Relationship between the mutation of leptin receptor gene and tumorigenesis of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the relationship of the mutations of leptin receptor gene exon 4, exon 6, exon9, and exon20 with the tumorigenesis of breast cancer.</p><p><b>METHODS</b>Genomic DNA was extracted from breast cancer tissues of 155 patients, benign lesions of 56 patients and normal tissues and blood samples from 100 health control subjects. The leptin receptor genes were assayed with polymerase chain reaction (PCR) amplification and direct sequence analysis.</p><p><b>RESULTS</b>Nucleotide substitutions no mutations were found at exon 4, and nucleotide substitutions occurred at codon 1029 in exon 9, no significant difference among the three groups (P = 0.574). The nucleotide substitutions at codon 668 in exon 6 resulted in Gln223Arg polymorphisms. The occurring frequencies of GG, GA, AA in breast cancer, breast benign lesions tissues and health tissues control group were 70.9% and 17.4%, 12.3%; 80.4%, 14.3% and 5.4%; and 81.0%, 16.0%, and 3.0%, respectively. Alleles of G and A in the three groups were 79.1% and 20.8%, 87.5% and 12.5%, and 89.0% and 11.0%, respectively. Compared the Gln223Arg genotype with the three allele groups, there were significant differences (χ(2) = 16.11, P < 0.005 and χ(2) = 11.41, P < 0.01), respectively. The nucleotide substitutions at codon 3057 in exon 20 resulted in Pro1019Pro polymorphisms. The occurrence frequencies of GG, GA, AA in the breast cancer, benign disease and health control groups were 11.6%, 30.3% and 56.1%; 32.1%, 44.0% and 28.5%; and 32.0%, 45.0% And 23.0%, respectively. Alleles of G and A in the three groups were 26.8% and 73.2%, 51.8% and 48.2%, and 54.5% and 45.5%, respectively. There are significant differences among the three groups (χ(2) = 6.56, P < 0.03 and χ(2) = 5.45, P < 0.05), respectively. Nucleotide substitutions occurred at relatively high frequencies at exon 6 and exon 20 in obese and overweight breast cancer patients compared with those in normal weight breast cancer patients, there were significant differences (P < 0.05 and P < 0.01).</p><p><b>CONCLUSIONS</b>Our findings show that there is no relationship between the variations of leptin receptor gene exon 9 and tumorigenesis of breast cancer. The variation rate of leptin receptor gene exon 6 and exon 20 are significantly increased in the obese and overweight breast cancer patients.</p>

Mechanism of oligochitosan-induced macrophage activation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the mechanism of oligochitosan-induced macrophage activation.</p><p><b>METHODS</b>Oligochitosan was chemically modified with fluorophore 2-aminoacridone (2-AMAC). The cellular events of 2-AMAC-oligochitosan-macrophage interaction were analyzed with confocal laser microscopy and the fluorescence intensity of cells was analyzed by BD LSR flow cytometer. The mechanism of oligochitosan uptake by macrophages was studied by competitive inhibition test and the effect of calcium, trypsin and colchicine on oligochitosan recognition and internalization were also determined. RT-PCR was performed to investigate the level of TNF-alpha secretion.</p><p><b>RESULT</b>Macrophage could bind and uptake oligochitosan, which was dependent on the temperature: the uptake proceeded rapidly at 37 degrees C and at 4 degrees C macrophage could only bind oligochitosan. EDTA decreased oligochitosan uptake. Trypsin treatment significantly reduced the internalization, and uptake was recovered by trypsin termination. Colchicine significantly inhibited the internalization process and was dose dependent. 0.1 mol/L mannose inhibited TNF-alpha expression induced by oligochitosan.</p><p><b>CONCLUSION</b>Macrophage could uptake oligochitosan via mannose receptor mediated pinocytosis. Mannose receptor is crucial for the oligochitosan-induced macrophages activation.</p>

A clinical study on docetaxel plus capecitabine as front-line combination therapy for breast cancer with liver metastases / 肿瘤研究与临床

Objective To determine the efficacy and tolerability of docetaxel plus capecitabine as first-line treatment for breast cancer with liver metastases(BCLM).Methods Forty-two patients with BCLM received oral capecitabine 1900 mg/m~2/d(950 mg/m~2 twice daily)on days 1 through 14 and intravenous infu- sion of Docetaxel at 75 mg/m~2 on day 1 of each 21-day treatment cycle.Patients were evaluated for the re- sponse after two cycles.Results Among these 42 patients,the overall response rate was 54.76% with 4 CR, 19 PR, 9 SD and 6 PD.The clinical benefit rate was 64.28% and the median overall survival time was 17.5 months.The most common treatment-related adverse events were leukopenia(76.1%),neutropenia(71.4%), hand-foot syndrome(45.2%),nausea and vomiting(52.3%),which were mainly gradeⅠ～Ⅱ.Conclusion The combination of docetaxel plus capocitabine is a highly active and generally well-tolerated regimen for first-line treatment of BCLM.