胰腺缺血再灌注加微球栓塞诱导鼠胰腺癌细胞凋亡的研究

目的探讨缺血再灌注(I/R)加微球栓塞对病理大鼠的胰腺癌形态学和癌细胞凋亡的影响.方法将二甲基苯并蒽(DMBA)置入鼠胰腺尾部被膜下的实质内,待胰腺肿瘤形成后,随机分为4组A组即正常对照组;B组即胰腺癌对照组;C组即胰腺癌缺血组;D组即胰腺癌I/R组;E组即胰腺癌I/R加微球栓塞组.14 d后观察病理改变并采用原位末端标记法(ISEL)检测凋亡指数(AI).结果 E组的AI与D组,C组和B组差异均有显著性(均P<0.01);E组肿瘤体明显缩小,与D组和C组比较均有显著性差异(P<0.01);E组炎性细胞浸润,纤维组织增生,并且出现广泛的坏死和出血.结论胰腺癌缺血再灌注和微球栓塞可诱发肿瘤坏死,且其细胞凋亡的程度明显大于单纯的胰腺癌缺血组或胰腺癌缺血再灌注组.     

术前化疗对胰腺癌细胞凋亡和组织结构的影响

探讨术前选择性动脉化疗对胰腺癌细胞生长的影响，为临床制定合理的胰腺癌化疗方案提供理论依据。方法运用ＤＮＡ末端标记法对３０例胰腺癌患者术前化疗和未化疗和术后病理切片进行肿瘤细胞凋亡的检测，同时对比观察它们ＨＥ染色的组织结构变化 。     

胰腺癌细胞凋亡相关基因的表达

我们采用免疫组化方法检测ｂｃｌ２、ｐ５３、ｃｍｙｃ等３种细胞凋亡相关基因在胰腺癌、胰腺癌转移组织和胰腺良性病变中的表达，旨在探讨这些基因产物的表达及相互关系。１．材料和方法：本院病理科存档的石蜡标本，取胰腺癌４８例，Ⅰ期１４例，Ⅱ期２０例，Ⅲ期８...     

细胞凋亡与胰腺癌

细胞凋亡是一种特殊的细胞死亡方式,参与肿瘤的发生发展。在胰腺癌组织中,许多因素可诱导胰腺癌细胞凋亡。随着其机制的进一步阐明,诱导细胞凋亡有望成为综合治疗胰腺癌的一个重要内容。     

反义K-ras基因对胰腺癌细胞增殖和凋亡的影响

目的 探讨反义K-ras癌基因对胰腺癌细胞增殖和凋亡及Fas/FasL、Bcl-2、Bax表达的影响.方法 将重组逆转录病毒载体pLXSN转染包装细胞PT-67,获得重组逆转录病毒.在细胞和动物水平将该重组逆转录病毒分别感染PC-3和BxPC-3胰腺癌细胞,经G418筛选获得稳定细胞系,应用MTT、流式细胞仪和免疫组化法分别研究其增殖、凋亡及其相关基因表达情况.结果 成功制备含反义K-ras基因的重组逆转录病毒.感染含反义K-ras基因重组病毒后,胰腺癌PC-3细胞和移植瘤(有K-ras基因第12密码子点突变GGT→GTT)增殖受到抑制,G<,0/1>期细胞增加而S期细胞明显减少,细胞凋亡增加.免疫组化显示含反义K-ras癌基因逆转录病毒感染后PC-3细胞Bax/Bcl-2比值升高,Fas表达上调.结论 反义K-ras基因可使胰腺癌细胞及移植瘤增殖受到抑制,并可通过上调Bax/Bcl一2比值和(或)促进Fas表达诱导细胞凋亡.     

术前介入动脉化疗对胰腺癌细胞凋亡和细胞增殖的影响

目的检测术前选择性介入动脉化疗对胰腺癌细胞凋亡和细胞增殖的作用,探讨区域性化疗抑制胰腺癌生长的分子机制.方法采用原位末端标记法(ISEL)对32例术前行介入化疗和未化疗的胰腺癌患者的病理切片进行细胞凋亡指数和增殖指数的检测,同时测定细胞凋亡调控基因bcl-2和bax的表达水平.结果(1)术前介入化疗组胰腺癌细胞凋亡率比未介入化疗组明显增高,两组的细胞凋亡率分别为(46.89±26.46)和(5.67±2.43)(P＜0.01);而细胞增殖指数(PCNA)在术前介入化疗组与非化疗组之间无显著差异(P＞0.05).(2)肿瘤细胞凋亡率与组织类型有关,高分化腺癌中的细胞凋亡率比低分化腺癌高(P＜0.05).(3)术前介入化疗组bcl-2表达率低于未介入化疗组,bax表达率高于未介入化疗组(P＜0.05).结论术前选择性的动脉介入化疗能够诱导胰腺细胞凋亡,诱导细胞凋亡是抑制胰腺癌细胞的生长重要途径.     

生长抑素对胰腺癌生长抑制和凋亡作用的实验研究

目的 :探讨外源性生长抑素类似物施他宁对胰腺癌细胞的生长抑制和凋亡作用。方法 :采用MTT和细胞流式仪观测施他宁对胰腺癌细胞的生长抑制和凋亡的作用 ,并分析其对胰腺癌移植瘤的生长影响。结果 :发现PC - 3细胞在高浓度施他宁的作用下生长缓慢 ,与低浓度比较抑制率有明显差异 (P <0 .0 5) ,并与施他宁浓度呈依赖关系。施他宁对胰腺癌细胞凋亡有促进作用 ,凋亡率为 6.31 % ,而非治疗组的细胞凋亡率为 0 .48% ,两组间有非常显著差异(P <0 .0 5)。在移植瘤中 ,施他宁治疗组在肿瘤重量和肿瘤生长速度上均小于对照组 ,其差异有统计学意义 (P <0 .0 5)。结论 :施他宁对胰腺癌生长起抑制作用和促进凋亡作用。有潜在的临床应用价值     

生长抑素对人胰腺癌细胞增殖作用的实验研究

胰腺癌的发病率仍在不断上升,目前胰腺癌的手术切除率仅15％左右,五年生存率徘徊在10％左右。     

胰腺癌组织中细胞凋亡与增殖相关性的研究

目的　通过对胰腺癌组织中细胞凋亡与增殖相关性的研究 ,探讨其在胰腺癌发生发展中的作用。方法　采用原位末端标记、增殖细胞核抗原免疫组织化学染色和HE染色的方法对 32例胰腺癌和 14例慢性胰腺炎组织中细胞凋亡指数 (AI)、增殖指数 (PI)和分裂细胞指数 (MI)进行检测。结果　胰腺癌组织中的AI(3.37± 2 .38)、PI(46 .6 8± 2 .2 9)、MI(0 .31± 0 .12 )均明显高于慢性胰腺炎(0 .5 1± 0 .2 3、5 .0 8± 2 .82、0 .0 6± 0 .0 3,P <0 .0 0 1) ,癌组织的PI/AI(2 1.16± 17.44 )高于慢性胰腺炎(9 .6 0± 2 .15 ,P <0 .0 5 ) ,癌组织中AI与PI呈负相关 ,随肿瘤进展 ,PI/AI值增大。结论　细胞增殖增多、细胞凋亡相对减少 ,共同促进胰腺癌的发生发展。     

生长抑素治疗良性胰腺疾病的现况

生长抑素能强有力地抑制胰腺分泌。随着人工合成生长抑素类似物的出现，临床上已广泛应用于多种良性胰腺疾病的治疗。本文总结了生长抑素的作用机制，评估了生长抑素类似物在急性胰腺炎、胰瘘、慢性胰腺炎、胰腺假性囊肿、胰源性腹水和胰腺切除术后的作用。     

Effects of the somatostatin analogue octreotide on renal function in conscious diabetic rats.

BACKGROUND: Studies performed during the last decade have indicated that growth hormone (GH) and insulin-like growth factors (IGFs) may mediate the early renal changes in diabetes mellitus, i.e. hypertrophy and hyperfiltration. This and other observations have led to the suggestion that GH/IGF inhibitors, such as long-acting somatostatin analogue (e.g. octreotide and lanreotide), may be useful in order to inhibit or prevent development of long-term diabetic complications. METHODS: The present study examined the acute and chronic effects of octreotide on renal function following induction of streptozotocin (STZ)-diabetes in rats. The studies were carried out in conscious, non-fasted diabetic animals. RESULTS: Chronic administration of octreotide for 7 days, from onset of diabetes, prevented the decrease of effective renal vascular resistance (ERVR), and the increases in filtration fraction (FF), glomerular filtration rate (GFR), and absolute proximal tubular fluid reabsorption (APR) induced by diabetes. The renal hypertrophy was only partially prevented. In the acute study, similar changes were observed in effective renal plasma flow (ERPF) and ERVR but FF increased and GFR remained unaltered. CONCLUSIONS: Chronic but not acute treatment with octreotide prevented the renal hyperfiltration caused by diabetes. This effect is most likely due to an increase in afferent arteriolar resistance.     

生长抑素对大肠癌细胞凋亡的影响

目的 探讨生长抑素对大肠癌细胞凋亡的影响.方法 采用巢式RT-PCR方法检测2004年1月至2006年10月皖南医学院附属弋矶山医院收治的79例大肠癌患者癌组织中生长抑素mRNA的表达情况,采用免疫组织化学法检测大肠癌组织中生长抑素、Fas、FasL、半胱天冬蛋白酶(caspase)3和8蛋白的表达情况,TUNEL法检测细胞凋亡指数(AI).采用χ~2检验、q检验、Spearman等级相关检验对结果进行分析.结果 大肠癌组织中生长抑素mRNA与其蛋白表达呈正相关(r=0.98,P<0.05).低分化和中分化大肠癌组织中生长抑素mRNA及其蛋白的表达明显低于高分化组织(χ~2=10.78,11.24,5.27,5.24,P<0.05);生长抑素mRNA及其蛋白在乳头状腺癌的阳性表达率明显高于黏液腺癌+印戒细胞癌及未分化癌(χ~2=6.56,6.99,5.44,7.39,P<0.05);Dukes A、B期的生长抑素mRNA及其蛋白阳性表达率明显高于C、D期(χ~2=5.17,4.06,P<0.05).生长抑素高表达组、中表达组的AI明显高于低表达组(q=5.66,4.21,P<0.05);Fas、caspase-8、caspase-3在生长抑素高表达组、中表达组的阳性表达率明显高于低表达组(χ~2=5.48,5.62,6.89,4.32,4.19,3.91,P<0.05).结论 生长抑素对大肠癌细胞凋亡的调控可能与Fas/FasL基因的表达失衡、功能和信号系统的紊乱有关.     

Leflunomide对结肠癌细胞增殖及凋亡的影响

目的:检测Leflunomide对结肠癌细胞增殖和诱导凋亡作用。方法:实验采用结肠癌细胞株SW260,与不同浓度的Leflunomide药物(0、5、10、20、40、80μg/ml)共同培养,以MTT方法和流式细胞仪技术检测细胞的增殖状态,用TUNEL染色和流式细胞仪技术检测细胞的凋亡。结果:Leflunomide在对结肠癌细胞增殖具有双重影响,即在低浓度下(5μg/ml和10μg/ml)有轻度的促进结肠癌细胞SW620增殖的作用,而提高浓度后(>40μg/ml)则表现为明显的抑制细胞的增殖作用,并随着剂量增加和作用时间延长,抑制作用更为明显,即存在着时相性和量-效依赖性。结论:Leflunomide可抑制结肠癌细胞增殖和诱导凋亡。可能对结肠癌病人有潜在的治疗作用。     

Long acting somatostatin analogue in dumping syndrome

The effect of long acting somatostatin analogue, SMS 201-995, on postprandial dumping syndrome was studied in eight patients with Billroth II gastric resection. Each patient was subjected to two oral glucose challenges with 75 g glucose. One challenge was premedicated with 50 micrograms SMS 201-995 subcutaneously 15 min before the oral intake of glucose, the other with placebo. With placebo all patients experienced the subjective symptoms of the early dumping syndrome with significant (P less than 0.001) increases (mean (s.d.)) in pulse rate (from 66 (8) to 102 (10) beats/min), in packed cell volume (from 0.36 (0.05) to 0.43 (0.1) l/l) and in the plasma levels of vasoactive intestinal polypeptide (from 3.0 (0.5) to 10.2 (1.8) pmol/l). During the somatostatin study the subjective symptoms and the changes in the various parameters were not detected. In the control study seven patients showed postprandial hypoglycemia. In these patients significant elevations (P less than 0.001) in the insulin level (from 10 (0.9) to 40 (9.1) microE/ml) and gastric inhibitory peptide (GIP) concentration (from 100 (13) to 220 (41) ng/l) were seen, compared with the initial values. During the application of SMS 201-995 hypoglycaemia did not develop and plasma insulin and GIP concentrations remained unchanged. These results indicate that the long acting somatostatin analogue alleviates the symptoms of early and late postprandial dumping syndromes.     

Modulation of insulin-like growth factor-I system of the bladder using a somatostatin analogue in chronic spinalized rats

PURPOSE: We have previously reported the possible role of the insulin-like growth factor-I (IGF-I) system of mitogens in the development of detrusor smooth muscle hyperplasia and hypertrophy after spinal cord injury. We evaluated the in vivo effects of the anti-growth factor somatostatin analogue octreotide on the IGF-I system as well as subsequent changes in bladder smooth muscle hypertrophy and function after spinal cord injury in rats. MATERIALS AND METHODS: Included in this study were 90 adult female Sprague-Dawley rats weighing 200 to 250 gm. Of the rats 18 served as sham operated controls, while the remaining 72 underwent were spinal cord transection at the level of the T10 vertebra. The spinalized animals were randomly divided into 4 equal groups of 18, of which 1 group served as paraplegic controls. The other 3 groups received octreotide (60 microgram. daily for 4 weeks) delivered via a subcutaneously implanted osmotic pump immediately, 2 and 4 weeks after spinal cord injury. At the end of the experiment (6 to 8 weeks) each group of animals was subdivided into 2 subgroups of 9. In the first group filling cystometrography was done, while in the second subgroup wet bladder weight was estimated and Northern blot analysis was performed. RESULTS: Mean wet bladder weight plus or minus standard deviation in sham operated and paraplegic controls was 0.11 +/- 0.01 and 0.64 +/- 0.33 gm., respectively (p <0.05). The increase in bladder weight in paraplegic controls was associated with over expression of the IGF-I gene and with marked suppression of IGF binding proteins-3 and 5 compared with sham operated controls. On the other hand, mean wet bladder weight in the animals that received octreotide immediately after spinal cord injury was 0.17 +/- 0.02 gm., which was associated with a dramatic decrease in IGF-I gene expression and increased expression of IGF binding proteins-3 and 5. Mean cystometric bladder capacity in paraplegic controls was 0.48 +/- 0.18 ml. with an associated voiding pressure of 71 +/- 13 cm. water. All paraplegic controls showed detrusor hyperreflexia. In animals that received octreotide immediately after spinal cord injury mean cystometric bladder capacity was 2.49 +/- 1.75 ml. with an associated voiding pressure of 32 +/- 7 cm. water. Detrusor hyperreflexia disappeared in 88.89% of the rats in this group. There were less marked changes in bladder weight (mean 0.24 and 0.29 +/- 0.3 gm.), IGF-I gene expression and its binding proteins and urodynamic parameters when the drug was given 2 and 4 weeks, respectively, after spinal cord injury. CONCLUSIONS: Modulating the IGF-I system of mitogens in detrusor smooth muscle with consequently decreased bladder hypertrophy and improved urodynamic behavior in spinal cord injured animals using somatostatin analogue could be a possible therapeutic modality in patients with spinal cord injury.     

Effect of somatostatin analogue and cholecystokinin receptor antagonist on bile-induced acute canine pancreatitis.

To determine whether a synthetic somatostatin analogue, octreotide, and a cholecystokinin receptor antagonist, L-364,718, may be beneficial in acute pancreatitis, 33 dogs were assigned to four groups. Each dog underwent laparotomy with injection of autologous bile into the dorsal pancreatic duct. Thirty minutes after the induction of pancreatitis, Group 1 received a subcutaneous injection of octreotide (200 micrograms/kg), Group 2 received an equal volume of the octreotide carrier, Group 3 received an hourly intravenous bolus of L-364,718 (60 micrograms/kg), and Group 4 received an equal volume of the L-364,718 carrier. Hemodynamic profiles, arterial blood gases, plasma glucose, and serum amylase were obtained before laparotomy, at bile injection, and at hourly intervals. The pancreas was removed after 8 hours for gross evaluation, measurement of water content, and histologic examination. A significant decrease in cardiac index and a significant increase in serum amylase and pancreatic edema occurred in all four groups 8 hours after the induction of pancreatitis (P less than 0.05), but there was no statistical difference between any group. Likewise, there was no difference in gross or histologic changes in the pancreas of any group. The somatostatin analogue, octreotide, and the cholecystokinin receptor antagonist, L-364,718, did not ameliorate the effects of severe, bile-induced pancreatitis in dogs.     

The combination of docetaxel and the somatostatin analogue lanreotide on androgen-independent docetaxel-resistant prostate cancer: experimental data

OBJECTIVE

To evaluate the effects of the association between docetaxel and the somatostatin analogue lanreotide on the androgen‐independent prostate cancer cell line PC3, either sensitive or made resistant to docetaxel (PC3R), as new drugs and new combinations have promising clinical activity in hormone‐refractory prostate cancer.

MATERIALS AND METHODS

We examined the effect of docetaxel and lanreotide on cell proliferation, with analysis of the mitogen‐activated protein kinase pathway and expression of cell‐cycle regulatory proteins.

RESULTS

Combined treatment with docetaxel and lanreotide inhibited PC3 cell growth in vitro through an enhanced induction of cell death, compared with treatment with either agent alone; this result was particularly evident on PC3R cells. The results suggested that lanreotide could act as a P glycoprotein inhibitor in PC3R cells.

CONCLUSION

The present results provide a promising therapeutic approach for using somatostatin analogues in hormone‐refractory prostate cancer, in which lanreotide could interact with docetaxel in PC3R cells, with possible explanatory mechanisms which involve P glycoprotein‐mediated docetaxel resistance.     

生长抑素类似物诱导胆管癌细胞凋亡和bcl-2/bax表达的研究

目的探讨生长抑素类似物SMS2 0 1 995 (SMS)对人胆管癌SK ChA 1细胞凋亡和凋亡调控基因bcl 2和bax的影响。方法用DNA凝胶电泳、流式细胞仪检测AnnexinV标记凋亡细胞、免疫组化和原位杂交方法研究SMS(10 0ng/ml)处理 6、12和 2 4h后人胆管癌SK ChA 1细胞凋亡和bcl 2 /bax表达的变化。结果SMS作用SK ChA 1细胞 6h对DNA无明显影响 ,作用 12和 2 4h后DNA凝胶电泳出现呈典型梯状条带。SMS作用 6、12和 2 4h后 ,AnnexinV标记的凋亡细胞分别为 (2 2±5 ) % ,(39± 7) %和 (5 8± 10 ) %。同时 ,SMS可使细胞bcl 2蛋白表达下降 ,使bax蛋白和mRNA表达升高。结论SMS能诱导SK ChA 1细胞发生凋亡 ,bax和bcl 2凋亡基因介导了SMS对SK ChA 1细胞凋亡的发生