肿瘤相关胰蛋白酶原-2免疫放射分析

本文建立了肿瘤相关胰蛋白酶原-2(TAT-2)IRMA,并初步应用于临床, 以探讨其对肿瘤早期诊断的可能性.以抗TAT-2 McAb T2C和T2L分别作为捕捉抗体和标记抗体.在pH9.6的碳酸缓冲液中, 将McAb T2C包被小珠, 成为固相抗体;用氯胺T方法将McAb T2L制成125I-标记抗体;并将两株McAb与不同量的TAT-2标准品, 在pH7.5的磷酸缓冲液中保温反应, 制作TAT-2标准曲线.检测肿瘤患者及正常人血清或尿液TAT-2含量, 并作对比.结果表明, 测定的TAT-2标准曲线(N=10):Bmax/T=(22±3.2)%, Bmax/B0=689.2±35.6倍, 非特异结合率小于0.5%, 检测下限在0.5ng/mL;批内CV为(4.3±0.26)%, 批间CV为(10.6±1.2)%;平均回收率为(98.5±3.1)%和(97.9±2.3)%.正常人血清(87份)和尿(20份)TAT-2浓度为7.58±5.46ng/mL和3.11±1.62ng/mL; 胃癌患者(45例)的血清TAT-2浓度63.2±62.9ng/mL, 胰腺癌和胆管癌患者(12例)和其它各种转移癌患者(16例)尿TAT-2浓度为236.6±185.3ng/mL, 104.9±171.2ng/mL;3组癌症患者血清、尿TAT-2浓度与正常人相比, 差别非常显著(P值均小于0.001).因此, TAT-2有希望成为一项肿瘤辅助诊断指标.     

Intrapancreatic course of the splenic artery with combined pancreatic anomalies

Summary In a 47-year-old male cadaver the splenic artery traveled partially through the substance of the pancreas. Additionally, the pancreas was apparently large and had an unusual shape; the neck of the organ could not be differentiated; the uncinate processus was absent; two pancreatic ducts were present. The probable reason for this combined anomaly was abnormal fusion of the ventral and dorsal pancreatic buds due to different levels of origin.

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Trajet intra-pancréatique de l'artère splénique associé à des anomalies pancréatiques

Résumé Sur le cadavre d'un homme de 47 ans, l'artère splénique présentait un trajet partiel à travers le pancréas. De plus, le pancréas paraissait volumineux et avait une forme inhabituelle, il n'était pas possible de différencier le col du pancréas, le processus uncinatus était absent, il y avait deux conduits pancréatiques. La raison probable de ces variations multiples se trouverait dans la fusion anormale des bourgeons pancréatiques dorsal et ventral en raison de leurs niveaux d'origine différents.

     

Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer.

Overexpression of the epidermal growth factor receptor (EGFR) has been reported as an important molecular abnormality in human pancreatic cancer. There is in vitro evidence that simultaneous overproduction of one of its ligands, transforming growth factor alpha (TGF-alpha), might result in an autocrine loop with an increased proliferation signal. We analysed by immunocytochemical staining a retrospective series of human pancreatic cancers, chronic pancreatitis, and normal fetal and adult pancreatic tissues for the presence of TGF-alpha and epidermal growth factor (EGF). Ductal epithelial cells showed TGF-alpha immunoreactivity in both normal tissue and chronic pancreatitis, and 95 per cent of tumours showed strong immunoreactivity. In contrast, EGF immunoreactivity was not found in normal pancreas, but was expressed in 12 per cent of pancreatic carcinomas. Well-defined areas of EGF immunoreactivity in exocrine ducts showing reactive changes in pancreatitis might represent a benign response to tissue damage similar to that previously described in the gastric mucosa.     

Epidermoid Cyst Derived from an Accessory Spleen in the Pancreas

A rare case of splenic epidermoid cyst (SEC) of the pancreas discovered in a 32-year-old Japanese female is reported. The lesion, 5x6cm in size including caseous material and serous fluid in the lumen, was discovered by ultrasonography and computed tomography at the tail of the pancreas and was easily removed. Histopathologically, the cystic wall consisted of three components: the inside was lined by mature squamous epithelium with keratinization, the middle layer consisted of splenic pulp with a sinus structure, and the peripheral layer was dense fibrous connective tissue in which some involutional pancreatic ducts and islets were recognized. The literature about SEC of the pancreas is discussed in comparison with other types of epidermoid cyst including lymphoepithelial cyst and dermoid cyst in the pancreas. Acta Pathol Jpn 41: 916 921, 1991.     

Correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma

Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor invasion and metastasis. This study aims to investigate the correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma. Immunohistochemistry was used to evaluate MMP-2 and TFPI-2 expression in tumor tissues and corresponding non-tumor tissues from 122 patients with pancreatic carcinoma. The results showed that the expression of MMP-2 was significantly (P < 0.05) higher in tumor tissues (78.7%) than in adjacent non-tumor tissues (27.9%), whereas the expression of TFPI-2 was significantly (P < 0.001) lower in tumor tissues (27.9%) than in adjacent non-tumor tissues (79.5%). Spearman’s rank correlation test showed a negative correlation between MMP-2 and TFPI-2 expression (r = -0.346, P < 0.001). Kaplan-Meier survival analysis showed that high MMP-2 expression was significantly correlated with decreased disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001), while high TFPI-2 expression was significantly associated with increased DFS (P < 0.001) and OS (P < 0.001) of the patients. Multivariate analysis showed that high MMP-2 expression can act as an independent predictive factor for poor DFS (P = 0.01); and low TFPI-2 expression as an independent prognostic factor for poor DFS (P < 0.001) and OS (P < 0.001). In conclusion, our findings suggested that the differential expression of MMP-2 and TFPI-2 have a negative correlation in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for prognosis of pancreatic carcinoma.     

Co-delivery of HIF1α siRNA and gemcitabine via biocompatible lipid-polymer hybrid nanoparticles for effective treatment of pancreatic cancer

Hypoxia-inducible factor 1α (HIF1α) has emerged as a promising new target for pancreatic cancer treatment over the past decade. High expression of HIF-1α increases the drug resistance of the current first line chemotherapeutic drug, gemcitabine (Gem). Here we employed biocompatible lipid-polymer hybrid nanoparticles to co-deliver HIF1α siRNA (si-HIF1α) and Gem for pancreatic cancer treatment in subcutaneous and orthotopic tumor models. The cationic ε-polylysine co-polymer (ENPs) can effectively absorb negatively charged si-HIF1α on the surface and encapsulate Gem to the hydrophilic core. Further coating of ENPs with PEGylated lipid bilayer resulted formation of LENPs, with reversed surface charge. The lipid bilayer of LENPs prevented nanoparticle aggregation and si-HIF1α degradation in serum, as well as Gem leakage. Those characteristics endow LENPs encapsulating drug prolonged lifetime in bloodstream and improved drug release via the enhanced tumor vasculature effect in tumor tissues. LENPs can co-deliver Gem and si-HIF1α (LENP-Gem-si-HIF1α) into tumor cells and effectively suppress the HIF1α expression both in vitro and in vivo. LENP-Gem-siHIF1α exhibited significant synergistic antitumor effects. Furthermore, LENP-Gem-si-HIF1α showed excellent capability to inhibit tumor metastasis in orthotopic tumor model.     

环氧合酶2抑制剂的抗胰腺癌作用及相关机制

目的探讨环氧合酶2(COX-2)抑制剂对胰腺癌细胞增殖、侵袭、迁移能力和对COX-2、基质金属蛋白酶(MMP)-14蛋白表达的影响以及可能的抗胰腺癌机制。方法不同浓度的COX-2抑制剂塞来昔布(20、60、100μmol/L)处理胰腺癌细胞后,用MTT比色法检测细胞的增殖能力;用Transwell侵袭实验和划痕实验检测细胞的侵袭能力和迁移能力;ELISA检测MMP-14和COX-2的蛋白表达情况。结果 MTT增殖实验、Transwell侵袭实验、划痕实验分别提示,COX-2抑制剂作用后胰腺癌细胞的增殖、侵袭、迁移能力均以浓度梯度形式下降(P0.05);ELISA结果显示,胰腺癌细胞中COX-2和MMP-14的蛋白表达水平相应降低(P0.05),两者表达具有显著正相关性(r=0.873,P0.05)。结论 COX-2抑制剂可能通过抑制COX-2表达下调MMP-14表达,进而以浓度梯度形式减弱胰腺癌细胞的增殖、侵袭、迁移能力,起到抗胰腺癌作用。     

