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Objective To detect the plasma concentration of fluorouracil in patients with advanced colorectal cancer who uesd fluorouracil , and to explore the relationship between chemotherapy efficacy , tumor response, toxicity and survival of patients with advanced colorectal cancer after chemotherapy with fluorouracil.Methods 174 patients with advanced colorectal cancer were collected from the General Hospital of Ningxia Medical University from January 2014 to December 2016.Patients with advanced colorectal cancer were treated with FOLFOX scheme , venous blood was taken from patients 18-24 hours after intravenous infusion of fluorouracil .The concentration of 5-FU in blood was measured by nami-enhanced immune assay.The targeted AUC range of 5-FU was 20-30 mg· h/L.The patients were divied into three groups-targeted range group , lower than the targeted range group and higher than the targeted range group . The therapeutic efficacy, toxicity and survival of patients were recorded , in order to observe the difference of different target range groups.To analyze the correlation between the different target groups and the clinical characteristics,a logistic method was used.Chi-square test was used to compare the efficacy and toxicity of the three groups.The survival curves were plotted by kaplan-meier method. Results To detected the concentration of fluorouracil at the same time after infusion of fluorouracil .The AUC was 2.267-31.06 mg· h/L,it was very different, the median AUC was 15.368 mg· h/L, and the highest AUC was 31.06 mg· h/L,it was 13.7 times that of the lowest blood concentration (2.267 mg· h/L) .The relationship between the concentration of fluorouracil and the clinical indicators was found as follows :(1)Clinical characteristics : the blood concentration of 5-Fu after infusion was different , which was related to the preoperative CEA status (r＝0.318,P＜0.05), EGFR(r＝0.558,P＜0.05), Lymph node metastasis status(r＝0.325,P＜0.05), and the number of metastatic organs ( r＝0.404, P＜0.05 ) .( 2 ) Effect of chemotherapy : There were significant differences in the effect of chemotherapy between different target groups (χ2＝6.78,P＜0.05). The effect of chemotherapy in the targeted range group was lower than that in the target range group , and the difference has statistically significant(χ2＝2.030,P＜0.05).(3)toxicity: there have statistical difference among the three groups,the toxicity of higher targeted range group was higher than the other two groups (χ2＝2.01,P＜0.05).(4)Survival: The survival time of patients with targeted range group was lower than that of targeted range group, and the difference has statistically significant (χ2＝7.263,P＜0.05).Conclusion The method of testing the concentration of fluorouracil in patients with advanced colorectal cancer is valuable to predict the efficacy , toxicity and prognosis of patients with colorectal cancer.
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Objective To detect gene polymorphisms of ABCB1/MDR1 in breast cancer and to analyze the association between ABCB1 gene polymorphisms and curative effect of paclitaxel-based chemotherapy in breast cancer.Methods Genotyping of ABCB1exon12 (1236),exon21 (2677)and exon26 (3435)was determined by polymerase chain reaction (PCR)-high resolution melting (HRM)method in 146 cases of female stage IV breast cancer to explore the relationship between the efficacy of chemotherapy in breast cancer patients with paclitaxel chemotherapy.Results In 146 patients with stage IV breast cancer,C1236T CC genotype accounted for 15.86%, CT genotype 44.83%,TT genotype 44.83%,G2677T/A GG genotype 16.67%,GT genotype 45.83%,GA genotype 6.25%,TT genotype 28.47%,AT genotype 2.78%,C3435 CC genotype 22.22%,CT genotype 56.25%,and TT genotype 21.53%.ABCB1 gene polymorphisms did not significantly differ between patients of Hui and Han Nationalities (P>0 .0 5 ).Hardy-Weinberg genetic equilibrium testing showed that polymorphisms of C1236T,G2677T/A and C3435T had group representation (P>0.05).In 146 stage IV breast cancer patients who had received paclitaxel-based chemotherapy,CT/TT genotype of C3435T site had a better response rate (74.11%) (χ2 =12.556,P<0.05),better curative effect than CC genotype (OR=4.183,95% CI 1.838 -9.521,P<0.05),T allele carriers more efficient than C allele carriers with paclitaxel-based chemotherapy (χ2 =8 .5 0 7 ,P<0 .0 5 ). Conclusion Detection of ABCB1 C3435T gene polymorphisms has a significantly clinical value in predicting the efficacy of taxanes chemotherapy in breast cancer patients.
