Baseline Hematologic Parameters Influencing Outcomes in Patients with Locally Advanced Rectal Cancer

Baseline Hematologic Parameters Influencing Outcomes in Patients with Locally Advanced Rectal Cancer Aim of the study: The link between the blood count and a systemic inflammatory response (SIR) is indisputable and well described. Pretreatment hematological parameters may predict the overall clinical outcomes in many types of cancer. Thus, this study aims to systematically evaluate the relationship between baseline blood count levels and treatment response in rectal cancer patients treated with neoadjuvant chemoradiotherapy. Patients and methods: From 2009-2015, 173 patients with locally advanced rectal cancer were retrospectively enrolled in the study and analyzed. The baseline blood count was recorded in all patients 1 week before chemoradiation. Tumor response was evaluated through pathologic findings. Blood count levels which included RBC (red blood cells), Hb (hemoglobin), PLT (platelet count), neutrophil count, WBC (white blood cells), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) were analyzed in relation to tumor downstaging, pCR (pathologic complete response), OS (overall survival), and DFS (disease-free survival). Results: Hb levels were associated with a response in logistic regression analysis: pCR (p = 0.05; OR 1.04, 95% CI 1.00-1.07); T downstaging (p =..

Hematopoietic Recovery after Transplantation CD117+B220- (lacZ+) Bone Marrow Cells in Lethally Irradiated Mice

Experiments presented here were aimed at the description of hematopoiesis repair and in vivo homing of transplanted separated CD117+B220– bone marrow cells after whole-body lethal irradiation at LD 9Gy. ROSA 26 mice were used as donors of marrow cells for transplantation [B6;129S/Gt (ROSA)26Sor] and were tagged with lacZ gene, and F2 hybrid mice [B6129SF2/J] were used as recipients of bone marrow transplanted cells. Hematopoiesis repair was provided by transplantation, both suspension of whole bone marrow cells (5x106) and isolated CD117+B220– cells (5x104). Mice survived up to thirty days after irradiation. We demonstrated that transplantation of suspension of whole bone marrow cells led to faster recovery of CFU-GM (Granulocyte-macrophage colony forming units) in bone marrow and in the spleen too. It is not clear what the share of residential and transplanted cells is in the repair process. Our results demonstrate that sufficient hematopoietic repair occurs after transplantation of CD117+B220– (lacZ+) in lethally irradiated mice, and the difference in CFU-GM numbers in the bone marrow and spleen found on day 8 posttransplant has no influence on the survival of lethally irradiated mice (30 days follow-up)

NADPH- and NADH-dependent metabolism of and DNA adduct formation by benzo[a]pyrene catalyzed with rat hepatic microsomes and cytochrome P450 1A1

ABSTRACT: Benzo[a]pyrene (BaP) is a human carcinogen that covalently binds to DNA after metabolic activation by cytochrome P450 (CYP) enzymes. Here we investigated the efficiencies of rat hepatic microsomes and rat recombinant CYP1A1 expressed with its reductase, NADPH:CYP oxidoreductase (POR), NADH:cytochrome b(5) reductase, epoxide hydrolase and/or cytochrome b(5) in Supersomes™ to metabolize this carcinogen. We also studied the effectiveness of coenzymes of two of the microsomal reductases, NADPH as a coenzyme of POR, and NADH as a coenzyme of NADH:cytochrome b(5) reductase, to mediate BaP metabolism in these systems. Up to eight BaP metabolites and two DNA adducts were generated by the systems, both in the presence of NADPH and NADH. Among BaP metabolites, BaP-9,10-dihydrodiol, BaP-4,5-dihydrodiol, BaP-7,8-dihydrodiol, BaP-1,6-dione, BaP-3,6-dione, BaP-9-ol, BaP-3-ol, and a metabolite of unknown structure were formed by hepatic microsomes and rat CYP1A1. One of two DNA adducts formed by examined enzymatic systems (rat hepatic microsomes and rat CYP1A1) was characterized to be 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N(2)-BPDE), while another adduct has similar chromatographic properties on polyethylaneimine–cellulose thin layer chromatography to a guanine adduct derived from reaction with 9-hydroxy-BaP-4,5-oxide. In the presence of either of the reductase cofactors tested, NADPH or NADH, cytochrome b(5) stimulated CYP1A1-mediated formation of both BaP-DNA adducts. The results demonstrate that NADH can act as a sole electron donor for both the first and the second reduction of CYP1A1 during its reaction cycle catalyzing oxidation of BaP, and suggest that the NADH:cytochrome b(5) reductase as the NADH-dependent reductase might substitute POR in this enzymatic system. GRAPHICAL ABSTRACT: [Image: see text

Technological advances in radiotherapy for esophageal cancer

Radiotherapy with concurrent chemotherapy and surgery represent the main treatment modalities in esophageal cancer. The goal of modern radiotherapy approaches, based on recent technological advances, is to minimize post-treatment complications by improving the gross tumor volume definition (positron emission tomography-based planning), reducing interfraction motion (image-guided radiotherapy) and intrafraction motion (respiratory-gated radiotherapy), and by better dose delivery to the precisely defined planning target volume (intensity-modulated radiotherapy and proton therapy). Reduction of radiotherapy-related toxicity is fundamental to the improvement of clinical results in esophageal cancer, although the dose escalation concept is controversial

