for the partial adhesion. Pyloroplasty was performed for avoiding delayed gastric emptying caused by combined resection of vagal nerve. The lymph nodes dissection at lesser curvature and right cardia was also performed with a negative result. Based on the histological findings, the final diagnosis of primary lesser omental SCC was confirmed. The pathologic staging showed locoregional disease.
The Kaohsiung journal of medical sciences 02/2012; 28(2):115-9. · 0.61 Impact Factor
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ABSTRACT: Solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm of low malignant potential that mostly affects young women in the second or third decade of life. The number of such patients reported in the literature has increased in recent years, while SPT in pregnancy is extremely rare. To the best of our knowledge, only one case of SPT in pregnancy has been reported in the English-language literature. We herein report a case of asymptomatic SPT in a 26-year-old Chinese female in the 14th week of pregnancy, and present our experience of the surgical management of SPT in pregnancy.
Acta gastro-enterologica Belgica 12/2011; 74(4):560-3. · 0.64 Impact Factor
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ABSTRACT: To examine the expression of membrane-type-1 matrix metalloproteinase (MT1-MMP) and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in gastric carcinoma, and investigate its clinical significance, at the same time analyze the correlation between MT1-MMP and RECK expression.
MT1-MMP and RECK expression in surgically resected tissue samples of gastric carcinoma was examined by immunohistochemical method (two-step method) , and its correlation with clinicopathological factors was analyzed.
Among the 44 gastric carcinoma samples, 37 (84.1%) were stained positive for MT1-MMP, and 31 (70.5%) for RECK. The expression of MT1-MMP was much higher in poorly differentiated gastric carcinoma samples than moderately and well-differentiated samples (P = 0.015). The expression level of MT1-MMP was associated with invasive depth of tumor cells (P = 0.007), but no difference between sex and lymph node metastasis. On the contrary, the well-differentiated samples showed higher expression of RECK than poorly and moderately differentiated gastric carcinoma samples (P = 0.006). The expression level of RECK did not correlate with sex, lymph node metastasis and invasive depth of tumor cells. RECK expression showed no relation to MT1-MMP expression in the gastric carcinoma.
Overexpression of MT1-MMP in gastric carcinoma may play an important role during tumor differentiation and metastasis, the RECK protein may have positive effects on the tumor differentiation.
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 10/2011; 25(5):364-7.
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ABSTRACT: Primary malignant fibrous histiocytoma (MFH) of the spleen is extremely rare. Since the first description of primary splenic MFH reported by Govoni et al in 1982, to the best of our knowledge, only 13 cases of MFH of the spleen have been reported in the English language literature in Medline. We herein report a rare case of primary splenic MFH accompanying with hepatic cyst in a 48-year-old Chinese female who treated successfully by laparoscopic splenectomy and fenestration, which has not yet been reported in the literature. Compared with the 13 previously cases of MFH of the spleen, our case is the first case accompanied with other disease, and also the first case treated successfully by laparoscopic splenectomy. A literature review of MFH of the spleen previously reported in the English language literature in Medline is also provided.
Journal of research in medical sciences 07/2011; 16(7):963-7. · 0.46 Impact Factor
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Xiao-Li Zhu,
Xin-Chen Sun,
Bao-An Chen,
Ning Sun,
Hong-Yan Cheng,
Fan Li,
Hong-Ming Zhang, Ji-Feng Feng,
Shu-Kui Qin,
Lu Cheng,
Zu-Hong Lu
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ABSTRACT: Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer (NSCLC) patients, and genetic factors are thought to represent important determinants of drug efficacy. We prospectively assessed the status of the XPC Ala499Val and Lys939Gln gene polymorphisms and investigated whether these SNPs can predict the response to cisplatin/carboplatin-based regimens in advanced NSCLC patients in a Chinese population.
The treatment outcomes of 96 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of xeroderma pigmentosum group C (XPC) gene was genotyped by the 3-D polyacrylamide gel-based DNA microarray method.
