Repurposing Radiation Therapy for Immuno-oncology.

Radiation therapy is traditionally used for the local control of tumour growth, but recent studies suggest that radiation therapy can have immunomodulatory properties that can be applied in combination therapy with immunotherapeutic agents. The paradigm of using radiation therapy for immunomodulation in cancer treatment is a rapidly progressing field, with multiple ongoing clinical trials exploring its use in combination with immune checkpoint blockades to induce an abscopal effect. Permutations of radiation therapy regimens, including variations in radiation dosing, radiation planning parameters and radiation modality, are being tested with varying degrees of success. The relative biological effectiveness was a concept introduced in the early days of radiation biology that allows the comparison of local tumour control across various radiation modalities and energies. Similarly, there remains a need for a new concept of comparing the immunological effectiveness of various radiation modalities. In this review, we will provide an overview of immunobiological models for preclinical and clinical monitoring of radiation therapy regimens and introduce the concept of relative immunological effectiveness to compare and screen for immune-activating functions of these regimens.

Assessment of occupational exposure to stainless steel welding fumes - A human biomonitoring study.

The aim of the study was to determine the concentration of hexavalent and trivalent chromium, nickel, manganese, and iron in welding fumes (WFs) and to evaluate the significant association between the concentration of metals in the biological material of welders. The studies were conducted in welders (n = 67) and controls (n = 52). Stainless steel WFs were continuously collected in the workers' breathing zone during a shift. The serum and urine concentrations of Cr and Ni were determined by ICP-MS. The content of Mn in the whole blood was determined using ET-AAS. The content of Cr in the erythrocytes was determined using ICP-MS. The Cr concentration in the welders' urine positively correlated with a work environment concentration of Cr (R = 0.59, p < 0.0001), Cr(VI) (R = 0.58, p < 0.0001), and Cr(III) (R = 0.64, p < 0.0001) in the inhalable fraction. The Ni concentration in the welders' urine positively correlated with the Ni concentration in the inhalable and respirable fraction (R = 0.34, p < 0.005 and R = 0.44, p < 0.002). The correlation between the Mn concentration in the work environment air and the Mn concentration in the welders' whole blood (R = 0.46, p < 0.0001) was observed.

Low-grade Albuminuria and Risk Factors of Atherosclerosis in Children with in Type 1 Diabetes.

AIMS: Microalbuminuria reflects generalized vascular dysfunction and the risk of cardiovascular disease. The study aim was to examine the relationship between low-grade albuminuria and the selected risk factors for atherosclerosis, markers of endothelial dysfunction and inflammation in diabetic children and adolescents. METHODS: In 154 children with diabetes duration of at least 5 years we assessed: HbA1c, lipid profile, apolipoproteins, lipoprotein (a), asymmetric dimethylarginine (ADMA), von Willebrand factor, fibrinogen, uric acid, cystatin C, creatinine, 24-h blood pressure monitoring (ABPM) and albuminuria. RESULTS: Median albuminuria in the whole group was 2.02 µg/min. No correlations were found between albuminuria and lipids, apolipoproteins, fibrinogen, von Willebrand factor, cystatin C and GFR, HbA1c, and uric acid. A significant negative correlation was found between AER and ADMA (R=-0.24, p=0.0023) and positive correlation with all ABPM variables: mean SBP (R=0.23, p=0.0049), mean DBP (R=0.24, p=0.0023), daytime MAP (R=0.31, p=0.0001), nocturnal MAP (r=0.31, p<0.0001) and with percentage of blood pressure dipping (R=-0.17, p=0.0323). A trend was noted for a positive correlation between albuminuria and Lp(a) (R=0.15, p=0.059) and BMI Z-score (R=0.14, p=0.089).Children with albuminuria below 5 µg/min. had significantly lower level of fibrinogen (2.96±0.57 g/l vs. 3.29±0.66 g/l, p=0.0167) and mean 24-h systolic and diastolic blood pressure, mean day and nocturnal blood pressure in comparison to the subjects with higher albuminuria. CONCLUSIONS: diabetic children with acceptable diabetes control but high-normal albuminuria together with higher level of Lp(a), fibrinogen and blood pressure may require more attention in terms of prevention of early macroangiopathy development.

Genetic variability of GCKR alters lipid profiles in children with monogenic and autoimmune diabetes.

PURPOSE: Mutations in the glucokinase (GCK) gene are associated with altered blood glucose and lipid concentrations. Our aim was to assess the effects on HbA1c and serum lipid levels of single nucleotide polymorphisms (SNPs) in 2 genes encoding proteins that interact with glucokinase: glucose-6-phospatase catalytic subunit 2 (G6PC2) and glucokinase regulatory protein (GCKR). METHODS: The study group included 129 children with GCK-MODY from the Polish Registry of Monogenic Diabetes and 395 with type 1 diabetes (T1DM), in whom we genotyped 2 SNPs in G6PC2 (rs560887) and GCKR (rs1260326). Lipid concentrations were assessed in fasting serum samples. RESULTS: Total and HDL cholesterol concentrations were significantly lower in the GCK-MODY group than in patients with T1DM (167.5±32.5 mg/dl vs. 174.4±31.1 mg/dl, p=0.0435 and 48.42±14.3 mg/dl vs. 58.7±12.7 mg/dl, p<0.0001, respectively). No differences in genotype distributions were found except for underrepresentation of GCKR TT homozygotes among GCK-MODY patients (10.9% in GCK-MODY vs. 17.7% in T1DM, p=0.0651). GCKR genotypes showed significant associations with lipid profiles and HbA1c levels, whereas no such associations were noted for G6PC2. After adjustment for confounders, TT homozygotes were shown to have higher total cholesterol and marginally higher LDL cholesterol and triglyceride levels (p=0.0245, p=0.0657 and p=0.0550, respectively). The difference between TT homozygotes and other genotypes was similar in magnitude within the GCK-MODY and T1DM groups. No significant interactions between the type of diabetes and the GCKR or G6PC2 genotype were detected. CONCLUSIONS: Individuals who are homozygous TT at rs1260326 of the GCKR gene have higher triglyceride, total and LDL cholesterol levels regardless of the presence of GCK mutations.