Immunotherapy and whole-body hyperthermia as combined modality treatment of a subcutaneous murine sarcoma

Interleukin–2 and hyperthermia have been used individually to treat a variety of tumors in both experimental and human trials. Combined adoptive immunotherapy and hyperthermia is an exciting new line of investigation. Previous work in our laboratory has shown that combined local hyperthermia and rIL-2 therapy can significantly decrease the rate of tumor growth. In this study, we investigated the effect of combined whole-body hyperthermia (WBHT) and rIL-2 on the growth of subcutaneous MCA-105 murine tumors in C57BL/6 mice. Treatment of both microscopic (day 3) and macroscopic (day 10) tumors was evaluated. In the treatment of microscopic tumors, animals received either no treatment; rIL-2 (3 × 10⁵ IU ip tid) on days 3–7; plus WBHT(41°C for 30 min) on days 3, 5, and 7; or WBHT only on days 3, 5, and 7. In treating macroscopic tumors, animals received either no treatment; rIL-2 on days 10–14; plus WBHT on days 10, 12, and 14; or WBHT only on days 10, 12, and 14. While combined treatment and WBHT alone had no significant effect on the growth of microscopic tumors, combined IL-2 and WBHT significantly reduced the rate of tumor growth of macroscopic tumors. These results suggest that the tumor microenvironment plays a critical role in combined WBHT and rIL-2 therapy, and may be due to effects of WBHT on the tumor vasculature. © 1993 Wiley-Liss, Inc.     

The epithelial-mesenchymal transition induces aggressivity of mucinous cystic neoplasm of the pancreas with neuroendocrine component: An immunohistochemistry study

Background

Pancreatic mucinous cystic neoplasms (MCN) are rare tumors that are usually diagnosed in females.

Rolipram forms a potent discriminative stimulus in drug discrimination experiments in rats

Long Evans rats were trained to discriminate 0.2 mg/kg IP (±)-rolipram from vehicle injection in a food-motivated two-lever operant task. Eight out of nine rats acquired the discrimination after an average of 91 sessions (min 65, max 137). The ED₅₀ of (±)-rolipram was 0.06 mg/kg IP. Generalization tests with (–)- and (+)-rolipram showed that the (–)-isomer was 8 times more active than (+)-rolipram with an ED₅₀ of 0.06 and 0.4 mg/kg IP respectively. The phosphodiesterase inhibitor RO 20-1724 partially (83%) generalized to (±)-rolipram in doses of 0.6 and 1.0 mg/kg IP. IBMX 5 mg/kg IP showed 63% generalization. Tests with imipramine and the (+)- and (–)-isomer of the noradrenaline uptake inhibitor oxaprotiline suggest that NA-uptake inhibiting drugs do not form an interoceptive cue which is (±)-rolipram-like. dbcAMP 12.5 mg/kg SC and 100 mg/kg SC dbcGMP did not generalize to the training drug. The nature of the discriminative stimulus produced by this dose of (±)-rolipram in rats remains to be elucidated. Offprint requests to: R. Ortman     

Accuracy in coronary graft flow measurement

A blood flow calibration apparatus is described for use with electromagnetic flow probes. It is an automatic gravity-flow system, which provides a constant level and therefore constant flow at any preset rate. On several occasions, the use of this device has helped to determine whether flow probes require simple adjustment, factory repair, or replacement. Using this system, a systematic error in the manufacturer's "precalibration" averaging +22% (range, 9 to 50%) has been discovered, and appropriate corrections have been made. The accuracy of these corrections has been confirmed by a rapid, in vivo method of calibration, which also is described and which can be carried out during the conduct of aortocoronary bypass operation. It is recommended that all groups measuring coronary graft flow become familiar with their electromagnetic flowmeter and probes by means such as those described, in the interest of accurate flow measurement after bypass operation.     

CD105和MMP-9在骨巨细胞瘤中的表达及意义

目的研究骨巨细胞瘤组织中CD105和MMP-9的表达及与肿瘤生物学行为的关系。方法运用免疫组织化学S-P法,检测CD105和MMP-9在38例骨巨细胞瘤中的表达,分析其与肿瘤临床病理特征及复发的关系。结果1)CD105标记的肿瘤内MVD值为(9.70±2.34),MVD值随肿瘤组织学级别的升高而递增,但差异无显著性(P>0.05)。按X线表现分型,浸润型肿瘤的MVD值明显高于静止型,差异有显著性(P<0.05)。复发组的骨巨细胞瘤其MVD值高于未复发组,差异有显著性(P<0.01)。肿瘤内MVD值与放射学分型、肿瘤复发有关。2)MMP-9在骨巨细胞瘤中的阳性表达率为60.53%,MMP-9阳性表达率在不同组织学分级的病例中差异无显著性(P>0.05),按X线表现分型,MMP-9在活动型、浸润性两组的阳性率高于静止型组,差异有显著性(P<0.01)。MMP-9在复发组的表达率高于未复发组,差异有显著性(P<0.01),提示MMP-9过表达与肿瘤的复发有关。3)MMP-9阳性组的MVD值高于MMP-9阴性组,差异有显著性(P<0.01),Spearman相关分析提示MMP-9表达与MVD值呈正相关。结论CD105标记的MVD值和MMP-9过表达可作为预测骨巨细胞瘤复发的客观依据。MMP-9过表达与骨巨细胞瘤内新生血管的形成有关。     

TGF-β1和CD105在胰腺癌中的表达及其临床意义

目的探讨TGF-β1和CD105在胰腺癌生长、浸润、转移过程中的作用，为对患者进行预后判断及生物治疗提供理论依据。方法应用免疫组织化学S-P法检测TGF-β1、CD105在52例胰腺癌和10例非肿瘤性胰腺组织中的表达，分析它们与胰腺癌临床病理参数及患者生存率的关系。结果TGF-β1在非肿瘤性胰腺组织、胰腺癌中的阳性表达率分别为30％和80．77％，两者间的差异具有统计学意义（P〈0．01）。TGF-β1的表达强度与胰腺癌临床分期及淋巴结有无转移呈正相关（P〈0．01）。在52例胰腺癌中，CD105标记的微血管密度（Micro Vessel Density，MVD）明显高于非肿瘤性胰腺组织（P〈0．01）。胰腺癌分化程度越低，CD105标记的MVD值越高，并且TNM分期Ⅲ、Ⅳ期MVD值显著高于Ⅰ、Ⅱ期（P〈0．01），淋巴结转移组的MVD值显著高于无淋巴结转移组（P〈0.01）。此外，生存单因素分析TGF-β1、CD105与胰腺癌的预后有关（P〈0．01）。结论TGF-β1和CD105在胰腺癌生长、浸润和转移过程中发挥了一定的作用。     

卵巢上皮性肿瘤CD105标记的微血管密度的研究

目的探讨卵巢上皮性肿瘤CD105表达及其标记的微血管密度(MVD)与肿瘤发生、发展的关系.方法应用免疫组织化学法检测25例良性肿瘤,10例交界性肿瘤和24例恶性上皮性肿瘤中CD105的表达及MVD.结果59例卵巢上皮性肿瘤中,CD105标记的MVD在恶性肿瘤中显著高于交界性及良性肿瘤(P＜0.01),CD105标记的恶性肿瘤中MVD与肿瘤临床分期、病理分级、患者年龄无统计学相关性(P＞0.05).结论CD105标记的MVD与卵巢上皮性肿瘤恶性进展相关,但不能作为卵巢上皮性恶性肿瘤的预后指标.     

CD105与肿瘤血管形成

CD105(endoglin,EDG)为细胞膜糖蛋白,是转化生长因子-β(TGF-β)受体超家族的组成成分。调节细胞对TGF的反应,在血管生成的各种组织及肿瘤组织边缘部分血管起源的内皮细胞中高表达是新生血管的标志,而新生血管生成是实体肿瘤普遍存在的特征,CD105与肿瘤的生长、浸润、转移密切相关,可能成为某些肿瘤诊断治疗的重要靶分子之一。