Orthotopic placement of the dunning R3327 AT-3 prostate tumor in the copenhagen X fischer rat

Orthotopic placement of in vitro propagated Dunning R3327 AT-3 tumor cells resulted in a greater percentage of tumor takes and a two-fold shift in the exponential growth curve compared to flank implantation. The orthotopic tumor appeared to disseminate preferentially to regional lymph nodes, rather than to the lungs which is characteristic of flank tumors. The results suggest an important role of stromal-epithelial interactions in the growth of this tumor. © 1995 Wiley-Liss, Inc.     

同种异体原位心脏移植成功3例报告

目的:总结分析3例同种异体原位心脏移植术的临床经验。方法:采用Shumway&Stanford方法对3例终末期扩张型心肌病病人行同种异体原位心脏移植术。其中1例伴有严重糖尿病和中度肺动脉高压,术前心跳骤停心肺复苏成功;1例极度肥胖,体重108kg(身高172cm);1例62岁高龄伴肾功能不全和中度肺动脉高压。供体均为脑死亡者,供心保护采用4℃改良StThomas液;术后免疫抑制治疗采用环孢素A、骁悉、强的松三联治疗,根据血环孢素浓度及心内膜活检调整环孢素A用量。结果:3例均康复,未发生术后超急性或急性排斥反应。例2术后出现一过性右心功能不全,经大量利尿和无创通气治疗,48h后完全恢复;例3术后并发急性肾功能衰竭和肺部感染,经连续肾脏替代(CRRT)和调整抗生素治疗痊愈。病人心功能均恢复正常。例1需长期胰岛素治疗糖尿病。3例均完全过上了正常人的生活,2例已恢复手术前工作。结论:同种异体原位心脏移植是治疗终末期心脏病的有效方法。     

Thrombus causing fatal left ventricular outflow tract obstruction in a heart transplant patient

A 60 year male, orthotopic heart transplant recipient developed a fatal left ventricular outflow obstruction secondary to thrombus at 38 months post transplant. Although he had episodes of mild to moderate rejection at 2 and 16 months post transplant, subsequent biopsies were negative and annual cardiac catheterizations showed mild left ventricular hypokinesis and normal coronary arteries. This case represents a catastrophic complication of transplant rejection and illustrates the problems with identifying rejection using current diagnostic methods.     

Metastatic dissemination of human malignant oral keratinocyte cell lines following orthotopic transplantation reflects response to TGF-beta 1

This study examined the behaviour of nine human malignant oral keratinocyte cell lines following orthotopic transplantation to the floor of the mouth of athymic mice. Tumourigenesis, local spread, and metastatic dissemination were correlated with known cellular responses to transforming growth factor-beta 1 (TGF-beta 1). Six of nine cell lines were tumourigenic; four of these cell lines showed local spread which was characterized by vascular and bone invasion. Metastatic spread was uncommon, with only 9% of animals with primary tumours developing metastases and these were almost exclusively found in the regional lymph nodes; there was one pulmonary metastasis and no liver deposits. Tumour cell behaviour did not reflect the clinical stage of the original tumours. Cell lines that were resistant to TGF-beta 1-induced growth inhibition were more likely to form primary tumours, exhibit local spread, and metastasize than cells that were growth-inhibited by the ligand. The data demonstrate that tumourigenicity and tumour behaviour in this orthotopic mouse model varied between cell lines and that the pattern of local invasion and metastasis was similar to that seen in human oral cancer. Furthermore, cell lines that were refractory to the growth inhibitory effects of TGF-beta 1 behaved more aggressively than cells that underwent ligand-induced cell-cycle arrest.     

Influence of organ site and tumor cell type on MUC1-specific tumor immunity

We investigated the influence of organ-specific parameters on tolerance and immunity to human MUC1. C57Bl/6 mice (wild-type) and C57Bl/6 transgenic for MUC1 (MUC1.Tg) were challenged in the pancreas with Panc02-MUC1, a C57Bl/6-syngeneic pancreatic cancer cell line expressing human MUC1. Wild-type mice produced immune responses to MUC1 when presented on tumor cells growing in the pancreas; however, the responses to tumors in the pancreas were less effective than responses produced by tumor challenge at the s.c. site. Tumor immunity specific for MUC1 was produced in wild-type mice by two different procedures: (i) s.c. immunization of wild-type mice with a low dose of Panc02-MUC1 or (ii) adoptive transfer of spleen and lymph node cells harvested from wild-type mice previously immunized s.c. with Panc02-MUC1. This demonstrates that immune responses to MUC1 presented at the s.c. site can be detected and adoptively transferred. MUC1.Tg mice were immunologically tolerant to MUC1; however, some immunological protection against orthotopic challenge with Panc02-MUC1 was conferred by adoptive transfer of CD4+ and CD8+ T cells from wild-type mice. These results show that it is more difficult to produce immune responses to tumors growing at the pancreatic site than the s.c. site. Panc02-MUC1 cells growing in the pancreas were accessible to the immune system, and immune responses evoked by s.c. presentation of this molecule in wild-type mice were effective in rejecting tumor cells in the pancreas of both wild-type and MUC1.Tg mice. No effective anti-tumor immune responses against MUC1 were produced in MUC1.Tg mice.     

