目的构建影像组学模型,提高~(18)F-PSMA-1007 PET/CT对局灶性前列腺癌的鉴别能力。方法回顾性收集2020年7月至2024年4月西安交通大学第一附属医院经前列腺穿刺活检确诊前列腺癌、~(18)F-PSMA-1007 PET/CT显示局灶性核素浓聚的74例患者,...目的构建影像组学模型,提高~(18)F-PSMA-1007 PET/CT对局灶性前列腺癌的鉴别能力。方法回顾性收集2020年7月至2024年4月西安交通大学第一附属医院经前列腺穿刺活检确诊前列腺癌、~(18)F-PSMA-1007 PET/CT显示局灶性核素浓聚的74例患者,中位年龄为71岁,42例患者Gleason评分<8,32例患者Gleason评分≥8,根据检查时间随机选出外部验证集,并将其余患者按照7∶3随机划分为训练集和测试集。在配准图像上半自动勾画病灶感兴趣区(region of interest,ROI)并手动调整,随后将ROI对称性移至对侧非肿瘤组织,通过方差和相关性分析筛选特征,使用Logistic回归构建模型,并与视觉判断比较,通过绘制受试者工作特征(receiver operating characteristic,ROC)曲线比较各个模型的效果。基于Gleason评分、血清tPSA水平和病灶位置划分亚组,获得肿瘤组织鉴别诊断的最佳特征。结果共筛选出8个特征,视觉评价、测试集和外部验证集中曲线下面积(area under the curve,AUC)分别为0.858、0.933和0.891,鉴别前列腺肿瘤的灵敏度分别为0.757、0.800和0.917,特异度分别为0.960、0.800和0.792。亚组分析结果显示,组学特征10percentile和skewness在肿瘤鉴别中价值较高,肿瘤组织10Percentile各组均高于非肿瘤组织(P值分别为0.012、0.002、<0.001、<0.001、<0.001、<0.001);当tPSA≤10 ng/mL且Gleason评分≥8时,肿瘤与非肿瘤组织skewness无统计学差异(P=0.08);tPSA≥20 ng/mL时,非肿瘤组织的skewness稍高于肿瘤组织,但无统计学差异(P值分别为0.285、0.791);肿瘤灶位于前列腺后部(左后部、右后部)时,skewness显著高于非肿瘤组织(P均<0.001)。结论影像组学模型在区分局灶性前列腺癌肿瘤与非肿瘤组织方面灵敏度和准确性优于视觉评价,但后者特异度更高;其中skewness和10percentile对于鉴别诊断有较高价值。展开更多
Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies.However,its application to solid tumors presents significant challenges due to the limited accessi...Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies.However,its application to solid tumors presents significant challenges due to the limited accessibility and heterogeneity.Localized delivery of tumor-specific T-cells using biomaterials has shown promise,however,procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time constraints.Methods:Polyethylene glycol(PEG)-based three-dimensional(3D)scaffolds were developed and conjugated with positively charged poly-L-lysine(PLL)using carbamide chemistry for efficient loading of lentiviruses(LVs)carrying tumor antigen-specific T-cell receptors(TCRs).The physical and biological properties of the scaffold were extensively characterized.Further,the scaffold loaded with OVA-TCR LVs was implanted in B16F10 cells expressing ovalbumin(B16-OVA)tumor model to evaluate the anti-tumor response and the presence of transduced T-cells.Results:Our findings demonstrate that the scaffolds do not induce any systemic inflammation upon subcutaneous implantation and effectively recruit T-cells to the site.In B16-OVA melanoma tumor-bearing mice,the scaffolds efficiently transduce host T-cells with OVA-specific TCRs.These genetically modified T-cells exhibit homing capability towards the tumor and secondary lymphoid organs,resulting in a significant reduction of tumor size and systemic increase in anti-tumor cytokines.Immune cell profiling revealed a significantly high percentage of transduced T-cells and a notable reduction in suppressor immune cells within the tumors of mice implanted with these scaffolds.Conclusions:Our scaffold-based T-cell therapy presents an innovative in situ localized approach for programming T-cells to target solid tumors.This approach offers a viable alternative to in vitro manipulation of T-cells,circumventing the need for large-scale in vitro generation and culture of tumor-specific T-cells.It offers an off-the-shelf alternative that facilitates the use of host cells instead of allogeneic cells,thereby,overcoming a major hurdle.展开更多
