Effect of glutamine on tumor and host growth

Background: Oral glutamine supplementation has been found to support gastrointestinal mucosal growth and increase intestinal and systemic toxicity after chemotherapy and radiation therapy. Glutamine is also an important nutrient for rapidly proliferating tumor cells. However, it is not clear whether long-term glutamine supplementation in the tumor-bearing host has a selective benefit for host growth or tumor cell proliferation. Methods: To study the effect of glutamine in tumor-bearing animals, 30 Lewis/Wistar rats with subcutaneous mammary tumor implants (MAC-33) were randomized to receive a 3% glutamine- or 3% glycerine-enriched (control) diet for 25 days. Results: No significant difference was found in carcass weight, primary tumor weight, or spontaneous pulmonary metastasis with glutamine supplementation. Tumor cell cycle kinetics (aneuploidy, %S and %S [synthetic] + G₂/M [growth fraction]) were similar between glutamine-supplemented and control animals. A trophic effect of glutamine on distal ileal mucosa was seen with increased DNA content (344±68 vs. 184±38 µg/100 mg tissue) (p<0.05) and RNA content (435±44 VS. 335±30 µg/100 mg tissue) (p=0.06) compared with control animals. No detectable differences were observed in liver or muscle, or in tumor DNA, RNA, or protein content. Conclusions: These findings confirm the trophic effect of glutamine on small intestinal mucosa and suggest that glutamine can be administered to the tumor-bearing host over a long period of time without significantly stimulating tumor growth kinetics or metastasis.     

重组人生长激素在体外对人胃癌细胞株BGC823作用的研究

目的　研究重组人生长激素 (rhGH)对人胃癌细胞生长的影响。方法　利用体外细胞培养测定不同浓度的rhGH对人胃癌细胞株BGC82 3的生长曲线、细胞抑制率和细胞倍增时间的影响。结果　rhGH在体外无明显促进BGC82 3细胞分裂增殖 ,rhGH组与对照组、rhGH +L OHP组与L OHP组比较差异均无显著意义 (P >0 0 5 ) ,且生长曲线没有升高 ;rhGH +L OHP组与对照组比较细胞抑制率为 6 3 2 %和 5 0 8% (P <0 0 1) ,细胞倍增时间为 82 5h和 39 6h(P <0 0 1) ;或rhGH+L OHP组与对应的rhGH组配对比较 ,细胞抑制率为 6 3 2 %和 1 7% (P <0 0 1) ,细胞倍增时间为82 5h和 37 2h(P <0 0 1)。结论　rhGH在体外无明显促进胃癌细胞的分裂增殖 ,与抗肿瘤药合用可提高抗肿瘤药的疗效。     

重组生长激素对严重感染后蛋白质代谢影响的实验研究

本文旨在探讨重组生长激素对腹腔严重感染后蛋白质代谢的影响及其作用机制。作者以大鼠盲肠结扎穿孔复制严重感染模型，并将其分为治疗组和感染组，分别于术后给予生长激素（ｒＧＨ）和生理盐水，进行观察研究。结果显示：（１）ｒＧＨ促进正氮平衡恢复，提高了血浆白蛋白水平；（２）ｒＧＨ促进肠粘膜谷氨酰胺利用酶活性的恢复，维持了肠粘膜正常形态结构，降低了门脉内毒素含量和循环ＴＮＦ水平；（３）ｒＧＨ直接促进了离体肝细胞合成白蛋白，感染时提高受抑的白蛋白ｍＲＮＡ表达水平。结果表明，ｒＧＨ可促进感染后肠粘膜对谷氨酰胺的利用，维持粘膜正常结构和功能，减轻了肠源性高代谢反应。同时，从分子水平揭示ｒＧＨ直接刺激肝细胞白蛋白ｍＲＮＡ的表达，促进了感染时白蛋白的合成，有利于正氮平衡的恢复，提高了生存率。     

