RESUMO
Constitutive Wnt/ß-catenin signaling is a key contributor to colorectal cancer (CRC). Although inactivation of the tumor suppressor adenomatous polyposis coli (APC) is recognized as an early event in CRC development, it is the accumulation of multiple subsequent oncogenic insults facilitates malignant transformation. One potential contributor to colorectal carcinogenesis is the POZ-ZF transcription factor Kaiso, whose depletion extends lifespan and delays polyp onset in the widely used Apc(Min/+) mouse model of intestinal cancer. These findings suggested that Kaiso potentiates intestinal tumorigenesis, but this was paradoxical as Kaiso was previously implicated as a negative regulator of Wnt/ß-catenin signaling. To resolve Kaiso's role in intestinal tumorigenesis and canonical Wnt signaling, we generated a transgenic mouse model (Kaiso(Tg/+)) expressing an intestinal-specific myc-tagged Kaiso transgene. We then mated Kaiso(Tg/+) and Apc(Min/+) mice to generate Kaiso(Tg/+):Apc(Min/+) mice for further characterization. Kaiso(Tg/+):Apc(Min/+) mice exhibited reduced lifespan and increased polyp multiplicity compared to Apc(Min/+) mice. Consistent with this murine phenotype, we found increased Kaiso expression in human CRC tissue, supporting a role for Kaiso in human CRC. Interestingly, Wnt target gene expression was increased in Kaiso(Tg/+):Apc(Min/+) mice, suggesting that Kaiso's function as a negative regulator of canonical Wnt signaling, as seen in Xenopus, is not maintained in this context. Notably, Kaiso(Tg/+):Apc(Min/+) mice exhibited increased inflammation and activation of NFκB signaling compared to their Apc(Min/+) counterparts. This phenotype was consistent with our previous report that Kaiso(Tg/+) mice exhibit chronic intestinal inflammation. Together our findings highlight a role for Kaiso in promoting Wnt signaling, inflammation and tumorigenesis in the mammalian intestine.
RESUMO
BACKGROUND: The aim of the study was to determine the significance of spinal anesthesia in the suppression of the metabolic, hormonal, and hemodynamic response to surgical stress in elective surgical patients compared to general anesthesia. MATERIAL AND METHODS: The study was clinical, prospective, and controlled and it involved 2 groups of patients (the spinal and the general anesthesia group) who underwent the same surgery. We monitored the metabolic and hormonal response to perioperative stress based on serum cortisol level and glycemia. We also examined how the different techniques of anesthesia affect these hemodynamic parameters: systolic arterial pressure (AP), diastolic AP, heart rate (HR), and arterial oxygen saturation (SpO2). These parameters were measured before induction on anesthesia (T1), 30 min after the surgical incisions (T2), 1 h postoperatively (T3) and 24 h after surgery (T4). RESULTS: Serum cortisol levels were significantly higher in the general anesthesia group compared to the spinal anesthesia group (p<0.01). Glycemia was significantly higher in the general anesthesia group (p<0.05). There was a statistically significant, positive correlation between serum cortisol levels and glycemia at all times observed (p<0.01). Systolic and diastolic AP did not differ significantly between the groups (p=0.191, p=0.101). The HR was significantly higher in the general anesthesia group (p<0.01). SpO2 values did not differ significantly between the groups (p=0.081). CONCLUSIONS: Based on metabolic, hormonal, and hemodynamic responses, spinal anesthesia proved more effective than general anesthesia in suppressing stress response in elective surgical patients.