The distributions of XPC Lys939Gln genotypes differed significantly between the response group (complete + partial responses) and the non-response group (stable + progressive disease; P = 0.022). The heterozygous A/C genotype carriers had a poorer response rate than the wild A/A genotype carriers in stage III (OR, 0.074; 95%CI, 0.008 - 0.704; P = 0.023). The XPC Ala499Val polymorphisms were not associated with response to platinum-based chemotherapy.
Polymorphisms of the XPC gene, Lys939Gln, may be a predictive marker of treatment response for advanced NSCLC patients in stage III.
Chinese medical journal 12/2010; 123(23):3427-32. · 0.86 Impact Factor
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Yue-Jiao Zhoang,
Bao-An Chen,
Lu Cheng, Ji-Feng Feng,
Yu-Feng Li,
Jun Qian,
Jia-Hua Ding,
Jian Cheng,
Feng Gao,
Guo-Hua Xia,
Ning Sun,
Yan Zhang,
Xiao-Ping Zhang,
Pei-Pei Xu,
Zu-Hong Lu
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ABSTRACT: This study was purposed to investigate the practicality of matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for detection of single nucleotide polymorphisms (SNP) on jak2 gene in multiple myeloma (MM) cells. The DNA fragment containing 2 SNPs of jak2 (C428T and C643T) was amplified using PCR and was purified. The purified product was used as the template for primer extension (PEX). The small products of allele-specific reaction were purified, the SNPs on jak2 gene of 5 patients with MM and 5 healthy persons were detected by MALDI-TOF MS. The results showed that the distribution of genotype C428T and C643T was not different between MM patients and healthy persons, both of which are homozygous T/T. In conclusion, the method based on MALDI-TOF MS and PEX technique for detecting SNP in jak2 gene is rapid, accurate and reliable method, and can be used in clinical practice.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 10/2009; 17(5):1234-7.
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ABSTRACT: Ribonucleotide reductase catalyzes the rate limiting step of deoxyribonucleotide formation, a crucially important step in DNA synthesis and repair. The regulatory subunit M1 of ribonucleotide reductase (RRM1) is the necessary part of the RR function and controls substrate specificity and global on/off enzyme activity. Despite recent research progress, the role of RRM1 in lung cancer sensitivity to chemotherapeutics remains to be elucidated. This study was to investigate the relationship between polymorphisms of the RRM1 gene and sensitivity to platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Genomic DNA samples from 214 NSCLC patients treated with platinum-based chemotherapy were used to determine the RRM1 promoter allelotypes. The RR37CC-RR524TT was the most frequent allelotype (38.50%), followed by RR37AC-RR524CT (26.76%) and RR37CC-RR524CT (14.95%). The average response rate for chemotherapy was 44.4%. The response rates to the treatment regimens in the RR37CC-RR524TT, RR37AC-RR524CT and RR37CC-RR524CT allelotypes were 43.9%, 52.6%, and 51.6%, respectively. The response rates to therapy among patients with RRM1 (-)524 allelotypes were significantly different (p=0.046), whereas that among patients with RRM1 (-)37 allelotypes were not significant. Further analysis showed that the response rate in the patients with RR524CT allelotype (52.3%) was the highest, compared with that with RR37CC-RR524TT allelotype (43.9%, p=0.28), or the Others (RR524CC and RR37AC-RR524TT, 30.2%, p=0.02). Our results suggest that the RR524CT allelotype may be associated with an increased sensitivity to platinum-based chemotherapy in NSCLC. Further research on determining RR524CT as a clinical marker for predicting response to platinum-based therapy in NSCLC patients is warranted.
Lung cancer (Amsterdam, Netherlands) 04/2009; 66(3):344-9. · 3.14 Impact Factor
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ABSTRACT: Genetic polymorphisms of DNA repair genes are associated with differential enzyme activity and may help explain interindividual differences in response rates after platinum-based chemotherapy for non small cell lung cancers (NSCLCs). This study was conducted to assess relationships between X-ray repair cross complementing group1 (XRCC1) and xeroderma pigmentosum group D (XPD) genetic polymorphisms and outcome in NSCLC patients.
