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1.
Cell Mol Life Sci ; 81(1): 276, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38909325

RESUMO

N6-methyladenosine (m6A) is one of the most prevalent and conserved RNA modifications. It controls several biological processes, including the biogenesis and function of circular RNAs (circRNAs), which are a class of covalently closed-single stranded RNAs. Several studies have revealed that proteotoxic stress response induction could be a relevant anticancer therapy in Acute Myeloid Leukemia (AML). Furthermore, a strong molecular interaction between the m6A mRNA modification factors and the suppression of the proteotoxic stress response has emerged. Since the proteasome inhibition leading to the imbalance in protein homeostasis is strictly linked to the stress response induction, we investigated the role of Bortezomib (Btz) on m6A regulation and in particular its impact on the modulation of m6A-modified circRNAs expression. Here, we show that treating AML cells with Btz downregulated the expression of the m6A regulator WTAP at translational level, mainly because of increased oxidative stress. Indeed, Btz treatment promoted oxidative stress, with ROS generation and HMOX-1 activation and administration of the reducing agent N-acetylcysteine restored WTAP expression. Additionally, we identified m6A-modified circRNAs modulated by Btz treatment, including circHIPK3, which is implicated in protein folding and oxidative stress regulation. These results highlight the intricate molecular networks involved in oxidative and ER stress induction in AML cells following proteotoxic stress response, laying the groundwork for future therapeutic strategies targeting these pathways.


Assuntos
Adenosina , Leucemia Mieloide Aguda , Estresse Oxidativo , RNA Circular , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Bortezomib/farmacologia , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Fatores de Processamento de RNA/metabolismo , Fatores de Processamento de RNA/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Proteínas Serina-Treonina Quinases , Peptídeos e Proteínas de Sinalização Intracelular
2.
Cell Mol Life Sci ; 80(8): 202, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37442828

RESUMO

The epidermal growth factor receptor (EGFR) is one of the main tumor drivers and is an important therapeutic target for many cancers. Calcium is important in EGFR signaling pathways. Sorcin is one of the most important calcium sensor proteins, overexpressed in many tumors, that promotes cell proliferation, migration, invasion, epithelial-to-mesenchymal transition, malignant progression and resistance to chemotherapeutic drugs. The present work elucidates a functional mechanism that links calcium homeostasis to EGFR signaling in cancer. Sorcin and EGFR expression are significantly correlated and associated with reduced overall survival in cancer patients. Mechanistically, Sorcin directly binds EGFR protein in a calcium-dependent fashion and regulates calcium (dys)homeostasis linked to EGF-dependent EGFR signaling. Moreover, Sorcin controls EGFR proteostasis and signaling and increases its phosphorylation, leading to increased EGF-dependent migration and invasion. Of note, silencing of Sorcin cooperates with EGFR inhibitors in the regulation of migration, highlighting calcium signaling pathway as an exploitable target to enhance the effectiveness of EGFR-targeting therapies.


Assuntos
Fator de Crescimento Epidérmico , Neoplasias , Humanos , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Cálcio , Transdução de Sinais , Receptores ErbB/genética , Receptores ErbB/metabolismo , Linhagem Celular Tumoral , Movimento Celular
3.
Cell Mol Life Sci ; 80(9): 245, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37566283

