Effect of breast conserving surgery on neurotensin and its receptor 1 in patients with breast cancer / 国际外科学杂志

Objective To investigate the effect of breast conserving surgery on neurotensin (NTS) and its receptor 1(NTR1) in patients with breast cancer.Methods From May 2012 to May 2015,200 patients with breast cancer,aged 44.7 years(range,32-56 years),were treated at Tiantan Hospital,Capital Medical University.All patients were divided into control group (n =100) and observation group (n =100).The patients in the control group were treated with radical operation and the patients in the observation group were treated with breastconserving surgery.The positive rate of NTS and NTR1 before and 1 week after operation,WHOQOL-100 (It includes four aspects:physiological state,psychological state,environmental condition and social function) 1 d before surgery,3 months and 6 months after surgery,and the incidence of postoperative complications 1 week after surgery were compared between the two groups.Measurement data with normal distribution were described as mean± standard deviation (Mean ± SD) and analyzed by the t test.Count data were analyzed by chi-square test.Results The positive rate of NTS (17.00％) in the observation group was significantly lower than that in the control group (36.00％) (t =9.267,P =0.002),The positive rate of NTR1 (19.00％) was significantly lower than that in the control group (33.00％) (t =5.094,P =0.024).The physiological status,psychological state,environmental condition and social function of 3 months after surgery of the observation group were (62.57 ± 5.73),(63.48 ±5.91),(68.73 ±6.32),(64.06 ±5.94) scores,respectively,and the control group were (53.47 ±5.38),(55.62 ±5.54),(60.38 ±6.14),(55.86 ±5.66) scores,respectively,showing statistically significant differences between the two groups (P ＜ 0.05).The physiological status,psychological state,environmental condition and social function of 6 months after surgery were (73.74 ±t 6.19),(76.27 ± 6.32),(78.85 ±6.77),(73.53 ±6.58) scores in the observation group,and (64.18 ±5.67),(67.38 ±6.02),(69.64 ± 6.43),(63.28 ± 6.17) scores in the control group,showing statistically significant differences between the two groups (P ＜ 0.05).The incidence of postoperative complications in the observation group (6.00％) was significantly lower than that in the control group (18.00％) (P ＜ 0.05).Conclusion Breast conserving surgery can reduce the expression level of NTS and NTR1 in breast cancer patients,It is related to reducing the incidence of postoperative complications and improving the quality of life of patients.

Binding chemistry and molecular heterogeneity of neurotensin binding protein(s)/receptor in adult chicken tissues.

The study focuses on the importance of Tyr11 amino acid (AA) and subsequent stereochemistry involved in the binding process of neurotensin (NT) with its receptor (NTR)/binding protein(s) as well as the size heterogeneity. Using the binding of 125I-NT with several chicken tissues, it is identified that one of the crucial factors behind all high affinity (Kd ~10 pM) interactions is due to phenolic-OH (Φ-OH) at the para (p) position of Tyr11 within RRPYIL-CO2H (NT8-13) sequence. Replacing the p-OH only in Tyr11 by substituting with p-Cl, p-F and p-NH2 results in significant change of the binding affinity (Kd); p-OH ≈ p-NH2 (~10 pM), p-Cl (~100 pM), p-F (~120 pM). Interestingly, p-NH2 equals to p-OH displaying the highest affinity. Experiments conducted by binding several of the 125I-azido–NT analogs having azido group attached at different positions within the NT molecule have further confirmed the necessity of RRPYIL sequence for high affinity ligand-receptor interaction. The role of Tryp11 in place of Tyr11 in addition to the results above establishes a significant possibility of H–bonding occurring between p-OH of NT and NTR inside the docking space. Photo labeling of the liver tissue by substituted 125I-Y3-azido-NT analogs shows several specifically labeled bands with considerable range of molecular weight (Mr ~90-30 kDa) variations. These results indicate the existence of molecular heterogeneity concerning the sizes of NTR or else any NT binding proteins in the avian tissues. Further, the study has revealed that besides liver, several other chicken tissues also express similar specific high affinity binding (Kd ~20 pM) with varying capacities (Bmax). The order for Bmax is: liver (1.2 pMol/mg) gall bladder (1.03 pMol/mg) > spleen (0.43 pMol/mg) > brain (0.3 pMol/mg) > colon lung (0.15 pMol/mg). In all cases, the binding was reduced by GTPgS (ED50 ~ 0.05 nM), NEM (ED50 ~ 0.50 mM) and NaCl (ED50 ~30 mM), indicating the existence of NTR identical to the mammalian type-1.

An Association Study of Neurotensin Receptor Gene's Polymorphism with Schizophrenia / 신경정신의학

OBJECTIVES: Neurotensin (NT), of which functions are evoked by its interaction with neurotensin receptors (NTR), coexists with mesolimbic dopamine and regulates endogenous dopamine release. Recent studies have shown that NT with NTR exerts neuroleptic-like activity within the central nervous system and may play an important role in the pathogenesis and in the treatment of schizophrenia. We have examined the genetic association between schizophrenia and tetranucleotide repeat polymorphism in the 3'-flanking region of the NTR gene to investigate the possible contribution of the NTR gene to the schizophrenia susceptibility. METHODS: Among 23 alleles identified, the subjects were 120 patients (male 91, female 29) with schizophrenia and 106 normal healthy controls (male 84, female 22). They were unrelated native Korean. PANSS was used to determine positive or negative subgroup in the schizophrenic patients.Using polymerase chain reaction and polyacrylamide gel electrophoresis, tetranucleotide repeat polymorphism (CCTT and CTTT) in the 3'-flanking region of NTR gene was observed. For a comparison of NTR gene's allelic frequencies between patients with schizophrenia and normal healthy controls, chi-square test and Bonferroni's correction was performed. RESULTS: The frequency of A10 allele (base pair size=399) was significantly higher in normal healthy controls than schizophrenia (x2=16.4902, df=1, p<.000). In the comparison between schizophrenic patients with negative symptoms and normal controls, the frequency of A10 allele was significantly higher in normal healthy control subjects than patients with schizophrenia (x2=21.33, df=1, p<0.001). In the case of male, the frequency of A10 allele of schizophrenia was significantly higher than normal controls (x2=13.71, df=1, p<0.001). CONCLUSIONS: NTR gene was negatively associated with schizophrenia. NTR gene's tetranucleotide repeat polymorphism may provide some protective function against schizophrenia.