ABSTRACT
Objective To explore the effect of gene mutations of arsenic transport proteins-muhidrug resistance-associated proteins(MRP1 and MRP2)on phenotype of endemic arsenic poisoning.Methods Two hundreds and thirty-nine rural residents in 3 villages of Shuocheng Region,Shanxi Province were interviewed and examined by simple random sampling who had been lived there for 20 yearn at least.All the objects were divided into two groups on the basis of clinical examination with"The Standard Diagnosis of Endemic Arsenic Poisoning" (WT/S 211-2001):subjectives with skin lesion as a arsenic poisoning group and without skin lesion as a control group. One hundred and ninety-three blood samples were collected from each participanL Seventy-five arsenic poisoning cases and 118 controls were detected the gene mutations in the 2,17,23 exons of M RPI and the 10,18,31 exons of MRP2 by PCR-single strand conformation polymorphism (PCR-SSCP) and compared by multivariate Logistic regression model. Results Seventy-five cases and 164 controls underwent questionnaires. Age[ (58.85±11.26) vs (45.73±11.92),OR = 3.378,P ＜ 0.05],gender[male,57.3%(43/75)vs 27.4%(45/164),OR = 3.553,P＜ 0.01 ],smoking[46.7%(35/75) vs 21.3%(35/164),OR = 3.225,P ＜ 0.01 ],drinking[ 17.3%(13/75) vs 8.5% (14/164),OR = 1.836,P ＞ 0.05],vegetable and fruit intake[5.3%(4/75) vs 9.1%(15/164),OR = 0.560,P ＞ 0.05],egg and meat intake[34.7%(26/75) vs 30.5%(50/164),OR = 1.210,P ＞ 0.05],exposure of pesticide [41.3%(31/75) vs 29.3%(48/164),OR = 1.864,P ＜ 0.05] were tested by Logistic regression model. There was no gene mutation detected in the 23 exon of MRP1 and the 18 exon of MRP2. The gene mutations frequencies of the 2 exons of MRP1 in arsenic poisoning and control groups were 8.00% (6/75) and 5.93% (7/118),respectively;they were 13.33%(10/75) and 8.47%(10/118) of the 17 exons of MRP1,respectively;they were 22.67%(17/75) and 18.64%(22/118) of the 10 exons of MRP2,respectively;they were 5.33%(4/75) and 2.54%(3/118) of the 31 exons of MRP2,respectively. There was no significant difference between two groups(x2 = 0.312,1.165,0.460, 2.794,respectively,all P ＞ 0.05). After age,gender,smoking,drinking,nutritional level and exposure of pesticide being adjusted by multivariate Logistic regression model,there was no significant difference between two groups (OR = 0.803,1.892,2.388,1.098,respectively,all P ＞ 0.05). Conclusions The gene mutations of 2,17,23 exons of MRPI and the 10,18,31 exons of MRP2 may have no effect on the phenotype of endemic arsenic poisoning.
ABSTRACT
Objective To investigate the expression and sensitivity of 6 muhidmg resistance gene products(MDR) : GST-π、LRP、MRP、Topo Ⅱ、P-gp、TS in gastric cancer during neoadjuvant chemotherapy. Methods Expression of the 6 muhidrug resistance gene was detected by immunohistoehemistry in 35 cases of stomach cancer tissues before and after neoadjuvant chemotherapy. The relationship between muhidrug resistance gene and neoadjuvant chemotherapy was analyzed. All patients were given FOLFOX4, and the effects were evaluated according to World Health Organization criteria. Results The overall response rates to chemotherapy was 46%, expression of the 6 mtdtidrug resistance gene in 35 cases of stomach cancer tissues were as follows:GST-π was 40% ,LRP was 69% ,MRP was 34% ,Topo Ⅱ was 37% ,P-gp was 86%, TS was 40%, expression of the 6 muhidrug resistance gene did not change during neoadjuvant chemotherapy; GST-π、LRP、MRP、Topo Ⅱ、P-gp were not correlated with chemotherapy sensitivity(P > 0.05), while TS was significantly correlated with chemotherapy sensitivity (P = 0.0048). Conclusion FOLFOX4 does not effect a change in the expression of the 6 muhidrug resistance gene: GST-π、LRP、MRP、Topo Ⅱ、P-gp and TS, while TS is significantly correlated with gastric cancer chemotherapy sensitivity.
ABSTRACT
Objective To investigate the expression of muhidrug resistance-related protein 1 (MRP1),lung resistance-related protein(LfuP)and glutathione S-transferase-π(GST-π)in carcinoma of the gallbladder and cholangiocarcinoma. Methoils MRP1,LRP,GST-πwere measured in experimental group(18 cases of carcinoma of the gallbladder,36 CSSeS Of cholangiocarcinoma)and control group(13cases of cholecystitis and cholangeitis)by immunohistochemistry.Statistical analysis used chi-square test and spearman test. Results The positive rate of MRP1,LRP,GST-π in carcinoma of the gallbladder and eholangiocarcinoma were 72%(13/18),78%(14/18),61%(11/18)and 86%(31/36),75%(27/36),69%(25/36),respectively,significantly higher than those of 23%(3/13),23%(3/13),23%(3/13)(X2=4.5,P＜0.05)in control group.The expression of LRP[93%(13/14)]in pafients＞60 years old was significantly higher than 64%(14/22)in patients younger than 60 yrs old(x2=3.9,P ＜0.05).In addition,their expression was not related to gender,age,staging,tumor differentiation and lymph node metastasis(P＞0.05).The expression of MRP1 was related with tllose Of GST-π,Spearman correlation coefficient=0.569(P＜0.05).Conclusions MRP1,LRP,GsT-π were over expressed in various degrees in carcinoma Of the gallbladder and cholangiocarcinoma witllout chemotherapy.and related to the primary muhidrug resistance Of cholangiocarcinoma and carcinoma of the gallbladder.