Simultaneously quantifying hundreds of acylcarnitines in multiple biological matrices within ten minutes using ultrahigh-performance liquid-chromatography and tandem mass spectrometry / 药物分析学报

Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances.Here,we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry(UPLC-MS/MS).This enabled simultaneous quantification of 1136 acyl-carnitines(C0-C26)within 10-min with good sensitivity(limit of detection＜0.7 fmol),linearity(cor-relation coefficient＞0.992),accuracy(relative error＜20％),precision(coefficient of variation(CV),CV＜15％),stability(CV＜15％),and inter-technician consistency(CV＜20％,n=6).We also established a quantitative structure-retention relationship(goodness of fit＞0.998)for predicting retention time(tR)of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters(tR,ion-pairs,and collision energy).Furthermore,we quantified 514 acylcarnitines in human plasma and urine,mouse kidney,liver,heart,lung,and muscle.This provides a rapid method for quantifying acyl-carnitines in multiple biological matrices.

Risk factors for the prognosis of pediatric medulloblastoma: a retrospective analysis of 40 cases

OBJECTIVES: In this study, we evaluated the association of molecular subtypes, clinical characteristics and pathological types with the prognosis of patients with medulloblastoma. METHODS: We analyzed forty patients with medulloblastoma who underwent surgical resection at our center between January 2004 and June 2014. Risk factors associated with survival, disease progression and recurrence were analyzed with a univariate Cox regression analysis, and the identified significant risk factors were further analyzed by Kaplan-Meier survival curves. RESULTS: Factors associated with overall survival included M stage (p=0.014), calcification (p=0.012), postoperative treatment, postoperative Karnofsky Performance Scale (KPS) score (p=0.015), and molecular subtype (p=0.005 for WNT and p=0.008 for SHH). Number of symptoms (p=0.029), M stage (p<0.001), and postoperative radiotherapy (p=0.033) were associated with disease progression. Patients with the WNT or SHH subtype had better survival outcomes than patients with non-WNT/SHH subtypes. Risk factors for disease progression-free survival were symptoms >2 and ≥M1 stage without postoperative radiotherapy. The risk of recurrence increased with advanced M stage. Protective factors for recurrence included M0 stage and a combination of chemotherapy and radiotherapy. CONCLUSION: We identified the risk factors associated with survival, disease progression and recurrence of medulloblastoma patients. This information is helpful for understanding the prognostic factors related to medulloblastoma.

Clinico pathologic characteristics and molecular phenotypes of young breast cancer patients and their clinical significance / 中国肿瘤临床

Objective:To study the clinico-pathologic characteristics, molecular phenotypes, and prognosis of young breast can-cer patients. Methods:Data from 133 low-age (age≤30 years) young breast cancer patients and 117 young (31 years≤age≤35 years) breast cancer patients who underwent surgery between January 2002 and December 2009 were reviewed. Cases of the middle and old-age elderly (age>35 years) breast cancer patients during the corresponding period were randomly selected as matched controls. The clinico-pathologic characteristics, molecular phenotypes, and prognosis were retrospectively analyzed. Results:The low-age young and young breast cancer patients significantly differed from the elderly patients in terms of tumor size, lymph node metastasis, histological grading, molecular phenotype, and relapse (P<0.05). The low-age young patients are more vulnerable to have triple-negative breast can-cer, recurrence, and distant metastasis (P<0.001). Moreover, the low-age young patients have lower overall survival and disease-free survival than the other groups (P<0.05). Conclusion:Young breast cancer patients have poor prognosis compared with the elderly. Ear-ly screening and prompt treatment are necessary for young breast cancer patients.

Immunohistochemical profile of high-grade ductal carcinoma in situ of the breast

OBJECTIVE: To determine the frequency of the immunohistochemical profiles of a series of high-grade ductal carcinoma in situ of the breast. METHODS: One hundred and twenty-one cases of high-grade ductal carcinoma in situ, pure or associated with invasive mammary carcinoma, were identified from 2003 to 2008 and examined with immunohistochemistry for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5, and epidermal growth factor receptor. The tumors were placed into five subgroups: luminal A, luminal B, HER2, basal-like, and “not classified”. RESULTS: The frequencies of the immunophenotypes of pure ductal carcinoma in situ were the following: luminal A (24/42 cases; 57.1%), luminal B (05/42 cases; 11.9%), HER2 (07/42 cases; 16.7%), basal-like phenotype (00/42 cases; 0%), and “not classified” (06/42 cases; 14.3%). The immunophenotypes of ductal carcinoma in situ associated with invasive carcinoma were the following: luminal A (46/79 cases; 58.2%), luminal B (10/79 cases; 12.7%), HER2 (06/79 cases; 7.6%), basal-like (06/79 cases; 7.6%), and “not classified” (11/79 cases; 13.9%). There was no significant difference in the immunophenotype frequencies between pure ductal carcinoma in situ and ductal carcinoma in situ associated with invasive carcinoma (p>0.05). High agreement was observed in immunophenotypes between both components (kappa=0.867). CONCLUSION: The most common immunophenotype of pure ductal carcinoma in situ was luminal A, followed by HER2. The basal-like phenotype was observed only in ductal carcinoma in situ associated with invasive carcinoma, which had a similar phenotype. .