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ABSTRACT: OX40L is an important costimulatory molecule that plays a crucial role in the regulation of T-cell-mediated immunity. The interaction of OX40-OX40L is involved in the pathogenesis of multiple autoimmune and inflammatory diseases such as systemic lupus erythematosus (SLE), carotid artery disease and cancer. The genetic variants of OX40L can increase the risk of SLE, atherosclerosis, systemic sclerosis and show gender-specific effects in some studies. Accordingly, we performed a case-control study including 557 breast cancer patients and 580 age- and sex-matched healthy controls to investigate whether single nucleotide polymorphisms (SNPs) in the OX40L gene are associated with sporadic breast cancer susceptibility and progression in Chinese Han women. Seven SNPs of OX40L (rs6661173, rs1234313, rs3850641, rs1234315, rs12039904, rs844648 and rs10912580) were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results indicated that rs3850641G allele could increase the susceptibility to breast cancer (P = 0.009662), even in the validation study (P = 0.0001515). A significant association between rs3850641 and breast cancer risk was observed under the additive model and dominant model (P = 0.01042 and 0.01942, respectively). The haplotype analysis showed that haplotype A(rs844648)A(rs10912580) was significantly associated with breast cancer, even after 10,000 permutations for haplotypes in block only (P = 0.0003). In clinicopathologic features analysis, the association between rs1234315 and C-erbB2 status was significant (P = 0.02541). Our data primarily indicates that rs3850641 of OX40L gene contributes to sporadic breast carcinogenesis in a northeast Chinese Han population.
PLoS ONE 01/2012; 7(8):e41277. · 4.09 Impact Factor
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ABSTRACT: Intracranial hemangiopericytomas (HPCs) are rare, and they have a tendency for local recurrence and metastases. The purpose of this study was to evaluate the relationship between CT perfusion (CTP) parameters and microvessel density (MVD) of HPCs and compare CTP parameters in parenchyma and peritumoral edema of HPCs.
The study was approved by the ethics committee, and written informed consent was obtained. Ten patients with HPCs and peritumoral edema, confirmed by pathological results, received 64-slice CT perfusion imaging before operation. To evaluate vascular attenuation of tumoral parenchyma, we immunostained the specimen sections for CD-34, measured the integrated optical density of all the positive stained CD-34 cells in the microscopic field, and calculated its ratio to total area of field as MVD. Perfusion analysis was calculated using the Patlak method. Using a 1-cm distance from the outer enhancing tumor margin as a boundary, the peritumoral edema was divided into an immediate and a distant part. The quantitative CTP parameters, including cerebral blood volume (CBV), permeability-surface area product (PS) of parenchyma, and immediate and distant peritumoral edemas, were compared. CBV and PS in parenchyma and immediate and distant peritumoral edemas of HPCs were also compared to their respective contralateral normal white matter. The correlations between MVD, CBV, and PS of tumoral parenchyma were analyzed.
Positive correlations existed between CBV and MVD, PS and MVD (P < 0.05) respectively in the 10 patients. Furthermore, the values of CBV and PS in parenchyma of HPCs were significantly higher than those of the contralateral normal white matter and peritumoral edema (P < 0.05). The value of CBV in peritumoral edema of HPCs were lower than that of contralateral normal white matter (P < 0.05), while the value of PS in immediate and distant peritumoral edemas of HPCs were not significantly difference with that of contralateral normal white matter (P > 0.05). Finally, the values of CBV and PS did not show a significant difference between immediate and distant peritumoral edemas.
CT perfusion imaging, especially determination of maximal CBV and corresponding PS values in the parenchyma, may be a useful and non-invasive technique for the preoperative evaluation of hemodynamic features of HPCs with peritumoral edema. CBV of peritumoral edema indicate that HPCs have a possibility of infiltration, this need further radiological-pathological research.
British Journal of Neurosurgery 11/2011; 26(3):340-6. · 0.88 Impact Factor
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ABSTRACT: Breast cancer is a polygenetic disorder with a complex inheritance pattern. Single nucleotide polymorphisms (SNPs), the most common genetic variations, influence not only phenotypic traits, but also interindividual predisposition to disease, treatment outcomes with drugs and disease prognosis. The co-stimulatory molecule CD40 plays a prominent role in immune regulation and homeostasis. Accumulating evidence suggests that CD40 contributes to the pathogenesis of cancer. Here, we set out to test the association between polymorphisms in the CD40 gene and breast carcinogenesis and tumor pathology.
Four SNPs (rs1800686, rs1883832, rs4810485 and rs3765459) were genotyped by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method in a case-control study including 591 breast cancer patients and 600 age-matched healthy controls. Differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed by the Chi-square test for trends. Our preliminary data showed a statistically significant association between the four CD40 gene SNPs and sporadic breast cancer risk (additive P = 0.0223, 0.0012, 0.0013 and 0.0279, respectively). A strong association was also found using the dominant, recessive and homozygote comparison genetic models. In the clinical features analysis, significant associations were observed between CD40 SNPs and lymph node metastasis, human epidermal growth factor receptor 2 (C-erbB2), estrogen receptor (ER), progesterone receptor (PR) and tumor protein 53 (P53) statuses. In addition, our haplotype analysis indicated that the haplotype C(rs1883832)G(rs4810485), which was located within the only linkage disequilibrium (LD) block identified, was a protective haplotype for breast cancer, whereas T(rs1883832)T(rs4810485) increased the risk in the studied population, even after correcting the P value for multiple testing (P = 0.0337 and 0.0430, respectively).
