Multi-institutional feasibility study of intensity-modulated radiotherapy with chemotherapy for locally advanced non-small cell lung cancer

International Journal of Clinical Oncology - This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced...     

Optimal cut-off value of preprocedural geriatric nutritional risk index for predicting the clinical outcomes of patients undergoing endovascular revascularization for peripheral artery disease

BackgroundMalnutrition measured by the geriatric nutritional risk index (GNRI) was reported to be associated with poor prognosis for patients with peripheral artery disease (PAD). However, the optimal cut-off value of preprocedural GNRI for critical limb ischemia (CLI) and intermittent claudication (IC) is unknown. We aimed to determine its optimal cut-off value for CLI or IC patients requiring endovascular revascularization.MethodsWe explored data of 2246 patients (CLI: n = 1061, IC: n = 1185) registered in the Tokyo-taMA peripheral vascular intervention research COmraDE (TOMA-CODE) registry, which prospectively enrolled consecutive PAD patients who underwent endovascular revascularization in 34 hospitals in Japan from August 2014 to August 2016. The optimal cut-off values of GNRI were assessed by the survival classification and regression tree (CART) analyses, and the survival curve analyses for major adverse cardiovascular and limb events (MACLEs) were performed for these cut-off values.ResultsIn addition to the first cut-off value of 96.2 in CLI and 85.6 in IC, the survival CART provided an additional cut-off value of 78.2 in CLI and 106.0 in IC for further risk stratification. The survival curve was significantly stratified by the GNRI-based malnutrition status in both CLI [high risk: 47.7% (51/107), moderate: 30.1% (118/392), and low: 10.2% (53/520), log–rank p < 0.001] and IC [high risk: 14.3% (7/49), moderate: 4.5% (29/646), and low: 0.5% (2/407), log–rank p < 0.001]. The multivariate Cox-proportional hazard analysis showed that a higher GNRI was significantly associated with a better outcome in both CLI [hazard ratio (HR) per 1-point increase: 0.97, 95% CI: 0.96–0.98, p < 0.001] and IC (HR: 0.94, 95% CI: 0.91–0.97, p < 0.001).ConclusionsPreprocedural nutritional status significantly stratified future events in patients with PAD. Given that the optimal cut-off value of GNRI in CLI was almost 10-points lower than that of IC, using a disease-specific cut-off value is important for risk stratification.     

3‐O‐Laurylglyceryl ascorbate improves the development of sensitive skin through the reduction of oxidative stress

Skin sensitivity is a serious problem for many people, and it can be induced by various factors such as UV irradiation, physical and mental stresses, air pollution, dry air and so on. Skin dryness triggered by UV and dry air is one of the most important causes inducing the development of sensitive skin, and it has been reported that oxidative stress contributes to skin dryness. In this study, we investigated whether treatment with 3‐O‐laurylglyceryl ascorbate (VC‐3LG), which is an amphipathic ascorbic acid derivative, can suppress the development of sensitive skin. The results demonstrate that VC‐3LG restores the expression levels of interleukin‐1α, nerve growth factor and matrix metalloprotease‐9 in the dry skin models of reconstructed human epidermal equivalents (RHEEs) and in H₂O₂‐treated keratinocytes. In addition, VC‐3LG suppresses the dendrite elongation of nerve cells induced in RHEEs by dry skin conditions and by H₂O₂ treatment of keratinocytes. Therefore, we consider that treatment of the skin with VC‐3LG is an effective approach to improve the development of sensitive skin.     

Supplementation of l‐arginine boosts the therapeutic efficacy of anticancer chemoimmunotherapy

Myeloid‐derived suppressor cells (MDSCs) play a crucial role in immunosuppression in tumor‐bearing hosts. MDSCs express arginase‐I and indoleamine 2,3‐dioxygenase; they suppress T‐cell function by reducing the levels of l ‐arginine and l ‐tryptophan, respectively. We examined the anticancer effects of supplementation of these amino acids in CT26 colon carcinoma‐bearing mice. Oral supplementation of l ‐arginine or l ‐tryptophan (30 mg/mouse) did not affect tumor growth, whereas oral supplementation of d ‐arginine was lethal. Supplementation of l ‐arginine showed a tendency to augment the efficacy of cyclophosphamide (CP). CP reduced the proportions of granulocytic MDSCs and increased the proportions of monocytic MDSCs in the spleen and tumor tissues of CT26‐bearing mice. l ‐Arginine supplementation alone did not affect the MDSC subsets. CP treatment tended to reduce the plasma levels of l ‐arginine in CT26‐bearing mice and significantly increased the number of tumor‐infiltrating CD8⁺ T cells. In addition, l ‐arginine supplementation significantly increased the proportions of tumor peptide‐specific CD8⁺ T cells in draining lymph nodes. Importantly, additional supplementation of l ‐arginine significantly increased the number of cured mice that were treated with CP and anti‐PD‐1 antibody. Totally, l ‐arginine supplementation shows promise for boosting the therapeutic efficacy of chemoimmunotherapy.     

Combined administration of lauric acid and glucose improved cancer‐derived cardiac atrophy in a mouse cachexia model

Cancer‐derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by Seahorse flux analysis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model in which cardiomyoblasts were treated with mouse cachexia ascites. Ascites‐treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that of the control, and ATP was restored to the level of the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS‐soluble MYL1, were observed. When LAA in CE‐2 diet was orally administered alone, no significant rescue was observed in the cancer‐derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Therefore, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer‐derived myocardial damage.