RESUMO

Heart failure is a major side effect of doxorubicin (DOX) treatment in patients with cancer. However, the mechanisms underlying the development of DOX-induced heart failure need to be addressed. This study aims to test whether the serine/threonine kinase MST1, a major Hippo pathway component, contributes to the development of DOX-induced myocardial injury. C57BL/6J WT mice and mice with cardiomyocyte-specific dominant-negative MST1 (kinase-dead) overexpression received three weekly injections of DOX, reaching a final cumulative dose of 18 mg/kg. Echocardiographic, histological and biochemical analyses were performed six weeks after the first DOX administration. The effects of MST1 inhibition on DOX-induced cardiomyocyte injury were also tested in vitro. MST1 signaling was significantly activated in cardiomyocytes in response to DOX treatment in vitro and in vivo. Wild-type (WT) mice treated with DOX developed cardiac dysfunction and mitochondrial abnormalities. However, these detrimental effects were abolished in mice with cardiomyocyte-specific overexpression of dominant-negative MST1 (DN-MST1) or treated with XMU-MP-1, a specific MST1 inhibitor, indicating that MST1 inhibition attenuates DOX-induced cardiac dysfunction. DOX treatment led to a significant downregulation of cardiac levels of SIRT3, a deacetylase involved in mitochondrial protection, in WT mice, which was rescued by MST1 inhibition. Pharmacological inhibition of SIRT3 blunted the protective effects of MST1 inhibition, indicating that SIRT3 downregulation mediates the cytotoxic effects of MST1 activation in response to DOX treatment. Finally, we found a significant upregulation of MST1 and downregulation of SIRT3 levels in human myocardial tissue of cancer patients treated with DOX. In summary, MST1 contributes to DOX-induced cardiomyopathy through SIRT3 downregulation.


Assuntos
Cardiomiopatias , Cardiopatias , Insuficiência Cardíaca , Sirtuína 3 , Humanos , Camundongos , Animais , Sirtuína 3/genética , Regulação para Baixo , Camundongos Endogâmicos C57BL , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Miócitos Cardíacos/metabolismo , Doxorrubicina/farmacologia , Cardiopatias/metabolismo , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Apoptose
4.
Int J Mol Sci ; 23(17)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36076927

RESUMO

Before entering human clinical studies to evaluate their safety and effectiveness, new drugs and novel medical treatments are subject to extensive animal testing that are expensive and time-consuming. By contrast, advanced technologies enable the development of animal-free models that allow the efficacy of innovative therapies to be studied without sacrificing animals, while providing helpful information and details. We report on the powerful combination of 3D bioprinting (3DB) and photo-thermal therapy (PTT) applications. To this end, we realize a 3DB construct consisting of glioblastoma U87-MG cells in a 3D geometry, incorporating biomimetic keratin-coated gold nanoparticles (Ker-AuNPs) as a photo-thermal agent. The resulting plasmonic 3DB structures exhibit a homogeneous cell distribution throughout the entire volume while promoting the localization of Ker-AuNPs within the cells. A 3D immunofluorescence assay and transmission electron microscopy (TEM) confirm the uniform distribution of fluorescent-labeled Ker-AuNPs in the volume and their capability to enter the cells. Laser-assisted (λ = 532 nm) PTT experiments demonstrate the extraordinary ability of Ker-AuNPs to generate heating, producing the highest temperature rise of about 16 °C in less than 2 min.


Assuntos
Glioblastoma , Hipertermia Induzida , Nanopartículas Metálicas , Terapia Fototérmica , Materiais Biomiméticos , Glioblastoma/terapia , Ouro/química , Humanos , Queratinas/química , Nanopartículas Metálicas/química , Terapia Fototérmica/métodos
5.
Int J Mol Sci ; 23(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36076963

RESUMO

Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is the most aggressive form of glioma and is characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, invasion, angiogenesis, and radio- and chemoresistance, that have direct impacts on treatment failure. Thus, there is still an increasing need to identify novel targets to limit GBM relapse. Polysialic acid (PSA) is a carbohydrate composed of a linear polymer of α2,8-linked sialic acids, primarily attached to the Neural Cell Adhesion Molecule (NCAM). It is considered an oncodevelopmental antigen that is re-expressed in various tumors. High levels of PSA-NCAM are associated with high-grade and poorly differentiated tumors. Here, we investigated the effect of PSA inhibition in GBM cells under low oxygen concentrations. Our main results highlight the way in which hypoxia stimulates polysialylation in U87-MG cells and in a GBM primary culture. By lowering PSA levels with the sialic acid analog, F-NANA, we also inhibited GBM cell migration and interfered with their differentiation influenced by the hypoxic microenvironment. Our findings suggest that PSA may represent a possible molecular target for the development of alternative pharmacological strategies to manage a devastating tumor like GBM.


