Fractionated Radiation Therapy for Large and Giant Cavernous Sinus Hemangioma: A Retrospective Study.

Purpose: Surgical resection has been traditionally used as a treatment for cavernous sinus hemangioma (CSH). However, this is usually difficult due to tumor vascularity and results in complications especially in large and giant CSH (volume >20 cm3). Previous studies have reported that radiotherapy (RT) provides an alternative treatment modality for hemangiomas. However, the optimized dose and fractions which control CSH and also protect the cognitive function remain unclear. This study reports our experience in the management of symptomatic large and giant CSH. Methods: Fifty-four patients with symptomatic large (20 cm3 40 cm3, >4 cm in diameter) CSH were enrolled in a retrospective study between January 2007 and December 2018. The prescription dose to the target margin was 50 Gy in 25 fractions. Results: The mean pre-RT tumor volume was 60.9 cm3 which ranged from 20.2 to 230.5 cm3. The clinical data obtained was analyzed retrospectively following a mean follow-up period of 35.0 months which ranged from 1 to 140 months. All patients experienced tumor shrinkage within 3 months after radiotherapy. There was an average mean tumor reduction of 79.7% (range, 48.4-98.5%) with no patients experiencing tumor progression and recurrence. All the 54 patients experienced symptomatic improvement within 1 month to 12 months after radiotherapy. Within the entire follow up period, no patients experienced any form of permanent complications or symptomatic radiation toxicity. Neurocognitive impairment studies were conducted before and after radiotherapy on 28 patients while the studies were conducted after the last follow up in 40 patients. The cognitive function of all the participants had normal MoCA-scores of 28.25 pre-radiotherapy. The post-treatment MoCA-scores were also clinically stable (28.04, p = 0.78), and the average MoCA-score did not show any decline until the last follow-up (27.61, p = 0.13). Conclusion: The optimal dose and fractions of radiotherapy treatment for symptomatic large and giant cavernous sinus hemangioma remain unclear. This study, therefore, used a marginal dose of 50 Gy in 25 fractions in radiotherapy and this was proven to be effective and relatively safe in the treatment of symptomatic large and giant CSHs.

Hypofractionated stereotactic radiation therapy activates the peripheral immune response in operable stage I non-small-cell lung cancer.

It has been reported that in patients with operable stage I non-small cell lung cancer (NSCLC), overall survival (OS) is better in those who undergo hypofractionated stereotactic radiation therapy (HSRT) than in those who undergo surgery. However, the reason that HSRT has a better OS has not been fully explored. Here, we analyzed reconstitution kinetics in immune cells in the peripheral blood of NSCLC patients after HSRT. We found that HSRT increased the frequency of total T cells, especially the proportion of CD8+ T cells, but decreased the frequency of inhibitory Tregs. Intracellular staining showed that after HSRT, peripheral CD8+ T cells were transformed into activated T cells, which express high levels of TNF-α, IFN-γ, granzyme B and IL-2. HSRT also increased the production of IL-2, TNF-α, and IFN-γ but down-regulated the production of TGF-ß in CD4+ T cells. The frequencies of naïve B cells and double-negative B cells were lower, while the proportions of MZ-like B cells, transitional B cells and plasmablast cells were higher after HSRT. Collectively, our results demonstrate that HSRT activates the peripheral immune response and indicate the dynamic variation in peripheral lymphocytes after HSRT, which is very important for optimizing combination treatments in clinical practice.

Ionizing radiation-induced microRNA expression changes in cultured RGC-5 cells.

MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate gene expression at the post­transcriptional level. It has been demonstrated that miRNAs serve a crucial role in tissue development and the pathogenesis of numerous diseases. The aim of the current study was to investigate the alterations in miRNA expression in a cultured retinal ganglion cell line (RGC­5 cells) following ionizing radiation injury. Cultured RGC­5 cells were exposed to X­rays at doses of 2, 4, 6 and 8 Gy using a medical linear accelerator. Alterations in cellular morphology were observed under a phase contrast microscope and cell viability was measured using the MTT assay. Subsequent to exposure to X­ray radiation for 5 days, the viability of RGC­5 cells was significantly reduced in the 6 and 8 Gy groups, accompanied by morphological alterations. Total RNA was then extracted from RGC­5 cells and subjected to miRNA microarray analysis subsequent to exposure to 6 Gy X­ray radiation for 5 days. The results of the microarray analysis indicated that the expression levels of 12 miRNAs were significantly different between the 6 Gy and control groups, including 6 upregulated miRNAs and 6 downregulated miRNAs. To verify microarray results, a reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis was performed. The data obtained from RT­qPCR analysis was similar to that of the the microarray analysis for alterations in the expression of the 12 miRNAs. The results of the current study indicated that miRNA expression was sensitive to ionizing radiation, which may serve an important role in mechanisms of radiation injury in retinal ganglion cells.

