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BACKGROUND@#The mortality rate of lung cancer meningeal metastasis is extremely high. Circulating tumor DNA (ctDNA) has been confirmed to be contain the genomic alterations present in tumors and has been used to monitor tumor progression and response to treatments. Due to the presence of blood-brain barrier and other factors, peripheral blood ctDNA cannot reflect the information of brain lesions for patients with meningeal metastases. However, cerebrospinal fluid ctDNA as a test sample can better reflect the genetic status of intracranial tumors and guide clinical targeted treatment of intracranial lesions. This study explored the feasibility of cerebrospinal fluid ctNDA for evaluating non-small cell lung cancer (NSCLC) meningeal metastasis and the potential clinical value of cerebrospinal fluid ctDNA detection in NSCLC meningeal metastasis.@*METHODS@#A total of 21 patients with NSCLC meningeal metastasis were included. Tumor genomic variation was performed on the cerebrospinal fluid and peripheral blood samples of patients by second-generation gene sequencing technology. The situation was examined, and pathological evaluation of cerebrospinal fluid cytology and head magnetic resonance imaging (MRI) enhanced examination were performed.@*RESULTS@#ctDNA was detected in the cerebrospinal fluid of 21 patients. The sensitivity of cerebrospinal fluid ctDNA detection was superior to cytology in the diagnosis of meningeal metastasis (P<0.001). The detection rate and gene mutation abundance of cerebrospinal fluid were higher than plasma (P<0.001). Cerebro-spinal fluid had a unique genetic profile. In 6 patients with dynamic detection, changes of ctDNA allele fraction occurred at the same time or earlier than clinical disease changes, which could timely monitor drug resistance mechanism and relapse trend.@*CONCLUSIONS@#The detection rate of ctDNA in cerebrospinal fluid is higher than that in cytology and imaging. The detection of ctDNA in cerebrospinal fluid can reveal the specific mutation map of meningeal metastasis lesions. The dynamic monitoring of ctDNA in cerebrospinal fluid has hint significance for clinical response of lung cancer patients.
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Objective To explore whether the mitochondrial toxicity markers of peripheral blood mononuclear cells (PBMC)are of significance in monitoring mitochondrial toxicity during highly active antiretroviral therapy (HAART)in patients with acquired immune deficiency syndrome (AIDS).Methods Mitochondrial DNA (mtDNA),mitochondrial thymidine kinase (TK2 )and p53-inducible ribonucleotide reductase small subunit 2 (p53R2 )were selected as mitochondrial toxicity markers.The expression changes of theses markers of PBMC in 22 AIDS patients were detected by real time quantitative polymerase chain reaction (q-PCR)at baseline,48 weeks and 96 weeks after initiation of the treatment. All the patients received stavudine/zidovudine and lamivudine as the mainstay of the HAART regimen. Independent-samples t test was used.Results The relative expression level of mtDNA in patients before HAART was 3.27 ± 0.94,and decreased to 2.16±0.85 at week 48 and 1 .66±0.66 at week 96, respectively.The differences were both significant compared with the level prior to the treatment (t =-3.90,P <0.01 and t =-6.29,P <0.01 ,respectively).The relative expression level of TK2 before HAART was 0.37 ±0.13,and increased to 1 .01 ±0.25 at week 48 and 2.13 ±0.61 at week 96 of the treatment.After pairwise comparisons of the three pairs of data (pre-HAART vs week 48 of the treatment,pre-HAART vs week 96 of the treatment and week 48 vs week 96 of the treatment),the differences were all significant (t = 10.77,8.00 and 3.56,respectively;all P < 0.01 ).The relative expression level of p53R2 was 0.86±0.39 before HAART,but gradually increased to 2.36 ±1 .14 and 7.73±0.65 ,respectively,at week 48 and week 96 of the treatment.The differences in p53R2 levels among three groups after pairwise comparison were all significant (t=3.27,12.26 and 13.25,respectively;all P < 0.01 ).Conclusions The expression levels of mtDNA,TK2 and p53R2 in PBMC could change significantly during HAART in AIDS patients,which might be used as indexes for monitoring mitochondrial toxicity.
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Objective To evaluate the clinical value of Gli1 expression in breast cancer.Methods Immunohistochemistry was used to analyze the protein expression of Glil in breast cancer tissues,adjacent cancer tissues and metastatic lymph node.Results ①Breast cancer tissues expressed high levels of Gli1 compared to paracancerous tissues.Gli1 overexpression was found in 93.3％ of breast cancer tissues with recurrence and metastasis and 81.2％ in breast cancer tissues without metastasis.Gli1 expression could be detected either in interstitial tissues of cancer or in cancer tissues,or in both.The rate of Gli1 overexpression was 89.3％ in the inter stitial tissues of the primary cancer with recurrence and metastasis and 13.4％ in interstitial tissues of breast cancer tissues without metastasis.The difference had statistical significance(P ＜ 0.001).②High expression of Gli1 in breast cancer tissues was closely related to early recurrence and metastasis of breast cancer.Gli1 expression displayed a significant correlation with relapse-free survival (RFS) (P =0.046).The recurrence rate was 17.8％ in the high expression group in breast cancer tissue,whereas it was only 6.2％ in the low expression group(P =0.046),while the recurrence rate was 31.2％ in the high expression group in interstitial tissues,whereas it was only 11.1％ in the low expression group(P ＜ 0.001).Conclusion The high expression of Gli1 in breast primary cancer tissues,metastasis tissues and interstitial tissues is associated with recurrence and metastasis of breast cancer.
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Objective To investigate the prevalence and risk factors of highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (LD) in patients with acquired immunodeficiency syndrome (AIDS) treated with HAART in China.Methods A total of 137 AIDS patients treated with HAART for more than 2 years were analyzed.Sixteen clinical parameters (including gender,age,baseline body mass index,baseline human immunodeficiency virus [HIV] viral load,stage of disease,routes of HIV transmission,baseline CD4+ T lymphocyte count,white blood cell count,fasting plasma glucose level,serum triglycerides level,serum cholesterol level and other laboratory results,and HAART regimens) that might be associated with HAART-LD occurrence were evaluated using Cox proportional hazards models.Results HAART regimens were significantly correlated with HAART-LD (P=0.031),while the remaining 15 factors were not associated with the risk of HAART-LD (all P＞0.05).Patients who received stavudine d4T)-containing regimen was 2.684 times more likely to develop HAART-LD than patients who received zidovudine (AZT)-containing regimen (95 ％ CI:1.302-5.531,P=0.007) ; HAART-LD prevalence rates were gradually increased with treatment duration in both groups.First HAART-LD was seen at 24 weeks in both d4T group and AZT group,and the prevalence rates were 2.7％,1.6％ at 24 weeks,27.0％,7.9％ at 48 weeks and 37.8％,15.9％ at 96 weeks respectively.The prevalence of HAART-LD in d4T group was much higher than that in AZT group and the difference was statistically significant (x2 =8.285,P=0.004).Conclusions HAART regimen is an independent predictor of HAART-LD.HAART-LD tend to occur more frequently in patients treated with d4T or AZT,especially d4T.Our study recommends to avoid the use of d4T-contained HAART regimen.
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ObjectiveTo investigate the clinical significance of determination of 20S proteasomal activities changes in circulating white blood cells (WBC) in patients with advanced gastric carcinoma.MethodsThe 20S proteasomal activities in circulating WBC separated from 80 patients with advanced gastric carcinoma were determined by 20S proteasome assay kit; the concentrations of interleukin-6(IL-6) in plasma were determined by radioimmunoassay method.The result was compared with that of 11 healthy volunteers.ResultsThe proteasomal activities in circulating WBC[(38.26 ±9.23),(101.85 ±27.63)pmol AMC/ ( s *mg pro) ] and concentrations of IL-6 [ (23.89 ± 6.76),(72.52 ± 20.71 ) ng/L ] of healthy volunteers and the patients with advanced gastric carcinoma had statistical significance (P ＜ 0.01 ).The proteasomal activities and the concentration of IL-6 were correlated with age,pathological type,weight changes,Karnofsky score and disease severe degree(P ＜ 0.01 );while they had no relationship with sex(P ＞ 0.05).Cox's proportional hazard regression model demonstrated that pathological type,Karnofsky score and proteasomal activities were the independent risk factors affecting the survival of patients with advanced gastric carcinoma (P ＜0.01 or ＜0.05).20S proteasomal activities and the concentration of IL-6 had positive correlation (r =0.691,P =0.000).ConclusionsThe proteasomal activites in circulating WBC and the concentration of IL-6 in plasma increase and are correlated with age,pathological type,weight changes,Karnofsky score and disease severe degree.Proteasomal activities in circulating WBC can be used as the prognostic reference factor of advanced gastric carcinoma.20S proteasomal activities and the concentration of IL-6 have positive correlation.
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0.05). The median duration of survival was 11.5 months for TEP gr oup versus 8.5 months for EP group (P0.05,no statistical difference). The main toxicity wa s myelosuppression for the two groups.The incidence rate of Ⅲ～Ⅳ degree neutro p enia and thrombocytopenia was higher in the TEP group than that in the EP group( P