重组生长激素对实验性肝硬化肝细胞生长激素受体表达的调控作用

目的探讨重组生长激素对肝硬化肝细胞表达生长激素受体的调控作用。方法检测不同浓度的重组生长激素 (0、13 3、133 3、1333ng/ml)干预后大鼠肝硬化肝细胞生长激素受体的数量变化。结果培养后肝硬化肝细胞生长激素受体的数量 (10 4 /cell)分别为 0 73± 0 13、1 14± 0 17、1 2 3± 0 2 1、0 6 8± 0 10 (P <0 0 5 )。结论在一定浓度范围内重组生长激素对肝硬化肝细胞的生长激素受体具有正性调控作用     

生长抑素和生长激素对急性坏死性胰腺炎肾损伤的保护作用

目的 实验性研究急性坏死性胰腺炎早期肾损伤的发病机制及生长激素和生长抑素的治疗作用。方法 经胰胆管逆行注射３．５％牛磺胆酸的２．５ｍｌ／ｋｇ建立大鼠ＡＮＰ模型,测定血淀粉酶、内毒素、ＩＬ－１、ＩＬ－６、ＩＬ－８和ＴＮＦ－α。观察肾病理变化和细胞超微结构发迹同时用ＲＴ－ＰＣＲ测定ＴＮＦ－αｍＲＮＡ表达的变化,探讨生长激素和生长抑素的疗效。结果 ＡＮＰ早期体内细胞因子和炎性介质过度升高,与肾损伤程度有     

重组人生长激素对摘除卵巢大鼠皮质骨的影响

目的 探讨重组人生长激素对摘除卵巢大鼠股骨和椎体皮质骨的影响。方法 ６个月龄ＳＤ大鼠４０只,摘除卵巢后３个月开始皮下注射高、低２种剂量生长激素。注射８周后处死,取出双侧股骨和Ｌ２椎体,测定股骨中段骨密度值,观测股骨中段和椎体皮质骨厚度的改变,测定股骨生物力学强度,并与雌激素注射组比较。结果 生长激素显著增加摘除卵巢大鼠股骨中段和腰椎体皮质骨尤其是外层皮质的厚度,股骨中段骨密度值和生物力学强度出显著     

Impact of exogenous growth hormone on host preservation and tumor cell-cycle distribution in a rat sarcoma model

Growth hormone (hGH) has been reported to improve nitrogen balances and accrue lean mass tissue in stable subjects. However, the ability of hGH to positively influence host preservation in stressed catabolic states such as cancer-induced cachexia remains unproven. Thirty-seven sham or tumor implanted Fischer 344 rats were randomized to receive either 0.5 mg/kg/day hGH or saline (SAL) subcutaneously from Days 14 to 23 postimplantation. Plasma levels of hGh and somatomedin C/insulin-like growth factor I (IGF I) as well as IGF I bioactivity were determined at sacrifice. Gastrocnemius muscle protein content was used as a index of host lean tissue mass and the tumor response was evaluated via flow cytometry for analysis of cell-cycle distribution. Host cachexia was not attenuated by hGH as muscle protein content was similar in hGH and saline-treated groups. Despite elevated hGH levels (range, 77-222 ng/ml (GH) vs less than 2 ng/ml (SAL], IGF I levels and bioactivity were not elevated in GH-treated groups. In contrast, cancer-induced anorexia markedly decreased IGF I levels (4 U/ml vs 9 U/ml, NTB; P less than 0.01) and this response remained refractory to hGH administration. While final tumor weights were similar between GH- and SAL-treated groups, hGH treatment caused a twofold increase in the proportion of aneuploid cells (P less than 0.05). In conclusion, hGH failed to attenuate lean mass dissolution in the tumor bearing host and this response may be related to the failure of IGF I induction. Conversely, the altered proportion of tumor aneuploid cells suggests a direct influence on tumor cell-cycling populations.     

Effects of laparoscopy on intraperitoneal tumor growth and distant metastases in an animal model.

