肺腺癌神经内分泌分化的生物学特性

目的探讨肺腺癌伴神经内分泌(neuroendocrine NE)分化的生物学特性。方法采用免疫组化S-P法检测47例肺腺癌神经内分泌标记物的表达。结果肺腺癌组织中NE标记物神经元特异性烯醇化酶(NSE)和突触素(Syn)的阳性表达率分别为63.83%、44.68%,均显著高于正常组织(P<0.01)。肺腺癌伴NE分化与肺癌的淋巴结转移、分化程度无关。NSE的表达在死亡组显著高于生存组(P<0.05)。结论肺腺癌伴有NE分化与生存时间呈负相关,与淋巴结转移和分化程度无相关性。     

凋亡抑制蛋白XIAP和促凋亡因子Smac在胰腺癌化疗抵抗中的作用

目的探讨x-相关凋亡抑制蛋白（XIAP）和促凋亡因子Smac在胰腺癌细胞化疗抵抗中的作用，以及转染胞浆表达型Smac基因靶向下凋XIAP对化疗药物诱导的胰腺癌细胞凋亡的影响。方法应用流式细胞术检测顺铂、5-FU介导的Panc-1、BXPC-3的凋亡率及胞浆染色分析细胞XIAP表达变化，Western blot分析XIAP、Smac、Caspase-3表达水平；构建pEGFP-NI／Smac真核表达载体并转染胰腺癌Panc-1细胞，流式细胞术检测转染Smac基因前后Panc-1细胞的凋亡敏感性。结果与BXPC-3细胞相比，Panc-1对顺铂或5-FU介导的凋亡具有较强抵抗性，Western blot分析显示Panc-1细胞高表达XIAP，在化疗药物作用下化疗敏感细胞BXPC-3胞浆内XIAP水平下降明显多于Panc-1细胞，而且凋亡的BXPC-3细胞释放入胞浆内的成熟Smac蛋白水平明显高于Panc-1细胞。转染胞浆表达型Smac基因至化疗抵抗Panc-1细胞，可明显下调其XIAP表达水平，促进效应Caspase-3分子活化，显著提高顺铂、5-FU诱导的细胞凋亡率。结论胰腺癌细胞XIAP的表达水平下调与其化疗敏感性有关，XIAP是克服化疗抵抗的重要靶分子，而上调Smac活性蛋白的胞浆表达作为一种有效调节信号，通过拮抗XIAP的凋亡抑制作用协同化疗药物促进胰腺癌细胞凋亡。     

胰腺导管腺癌和慢性胰腺炎中18q21杂合性缺失及相关性分析

目的 探讨18q21在人胰腺导管腺癌和慢性胰腺炎中杂合性缺失(LOH)的情况及其相关因素.方法 选择18q21上的位点RP11-729G3和RP11-850A17作为目的 片段,选择接近18号染色体着丝粒的位点RP11-621L6作为参照位点,利用细菌人工染色体(BAC)提取、纯化相应位点的DNA,用切口平移法分别标记生物素和地高辛后制成双色探针,应用荧光原位杂交技术(FISH)检测30例胰腺导管腺癌和10例慢性胰腺炎石蜡包埋组织切片中18q21 LOH情况,并收集、整理相应临床病理资料进行相关性分析.结果 30例胰腺导管腺癌中在RP11-729G3位点有25例(83.3%)有LOH,在RP11-850A17位点26例(86.6%)有LOH,其中25例在RP11-729G3和fuP11-850A17两个位点均有LOH,1例仅在RP11-850A17位点有LOH.10例慢性胰腺炎中均未发现18q21 LOH.经统计学分析发现,18q21 LOH在慢性胰腺炎和胰腺导管腺癌中差异有统计学意义(P<0.01),且RP11-729G3和RP11-850A17两个位点LOH有高度相关性(Phj系数=0.877),但和临床病理各因素间未发现明显相关.结论 18q21 LOH在胰腺导管腺癌中属于高频事件,并且位点RP11-729G3和RP11-850A17的LOH有高度相关性,可能在胰腺导管腺癌发生发展中起重要作用.在临床诊断中18q21LOH也能作为较特异的标记辅助诊断.     

Development of patient derived organoids for cancer drug screening applications

Cancer is a disease characterised by abnormal cell growth that can invade or spread to other regions of the body. Organoids are three-dimensional ex vivo tissue cultures made from embryonic stem cells, induced pluripotent stem cells, progenitor cells or tissue that serve as a physiological model for cancer research. These are designed to recapitulate the in vivo properties of tumours. Importantly, effective recapitulation of the structure of tissues and function is believed to predict patient response, allowing for the creation of personalised therapy in a timely manner that may be used in the clinic. This Review discusses the pre-clinical model and different types of human organoids as models for the development of high throughput drug screening and also aims to highlight how organoids are shaping the future of cancer research.     