文摘目的构建影像组学模型,提高~(18)F-PSMA-1007 PET/CT对局灶性前列腺癌的鉴别能力。方法回顾性收集2020年7月至2024年4月西安交通大学第一附属医院经前列腺穿刺活检确诊前列腺癌、~(18)F-PSMA-1007 PET/CT显示局灶性核素浓聚的74例患者,中位年龄为71岁,42例患者Gleason评分<8,32例患者Gleason评分≥8,根据检查时间随机选出外部验证集,并将其余患者按照7∶3随机划分为训练集和测试集。在配准图像上半自动勾画病灶感兴趣区(region of interest,ROI)并手动调整,随后将ROI对称性移至对侧非肿瘤组织,通过方差和相关性分析筛选特征,使用Logistic回归构建模型,并与视觉判断比较,通过绘制受试者工作特征(receiver operating characteristic,ROC)曲线比较各个模型的效果。基于Gleason评分、血清tPSA水平和病灶位置划分亚组,获得肿瘤组织鉴别诊断的最佳特征。结果共筛选出8个特征,视觉评价、测试集和外部验证集中曲线下面积(area under the curve,AUC)分别为0.858、0.933和0.891,鉴别前列腺肿瘤的灵敏度分别为0.757、0.800和0.917,特异度分别为0.960、0.800和0.792。亚组分析结果显示,组学特征10percentile和skewness在肿瘤鉴别中价值较高,肿瘤组织10Percentile各组均高于非肿瘤组织(P值分别为0.012、0.002、<0.001、<0.001、<0.001、<0.001);当tPSA≤10 ng/mL且Gleason评分≥8时,肿瘤与非肿瘤组织skewness无统计学差异(P=0.08);tPSA≥20 ng/mL时,非肿瘤组织的skewness稍高于肿瘤组织,但无统计学差异(P值分别为0.285、0.791);肿瘤灶位于前列腺后部(左后部、右后部)时,skewness显著高于非肿瘤组织(P均<0.001)。结论影像组学模型在区分局灶性前列腺癌肿瘤与非肿瘤组织方面灵敏度和准确性优于视觉评价,但后者特异度更高;其中skewness和10percentile对于鉴别诊断有较高价值。
基金Department of Biotechnology(DBT,Govt of India)(BT/PR31315/MED/32/667/2019)DBT along with Wadhwani Research Center for Bioengineering,IIT Bombay(BT/INF/22/SP23026/2017)Department of Biotechnology(DBT,Govt of India)(BT/INF/22/SP17358/2016).
文摘Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies.However,its application to solid tumors presents significant challenges due to the limited accessibility and heterogeneity.Localized delivery of tumor-specific T-cells using biomaterials has shown promise,however,procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time constraints.Methods:Polyethylene glycol(PEG)-based three-dimensional(3D)scaffolds were developed and conjugated with positively charged poly-L-lysine(PLL)using carbamide chemistry for efficient loading of lentiviruses(LVs)carrying tumor antigen-specific T-cell receptors(TCRs).The physical and biological properties of the scaffold were extensively characterized.Further,the scaffold loaded with OVA-TCR LVs was implanted in B16F10 cells expressing ovalbumin(B16-OVA)tumor model to evaluate the anti-tumor response and the presence of transduced T-cells.Results:Our findings demonstrate that the scaffolds do not induce any systemic inflammation upon subcutaneous implantation and effectively recruit T-cells to the site.In B16-OVA melanoma tumor-bearing mice,the scaffolds efficiently transduce host T-cells with OVA-specific TCRs.These genetically modified T-cells exhibit homing capability towards the tumor and secondary lymphoid organs,resulting in a significant reduction of tumor size and systemic increase in anti-tumor cytokines.Immune cell profiling revealed a significantly high percentage of transduced T-cells and a notable reduction in suppressor immune cells within the tumors of mice implanted with these scaffolds.Conclusions:Our scaffold-based T-cell therapy presents an innovative in situ localized approach for programming T-cells to target solid tumors.This approach offers a viable alternative to in vitro manipulation of T-cells,circumventing the need for large-scale in vitro generation and culture of tumor-specific T-cells.It offers an off-the-shelf alternative that facilitates the use of host cells instead of allogeneic cells,thereby,overcoming a major hurdle.