Assuntos
Glioblastoma , Neuroblastoma , Glioblastoma/metabolismo , Humanos , Hipóxia/metabolismo , Recidiva Local de Neoplasia , Moléculas de Adesão de Célula Nervosa/genética , Moléculas de Adesão de Célula Nervosa/metabolismo , Neuroblastoma/metabolismo , Ácidos Siálicos/metabolismo , Microambiente Tumoral
6.
Int J Clin Pract ; 75(3): e13699, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32910514

RESUMO

AIMS: Shear wave elastosonography (SWE) is a non-invasive ultrasound imaging modality used to assess the mechanical properties of tissues such as rigidity and elasticity. In this prospective study, we investigated the effect of laparoscopic varicocelectomy on the elasticity, degree of fibrosis and function of the testes through SWE and we evaluated the correlation with semen parameters and histology findings. METHODS: Male patients with monolateral left varicocele and progressive alteration of the semen quality were enrolled prospectively. Patients were evaluated before varicocelectomy, 3 and 6 months after surgery with semen analysis, ecocolordoppler US and SWE. In all patients, a left testicular biopsy was performed at the time of varicocelectomy and it was repeated after 6 months in 55% of patients in order to investigate the histological findings and to correlate with SWE results. RESULTS: The study was conducted on 82 patients. SWE showed a statistically significant difference between left and right testicles. Three months after surgery the mean left testicular volume increased, mean left SWE features decreased, and sperm count increased (P values < .0001). The SWE parameters, testicular volume and semen analysis values showed a statistically significant positive correlation between the pre and postoperative results (P value < .0001). The histological alterations were significantly changed 6 months postoperative with a complete morphology recovery in accordance with SWE results. CONCLUSIONS: SWE showed a statistically significant positive correlation with testicular volume, semen analysis and histological findings. This study represents the first investigation that correlates the varicocele, the testis volume, the quality of the seminal fluid ant the histological findings with the ultrasound and SWE values.


Assuntos
Técnicas de Imagem por Elasticidade , Varicocele , Humanos , Masculino , Estudos Prospectivos , Sêmen , Análise do Sêmen , Varicocele/diagnóstico por imagem , Varicocele/cirurgia
7.
Int J Mol Sci ; 22(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916025

RESUMO

Nucleophosmin (NPM), a nucleolar multifunctional phosphoprotein, acts as a stress sensor in different cell types. NPM can be actively secreted by inflammatory cells, however its biology on endothelium remains unexplored. In this study, we show for the first time that NPM is secreted by human vein endothelial cells (HUVEC) in the early response to serum deprivation and that NPM acts as a pro-inflammatory and angiogenic molecule both in vitro and in vivo. Accordingly, 24 h of serum starvation condition induced NPM relocalization from the nucleus to cytoplasm. Interestingly, NPM was increasingly excreted in HUVEC-derived conditioned media in a time dependent fashion upon stress conditions up to 24 h. The secretion of NPM was unrelated to cell necrosis within 24 h. The treatment with exogenous and recombinant NPM (rNPM) enhanced migration as well as the Intercellular Adhesion Molecule 1 (ICAM-1) but not Vascular cell adhesion protein 1 (VCAM-1) expression and it did not affect cell proliferation. Notably, in vitro tube formation by Matrigel assay was significantly increased in HUVEC treated with rNPM compared to controls. This result was confirmed by the in vivo injection of Matrigel plug assay upon stimulation with rNPM, displaying significant enhanced number of functional capillaries in the plugs. The stimulation with rNPM in HUVEC was also associated to the increased expression of master genes regulating angiogenesis and migration, including Vascular Endothelial Growth Factor-A (VEGF-A), Hepatocyte Growth Factor (HGF), Stromal derived factor-1 (SDF-1), Fibroblast growth factor-2 (FGF-2), Platelet Derived Growth Factor-B (PDGF-B), and Matrix metallopeptidase 9 (MMP9). Our study demonstrates for the first time that NPM is physiologically secreted by somatic cells under stress condition and in the absence of cell necrosis. The analysis of the biological effects induced by NPM mainly related to a pro-angiogenic and inflammatory activity might suggest an important autocrine/paracrine role for NPM in the regulation of both phenomena.


