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Tumours of the urinary tract are the fifth most frequent type of cancer. The most common types are urothelial tumours, among which, non-invasive urothelial neoplasms represent 45% of all cases. The 2016 WHO classification of urinary tract tumours introduced new classifications of non-invasive lesions. Besides urothelial papilloma (UP) and papillary urothelial neoplasm of low malignant potential (PUNLMP), as described in the former classification, the new classification also includes new entities such as urothelial proliferation of uncertain malignant potential (UPUMP) and urothelial dysplasia (UD). Of the aforementioned, UPUMP is the lesion that most commonly progresses, but solely to non-invasive carcinomas. UD is associated with a high risk of progression to invasive carcinoma. Understanding the biological character, and establishing the correct differential diagnosis in cases of non-invasive, non-cancerous lesions of the urinary bladder, will be of importance in establishing outcome predictions for future patients. A systematic review of the current literature allows us to systematize genetic, morphologic and prognostic factors of such lesions. Moreover, the collected data provide the basis for a proposed diagnostic algorithm which facilitates quick and effective differential diagnoses in cases of non-invasive non-cancerous urinary bladder lesions.
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Carcinoma/diagnóstico , Hiperplasia/diagnóstico , Papiloma/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias Urológicas/diagnóstico , Carcinoma/patologia , Proliferação de Células , Diagnóstico Diferencial , Progressão da Doença , Humanos , Hiperplasia/patologia , Papiloma/patologia , Prognóstico , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia , Urotélio/patologiaRESUMO
PURPOSE: Disseminated malignancies are a diagnostic and therapeutic challenge that is often encountered in radiology. Finding the primary tumour is crucial for planning proper surgical and oncological treatment. Computed tomography (CT) of the thorax and abdomen is typically the initial examination. However, abdominal magnetic resonance imaging (MRI) or positron emission tomography (PET/CT) or PET/MRI are often subsequently performed. Histopathological examination of metastatic tumours is performed as well, followed by immunohistochemistry. The aim of the report was to present diagnostic workup in a rare case of skin metastases. CASE REPORT: A 72-year-old patient was admitted to a dermatology ward because of skin lesions - violaceous nodules localised on the hair-covered skin of the head. On abdominal CT, a generalised neoplastic process with metastases in the liver, pancreas, adrenal glands, lymph nodes, bones, thoracic wall, and a suspected metastasis in the right breast was revealed. Histopathology of the skin nodules confirmed a neuroendocrine tumour. Metastases of a pancreatic neuroendocrine tumour or small-cell lung cancer were suspected on immunohistochemistry. The patient died before we were able to localise the primary source of the tumour and provide treatment. CONCLUSIONS: Skin metastases are relatively rare, aggravate the prognosis, and usually indicate spread of the neoplastic process in the internal organs. It is not always possible to localise the primary tumour using radiological imaging. In such cases, co-operation with the pathologist is crucial as are the results of histopathological and immunohistochemical examinations.
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Congenital and adult-onset hyperinsulinism (CHI) must be taken under consideration in the differential diagnosis of hypoglycaemia symptoms with endogenous hyperinsulinism, especially in cases in which there was failure to find an insulinoma. Histological examination is necessary for a definitive diagnosis. CHI is a disorder with three histopathological variants: focal CHI, diffuse CHI, and atypical CHI. These variants are clinically indistinguishable. According to published statistics, 0.5 to 5% of nesidioblastosis cases occur in adults. Clinical manifestation ranges from mildly symptomatic up to life-threatening hypoglycaemia. Early diagnosis and treatment are important in young and very young patients because early treatment accounts for favourable mental outcomes.
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Hiperinsulinismo/etiologia , Nesidioblastose/diagnóstico , Nesidioblastose/terapia , Feminino , Humanos , Hiperinsulinismo/terapia , Lactente , Masculino , Pessoa de Meia-Idade , Nesidioblastose/complicaçõesRESUMO
BACKGROUND: The study aimed to compare catecholamine, cortisol, and immune response in sprint- and endurance-trained athletes under the same training, aiming to observe if their sport specialization affects these markers during a 9-day training camp. METHODS: The study involved twenty-four young male (age 15.7 ± 1.6 years) and female (age 15.1 ± 1,3 years) athletes specializing in sprint and endurance athletics discipline. Blood samples for all measured parameters were taken at rested baseline, on the 4th day, and on the 9th day of training. RESULTS: In both investigated groups a nonsignificant decrease in catecholamine levels was observed after 4 days of training, which remained stable throughout the camp. The cortisol level increased significantly in both athlete groups (sprint: T-0 vs. T-1 p = 0.0491; T-0 vs. T-3 p = 0.0001; endurance: T-0 vs. T-1 p = 0.0159; T-0 vs. T-3 p = 0.0005). The level of hs-CRP (sprint: T-0 vs. T-1 p = 0.0005; T-0 vs. T-3 p = 0.0001; endurance: T-0 vs. T-3 p = 0.0005), and myoglobin (sprint: T-0 vs. T-1 p = 0.0014; T-0 vs. T-3 p = 0.0001; endurance: T-0 vs. T-3 p = 0.0005) have increased and of hs-CRP and myoglobin level was significantly higher in sprint compared to endurance athletes (p < 0.05). The leukocyte level significantly decreased until the end of camp in both groups (sprint: T-0 vs. T-1 p = 0.0178; T-0 vs. T-3 p = 0.0175; endurance: T-0 vs. T-1 p = 0.0362; T-0 vs. T-3 p = 0.0362). CONCLUSIONS: The applied training loads had a strong physiological impact leading to changes in stress hormones and immune responses depending on athletes` sport specialization. Training loads caused stronger responses in sprint athletes. However, both groups showed signs of severe fatigue development. TRIAL REGISTRY: ClinicalTrials.gov ID: NCT06150105, retrospectively registered on 29.11.2023.
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The purpose of the present study was to verify whether impaired iron metabolism in young athletes is a consequence of an excessive workload during the tournament season. Low levels of ferritin (under 25 µg·L(-1)) have been frequently observed in young tennis players. We considered this finding to be related to the high-intensity workload or to insufficient rest, which both trigger a strong immune response. Groups of male, well-trained young tennis players (16 ± 0.9 years old, average of 10-year training experience) and a control peer group participated in this study. The research consisted of two examination sessions (March and September 2010). Blood samples were collected to determine haematological and immunological parameters. Additionally, body composition and physical capacity were assessed. In both periods of the study, the trained groups were characterised by low levels of ferritin, but also elevated levels of pro- inflammatory cytokine IL-1ß. Moreover, an inverse correlation between IL-1ß and blood ferritin was observed. Additionally, an increased concentration of the iron homeostasis regulator hepcidin was found in blood samples (mean 71 ng·ml(-1); range from 48 to 100 ng·ml(-1)). We concluded that the pro- inflammatory cytokine IL-1ß, most likely induced by an extensive workload during the tournament season, was responsible for the low level of ferritin in young, professional athletes. Key PointsThe first research demonstrating low grade inflammation-induced iron deficiency to be associated with elevated blood hepcidin levels in young tennis athletes.Evaluation of immunological response after the complete tournament season in young male tennis players.Conclusion to introduce the assessment of hepcidin to monitor trainings as well as symptoms of overreaching more effectively.Research providing practical information for coaches that changes in diet and modifications in workloads applied in physical training could be more effective than iron supplementation in iron deficient athletes.
