Further development of local IL-2 therapy of cancer: multiple versus single IL-2 treatment of transplanted murine colon carcinoma

We have compared the effect of one and up to four local IL-2 treatments of transplanted MC38 colon carcinoma. A single IL-2 treatment prolonged the survival time (p=0.015), but no cure was obtained. One local IL-2 treatment inhibited tumor growth for about 1 week. After the start of tumor regrowth, a further IL-2 injection was given. After four IL-2 injections 6 out of 13 mice were cured. Histological studies show that IL-2 induced a local vascular leakage syndrome leading to massive peritumoral edema and subsequent necrosis of tumor tissue. IL-2 also attracted infiltrating cells, mainly macrophages. Subsequent IL-2 injections led to complete tumor regression. We believe that the combination of necrotic tumor debris and the IL-2–induced macrophage reaction enhanced a tumor-specific immune response. This local IL-2 application was not toxic.     

Elevated GAPDH expression is associated with the proliferation and invasion of lung and esophageal squamous cell carcinomas

Glyceraldehyde‐3‐phosphate dehydrogenase, is one of the most investigated housekeeping genes and widely used as an internal control in analysis of gene expression levels. The present study was designed to assess whether GAPDH is associated with cancer cell growth and progression and, therefore may not be a good internal control in cancer research. Our results from clinical tissue studies showed that the levels of GAPDH protein were significantly up‐regulated in lung squamous cell carcinoma tissues, compared with the adjacent normal lung tissues, and this was confirmed by western blotting and immunohistochemistry. GAPDH knockdown by siRNA resulted in significant reductions in proliferation, migration, and invasion of lung squamous carcinoma cells in vitro. In a nude mouse cancer xenograft model, GAPDH knockdown significantly inhibited the cell proliferation and migration/invasion in vivo. In summary, GAPDH may not be an appropriate internal control for gene expression studies, especially in cancer research. The role of GAPDH in cancer development and progression should be further examined in pre‐clinical and clinical studies.     

放疗联合食管支架对晚期食道癌患者预后影响的COX分析

目的:分析放疗联合食管支架对晚期食道癌患者预后影响。方法:选取我院收治晚期食道癌患者90例,经西医诊断标准经病理学及CT检查确诊为晚期食道癌,根据治疗方法不同分为实验组(放疗联合食管支架术)与对照组(食管支架术)。比较患者肝、肾功能,及生存率。采用Cox分析法对患者预后与放疗的相关性分析。结果:两组患者半年、1年、3年、5年生存率相比较,实验组与对照组相比较,生存率升高,差异具有统计学意义(P0.05);经COX分析,食管癌患者的生存率与患者的淋巴结转移书、TNM分期以及是否放疗有关(P0.05);经COX分析后可见,是否有食管瘘、是否根治术、病理分型、TNM分期、是否放疗为影响食管癌患者生存的独立影响因素(P0.05)。结论:是否有食管瘘、是否根治术、病理分型、TNM分期、是否放疗是食管癌患者生存的独立影响因素。术后的放疗治疗对患者的生存有积极意义。     

新疆食管癌中Myc、TP53表达及其与临床病理因素相关性研究

目的:检测Myc和TP53在食管癌组织和远端无癌组织的表达情况,并分析其与临床病理因素之间的关系,初步探讨Myc和TP53在新疆食管癌发生发展中可能存在的特点。方法:经Trizol一步法提取88例新疆地区食管癌组织及其远端无癌组织标本总RNA,m RNA逆转录为c DNA,经聚合酶链式反应生成产物,运用光密度值即半定量RT-PCR技术检测88例新疆地区食管癌组织、远端无癌组织中Myc和TP53的m RNA表达情况及二者阳性表达率,并分析Myc和TP53的表达与临床病理因素之间的相关性。结果:1 Myc的m RNA相对表达量在食管癌组织中高于远端无癌组织,差异有显著性(P0.01);TP53的m RNA相对表达量在远端无癌组织中高于癌组织(P0.05);2 Myc的阳性表达率在88例食管癌组织中高于远端无癌组织(P0.05);TP53的阳性表达率在远端无癌组织中高于癌组织(P0.05);3Myc的表达与分化程度(P0.01)、TNM分期(P0.01)、淋巴结转移(P0.05)、侵犯深度(P0.05)和族别(P0.05)有关,与性别无关;TP53的表达与侵犯程度(P0.01)有关,与性别、分化程度、TNM分期、淋巴结转移和族别均无关;4 88例食管癌组织中,Myc和TP53的表达呈现负相关(r=-0.501,P0.0 1)。结论:Myc在新疆地区食管癌组织中表达上调,TP53则表达减弱。说明Myc参与食管癌的发生和发展,而TP53则可能保护正常组织不发生癌变。     