Assuntos
Células Endoteliais/fisiologia , Neovascularização Patológica , Proteínas Nucleares/metabolismo , Estresse Fisiológico , Células Endoteliais da Veia Umbilical Humana , Humanos , Nucleofosmina
8.
Eur Spine J ; 29(6): 1410-1415, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32300951

RESUMO

PURPOSE: Degenerative disc disease (DDD) is a common condition causing low-back pain, disability and, eventually, neurological symptoms. This investigation aimed to investigate intervertebral disc DDD-related changes, evaluating histomorphology and cytokines secretion, and their clinical-radiological correlations. METHODS: This is a monocentric prospective observational study. A cohort of patients who underwent microdiscectomy for DDD, from June 2018 to January 2019, were enrolled. Discs samples were examined for histomorphology, chondrons count, immunohistochemistry for Hif-1α, Nf200 and Egr-1. Demographical and clinical data were also collected. RESULTS: Twenty patients were finally included. MRI evaluation showed a Modic I alteration in nine patients and a Modic II in 11. The disability grade was low-moderate (ODI score was ≤ 40%) in eight patients and high (ODI score > 40%) in 12. The Modic I was associated with a low-moderate disability in two (22%) patients and to a high disability in seven (88%) (p < 0.01). In Modic I group and in ODI > 40% groups, there were a significative higher mean disability grade 48.4 (± 8.3)%, number of chondrons per section, cells per chondron, Nf200+ nerve fibers and Hif-1α expression, compared with Modic II and ODI ≤ 40% groups, respectively. There were no differences in terms of Egr-1 expression. CONCLUSIONS: The discs with Modic I MRI signal could represent potential targets for medical treatments, whereas Modic II seems to be a more likely point of no return in a degenerative process. Therefore, further investigations are to better investigate inflammatory pathways and degenerative mechanisms in DDD.


Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Disco Intervertebral , Discotomia , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Estudos Prospectivos
9.
J Cell Physiol ; 233(9): 6866-6877, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29319175

RESUMO

Glioblastoma (GBM) cells express large-conductance, calcium-activated potassium (BK) channels, whose activity is important for several critical aspects of the tumor, such as migration/invasion and cell death. GBMs are also characterized by a heavy hypoxic microenvironment that exacerbates tumor aggressiveness. Since hypoxia modulates the activity of BK channels in many tissues, we hypothesized that a hypoxia-induced modulation of these channels may contribute to the hypoxia-induced GBM aggressiveness. In U87-MG cells, hypoxia induced a functional upregulation of BK channel activity, without interfering with their plasma membrane expression. Wound healing and transwell migration assays showed that hypoxia increased the migratory ability of U87-MG cells, an effect that could be prevented by BK channel inhibition. Toxicological experiments showed that hypoxia was able to induce chemoresistance to cisplatin in U87-MG cells and that the inhibition of BK channels prevented the hypoxia-induced chemoresistance. Clonogenic assays showed that BK channels are also used to increase the clonogenic ability of U87-MG GBM cells in presence, but not in absence, of cisplatin. BK channels were also found to be essential for the hypoxia-induced de-differentiation of GBM cells. Finally, using immunohistochemical analysis, we highlighted the presence of BK channels in hypoxic areas of human GBM tissues, suggesting that our findings may have physiopathological relevance in vivo. In conclusion, our data show that BK channels promote several aspects of the aggressive potential of GBM cells induced by hypoxia, such as migration and chemoresistance to cisplatin, suggesting it as a potential therapeutic target in the treatment of GBM.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Hipóxia/patologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/antagonistas & inibidores , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Hipóxia/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
10.
J Cell Physiol ; 233(8): 5823-5828, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29230805

