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Recent advancements in proteomics have enhanced our understanding of clear cell renal cell carcinoma (CCRCC). Utilizing a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by immunohistochemical validation, we investigated the expression levels of UCHL1, PAK4, and SNRNP200 in high-grade CCRCC samples. Our analysis also integrated Reactome pathway enrichment to elucidate the roles of these proteins in cancer-related pathways. Our results revealed significant upregulation of UCHL1 and SNRNP200 and downregulation of PAK4 in high-grade CCRCC tissues compared to non-cancerous tissues. UCHL1, a member of the ubiquitin carboxy-terminal hydrolase family, showed variable expression across different tissues and was notably involved in the Akt signaling pathway, which plays a critical role in cellular survival in various cancers. SNRNP200, a key component of the RNA splicing machinery, was found to be essential for proper cell cycle progression and possibly linked to autosomal dominant retinitis pigmentosa. PAK4's role was noted as critical in RCC cell proliferation and invasion and its expression correlated significantly with poor progression-free survival in CCRCC. Additionally, the expression patterns of these proteins suggested potential as prognostic markers for aggressive disease phenotypes. This study confirms the upregulation of UCHL1, SNRNP200, and PAK4 as significant factors in the progression of high-grade CCRCC, linking their enhanced expression to poor clinical outcomes. These findings propose these proteins as potential prognostic markers and therapeutic targets in CCRCC, offering novel insights into the molecular landscape of this malignancy and highlighting the importance of targeted therapeutic interventions.
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INTRODUCTION: Klotho has been recently described as a carcinogenesis suppressor. Large cell neuroendocrine lung carcinoma (LCNEC) is a rare, highly malignant neoplasm. In the light of increasing incidence of neuroendocrine tumours, biomarkers predicting survival are needed. We consider that Klotho might be one. MATERIAL AND METHODS: We analysed records of all patients diagnosed with LCNEC, atypical carcinoid and typical carcinoid operated on in our institution between 2007 and 2015. Initially, we found 134 cases. Forty-six specimens were unattainable and thus excluded from research. All patients diagnosed with LCNEC according to the WHO classification were included in the study. Immunohistochemical staining for Klotho was performed. We retrospectively reviewed patient charts and analysed multiple variables. RESULTS: Positive staining for Klotho was present in 36 tissue specimens, while 12 patients were Klotho-negative. Survival length was significantly higher in Klotho-positive cases (p = 0.024), while advanced nodal status (N1 and N2) represented a marker of poor outcome (p = 0.011). In multivariate analysis, both Klotho presence (p = 0.015; HR = 0.37; 95% CI: 0.17-0.86) and nodal involvement (p = 0.007; HR = 3.04; 95% CI: 1.37-6.82) were independent prognostic factors. Tumour vessel invasion and visceral pleura infiltration were not associated with worse treatment results. Klotho presence predicted a favourable prognosis in these groups (p = 0.018; p = 0.007). CONCLUSIONS: Our results suggest that Klotho might be a positive factor for predicting survival in LCNEC and nodal involvement a negative one. Thus, these two markers may assist in the selection of subjects with unfavourable prognosis and to personalise therapy regimens.
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BACKGROUND: Ghrelin is a hormone that occurs in acylated (AG) or unacylated (UG) form. Ghrelin strongly stimulates growth hormone (GH) secretion from anterior pituitary, as well as regulates the energy balance and various metabolic parameters. Increased consideration is given to UG, thought to be inactive. OBJECTIVES: We aimed to evaluate the levels of total ghrelin, AG and UG in medically naive and treated patients with biochemically active acromegaly, with respect to variables of lipid and glucose metabolism. MATERIAL AND METHODS: We studied total ghrelin, AG and calculated UG levels in a group of 24 patients with active acromegaly and 15 healthy controls. Plasma levels of GH, insulin-like growth factor 1 (IGF-1), insulin, glucose, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and calculated low-density lipoprotein (LDL) cholesterol, triglycerides (TG), apolipoproteins A1 (APO A1), and B-100 (APO B-100) were measured. RESULTS: Patients with acromegaly revealed lower levels of total ghrelin than healthy controls. In pooled data of all subgroups, simple linear regression analysis revealed that total ghrelin concentration was significantly associated with APO A1 concentration (ß = 0.8087; p = 0.0315) and AG concentration was significantly associated with fasting insulin concentration (ß = 15.5183; p = 0.011). There was an inverse association between UG and the patients' age, and positive association between UG and APO A1. CONCLUSIONS: Our results suggest that ghrelin may influence metabolic disturbances in acromegaly. It seems that the assessment of AG and UG is superior to total ghrelin measurement. Mechanisms regulating ghrelin acylation and function of each form need elucidation in order to improve diagnostics and treatment of metabolic disturbances, not only acromegaly.