The impact of matrix metalloproteinase 2 on prognosis and clinicopathology of breast cancer patients: a systematic meta-analysis.

BACKGROUNDS: Matrix metalloproteinase 2 (MMP-2) plays a crucial role in the progression of breast cancer (BC). The prognostic role of MMP-2 expression in BC patients has been widely reported, but the results were inconsistent. Thus, a meta-analysis was conducted to gain a better insight into the impact of MMP-2 expression on survival and clinicopathological features of BC patients. METHODS: Identical search strategies were used to search relevant literatures in electronic databases update to August 1, 2014. Individual hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were extracted and pooled to evaluate the strength of the association between positive MMP-2 expression and survival results and clinicopathological features of BC patients. Begg's tests, Egger's tests and funnel plots were used to evaluate publication bias. Heterogeneity and sensitivity analysis were also assessed. All the work was completed using STATA. RESULTS: Pooled HRs and 95% CIs suggested that MMP-2 expression had an unfavorable impact on both OS (HR: 1.53, 95% CI: 1.29-1.82) and DFS/RFS/DDFS (HR: 1.41, 95% CI: 1.07-1.86) in BC patients. Furthermore, MMP-2 expression was significantly associated with lymph node metastasis (positive vs negative: OR 1.91, 95% CI 1.17-3.12). CONCLUSION: In conclusion, positive MMP-2 expression might be a significant predictive factor for poor prognosis in patients with BC.

Meta-analysis demonstrates lack of association of the GSK3B -50C/T polymorphism with risk of bipolar disorder.

Published data on the association between GSK3B -50C/T (rs334558) and bipolar disorder (BD) are inconclusive. We performed this meta-analysis to evaluate the relationship of this single-nucleotide polymorphism with the susceptibility, and with the age at onset of BD. A literature search was conducted though PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure databases to identify relevant studies up to February 14, 2014. We identified a total of 6 publications including 1,251 cases and 1,804 controls to investigate the effect of GSK3B -50C/T on BD risk, and found no significant association in any genetic models (C vs. T: OR = 1.03, 95 % CI: 0.92-1.15; CC vs. TT+TC: OR = 1.04, 95 % CI: 0.84-1.28; TC+CC vs. TT: OR = 1.16, 95 % CI: 0.97-1.39; and CC vs. TC vs. TT: OR = 1.08, 95 % CI: 0.96-1.22). Subgroup analysis by ethnicity did not change the results. The association between GSK3B -50C/T and age at onset of BD was explored by 6 identified studies with a total of 659 BD type I patients. Similarly, we did not observe significant results in any genetic models (TC+CC vs. TT: SMD = 0.20, 95 % CI: -0.07 to 0.47; CC vs. TT+TC: SMD = 0.11, 95 % CI: -0.10 to 0.32; CC vs. TT: SMD = 0.32, 95 % CI: -0.13 to 0.77). The power analysis and tests for publication bias ensured the reliability of our results. In summary, this meta-analysis suggests that the functional polymorphism -50C/T within the GSK3B gene promoter is unlikely to relate with BD risk. However, more larger and well-designed studies are still needed to yield a conclusive result on the topic.

Lack of association between MDR1 C3435T polymorphism and chemotherapy response in advanced breast cancer patients: evidence from current studies.

The transmembrane transport of anticancer drugs is mainly regulated by P-glycoprotein encoded by the human multidrug resistance gene 1 gene (MDR1). Since there were controversies regarding the association between MDR1 C3435T polymorphism and response to chemotherapy among patients with advanced breast cancer, a meta-analysis of the link was conducted. A total of 7 studies consist of 464 advanced breast cancer patients relating MDR1 C3435T polymorphism to the response of chemotherapy were included in this meta-analysis. The main analysis revealed a lack of association between the MDR1 C3435T and response to chemotherapy, with odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) of 1.37 (95% CI: 0.78-2.40), 1.17 (95% CI: 0.69-2.01), 1.18 (95% CI: 0.76-1.84) and 1.61 (95% CI: 0.70-3.68) for homozygous comparison, heterozygous comparison, dominant model and recessive model, respectively. The subgroup analysis by ethnicity did not change the pattern of results, with ORs of 0.99 (95% CI: 0.11-9.07), 0.68 (95% CI: 0.29-1.60), 0.81 (95% CI: 0.36-1.85) and 1.51 (95% CI: 0.77-2.96), in homozygous comparison, heterozygous comparison, dominant model and recessive model, respectively in Caucasian, and 1.50 (95% CI: 0.75-3.03), 1.72 (95% CI: 0.85-3.47), 1.59 (95% CI: 0.90-2.80) and 2.29 (95% CI: 0.51-10.35), respectively in Asian. The available evidence indicates that MDR1 C3435T polymorphism cannot be considered as a reliable predictor of response to chemotherapy in patients with advanced breast cancer.