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Objective To investigate the distribution of the MDR1 exon12 (C1236T), exon21 (G2677T/A) and exon 26 (C3435T) gene polymorphisms in breast cancer patients, and to analyse their relationship with molecular subtypes of breast cancer. Methods The genotyping of C1236T, G2677T/A and C3435T were detected by polymerase chain reaction (PCR)-high resolution melting (HRM) method in 400 cases of breast cancer. The Hardy-Weinberg equilibrium test was used for ge?netic equilibrium distribution of genotype. The molecular subtypes of breast cancer were classified based on St.Gallen Con?sensus 2013. The genotype distributions of C1236T, G2677T/A and C3435T in breast cancer were analyzed. Their relation?ship with molecular subtypes in breast cancer was analyzed as well. Results ①In 400 cases of breast cancer, there were 2, 3 and 2 specimens did not get genotyping results in C1236T, G2677T/A and C3435T genotype detection. The CC, CT and TT genotypes of C1236T accounted for 16.08% (64/398), 44.22% (176/398) and 39.70% (176/398). GG, GT, GA, TT and AT genotypes of G2677T/A accounted for 16.62%(66/397), 44.33%(176/397), 7.05%(28/397), 27.46%(109/397) and 4.54%(18/397). CC, CT and TT genotypes of C3435T accounted for 21.11%(84/398), 56.03%(223/398) and 22.86%(91/398) re?spectively. Hardy-Weinberg genetic equilibrium testing showed that polymorphisms of C1236T, G2677T/A and C3435T had group representation (P0.05). Conclusion C3435T gene polymor?phism can explain more accurately heterogeneity of breast cancer. CT/TT genotype in different molecular subtypes of breast cancer may be more sensitive to drug treatment.
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Objective To examine the effects of genetic polymorphisms in GSTM1, GSTT1 and GSTP1 (rs1695) genes on hematologic toxicities of breast cancer patients receiving Anthracycline/Paclitaxel- based chemotherapy. Methods Multiply PCR technique and High Resolution Melting method were used to examine these 3 genes polymorphsim in female breast cancers (n=252). Results The GSTP1(rs1695) AG/GG genotype was a risk factor forⅢ-Ⅳdegree of neu-trophil toxicity when patients received Paclitaxel-based chemotherapy and Anthracycline-Paclitaxel-based chemotherapy (OR=6.111, 95%CI 1.526-24.469, P0.05);There was no statistic difference onⅢ-Ⅳdegree hematologic toxicities rates between GSTM1(+) and GSTM1(-), GSTT1(+) and GSTT1(-), GSTP1AA and GSTP1AG/GG patients after they receiced Anthracycline-based chemotherapy (P>0.05). Conclusion The genetic polymorphisms in GSTP1(rs1695) can be used as a gene marker for forecasting the chemotherapy, inducing neutrope-nia toxicities in breast cancer patients receiving Paclitaxel-based chemotherapy.
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Objective To study the role of expressions of vascular endothelial growth factor C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3) and lymphatic vessel hyaluronan receptor-1(LYVE-1) on the lymphangio-genesis and prognosis in gastric cancer. Methods The tissue microarray technology was used to detect the expressions of VEGF-C, VEGFR-3 and LYVE-1 in 125 gastric cancer specimens, 96 adjacent normal tissues and 20 benign gastric lesion samples. The lymphatic vessel density (LVD) marked by Podoplanin was detected as well. Results The positive rates of VEGF-C, VEGFR-3 and LYVE-1 in gastric cancer tissues were 62.4%, 56.0%and 58.4%, which were significantly higher than those in adjacent normal tissues (10.4%,12.5%and 9.4%) and benign gastric lesion tissues (20%, 30%and 25%, P<0.05). The LVD score was significantly higher in gastric intra-tumoral and peri-tumoral samples (2.98±0.81 and 4.22±1.09) than that in adjacent normal tissues or benign gastric lesion samples (1.82±0.63 or 0.89±0.45, P<0.01). The LVD score was significantly higher in peri-tumoral samples than that of intra-tumoral samples (P<0.01). There was a positive relationship between expression levels of VEGF-C,VEGFR-3 and LYVE-1 with LVD (P<0.05). The positive expressions of the three indexes were the risk factors of lymph node metastasis and distant metastasis (P<0.05). There was a significantly longer 5-year survival rate in patients with negative expression of the three indexes (P<0.05). Conclusion VEGF-C, VEGFR-3 and LYVE-1 proteins were positively highly expressed in gastric cancer tissues, which were risk factors affecting the progno-sis of gastric cancer. The expression levels of the three indexes can be used to predict the prognosis and lymphangiogenesis of gastric cancer.
