[目的]探讨底板反应蛋白1(SPON1)介导波形蛋白(Vimentin)/上皮型钙粘素(E-cadherin)信号通路对于结直肠癌细胞转移的影响。[方法]采集2021年4月-2022年7月手术的78例结直肠癌患者的癌组织及癌旁组织制作石蜡标本,免疫组化法检测其SPON1...[目的]探讨底板反应蛋白1(SPON1)介导波形蛋白(Vimentin)/上皮型钙粘素(E-cadherin)信号通路对于结直肠癌细胞转移的影响。[方法]采集2021年4月-2022年7月手术的78例结直肠癌患者的癌组织及癌旁组织制作石蜡标本,免疫组化法检测其SPON1蛋白水平。随机将SW620细胞分为空白组、阴性对照组和SPON1敲低组,将阴性对照质粒、SPON1敲低质粒分别转入阴性对照组和SPON1敲低组的SW620细胞中,构建细胞模型,检测EMT相关蛋白Vimentin、E-cadherin蛋白表达。[结果]结直肠癌组织SPON1蛋白阳性表达率85.90%(67/78)高于癌旁组织16.67%(13/78),其SPON1蛋白高表达率84.62%(66/78)高于癌旁组织19.23%(15/78)。与空白组、阴性对照组的SW620细胞比较,SPON1敲低组的SW620细胞侵袭数量与迁移率降低(89.26±8.19 vs 89.26±8.19 vs 22.38±5.11/个;75.23%±6.28%vs 78.15%±11.29%vs 26.73%±3.16%);SPON1敲低组的SW620细胞中SPON1 mRNA、SPON1和Vimentin蛋白水平下降(P<0.05),E-cadherin蛋白水平增加(P<0.05)。[结论]SPON1在结肠癌中表达上调,敲低SPON1的表达能下调Vimentin表达,上调E-cadherin表达,抑制结肠癌细胞的转移。展开更多
腹膜后肿瘤是一类发生在复杂解剖间隙的肿瘤类别,兼具临床诊治挑战性与科研发掘价值性。本文系统梳理了腹膜后肿瘤的基础特征与诊疗进展:1) 解剖学层面,腹膜后间隙包含多脏器与神经血管结构,其潜在腔隙特性导致肿瘤生长隐匿且易广泛粘连...腹膜后肿瘤是一类发生在复杂解剖间隙的肿瘤类别,兼具临床诊治挑战性与科研发掘价值性。本文系统梳理了腹膜后肿瘤的基础特征与诊疗进展:1) 解剖学层面,腹膜后间隙包含多脏器与神经血管结构,其潜在腔隙特性导致肿瘤生长隐匿且易广泛粘连,约50%患者确诊即晚期;2) 病理分型涵盖15类组织来源,其中恶性肿瘤占80%,以脂肪肉瘤(33%)、平滑肌肉瘤最为常见;3) 诊断体系依赖多模态影像技术(CT/MRI定位准确率85%)、液体活检及人工智能辅助分析,但早期诊断仍面临特异性生物标志物缺失的瓶颈;4) 治疗策略以根治性切除为核心(R0切除率68.4%),联合新辅助放化疗(5年生存率提升12%~28%)、靶向治疗(如MDM2/CDK4抑制剂)及免疫治疗形成MDT模式,但巨大肿瘤(>10 cm)的R0切除率仅25%;5) 预后受多重因素影响,肿瘤分期(III期5年生存率40%~50%)、切除程度(R0与R2切除生存率相差3倍)及分子分型构成关键变量。未来研究将聚焦于肿瘤微环境调控机制解析、基于影像组学的术前精准评估体系构建,以及新型治疗靶点(如PPAR-γ激动剂、海洋化合物)的临床转化,以期突破当前诊疗困境。Retroperitoneal tumors are a type of tumor that occurs in complex anatomical gaps, which have both the challenges of clinical diagnosis and treatment and the value of scientific research and development. This paper systematically sorts out the basic characteristics and diagnosis and treatment progress of retroperitoneal tumors: 1) At the anatomical level, the retroperitoneal space contains multiple organs and neurovascular structures, and its potential lacunarity causes tumor growth to be hidden and prone to widespread adhesions. About 50% of patients are diagnosed as advanced;2) Pathological typing covers 15 types of tissue sources, of which malignant tumors account for 80%, with liposarcoma (33%) and leiomyosarcoma being the most common;3) The diagnostic system relies on multimodal imaging technology (85% accuracy of CT/MRI positioning), liquid biopsy and artificial intelligence-assisted analysis, but early diagnosis still faces bottlenecks of specific biomarker deletion;4) The treatment strategy focuses on radical resection (R0 resection rate 68.4%), combined with neoadjuvant chemoradiation and chemotherapy (5-year survival rate increased by 12%~28%), targeted therapy (such as MDM2/CDK4 inhibitors) and immunotherapy formed an MDT pattern, but the R0 resection rate of huge tumors (>10 cm) was only 25%;5) The prognosis was affected by