[Multiplex PCR and genetic polymorphism of STR loci D4S1627, D14S1426, D1S1649].

OBJECTIVE: To prepare the allelic ladder materials of three STR loci includes D1S1649, D4S1627, D14S1426, and construct a synchronous detection method by multiplex amplification of the three loci. METHODS: Multiplex PCR method, PAGE (polyacrylamide gel electrophoresis) and silver staining were applied to detect 120 unrelated Chinese Han population from Chengdu whose allele and gene frequency distributing of these three loci. The electrophoretic bands of the multiplex PCR of these three loci were clear, no overlap of each alleles were observed, and the results were the same with single-locus test results. The results of the multiplex PCR demonstrated that the genotype of these three STR loci in Chengdu Han population in the genotype distribution met with Hardy-Weinberg equilibrium. 6 alleles (10-15) were detected in D4S1627, 9 alleles(5, 6, 8-14, without 7) were detected in D14S1426, 6 alleles (7-12) were detected in D1S1649. CONCLUSION: The results suggested that the multiplex PCR system of these three loci is of practical value in genetic research and forensic identification.

[The expression of BDNF and PSD-95 in hippocampal CA1 region of morphine-withdrawn rat with different dependent times].

OBJECTIVE: To observe the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density-95 (PSD-95) in hippocampal CA1 region of rat with morphine dependence for different times and withdrawn for 1 week, and investigate the influence of that morphine dependence is withdrawn on rat hippocampal CA1 area. METHODS: Animal models of rats with morphine withdrawal for 1 week and different morphine dependent times(1 week, 2 weeks, 4 weeks) were established. The expression of BDNF and PSD-95 in hippocampal CA1 were identified with RT-PCR. RESULTS: The expression of BDNF and PSD-95 in hippocampal CA1 decreased in the withdrawn group with morphine dependence for 1 week as compared with that in normal saline (NS) group (P < 0.01), and it increased in the withdrawn group with morphine dependence for 2 weeks as compared with that in morphine-dependent group for 1 week (P < 0.05) but still decreased as compared with that in NS group (P < 0.01), and it decreased in the withdrawn group with morphine dependence for 4 weeks as compared with the other three groups (P < 0.01). CONCLUSION: The expression of BDNF and PSD-95 in hippocampal CA1 decreases in morphine-depended rats withdrawn for 1 week. Morphine withdrawal has a manifest harm in hippocampal CA1 region of rat.

[Genetic polymorphisms of five STR gene loci GATA30F04, GATA23B10, D18S847, GATA83B04 and GATA167A05 alleles in Chinese Han population of Chengdu area].

OBJECTIVE: To get the preliminary genotype and allele frequency distributions of GATA30F04, GATA23B10, D18S847, GATA83B04 and GATA167A05 loci in Chinese Han population in Chengdu area, and to validate more short tandem repeat (STR) systems for forensic application. METHODS: The polymerase chain reaction (PCR) was used to this study. Five STRs (GATA30F04, GATA23B10, D18S847, GATA83B04 and GATA167A05) were amplified from DNA samples, which were extracted with Chelex-100 method from EDTA-blood of 100 unrelated individuals. The PCR products were analyzed by PAG vertical electrophoresis. RESULTS: No deviations from Hardy-Weinberg equilibrium were observed. The expected heterozygosities observed were 0.694, 0.918, 0.836, 0.889 and 0.880 for GATA30F04, GATA23B10, D18S847, GATA83B04 and GATA167A05 respectively. The discriminating powers were 0.697, 0.901, 0.875, 0.900 and 0.891. CONCLUSION: The last four loci in this study are useful markers for genetics purposes in individual identification and paternity test.

[Genetic polymorphisms at five STR loci in Chengdu Han population].

OBJECTIVE: To understand the allele structure and genetic polymorphisms at five STR loci in Chengdu Han population, to obtain a preliminary database and to analyze the value in forensic medicine. METHODS: EDTA-blood specimens were collected from unrelated individuals. The DNA of samples was extracted with Chelex-100 method. And then the PCR amplification, PAGE horizontal electrophoresis and gel silver staining were performed for analyzing the polymorphisms of five STR loci in Chengdu Han population. RESULTS: In the five STR loci,10, 7, 5, 7 and 7 alleles were found respectively. The observed heterozygosity of 83%, 80%, 64%, 66% and 77% and discrimination power of 95.44%, 91.0%, 84.3%, 86.1% and 86.8% were identified for the five STR loci respectively. All loci obeyed Hardy-Weinberg equilibrium. CONCLUSION: The five STR loci display the high discrimination power. The obtained data are desirable for forensic analysis and benefiting to the research of the population genetics.