RESUMO

Aim of the study was to evaluate USPIO labeling in different macrophage populations using a clinical 3.0T MR unit with optical and electron microscopy as the gold standard. Human monocytic cell line THP-1 cells were differentiated into macrophages. Afterwards, M0 macrophages were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). These groups were incubated with USPIO-MR contrast agent (P904) for 36 hr; M0, M0 + P904, M1 + P904, and M2 + P904 were analyzed in gel phantoms with a 3.0T MR scanner. m-RNA of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages. M2 + P904 showed a much higher T1 signal (p < 0.0001), a significantly lower (p < 0.0001) T2* signal, and significantly higher R* (p < 0.0001) compared to the other populations. Hystological analysis confirmed higher iron content in the M2-polarized population compared to both M1-polarized (p = 0.04) and M0-P904 (p = 0.003). Ultrastructure analysis demonstrated ubiquitous localization of P904 within the cellular compartments. Our results demonstrate that a selective USPIO-labeling of different macrophage populations can be detected in vitro using the 3.0T clinical scanner.


Assuntos
Rastreamento de Células/métodos , Meios de Contraste/farmacologia , Dextranos/farmacologia , Macrófagos/ultraestrutura , Imageamento por Ressonância Magnética/métodos , Coloração e Rotulagem/métodos , Diferenciação Celular , Linhagem Celular , Polaridade Celular/fisiologia , Humanos , Ativação de Macrófagos , Macrófagos/citologia , Nanopartículas de Magnetita , Microscopia Eletrônica/métodos , Monócitos/citologia
11.
Mol Cancer ; 16(1): 88, 2017 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-28486946

RESUMO

BACKGROUND: Thymoma and thymic carcinoma are the most frequent subtypes of thymic epithelial tumors (TETs). A relevant advance in TET management could derive from a deeper molecular characterization of these neoplasms. We previously identified a set of microRNA (miRNAs) differentially expressed in TETs and normal thymic tissues and among the most significantly deregulated we described the down-regulation of miR-145-5p in TET. Here we describe the mRNAs diversely regulated in TETs and analyze the correlation between these and the miRNAs previously identified, focusing in particular on miR-145-5p. Then, we examine the functional role of miR-145-5p in TETs and its epigenetic transcriptional regulation. METHODS: mRNAs expression profiling of a cohort of fresh frozen TETs and normal tissues was performed by microarray analysis. MiR-145-5p role in TETs was evaluated in vitro, modulating its expression in a Thymic Carcinoma (TC1889) cell line. Epigenetic transcriptional regulation of miR-145-5p was examined by treating the TC1889 cell line with the HDAC inhibitor Valproic Acid (VPA). RESULTS: Starting from the identification of a 69-gene signature of miR-145-5p putative target mRNAs, whose expression was inversely correlated to that of miR-145-5p, we followed the expression of some of them in vitro upon overexpression of miR-145-5p; we observed that this resulted in the down-regulation of the target genes, impacting on TETs cancerous phenotype. We also found that VPA treatment of TC1889 cells led to miR-145-5p up-regulation and concomitant down-regulation of miR-145-5p target genes and exhibited antitumor effects, as indicated by the induction of cell cycle arrest and by the reduction of cell viability, colony forming ability and migration capability. The importance of miR-145-5p up-regulation mediated by VPA is evidenced by the fact that hampering miR-145-5p activity by a LNA inhibitor reduced the impact of VPA treatment on cell viability and colony forming ability of TET cells. Finally, we observed that VPA was also able to enhance the response of TET cells to cisplatin and erlotinib. CONCLUSIONS: Altogether our results suggest that the epigenetic regulation of miR-145-5p expression, as well as the modulation of its functional targets, could be relevant players in tumor progression and treatment response in TETs.


Assuntos
Epigênese Genética , MicroRNAs/genética , Neoplasias Epiteliais e Glandulares/genética , Timoma/genética , Neoplasias do Timo/genética , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cloridrato de Erlotinib/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/patologia , RNA Mensageiro/genética , Timoma/tratamento farmacológico , Timoma/patologia , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/patologia
12.
World J Urol ; 35(10): 1595-1601, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28243790