BACKGROUND AND AIMS: Laparoscopic surgery for colorectal cancer is currently being evaluated in humans. The aim of this study was to examine the effect of laparoscopy on intraperitoneal tumor growth and distant metastases in an animal model. We also examined the effect of combining laparotomy with laparoscopy and on infusing the peritoneal cavity with normal saline solution (NaCl), water, and sodium hypochlorite after laparoscopy on intraperitoneal tumor growth. MATERIAL AND METHODS: Female Fischer rats were given MtLn3 adenocarcinoma cells by intraperitoneal injection to produce intraperitoneal tumor growth and by tail vein injection to produce lung metastases. A pneumoperitoneum was then induced to a pressure of 8 mm Hg with carbon dioxide (CO2), helium, or room air. After this, animals were allowed to either recover or underwent laparotomy or infusion of NaCl, water, or sodium hypochlorite before recovery, depending on the experiment. At 21 days all animals were killed and intraperitoneal tumor growth was assessed by counting the number of peritoneal and serosal nodules and by weighing the omental pad of tumor. Lung metastases were assessed by counting the number of metastases after fixation. RESULTS: Laparoscopy caused a marked intraperitoneal dissemination of tumor with a median of 17 (10 to 20) peritoneal and serosal nodules for CO2, 19.5 (12.5 to 25) for helium, and 15.0 (9.5 to 17.7) for room air compared with 0 (0 to 1) for controls (P < .0001). The weight of omental tumor was also significantly increased (P < .02) in the CO2, helium, and room air groups. Infusion with NaCl, water, or sodium hypochlorite had no effect on tumor dissemination after laparoscopy. The combination of laparoscopy and laparotomy caused a significant reduction (P < .05) in the number of peritoneal nodules but had no significant effect on omental tumor growth. Laparoscopy also had no effect on the number of pulmonary metastases induced compared with controls. CONCLUSIONS: This study shows that laparoscopy promotes intraperitoneal dissemination of tumor. This effect is independent of the insufflating gas used and is not affected by use of a cytotoxic agent. The use of gasless laparoscopy should be encouraged by those undertaking curative laparoscopic surgery for colorectal cancer.     

Interactions between malignant tumor growth and allogeneic graft rejection in an experimental rat model

Abstract We describe a combined tumor and simultaneous transplant model in rats in tended to investigate interactions between tumor growth and graft rejection. To study the influence of tumor growth on graft rejection. Novikoff hepatoma cells were injected subcutaneously into the back of Lewis rats. Eight days later, the grown solid tumor was resected, and allogeneic heart transplantation was performed. Four groups were formed, receiving 5-fluorouracil (5-FU), cyclosporin A (CsA), 5-FU + CsA, and placebo, respectively. In the corresponding groups, tumor injection was omitted. Graft survival was significantly prolonged when CsA was given 5-FU did not abrogate or augment CsA efficiency nor influence graft survival when given alone. In the corresponding control groups, graft survival was similar, thus excluding an immunomodulating effect of the prior tumor growth on graft survival. To study the reverse interaction of allogeneic graft on tumor growth, heart grafting and tumor cell injection were performed on the same day. In different groups, 5-FU, CsA, 5-FU + CsA, and placebo was given. For the control, no transplantation was carried out. The tumor was resected on the 8th postoperative day and examined by immunohistology. A slight decrease of tumor growth by 5-FU, but a marked increase by CsA were found, whereas the graft alone showed no immunomodulation.     

危重患者术后血浆蛋白和免疫功能的变化及重组人生长激素的治疗作用

目的 观察外科危重患者术后血浆蛋白和免疫功能变化及重组人生长激素（rhGH）的治疗作用。方法 将45例外科危重患者术后随机分为对照组30例和rhGH组15例。两组患者术后治病和营养支持方案相同。rhGH组术后48h开始加用rhGH8U／d肌注,连续7d。观察两组患者血浆蛋白浓度、细胞免疫、体液免疫功能变化及临床结果。结果 两组患者术后血清转铁蛋白、前白蛋白、白蛋白水平;CD3、VD4、VD8、NK活性及CD4／CD8比值均用于正常。rhGH组使用rhGH后第4天血清前白蛋白浓度明显高于治疗前和对照组（P＜0．05）,使用rhGH后第8天血清转铁蛋白、前白蛋白、白蛋白浓度均显著高于对照组（P＜0．05,P＜0．01,P＜0．05）,CD4、NK活性及CD4／CD8比值均明显高于对照组（P＜0．05,P＜0．01,P＜0．05）。结论 术后营养支持加rhGH迅速改善外科危重患者的营养状况和免疫功能。     

应用GSI药物阻断Notch-1通路对骨肉瘤小鼠模型肿瘤生长及血管形成的影响

[目的]研究Notch-1通道阻断剂γ分泌酶抑制剂(gamma-secretase inhibitor,GSI)在抑制骨肉瘤小鼠模型中肿瘤增长以及其抑制肿瘤血管生成作用,进而探讨Notch-1信号通路在小鼠骨肉瘤模型中的作用及其作用机制。[方法]建立人骨肉瘤荷瘤SCID小鼠模型,将荷瘤成功后小鼠随机分为三组,实验组肿瘤内注射Notch通路阻断药物GSI,对照组注射PBS和DMSO。研究各组小鼠生物学指标、肿瘤增长变化及肿瘤组织检测微血管密度(microvessel density,MVD)的表达情况与差异。[结果]处死小鼠测量瘤体,同对照组相比,GSI治疗组小鼠的生物学指标明显较好,其小鼠的体重、饮食、睡眠、运动情况、精神状态、对刺激的反应及小鼠的皮毛光泽度等优于对照组,其皮下肿瘤体积明显较小,实验组平均体积为(196.3 mm3)较DMSO对照组平均体积(650.3 mm3)及PBS对照组平均体积(694.6 mm3)明显缩小,差别具有统计学意义,P0.01。实验组及对照组内瘤体切片内血管均见不同程度的CD31表达,其表达于血管内皮细胞内,与对照组相比实验组CD31表达均明显降低,实验组及PBS、DMSO对照组CD31平均秩次分别为4.03、28.9和32.5,P0.05,差异具有统计学意义。[结论](1)证实GSI可抑制SCID小鼠骨肉瘤动物模型肿瘤的生长;(2)GSI对SCID小鼠骨肉瘤动物模型的治疗作用可通过抑制Notch通路进而干预肿瘤血管形成来实现;(3)应用GSI药物阻断Notch信号通路有望成为骨肉瘤抗肿瘤治疗的新方法。     

缺锌大鼠烫伤后补锌对血清和组织锌、碱性磷酸酶及生长激素的影响

目的 观察缺锌大鼠烫伤后补锌对体内锌、含锌酶、激素的影响。方法 用4ug/g低锌饲料大鼠1周,造成缺锌状态后15%深Ⅱ度烫伤,分3组进食不同含锌量饲料,L组（缺锌组）、M组（低补锌组）、H组（高补锌组）。伤后1、3、7d,分别活杀各组大鼠,留取血、组织标本。结果 血清锌,L、M组下降,H组上升,肝脏锌,各组均呈上升趋势,以H组最明显,骨骼锌：L组进行性下降。M组缓慢上升,H组上升最明显。烫伤皮肤锌：各组均呈上升趋势,以H组最明显,碱性磷酸酶（ALP）：L组明显降低,H组高于L、M组。生长激素（GH）：L、M组烫伤后第1天下降,而后各组逐渐升高,以H组最明显。结论 低锌状态下烫伤进一步加重机体缺锌,补锌可以纠正血清锌降低,增加肝脏、骨骼、皮肤含锌量;增加ALP活性,提高GH水平。     

