Modulating tumor reactive stroma by extracorporeal shock waves to control prostate cancer progression.

BACKGROUND: Prostate cancer is the second most common cancer worldwide. Tumor microenvironment is composed of activated fibroblasts, the so called carcinoma-associated fibroblasts (CAFs). They express high levels of α-smooth muscle actin (α-SMA) and type I collagen (COL1), and support proliferation and migration of tumor epithelial cells. Extracorporeal shock waves (ESWs), acoustic waves, are effective in the treatment of hypertrophic scars, due to their ability to modulate fibrosis. Based on this rationale, the study evaluated the effects of ESWs on CAF activation and the influence of ESW-treated CAFs on the growth and migration of epithelial prostatic carcinoma cells. METHODS: Primary cultures of CAFs (n = 10) were prepared from tumors of patients undergoing surgery for high-risk prostate carcinoma. CAFs were treated with ESWs (energy levels: 0.32 mJ/mm2 , 1000 pulses; 0.59 mJ/mm2 , 250 pulses). After treatment, the messenger RNA and protein levels of the stromal activation markers α-SMA and COL1 were determined. Subsequently, two different stabilized cell lines (PC3 and DU145) of androgen-resistant prostate cancer were treated with the conditioned media produced by ESW-treated CAFs. At different times, viability and migration of PC3 and DU145 cells were evaluated. Viability was also assessed by coculture system using CAFs and PC3 or DU145 cells. RESULTS: ESWs reduced gene expression and protein level of α-SMA and COL1 in CAFs. The treatment of PC3 and DU145 with conditioned media of ESW-treated CAFs determined a reduction of their growth and invasive potential. Coculture systems between ESW-treated CAFs and PC3 or DU145 cells confirmed the epithelial cell number reduction. CONCLUSIONS: This in vitro study demonstrates for the first time that ESWs are able to modulate the activation of prostate CAFs in favor of a less "reactive" stroma, with consequent slowing of the growth and migration of prostate cancer epithelial cells. However, only further studies to be performed in vivo will confirm the possibility of using this new therapy in patients with prostate cancer.

Near-infrared spectroscopy is a promising noninvasive technique for monitoring the effects of feeding regimens on the cerebral and splanchnic regions.

AIM: The effects of different milk and, or, administration regimens on cerebro-splanchnic perfusion are still a matter of debate. We investigated the effects of the bolus administration of breast milk or formula on cerebro-splanchnic oximetry, function and perfusion, assessed by near-infrared spectroscopy (NIRS). METHODS: This observational study of 30 infants fed with breast (n = 15) or formula (n = 15) milk, and matched for gestational age and birth weight, was carried out in the neonatal intensive care unit of the C Arrigo Children's Hospital, Alessandria, Italy, a tertiary-level referral centre, from October 2015 to December 2016. NIRS monitoring parameters, such as cerebral and splanchnic oximetry, fraction of tissue oxygen extraction and the cerebral-splanchnic ratio, were recorded before, during and after feeding. RESULTS: Breast milk led to a significant increase in cerebro-splanchnic oximetry and tissue oxygen extraction (p < 0.001) during and after feeding, and the cerebro-splanchnic perfusion ratio was significantly higher (p < 0.001) in the breast than formula group. CONCLUSION: Our study results suggest that breast milk was better tolerated than formula, requiring lower energy expenditure and lower cerebro-splanchnic haemodynamic redistribution. The findings could prompt investigations using NIRS as a promising noninvasive tool for cerebral and splanchnic longitudinal monitoring during neonatal feeding.

Cerebral NIRS patterns in late preterm and very preterm infants becoming late preterm.

BACKGROUND: Near Infrared Spectroscopy (NIRS) has been proposed as a useful, noninvasive monitoring technique providing reliable information about central nervous system (CNS) oximetry and function. Recently, brain damage has been reconsidered as a dynamic process evolving over the weeks of gestation. We therefore investigated NIRS cerebral pattern differences between healthy late preterm infants (LPTo) and very preterm infants becoming late preterm (LPT). METHODS: We conducted an observational study in 40 healthy late preterm infants, matched for gestational age at monitoring, of whom 20 where LPTo and 20 LPT. Clinical, diagnostic and laboratory monitoring procedures and cerebral oximetry (crSO2) and function (cFTOE) were recorded on admission into the study. RESULTS: No significant differences (p > .05, for all) were found between groups regarding clinical, diagnostic or laboratory parameters. Higher crSO2 and lower cFTOE (p < .001, for both) were found in the LPTo group. CONCLUSIONS: Our results, showing impaired oximetry and function of CNS in LPT, offer additional support to NIRS parameters as a useful tool for longitudinal CNS monitoring of very preterm infants becoming LPT. Future studies correlating NIRS variables and long-term neurological outcome in LPT are needed to elucidate the concept of dynamic brain damage pathogenesis.