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Acromegalia/sangue , Apolipoproteína A-I/sangue , Grelina/sangue , Hormônio do Crescimento/efeitos dos fármacos , Biomarcadores/sangue , Glicemia/metabolismo , Colesterol/sangue , Grelina/farmacologia , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/análiseRESUMO
OBJECTIVES: The aim of this study was to investigate the fluorine-18-fluorodeoxyglucose (F-FDG) uptake on integrated PET [PET/computed tomography (CT)] images and its correlation with nestin expression in a series of neuroendocrine lung tumours. As the incidence of neuroendocrine lung tumours is rising, tools predicting diagnosis, outcome and assisting in the selection of treatment regimens are needed. PATIENTS AND METHODS: We reviewed records of patients diagnosed with large cell neuroendocrine lung carcinoma, atypical carcinoid and typical carcinoid who were operated upon in our institution. Into the study, we included those who underwent F-FDG PET/CT before the operation. Immunohistochemical staining for nestin was performed. We retrospectively reviewed patient charts and analyzed multiple variables. RESULTS: Maximal standardized uptake value (SUVmax) was significantly higher in poorly differentiated than in well-differentiated tumours (P<0.001). The estimated SUVmax cut-off value, which distinguishes large cell neuroendocrine lung carcinoma from carcinoid with the highest sensitivity and specificity (88.6%; 85%), was 6.3. Positivity of the tumour on F-FDG PET/CT was associated with shorter survival of the patient (P=0.0057). Multivariate analysis showed that nodal involvement and SUVmax were predictors of adverse outcome. Nestin expression did not correlate with lymph node metastases (P=0.97), SUVmax (P=0.9), maximal size of the lesion (P=0.49) or Ki-67 (P=0.93). Nestin expression did not influence survival on multivariate analysis. CONCLUSION: The study revealed a comparable expression of nestin in tumours with different activity of glucose metabolism measured by F-FDG uptake at PET/CT. It did not show any significant influence of nestin expression on survival. The study confirmed that F-FDG PET/CT is useful in the preoperative evaluation of patients with pulmonary neuroendocrine tumours.
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Fluordesoxiglucose F18 , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico por imagem , Nestina/metabolismo , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/metabolismo , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: The study was designed to evaluate the relationship between thyroid antibodies and gland dysfunction, with the aim of finding a clinically useful threshold value of thyreoperoxidase antibodies, which could prove to be predictive for thyroid failure. MATERIAL AND METHODS: The study was conducted on 99 women, ages ranging from 18-91 years (mean age: 45.5 ±17.0), were treated as outpatients in the Department of Endocrinology, Metabolism and Internal Medicine. Analysis of serum samples for TSH concentration and anti-TPO titers was conducted. RESULTS: The most common disorder was hypothyroidism. Anti-TPO titers above reference range values were observed in 35 patients (35.4%): 21 (60%) were hypothyroid and 11 (31.4 %) were euthyroid. The anti-TPO and TSH serum levels correlated both in patients with high thyroid antibody titers, and in the anti-TPO negative groups. To find the threshold value of anti- TPO that would help predict hypothyroidism, receiver operating curves were used. With this approach, TPO antibody titers over 17 IU/ml indicated hypothyroidism with a 90% sensitivity and 75% sensibility. CONCLUSIONS: It can be postulated that the cutoff values of anti-TPO in the general population should be decreased in order to improve autoimmune thyroid disorder screening. Obviously, using that margin may lead initially to the detection of some false positive subjects. However, with lower cut-off values, more patients can be enrolled into thyroid follow-up groups. In this way, many people could avoid complications of undiagnosed, insidious thyroid failure.
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Autoanticorpos/sangue , Hipotireoidismo/sangue , Iodeto Peroxidase/imunologia , Tireotropina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipotireoidismo/enzimologia , Hipotireoidismo/imunologia , Pessoa de Meia-Idade , Glândula Tireoide/metabolismo , Adulto JovemRESUMO
Nestin is considered to be a cancer stem cell marker. Nestin expression in neuroendocrine tumours might be useful to predict prognosis and facilitate treatment planning. 88 patients with neuroendocrine lung tumours operated in the Department of Thoracic Surgery from 2007 to 2015 were included into the study. Immunohistochemical staining for nestin was performed. Clinicopathological and survival data were retrospectively analyzed. Nestin expression was detected in 15 (17%) specimens. Multivariate analysis showed that lymph node metastases (p = 0.0001; hazard ratio (HR) = 3.93; confidence interval (CI) 95%: 1.96-7.87), nestin expression (p = 0.034; HR = 2.30; CI 95%: 1.06-4.99) and patient's age (p = 0.024; HR = 1.04; CI 95%: 1.00-1.09) were independent negative prognostic factors. Nestin expression was significantly higher in large cell neuroendocrine carcinoma when compared with carcinoids (p = 0.001). Collected data support the thesis that nestin can be regarded as a biomarker in patients with neuroendocrine lung tumours.
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Biomarcadores Tumorais/análise , Tumor Carcinoide/química , Neoplasias Pulmonares/química , Nestina/análise , Tumores Neuroendócrinos/química , Adulto , Fatores Etários , Idoso , Tumor Carcinoide/mortalidade , Tumor Carcinoide/secundário , Tumor Carcinoide/cirurgia , Distribuição de Qui-Quadrado , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/cirurgia , Pneumonectomia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of our study was to evaluate the possible association between autoimmunity and thyroid nodular disease (TND). DESIGN AND SETTING: We conducted a study on 58 patients who were treated in outpatient setting at the Department of Endocrinology, Metabolism and Internal Medicine. Serum samples were analyzed for TSH concentration and anti-TPO antibodies titers. Thyroid ultrasonography was performed in each subject in order to evaluate volume of the gland, and the number and size of nodules. RESULTS: TND occurred in 70% of anti-TPO positive subjects and in 57.9% of anti-TPO negative subjects, but statistical analysis did not demonstrate a significant concordance between the presence of anti-TPO antibodies and prevalence of TND (p>0.05). We showed that the mean (0.82 vs 0.75; p=0.49), minimal (0.2 vs 0.3; p=0.89) and maximal (2.7 vs 2.4; p=0.49) diameters of a nodule were similar in both groups. Solely in anti-TPO positive patients, anti-TPO titers positively correlated with the number of nodules (p=0.04). CONCLUSION: Our results favor the role of autoimmunity in TND development although associations between thyroid nodules and thyroid autoimmunity are complicated and may be the subject of much controversy. Increased anti-TPO may influence the number of nodules rather than the presence of TND itself.