Search

Purpose: Ionizing radiation (IR) treatment activates inflammatory processes causing the release of a great amount of molecules able to affect the cell survival. The aim of this study was to analyze the cytokine signature of conditioned medium produced by non-tumorigenic mammary epithelial cell line MCF10A, as well as MCF7 and MDA-MB-231 breast cancer cell lines, after single high doses of IR in order to understand their role in high radiation response., Materials and Methods: We performed a cytokine profile of irradiated conditioned media of MCF10A, MCF7 and MDA-MB-231 cell lines treated with 9 or 23 Gy, by Luminex and ELISA analyses., Results: Overall, our results show that both 9 Gy and 23 Gy of IR induce the release within the first 72 h of cytokines and growth factors potentially able to influence the tumor outcome, with a dose-independent and cell-line dependent signature. Moreover, our results show that the cell-senescence phenomenon does not correlate with the amount of 'senescence-associated secretory phenotype' (SASP) molecules released in media. Thus, additional mechanisms are probably involved in this process., Conclusions: These data open the possibility to evaluate cytokine profile as useful marker in modulating the personalized radiotherapy in breast cancer care.

Phosphatase and tensin homolog (PTEN) gene is considered a tumor suppressor gene. However, PTEN mutations rarely occur in hepatocellular carcinoma (HCC), whereas heterozygosity of PTEN, resulting in reduced PTEN expression, has been observed in 32-44% of HCC patients. In the present study, we investigated the effects of the small molecule PTEN inhibitor VO-OHpic in HCC cells. VO-OHpic inhibited cell viability, cell proliferation and colony formation, and induced senescence-associated β-galactosidase activity in Hep3B (low PTEN expression) and to a lesser extent in PLC/PRF/5 (high PTEN expression) cells, but not in PTEN-negative SNU475 cells. VO-OHpic synergistically inhibited cell viability when combined with PI3K/mTOR and RAF/MEK/ERK pathway inhibitors, but only in Hep3B cells, and significantly inhibited tumor growth in nude mice bearing xenografts of Hep3B cells. Therefore, we demonstrated for the first time that VO-OHpic inhibited cell growth and induced senescence in HCC cells with low PTEN expression, and that the combination of VO-OHpic with PI3K/mTOR and RAF/MEK/ERK inhibitors resulted in a more effective tumor cell kill. Our findings, hence, provide proof-of-principle evidence that pharmacological inhibition of PTEN may represent a promising approach for HCC therapy in a subclass of patients with a low PTEN expression.

Retinoblastoma is the most common intraocular malignancy of childhood. In developing countries, treatment is limited, long-term survival rates are low and current chemotherapy causes significant morbidity to pediatric patients and significantly limits dosing. Therefore there is an urgent need to identify new therapeutic strategies to improve the clinical outcome of patients with retinoblastoma. Here, we investigated the effects of two natural compounds okadaic acid (OKA) and parthenolide (PN) on human retinoblastoma Y79 cells. For the first time we showed that OKA/PN combination at subtoxic doses induces potent synergistic apoptotic effects accompanied by lowering in p-Akt levels, increasing in the stabilized forms of p53 and potent decrease in pS166-Mdm2. We also showed the key involvement of PTEN which, after OKA/PN treatment, potently increased before p53, thus suggesting that p53 activation was under PTEN action. Moreover, after PTEN-knockdown p-Akt/ pS166Mdm2 increased over basal levels and p53 significantly lowered, while OKA/PN treatment failed both to lower p-Akt and pS166-Mdm2 and to increase p53 below/over their basal levels respectively. OKA/PN treatment potently increased ROS levels whereas decreased those of GSH. Reducing cellular GSH by l-butathionine-[S,R]-sulfoximine treatment significantly anticipated the cytotoxic effect exerted by OKA/PN. Furthermore, the effects of OKA/PN treatment on both GSH content and cell viability were less pronounced in PTEN silenced cells than in control cells. The results provide strong suggestion for combining a treatment approach that targets the PTEN/Akt/Mdm2/p53 pathway.

Objective: The objective of this paper is to describe the effects of a rehabilitation programme in obese patients affected with chronic ischaemic heart disease; to identify the factors that influence weight loss and improvement in exercise capacity in everyday practice., Methods and Results: We studied 562 white patients (381 men) who followed a 23.3 +/- 3.9 days in-hospital programme. They attended daily sessions of aerobic activity (cycloergometer, walking, and strength exercise); a low-calorie diet was set at approximately 80% of resting energy expenditure. By the end of the programme BMI decreased from 38.0 +/- 4.9 to 36.7 +/- 4.8 kg/m2 (P < 0.001 ). Attained metabolic equivalents (METs) increased from 6.2 +/- 2.5 METs to 7.3 +/- 2.7 (P < 0.001). Age, sex, presence of diabetes and education level were significantly related to the outcomes. Patients who took beta-blockers and statins had less BMI improvement: -1.2 +/- 0.7 kg/m2 vs. -1.4 +/- 0.6 (P = 0.013) and -1.3 +/- 0.6 vs. -1.4 +/- 0.7 (P = 0.023), respectively. Patients that took diuretics and angiotensin receptor blockers (ARB) had less improvement in exercise capacity: 0.9 +/- 1.0 METS vs. 1.3 +/- 1.3 (P < 0.001) and 0.8 +/- 1.3 vs. 1.2 +/- 1.3 (P = 0.011 ), respectively. After a median interval of 358 days, 152 patients were seen at a follow-up visit: their BMI increased by 1.0 +/- 2.4 kg/m2 and only 21% of patients lost weight., Conclusions: Rehabilitation improves exercise capacity and induces significant weight loss in obese patients with stable IHD, but women, diabetic, elderly and poorly educated subjects obtained unsatisfactory results. Use of diuretics and ARB seem to worsen the results. At follow-up only a small percentage of patients further improves BMI.

Catheter ablation techniques for atrial fibrillation are evolving with targets for radiofrequency ablation of atrial fibrillation increasingly being selected based on anatomic considerations. Such anatomic ablation techniques require precise catheter localization and stable contact during ablation. Even experienced electrophysiologists occasionally encounter difficulties in maintaining stable catheter contact, especially in some regions of complex anatomy where catheter stability is crucial. Limitations of manually deflected conventional ablation catheters in performing complex catheter maneuvers may also contribute to these challenges. The CARTO RMT version 8 has been recently released to guide left atrial mapping and ablation in conjunction with the Stereotaxis system for remote control of the ablation catheter. We aim to describe how this system works and why it is needed in the field of catheter ablation.