HPV-positive cancer is strongly immunogenic tumor which induces cell type response in surrounding microenvironment. Systemic inflammation is generally accompanied by cancer disease and it weakens ...cell response and negatively influences organism reaction to cancer
The aim of present study was to compare laboratory parameters of the immune system: leukocyte count (WBC), neutrophil count (Neut) and lymphocyte count (Lym), monocyte count (Mono), C-reactive protein (CRP), Interleukine 6 (Il-6), in patients with HPV-positive and HPV-negative OPC.
75 patients were treated with curative intent with radiotherapy alone (32 %) or combined with platinum-based chemotherapy (68%). There were 47% patients with T1/2 and 53% with T3/4 of primary tumor stage and 44% and 56% of patients with N0 and N+ nodal stage disease, respectively. Complete blood counts (CBC), C-reactive protein (CRP) and Il-6 were estimated in blood or serum before and after the treatment. HPV DNA was determined in plasma by QPCR method.
In patients with HPV-negative OPC WBC count (p=0,006 median: 6,88 vs 5,69), Lym count (p=0,02 median: 1,96 vs 1,49) and CRP (p=0,0001 median: 5,88 vs 1,35 mg/dl) was higher than for HPV-positive OPC before treatment. Additionally, in patients with HPV-negative OPC WBC count (p=0,03 median: 5,53 vs 4,17), Lym count (p=0,02 median: 0,69 vs 0,44), Mono count (p=0,003 median: 0,58 vs 0,43) and Il-6 (p=0,05 median: 25,53 vs 11,65 pg/ml) was higher than for HPV-positive OPC after therapy. Before treatment significantly longer overall survival (OS) for patients with low WBC count (p=0,001)(Fig.1), low concentration of CRP (p=0,0001) (Fig. 2) and Il-6 (p=0,01) was also found.
Inflammation processes are more severe in HPV-negative OPC. Low levels of inflammatory indicators like WBC count, Lym count, CRP, Il-6 may be associated with longer OS in this group of patients. Systemic inflammation reflects host reaction on cancer, characterized by a significant weakness of cellular immunity. It is more characteristic for patients with HPV–negative OPC
Our previous in vitro studies proved a higher clonogenic potential of peripheral blood progenitor cells cryopreserved in 7.5% dimethyl sulfoxide (Me2SO) than in 10% Me2SO containing medium. Based on ...this findings 7.5% Me2SO cryopreservation medium was introduced to our protocol and both the hematopoietic recovery and infusion-related toxicity were compared with that obtained with standard 10% Me2SO containing solution. Two cohorts of consecutive patients treated with autologous hematopoietic stem cell transplantation were included in the analysis: 56 patients with PBPCs cryopreserved in 7.5% Me2SO solution and 52 patients who obtained cells cryopreserved in 10% Me2SO. Both study groups did not differ significantly with regard to age, diagnosis, and the number of transplanted CD34+ cells. The time to leukocyte recovery was shorter for patients in the 7.5% Me2SO treated group than in the 10% one. Reconstitution of platelets and the frequency of adverse events did not differ in both groups. Reduction of Me2SO concentration from 10% to 7.5% in cryoprotective mixture has a beneficial impact on leukocyte recovery. These findings require verification in a prospective, randomized trial.
Abstract 3018
Cryopreservation of autologous peripheral blood progenitor cells (PBPCs) in 10% DMSO is a routine in most transplantation centers. During ASH 2011 Meeting, we presented the results of ...in vitro research, concerning the optimization of DMSO concentrations for recovery and clonogeneic potential of PBPCs after thawing. We concluded, that reduction of DMSO concentration from 10% to 7.5% may have favorable impact for cell clonogeneicity. Accordingly, we implemented new cryoprotective mixture (7.5% instead of 10% DMSO) into clinical practice. The purpose of this study was to clinically evaluate the changed protocol.
In our department, between Jan 2012-Aug 2012, 56 patients were transplanted with autologous PBPCs cryopreserved in 7.5% DMSO solution (median of age: 57 years, range: 21–66). We compared the data concerning hematopoietic engraftment and the frequency of side effects with historical control – 52 subsequent patients treated with transplantation of PBPSc cells cryopreserved in 10% DMSO (median of age: 57 years, range: 21–66) in a preceding period. Both study groups did not differ significantly with regard to the diagnosis (mostly lymphoproliferative disorders) or disease status at transplantation. As well, the number of transplanted CD34+ cells was comparable: median 6.5′106/kg (range 1.5–24.7) for 7.5% DMSO and 7.5′106/kg (2.1–24.6) for 10% DMSO group, p=0.68. All received G-CSF (filgrastim) starting on day +7 after transplantation.