CA724 is a novel factor for predicting the unresectability in pancreatic adenocarcinoma

This study aimed to assess the relationship between serum CA724 levels and the unresectability of pancreatic adenocarcinoma. A total of 302 patients with pancreatic adenocarcinoma were analyzed for the potential association between serum CA724 levels and the unresectability of pancreatic adenocarcinoma. Serum CA724 levels in patients with unresectable pancreatic adenocarcinoma were remarkably higher than those with resectable pancreatic adenocarcinoma (P < 0.001). Patients with elevated serum CA724 levels exhibited a 12.27-fold higher risk of unresectability than those with normal serum CA724 levels after adjusting for age, sex, and tumor location (95% CI = 5.28-28.51, P < 0.001). The analysis of receiver operating characteristics demonstrated that CA724 had superior predictive value to other tumor markers (AUC was 0.77 ± 0.03, 0.65 ± 0.04, and 0.62 ± 0.04 for CA724, CA125, and CA199, respectively). CA724 appeared to be a better predictor of unresectability than CA199 and CA125.     

Acute experimental pancreatitis in rat induced by sodium taurocholic acid: objective quantification of pancreatic necrosis

Summary Retrograde injection of 5% sodium taurocholic acid (TA) in Wistar rat pancreatic duct is followed by acute pancreatitis, resulting in 100% mortality within 36 h. Biochemical determinations show raised levels of amylase in ascites and blood. Necrosis has been measured using seven morphometric characteristics of pathological changes that add precise information on the type and extension of the pancreatic lesion. The percentage of necrotic tissue (by area) seems to be the most objective parameter. Necrosis appears 6 h after TA infusion, being 5.77% in extent after 12h, 14.9% after 24 h and animals die with an area of 29.5% necrosis. This experimental model seems to one in which physiopathological and therapeutic trials on acute pancreatitis may be camed out.     

The amphicrine pancreatic cell line AR42J: a model system for combined studies on exocrine and endocrine secretion

Summary Secretory vesicles of both the exocrine and the endocrine pancreas have been isolated and characterized in molecular terms from pancreatic tissue and primary cell cultures. Studies on pancreatic secretory processes could be further facilitated by the use of permanent cell lines that respond to secretory stimuli with a regulated secretory response. We now present biochemical, morphological and secretory studies on the rat pancreatic acinar cell line AR42J. This cell line is characterized by the presence of digestive enzyme-containing dense core vesicles, which are released in response to cholecystokinin. In addition, we present evidence that these cells also contain small neuroendocrine-specific vesicles, as evidenced by the expression of the neuroendocrine-specific vesicle proteins synaptophysin and S.V.2. Corresponding to these mixed exocrine-neuroendocrine features, we also found considerable amounts of the neurotransmitters glycine, glutamine and gammaaminobutyric acid (GABA), as well as the rate-limiting enzyme in GABA synthesis, glutamic acid decarboxylase (GAD) (EC 4.1.1.15) expressed in these cells. We demonstrated a specific uptake mechanism for radioactively-labelled GABA by these cells. In addition, GABA was released from intracellular storage pools by nicotinic receptor stimulation or membrane depolarization. In summary, AR42J cells represent the first amphicrine pancreatic cell line with the combined expression of exocrine and neuroendocrine secretory organelles, both of which follow a regulated secretory pathway in response to various secretory stimuli.Abbreviations DCV dense core vesicles - GABA gammaaminobutyric acid - SDS-PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis