Adenocarcinoma of the ileocolic junction and multifocal hepatic sarcomas in an aged rhesus macaque (Macaca mulatta).

An aged male rhesus macaque in our colony had decreased appetite and a loss of interest in behavioral testing. CBC analysis revealed a regenerative, microcytic, hypochromic anemia with thrombocytosis, consistent with iron deficiency. A fecal occult blood test was positive. Ultrasound imaging revealed numerous, vascularized focal liver lesions that suggested metastases. The macaque's appetite continued to decrease, and he became more lethargic. At this point, the investigator elected to euthanize the macaque. At necropsy, the ileocolic junction was white and abnormally thickened, and the liver was pale tan with approximately 18 discrete white masses randomly scattered throughout the hepatic parenchyma. Histologically, the mass at the ileocolic junction was identified as an intestinal adenocarcinoma, whereas the liver masses were confirmed to be undifferentiated hepatic sarcomas. This case report describes a rhesus macaque that had 2 unrelated primary neoplasms. A review of the literature indicates that this rhesus macaque is the first reported to have an adenocarcinoma of the ileocolic junction and multiple hepatic sarcomas simultaneously.

Cyclin D1 is transcriptionally regulated by and required for transformation by activated signal transducer and activator of transcription 3.

Signal transducers and activators of transcription 3 (STAT3) is a transcription factor that is aberrantly activated in many cancer cells. Constitutively activated STAT3 is oncogenic, presumably as a consequence of the genes that it differentially regulates. Activated STAT3 correlated with elevated cyclin D1 protein in primary breast tumors and breast cancer-derived cell lines. Cyclin D1 mRNA levels were increased in primary rat-, mouse-, and human-derived cell lines expressing either the oncogenic variant of STAT3 (STAT3-C) or vSrc, which constitutively phosphorylates STAT3. Mutagenesis of STAT3 binding sites within the cyclin D1 promoter and chromatin immunoprecipitation studies showed an association between STAT3 and the transcriptional regulation of the human cyclin D1 gene. Introduction of STAT3-C and vSrc into immortalized cyclin D1(-/-) and cyclin D1(-/+) fibroblasts led to anchorage-independent growth of only cyclin D1(-/+) cells. Furthermore, knockdown of cyclin D1 in breast carcinoma cells led to a reduction in anchorage-independent growth. Phosphorylation of the retinoblastoma (Rb) protein [a target of the cyclin D1/cyclin-dependent kinase 4/6 (cdk4/6) holoenzyme] was delayed in the cyclin D1(-/-) cells relative to cyclin D1(-/+) cells. The E7 oncogene, whose activity includes degradation of Rb and dissociation of Rb from E2F, did not confer anchorage-independent growth to the cyclin D1(-/-) cells but, in conjunction with vSrc, resulted in robust growth in soft agar. These results suggest both a cdk-dependent and cdk-independent role for cyclin D1 in modulating transformation by different oncogenes.

Effect of Eucommia ulmoides on systolic blood pressure in the spontaneous hypertensive rat.

Experiments were conducted to establish the safety and efficacy of Eucommia ulmoides (Du-Zhong) extract in the treatment of hypertension. Pilot experiments using rats demonstrated that E. ulmoides extract was safe to the saturation limits of the compound. The maximum tolerated dose (MTD) was 1200 mg/kg when administered by gastric gavage at a concentration of 1200 mg/ml. Also, rats given 200 mg/kg, 600 mg/kg or 1200 mg/kg doses of E. ulmoides extract daily for 28 days demonstrated no evidence of acute toxicity as determined by clinical appearance, histopathology and serum chemistry evaluation. Lastly, spontaneous hypertensive rats (SHRs) were administered E. ulmoides extract daily for 22 days. Systolic blood pressure (BP) was measured on treatment days 1, 8, 15 and 22 at 0, 1, 2 and 3 hours post-treatment. Beginning on day 8, E. ulmoides extract administered at the mid or high dosages lowered BP in male, but not female, rats. BP declined at a rate of approximately 10 mmHg per hour. The mid dosage of 600 mg/kg was found to be the minimum effective dose. In conclusion, E. ulmoides extract was non-toxic and effective in reducing systolic BP in the SHR.

Transient expansion of synaptically connected dendritic spines upon induction of hippocampal long-term potentiation.

Dendritic spines are small protrusions from dendritic shafts that contain the postsynaptic sites of glutamatergic synapses in the brain. Spines undergo dramatic activity-dependent structural changes that are particularly prominent during neuronal development. Although changes in spine shape or number have been proposed to contribute to forms of synaptic plasticity that underlie learning and memory, the extent to which spines remain plastic in the adult brain is unclear. We find that induction of long-term potentiation (LTP) of synaptic transmission in acute hippocampal slices of adult mice evokes a reliable, transient expansion in spines that are synaptically activated, as determined with calcium imaging. Similar to LTP, transient spine expansion requires N-methyl-D-aspartate (NMDA) receptor-mediated Ca2+ influx and actin polymerization. Moreover, like the early phase of LTP induced by the stimulation protocol, spine expansion does not require Ca2+ influx through L-type voltage-gated Ca2+ channels nor does it require protein synthesis. Thus, transient spine expansion is a characteristic feature of the initial phases of plasticity at mature synapses and so may contribute to synapse remodeling important for LTP.