The volume of infused DMSO was significantly lower in patients who obtained PBPBc cryopreserved in 7.5% DMSO (median 22.5 ml, range 7.5–45) than 10% DMSO (median: 30 ml, range, 10–160); p=0.02. The time to leukocyte recovery >1′109/L was faster for 7.5% DMSO (median: 11 days, range: 9–12) than in 10% DMSO (median 11 days, range: 10–13), p=0.03. Similarly, reconstitution of neutrophils >0.5′109/L was faster for 7.5% DMSO group: median 11 days (range 9–13 days) vs. 11 days (range 10–13 days), respectively; p = 0.04. We didn’t observe significant difference with regard to platelet recovery >50′109/L (median 12 days, range: 0–21 days for 7.5% DMSO vs. median 12.5, range: 0–19 days for 10% DMSO). Hospital stay since HSCT was shorter in case of 7.5% group (median: 14 days, range: 11–21) than 10% group (median: 15 days, range: 13–25); p=0.04. Number of RBC and platelets transfusions as well as transfusion-related complications did not differ between the groups. Adverse events after transplantation were mild and transient, usually grade 1 nausea, and occurred in 20 (38%) patients in 10% DMSO group compared to 24 (43%) in 7.5% DMSO group (p=0.7).
The analysis of newly implemented cryopreservation protocol suggest that reduction of the DMSO concentration from 10% to 7.5% is associated with faster leukocyte and neutrophil recovery as well as shorter hospital stay. These findings require verification in a prospective, randomized trial. Display omitted
No relevant conflicts of interest to declare.
Abstract 1930
Hematopoietic stem cells mobilized to peripheral blood and collected by leukapheresis are predominantly used for autologous transplantation. Prior to cryopreservation the cells need to ...be processed including the addition of DMSO (dimethyl sulfoxide), which enhance cell survival, but is potentially toxic to stem cell recipient. The most commonly used concentration of DMSO is 10%. The goal of our study was to test if the concentration may be reduced without negative impact on cell recovery and clonogenicity.
Samples were prospectively collected from 12 patients with lymphomas mobilized with chemotherapy combined with G-CSF. Small volumes (2–3 ml) of cell suspensions obtained from the leukapheresis product were divided into 4 parts placed in separate small vials, each containing different cryoprotective mixture - with 10%, 7.5%, 5% and 2.5% DMSO. The final volume of cell suspensions equaling 1 ml, the cell concentration (0.8–1 × 108 /ml) and the proportions of human albumin and plasma were the same in all vials. The cells were frozen in IceCube, using a computer controlled cooling program and stored in liquid nitrogen for 2 weeks – 4 months. The quality of cryoprotective mixtures was evaluated by cell recovery and clonogenic potential. The recovery was determined by comparing number of living cells before and after cryopreservation, using trypan blue staining. Clonogenic potential was carried out by colony forming unit (CFU) assays. Depending on CD34+ percentage, 5 or 10 × 103 living cells were plated (in triplicates) in medium MethoCult and cultured for 14 days.
The median recovery of nucleated cells for 10% DMSO was 62.4% (range 41.2–86.8) and was significantly higher compared to 7.5% DMSO (54.9%, 41.2–89.1; p=0.04), 5% DMSO (49.2%, 28.1–69.8; p=0.002) and 2.5% DMSO (37.2%, 19.3–54.3; p=0.002). The number of CFUs calculated per 100 000 cryopreserved cells did not differ significantly according to DMSO concentration: 217 (14–1795) for 10% DMSO, 225 (27–2718) for 7.5% DMSO, 196 (26–2761) for 5% DMSO, and 178 (14–2208) for 2.5% DMSO. Neither cell recover nor clonogenic potential correlated with the percentage of CD34+ cells in the leukapheresis product.
Reduction of DMSO concentration to equal or below 7.5% is associated with impaired recovery of nucleated cells after cryopreservation. However, it does not appear to negatively affect clonogenic potential of leukapheresis product, suggesting relative resistance of hematopoietic progenitor cells. Therefore, considering potential toxicity of DMSO to stem cell recipient, its lower concentrations may be clinically beneficial. This hypothesis requires prospective verification in a setting of autologous transplantation.
No relevant conflicts of interest to declare.
Female preferences for specific male phenotypes have been documented across a wide range of animal taxa, including numerous species where males contribute only gametes to offspring production. Yet, ...selective pressures maintaining such preferences are among the major unknowns of evolutionary biology. Theoretical studies suggest that preferences can evolve if they confer genetic benefits in terms of increased attractiveness of sons ("Fisherian" models) or overall fitness of offspring ("good genes" models). These two types of models predict, respectively, that male attractiveness is heritable and genetically correlated with fitness. In this meta-analysis, we draw general conclusions from over two decades worth of empirical studies testing these predictions (90 studies on 55 species in total). We found evidence for heritability of male attractiveness. However, attractiveness showed no association with traits directly associated with fitness (life-history traits). Interestingly, it did show a positive correlation with physiological traits, which include immunocompetence and condition. In conclusion, our results support "Fisherian" models of preference evolution, while providing equivocal evidence for "good genes." We pinpoint research directions that should stimulate progress in our understanding of the evolution of female choice.