Cardiotoxicity of radiation therapy in esophageal cancer

With a development of radiotherapeutic techniques, availability of radiotherapy data on cardiotoxicity, and slowly improving esophageal cancer outcomes, an increasing emphasis is placed on the heart protection in radiation treated esophageal cancer patients. Radiation induced heart complications encompass mainly pericardial disease, cardiomyopathy, coronary artery atherosclerosis, valvular heart disease, and arrhythmias. The most frequent toxicity is pericardial effusion which is usually asymptomatic in the majority of patients. The use of modern radiotherapy techniques is expected to reduce the risk of cardiotoxicity, although this expectation has to be confirmed by clinical data

Vliv zvýšené teploty základní desky na mikrostrukturu, mechanické vlastnosti a vyhodnocení tepelného napětí pomocí numerické simulace austenitické nerezové oceli 316L vyrobené technologií přímé depozice

V této studii byl zkoumán vliv depozice materiálu při zvýšené teplotě základní desky na mikrostrukturu a mechanické vlastnosti a výsledky byly porovnány s unikátní tepelnou historií získanou pomocí numerické simulace. Dosažené numerické výsledky dobře korelovaly s experimentálními výsledky a to jak u mikrostruktury a tak u mechanických vlastností. Numerické výsledky odhalily významný pokles teplotního gradientu a 40% pokles teplotního napětí, které vzniká v důsledku depozice materiálu na základovou desku se zvýšenou teplotou. Snížené tepelné napětí a teplotní gradient měly za následek zhrubnutí zrna, což následně vedlo ke snížení tvrdosti a pevnosti v tahu, a to zejména ve spodní oblasti v blízkosti základní desky. Nebyl zjištěn žádný významný vliv na tažnost. Bylo zjištěno, že zvýšení teploty základní desky způsobuje nižší výslednou heterogenitu v tvrdosti materiálu a také v tahových vlastnostech a to ve směru stavby materiálu. Předložená práce demonstruje komplexní pochopení vlivu předehřívání základní desky na tepelné namáhání, mikrostrukturu a mechanické vlastnosti a jejich vzájemné korelace.In the present study, the effect of material deposition at the elevated temperature baseplate on the microstructure and mechanical properties was investigated and correlated to the unique thermal history by using numerical simulation. Numerical results agreed well with the experimental results of microstructure and mechanical properties. Numerical results revealed a significant decrease in temperature gradient and a 40% decrease in thermal stress due to material deposition on the elevated temperature baseplate. The reduced thermal stress and temperature gradient resulted in coarser grain features, which in turn led to a decrease in hardness and tensile strength, especially for the bottom region near the baseplate. Meanwhile, no significant effect could be found for ductility. In addition, an elevated temperature baseplate promoted less heterogeneity in hardness and tensile properties along the building direction. The current work demonstrates a collective and direct understanding of the baseplate preheating effect on thermal stress, microstructure and mechanical properties and their correlations, which is believed beneficial for the better utilization of baseplate preheating positive effects

Elevated Temperature Baseplate Effect on Microstructure, Mechanical Properties, and Thermal Stress Evaluation by Numerical Simulation for Austenite Stainless Steel 316L Fabricated by Directed Energy Deposition

In the present study, the effect of material deposition at the elevated temperature baseplate on the microstructure and mechanical properties was investigated and correlated to the unique thermal history by using numerical simulation. Numerical results agreed well with the experimental results of microstructure and mechanical properties. Numerical results revealed a significant decrease in temperature gradient and a 40% decrease in thermal stress due to material deposition on the elevated temperature baseplate. The reduced thermal stress and temperature gradient resulted in coarser grain features, which in turn led to a decrease in hardness and tensile strength, especially for the bottom region near the baseplate. Meanwhile, no significant effect could be found for ductility. In addition, an elevated temperature baseplate promoted less heterogeneity in hardness and tensile properties along the building direction. The current work demonstrates a collective and direct understanding of the baseplate preheating effect on thermal stress, microstructure and mechanical properties and their correlations, which is believed beneficial for the better utilization of baseplate preheating positive effects

Validation of dose distribution computation on sCT images generated from MRI scans by Philips MRCAT

AimTo evaluate calculation of treatment plans based on synthetic-CT (sCT) images generated from MRI.BackgroundBecause of better soft tissue contrast, MR images are used in addition to CT images for radiotherapy planning. However, registration of CT and MR images or repositioning between scanning sessions introduce systematic errors, hence suggestions for MRI-only therapy. The lack of information on electron density necessary for dose calculation leads to sCT (synthetic CT) generation. This work presents a comparison of dose distribution calculated on standard CT and sCT.Materials and methods10 prostate patients were included in this study. CT and MR images were collected for each patient and then water equivalent (WE) and MRCAT images were generated. The radiation plans were optimized on CT and then recalculated on MRCAT and WE data. 2D gamma analysis was also performed.ResultsThe mean differences in the majority of investigated DVH points were in order of 1% up to 10%, including both MRCAT and WE dose distributions. Mean gamma pass for acceptance criteria 1%/1mm were greater than 82.5%. Prescribed doses for target volumes and acceptable doses for organs at risk were met in almost all cases.ConclusionsThe dose calculation accuracy on MRCAT was not significantly compromised in the majority of clinical relevant DVH points. The introduction of MRCAT into practise would eliminate systematic errors, increase patients’ comfort and reduce treatment expenses. Institutions interested in MRCAT commissioning must, however, consider changes to established workflow