multiple factors, and tumor stage (40%~50% of phase III 5-year survival rate), resection degree (3 times different survival rate of R0 and R2 resection) and molecular typing constituted key variables. Future research will focus on the analysis of tumor microenvironment regulation mechanisms, the construction of preoperative precise evaluation system based on imaging complications, and the clinical transformation of new therapeutic targets (such as PPAR-γ agonists and marine compounds), in order to break through the current diagnosis and treatment dilemma.展开更多
目的:探索术前血清CA19-9与腹膜假黏液瘤(pseudomyxoma peritonei,PMP)病理级别的关系,分析CA19-9对预后的影响。方法:回顾性分析2004年10月至2024年10月于本团队初次行肿瘤细胞减灭术联合腹腔热灌注化疗(cytoreductive surgery plus hy...目的:探索术前血清CA19-9与腹膜假黏液瘤(pseudomyxoma peritonei,PMP)病理级别的关系,分析CA19-9对预后的影响。方法:回顾性分析2004年10月至2024年10月于本团队初次行肿瘤细胞减灭术联合腹腔热灌注化疗(cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy,CRS+HIPEC)的321例PMP患者的临床资料,受试者工作曲线用于分析CA19-9对病理级别的鉴别价值,K-M法评估不同水平CA19-9对总体生存期的影响。结果:46.1%(148/321)的患者术前CA19-9水平升高,且与病理级别相关;术前CA19-9>693.3 U/mL时,病理级别更倾向于腹膜高级别黏液癌伴印戒细胞(曲线下面积:0.67,95%CI:0.54~0.80,P=0.021);术前CA19-9是影响PMP患者总生存期的独立危险因素(升高组vs.正常组,中位生存期53.62个月vs.未达到,P<0.001)。结论:初次行CRS+HIPEC的PMP患者,其术前血清CA19-9水平与病理级别相关,是影响总生存期的不良因素。展开更多
文摘[目的]探讨底板反应蛋白1(SPON1)介导波形蛋白(Vimentin)/上皮型钙粘素(E-cadherin)信号通路对于结直肠癌细胞转移的影响。[方法]采集2021年4月-2022年7月手术的78例结直肠癌患者的癌组织及癌旁组织制作石蜡标本,免疫组化法检测其SPON1蛋白水平。随机将SW620细胞分为空白组、阴性对照组和SPON1敲低组,将阴性对照质粒、SPON1敲低质粒分别转入阴性对照组和SPON1敲低组的SW620细胞中,构建细胞模型,检测EMT相关蛋白Vimentin、E-cadherin蛋白表达。[结果]结直肠癌组织SPON1蛋白阳性表达率85.90%(67/78)高于癌旁组织16.67%(13/78),其SPON1蛋白高表达率84.62%(66/78)高于癌旁组织19.23%(15/78)。与空白组、阴性对照组的SW620细胞比较,SPON1敲低组的SW620细胞侵袭数量与迁移率降低(89.26±8.19 vs 89.26±8.19 vs 22.38±5.11/个;75.23%±6.28%vs 78.15%±11.29%vs 26.73%±3.16%);SPON1敲低组的SW620细胞中SPON1 mRNA、SPON1和Vimentin蛋白水平下降(P<0.05),E-cadherin蛋白水平增加(P<0.05)。[结论]SPON1在结肠癌中表达上调,敲低SPON1的表达能下调Vimentin表达,上调E-cadherin表达,抑制结肠癌细胞的转移。
文摘腹膜后肿瘤是一类发生在复杂解剖间隙的肿瘤类别,兼具临床诊治挑战性与科研发掘价值性。本文系统梳理了腹膜后肿瘤的基础特征与诊疗进展:1) 解剖学层面,腹膜后间隙包含多脏器与神经血管结构,其潜在腔隙特性导致肿瘤生长隐匿且易广泛粘连,约50%患者确诊即晚期;2) 病理分型涵盖15类组织来源,其中恶性肿瘤占80%,以脂肪肉瘤(33%)、平滑肌肉瘤最为常见;3) 诊断体系依赖多模态影像技术(CT/MRI定位准确率85%)、液体活检及人工智能辅助分析,但早期诊断仍面临特异性生物标志物缺失的瓶颈;4) 治疗策略以根治性切除为核心(R0切除率68.4%),联合新辅助放化疗(5年生存率提升12%~28%)、靶向治疗(如MDM2/CDK4抑制剂)及免疫治疗形成MDT模式,但巨大肿瘤(>10 cm)的R0切除率仅25%;5) 预后受多重因素影响,肿瘤分期(III期5年生存率40%~50%)、切除程度(R0与R2切除生存率相差3倍)及分子分型构成关键变量。未来研究将聚焦于肿瘤微环境调控机制解析、基于影像组学的术前精准评估体系构建,以及新型治疗靶点(如PPAR-γ激动剂、海洋化合物)的临床转化,以期突破当前诊疗困境。Retroperitoneal tumors are a type of tumor that occurs in complex anatomical gaps, which have both the challenges of clinical diagnosis and treatment and the value of scientific research and development. This paper systematically sorts out the basic characteristics and diagnosis and treatment progress of retroperitoneal tumors: 1) At the anatomical level, the retroperitoneal space contains multiple organs and neurovascular structures, and its potential lacunarity causes tumor growth to be hidden and prone to widespread adhesions. About 50% of patients are diagnosed as advanced;2) Pathological typing covers 15 types of tissue sources, of which malignant tumors account for 80%, with liposarcoma (33%) and leiomyosarcoma being the most common;3) The diagnostic system relies on multimodal imaging technology (85% accuracy of CT/MRI positioning), liquid biopsy and artificial intelligence-assisted analysis, but early diagnosis still faces bottlenecks of specific biomarker deletion;4) The treatment strategy focuses on radical resection (R0 resection rate 68.4%), combined with neoadjuvant chemoradiation and chemotherapy (5-year survival rate increased by 12%~28%), targeted therapy (such as MDM2/CDK4 inhibitors) and immunotherapy formed an MDT pattern, but the R0 resection rate of huge tumors (>10 cm) was only 25%;5) The prognosis was affected by multiple factors, and tumor stage (40%~50% of phase III 5-year survival rate), resection degree (3 times different survival rate of R0 and R2 resection) and molecular typing constituted key variables. Future research will focus on the analysis of tumor microenvironment regulation mechanisms, the construction of preoperative precise evaluation system based on imaging complications, and the clinical transformation of new therapeutic targets (such as PPAR-γ agonists and marine compounds), in order to break through the current diagnosis and treatment dilemma.
文摘目的:探索术前血清CA19-9与腹膜假黏液瘤(pseudomyxoma peritonei,PMP)病理级别的关系,分析CA19-9对预后的影响。方法:回顾性分析2004年10月至2024年10月于本团队初次行肿瘤细胞减灭术联合腹腔热灌注化疗(cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy,CRS+HIPEC)的321例PMP患者的临床资料,受试者工作曲线用于分析CA19-9对病理级别的鉴别价值,K-M法评估不同水平CA19-9对总体生存期的影响。结果:46.1%(148/321)的患者术前CA19-9水平升高,且与病理级别相关;术前CA19-9>693.3 U/mL时,病理级别更倾向于腹膜高级别黏液癌伴印戒细胞(曲线下面积:0.67,95%CI:0.54~0.80,P=0.021);术前CA19-9是影响PMP患者总生存期的独立危险因素(升高组vs.正常组,中位生存期53.62个月vs.未达到,P<0.001)。结论:初次行CRS+HIPEC的PMP患者,其术前血清CA19-9水平与病理级别相关,是影响总生存期的不良因素。
文摘目的探讨Egl-9家族缺氧诱导因子1(Egl-9 family hypoxia inducible factor 1,EGLN1)缺失对结直肠癌(colorectal cancer,CRC)细胞增殖、迁移、侵袭及自噬通路的影响,为CRC精准治疗提供潜在靶点。方法利用CRISPR-Cas9技术构建EGLN1敲除的LoVo与RKO细胞株;通过CCK-8法、集落形成、Transwell实验及划痕愈合实验,分别检测细胞的增殖、侵袭及迁移能力。Western blot分析自噬标志物LC3B-Ⅱ/LC3B-Ⅰ值与p62蛋白表达水平,评估自噬通路激活情况。通过建立裸鼠皮下移植瘤模型,评估自噬激活剂雷帕霉素对EGLN1敲除异种移植瘤生长的影响。采用苏木精-伊红(hematoxylin and eosin,HE)染色和Ki-67免疫组化检测异种移植瘤组织细胞增殖情况。结果成功构建稳定的EGLN1敲除细胞系。EGLN1的缺失显著增强LoVo和RKO细胞增殖、迁移和侵袭(均P<0.05);自噬相关蛋白分析结果显示,EGLN1敲除后LC3B-Ⅱ/LC3B-Ⅰ值下降,p62显著积累。采用晚期自噬抑制剂氯喹或早期抑制剂3-甲基腺嘌呤处理进一步加剧自噬抑制。体内实验表明,EGLN1敲除组的肿瘤体积显著大于EGLN1野生型组(P<0.05),而雷帕霉素治疗有效抑制了肿瘤生长。HE染色和Ki-67免疫组化证实,EGLN1敲除促进异种移植瘤中的细胞增殖,而雷帕霉素可逆转该促瘤效应。结论EGLN1通过激活自噬通路抑制CRC细胞的恶性表型,其缺失可能导致自噬抑制,从而促进肿瘤细胞增殖、迁移与侵袭。靶向EGLN1/自噬轴可能是治疗CRC的有效策略。
