Vellingfriedman2109

In phase 2 prospective trials using ultra APBI, encouraging results were observed regarding oncological outcome and toxicity profile. In phase 3 trials, adjuvant ET without RT significantly increased the rate of local relapse with no impact on overall survival while RT alone proved effective. Elderly patients aged 60 or more with low-risk, luminal A breast cancer were chosen as the target population in a phase 3 randomized trial comparing APBI+5-year ET vs. uAPBI (16Gy 1f) alone.

To investigate de-escalation adjuvant treatment for elderly breast cancer patients, we have defined a road map for testing more convenient strategies. This EPOPE phase 3 randomized trial is supported by the GEC-ESTRO breast cancer working group.

To investigate de-escalation adjuvant treatment for elderly breast cancer patients, we have defined a road map for testing more convenient strategies. This EPOPE phase 3 randomized trial is supported by the GEC-ESTRO breast cancer working group.

Neutrophil-lymphocyte ratio (NLR) has been associated with overall survival (OS) in non-small cell lung cancer (NSCLC). We aimed to assess the utility of NLR as a predictor of lung cancer-specific survival (LCS) and identify an optimal, pretreatment cutoff point in patients with localized NSCLC treated with stereotactic body radiotherapy (SBRT) within the Veterans Affairs' (VA) national database.

In the VA database, we identified patients with biopsy-proven, clinical stage I NSCLC treated with SBRT between 2006 and 2015. Cutoff points for NLR were calculated using Contal/O'Quigley's and Cox Wald methods. Primary outcomes of OS, LCS, and non-lung cancer survival (NCS) were evaluated in Cox and Fine-Gray models.

In 389 patients, optimal NLR cutoff was identified as 4.0. In multivariable models, NLR > 4.0 was associated with decreased OS (HR 1.44, p = 0.01) and NCS (HR 1.68, p = 0.01) but not with LCS (HR 1.32, p = 0.09). GSK1070916 In a subset analysis of 229 patients with pulmonary function tests, NLR > 4.0 remained associated with worse OS (HR 1.51, p = 0.02) and NCS (HR 2.18, p = 0.01) while the association with LCS decreased further (HR 1.22, p = 0.39).

NLR was associated with worse OS in patients with localized NSCLC treated with SBRT; however, NLR was only associated with NCS and not with LCS. Pretreatment NLR, with a cutoff of 4.0, offers potential as a marker of competing mortality risk which can aid in risk stratification in this typically frail and comorbid population. Further studies are needed to validate pretreatment NLR as a clinical tool in this setting.

NLR was associated with worse OS in patients with localized NSCLC treated with SBRT; however, NLR was only associated with NCS and not with LCS. Pretreatment NLR, with a cutoff of 4.0, offers potential as a marker of competing mortality risk which can aid in risk stratification in this typically frail and comorbid population. Further studies are needed to validate pretreatment NLR as a clinical tool in this setting.Diacylglycerol kinase (DGK) η translocates from the cytoplasm to punctate vehicles via osmotic shock. Apoptosis signal-regulating kinase (ASK) 3 (MAP kinase kinase kinase (MAPKKK) 15) is also reported to respond to osmotic shock. Therefore, in the present study, we examined the subcellular localization of DGKη and ASK3 expressed in COS-7 cells under osmotic stress. We found that DGKη was almost completely colocalized with ASK3 in punctate structures in response to osmotic shock. In contrast, DGKδ, which is closely related to DGKη structurally, was not colocalized with ASK3, and DGKη failed to colocalize with another MAPKKK, C-Raf, even under osmotic stress. The structures in which DGKη and ASK3 localized were not stained with stress granule makers. Notably, DGKη strongly interacted with ASK3 in an osmotic shock-dependent manner. These results indicate that DGKη and ASK3 undergo osmotic shock-dependent colocalization and associate with each other in specialized structures.Serpinb1a, a serine protease inhibitor family protein, has been implicated in immunoregulation and several metabolic disorders, such as diabetes and obesity; however, its roles in bone remain unknown. Therefore, we herein investigated the physiological functions of Serpinb1a in osteoclastic and osteoblastic differentiation using mouse cell lines. Serpinb1a overexpression markedly reduced the number of tartrate-resistant acid phosphatase (TRAP)- and calcitonin receptor-positive multinucleated cells increased by receptor activator nuclear factor κB ligand (RANKL) in mouse preosteoclastic RAW 264.7 cells. Moreover, it significantly decreased the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), TRAP and cathepsin K in these cells. Regarding osteoblasts, Serpinb1a overexpression significantly reduced the mRNA levels of alkaline phosphatase (ALP) and osteocalcin as well as ALP activity induced by bone morphogenetic protein-2 (BMP-2) in mouse mesenchymal ST2 cells, although it did not alter osteoblast differentiation in mouse osteoblastic MC3T3-E1 cells. Concerning the pathophysiological relevance of Serpinb1a, Serpinb1a mRNA levels were decreased in the soleus and gastrocnemius muscles of mice 4 weeks after bilateral sciatic nerve resection. In conclusion, we herein revealed for the first time that Serpinb1a inhibited osteoclast formation induced by RANKL in RAW 264.7 cells and suppressed BMP-2-induced ALP activity in ST2 cells.miR-21 expression stimulates osteoclast cells in the context of osteoclastogenesis. A previous report showed that NFκB-miR-21 pathway could serve as an innovative alternative to devise therapeutics for healing diabetic ulcers. Furthermore, our study demonstrated that a highly water-soluble curcuminoids-rich extract (CRE-Ter) inhibits osteoclastogenesis through NFκB pathway. The interplay between miR-21 and CRE-Ter in osteoclastogenesis has not yet been investigated. In this study, we examined the relation of CRE-Ter and miR-21 gene expression in receptor of the nuclear factor κB (NFκB) ligand (RANKL) - induced murine monocyte/macrophage RAW 264.7 cells, osteoclast cells, in osteoclastogenesis. Effect of CRE-Ter on generation of intracellular reactive oxygen species (ROS) was estimated by dichlorofluorescein diacetate (DCFH-DA). The results reveal that CRE-Ter reduced expression levels of miR-21 gene in osteoclasts. The inhibitory effects of CRE-Ter on in vitro osteoclastogenesis were evaluated by reduction in tartrate-resistant acid phosphatase (TRAP) content, and by reduction in expression levels of an osteoclast-specific gene, cathepsin K.