Effects of Na+, K+ and Mg2+ on45Ca2+ uptake by pancreatic islets

Microdissected pancreatic islets of noninbredob/ob-mice were used to study ionic effects on the lanthanum-nondisplaceable⁴⁵Ca²⁺ uptake by islet cells. Omission of Mg²⁺ from the incubation medium had no effect, but the⁴⁵Ca²⁺ uptake was increased by omission of Na⁺ and decreased by omission of K⁺. Excess Mg²⁺ (1.2–15 mM) inhibited and excess K⁺ (4.7–25 mM) stimulated the⁴⁵Ca²⁺ uptake in a concentration-dependent manner. Stimulation of⁴⁵Ca²⁺ uptake in Na⁺-deficient islets was associated with an enhancement of the basal insulin release. Total abolishment of glucose-stimulated⁴⁵Ca²⁺ uptake in K⁺-deficient islets did not preclude a significant secretory response to glucose. It is concluded that the lanthanum-nondisplaceable⁴⁵Ca²⁺ uptake shows a partial correlation to insulin release.     

Fine-needle aspiration of dermoid cyst of the pancreas: A case report

A 53-yr-old woman presented with a left upper quadrant abdominal mass attached to the body of the pancreas. Fine-needle aspiration (FNA) yielded cyst fluid containing numerous benign, mature squamous cells, keratin debris, and inflammatory cells. The diagnosis of dermoid cyst was subsequently rendered on the resected specimen. The cytologic and histologic features are presented. FNA cytology proves to be a valuable diagnostic adjunct in the preoperative evaluation of a patient with dermoid cyst of the pancreas.     

Pancreatoblastoma with marked elevation of serum alpha-fetoprotein

Summary The autopsy findings in a pancreatoblastoma in a 7-year-old Japanese girl is reported. The tumour was in the head and body of the pancreas, and was associated with diffuse carcinomatous peritonitis and hepatic and pulmonary metastases. There was marked elevation (more than 10000 ng/ml) of serum alpha-fetoprotein (AFP). Histopathologically the tumour was composed of solid epithelial elements with fibrous stroma, showing acinar arrangement, squamoid clusters and tubular structures. The epithelial elements contained numerous fine PAS positive granules in the cytoplasm. Immunocytochemical results suggested epithelial differentiation with positivity to alpha-1-antitrypsin (AAT), keratin, CA19-9, and AFP. No endocrine elements were recognized. Characteristic feature of this tumour are discussed and compared with prevoius reports.     

Secretagogue effects on intracellular calcium in pancreatic duct cells

Regulation of intracellular free calcium ([Ca²⁺]_i) in single epithelial duct cells of isolated rat and guinea pig pancreatic interlobular ducts by secretin, carbachol and cholecystokinin was studied by microspectrofluorometry using the Ca²⁺-sensitive, fluorescent probe Fura-2. Rat and guinea pig duct cells exhibited mean resting [Ca²⁺]_i of 84 nM and 61 nM, respectively, which increased by 50%–100% in response to carbachol stimulation, thus demonstrating the presence of physiologically responsive cholinergic receptors in pancreatic ducts of both species. The carbachol-induced increase in [Ca²⁺]_i involved both mobilization of Ca²⁺ from intracellular stores and stimulation of influx of extracellular Ca²⁺. In contrast, neither cholecystokinin nor secretin showed reproducible or sizeable increses in [Ca²⁺]_i. Both rat and guinea pig duct cells showed considerable resting Ca²⁺ permeability. Lowering or raising the extracellular [Ca²⁺]_i led, respectively, to a decrease or increase in the resting [Ca²⁺]_i. Application of Mn²⁺ resulted in a quenching of the fluorescence signal indicating its entry into the cell. The resting Ca²⁺ and Mn²⁺ permeability could be blocked by La³⁺ suggesting that it is mediated by a Ca²⁺ channel.     

Immunocytochemical evidence of phospholipase A2 in pancreatic tumors — Diagnostic values

Summary Phospholipase A₂ is an enzyme which is produced in acinar cells, and persists even in regressive states of chronic pancreatitis, when the production of other enzymes diminishes. We therefore tested this enzyme as a marker of acinar descent in various pancreatic tumors. This enzyme could be seen in 50% of the acinar-cell carcinomas, in 60% of solid and papillary pancreatic tumors, and in 50% of microglandular carcinomas. Ductal cancers and isletcell cancers were negative. In contrast to other markers of acinar matrix (amylase, antitrypsin), phospholipase A₂ gave fewer false-positive or false-negative results.Supported by a grant of the J. and F. Marohn Stiftung at the University of Erlangen/Nürnberg     

The role of phospholipase A2 in human acute pancreatitis

Summary Several studies suggest that the activation of pancreatic phospholipase A₂ (PLA₂) and its release from injured acinar cells play an important role in the pathogenesis of acute pancreatitis. Elevated catalytic activity of PLA₂ in serum is associated especially with severe forms of the disease. PLA₂ has been purified from human cadaver pancreas and an antiserum raised against the enzyme in rabbits. Immuno-histochemical localization of PLA₂ in pancreatic tissue was abnormal in acute pancreatitis. A time-resolved fluoroimmunoassay for human pancreatic PLA₂ has been developed. Increased serum concentrations of immunoreactive PLA₂ were found in acute pancreatitis during the first week after hospital admission. The values returned to normal somewhat more slowly than corresponding serum amylase values. The immunochemical determination of PLA₂ in serum provides a fast and specific detection of injury to pancreatic acinar cells. The pancreas is not the only source of PLA₂ in acute pancreatitis. The nonpancreatic PLA₂ may originate from various inflammatory cells, but this hypothesis remains to be proven.