沉默SUV39H1基因对急性髓系白血病KG-1细胞凋亡的影响

摘要本研究旨在探讨沉默SUV39H1基因对急性髓系白血病细胞株KG-1增殖和凋亡的影响。将SUV39HIsiRNA经Lipofectamine…2000转染至KG-1细胞,应用MTS法检测细胞增殖率,观察sUV39111siRNA对KG-1细胞增殖的影响;流式细胞术分析细胞凋亡;Westernblot检测SUV39H1siRNA作用后P15和凋亡相关蛋白BCL-2、procaspase-9、procaspase-3、C-MYC的表达。结果表明,沉默SUV39H1基因可抑制细胞增殖,SUV39H1siRNA浓度为30、60、120、240nmol／L作用48h后,KG-1细胞的增殖率分别为（76．43±1．98）％、（51．31±1．84）％、（37．31±1．61）％、（18．94±3．22）％,差异具有统计学显著意义（P〈0．05）;SUV39HIsiRNA可上调P15基因的表达;SUV39H1siRNA可诱导细胞凋亡,30、60、120nmoL／LSUV39H1siRNA作用48h后,KG-1细胞凋亡率分别为（40．2±5．1）％、（56．8±4．8）％、（71．6±5．6）％,差异有统计学显著意义（P〈0．05）;抗凋亡相关蛋白BCL-2、procaspase-9、procaspase-3、C-MYC的表达减少。结论：SUV39H1siRNA能抑制KG-1细胞的增殖并诱导其凋亡,有望成为白血病治疗的-个新的靶点。     

Positron emission tomography for predicting recurrence in stage I lung adenocarcinoma: standardized uptake value corrected by mean liver standardized uptake value

Objective: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has become an important staging tool for patients with lung cancer, and determination of the standardized uptake value (SUV) is probably the most widely used method for evaluating patients. Although SUV is recognized as a powerful surrogate marker for lung cancer outcomes, SUV standardization and reproducibility in clinical practice remain major concerns. The aim of this study was to evaluate the corrected SUV as a universal marker for lung cancer recurrence. Methods: We conducted a case–control study in our institute. From May 2004 to February 2010, 141 patients with pathological stage IA and IB adenocarcinomas underwent PET-computed tomography scanning and SUV determination. The corrected SUV was defined as the SUV index, which was calculated as the ratio of tumor SUV_max to liver SUV_mean. We examined the association between disease-free survival and several clinicopathological factors, including the SUV index. Results: The 3-year overall survival rate after surgery was 94.3% and the 3-year disease-free survival rate was 90.4%. Univariate analysis showed that male gender (p = 0.04), smoking (p = 0.02), and SUV index (p < 0.01) were independent predictive factors for recurrence. Multivariate analysis showed that the SUV index was significantly associated with a high risk for recurrence (p = 0.03). No patient with an SUV index <1.0 experienced a recurrence. Conclusions: The SUV index is a significantly predictive and reproducible factor for recurrence in pathological stage I lung cancers. Patients with an SUV index <1.0 were more likely to have a good prognosis. Additional multi-institutional studies are needed to confirm these study results.     

18F-FDG Uptake of Human Testis on PET/CT: Correlation with Age,Sex Hormones,and Vasectomy

Purpose

The purpose of this study was to evaluate glucose metabolism of normal human testis on ¹⁸F-FDG PET/CT and to assess possible correlations among age, the serum levels of sex hormones, and vasectomy.

Methods

¹⁸F-FDG PET/CT was performed in 66 normal healthy men (50.8 ± 13.6 years, range 22–81), and mean standard uptake values (SUV) of ¹⁸F-FDG in testis and adductor muscle were measured. Testis-muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex-hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. ¹⁸F-FDG PET/CT was also performed in 32 vasectomized men (55.7 ± 7.8 years, range 38–71) and 52 nonvasectomized men (55.4 ± 11.6 years, range 37–72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated.

Results

A significant age-related decline was found in T/M ratio (r = −0.509, p < 0.0001). Serum levels of total testosterone and free testosterone were also found to be positively correlated with T/M ratio (r = 0.427, p = 0.0003; r = 0.435, p = 0.0003, respectively). The mean SUV and T/M ratio of vasectomized men were significantly lower than those of nonvasectomized men (p < 0.0378 and p = 0.0001, respectively).

Conclusions

Glucose metabolism in the testis in an adult population was found to be correlated with age, serum sex hormone level, and vasectomy history. These results indicate that testicular ¹⁸F-FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular ¹⁸F-FDG uptake in the normal adult population.     

4D PET/CT对肺部结节呼吸伪影纠正及SUV值影响的初步探讨

目的 通过与3D PET/CT的采集方式进行对比,探讨4D采集对肺部结节呼吸伪影纠正的应用价值. 方法 选择在我科进行常规3D PET/CT显像并同意进行呼吸门控4D显像的患者14例,均伴有多个肺部结节.3D PET采集时间2 min/床位,4D PET采集时间6 min/床位,分为6个呼吸时相,平均每时相1 min.SUV值由AW系统全自动分析获得.每个结节在3D PET以及4D PET的6个时相中共测量7次. 结果 所有患者4D和3D胸部PET/CT图像清晰,PET信噪比分别为4.00 ±0.35和3.98 ±0.55,二者之间差异没有统计学意义(Z=-1.109,P=0.267);而4D CT噪声水平较3D CT略增高,在肺结节特性显示中某些时相优于常规CT.14例患者37个肺部结节中,3D PET/CT发现呼吸伪影33个,4D PET/CT纠正伪影31个(93.9％);4D PET显像可以提高病灶的SUV值,3D和4D PET所获得的SUVmax相关性非常好(r=0.971),但4D PET得到的SUV一明显高于3D PET/CT(13.69 ±6.70 vs 12.76 ±6.74,t=3.475,P=0.001). 结论 采用4D PET/CT显像图像质量清晰,呼吸伪影校正良好,能达到诊断的要求,且4D PET/CT所获得的肺部结节SUVmax比3D常规采集明显升高,可以为临床诊断提供更多的临床依据.     

Predictive significance of standardized uptake value parameters of FDG-PET in patients with non-small cell lung carcinoma

¹⁸F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is widely used to diagnose and stage non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the predictive ability of different FDG standardized uptake values (SUVs) in 74 patients with newly diagnosed NSCLC. ¹⁸F-FDG PET/CT scans were performed and different SUV parameters (SUV_max, SUV_avg, SUV_T/L, and SUV_T/A) obtained, and their relationship with clinical characteristics were investigated. Meanwhile, correlation and multiple stepwise regression analyses were performed to determine the primary predictor of SUVs for NSCLC. Age, gender, and tumor size significantly affected SUV parameters. The mean SUVs of squamous cell carcinoma were higher than those of adenocarcinoma. Poorly differentiated tumors exhibited higher SUVs than well-differentiated ones. Further analyses based on the pathologic type revealed that the SUV_max, SUV_avg, and SUV_T/L of poorly differentiated adenocarcinoma tumors were higher than those of moderately or well-differentiated tumors. Among these four SUV parameters, SUV_T/L was the primary predictor for tumor differentiation. However, in adenocarcinoma, SUV_max was the determining factor for tumor differentiation. Our results showed that these four SUV parameters had predictive significance related to NSCLC tumor differentiation; SUV_T/L appeared to be most useful overall, but SUV_max was the best index for adenocarcinoma tumor differentiation.     

Diagnostic accuracy of 18-F FDG-PET/CT in evaluation of malignant neuronal involvement in neurologically manifested cancer patients

Aim and objectives

The aim of this study was to assess the role of 18-F FDG-PET/CT in evaluating the peripheral malignant neuronal affection as well as perineural tumoral spread that occurs in patients with cancers.

Histone Mark Profiling in Pediatric Astrocytomas Reveals Prognostic Significance of H3K9 Trimethylation and Histone Methyltransferase SUV39H1

Alterations in global histone methylation regulate gene expression and participate in cancer onset and progression. The profile of histone methylation marks in pediatric astrocytomas is currently understudied with limited data on their distribution among grades. The global expression patterns of repressive histone marks H3K9me3, H3K27me3, and H4K20me3 and active H3K4me3 and H3K36me3 along with their writers SUV39H1, SETDB1, EZH2, MLL2, and SETD2 were investigated in 46 pediatric astrocytomas and normal brain tissues. Associations between histone marks and modifying enzymes with clinicopathological characteristics and disease-specific survival were studied along with their functional impact in proliferation and migration of pediatric astrocytoma cell lines using selective inhibitors in vitro. Upregulation of histone methyltransferase gene expression and deregulation of histone code were detected in astrocytomas compared to normal brain tissues, with higher levels of SUV39H1, SETDB1, and SETD2 as well as H4K20me3 and H3K4me3 histone marks. Pilocytic astrocytomas exhibited lower MLL2 levels compared to diffusely infiltrating tumors indicating a differential pattern of epigenetic regulator expression between the two types of astrocytic neoplasms. Moreover, higher H3K9me3, H3K36me3, and SETDB1 expression was detected in grade IIΙ/IV compared to grade II astrocytomas. In univariate analysis, elevated H3K9me3 and MLL2 and diminished SUV39H1 expression adversely affected survival. Upon multivariate survival analysis, only SUV39H1 expression was revealed as an independent prognostic factor of adverse significance. Treatment of pediatric astrocytoma cell lines with SUV39H1 inhibitor reduced proliferation and cell migration. Our data implicate H3K9me3 and SUV39H1 in the pathobiology of pediatric astrocytomas, with SUV39H1 yielding prognostic information independent of other clinicopathologic variables.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01090-x.     

Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.