Angiotensin II: A Potential Link Between Inflammation and Hypertension in SLE

The disease Systemic Lupus Erythematosus is a chronic inflammatory, autoimmune disorder that primarily affects women during their reproductive years. Women with SLE are at a greater risk of developing hypertension, which increases their risk of mortality from a cardiac related event. A proposed mechanism for SLE hypertension suggests that inflammation in the kidneys causes renal dysfunction, presumably resulting in less water excretion, increased plasma volume, and thus high blood pressure. This experiment tests the hypothesis that the T-cells from a mouse model of SLE hyper secrete the inflammatory cytokines IL-17, IL-10, and IFN- y, and are more sensitive to the cytokine-stimulating hormone angiotensin II (ANGII). To test this hypothesis, T lymphocytes were isolated from control and SLE mice, and cytokine secretion into the culture media was determined in the presence or absence of ANG II. Thymocytes from SLE mice secreted greater levels of all three inflammatory cytokines, although excess IL-17 secretion occurred only after the onset of renal damage. Angiotensin II increased production of IFN- y, but there was no major difference between the SLE and Control groups. These results indicate that hyper secretion of IL-17, IL-10, and IFN- y by SLE T-cells may be contributing to renal inflammation, kidney damage, and therefore SLE hypertension. T-cell hypersensitivity to ANG II could not account for the hypertension, suggesting that these cells are excessively sensitive to another factor (that is present in the culture media) or have an innately higher secretion rate

Hypofractionated Stereotactic Radiotherapy for Non-breast or Prostate Cancer Oligometastases: A Tail of Survival Beyond 10 Years

Purpose and Objective(s): We sought to analyze the long-term follow-up of patients treated with hypofractionated, stereotactic radiotherapy (HSRT) for oligometastases from malignancies other than breast or prostate cancer.Materials and Methods: From 2001 to 2006, 82 cancer patients with 1–5 radiographically apparent metastatic lesions (in 1–3 organs) from primary sites other than breast or prostate cancer, were enrolled on a prospective study of HSRT. Freedom from widespread metastasis (FFWM) was defined from date of enrollment until death, an event (i.e., widespread distant metastasis not amenable to local therapy), or last radiographic study. Local recurrence was scored as an event if pathologically confirmed or if a treated lesion increased by ≥20% using RECIST criteria. Prognostic variables were assessed using Cox regression analysis.Results: The mean age was 61 ± 11 years, with a male to female ratio of 46:36. The most common metastatic sites were liver (50%), lung (48%), thoracic lymph nodes (18%), and bone (5%). Sixty-one patients (74%) had 1 involved organ and 18 (22%) had 1 lesion treated. The preferred dose-fractionation scheduled was 50 Gy in 10 fractions (52 patients). The median follow-up was 1.7 years. Eleven patients lived >5 years, and 6 lived >10 years. The 5-year OS, PFS, FFWM, and LC rates were 13.4, 7.3, 18.3, and 63.4%, and the 10-years OS, PFS, FFWM, and patient LC rates were 7.3, 6.1, 13.4, and 62.2%, respectively. A greater net gross tumor volume (GTV) was significantly adverse for OS (p < 0.01) and LC (p < 0.01). For FFWM, net GTV was not a significant factor (p = 0.14). Four patients remain alive at >13 years from enrollment and treatment, without evidence of active disease.Conclusion: A small subset of select non-breast, non-prostate cancer patients with limited metastasis treated with HSRT are long-term survivors. Net GTV is a significant factor for tumor control and survival. Further research is needed to help better select patients most likely to benefit from local therapy for metastatic disease

Angiotensin II as a Potential Regulator of Inflammatory Cytokines in Inducing Hypertension in Systemic Lupus Erythematosus

The disease Systemic Lupus Erythematosus is a chronic inflammatory, autoimmune disorder that primarily affects women during their reproductive years. Women with SLE are at a greater risk of developing hypertension, which increases their risk of mortality from a cardiac related event. A proposed mechanism for SLE hypertension suggests that inflammation in the kidneys causes renal dysfunction, presumably resulting in less water excretion, increased plasma volume, and thus high blood pressure. This experiment tests the hypothesis that the T-cells from a mouse model of SLE hyper secrete the inflammatory cytokines IL-17, IL-10, and DFN- y, and are more sensitive to the cytokine-stimulating hormone angiotensin II (ANG II). To test this hypothesis, T lymphoc}^es were isolated from control and SLE mice, and cj^okine secretion into the culture media was determined in the presence or absence of ANG II. Thymocytes from SLE mice secreted greater levels of all three inflammatory cytokines, although excess IL-17 secretion occurred only after the onset of renal damage. Angiotensin II increased production of IFN- y, but there was no major difference between the SLE and Control groups. These results indicate that hyper secretion of IL-17, IL-10, and IFN- y by SLE T-cells may be contributing to renal inflammation, kidney damage, and therefore SLE hypertension. T-cell hypersensitivity to ANG II could not account for the hypertension, suggesting that these cells are excessively sensitive to another factor (that is present in the culture media) or have an innately higher secretion rate