生长抑素和生长激素对急性重症胰腺炎脑损伤的保护作用

目的观察生长抑素和生长激素对急性重症胰腺炎(SAP)大鼠脑损伤的保护作用。方法经胰胆管逆行注射35%牛磺胆酸钠25ml/kg建立大鼠SAP模型,将100只大鼠随机分成5组重症胰腺炎组(SAP组);生理盐水对照组(NS组);生长抑素组(S组);生长激素组(G组);联合治疗组(S G组)。观察双激素治疗前后脑组织水肿、血脑屏障及与脑组织IL6mRNA、TNFαmRNA的变化程度。结果SAP早期脑组织IL6mRNA、TNFαmRNA和血TNFα、IL6升高,与脑组织水肿、血脑屏障损伤程度呈正相关。生长激素和生长抑素联合治疗可以降低脑组织TNFαmRNA、IL6mRNA表达,减轻脑组织的炎性反应,改善脑水肿和血脑屏障的通透性。同时观察到SAP大鼠脑电图呈三相波和尖慢波改变,联合治疗组明显好转。结论生长激素和生长抑素联合治疗可降低SAP大鼠脑组织TNFαmRNA、IL6mRNA的表达,改善脑组织水肿和血脑屏障的通透性,对SAP大鼠脑损伤有保护作用。     

重组生长激素对腹部大手术患者血浆蛋白的影响

目的研究重组人生长激素（rhGH）对腹部大手术患者术后代谢、免疫功能和术后并发症的影响。方法回顾性分析腹部大手术患者79人，其中37人为治疗组，42人为对照组。治疗组手术后第2天开始，每天皮下注射思真（重组人生长激素，瑞士雪兰诺公司生产）8U，对照组给予安慰剂（生理盐水），共用7d；分别在治疗前，治疗后3、7、10、14d检测血浆白蛋白、前白蛋白及转铁蛋白水平。记录切口愈合情况及术后并发症情况。结果（1）治疗前，两组白蛋白、前白蛋白及转铁蛋白水平差异无统计学意义（P〉0．05）；治疗后3d，两组白蛋白水平差异无统计学意义（P〉0．05），且均低于治疗前；治疗组前白蛋白、转铁蛋白均高于对照组（P〈0．05）；治疗后7d，治疗组3项指标均高于对照组。（2）治疗组切口愈合情况明显优于对照组（P〈0.05）。（3）治疗组术后并发症发生率明显低于对照组（P〈0．05）。结论腹部大手术患者术后应用重组人生长激素可以提高免疫功能，促进切口愈合，减少术后并发症的发生。     

大鼠肝癌肝移植模型的建立

目的　建立肝癌肝移植动物模型并观察术后肝癌复发的生物学特点。方法　 130只近交系SD雄性大鼠 ,10 0ppm二乙基亚硝胺饲喂诱癌。共 98只大鼠据Kamada袖套技术行原位肝移植 ,术中根据肿瘤大小分为三组 :1组有明确肝癌结节但直径 <1 0cm (n =2 5 ) ,2组肝癌结节直径1 0～ 1 5cm(n =4 1) ,3组肝癌结节直径 >1 5cm(n =32 )。不行肝移植术的 10只大鼠作对照组。结果　三组大鼠肝移植术中死亡率 2 6 5 % (2 6 / 98) ,术后 30d累计死亡率 71 5 % (70 / 98)。术后存活 30d后计算平均生存期 ,1组 (81 3± 33 2 )d ,2组 (6 7 6± 2 4 9)d ,3组 (5 4 4± 2 4 9)d。对照组从诱癌开始 15 0d后计算 ,平均生存期为 (2 9 4± 12 9)d。术后肝癌复发率 35 7% (10 / 2 8) ,单纯移植肝内复发7 1% (2 / 2 8) ,肝和肺同时复发 10 7% (3/ 2 8) ,肝和腹腔同时复发 3 6 % (1/ 2 8) ,单纯腹腔肿瘤 7 1% (2 /2 8) ,单纯肺部肿瘤 7 1% (2 / 2 8)。结论　大鼠肝癌肝移植良好地模仿了临床过程 ,但诱癌大鼠体质差导致术中和术后短期死亡率高。大鼠术后长时间存活是观察到肿瘤复发的重要条件 ,肝癌复发的形式多样。该模型为肝癌肝移植术后抗复发和复发机制研究提供了极好的平台。     