From March 1, 2005 to December 31, 2008, the polymerase chain reaction-restriction fragment length polymorphism method was applied to evaluate genetic polymorphisms of the XRCC1 codon399 (Arg/Gln) and XPD codon751 (Lys/Gln) DNA repair genes in 108 patients with stage IIIB and IV NSCLCs treated with platinum-based chemotherapy in the Department of Chemotherapy of Jiangsu Cancer Hospital and Research Institute.
Among the assessed NSCLC patients, the overall response rate of chemotherapy was 21.6%. No association was found with either of the genetic polymorphisms, although the XRCC1 399Arg/Arg genotype was associated with a non-significant higher median survival time (29 months versus 21 months for the Arg/Gln genotype and 15 months for the Gln/Gln genotype, P= 0.09).
Our results suggested no influence of the XRCC1 codon399 (Arg/Gln) and XPD codon751 (Lys/Gln) genetic polymorphisms on treatment response and survival in advanced NSCLC patients with platinum-based chemotherapy.
Asian Pacific journal of cancer prevention: APJCP 01/2009; 10(5):859-64. · 0.66 Impact Factor
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Mei Dong,
Feng-Yi Feng,
Yang Zhang,
Guang-Ru Xie,
Ya-Jie Wang,
Ji-Wei Liu,
San-Tai Song,
Qing-Hua Zhou,
Jun Ren,
Shun-Chang Jiao,
Jin Li,
Xiu-Wen Wang,
Qiang Chen,
Zhe-Hai Wang,
Nong Xu, Ji-Feng Feng
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ABSTRACT: To evaluate the efficacy and safety of zoledronic acid in the treatment of bone pain in patients with bone metastasis from solid tumor or multiple myeloma.
A randomized, double-blind, double-simulated and multi-center phase III clinical trail with pamidronate as control was conducted. Patients with moderate to severe bone pain (VAS > 50 mm) induced by solid tumor or multiple myeloma were randomized to receive intravenous zoledronic acid 4 mg or pamidronate 90 mg. Then the change of VAS and urinary NTX/Cr and CTX/Cr were observed in two groups.
From July 2005 to September 2006, 228 patients with bone pain induced by bone metastasis from 15 cancer centers were randomize into two groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. Significant improvement in bone pain after treatment were observed both in zoledronic acid group and the control group when compared with baseline VAS on D8 (-11.77% vs. -10.87%), D15 (-24.60% vs. -21.06%) and D28 (-32.37% vs. -31.26%) (P< or =0.0001), but no significant difference existed between two groups (P =0.6587). Compared with baseline, urine NTX/Cr and CTX/Cr level were decreased rapidly after treatment in both groups, the nadir was on D8, the median decreased on D28, which was -36.9% vs. -32.1% for NTX/Cr (P = 0.7922) and -63.2% vs. -47.9% for CTX/Cr (P =0.834). The frequently observed adverse events were pyrexia (19.0% vs. 31.3%), vomiting (6.0% vs. 8.9%), nausea (4.3% vs. 4.5%), fatigue (3.4% vs. 2.7%) and constipation (2.6% vs. 1.8%) in the two groups. Compared with baseline, the serum creatinine level was not significantly increased throughout the study.
Intravenous injection of 4 mg zoledronic acid can significantly reduce bone pain and bone resorption marker in urine in the Chinese patients with bone metastasis from solid tumor or multiple myeloma, which is tolerable and also comparable to pamidronate in the efficacy and safety.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 04/2008; 30(3):215-20.
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ABSTRACT: To investigate the relationship between polymorphism in the 3'-untranslated region (3'-UTR) of the thymidylate synthase (TS) gene and sensitivity of gastric cancer to 5-fluorouracil (5-FU)-based chemotherapy, 106 cases of advanced gastric cancer were analyzed. All patients were treated with 5-FU-based chemotherapy; DNA from peripheral blood leukocytes was obtained before therapy. TS 3'-UTR genotypes were detected by PCR-RFLP. Polymorphism in the TS 3'-UTR can be classified into three groups according to the presence or absence of a 6 bp nucleotide fragment: the -6/-6 bp, -6/+6 bp and +6/+6 bp groups. The response rate of the -6/-6 bp and -6/+6 bp groups was found to be significantly higher than the +6/+6 bp group. These results show that the presence of the TS 3'-UTR 6 bp nucleotide fragment can be correlated with the sensitivity of gastric cancer to 5-FU-based chemotherapy, and that the TS 3'-UTR polymorphism profile can be used to guide the choice of 5-FU-based chemotherapy in advanced gastric cancer.
