Association of XPD Asp312Asn single nucleotide polymorphisms with oxaliplatin based chemotherapy / 中国医师杂志

Objective This study was to determine the role of the Xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism in predicting response to Oxaliplatin based chemotherapies and survival in patients with metastatic colorectal cancer.Methods This study enrolled a total of 106 patients treated with FOLFOX4 (n =72) or XELOX (n =34) regimen.The genotype of XPD Asp312Asn was analyzed by TaqMan probe based real-Time polymerase chain reaction (PCR).Logistic regression was used to predict the response to the treatments.Cox proportion hazards models and Kaplan-Meier method were applied to predict the survival.Results The effective rate of chemotherapy in 106 patients with colorectal cancer was 57.6％ (61/106).There was no significant difference in the distribution of G/G,G/A and A/A genotypes between the two groups (P ＞ 0.05).Multivariate survival analysis showed that the survival time of patients with A/A genotype,carcinoembryonic antigen (CEA) (＞5 ng/ml) and age (＞65 years) was relatively short,with statistical significance (P ＜ 0.05).Conclusions XPD Asp312Asn single nucleic acid polymorphism can be used as a predictor of survival in patients with metastatic colorectal cancer,but it is not associated with oxaliplatin sensitivity and needs further study.

Inhibitory effects of lobaplatin on human ovarian cancer and its regulation of apoptosis-related genes in nude mice / 中国医师杂志

Objective To explore the inhibitory effects of lobaplatin and cisplatin and their regulation of apoptosis-related genes in ovarian cancer cells in nude mice.Methods SKOV3 cells were implanted into nude mice.In monotherapy treatment study,the nude mice bearing human SKOV3 cells were randomly divided into control,lobaplatin,and cisplatin groups,with 7 mice in each group.The mice in each group were received corresponding treatment.The volume of tumor and the weight of nude mice were measured three times per week,respectively.Tumor inhibitory rate was calculated.The protein expressions of bax and bcl-2 were detected by flow cytometry.Results The growth inhibitory rate was 47.2％ in lobaplatin group and 42.8％ in cisplatin group,without significant difference between two groups (P ＞ 0.05).The expression of bcl-2 was decreased but the bax was increased in lobaplatin and ciaplatin groups compared to the control group.Conclusions Lobaplatin can significantly inhibit the growth of ovarian cancer cells,induce apoptosis by down-regulation of bcl-2 and up-regulation of bax.

The comparison of efficacy of cisplatin and nedaplatin for concurrent chemoradiotherapy for patients with locallyadvanced cervical cancer / 中国医师杂志

Objective To investigate the clinical effect of cisplatin and nedaplatin through comparing the effects of synchronous radiotherapy and chemotherapy of cisplatin and nedaplatin on patients with locally advanced cervical cancers.Methods Clinical data of 54 cases of patients with locally advanced cervical cancers received treatment at our hospital from 2009 to 2011 were analyzed retrospectively.Patients were divided into two groups according to the treatment:group DDP (cisplatin) and group NDP (nedaplatin).The general information,short-term effect,long-term curative effect,and adverse reactions were compared between two groups.Results The general information including gender,age,body mass index (BMI),stages,and pathology had no statistically significant difference between two groups.The response rate (RR)of patients in each group was 100％.The complete remission (CR) rate between groups NDP and DDP had no statistically significant difference.Among the patients ≤60 years old,the CR rate,the survival rate of 1,2,and 3 years,and the median progression-free survival (PFS) had no statistically significant difference.Among the patients ＞ 60 years old,the survival rate of 1,2,and 3 years,and the median PFS had no statistically significant difference,but the CR rate had statistically significant difference.In the non-hematological toxicity,the incidence rate of nausea and vomiting,the effect on renal function in group NDP were obviously lower than those in group DDP.There was no significant difference in liver function damage.In the hematological toxicity,there was no statistically significant difference in the incidence rate of anemia and leukopenia.The incidence rate of decrease of platelet in group NDP was higher than that in group DDP,but it was mainly reflected in the Ⅰ and the Ⅱ level.Conclusions Cisplatin had the same efficacy of concurrent chemoradiotherapy with nedaplatin for the treatment of locally advanced cervical carcinoma with a worse tolerance.