Our findings primarily show that CD40 gene polymorphisms contribute to sporadic breast cancer risk and have a significant association with clinicopathological features among Chinese Han women from the Heilongjiang Province.
PLoS ONE 01/2011; 6(8):e23762. · 4.09 Impact Factor
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ABSTRACT: Infiltrating ductal carcinoma (IDC) is the most common malignant breast cancer in women, and genetic factors appear to play a significant role in the susceptibility to IDC. Alteration of DNA methylation is an epigenetic change in human cancers, including breast cancer. DNA-methyltransferase 1 (DNMT1) is a major enzyme that determines genomic methylation patterns. In order to clarify the association of DNMT1 polymorphisms with IDC, a case-control study was conducted in women from the Heilongjiang Province, in the northeast of China.
We scrutinized the 2 genetic polymorphisms in exons of DNMT1 that may influence the activity of DNMT1. Our research subjects consisted of 305 patients with IDC and 314 age-matched healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Data were analyzed using the χ2 test by SPSS, version 13.0, and Haploview, version 4.1. The association between DNMT1 polymorphisms and the clinical features of IDC was analyzed.
In rs16999593, the frequency of CT genotype and C allele were lower in patients than in controls (P = .028 and P = .017, respectively). Also, rs2228611 AG genotype was higher in patients than in controls (P = .015). The frequency of haplotype CA was lower in patients than in controls (P = .034). Significant association was shown between the 2 single nucleotide polymorphisms of the DNMT1 gene and progesterone receptor (PgR) and p53 status. No association was found between DNMT1 gene polymorphisms and tumor size or estrogen receptor status.
Our results was a previous study, which suggested that DNMT1 gene polymorphisms in exons may provide valuable information for predicting the sporadic IDC risk and may be associated with prognosis factors such as PgR and p53 status in Chinese Han women in the Heilongjiang Province.
Clinical Breast Cancer 10/2010; 10(5):373-7. · 2.38 Impact Factor
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ABSTRACT: The application of a fluid-attenuated inversion-recovery pulse with a conventional diffusion-weighted MRI sequence (FLAIR DWI) decreases the partial volume effects from cerebrospinal fluid on apparent diffusion coefficient (ADC) measurements. For this reason, FLAIR DWI may be more useful in the evaluation of ischemic stroke, but few studies have looked at the effect of FLAIR on ADC measurements in this setting. This study quantitatively compares FLAIR DWI and conventional DWI in ischemic stroke of varying ages to assess the potential advantages of this technique.
We respectively analyzed 139 DWI studies in patients with ischemic stroke with and without FLAIR at varying time points ranging from hyperacute to chronic. ADC values were measured in each lesion, as well as in the contralateral normal side. Comparisons were made between the ADC values obtained from the DWI sequences with and without FLAIR for both the lesion and the normal contralateral side.
The ADC measurements within the ischemic lesion were very similar on FLAIR DWI and conventional DWI for lesions less than 14 days old (p>0.05), but were significantly decreased on FLAIR DWI for lesions between 15 and 30 days old and in lesions >31 days old (chronic stage) (p<0.01). The contralateral ADC values were all significantly decreased on the FLAIR DWI sequence compared with conventional DWI (p<0.01).
The application of an inversion pulse does not significantly affect the ADC values for early stage ischemic stroke (less than 14 days from symptom onset), but results in a more accurate relative ADC measurement by reducing the cerebrospinal fluid partial volume effects of the normal contralateral side. In addition, combined with the conventional DWI, FLAIR DWI may be helpful in determining the age of ischemic lesions.
European journal of radiology 08/2010; 75(2):e76-81. · 2.65 Impact Factor
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ABSTRACT: The aim of the study is to investigate the alterations in expression of estrogen receptor alpha (ER), progesterone receptor (PgR), c-erbB2 gene (HER-2/neu), and P53 protein in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDC), and the association between their expression and clinicopathologic findings. The mastectomy specimens of 520 cases containing both DCIS and IDC were examined. The expression of ER, PgR, HER-2/neu, and P53 proteins were examined by immunohistochemistry. Linear regression was used to investigate the correlation among ER, PgR, HER-2/neu, P53 protein expression, and the clinicopathologic factors. There was a significant decrease of ER and PgR expression in IDC compared to DCIS (32.81 vs. 21.05%, chi(2) = 4.45, P = 0.035; 26.56 vs. 15.57%, chi(2) = 4.82, P = 0.028, respectively). In contrast, there was a significant increase of HER-2/neu expression in IDC compared to DCIS (10.94 vs. 21.27%, chi(2) = 3.88, P = 0.049). However, there was no significant difference in expression of p53 between DCIS and IDC. In both DCIS and IDC, a significant positive correlation was observed between ER and PgR receptor expression (r = 0.67, P = 0.00; r = 0.56, P = 0.00, respectively). In conclusion, these findings substantiate the notion that breast cancer progression is often associated with alterations in expressions of ER, PgR, and HER-2/neu. The underlying mechanisms of these alterations need further investigation.
Medical Oncology 09/2009; 27(3):747-52. · 2.14 Impact Factor