Journal of Human Genetics 02/2006; 51(3):155-60. · 2.57 Impact Factor
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ABSTRACT: The combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and folinic acid (FA), being one of the effective regimens for advanced gastric cancer, is used in form of chronomodulated chemotherapy for advanced gastric cancer to investigate its efficacy and safety.
Twenty-six patients received a 4-day chronomodulated infusion of L-OHP, 5-Fu and FA. L-OHP (25 mg.m(-2).d(-1)) infused from 10:00 am to 22:00 pm, and followed by 5-Fu (600 mg.m(-2).d(-1)) and FA (300 mg.m(-2).d(-1)) from 22:00 pm to 10:00 am for 4 days using a multichannel programmable pump, every 2 weeks as an cycle for at least 2 cycles.
Twenty-six patients with previously untreated advanced gastric cancer were eligible. Two complete and 13 partial remissions were observed with an overall response rate of 57.7%. Stable disease was observed in 6 patients (23.1%) and progressive disease in five (19.2%). Four of these patients underwent surgery. The median remission time was 3.5 months and time to tumor progression (TTP) was 4.5 months. The median overall survival time was 8 months. A total of 80 cycles were given without any grade 4 toxicity observed, but grade 3 thrombocytopenia (1.3%) and mucositis (1.3%) in one patient, two grade 3 neutropenia (2.5%) and nausea/vomiting (2.5%) in 2.
Chronomodulated intravenous chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid is effective and safe in the treatment of advanced gastric cancer.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 12/2005; 27(11):695-7.
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ABSTRACT: To investigate the relationship between polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the response to fluoropyrimidine (5-FU)-based chemotherapy in advanced stomach cancer (SC).
75 cases with advanced SC were analyzed. All patients were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. MTHFR genotypes were detected by PCR-RFLP method.
(1) Of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 32.0%, 44.0% and 24.0%, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotype were 69.3%, 29.3% and 1.3%, respectively. The overal response rate to 5-FU-based chemotherapy was 29.3%. (2) The response rate to therapy among MTHFR C677T T/T genotype patients (83.3%) was significantly higher than the C677T C/T genotype (15.2%, chi(2) = 22.27, P = 0.000) or the C677T C/C genotype (8.3%, chi(2) = 23.44, P = 0.000). As compared with patients with C677T C allele, patients with C677T T/T genotype had a 7.64-fold sensitivity to 5-FU-based chemotherapy (adjusted for sex, age, prior adjuvant therapy and chemotherapy program, 95% CI: 3.14 - 18.62). The response rate to therapy among patients with MTHFR A1298C A/A genotype (36.5%) was significantly higher than patients with A1298C C allele (13.0%, chi(2) = 4.19, P = 0.041, adjusted OR = 3.75, 95% CI: 0.94 - 14.87). The response rate to therapy among patients with MTHFR C677T T/T and A1298C A/A genotypes (86.7%) was significantly higher than other groups of C677T and A1298C genotypes (15.0%, Fisher exact: P = 0.000, adjusted OR = 6.57, 95% CI: 2.8 - 15.6). (3) The incidence rates of nausea/vomiting in MTHFR C677T T/T, C/T or A1298C A/A genotypes were significantly higher than other genotypes, but the incidence rates of other treatment-related adverse reaction in MTHFR C677T or A1298C genotypes were not significantly different.
These results in the present study suggested that the polymorphisms of MTHFR were associated with clinical response to 5-FU-based chemotherapy, suggesting that MTHFR genotypes could identify advanced SC patients that would be responsive to 5-FU-based chemotherapy.
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 01/2005; 25(12):1054-8.