Compostos coordenados híbridos de platina no tratamento do câncer / Platinum hybrid coordinated compounds in cancertreatment

O câncer, ou neoplasia, é uma doença caracterizada pela propagação descontrolada de formas anormais das próprias células corporais e corresponde à segunda doença que mais causa mortes no mundo. A história da platina no tratamento do câncer teve início com a descoberta da sua atividade, em 1965, com a aprovação para uso clínico acontecendo apenas após 10 anos. Atualmente, os fármacos com platina estão entre os mais bem sucedidos agentes anticancerígenos, onde se destacam cisplatina (1), carboplatina (2) e oxaliplatina (3). Seus mecanismos de ação são similares: estes fármacos formam adutos com o DNA, impedindo a sua síntese e reparo, levando à morte celular. Contudo, os efeitos adversos desencadeados pelo tratamento e o desenvolvimento de resistência ao medicamento têm limitado suas aplicações. Uma das principais estratégias para a diminuição de tais efeitos consiste em alterar a estrutura destas moléculas, levando à formação de compostos híbridos, que se caracterizam pela presença de pelo menos dois fragmentos funcionais distintos em uma mesma molécula e podem apresentar maior espectro de atividade antitumoral. Dentre as alterações mais comuns encontram-se a modificação da solubilidade, através da inserção de grupos abandonadores mais ou menos hidrofóbicos e a introdução de ligantes com atividade biológica própria. Dessa forma, esta revisão visa verificar os avanços mais recentes na síntese de compostos híbridos de platina, bem como as melhorias na atividade anticâncer dos novos compostos platinados...

Cancer, or neoplasm, is a disease characterized by the uncontrolled propagation of abnormal cells of the body and is the second leading death-causing disease. The history of platinum in cancer treatment goes back to the discovery of its activity in 1965 and its approval for clinical use just 10 years later. Some of the most successful anticancer agents are Pt-based chemotherapeutics, among which cisplatin (1), carboplatin (2), and oxaliplatin (3) stand out. They have similar mechanisms of action: they form adducts with DNA, preventing its synthesis and repair and leading to cell death. However, adverse effects triggered by treatment and the development of resistance to these drugs have limited their application. One of the most important strategies to reduce such effects is to carry out structural modifications of these molecules, leading to hybrid compounds that are characterized by the presence of at least two distinct functional fragments on the same molecule and can exhibit a broader antitumor activity spectrum. Among the most typical modifications are changes to the solubility pattern, created by the insertion of leaving groups with high or low hydrophobicity, and the introduction of biologically active ligands as non-leaving groups. The purpose of these strategies is to obtain compounds capable of reducing systemic toxicity and/or overcoming acquired resistance factors to cisplatin. Therefore, the aim of this review is to discuss the most recent advances in the synthesis of hybrid platinum compounds, as well as improvements in the anticancer activity of Pt-compounds...

Relation between breast cancer susceptibility gene 1 expression and the efficacy of platinum-based chemotherapy in colorectal cancer / 中华消化杂志

