Hypofractionated radiation therapy for prostate cancer: The McGill University Health Center experience.

PURPOSE: In 2002, at the McGill University Health Centre, we began a program of hypofractionated radiotherapy for patients with low risk prostate cancer as an alternative to conventionally fractionated radiotherapy. MATERIAL AND METHODS: Our initial hypofractionation regimen was 66 Gy given in 22 fractions, prescribed to the isocenter, delivered with 3D-conformal radiotherapy plan. The clinical target volume was the prostate gland and the planning target volume consisted of the clinical target volume plus a 7-mm margin in all directions. Hormonal therapy was not given to any patient. RESULTS: The long-term results for this group of patients confirmed the feasibility, good tolerance and excellent disease control of the regimen with the extra-benefit of being convenient to both patients and the health system by shortening treatment duration. The outcomes of this approach stimulated us to use hypofractionation in patients with intermediate-risk. Analysis of 100 intermediate-risk patients receiving our hypofractionated radiotherapy regimen (no hormones) shows, at median follow-up of 75 months, 8-year biochemical recurrence free and cancer specific survival rates of 90% and 95%, respectively, with acceptable toxicity. DISCUSSION: Our technique changed from 3D to intensity modulated radiotherapy with the dose adjusted to 60 Gy in 20 fractions. Lastly, we have expanded the program to high-risk patients where IMRT treatments are given to the pelvic nodes (44 Gy in 20 fractions) with a simultaneous integrated boost delivery to the prostate (60 Gy in the same 20 fractions). Our long-term results have shown that moderate hypofractionated radiotherapy for prostate cancer is safe and provides good tumor control comparable to high-dose conventionally fractionated radiotherapy. This hypofractionated regimen has been routinely used in our institution.

Physical training induces expression of TGF-beta in kidney of pregnant hypertensive rats.

AIM: This study aimed to determine the morphological renal impairment in pregnant rats spontaneously hypertensive (SHR) submitted to swimming when compared with those who did not perform the activity, and to analyze the relationship of expression of cytokines in inflammatory fibrotic and protrained and sedentary animals. METHODS: SHRs and their respective control normotensive rats (WKY) were submitted or not to a swimming protocol during 9 weeks, resulting in four pregnant experimental groups: sedentary hypertensive (HS), trained hypertensive (HT), sedentary normotensive (NS), and trained normotensive (NT). RESULTS: Pregnant untrained hypertensive rats presented higher resting mean blood pressure (MAP) compared with both sedentary and trained normotensive groups (P<0.05). We can observe too, that the exercise training did not change the heart rate (HR) in both hypertensive and normotensive groups (P=0.127). The HT rats showed lower area of mesangial matrix (MM) compared to NT group (P=0.018). The perceptual of fibrosis (%F) in hypertensive rats was significantly higher compared with the % F in normotensive rats (P<0.001). The rats in the HT group showed higher expression of TGF-b (P<0.001) and of IL-10 (P<0.001) when compared with the other groups. CONCLUSION: The main conclusion is that in SHR rats it is shown a greater expression of TGF-beta, resulting in increased fibrosis in renal parenchyma due to the increased number of inflammatory cells that secrete this cytokine, and thus the practice of swimming can attenuate inflammatory processes, and mitigate the blood pressure of these animals.

Low dose of propranolol down-modulates bone resorption by inhibiting inflammation and osteoclast differentiation.

BACKGROUND AND PURPOSE: Bones are widely innervated, suggesting an important role for the sympathetic regulation of bone metabolism, although there are controversial studies. We investigated the effects of propranolol in a model of experimental periodontal disease. EXPERIMENTAL APPROACH: Rats were assigned as follows: animals without ligature; ligated animals receiving vehicle and ligated animals receiving 0.1, 5 or 20 mg·kg(-1) propranolol. After 30 days, haemodynamic parameters were measured by cardiac catheterization. Gingival tissues were removed and assessed for IL-1ß, TNF-α and cross-linked carboxyterminal telopeptides of type I collagen (CTX) by elisa, or intercellular adhesion molecule 1 (ICAM-1), receptor activator of NF-κ B ligand (RANKL) and osteoprotegerin (OPG) by Western blot analysis. Sections from the mandibles were evaluated for bone resorption. Also, we analysed the ability of propranolol to inhibit osteoclastogenesis in vitro. RESULTS: Propranolol at 0.1 and 5 mg·kg(-1) reduced the bone resorption as well as ICAM-1 and RANKL expression. However, only 0.1 mg·kg(-1) reduced IL-1ß, TNF-α and CTX levels as well as increased the expression of OPG, but did not alter any of the haemodynamic parameters. Propranolol also suppressed in vitro osteoclast differentiation and resorptive activity by inhibiting the nuclear factor of activated T cells (NFATc)1 pathway and the expression of tartrate-resistant acid phosphatase (TRAP), cathepsin K and MMP-9. CONCLUSIONS AND IMPLICATIONS: Low doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters.