Cachexia induced by Yoshida ascites hepatoma in Wistar rats is not associated with inflammatory response in the spleen or brain.

Recent data indicate that peripheral, as well as hypothalamic pro-inflammatory cytokines play an important role in the development of cancer cachexia. However, there are only a few studies simultaneously investigating the expression of inflammatory molecules in both the periphery and hypothalamic structures in animal models of cancer cachexia. Therefore, using the Yoshida ascites hepatoma rat's model of cancer cachexia we investigated the gene expression of inflammatory markers in the spleen along with the paraventricular and arcuate nuclei, two hypothalamic structures that are involved in regulating energy balance. In addition, we investigated the effect of intracerebroventricular administration of PS-1145 dihydrochloride (an Ikß inhibitor) on the expression of selected inflammatory molecules in these hypothalamic nuclei and spleen. We observed significantly reduced food intake in tumor-bearing rats. Moreover, we found significantly decreased expression of IL-6 in the spleen as well as decreased NF-κB in the paraventricular nucleus of rats with Yoshida ascites hepatoma. Similarly, expression of TNF-α, IL-1ß, NF-κB, and COX-2 in the arcuate nucleus was significantly reduced in tumor-bearing rats. Administration of PS-1145 dihydrochloride reduced only the gene expression of COX-2 in the hypothalamus. Based on our findings, we suggest that the growing Yoshida ascites hepatoma decreased food intake by mechanical compression of the gut and therefore this model is not suitable for investigation of the inflammation-related mechanisms of cancer cachexia development.

Ambiguous effect of signals transmitted by the vagus nerve on fibrosarcoma incidence and survival of tumor-bearing rats.

While the parasympathetic nervous system appears to be involved in the regulation of tumor progression, its exact role is still unclear. Therefore, using a rat BP6-TU2 fibrosarcoma tumor model, we investigated the effect of (1) reduction of vagal activity produced by subdiaphragmatic vagotomy; and (2) enhancement of vagal activity produced by continuous delivery of electric impulses to the cervical part of the vagus nerve on tumor development and survival of tumor-bearing rats. We also evaluated the expression of cholinergic receptors within in vitro cultivated BP6-TU2 cells. Interestingly, we found that both, vagal stimulation and subdiaphragmatic vagotomy slightly reduced tumor incidence. However, survival of tumor-bearing rats was not affected by any of the experimental approaches. Additionally, we detected mRNA expression of the α1, α2, α5, α7, and α10 subunits of nicotinic receptors and the M1, M3, M4, and M5 subtypes of muscarinic receptors within in vitro cultivated BP6-TU2 cells. Our data indicate that the role of the vagus nerve in modulation of fibrosarcoma development is ambiguous and uncertain and requires further investigation.

Chemical sympathectomy increases neutrophil-to-lymphocyte ratio in tumor-bearing rats but does not influence cancer progression.

The sympathetic nervous system regulates many immune functions and modulates the anti-tumor immune defense response, too. Therefore, we studied the effect of 6-hydroxydopamine induced sympathectomy on selected hematological parameters and inflammatory markers in rats with Yoshida AH130 ascites hepatoma. We found that chemically sympathectomized tumor-bearing rats had significantly increased neutrophil-to-lymphocyte ratio, leukocyte-to-lymphocyte ratio, and plasma levels of tumor necrosis factor alpha. Although our findings showed that sympathetic denervation in tumor-bearing rats led to increased neutrophil-to-lymphocyte ratio, that is an indicator of the disease progression, we found no significant changes in tumor growth and survival of sympathectomized tumor-bearing rats.