Objective To explore the expression of breast cancer susceptibility gene 1 (BRCA1) in human colorectal cancer and its correlation with the efficacy of platinum-based chemotherapy.Methods Seventy-eight cases of colorectal cancer patients treated with platinum-based chemotherapy after surgery were collected.The surgical specimens of them were taken.Fourteen normal colonic mucosa specimens and 12 non-cancerous tissues of colorectal cancer specimens were obtained.The expression of BRCA1 in tissues was detected by immunohistochemistry and analyzed by x2 test.The colorectal cancer patients were followed up for survival time.Comparison of survival analysis was performed by Kaplan-Meier survival curves and Log-rank test.Results The positive rate of the BRCA1 expression in colorectal cancer tissue (52.6 ％,41/78) was lower than that of para-cancer tissue (11/12,x2 =6.518,P=0.011) and normal colonic mucosa tissue (13/14,x2 =7.949,P=0.005).The poorer the differentiation of colorectal cancer,the lower the positive rate of BRCA1 (x2=14.160,P=0.001).The median disease-free survival time of BRCA1 negative colorectal cancer patients was 51.0 months (95 ％ CI:47.7 to 54.4 months),which was longer than that of BRCA1 positive patients (45.0 months,95 ％CI:36.6 to 53.4 months,x2 =4.367,P=0.032).Conclusions Receiving oxaliplatin based chemotherapy may be a survival benefit for BRCA1 negative colorectal cancer patients.The expression of BRCA1 may be an index for chemotherapy options and prognosis evaluation for colorectal cancer patients after surgery.

The efficacy and safety evaluation of 5-FU/LV and FOLFOX4 chemotherapy regimen for colorectal cancer / 中国医师杂志

ObjectiveTo evaluate the efficacy and safety of two different adjuvant chemotherapy regimens of 5-FU/LV and FOLFOX4 in patients who suffered from colorectal cancer after having radical surgery.MethodsBy 123 patient who had colorectal cancer and received radical surgery from December 2005,to May 2007 were enrolled in this using retrospective analysis.68 cases received 5 FU/LV chemotherapy regimens and 35 cases received FOLFOX4 chemotherapy regimens.The results of survival rate and side effects were compared between the two groups.ResultsThe survival rates within 3 years of 5-FU/LV and FOLFOX were 77.3％ and 80％ respectively.There was no significant differences between two chemotherapy regimens ( x2 =1.26,P =0.28).The main side effects included anorexia,nausca/vomiting,alopecia and et al.However there was no significant difference in adverse reactions of two groups ( P ＞0.05 ).Conclusions5-FU/LV and FOLFOX4 were effective and safe chemotherapy regiments for patients with colorectal cancer after having radical surgery,and the side effects were acceptable in these two groups.

Predictive effect of combined evaluation of XRCC1, XPD and GSTP1 single nucleotide polymorphisms in platinum based chemotherapy / 中国医师杂志

Objective To investigate the predictive value of combined analysis on single nucleotide polymorphisms (SNPs) of X-ray cross-complementing1 ( XRCC1 ) gene 194 and 399 codon,xeroderma pigmentosum group D (XPD) gene 312 codon and glutathione S-transferase P1 (GSTP1) gene 105 codon in platinum based chemotherapy.Methods Direct sequencing was performed to detect XRCC1,XPD and GSTP1 genotypes in peripheral blood from 50 cancer patients receiving platinum-based chemotherapy.Genetic polymorphisms of these genes related to sensitivity of platinum were reviewed.Results Favorable genotypes were Arg/Trp and Trp/Trp in XRCC1 194 codon,Arg/Arg in XRCC1 399 codon,Asn/Asn in XPD 312 codon and Val/Val in GSTP1 105 codon.The response rate to chemotherapy was 57.1％,75.0％,60.9％,85.7％ and 87.5％,respectively.The response rate for patients possessing ≥2 favorable genotypes and those possessing 1 or 0 favorable genotype was 78.9％,36.4％ and 0,respectively.Patients possessing ≥2 favorable genotypes demonstrated higher sensitivity to platinum based chemotherapy,compared with those possessing 1 or 0 favorable genotype ( x2 =25.79,P ＜ 0.01 ).Conclusions Combination analysis of genomic polymorphisms of XRCC1,XPD and GSTP1 may be useful in predicting sensitivity of platinum based chemotherapy.

Combined oxaliplatin with adenosine triphosphate tumor chemosensitivity assay (ATP-TCA) for direction of indiyidual chemotherapy of hepatocellular carcinoma / 中国医师杂志

ObjectiveTo investigate the effectiveness of combined oxaliplatin regimen as adjuvant chemotherapy for hepatocellular carcinoma and to evaluate the efficacy of using adenosine triphosphate tumor chemosensitivity assay (ATP-TCA) for direction of individual chemotherapy.MethodsThe twenty-six patients with primary hepatocellular carcinoma were operated.Specimens were collected and adenosine triphosphate tumor chemosensitivity assay (ATP-TCA) was applied to evaluate the sensitiveness of chemotherapy agent(Adriamycin, Mitomycin, Mitoxantrone, Oxaliplatin, Irinotecan, 5-FU, Gemzar, Carboplatin, Cisplatin, Docetaxel and Etoposide).Sensitive group (SG) was from from 11 patients who were sensitive to oxaliplatin, and control group was from the other 16 patients who were not sensitive to oxaliplatin.All the twenty-six patients received oxaliplatin combined with 5-FU or capecitabine regimen chemotherapy.The effectiveness (CR,PR,SD,PD,ORR,OS and DFS) of the regimen according to RECIST criteria and WHO criteria for anticancer drugs toxicity and efficacy of ATP-TCA were evaluated.ResultsTwenty-six patients were successfully evaluated.In SG, six patients obtained complete remission(CR), three got partial remission(PR), one got stable disease (SD) and one patient got progression disease (PD).While in control group,four patients obtained CR,two patients got PR, five patients got SD and four got PD.No significant differences were found in overall survival (OS, P = 0.1116) and disease-free survival (DFS, P = 0.2328)between sensitive group and control group.But significant differences were found in overall response rate (ORR) (81.8％ vs 40.0％, P =0.0401) between two groups.Common toxicities were as follows:I to Ⅱdegree of myelosuppression was 53.8％, I to Ⅱ degree of gastrointestinal tract response was 50％, I to Ⅱ degree of liver function damage was 57.7％ and I to Ⅱ degree of neuropathy was 23.1％, respectively.Most of these toxicities were tolerable at grade 1 ～ 2.No significant differences were found in the toxicities between two groups.ConclusionsCombined oxaliplatin regimen might be an effective choice for adjuvant chemotherapy for HCC, which has with tolerable systemic toxicity.Application of ATP-TCA system might further improve the efficacy of this regimen by selecting right candidate.

Efficacy and tolerability of the combination of oxaliplatin, ifosfamide, and epirubicin in treatment of recurrent or platinum-resistant ovarian epithelial cancer patients / 中华妇产科杂志

Objective To evaluate the efficacy and tolerability of the combination of oxaliplatin,ifosfamide and epirubicin(IAP)in treatment of recurrent or platinum-resistant ovarian cancer patients.Methods A total of 25 patients received the combined chemotherapy of ifosfamide(3-4 g/m2),epirubicin(50-60 mg/m2)and oxaliplatin(130 mg/m2).The cycles were repeated every 21 days.The efficacy and toxicity were evaluated in 21 patients who received more than 2 cycles of IAP chemotherapy.Results The overall response rate was 71%,with a complete response in 10(48%),partial response in 5(24%),stable disease in one(5%),and disease progression in 5(24%).The median progression-free and overall survival time were 11(1 to 33)months and 31(1 to 71)months.While overall response rate was 60%in 10 patients with primary platinum resistant,and 88%in 8 patients with secondary platinumresistant.Grade Ⅲ-Ⅳ myelosuppression rate wss 30%.The most common non-hematologic toxicity was perineurotoxicity(38%).Conclusions The combination of oxaliplatin,ifasfamide and epirubicin appears to be effective for recurrent or platinum-resistant ovarian cancer patients as salvage chemotherapy and the toxicity is also tolerable.However,it needs to be evaluated by multiple clinical trials.