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Heat shock proteins (Hsp) represent proteins' groups, whose protective function, may be induced by heat, reactive oxygen species, cytokines etc. We evaluated blood levels of Hsp27 and Hsp70, and their relation to skeletal muscle damage and inflammation in young tennis players before and after the conditioning camp. Blood samples were collected directly after tournament season, 3-day rest and 14-day conditioning camp that followed. Hydrogen peroxide (H2O2) demonstrated the highest concentration directly after tournament season, which significantly decreased at camp's end. The pro-inflammatory cytokines IL-1ß and TNFα decreased, whereas anti-inflammatory cytokines IL-6 and IL-10 increased after 3d rest and 14d camp. Hsp27 increased after 3d rest and remained so after 14d camp, while Hsp70 decreased from baseline to camp's completion. Hsp27 and Hsp70 correlated significantly with H2O2, IL-1ß and TNFα. Muscle damage, observed as creatine kinase (CK) activity changes, increased after 14d camp similarly to Hsp27 and anti-inflammatory cytokines IL-6 and IL-10. Obtained data allows to conclude that decrease of Hsp27 and increase in pro-inflammatory cytokines could be a good indicator of overreaching. Reverse tendencies in these proteins may verify accuracy of conditioning camp. Finally, this training program caused an increase in the anti-inflammatory cytokines concentrations, improving individual status of recovery. Key PointsThe study demonstrating low grade inflammation-induced by the tournament season in young tennis player.Three days of active rest stimulated the anti-inflammatory response via rise of Hsp27 and anti-inflammatory cytokine IL-10.Observed decrease of blood Hsp70 may support mental recovery.Thirteen-day appropriate training program led to maintaining an immunological response balance.
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BACKGROUND: We examined the effect of the 2000-m ergometer test on gut injury in competitive elite rowers in two different training phases. Given that inflammatory markers during the competitive phase are higher, we hypothesise that markers of intestinal injury are also more elevated during that phase. METHODS: We performed this study during the preparatory phase (Test I) and competitive phase (Test II) of annual training. We included 10 competitive elite rowers, members of the Polish Rowing Team, in the study after applying the inclusion/exclusion criteria. The participants performed a 2000-m ergometer test during both phases (Tests I and II). We collected blood samples before the test, immediately after the test and after 1 h of recovery. We measured the levels of interleukin 6 (IL-6), intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), lipopolysaccharide-binding protein (LBP), and zonulin. RESULTS: There were no significant changes over time in Test I and Test II in the gut integrity markers. There were significantly lower I-FABP and IL-6 levels after the test for Test II compared with Test I. The pre-test LPS level was significantly lower for Test II compared with Test I. The pre-test LBP and zonulin levels were numerically lower in Test II, but the differences were not significant. CONCLUSIONS: The 2000-m ergometer test showed no influence on gut integrity markers. However, there were differences in the response to exercise between Tests I and II. The lower level of gut injury markers after extreme exercise tests carried out during the preparation period may be the result of adaptive mechanisms and could indicate that rationally conducted training significantly decreases intestinal injury.
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Introduction: The purpose of this research was to explore the correlation between Gleason score and pattern and the expression of the MLH1, MSH2, MDC1, TP53BP1 proteins in prostate cancer (PC). Prostate cancer development is related to errors in DNA, among others double-strand breaks (DSB) and changes in the base sequence of the DNA. These errors should be repaired through mismatch (MMR) or DSB repair proteins such as MSH2, MLH1, MDC1 and TP53BP1. Material and methods: A total of 500 prostate cancer specimens were recruited in this study. From among all gathered specimens the 52 most suitable cases were selected. The expression of examined proteins was detected by immunohistochemistry, and its correlation with the Gleason score and pattern were further analyzed through standard statistical algorithms. Results: The results show a significant correlation between Gleason pattern and the nuclear expression of the MSH2 protein and the cytoplasmic expression of the MLH1 protein. Gleason score significantly correlates with the nuclear and the cytoplasmic expression of the MSH2 protein and the cytoplasmic expression of the MDC1 protein. There is no correlation between the nuclear or cytoplasmic expression of the TP53BP1 protein and Gleason pattern or score. Conclusions: Our study suggests that the aberration in the MMR repair mechanism may be significantly more important regarding the grading among PC cells in comparison to the impact of alterations in the DSB repair mechanism. The lack of correlation between expression of the TP53BP1 protein and Gleason pattern and Gleason score suggests that the radiation resistance of PC is independent of alterations connected with TP53BP1.
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Bovine colostrum supplementation has been suggested as a potential factor in reducing oxidative stress and inflammation. The primary objective of this study was to evaluate the effects of six months of bovine colostrum supplement intake (3.2 g; four capsules/day) in highly trained female athletes on changes in oxidative stress level, inflammation, and iron metabolism biomarkers after intense exercise. In this study, 20 trained female athletes were recruited. Participants were divided into two groups: 11 in the bovine colostrum (6-month supplementation) and 9 in the placebo group (6-month placebo supplementation). All participants completed an intense exercise test at the beginning of the experiment and after six months post-treatment. Blood samples were taken before, following exercise, and after 3 h recovery. Compared to the placebo group, the colostrum group showed a significant decrease in TBARS level (p< 0.01) at all time points, whereas a marked increase was observed in IL-6 (p < 0.01; pre-exercise) and SOD activity (p < 0.01), and transferrin (p < 0.01; rest period) and lactoferrin (p < 0.05; post-exercise) levels. The results suggested that 6-months of bovine colostrum supplementation is beneficial in the reduction of the harmful effects produced by free radicals (ROS), oxidative stress, and inflammation. In consequence, alleviation of the inflammatory response by bovine colostrum supplementation may also cause positive action on iron homeostasis in female athletes.
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Colostro , Inflamação , Gravidez , Humanos , Animais , Bovinos , Feminino , Suplementos Nutricionais , Estresse Oxidativo , Atletas , Homeostase , Ferro , Método Duplo-CegoRESUMO
BACKGROUND: Gut microbiota is considered to have a great impact on human health and disease. While it is widely recognized that the gut microbiota of healthy individuals differs from those with obesity, inflammatory bowel disease, metabolic syndrome, and other chronic diseases, the alterations of gut microbiota with physical activity are not fully understood. Accordingly, we performed this systematic review to address the question regarding the effects of mild and intense exercise on the gut microbiota in humans. METHODS: The comparative analyses of gut microbiota were conducted following the PRISMA protocol to determine the differences in the active vs. non-active individuals (phenotypes) (n = 11), including the influence of physical activity intervention on the human gut microbiota (n = 13); the differences in the gut microbiota of athletes vs. non-athletes (n = 8); and the microbiota status at different stages of athletic performance or intervention (n = 7), with various of physical activities, sport disciplines, and activity duration. Literature searches were completed using four databases: PubMed, Web of Science, Scopus, and EBSCO, and 2090 articles were retrieved by using appropriate keywords. The low heterogeneity of the studies hasn't allowed us to prepare a meta-analysis. After excluding 2052 articles, we ultimately selected 38 articles that met the eligibility criteria for this review. RESULTS: The data analyses revealed that in non-athletes rising physical activity markedly influenced the relative abundance of short-chain fatty acid (SCFA). Aerobic training that lasted 60 min, and physical activity that characterized 60% HRmax or more also influenced beta diversity indexes. The results showed that athletes harbor a more diverse type of intestinal microflora than non-athletes, but with a relatively reduced abundance of SCFA- and lactic acid-producing bacteria, thereby suggesting an adverse effect of intense exercise on the population of gut microbiota. CONCLUSION: It is concluded that the level of physical activity modulates the gastrointestinal microbiota in humans. For a long period, increasing the intensity and volume of exercise may lead to gut dysbiosis. Perhaps, proper supplementation should be considered to keep gut microbiota in large biodiversity and richness, especially under unfavorable gut conditions associated with intense exercise. TRIAL REGISTRATION: Prospero CRD42021264064.
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BACKGROUND: Bovine colostrum (BC) contains a myriad of bioactive molecules that are renowned for possessing unique medicinal benefits in children and adults, and BC supplements are considered safe and cost-effective options to manage/prevent the incidence of upper respiratory tract infections and gut-related problems in athletes. In this review, we will try to answer the question: How will BC supplementation ameliorate gut permeability problems among athletes? METHODS: Literature searches were performed using PRISMA guidance to identify studies assessing the influence of BC supplements on gut permeability. Studies were selected using four databases: PubMed, Web of Science, Scopus, and EBSCO, and a total number of 60 articles were retrieved by using appropriate keywords. RESULTS: Nine studies were selected that met the eligibility criteria for this review. The data analysis revealed that vigorous exercise profoundly increases intestinal permeability, and BC supplementation helps to reverse gut permeability in athletes. CONCLUSION: BC supplementation may be highly beneficial in improving gut permeability in athletes. However, well-designed, placebo-controlled, and randomized studies are needed to evaluate the long-term safety and efficacy and to determine the optimal dose schedules of BC supplementation in high-performance athletes.
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Atletas , Colostro , Adulto , Animais , Biomarcadores , Bovinos , Criança , Suplementos Nutricionais , Feminino , Humanos , Permeabilidade , GravidezRESUMO
Desmoplasia is crucial for the development, progression and treatment of immune-resistant malignancies. Targeting desmoplasia-related metabolic pathways appears to be an interesting approach to expand our stock of disposable anti-tumor agents. CXCL12/CXCR4 axis inhibition reduces fibrosis, alleviates immunosuppression and significantly enhances the efficacy of PD-1 immunotherapy. CD40L substitute therapy may increase the activity of T-cells, downregulate CD40+, prolong patients' survival and prevent cancer progression. Although FAPα antagonists used in preclinical models did not lead to permanent cure, an alleviation of immune-resistance, modification of desmoplasia and a decrease in angiogenesis were observed. Targeting DDR2 may enhance the effect of anti-PD-1 treatment in multiple neoplasm cell lines and has the ability to overcome the adaptation to BRAF-targeted therapy in melanoma. Reprogramming desmoplasia could potentially cooperate not only with present treatment, but also other potential therapeutic targets. We present the most promising metabolic pathways related to desmoplasia and discuss the emerging strategies to improve the efficacy of immunotherapy.
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Imunoterapia , Melanoma , Linhagem Celular Tumoral , Humanos , Terapia de Alvo Molecular , Linfócitos TRESUMO
The existence, the functional role and clinical relevance of GDF15 and its signaling through a GFRAL/RET-dependent complex in gastric cancer (GC) and other human tumors remain to be elucidated, despite the widespread recognition of obesity as an important cancer-predisposing factor. Therefore, we aimed to analyze the expression levels of GDF15, GFRAL and RET in GC tissues in relation to each other and clinicopathological features, including patient survival, in order to establish a potential implication of the body-weight signaling pathway in the pathology and clinical outcome of GC. Protein expression was examined by immunohistochemistry on tissue microarrays containing 104 and 30 consecutive GC and normal gastric mucosa samples, whereas gene expression data for The Cancer Genome Atlas cohort of 413 GC patients were obtained from public sources. We found that the protein expression of GDF15, GFRAL and RET was significantly elevated and positively correlated in our set of GC tissues, which was reflected in their tendency to be overexpressed in low-grade and intermediate-grade tumors rather than high-grade ones. No other relationships between the expression status of the examined proteins and clinicopathological characteristics of GC patients were found. Through in silico data analysis, we showed that high GDF15 expression was associated with better overall survival (OS) of GC patients, whereas the opposite was true for high levels of GFRAL or RET. Specifically, GFRAL and RET emerged as independent prognostic factors associated with poor OS. Furthermore, high combined expression of the three markers: GDF15+GFRAL+RET was significantly associated with reduced OS, and it was an independent prognostic factor of borderline significance in terms of OS, when adjusted for covariates. If validated in large-scale studies, the individual and combined expression of GDF15, GFRAL and RET may provide significant clinical implications for the prognosis prediction of GC patients.
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Available biomarkers for pancreatic adenocarcinoma (PAC) are inadequate to guide individual patient prognosis or therapy. Therefore, herein we aimed to verify the hypothesis that differences in the expression of KIF11 and KIF14, i.e., molecular motor proteins being primarily implicated in cell division events could account for the differences in the clinical outcome of PAC patients. In-house immunohistochemistry was used to evaluate the protein expressions of KIF11 and KIF14 in PAC, whereas RNA-seq datasets providing transcript expression data were obtained from public sources. IHC and mRNA results were correlated with clinicopathological features and overall survival (OS). Furthermore, the genes co-expressed with KIF11 or KIF14 were predicted and functionally annotated. In our series, malignant ducts displayed more intense but less abundant KIF11 staining than normal-appearing ducts. The former was also true for KIF14, whereas the prevalence of positive staining was similar in tumor and normal adjacent tissues. Based on categorical immunoreactive scores, we found KIF11 and KIF14 to be frequently downregulated or upregulated in PAC cases, respectively, and those with elevated levels of either protein, or both together, were associated with better prognosis. Specifically, we provide the first evidence that KIF11 or KIF14 proteins can robustly discriminate between patients with better and worse OS, independently of other relevant clinical risk factors. In turn, mRNA levels of KIF11 and KIF14 were markedly elevated in tumor tissues compared to normal tissues, and this coincided with adverse prognosis, even after adjusting for multiple confounders. Tumors with low predicted KIF11 or KIF14 expression were seen to have enrichment for circadian clock, whereas those with high levels were enriched for the genomic instability-related gene set. KIF11 and KIF14 were strongly correlated with one another, and CEP55, ASPM, and GAMT were identified as the main hub genes. Importantly, the combined expression of these five genes emerged as the most powerful independent prognostic indicator associated with poor survival outcome compared to classical clinicopathological factors and any marker alone. In conclusion, our study identifies novel prognostic biomarkers for PAC, which await validation.
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The study was designed to investigate whether sports-induced elevation of testosterone level impacts on the growth hormone/insulin-like growth factor-I (GH-IGF-I) axis and body composition, especially skeletal muscle mass. The study included 12 male wrestlers aged 21.1 ± 1.7 years and 10 male nonathletes aged 21.1 ± 1.2 years. Anthropometric and biochemical measurements in the group of nonathlete men were carried out once, while for wrestlers they were carried out twice, that is, on the 1st and 14th days of the training camp. The levels of resting free testosterone (fT), cortisol (C), and human growth hormone (hGH) were significantly higher in the athletes than in nonathletes. A 2-week sports training induced a significant reduction in fT, IGF-I, and IGF binding protein-3 (IGFBP-3) levels and a rise in C level. Increased C level and reduced fT level in the athletes' blood caused a rise in C/fT from the level of 39.95 ± 4.97 nmol/L to 59.73 ± 10.09 nmol/L (p < .05). A negative correlation was demonstrated between C/fT ratio and IGF-I level (r = -0.474, p < .05), which may indicate an inhibitory impact of high C level and low fT concentration on IGF-I release in response to sports training. Sports activity induces significant changes in the C/fT ratio that can impact on the secretion of GH and IGF-I from the liver and finally on the fat-free body mass. The quantification of GH-IGF-I axis in relation to testosterone level could be a useful diagnostic tool in biochemical assessment of the regenerative ability of skeletal muscle or provide evidence of the early stages of muscle functional overload.
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Atletas , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/análise , Testosterona/sangue , Antropometria , Composição Corporal , Humanos , Masculino , Músculo Esquelético/lesões , Células Satélites de Músculo Esquelético , Adulto JovemRESUMO
Prostate cancer (PCa) is the second most commonly diagnosed malignant tumor and the fifth leading cause of cancer death in men in the world. The most common types of tumors are adenocarcinomas. Prostate cancer is a slow-growing cancer. The incidence increases with age. Evaluation of proinflammatory factors such as IL-17A, IL-17F, IL-17RA, and IL-17RC expression makes it possible to assess the impact of inflammatory process on progression of PCa. The aim of the study was to retrospectively assess the histological material of PCa divided into few groups using the Gleason score. Studies were carried out on archival tissue material in the form of paraffin blocks of 40 men with PCa after radical prostatectomy. The control group was composed of 10 men with benign prostatic hyperplasia (BPH). The material was obtained by the transurethral resection of the prostate (TURP). Immunohistochemistry was performed on prepared material using specific primary antibodies against IL-17A, IL-17F, IL-17RA, and IL-17RC. Expression of the antibody to be examined using light microscopy and the Remmele-Stegner score (IRS) in cancer staining was then evaluated. Expression of IL-17 RA was not shown in a group of patients with PCa and in the control group. In the group of patients with Gleason score 8 and 9 PCa, the expression of IL-17A was higher compared to that of IL-17F. In addition, in PCa with an increased grade of Gleason scale, a decrease in the expression of the study inflammatory parameters was found. The inflammatory process has an impact on PCa. A study on IL-17 may become a starting point for further research on an attempt to use, for example, immunotherapy in PCa.
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Imunoterapia/métodos , Interleucina-17/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Receptores de Interleucina-17/metabolismo , Receptores de Interleucina/metabolismo , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Prostatectomia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Lymph node (LN) metastases increase the risk of death from prostate cancer (CaP). The dysfunction of factors responsible for DNA injury detection may promote the evolution of localized primary tumors into the metastatic form. METHODS: In this study, 52 cases of CaP were analyzed. The cases were divided into groups of CaP without metastases (N0), with metastases to the LNs (N+), and metastatic LN tissue. Immunohistochemical examinations were performed with antibodies against MDC1, TP53BP1, MLH1, MSH2, MSH6, and PMS2. RESULTS: Statistical analysis showed lower nuclear expression of TP53BP1 in N+ cases than in N0 cases (Pâ¯=â¯0.026). Nuclear TP53BP1 expression was lower in LN cases than in N+ cases (Pâ¯=â¯0.019). Statistical analysis showed lower nuclear expression of MLH1 in N+ cases than in to N0 cases (Pâ¯=â¯0.003). CONCLUSION: Decreased expression of both MLH1 and TP53B1 were demonstrated in N+ cases of CaP. This observation could help to determine the risk of nodal metastasis, and to select appropriate treatment modalities for patients with locally advanced CaP.
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Metástase Linfática , Proteína 1 Homóloga a MutL/fisiologia , Neoplasias da Próstata/patologia , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/fisiologia , Idoso , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Intermittent exposure to hypoxia (IHE) increases the production of reactive oxygen and nitrogen species as well as erythropoietin (EPO), which stimulates the adaptation to intense physical activity. However, several studies suggest a protective effect of moderate hypoxia in cardiovascular disease (CVD) events. The effects of intense physical activity with IHE on oxi-inflammatory mediators and their interaction with conventional CVD risk factors were investigated. Blood samples were collected from elite athletes (control n = 6, IHE n = 6) during a 6-day IHE cycle using hypoxicator GO2 altitude. IHE was held once a day, at least 2 hours after training. In serum, hydrogen peroxide (H2O2), nitric oxide (NO), 3-nitrotyrosine (3-Nitro), proinflammatory cytokines (IL-1ß and TNFα), high sensitivity C-reactive protein (hsCRP), and heat shock protein 27 (HSP27) were determined by the commercial immunoenzyme (ELISA kits) or colorimetric methods. Serum erythropoietin (EPO) level was measured by ELISA kit every day of hypoxia. IHE was found to significantly increase H2O2, NO, and HSP27 but to decrease 3NT concentrations. The changes in 3NT and HSP27 following hypoxia proved to enhance NO bioavailability and endothelial function. In the present study, the oxi-inflammatory mediators IL-1ß and hsCRP increased in IHE group but they did not exceed the reference values. The serum EPO level increased on the 3rd day of IHE, then decreased on 5th day of IHE, and correlated with NO/H2O2 ratio (r s = 0.640, P < 0.05). There were no changes in haematological markers contrary to lipoproteins such as low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) which showed a decreasing trend in response to hypoxic exposure. The study demonstrated that IHE combined with sports activity reduced a risk of endothelial dysfunction and atherogenesis in athletes even though the oxi-inflammatory processes were enhanced. Therefore, 6-day IHE seems to be a potential therapeutic and nonpharmacological method to reduce CVD risk, especially in elite athletes participating in strenuous training.
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Endotélio/fisiopatologia , Hipóxia/fisiopatologia , Adaptação Fisiológica/fisiologia , Altitude , Aterosclerose/sangue , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Citocinas/sangue , Endotélio/metabolismo , Eritropoetina/sangue , Exercício Físico/fisiologia , Humanos , Peróxido de Hidrogênio/sangue , Hipóxia/sangue , Hipóxia/metabolismo , Inflamação/sangue , Inflamação/metabolismo , Inflamação/fisiopatologia , Lipoproteínas/sangue , Masculino , Óxido Nítrico/sangue , Oxigênio/metabolismo , Esportes/fisiologia , Tirosina/análogos & derivados , Tirosina/sangueRESUMO
Intermittent exposure to hypoxia (IHE) increases production of reactive oxygen and nitrogen species which, as signalling molecules, participate in tissue injury-repair-regeneration cascade. The process is also stimulated by arginine whose bioavailability is a limiting factor for NO synthesis. The effects of IHE in combination with arginine (Arg) intake on myogenesis and angiogenesis mediators were examined in a randomized and placebo-controlled trial. Blood samples were collected from 38 elite athletes on the 1st, 7th and 14th days during the training camp. The oral doses of arginine (2 × 6 g/day) and/or IHE using hypoxicator GO2Altitude (IHE and Arg/IHE) were applied. Serum NO and H2O2 concentrations increased significantly and were related to muscle damage (CK activity >900 IU/mL) in IHE and Arg/IHE compared to placebo. The changes in NO and H2O2 elevated the levels of circulating growth factors such as HGF, IHG-1, PDGFBB, BDNF, VEGF and EPO. Modification of the lipid profile, especially reduced non-HDL, was an additional beneficial effect of hypoxic exposure with arginine intake. Intermittent hypoxic exposure combined with high-dose arginine intake was demonstrated to affect circulating mediators of injury-repair-regeneration. Therefore, a combination of IHE and arginine seems to be a potential therapeutic and non-pharmacological method to modulate the myogenesis and angiogenesis in elite athletes.
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Arginina/administração & dosagem , Hipóxia/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Regeneração/efeitos dos fármacos , Luta Romana/fisiologia , Altitude , Método Duplo-Cego , Humanos , Peróxido de Hidrogênio/sangue , Masculino , Óxido Nítrico/sangue , Consumo de OxigênioRESUMO
The BRAF V600E mutation is an important oncological target in certain central nervous system (CNS) tumors, for which a possible application of BRAF-targeted therapy grows continuously. In the present study, we aim to determine the prevalence of BRAF V600E mutations in a series of ganglioglioma (GG) and pilocytic astrocytoma (PA) cases. Simultaneously, we decided to verify whether the combination of fully automated tests-BRAF-VE1 immunohistochemistry (IHC) and Idylla BRAF mutation assay-may be useful to accurately predict it in the case of specified CNS tumors. The study included 49 formalin-fixed, paraffin-embedded tissues, of which 15 were GG and 34 PA. Immunohistochemistry with anti-BRAF V600E (VE1) antibody was performed on tissue sections using the VentanaBenchMark ULTRA platform. All positive or equivocal cases on IHC and selected negative ones were further assessed using the Idylla BRAF mutation assay coupled with the Idylla platform. The BRAF-VE1 IHC was positive in 6 (6/49; 12.3%) and negative in 39 samples (39/49; 79.6%). The interpretation of immunostaining results was complicated in 4 cases, of which 1 tested positive for the Idylla BRAF mutation assay. Therefore, the overall positivity rate was 14.3%. This included 2 cases of GG and 5 cases of PA. Our study found that BRAF V600E mutations are moderately frequent in PA and GG and that for these tumor entities, IHC VE1 is suitable for screening purposes, but all negative, equivocal, and weak positive cases should be further tested with molecular biology techniques, of which the Idylla system seems to be a promising tool.