十二指肠复合神经节细胞瘤/神经瘤-神经内分泌肿瘤1例

十二指肠复合神经节细胞瘤/神经瘤-神经内分泌肿瘤(compositegangliocytoma/neuromaand neuroendocrinetumor,CoGNET)是一种较罕见的肿瘤。CoGNET先前被称为节细胞性副神经节瘤(gangliocytic paraganglioma,GP),在2022年世界卫生组织神经内分泌肿瘤分类中,其被重新命名。本文报告1例65岁CoGNET男性患者,因反酸、烧心伴便血就诊。术后病理显示肿物由梭形细胞、神经节细胞和上皮样细胞3种细胞成分组成。3种细胞成分具有不同的免疫组织化学染色模式:梭形细胞示神经丝蛋白(neurofilament protein,NFP)(+),中枢神经特异蛋白(central nervous system specific protein,S-100)(+),与性别决定区域Y相关的高迁移率组盒蛋白10(sex deciding region y-box[SRY]-related high motility[HMG]-box 10,SOX10)(+);神经节细胞示NFP(+),S-100(+),SOX10(-);上皮样细胞示广谱细胞角蛋白(pan cytokeratin,AE1/AE3)(+),细胞黏附分子5.2(cell adhesion molecules 5.2,CAM5.2)(+),突触素(synaptophysin,Syn)(+),嗜铬素A(chromograninA,CgA)(+),孕激素受体(progesterone receptor,PR)(+),GATA结合蛋白3(GATA binding protein 3,GATA-3)(-),胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)(-),分化抗原簇117(cluster of differentiation 117,CD117)(弱+)。病理诊断为CoGNET,神经内分泌肿瘤成分为高分化神经内分泌瘤。患者术后未行进一步治疗,术后随访19个月,无复发及转移。

大脑表浅肿瘤CT和MRI诊断与鉴别诊断

目的:分析大脑表浅肿瘤的CTMRI表现并探讨其影像诊断特征。材料和方法:收集复旦大学附属华山医院经病理证实的大脑表浅肿瘤80例,行CT、MRI检查。结果:少枝胶质瘤47例,间变性少枝胶质瘤10例,节细胞胶质瘤15例,胚胎发育不良性神经上皮瘤5例,多形黄色细胞瘤3例。结论:脑浅表肿瘤存在影像特征,CT及MRI对其诊断有一定的价值。

复杂性腹膜后节细胞神经瘤的诊断与治疗

腹膜后节细胞神经瘤是一种罕见的神经源性良性肿瘤,行手术彻底切除,预后良好,但手术难度较大.2013年3月重庆医科大学附属第一医院收治1例复杂性腹膜后节细胞神经瘤患者,入院前9个月彩色多普勒超声检查发现胰头部低回声包块影,大小为6.5 cm×4.5 cm,无任何临床症状.术前腹部CT检查及术中发现肿瘤大小为8.5 cm×7.5 cm×4.5 cm,位于胰腺后方,包绕腹腔干、肝总动脉、脾动脉及肠系膜上动脉等重要血管,包绕胰头部及钩突部,无法分离;与门静脉、肠系膜上静脉、脾静脉、左肾静脉关系密切.术中将肿瘤与各重要血管及胰腺体尾部分离、解剖,但肿瘤与胰头部无法分离,遂行肿瘤切除及胰十二指肠切除术.虽手术难度大,但肿瘤切除彻底,重要血管得到保护,患者术后恢复良好.