重组生长激素对腹部大手术患者血浆蛋白的影响

目的研究重组人生长激素(rhGH)对腹部大手术患者术后代谢、免疫功能和术后并发症的影响。方法回顾性分析腹部大手术患者79人,其中37人为治疗组,42人为对照组。治疗组手术后第2天开始,每天皮下注射思真(重组人生长激素,瑞士雪兰诺公司生产)8U,对照组给予安慰剂(生理盐水),共用7d;分别在治疗前,治疗后3、7、10、14d检测血浆白蛋白、前白蛋白及转铁蛋白水平。记录切口愈合情况及术后并发症情况。结果(1)治疗前,两组白蛋白、前白蛋白及转铁蛋白水平差异无统计学意义(P>0.05);治疗后3d,两组白蛋白水平差异无统计学意义(P>0.05),且均低于治疗前;治疗组前白蛋白、转铁蛋白均高于对照组(P<0.05);治疗后7d,治疗组3项指标均高于对照组。(2)治疗组切口愈合情况明显优于对照组(P<0.05)。(3)治疗组术后并发症发生率明显低于对照组(P<0.05)。结论腹部大手术患者术后应用重组人生长激素可以提高免疫功能,促进切口愈合,减少术后并发症的发生。     

新型鼠肿瘤皮窗模型

目的建立一种能动态显示活体内肿瘤细胞生长、新生血管形成及靶基因表达水平等的新型动物模型。方法以海洋水母中分离到的绿色荧光蛋白(GFP)作为报告基因,将1×10     

A proteinase inhibitor decreases tumor growth in a laparoscopic rat model

BACKGROUND: The balance between proteolysis and protease inhibition in the formation and breakdown processes of the extracellular matrix plays a major role in tumor cell invasion. An understanding of this relationship gave rise to the therapeutic concept of lowering tumor cell invasion by inhibiting protease activity. Phosphoramidon is an unspecific proteinase inhibitor. This experimental study investigated the effect of intraperitoneal phosphoramidon administration on tumor growth in a laparoscopic rat model. METHODS: In the first phase of the study, we investigated the influence of phosphoramidon on tumor cell invasion in a collagen matrix gel chamber in vitro. In a second experiment, a suspension of colon carcinoma cells (CC531) was introduced into the peritoneal cavity of male WAG rats. Prior to laparoscopy (at 6 mmHg for 20 min), the animals were randomized to two groups. At the start of laparoscopy, the test substance was applied intraperitoneally (group 1: controls, 1 ml 0.9% NaCl; group 2: 250 mg phosphoramidon in 1 ml 0.9% NaCl). Three weeks after the injection of tumor cells, the animals were autopsied and the tumor mass determined. RESULTS: In comparison with the control group (tumor weight 7.42 +/- 1.01 g), intraperitoneal tumor growth in the experimental group was significantly (p < 0.001) reduced by the application of phosphoramidon (tumor weight, 3.22 +/- 1.06 g). Phosphoramidon also significantly (p < 0.05) reduced tumor cell invasion through the matrix gel. Conclusion: The proteinase inhibitor phosphoramidon reduced tumor cell invasion in vitro and tumor cell growth in vivo in this laparoscopic rat model.     

重组人生长激素对结直肠癌根治术后血浆蛋白的影响

目的 研究重组人生长激素(rhGH)对结直肠癌患者术后代谢、营养状态和术后切口愈合的影响.方法 前瞻性地将82例结直肠癌患者随机分为治疗组(43例)和对照组(39例),治疗组手术后第1 d开始皮下注射rhGH,对照组给予安慰剂,共用7 d,分别在术前及术后3、7、14 d检测血浆白蛋白(ALB)、前白蛋白(PA)及转铁蛋白(TF)水平.记录切口愈合情况.结果 治疗组术后7 d和术后14 d的ALB、PA及TF水平均高于对照组(P<0.05),而对照组术后7 d和术后14 d的ALB、PA及TF水平高于术前和术后第3 d(P<0.05).治疗组术后切口愈合不良14例,对照组术后切口愈合不良24例;治疗组的切口愈合不良明显低于对照组(P<0.05).结论 结直肠癌根治术后的患者早期予以皮下注射rhGH可促进合成代谢、改善营养状态以及减少切口愈合不良的发生.