Circulating metastasis associated in colon cancer 1 transcripts in gastric cancer patient plasma as diagnostic and prognostic biomarker

AIM: To evaluate the diagnostic and prognostic value of circulating Metastasis Associated in Colon Cancer 1(MACC1) transcripts in plasma of gastric cancer patients.METHODS: We provide for the first time a blood-based assay for transcript quantification of the metastasis inducer MACC1 in a prospective study of gastric cancer patient plasma.MACC1 is a strong prognostic biomarker for tumor progression and metastasis in a variety of solid cancers.We conducted a study to define the diagnostic and prognostic power of MACC1 transcripts using 76 plasma samples from gastric cancer patients,either newly diagnosed with gastric cancer,newly diagnosed with metachronous metastasis of gastric cancer,as well as follow-up patients.Findings were controlled by using plasma samples from 54 tumor-free volunteers.Plasma was separated,RNA was isolated,and levels of MACC1 as well as S100A4 transcripts were determined by quantitative RT-PCR.RESULTS: Based on the levels of circulating MACC1 transcripts in plasma we significantly discriminated tumorfree volunteers and gastric cancer patients(P < 0.001).Levels of circulating MACC1 transcripts were increased in gastric cancer patients of each disease stage,compared to tumor-free volunteers: patients with tumors without metastasis(P = 0.005),with synchronous metastasis(P = 0.002),with metachronous metastasis(P = 0.005),and patients during follow-up(P = 0.021).Sensitivity was 0.68(95%CI: 0.45-0.85) and specificity was 0.89(95%CI: 0.77-0.95),respectively.Importantly,gastric cancer patients with high circulating MACC1 transcript levels in plasma demonstrated significantly shorter survival whencompared with patients demonstrating low MACC1 levels(P = 0.0015).Furthermore,gastric cancer patients with high circulating transcript levels of MACC1 as well as of S100A4 in plasma demonstrated significantly shorter survival when compared with patients demonstrating low levels of both biomarkers or with only one biomarker elevated(P = 0.001).CONCLUSION: Levels of circulating MACC1 transcripts in plasma of gastric cancer patients are of diagnostic value and are prognostic for patient survival in a prospective study.

Human primary muscle stem cells regenerate injured urethral sphincter in athymic rats

Background:The aim of the study was to demonstrate the efficacy of human muscle stem cells(MuSCs)isolated using innovative technology in restoring internal urinary sphincter function in a preclinical animal model.Methods:Colonies of pure human MuSCs were obtained from muscle biopsy speci-mens.Athymic rats were subjected to internal urethral sphincter damage by electro-cauterization.Five days after injury,2×105 muscle stem cells or medium as control were injected into the area of sphincter damage(n=5 in each group).Peak bladder pressure and rise in pressure were chosen as outcome measures.To repeatedly obtain the necessary pressure values,telemetry sensors had been implanted into the rat bladders 10 days prior to injury.Results:There was a highly significant improvement in the ability to build up peak pressure as well as a pressure rise in animals that had received muscle stem cells as compared to control(p=0.007)3 weeks after the cells had been injected.Only mini-mal histologic evidence of scarring was observed in treated rats.Conclusion:Primary human muscle stem cells obtained using innovative technology functionally restore internal urethral sphincter function after injury.Translation into use in clinical settings is foreseeable.

Dysferlin缺陷性肌营养不良症:gadofluorine M在小鼠模型MRI的适合性

目的 比较gadofluorine M和Gadomer在7．0T MRI上评估Dysferlin缺陷性肌营养不良症的有效性。方法 实验经当地审查委员会批准通过。患Dysferlin缺陷性肌营养不良症的SJL／J小鼠（n=24）和对照组C57BL／6小鼠（n=24）在12～15周（青年）或30周（老年）静脉注射动态增强对比剂gadofluorine M 2 μmol或Gadomer 4 μmol，在静注前、中、后行MRI预反转自由稳态进动序列成像。

Phosphatidylinositol 4-kinase β mutations cause nonsyndromic sensorineural deafness and inner ear malformation

Congenital hearing loss is a common disorder worldwide.Heterogeneous gene variation accounts for approximately 20-25%of such patients.We investigated a five-generation Chinese family with autosomaldominant nonsyndromic sensorineural hearing loss(SNHL).No wave was detected in the pure-tone audiometry,and the auditory brainstem response was absent in all patients.Computed tomography of the patients,as well as of two sporadic SNHL cases,showed bilateral inner ear anomaly,cochlear maldevelopment,absence of the osseous spiral lamina,and an enlarged vestibular aqueduct.Such findings were absent in nonaffected persons.We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4 KB gene(p.Gln121 Arg)encoding phosphatidylinositol 4-kinaseβ(PI4 KB)from the patients in this family.In addition,3 missense PI4 KB(p.Val434 Gly,p.Glu667 Lys,and p.Met739 Arg)mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases.No such mutations were present within 600 Chinese controls,the 1000 genome project,gnom AD,or similar databases.Depleting pi4 kb m RNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment,mimicking the patient phenotypes.Moreover,overexpression of 4 human missense PI4 KB mutant m RNAs in zebrafish embryos resulted in impaired hearing function,suggesting dominant-negative effects.Taken together,our results reveal that PI4 KB mutations can cause SNHL and inner ear malformation.PI4 KB should be included in neonatal deafness screening.