EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells

Carcinomas of the prostate and other lineages often present an autocrine stimulatory loop acting via the EGF receptor (EGFR). We have recently shown that EGFR-mediated signals enhance DU-145 prostate carcinoma cell transmigration of an extracellular matrix in vitro, and that this increased invasiveness was independent of proteolytic degradation of the matrix (Xie et al., 1995, Clin Exp Metastasis, 13, 407). To determine whether up-regulated EGFR signaling promotes tumor progression in vivo and to define the EGFR-induced cell property responsible, we inoculated athymic mice with genetically-engineered DU-145 cells. Parental DU-145 cells and those transduced to overexpress a full-length wild type (WT) EGFR formed tumors and metastasized to the lung when inoculated in the prostate and peritoneal cavity. The WT DU-145 tumors were more invasive. DU-145 cells expressing a mitogenically-active, but motility-deficient (c'973) EGFR formed small, non-invasive tumors without evidence of metastasis. All three sublines demonstrated identical, EGFR-dependent rates of cell growth in vitro, suggesting that the differential invasiveness was not due to altered growth rates. To determine whether cell motility may be, in part, responsible for tumor invasiveness, we treated WT DU-145 intraperitoneal tumors with a pharmacologic agent (U73122) which blocks EGFR-mediated cell motility but not mitogenesis. Under this treatment regimen, the WT DU-145 cells formed tumors of similar numbers and size to those formed without treatment; however, these tumors were much less invasive. These data suggest that EGFR-mediated cell motility is an important mechanism involved in tumor progression, and that this cell property may represent a novel target to limit the spread of tumors.     

Proprioceptive evoked potentials in man: cerebral responses to changing weight loads on the hand

The retrotrapezoid nucleus (RTN), a part of the rostral ventrolateral medulla, is involved in the control of breathing. The mechanisms by which the RTN modulate the activity of respiratory neurons during chemoreceptor stimulation are not fully understood. This electrophysiological study performed in the cat demonstrates that 18 out of 22 RTN neurons receive inputs from the commissural subnucleus of the solitary tract (cNTS), the peripheral chemoreceptor afferents projection site. Moreover, six RTN neurons are found to present interconnection between RTN and the ventrolateral subnucleus of the solitary tract, an area containing mainly bulbo-spinal respiratory neurons. The present data suggest that RTN play a key role by concomitantly integrating chemosensitive informations relayed by the cNTS and providing an influence on the respiratory network.     

Cholecystokinin antagonist and lipid intake as a function of caloric density and familiarity.

The effect of treatment with the cholecystokinin antagonist L364,718 on intake of different dilutions of corn oil emulsion was tested under two levels of familiarity with the oil emulsion. No increase in intake was observed. To see if the CCK antagonist was effective under our conditions, exogenous CCK was administered under the same conditions. A complete suppression of the large reduction produced by CCK on intake was found.     

衰老时海马神经元树突的可塑性增生

用形态计量的方法对老年(30个月)和成年(17个月)大鼠脑(Golgi染色标本)的海马CA3区锥体细胞的树突分支进行分级计数和测量了终末支的长度。结果是CA3神经元基树突和顶树突共有9级分支,衰老时第4级和第9级分支有显著的增多(P<0.02,P<0.03)。基树突终末支的长度衰老时无明显改变,顶树突终末支长度较成年组增加(P<0.05)。提示衰老时海马神经元的树突仍具有一定的增生和分化能力。这可能是对神经元退变的一种代偿机制。     

Effect of anti-inflammatory medication on monocyte response to titanium particles

