Interleukin-15 Plays a Central Role in Human Kidney Physiology and Cancer through the γc Signaling Pathway

The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows that RPTEC express a functional heterotrimeric IL-15Rαβγc complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the γc-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of γc-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the γc/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Rαβ heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/γc-dependent signaling (STAT5), by co-transfecting γc and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and γc-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation) and RCC (down-regulation)

Mother-male bond, but not paternity, influences male-infant affiliation in wild crested macaques

In promiscuous primates, interactions between adult males and infants have rarely been investigated. However, recent evidence suggests that male affiliation towards infants has an influence on several aspects of the infants’ life. Furthermore, affiliations may be associated with male reproductive strategy. In this study, we examined which social factors influenced male-infant affiliation initiated by either male or infant, in wild crested macaques (Macaca nigra). We combined behavioral data and genetic paternity analysis from 30 infants living in three wild groups in Tangkoko Reserve, Indonesia. Our results indicate that adult males and infants do not interact at random, but rather form preferential associations. The social factors with the highest influence on infant-initiated interactions were male rank and male association with the infant’s mother. While infants initiated affiliations with males more often in the absence of their mothers, adult males initiated more affiliations with infants when their mothers were present. Furthermore, males initiated affiliations more often when they were in the same group at the time the infant was conceived, when they held a high dominance rank or when they had a close relationship with the mother. Interestingly, paternity did not affect male-infant affiliation despite being highly skewed in this species. Overall, our results suggest that adult males potentially associate with an infant to secure future mating with the mother. Infants are more likely to associate with a male to receive better support, suggesting a strategy to increase the chance of infant survival in a primate society with high infant mortality

Irreversible electroporation of hepatocellular carcinoma: patient selection and perspectives

Asha Zimmerman,1 David Grand,2 Kevin P Charpentier1 1Department of Surgery, 2Department of Radiology, Rhode Island Hospital, Brown University, Providence, RI, USA Abstract: Irreversible electroporation (IRE) is a novel form of tissue ablation that uses high-current electrical pulses to induce pore formation of the cell lipid bilayer, leading to cell death. The safety of IRE for ablation of hepatocellular carcinoma (HCC) has been established. Outcome data for ablation of HCC by IRE are limited, but early results are encouraging and suggest equivalency to the outcomes obtained for thermal ablation for appropriately selected, small (<3 cm) tumors. Long-term oncologic efficacy and histopathologic response data have not been published, and therefore, application of IRE for the treatment of HCC should still be viewed with caution. Keywords: ablation, liver, tumors, IRE, hepati

Palliative treatment of presacral recurrence of endometrial cancer using irreversible electroporation: a case report

INTRODUCTION: Irreversible electroporation (IRE) is a new minimally invasive tumor ablation technique which induces irreversible disruption of cell membrane integrity by changing the transmembrane potential resulting in cell death. Irreversible electroporation is currently undergoing clinical investigation as local tumor therapy for malignant liver and lung lesions. This is the first case report to describe the successful palliative ablation of a presacral recurrence of an endometrial cancer to achieve locoregional tumor control and pain relief. CASE PRESENTATION: A 56-year-old Caucasian woman was referred for interventional treatment of an advanced local recurrence of endometrial cancer (11.9 × 11.6 × 14.9cm) with infiltration of the sacral bone and nerve plexus. Due to the immediate proximity to the sacral plexus, the patient could neither undergo surgical therapy nor a second radiation therapy. Due to its ablation mechanism irreversible electroporation was deemed to be the best therapy option. CONCLUSION: We showed in this case that a large tumor mass adjacent to a bundle of neural structures, the sacral plexus, can be widely ablated by irreversible electroporation with only minor temporary impairment of the neural function, even though a large infiltrating tissue volume (941cm3) was ablated