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<p><b>OBJECTIVE</b>To study the expression of angiotensin-2 (Ang-2), Tie-2 and vascular endothelial growth factor receptor-2 (VEGFR-2) in colorectal cancer and analyze their relationship with the occurrence, recurrence, metastasis, angiogenesis and prognosis of colorectal cancer.</p><p><b>METHODS</b>Immunohistochemistry with SP method was used to detect the expressions of Ang-2, Tie-2 and VEGFR-2 in 118 colorectal cancer, 40 adjacent normal tissue and 40 benign colorectal lesion specimens.</p><p><b>RESULTS</b>The positivity rates of Ang-2, Tie-2 and VEGFR-2 in colorectal cancer tissue were 74.58%, 69.49%, and 61.02%, respectively, significantly higher than those in the adjacent normal tissues (25.00%, 17.50%, and 17.50%, P<0.05) and benign colorectal lesion tissues (35.00%, 32.50%, and 32.50%, P<0.05). The rates of two or three coexpression were significantly higher than that of a single expression in the cancer tissues (61.02% vs 15.25%). The microvascular density (MVD) of colorectal cancer tissues was 31.43∓10.50, significantly higher than that of the adjacent normal tissues (10.61∓3.76) and benign colorectal lesions (16.89∓3.83) (P<0.05). The expressions of Ang-2, Tie-2, and VEGFR-2 were positively correlated with carcinoembryonic antigen (CEA) and MVD (P<0.05). The expression of Ang-2, but not Tie-2 and VEGFR-2, was positively correlated with CA199. Ang-2, Tie-2, and VEGFR-2 expressions showed significant differences between cases with tumor recurrence/metastasis and those without 5 years after radical mastectomy, and were all positively correlated with the 5-year survival rates (P<0.05).</p><p><b>CONCLUSION</b>Ang-2, Tie-2 and VEGFR-2 are involved in the development, invasion, metastasis, and prognosis of colorectal cancer, and play important roles in the angiogenesis of the tumors.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Angiopoietin-2 , Metabolism , Colorectal Neoplasms , Metabolism , Neovascularization, Pathologic , Metabolism , Prognosis , Receptor, TIE-2 , Metabolism , Vascular Endothelial Growth Factor Receptor-2 , MetabolismABSTRACT
Objective To investigate the expression and the significance of the MDR1, breast cancer resistance protein, lung cancer resistance protein mRNA and corresponding proteins P-gp, BCRP and LRP in breast cancer tissues and adjacent breast tissues. Methods RT-PCR was used to exam the expression of MDR1, BCRP, LRP mRNA in 42 breast cancer tissues and 42 adjacent tissues. IHC was used to exam the expression of P-gp, BCRP and LRP in 126 breast cancer tissues and 42 adjacent tissues, and theirs relationships with clinicopathological parameters in breast cancer, axillary lymph node status and 5-year recurrence and metastasis. Results The relative expression levels of MDR1, BCRP and LRP mRNA were 0.81 ±0.17,0.78 ±0.14,0.79 ±0.13 in breast cancer tissues and 0.33 ±0.11,0.45 ±0.09,0.36 ±0.10 in adjacent tissues respectively. There were significant differences between cancer tissues and adjacent tissues ( t = 4.613, 4.850 and 8. 089, P < 0.01 ). The positivities of P-gp, BCRP and LRP were 41% ( 52/126) ,39% (49/126) and 66% (83/126) in breast cancer tissues. There were significant differences between cancer tissues and adjacent tissues (x2 = 10.147, 7.020, 27.820, P < 0.01 ). The expression of MDR1 mRNA/P-gp was significantly associated with tumor stage and lymph node metastasis ( r = 0.369,0.398, P < 0.05 ). The expression of BCRP (mRNA/protein) was significantly associated with lymph node metastasis (r = 0.355, P < 0.05 ) . The positivities of P-gp were significantly different between 39 recurrence/metastasis patients occurred in 5 years and 32 unrecurrence/nonmetastasis patients in 5 years (x2 = 11.771, P < 0.01 ). The positivities of BCRP and LRP were not significantly different in these two groups(x2 =2.261,0.078,P >0.05). The coincidence rates for expression of MDR1 ,BCRP,LRP mRNA and their proteins in breast cancer tissues were 90.48% ,92.85% and 85.71% respectively (the Kappa values were 0.806,0.751 and 0.697, P < 0.01 ). Conclusions Multidrug resistance is common in breast cancer. The three drug resistance genes and proteins are involved in the formation of multidrug resistance of breast cancer. Detection of multidrng resistance genes in breast cancer may be useful to choose chemotherapy,especially patients with P-gp positive expression are not advised to use the CAF chemotherapy.