区域效应－一个前列腺癌早期诊断的新思路

目前临床上有许多怀疑前列腺癌但穿刺阴性的病例,为了避免漏诊,多数患者必须接受重复穿刺。尽管部分患者经重复穿刺确诊为前列腺癌,而更多患者经过长期随访以及反复穿刺最终确诊为良性病变。近期研究证实,癌灶附近的组织学表现正常的组织中也可发生与癌灶相似的分子改变。因此,我们认为在前列腺癌的发生过程中存在区域效应。在这一理论指导下,选择适当的可反映前列腺癌区域效应的标记物,在穿刺阴性的标本中检出与癌灶相似的分子改变,就可以帮助临床医生在常规病理诊断之前,提前预测前列腺癌的发生。如果能够找到这样的标记物,并在大规模的诊断试验中证实其可行性,那么就可以极大地改善前列腺癌诊断的现状。     

Peroxiredoxin 1 is involved in disassembly of flagella and cilia

Cilia/flagella are evolutionarily conserved cellular organelles. In this study, we demonstrated that Dunaliella salina Peroxiredoxin 1 (DsPrdx1) localized to the flagella and basal bodies, and was involved in flagellar disassembly. The link between DsPrdx1 and flagella of Dunaliella salina (D. salina) encouraged us to explore the function of its human homologue, Homo sapiens Peroxiredoxin 1 (HsPrdx1) in development and physiology. Our results showed that HsPrdx1 was overexpressed, and cilia were lost in esophageal squamous cell carcinoma (ESCC) cells compared with the non-cancerous esophageal epithelial cells Het-1A. Furthermore, when HsPrdx1 was knocked down by short hairpin RNA (shRNA) lentivirus in ESCC cells, the phenotype of cilia lost can be reversed, and the expression levels of tumor suppressor genes LKB1 and p-AMPK were increased, and the activity of the oncogene Aurora A was inhibited compared with those in cells transfected with scrambe-shRNA lentivirus. These findings firstly showed that Prdx1 is involved in disassembly of flagella and cilia, and suggested that the abnormal expression of the cilia-related gene including Prdx1 may affect both ciliogenesis and cancernogenesis.     

Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells

Wnt/β-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that β-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of β-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of β-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/β-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.     

原位可注射壳聚糖基温敏水凝胶的制备及其在预防ESD术后食管狭窄中分阶段释药应用研究

摘要 目的：构建一种可以分阶段释放药物的原位可注射水凝胶，通过直接注射在ESD（Endoscopic Submucosal Dissection，内镜黏膜下剥离术）术后伤口处，形成水凝胶敷料，起到保护伤口的作用。同时凝胶中的两种药物通过分阶段释放的方式，更好地促进伤口的无瘢痕愈合，为ESD术后食管狭窄的预防提供一种新的参考方案。方法：在壳聚糖/β-甘油磷酸钠（CS/β-GP）温敏水凝胶的体系中加入聚多巴胺（PDA），制备壳聚糖/β-甘油磷酸钠/聚多巴胺（CS/?β-GP/PDA）水凝胶。通过在载药水凝胶中加入聚乙二醇-聚乳酸-羟基乙酸（PEG-PLGA）纳米载药微粒制备CS/β-GP/PDA/NPs双载药水凝胶，通过两种载药体系的复合，实现药物的分阶段释放。通过流变学实验测定CS/β-GP、CS/β-GP/PDA、CS/β-GP/PDA/NPs凝胶体系的相转变温度以及凝胶强度。通过高效液相色谱法检测CS/β-GP/PDA/NPs水凝胶中两种药物的释放动力学特征。通过CCK-8细胞增殖实验评价CS/β-GP/PDA、CS/β-GP/PDA/NPs温敏水凝胶的生物相容性。在体外猪食管中，模拟ESD术后创口，通过内镜辅助将水凝胶母液注射在伤口处，并通过内镜观察水凝胶的凝胶状态。结果：得到了粘附性显著增强的壳聚糖/β-甘油磷酸钠/聚多巴胺（CS/β-GP/PDA）凝胶体系。流变学实验证明聚多巴胺（PDA）的加入可以显著降低水凝胶的凝胶温度，缩短原位成胶时间。CCK-8实验显示CS/β-GP/PDA、CS/β-GP/PDA/NPs凝胶体系无潜在的细胞毒性。在体外猪食管模拟实验中，将其凝胶母液注射在伤口处后，可原位形成凝胶，且凝胶贴合伤口，具有较强的粘附性。通过体外释药速率测定，验证了CS/β-GP/PDA/NPs水凝胶中所载两种药物释放速率存在明显差异，可实现药物的分阶段释放。结论：设计的CS/β-GP/PDA/NPs凝胶体系适用于ESD术后的伤口修复，并能够实现分阶段释药，对于预防ESD术后食管狭窄具有潜在的应用价值。