公民逝世后器官捐献原位肝移植后早期肝功能不全的危险因素分析

目的 观察公民逝世后器官捐献原位肝移植术后早期肝功能不全（early allograft dysfunction,EAD）的发生情况,探讨早期肝功能不全的危险因素。方法 回顾性分析2017年1月至2019年12月间我院65例行肝移植供、受体资料。根据术后情况将患者分为EAD组（n=29）及非EAD组（n=35）。对相关因素先进行单因素分析,然后将统计学差异的因素进行多因素Logistic回归模型分析。结果 65例原位肝移植患者术后早期肝功能不全的患者有29例,发生率为44.6%。单因素分析显示EAD组与非EAD组供体血清钠[（157.53±21.71）mmol/L vs（146.06±15.24）mmol/L,P=0.019]、热缺血时间[（21.6±6.5）min vs（10.6±4.3）min,P=0.016]、冷缺血时间[（8.3±1.2）h vs（5.4±1.2）h,P=0.012]、ICU住院时间[（78.1±19.5）h vs（49.7±17.6）h,P=0.007]及受体的无肝期时间[（98.3±16.3）h vs（66.0±17.6）h,P=0.037]差异均有统计学意义。多因素Logistic回归分析结果显示影响术后早期肝功能不全的独立危险因素为供体血清钠水平（OR 18.372,95%CI 1.846～24.173,P=0.019）及热缺血时间（OR 8.105,95%CI 1.513～37.205,P=0.013）。结论 供体血清钠水平及热缺血时间是公民逝世后器官原位肝移植术后EAD的独立危险因素。     

Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation

Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft. Received for publication on March 8, 1999; accepted on April 30, 1999     

乌司他丁对原位肝移植术肺损伤的保护作用

目的:观察原位肝移植术(OLT)中肺损伤的程度,探讨乌司他丁(UTI)对OLT中肺损伤的保护作用.方法:40例择期行OLT手术患者随机分为UTI组和对照组各20例,UTI组(n=20)切皮后将UTI 100万单位加入100mL生理氯化钠溶液,持续静脉输注,之后每隔4 h重复使用.对照组(n=20)以等容量生理氯化钠溶液代替.于麻醉后切皮前、无肝前期120 min、无肝期30 min、新肝期10 min、新肝期60 min和术毕对肺顺应性、吸气阻力、呼气阻力、峰值压力和平台压力进行观察.结果:在新肝期10 min、新肝期60 min和术毕时,对照组的肺顺应性显著下降,吸气阻力、呼气阻力、峰值压力和平台压力显著升高(P<0.05).UTI组的吸气阻力、呼气阻力、峰值压力和平台压力值均明显低于对照组(P<0.05),而肺顺应性值明显高于对照组(P<0.05).结论:0LT过程造成肺损伤,UTI在OLT中对肺损伤有保护作用.     

Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide

Glioblastoma (GBM) causes poor survival in patients even when applying aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment, but resistance always ensues. In previous years, efforts have focused on new therapeutic regimens with conventional drugs to activate immune responses that may enhance tumor regression and prevent regrowth, for example the “metronomic” approaches. In metronomic scheduling studies, cyclophosphamide (CPA) in GL261 GBM growing subcutaneously in C57BL/6 mice was shown not only to activate antitumor CD8⁺ T‐cell response, but also to induce long‐term specific T‐cell tumor memory. Accordingly, we have evaluated whether metronomic CPA or TMZ administration could increase survival in orthotopic GL261 in C57BL/6 mice, an immunocompetent model. Longitudinal in vivo studies with CPA (140 mg/kg) or TMZ (range 140–240 mg/kg) metronomic administration (every 6 days) were performed in tumor‐bearing mice. Tumor evolution was monitored at 7 T with MRI (T₂‐weighted, diffusion‐weighted imaging) and MRSI‐based nosological images of response to therapy. Obtained results demonstrated that both treatments resulted in increased survival (38.6 ± 21.0 days, n = 30) compared with control (19.4 ± 2.4 days, n = 18). Best results were obtained with 140 mg/kg TMZ (treated, 44.9 ± 29.0 days, n = 12, versus control, 19.3 ± 2.3 days, n = 12), achieving a longer survival rate than previous group work using three cycles of TMZ therapy at 60 mg/kg (33.9 ± 11.7 days, n = 38). Additional interesting findings were, first, clear edema appearance during chemotherapeutic treatment, second, the ability to apply the semi‐supervised source analysis previously developed in our group for non‐invasive TMZ therapy response monitoring to detect CPA‐induced response, and third, the necropsy findings in mice cured from GBM after high TMZ cumulative dosage (980–1400 mg/kg), which demonstrated lymphoma incidence. In summary, every 6 day administration schedule of TMZ or CPA improves survival in orthotopic GL261 GBM with respect to controls or non‐metronomic therapy, in partial agreement with previous work on subcutaneous GL261.