Low-dose non-targeted radiation effects in human esophageal adenocarcinoma cell lines

<p><b>Purpose:</b> To investigate non-targeted radiation effects in esophageal adenocarcinoma cell lines (OE19 and OE33) using human keratinocyte and colorectal cancer cell reporters following γ-ray exposure.</p> <p><b>Materials and methods:</b> Both clonogenic assays and ratiometric calcium endpoints were used to check for the occurrence of bystander signals in reporter cells.</p> <p><b>Results:</b> We report data suggesting that γ-irradiation increases cell killing over the expected linear quadratic (LQ) model levels in the OE19 cell line exposed to doses below 1 Gy, i.e. which may be suggestive to be a low hyper-radiosensitive (HRS) response to direct irradiation. Both EAC cell lines (OE19 and OE33) have the ability to produce bystander signals when irradiated cell conditioned medium (ICCM) is placed onto human keratinocyte reporters, but do not seem to be capable of responding to bystander signals when placed on their autologous reporters. Further work with human keratinocyte reporter models showed statistically significant intracellular calcium fluxes following exposure of the reporters to ICCM harvested from both EAC cell lines exposed to 0.5 Gy.</p> <p><b>Conclusion:</b> These experiments suggest that the OE19 and OE33 cell lines produce bystander signals in human keratinocyte reporter cells. However, the radiosensitivity of the EAC cell lines used in this study cannot be enhanced by the bystander response since both cell lines could not respond to bystander signals.</p

Assessing patient characteristics and radiation-induced non-targeted effects in vivo for high dose-rate (HDR) brachytherapy

<div><p><i>Purpose</i>: To test whether blood, urine, and tissue based colony-forming assays are a useful clinical detection tool for assessing fractionated treatment responses and non-targeted radiation effects in bystander cells.</p><p><i>Materials and methods</i>: To assess patients’ responses to radiation treatments, blood serum, urine, and an esophagus explant-based in vivo colony-forming assay were used from oesophageal carcinoma patients. These patients underwent three fractions of high dose rate (HDR) intraluminal brachytherapy (ILBT).</p><p><i>Results</i>: Human keratinocyte reporters exposed to blood sera taken after the third fraction of brachytherapy had a significant increase in cloning efficiency compared to baseline samples (<i>p</i> < 0.001). Such results may suggest an induced radioresistance response in bystander cells. The data also revealed a clear inverse dose-rate effect during late treatment fractions for the blood sera data only. Patient characteristics such as gender had no statistically significant effect (<i>p</i> > 0.05). Large variability was observed among the patients’ tissue samples, these colony-forming assays showed no significant changes throughout fractionated brachytherapy (<i>p</i> > 0.05).</p><p><i>Conclusion</i>: Large inter-patient variability was found in the urine and tissue based assays, so these techniques were discontinued. However, the simple blood-based assay had much less variability. This technique may have future applications as a biological dosimeter to predict treatment outcome and assess non-targeted radiation effects.</p></div

Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review

<div><p>Background</p><p>Soy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and red clover for efficacy in improving menopausal symptoms in women with breast cancer, and for potential impact on risk of breast cancer incidence or recurrence.</p> <p>Methods</p><p>We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to March 2013 for human interventional or observational data pertaining to the safety and efficacy of soy and red clover isoflavones in patients with or at risk of breast cancer. </p> <p>Results</p><p>Of 4179 records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials, and 80 observational studies. Five RCTs reported on the efficacy of soy for hot flashes, showing no significant reductions in hot flashes compared to placebo. There is lack of evidence showing harm from use of soy with respect to risk of breast cancer or recurrence, based on long term observational data. Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence. Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues. Prospective data of soy use in women taking tamoxifen does not indicate increased risk of recurrence. Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects. </p> <p>Conclusion</p><p>Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors. While there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (≥100mg) isoflavones can be recommended for breast cancer patients. </p> </div

Literature Flowchart.

<p>Literature Flowchart.</p

Risk of Breast Cancer Associated with Intake of Soy Food or Soy Protein.

<p>Risk of Breast Cancer Associated with Intake of Soy Food or Soy Protein.</p

Risk of Breast Cancer Associated with Intake of Soy Isoflavones.

<p>Risk of Breast Cancer Associated with Intake of Soy Isoflavones.</p

Risk of Mortality Associated with Intake of Soy Protein or Isoflavones.

<p>Risk of Mortality Associated with Intake of Soy Protein or Isoflavones.</p