Individualized Chemotherapy in Advanced NSCLC Patients Based on mRNA Levels of BRCA1 and RRM1

Objective： Experimental evidence suggests that the overexpression of breast cancer-specific tumor suppressor protein 1 （BRCA1） gene enhances sensitivity to docetaxel and resistance to cisplatin and ribonucleotide reductase M1 （RRM1） gene overexpression enhances resistance to gemcitabine. To further examine the effect of BRCA1 and RRM1 mRNA levels on outcome in advanced non-small cell lung cancer （NSCLC）, we performed this non-randomized phase II clinical trial which tested the hypothesis that customized therapy would confer improved outcome over non-customized therapy. Methods： RNA was isolated from fresh tumor tissue. Patients received chemotherapy regimen based on their BRCA1 and RRM1 mRNA levels： both low-cisplatin plus gemcitabine （GP）; both high-vinorelbine plus cisplatin （NP）; BRCA1 low and RRM1 high-cisplatin plus docetaxel （TP）; BRCA1 high and RRM1 low-vinorelbine plus gemcitabine （GN）. Results： From Dec 2005 to Nov 2008, 94 metastatic and locally advanced NSCLC patients from our institute were enrolled in this study. The median age was 58 years old. Among them, 21 patients received GP, 30 patients received TP and 43 patients received NP chemotherapy. GP group had a higher response rate, and longer median time to progression （TTP） and median overall survival （OS） time than the other 2 groups. The response rates in the GP, TP and NP groups were 42.9%, 36.7% and 27.9%, respectively （P=0.568）. The median TTP was 5.6, 5.0, 4.8 months （P=0.975）, respectively, and the median OS time was 12.5, 11.0, 9.7 months （P=0.808）, respectively. Conclusion： Chemotherapy customized according to BRCA1 and RRM1 expression levels is associated with higher response rate and longer TTP and OS time in the GP group. This suggests that BRCA1 and RRM1 mRNA levels could be used as biomarkers in individual therapy in NSCLC.

Hepatocellular carcinoma with concomitant hepatic angiomyolipoma and cavernous hemangioma in one patient

The risk of developing hepatocellular carcinoma(HCC) is strongly associated with hepatitis B virus infection.Hepatic angiomyolipoma(AML),a rare benign tumor,is composed of a heterogeneous mixture of adipose cells,smooth muscle cells and blood vessels.Here,we report the case of a 44-year-old man who developed HCC with a concomitant hepatic AML and a cavernous hemangioma,in the absence of cirrhosis.To our knowledge,based on an extensive literature search using the www.pubmed.gov website,this is the first report of an HCC case with both concomitant AML and cavernous hemangioma at the same position in the liver.The presence of the hepatitis B surface antigen was detected,but the liver function was normal.Clinical and pathological data were collected before and during the treatment.Hepatic AML was diagnosed based on the typical histological characteristics and immunohistochemical staining,which revealed,a positive staining with a melanocytic cell-specific monoclonal antibody.There was no evidence of tuberous sclerosis complex in this patient.Although the HCC was poor- to moderately-differentiated,the characteristics of the AML and the cavernous hemangioma in this patient did not match any criteria for malignancy.Hepatectomy followed by transarterial chemoembolization treatment were effective therapeutic methods for the adjacent lesions in this patient.This case is an interesting coincidence.

Effects of hypoxic exercise training on microRNA expression and lipid metabolism in obese rat livers

To investigate the effects of hypoxic exercise training on microRNA （miRNA） expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic sedentary group （N, n=10） and a hypoxic exercise training group （H, n=10）. After four weeks, measurements were taken of body weight, body length, fat mass, serum lipid concentration, miRNAs differentially expressed in rat liver, and gene and protein expression levels of perexisome proliferator activated receptor a （PPARα）, fatty acid synthetase （FAS）, and carnitine palmitoyl transferase 1A （CPTIA） in rat liver. Body weight, Lee＇s index, fat mass, fat/weight ratio, and serum levels of total cholesterol （TC） and high density lipoprotein cholesterol （HDL-C） were all significantly lower in the H group than in the N group （P〈0.01）. Six miRNAs expressed significantly differently in the liver （P〈0.05）. Specifically, expression levels of miR-378b were significantly lower in the H group than in the N group （P〈0.05）. Compared with the normoxic sedentary group, hypoxic exercise training resulted in a lower ratio of FAS mRNA to CPTIA mRNA （P〈0.05）, as well as lower CPT1A protein levels （P〈0.01）, while a higher ratio of FAS to CPT1A protein levels （P〈0.01） was observed. In conclusion, hypoxic training may elevate the resistance of high fat diet induced obesity in rats by reducing the expression of miR-378b, and decrease the fatty acid mitochondrial oxidation in obese rat livers by decreasing the protein expression of CPTIA and increasing the protein expression ratio of FAS/CPTIA.