Effect of 5-FU on modulation of disarrangement of immune-associated cytokines in experimental acute pancreatitis

AIM： To investigate the effects of 5-Fluorouracil （5-FU） on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METHODS： Male Sprague Dawley rats were assigned to 3 Groups： Group A, sham operated rats as controls （n = 7）; Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation （n = 7）, and blood samples were taken for measurement of tumor necrosis factor-α （TNF-α）, interleukin-1 （IL-1）, interleukin-6 （IL-6） （by bioassay）, and interleukin-10 （IL-10）, transforming growth factor-β （TGF-β） （by ELISA）. The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured. RESULTS： Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines （TNF-α, IL-1, IL-6） at the 2 and 6 h period and the anti-inflammatory cytokines （IL-10, TGF-β） at 24 h increased significantly （P 〈 0.05） in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation （P 〈 0.05）, and IL-IO, TGF-13 were inhibited at 24 h compared to Group B （P 〈 0.05）. Obvious improvements in the severity of the acute pancreatitis, including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU. CONCLUSION： 5-FU is an anti-metabolic and immunosuppressive agent which can minimize the abnormal immune o/tokine response and relieve the pathophysiological disorders associated with experimental acute pancreatitis.

TGF-β1-promoted epithelial-to-mesenchymal transformation and cell adhesion contribute to TGF-β1-enhanced cell migration in SMMC-7721 cells

Transforming growth factor-b 1 (TGF-β1), a multi-function polypeptide, is a double-edged sword in cancer. For some tumor cells, TGF-β1 is a potent growth inhibitor and apoptosis inducer. More commonly, TGF-β1 loses its growth-inhibitory and apoptosis-inducing effects, but stimulates the metastatic capacity of tumor cells. It is currently little known about TGF-β1-promoted cell migration in hepatocellular carcinoma (HCC) cells, let alone its mechanism. In this study, we found that TGF-β1 lost its tumor-suppressive effects, but significantly stimulated cell migration in SMMC-7721 human HCC cells. By FACS and Western blot analysis, we observed that TGF-β1 enhanced the expression of α5β1 integrin obviously, and subsequently stimulated cell adhesion onto fibronectin (Fn). Furthermore, we observed that TGF-β1 could also promote SMMC-7721 cells adhesion onto laminin (Ln). Our data also provided evidences that TGF-β1 induced epithelial-to-mesenchymal transformation (EMT) in SMMC-7721 cells. First, SMMC-7721 cells clearly switched to the spindle shape morphology after TGF-β1 treatment. Furthermore, TGF-β1 induced the down-regulation of E-cadherin and the nuclear translocation of β-catenin. These results indicated that TGF-β1-promoted cell adhesion and TGF-β1-induced epithelial-to-mesenchymal transformation might be both responsible for TGF-β1-enhanced cell migration.

Co-expression of heat shock protein 70 and glucose-regulated protein 94 in human gastric carcinoma cell line BGC-823

AIM:To investigate the co-expression and significance of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human gastric carcinoma cell line BGC-823. METHODS: The expression and localization of HSP70 and grp94 in human gastric carcinoma cell line BGC-823 were determined by immunocytochemistry and indirect immunofluorescence cytochemical staining. Flow cytometry was used to analyze the correlation between expression of HSP70, grp94 and cell cycle in BGC-823 cell line. RESULTS: Gastric cancer cell line BGC-823 expressed high level of HSP70 and grp94. The positive rate of HSP70 and grp94 was 84.9±4.94% and 79.6±5.16%, respectively. Both of them were stained in cell plasma. There was a significant difference compared with control group (1.9±0.94%, P<0.01). During the cell cycle, HSP70 and grp94 were continuously expressed in BGC-823. CONCLUSION: HSP70 and grp94 are highly expressed in human gastric carcinoma BGC-823 cells through the whole cell cycle. There is no relationship between expression of HSP70, grp94 and cell cycle.

The Characteristics of Celiac Trunk Lymph-node Metastases of Esophageal Cancer in the Thoracic Segment and Clinical Significance for Wide-Excision