Cytokines produced by macrophages in the periprosthetic membranes surrounding joint replacements have been implicated as causal agents in osteolysis and prosthetic loosening. The present study characterizes the response of human peripheral blood monocytes to titanium particles. Monocytes were obtained from donated blood and were cultured in the presence of different-sized titanium particles. Exposure to titanium-aluminum-vanadium particles significantly changed the release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 (IL-1), whereas there was no significant effect on the release of prostaglandin E(2) (PGE(2)). When monocytes were cultured with particles, the titanium alloy particles induced significantly more release of TNF-alpha and less IL-1 secretion. Ciprofloxacin inhibited production of TNF-alpha, IL-6, IL-1, and PGE(2) in human monocytes exposed to titanium particles. In contrast to ciprofloxacin, indomethacin was not a potent inhibitor of TNF-alpha production but potentiated IL-6 production in titanium-stimulated monocytes. Indomethacin had no effect on the production of IL-1 and was a potent inhibitor of PGE(2) production in titanium-stimulated monocytes. Pentoxifylline had an inhibitor effect on TNF-alpha production in titanium-stimulated monocytes. Pentoxifylline potentiated IL-6 and IL-1 production in monocytes exposed to titanium particles and had a biphasic effect on the PGE(2) production. The results of this study support our hypothesis that human monocytes release bone resorption mediators after in vitro exposure to TiAlV alloy particles. The results also demonstrate the differences of bone-resorbing mediators in response to different wear particle size. The pharmacologic agents (ciprofloxacin, pentoxifylline, and indomethacin) that can modulate the release of bone resorbing mediators such as PGE(2), TNF-alpha, IL-1, and IL-6 release from human monocytes. The results help to elucidate the differences in cellular response to wear particles but may not be directly transposed to the human situation.     

MTEC 1分泌的趋化因子引起特定亚群胸腺细胞的定向迁移

分析胸腺髓质上皮样细胞系ＭＴＥＣ１分泌的化学趋化因子对胸腺细胞亚群的趋化作用。方法以抗体加补体杀伤结合免疫磁珠及ｐａｎｎｉｎｇ法，将小鼠胸腺细胞分离纯化，获得ＣＤ４＋ＣＤ８＋（ＤＰ），ＣＤ４－ＣＤ８－（ＤＮ），ＣＤ４＋ＣＤ８－（ＣＤ４ＳＰ）及ＣＤ４－ＣＤ８＋（ＣＤ８ＳＰ）四亚群细胞，用Ｂｏｙｄｅｎ小室分析ＭＴＥＣ１┐ＳＮ对四群胸腺细胞的趋化作用。结果ＭＴＥＣ１┐ＳＮ对ＤＰ及ＣＤ４ＳＰ胸腺细胞有趋化活性（ＣＩ＝６．６±１．０及６．１±１．８）；对ＣＤ８ＳＰ细胞有中度趋化活性（ＣＩ＝３．２±１．０）；对ＤＮ趋化活性微弱（ＣＩ＝１．３±０．６）。化学趋化因子ＭＣＰ┐１纯品对ＣＤ４ＳＰ胸腺细胞显示强趋化活性（ＣＩ＝５．６），对ＤＮ胸腺细胞则无可测出趋化活性。结论ＭＴＥＣ１分泌的化学趋化因子对ＤＰ，ＣＤ４ＳＰ及ＣＤ８ＳＰ胸腺细胞有显著趋化作用，对ＤＮ胸腺细胞几乎无趋化作用。提示此类化学趋化因子有趋使胸腺发育中后期阶段的细胞向胸腺髓质区迁移和定位的作用。     

系统性红斑狼疮临床特征与HLA—DR,DQ基因的相关研究

采用聚合酶链反应结合顺序特异物寡核苷酸（ＰＣＲ／ＳＳＯ）探针杂交方法对ＨＬＡ－ＤＲ，ＤＱ亚区作ＤＮＡ分型，分析了系统性红斑狼疮（ＳＬＥ）的各种临床特征与ＨＬＡ－ＤＲ、ＤＱ基因的关联，结果发现汉族ＳＬＥ中肾脏损害与ＤＲ２相关，而与ＤＲ４呈负相关，口、鼻腔粘膜溃疡与ＤＲ１２相关，未发现ＳＬＥ的其他临床特征与ＤＲ、ＤＱ基因有关，发病年龄小于３５ａ者，ＤＲ２，ＤＱ６阳性率高，而ＤＲ３则多见于发病年龄大于３