[Polymorphism of five short tandem repeat systems in Chinese Han population in Chengdu].

OBJECTIVE: To obtain population genetic data of loci D11S4951, D11S4957, GATA193H05, D2S2951, and D6S2421 in Han population in Chengdu area and to validate the value of their forensic application. METHODS: Blood samples were collected in EDTA tubes from unrelated individuals. DNAs were extracted with Chelex-100 and were analyzed by PCR and horizontal PAGE followed by silver staining. RESULTS: Alleles 7, 10, 8, 6 and 8 were found in 5 STR loci, respectively. No deviations from Hardy-Weinberg balance were observed. The heterozygosities observed were 0.743, 0.772, 0.833, 0.650 and 0.800, respectively. The chances of exclusion were 0.497, 0.549, 0.662, 0.356 and 0.599, and the discrimination powers were 0.863, 0.912, 0.947, 0.829 and 0.931. CONCLUSION: All of the five loci studied may be useful markers for individual identification and paternity testing.

[Genetic polymorphisms of three loci and implication to forensic medicine].

OBJECTIVE: To obtain population genetic data of short tandem repeat (STR) locus D2S1327, D1S1390, and D11S2008 and to investigate the disparity of allelic frequency distributions among populations from different regions. METHODS: Blood samples of 300 unrelated individuals from Chengdu (Han), Bangkok (Thai) and Maint (Germany) were taken and analyzed with single PCR, polyacrylamide gel electrophoresis and silver staining. RESULTS: In the three loci, 9, 6, and 8 alleles and 32,14, and 22 genotypes were found respectively. The observed heterozygosity of 79%-82%, 63.0%-74.3%, and 72.0%-74.3% and discrimination power of 87.8%-92.6%, 79.6%-82.5%, and 87.6%-89.0% were identified for the three loci respectively. The genotype distributions of the three loci in the three populations fitted well with Hardy-Weinberg equilibrium. There was no significant difference in allelic frequency distributions among the three populations. CONCLUSION: The methods described in this paper are easy to perform and have high sensitivities. The discrimination power and exclusion chances of these three loci are desirable for forensic analysis and application.

[Analysis of the multi-amplified 5 STR loci and their allelic distribution in both Han populations in Chengdu City and Yunnan province].

OBJECTIVE: To illuminate the multi-amplified 5 STR loci and their allelic distribution in Hans by means of STR-DNA typing with improved efficiency and decreased cost. METHODS: We have established an allelic ladder of D7S820, D13S317, D5S818, D3S1358 and Amelogenin loci via the cloning techniques. With this homemade allelic ladder, we established successfully a multiplexing polymerase chain reaction (PCR) method, followed by denaturing polyacrylamide gel electrophoresis (PAGE) and silver staining. DNA samples collected from 130 unrelated Han individuals in Yunnan and Chengdu were analyzed. The non-overlapping of the allelic fragments of the five loci allowed the detection to be accomplished successfully. RESULTS: No difference of the genotyping results of the single locus amplification and multiplexing was observed. The genotype distributions of 4 STR were in accordance with the Hardy-Weinberg equilibrium. 7, 7, 8 and 8 alleles of D7S820, D13S317, D5S818, and D3S1358 loci were observed in Yunnan Han population, as well as 8, 7, 8 and 7 alleles in Chengdu Han population respectively. No significant difference in the allele distribution of these loci was seen between these two Han populations. CONCLUSION: This multiplexing system with home-made allelic ladder has a high combined discrimination power and exclusion power. It is a valuable tool in forensic science practice.

[Primary study on the influence of blood transfusion on the STR genotypes of recipient's blood].

OBJECTIVE: To investigate whether any change occurred in recipients' blood collected at different times after transfusion with different quantity of blood. METHODS: Three patients were transfused with 400 ml, 800 ml and 1200 ml blood separately. The blood samples were collected from the recipients before transfusion and at 4 h, 8 h, 12 h after transfusion, and from the donors. DNA were extracted by Chelex-100 method and were amplified by the polymerase chain reaction (PCR). Six loci of D1S549, D18S865, D3S1754, D12S391, D12S375, D6S477 were selected. The PCR products were analyzed by polyacrylamide gel (PAG) vertical electrophoresis and silver staining. RESULTS: The investigations on the six STR loci revealed that the patients' STR genotypes remained unchanged within 12 h after blood transfusion. CONCLUSION: The STR genotypes of the donors would have no influence on the STR genotypes of the patients within 12 h after transfusion providing the volume of blood transfused is less than 1200 ml.