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81.

Purpose

To evaluate the mechanism for enhancing cell death induced by microwave ablation (MWA) combined with doxorubicin treatment in breast cancer cells.

Materials and methods

Different temperatures of heat treatment were used to mimic the tumor affected by sublethal heat during MWA in vitro. Breast cancer cells were treated at 43 °C and 45 °C, with or without doxorubicin. Cell viability, apoptosis, and intracellular reactive oxygen species (ROS) were evaluated in MDA-MB-231 and SUM-1315 cells. Nude mice breast cancer models were randomly divided into control, MWA, doxorubicin, and combined treatment groups. Tumor apoptosis and DNA damage were evaluated in these groups.

Results

The combined group had lower cell viability than the heat or doxorubicin group (all P < 0.05), and enhanced apoptosis rate was observed in the combined group compared to others (all P < 0.01) in MDA-MB-231 and SUM-1315. Increased capase3 (all P < 0.01) and decreased Bcl-Xl (all P < 0.01) were detected after combined therapy compared to single treated group in vitro. The raisedCaspase3 and DNA damage marker histone H2A.X induced by combined treatment were also approved in the nude mice models. Combined treatment promoted ROS generation compared to doxorubicin or MWA treatment (all P < 0.01). NF-κB expression in the combined group was higher than that of the single treatment group (all P < 0.05). N-acetylcysteine (NAC), a ROS scavenger, partly restrained the combined treatment induced cell proliferation inhibition, Caspase3 and NF-κB compared to doxorubicin treatment (all P < 0.05).

Conclusion

MWA combined with doxorubicin promote cell death via ROS induced cell apoptosis and DNA damage. Increasing ROS has potential for improving the efficiency of combined treatment.  相似文献   
82.
目的评估不同直径混合肌腱(同种异体肌腱加强自体肌腱)重建前交叉韧带(ACL)对膝关节运动学特征影响。 方法回顾性分析2017年8月至2018年6月在南方医科大学第三附属医院使用混合肌腱行ACL重建术的57例患者资料。纳入标准:单侧膝ACL损伤并使用直径8 mm或9 mm混合肌腱重建ACL患者;年龄18至55岁并且有影像学证据显示骨骺闭合。排除标准:X片提示膝骨关节炎;术前膝关节活动受限;其他膝关节手术史;膝关节其他韧带损伤;需同时行半月板移植及软骨修复者。根据移植物直径大小不同分为:8 mm组(32例)、9 mm组(25例)。患者在术前、术后6个月、1年、2年完成随访,分析患侧膝关节6自由度的活动度及胫股运动学改变(以对侧膝关节为对照组)、移植物信号/噪声商(SNQ)值、Lysholm评分。各组术前及术后指标比较采用重复测量方差分析。 结果8 mm组(6.3%)、9 mm组(0%)的手术失败率差异无统计学意义(P=0.499)。8 mm组在术后6个月的屈曲角度、术后1年的外旋角度比9 mm组高,差异具有统计学意义(F=3.507,P=0.034;F=4.563,P=0.013);8 mm组在术后6月的外侧位移、术后2年的外旋角度比对照组高,差异具有统计学意义(F=3.596,P=0.031;F=9.997,P<0.001)。相较术后6个月、1年,两组在术后2年的移植物近端、中段、远端的SNQ值均呈下降趋势(F=9.634、8.593、7.636,均为P<0.001)。9 mm组的Lysholm评分比8 mm组高,差异具有统计学意义(F=6.116,P=0.017)。 结论直径8 mm、9 mm的混合肌腱重建前交叉韧带有相似的手术失败率和移植物成熟度,但后者的膝关节运动学特征比前者更接近正常膝关节。  相似文献   
83.
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85.
SPARC is a secreted glycoprotein that plays a complex and multifaceted role in tumour formation and progression. However, whether SPARC is an oncogene or a tumour suppressor is still unclear. Moreover, SPARC demonstrates potential in clinical pancreatic adenocarcinoma (PAAD) treatment, although it has been identified as an oncogene in some studies and a tumor suppressor in others. In the present study, a pan-cancer analysis of SPARC was carried out using The Cancer genome Atlas data, which demonstrated that SPARC was an oncogene in most cancer types and a cancer suppressor in others. In addition, SPARC expression was significantly upregulated in PAAD and associated with poor prognosis. SPARC also promoted the proliferation and migration of PANC-1 and SW1990 cell lines in vitro. SPARC was detected in the culture supernatant of PAAD cells and pancreatic acinar AR42J cells. SPARC regulated PAAD cell proliferation only when secreted into the extracellular milieu, thus explaining why the prognosis of patients with PAAD is correlated with the SPARC expression of both tumour cells and stromal cells. Collectively, the present findings demonstrated that the function of SPARC was associated with tumour type and that SPARC may represent an important oncogene in PAAD that merits further study.  相似文献   
86.
87.
Interleukin-10 (IL10), a pleiotropic cytokine secreted by type-2 helper (Th2) T cells, contributes to the oncogenic activation or inactivation of tumor-suppressor genes. The present study investigated whether hypomethylation of IL10 CpG island (CGI) was associated with the risk of developing gastric cancer (GC) and the prognosis of patients with GC. A fragment (hg18, chr1: 206945638-206945774) at the CGI of IL10 was selected for the present methylation assay. Quantitative methylation-specific PCR was used to evaluate the methylation of IL10 CGI in 117 tumor samples from patients with GC. The results demonstrated that IL10 CGI methylation was significantly lower in the tumor tissues compared with that in the paired adjacent non-tumor tissues (median percentage of methylated reference, 29.16 vs. 42.82%, respectively; P=4×10−8). Furthermore, results from receiver operating characteristic curve analysis identified a significant area under the curve of 0.706, with a sensitivity and a specificity of 77.8 and 58.1%, respectively, between cancer tissues and paired adjacent non-tumor tissues. Furthermore, the methylation of IL10 CGI was significantly associated with patients'' age at diagnosis (r=−0.201; P=0.03). Subgroup analyses demonstrated that the association between IL10 CGI hypomethylation and the risk of GC was specific for patients with low differentiation (P=1×10−7) and Borrmann types III+IV (P=1×10−7). In addition, IL10 CGI hypomethylation was significantly associated with the risk of GC for patients without smoking history (P=3×10−7) or a family history of cancer (P=2×10−7). The results from Kaplan-Meier survival analysis demonstrated that IL10 CGI hypomethylation was associated with a significantly shorter overall survival of patients with GC (P=0.041). Similar results were identified for patients with GC who did not have smoking history (P=0.037) or a family history of cancer (P=0.049). The results from this study demonstrated that IL10 CGI hypomethylation may be considered as a potential biomarker for the diagnosis and prognosis of patients with GC in the Chinese population.  相似文献   
88.
Prostate and breast cancers are hormone-related malignancies and are characterized by a complex interplay of hundreds of susceptibility loci throughout the genome. Prostate cancer could be inhibited by eliminating androgens through castration or estrogen administration, thus facilitating long-term treatment of prostate cancer; however, the role of estrogen in prostate cancer remains unclear. This study aimed to determine whether polygenic risk scores (PRSs) comprising combinations of genome-wide susceptibility variants influence the clinical outcomes of prostate cancer patients. The study subjects were recruited from four medical centers in Taiwan, and genome-wide genotyping data were obtained from 643 prostate cancer patients. We derived the PRS for prostate cancer (PRS-PC) and for breast cancer (PRS-BC) for each patient. The association between the PRS-PC/PRS-BC at the age of prostate cancer onset and recurrence within seven years was evaluated using a regression model adjusted for population stratification components. A higher PRS-PC was associated with an earlier onset age for prostate cancer (beta in per SD increase in PRS = -0.89, P = 0.0008). In contrast, a higher PRS-BC was associated with an older onset age for prostate cancer (beta = 0.59, P = 0.02). PRS-PC was not associated with the risk of recurrence (hazard ratio = 1.03, P = 0.67), whereas a higher PRS-BC was associated with a low recurrence risk (hazard ratio = 0.86, P = 0.03). These results indicate that the genetic predisposition to breast cancer is associated with a low risk of prostate cancer recurrence. Further studies are warranted to explore the role of breast cancer susceptibility variants and estrogen signaling in prostate cancer progression.  相似文献   
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