In times of pandemic, health literacy (HL) is very important, as it helps to find, understand, and use essential health information and services. According to WHO, HL is pivotal in fighting infodemic ...effectively, and education is a vital tool for developing it. In the presented work, we analyze 247 educational materials dedicated to children, adolescents, and their carers explaining the pandemic, prepared by the Chinese, American, German, Italian and Polish governments and international non-governmental organizations. Focusing on the textual and visual side of the documents, we investigated how the pandemic is explained and what discursive measures were used to inform young citizens about the risks and consequences of pandemic restrictions. Additionally, we verified whether the materials helped developing critical thinking, which is crucial to prevent spreading fake news and conspiracy theories. Although the analyzed materials were prepared in different cultural contexts, we identified that all of them contained simple instructions on the desired behaviours during the pandemic. Key messages relating to the importance of hygienic behaviors were often supplemented with guidelines on how to successfully complete each action. While the cultural particularities in presenting the state of the pandemic are visible, the challenges of dealing with the emotional and social crises were dominant all around the world. In our study, we argue that the possibilities of building HL were not fully exploited by the national and international institutions. Citizens were taught how to behave in unusual circumstances but not why they should behave differently. The educational materials lacked reliable knowledge that would allow them to deal with infodemic and develop critical thinking. We conclude that health education expertise worldwide should be focused on enhancing individuals' ability to make informed health decisions and provide three recommendations regarding the process of development of health educational resources for children and the youth.
In times of pandemic, health literacy (HL) is very important, as it helps to find, understand, and use essential health information and services. According to WHO, HL is pivotal in fighting infodemic ...effectively, and education is a vital tool for developing it. In the presented work, we analyze 247 educational materials dedicated to children, adolescents, and their carers explaining the pandemic, prepared by the Chinese, American, German, Italian and Polish governments and international non-governmental organizations. Focusing on the textual and visual side of the documents, we investigated how the pandemic is explained and what discursive measures were used to inform young citizens about the risks and consequences of pandemic restrictions. Additionally, we verified whether the materials helped developing critical thinking, which is crucial to prevent spreading fake news and conspiracy theories. Although the analyzed materials were prepared in different cultural contexts, we identified that all of them contained simple instructions on the desired behaviours during the pandemic. Key messages relating to the importance of hygienic behaviors were often supplemented with guidelines on how to successfully complete each action. While the cultural particularities in presenting the state of the pandemic are visible, the challenges of dealing with the emotional and social crises were dominant all around the world. In our study, we argue that the possibilities of building HL were not fully exploited by the national and international institutions. Citizens were taught how to behave in unusual circumstances but not why they should behave differently. The educational materials lacked reliable knowledge that would allow them to deal with infodemic and develop critical thinking. We conclude that health education expertise worldwide should be focused on enhancing individuals’ ability to make informed health decisions and provide three recommendations regarding the process of development of health educational resources for children and the youth.
Novel transition metal complexes (Au, Pd, Pt) with berenil and 2-(1-methyl-5-nitroimidazol-2-yl)ethanol were obtained through two-step synthesis. The cytotoxicity assay against MCF-7 and MDA-MB-231 ...breast cancer cells revealed that novel platinum and palladium complexes cause a reduction on the viability of MCF-7 and MDA-MB-231 breast cancer cells to a greater extent than cisplatin. The complexes showed lower cytotoxicity on normal MCF-10A human breast epithelial cells than on tumor cells. Furthermore, we observed that these complexes selectively concentrate in tumor cell mitochondria due to the characteristic for these cells increased membrane potential that may explain their increased proapoptotic activity. The activity of the synthesized compounds against topoisomerase type IIα and their increased impact on DNA defragmentation also were documented. The novel complexes also induced autophagosome changes and inhibited tumor growth in xenograft models (established using breast cancer cells).
Proline metabolism has been identified as a significant player in several neoplasms, but knowledge of its role in gliomas is limited despite it providing a promising line of pursuit. Data on proline ...metabolism in the brain are somewhat historical. This study aims to investigate alterations of proline metabolism in gliomas of WHO grade 4 (GG4) in the context of the brain. A total of 20 pairs of samples were studied, consisting of excised tumor and unaffected brain tissue, obtained when partial brain resection was required to reach deep-seated lesions. Levels of proline oxidase/proline dehydrogenase (POX/PRODH), Δ
-pyrroline-5-carboxylate reductases (PYCR1/2/3), prolidase (PEPD), and metalloproteinases (MMP-2, MMP-9) were assessed, along with the concentration of proline and proline-related metabolites. In comparison to normal brain tissue, POX/PRODH expression in GG4 was found to be suppressed, while PYCR1 expression and activity of PEPD, MMP-2, and -9 were upregulated. The GG4 proline concentration was 358% higher. Hence, rewiring of the proline metabolism in GG4 was confirmed for the first time, with a low-POX/PRODH/high-PYCR profile. High PEPD and MMPs activity is in keeping with GG4-increased collagen turnover and local aggressiveness. Further studies on the mechanisms of the interplay between altered proline metabolism and the GG4 microenvironment are warranted.
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