OBJECTIVE To understand the characteristics of celiac trunk lymph-node metastases of thoracic esophageal carcinoma and their influence on prognosis of the patients, and to investigate a reasonable range for regional celiac trunk lymph-node clearance. METHODS Clinical specimens of 241 patients receiving resection of a thoracic esophageal carcinoma were analyzed retrospectively. RIESULTS The rate of the patient celiac lymph-node metastases was 32.4%（78/241）, and of the lymph nodes examined, 9.8% were found to have metastasis. The extent of metastases adjacent to the common hepatic artery and celiac trunk and within the hepatoduodenal ligaments was 6.6%, 6.9% and 6.3%, respectively. The tumor site, extent of invasion and level of cell differentiation were the factors influencing lymph-node metastases, but they were unrelated to the length of the tumor. The overall rate of regional celiac recurrence for the patients 3 years after operation was 5.4%. The 3-year survivals for the patients with metastases of the celiac lymph nodes was 42.3%, which was lower compared to the non-metastatic patients （70.6%） （P〈0.01）. CONCLUSION Celiac lymph-node metastases are one of key factors affecting the prognosis of the patients receiving resection of esophageal cancer, and extensive clearance of the celiac-trunk lymph nodes can reduce the rate of postoperative regional metastases.

Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model

Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4＋CD25＋ regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were re- cipients. Rats were randomly assigned to the following four groups： control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3＋CD4＋CD25＋ regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body in＇adiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased signifi- cantly to （459.2±76.9） U L^- 1, total bilirubin increased to （124.1±33.7） μmol L-1 （P〈0.05） and the ratio of Foxp3＋CD4＋CD25＋ regulatory T cells decreased significantly to 1.50%±0.50% （P〈0.05） compared with the other groups. Analysis of the T cell subpopulations in the acute rejection group varied from the other groups. Histological analysis showed typical changes of acute rejection in the acute rejection group only. Preconditioning of the donors with total body irradiation eliminated passenger lymphocytes of the liver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.

Biomaterial scaffold-based local drug delivery systems for cancer immunotherapy

Immunotherapy has attracted tremendous attention due to the remarkable clinical successes for treating a broad spectrum of tumors. One challenge for cancer immunotherapy is the inability to control localization and sustain concentrations of therapeutics at tumor sites. Local drug delivery systems(LDDSs) like the biomaterial scaffold-based drug delivery systems have emerged as a promising approach for delivering immunotherapeutic agents facilely and intensively in situ with reduced systemic toxicity. In this review, recent advances in biomaterial scaffold-based LDDSs for the administration of immunotherapeutic agents including vaccines, immunomodulators, and immune cells are summarized. Moreover, codelivery systems are also evaluated for local immunotherapy-involving combination anti-tumor therapy,including chemotherapy-immunotherapy, photothermal-immunotherapy, and other combination therapies. Finally, the current challenges and future perspectives on the development of next-generation LDDSs for cancer immunotherapy are discussed.

A novel synthetic small molecule YF-452 inhibits tumor growth through antiangiogenesis by suppressing VEGF receptor 2 signaling

Tumor angiogenesis is characterized by abnormal vessel morphology, endowing tumor with highly hypoxia and unresponsive toward treatment. To date, mounting angiogenic factors have been discovered as therapeutic targets in antiangiogenic drug development. Among them, vascular endothelial growth factor receptor 2 （VEGFR2） inhibitors exerts potent antiangiogenic activity in tumor therapy. Therefore, it may provide a valid strategy for cancer treatment through targeting the tumor angiogenesis via VEGFR2 pathway. In this study, we established a high-profile compounds library and certificated a novel compound named N-（N-pyrrolidylacetyl）-9-（4-bromobenzyl）-l,3,4,9-tetrahydro-^-carboline （YF-452）, which remarkably inhibited the migration, invasion and tube-like structure formation of human umbilical vein endothelial cells （HUVECs） with little toxicity invitro. Rat thoracic aorta ring assay indicated that YF-452 significantly blocked the formation ofmicrovascular exvivo. In addition, YF-452 inhibited angiogenesis in chick chorioallantoic membrane （CAM） and mouse corneal micropocket assays. Moreover, YF-452 remarkably suppressed tumor growth in xenografts mice model. Furthermore, investigation of molecular mechanism revealed that YF-452 inhibited VEGF-induced phosphorylation of VEGFR2 kinase and the downstream protein kinases including extracellular signal regulated kinase （ERK）, focal adhesion kinase （FAK） and Src. These results indicate that YF-452 inhibits angiogenesis and may be a potential antiangiogenic drug candidate for cancer therapy.