The expression of MDR1, P- gp and GST- Pi biomarkers in peripheral blood from patients with refracto- ry epilepsy / 中国神经精神疾病杂志

Objective The pathogenesis of intractable epilepsy was explored by examining the expression of the P-gp , GST-Pi as well as MDR1 in peripheral blood of the patients with intractable epilepsy. The potential of the above mentioned three genes as the biomarkers for treatment of intractable epilepsy was investigated. Methods Thirty-one sub?jects with refractory epilepsy, 33 subjects under good circumstances by antiepileptic drugs, and 37 healthy subjects were included in the present study. fluorescence quantitative polymerase chain reaction and flow cytometry were used to detect mRNA levels of MDR1 and GST-Pi and P-gp of MDR1 in the peripheral blood of the patients, respectively. Results The expression levels of MDR1 and GST-Pi were significantly higher in the AEDs intractable group(1.36±0.14,0.585±0.257) than in the treatment group(0.82±0.15,0.309±0.217, P<0.05)The expression levels of MDR1 and GST-Pi were signifi?cantly higher in the AEDs treatment group than in the normal group(0.27±0.07,0.134±0.223,P<0.05). The expression levels of P-gp were significantly higher in the AEDs of the intractable group(0.104±0.084)than in the treatment group (0.063 ± 0.030, P<0.05). The GST-Pi gene expression levels were significantly higher in three(0.535 ± 0.256)or two (0.425±0.254)kinds of antiepileptic drugs combination therapy than in single drug treatment(0.267±0.265, P<0.05). Leucocyte P-gp levels were significantly higher in combination therapy of three kinds of antiepileptic drugs(0.141 ± 0.096)than in combination therapy of two kinds of antiepileptic drugs(0.071±0.020)or in monotherapy(0.050±0.020, P<0.05). Conclusion MDR1 and GST-Pi gene expression levels of peripheral blood can be used as the reference in?dex for treatment of intractable epilepsy and the resistant index of combination treatment for intractable epilepsy.

Immunohistochemical Expression of Placental Form of Glutathione S-transferase (GST-pi) in Fetal Skin / 대한피부과학회지

BACKGROUND: Glutathione S-transferases(GST) are a family of multi-functional enzymes involved in cellular detoxification and excretion of a variety of exogenous and endogenous toxic or carcinogenic compounds. The GST family has been divided into three classes, alpha, mu, and pi, based on substrate specificity and sequence homology. GST-pi is an acidic type and predominant in skin, small intestine, breast, lung and prostate. The overexpression of GST-pi associated with skin tumor and tumor-like lesion suggests that GST-pi is a major detoxifying enzyme in skin tumors. OBJECTIVE: The purpose of this study was to observe the expression and the distribution pattern of GST-pi in the human fetal skin. METHODS: Skin was obtained from the scalp, chest, and sole of 49 human fetuses, ranging from 8th to 40th weeks of gestational age. Immunohistochemical staining was performed using avidin biotin peroxidase complex method on paraffin embedded tissue using antirabbit polyclonal antibody against the human GST-pi. RESULTS: GST-pi was expressed in intermediated layer of epidermis at 8th week, and gradually increased in strength of expression stronger in suprabasal layer. In hair unit, GST-pi was expressed in sebaceous gland, bulge, hair matrix cell and outer root sheath cell from 15th week. In eccrine gland, also GST-pi was expressed in central differentiated cells of intradermal eccrine duct from 18th week, and in terminal duct and acini from 26th week of fetal age. CONCLUSION: GST-pi was expressed from the 8th week of gestation suggesting that GST-pi plays an important role in detoxification for the protection of the skin in fetal stage from the various toxic agent.

Multidrug Resistance-Related Gene Expressions in Germ Cell Tumors in Testis / 대한비뇨기과학회지

The development of drug resistance is a major obstacle in effective cancer chemotherapy. Multidrug resistance(MDR) is a widely studied phenomenon of interest to both clinicians and research workers because many different cancer chemotherapeutic agents are involved and the genetic basis of MDR is understood to a large extent. Several studies show that the P-glycoprotein (P-gp), multidrug resistance-associated protein(MRP), glutathione-s-transferase-pi(GST-pi), and DNA topoisomerase II(topo II) have a complex role for the malignant phenotypes and MDR. Clearly, there is a need to investigate links between the diverse characteristics of tumors and the emergence of drug resistance. We have therefore used reverse transcription-polymerase chain reaction(RT-PCR) assay to analyze expressions of MDR-related genes including the mdr1, MRP, topo II and GST-t gene in normal testis and testis tumors. The results are as follows: 1. The expression levels of topo II and GST-n genes in testis tumors, especially in the nonseminomatous germ cell tumor(NSGCT), were significantly higher than in normal testis(p=0.015 and 0.025, respectively). 2. The MDR-related gene expressions in testis tumors did not appear to be correlated with stage(p>0.05 in each case) and chemotherapy status(p>0.05 in each case). 3. MRP expression levels in primary tumors were much higher than in metastatic tumors. 4. In NSGCT, the coexpressions of the topo II and GST-r or MRP genes were significantly correlated but, seminoma showed no correlation between MDR-related genes in the same sample. Although the mechanism of these connection are not known, the results suggest that these expression patterns and higher GST-rexpression in NSGCF compared to seminoma confer diverse characteristics including difference in the presentation of tumor markers and the responsiveness to chemotherapy on NSGCF and seminoma.

Immunohistochemical Observation of Placental Form of Glutathione S-Transferase in Squamous Cell Carcinoma

Glutathione S-Transferase (GST) is a conjugation enzyme in the metabolism of exogenous and endogenous lipophilic compounds for their excretion and detoxification. Acidic isozyme of GST, GST-Pi, has been recognized as a preneoplastic marker in the experimental hyperplastic nodules of liver in rats, and GST-Pi is abundant in the squamous cells of the skin, also. This histochemical study was carried out to evaluate the distribution and the relationship between the differentiation status of squamous cells in dysplastic or neoplastic epithelium in various organs. The human placental form of glutathione S-transferase (GST-Pi) were stained immunohistochemically with specific anti GST-Pi rabbit antibody in 23 cases of human squamous cell carcinomas. The patients consisted of 14 cases from the uterine cervix, 3 cases from the esopahgus, 3 cases from the lung and 3 cases from the larynx. The results obtained were as follows; 1. Basal cells in normal mucosa were stained negative for GST-Pi while superficial keratinocytes were stained moderately positive. Basal dysplastic cells were stained negatively or weakly positive. Carcinoma cells especially large cells either keratinizing or nonkeratinizing were stained moderately to strongly. Carcinoma cells surrounding keratin pearl were strongly reacted with GST-Pi than other carcinoma cells. 2. Differentiated cells of squamous cell carcinoma showed moderate to strong positive reaction to GST-Pi staining irrespective of its site of origin. 3. Therefore, Immunohistochemical staining pattern of GST-Pi in various squamous carcinoma cells showed similar immunohistochemical reaction to the GST-pi, which is closely correlated to the degree of differentiation, keratinigation and also suggested that squamous carcinoma cells had abundant GST-Pi related detoxifying system.