RESUMO

OBJECTIVES: Monopolar transurethral resection of the prostate (TURP) is the gold standard surgical treatment for bothersome moderate to severe lower urinary tract symptoms (LUTS) secondary to benign prostate obstruction. The aim of the study is to compare monopolar versus bipolar TURP focusing on operative and functional outcomes, and evaluating complications with a long-term follow-up. METHODS: From January 2007 to July 2014, a total of 497 patients were randomized and prospectively scheduled to undergo bipolar (251) or monopolar (246) TURP. International prostate symptom score (IPSS), IPSS-Quality of life (QoL), post-void residual and maximum flow rate were assessed preoperatively and postoperatively at 3, 12, 24 and 36 months. Operative time, length of catheterization and hospitalization were all recorded. Complications were classified and reported. RESULTS: All patients completed the 36-month follow-up visit. Perioperative results showed no statistical significance between the two groups in terms of catheterization days, post-void residual, IPSS, IPSS-QoL score. The hospitalization length was found statistically significant in favor of the bipolar group. The 3-, 12-, 24- and 36-month follow-up showed significant and equal improvements in LUTS related to BPO in the two treatment groups. Regarding TURP complications, significant differences were observed in relation to urethral strictures, blood transfusion and TUR syndrome in favor of the bipolar group. CONCLUSIONS: Monopolar and bipolar TURP are safe and effective techniques for BPH management. Bipolar TURP in our prospective study reported the same efficacy of monopolar prostate resection, with a significant reduction of related complications.


Assuntos
Complicações Pós-Operatórias , Próstata , Ressecção Transuretral da Próstata , Obstrução Uretral , Idoso , Hospitalização/estatística & dados numéricos , Humanos , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Tamanho do Órgão , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/psicologia , Próstata/patologia , Próstata/cirurgia , Hiperplasia Prostática/patologia , Hiperplasia Prostática/fisiopatologia , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Avaliação de Sintomas , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Resultado do Tratamento , Obstrução Uretral/diagnóstico , Obstrução Uretral/etiologia
14.
J Comput Assist Tomogr ; 40(5): 740-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27224230

RESUMO

OBJECTIVE: The aim of the study was to assess the diagnostic value of computed tomography perfusion (CTp) of prostate in distinguishing between normal tissue and malignant lesion by using quantitative threshold values of CTp parameters. MATERIALS AND METHODS: Sixty-one consecutive men with indication for radical prostatectomy were prospectively enrolled. All patients were intravenously injected with 80-mL bolus of nonionic iodinated contrast medium during cine-mode acquisition protocol. Perfusion data sets were analyzed by a dedicated software system and values for each of the 4 CTp parameters (blood volume, blood flow, mean transit time, and permeability surface-area product measurements) were recorded. Receiver operating characteristic curves were calculated to find which CTp parameter and which cutoff value might reveal the best diagnostic accuracy. Histopathology was used as reference standard. RESULTS: Statistical correlation between radiological and pathological results was performed on 48 patients using 3456 segmented squares. Blood volume and permeability surface revealed the best diagnostic accuracy for differentiating between malignant and benign squares, with cutoff values of 6.1 and 16.5, respectively, and a sensitivity of 84.8% and 81.8%, respectively. All parameters showed also a high negative predictive value: 97.1% for blood volume and 95.4% for permeability surface. CONCLUSIONS: Blood volume and permeability surface are the 2 CTp parameters with the highest diagnostic accuracy in differentiating between normal tissue and prostatic neoplasia. Due to the extremely high negative predictive value, they are particularly valuable in excluding the presence of cancer and thus resulting potentially useful in assessing cancer response to adjuvant therapy.


Assuntos
Velocidade do Fluxo Sanguíneo , Volume Sanguíneo , Angiografia por Tomografia Computadorizada/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/fisiopatologia , Simulação por Computador , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Knee Surg Sports Traumatol Arthrosc ; 24(12): 3779-3786, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26003482

RESUMO

PURPOSE: To evaluate a possible association of shoulder pain with the clinical features and the histopathological changes occurring in the ruptured tendon and subacromial bursa of patients with rotator cuff tear. METHODS: One hundred and eighty patients were clinically evaluated with the constant score and the visual analogue pain scale. Radiographs and MRI were performed. The chronology of the rupture, the muscle fatty degeneration according to Goutallier's scale and the tear size were evaluated. For each patient, a biopsy of the supraspinatus tendon and subacromial bursa was performed during arthroscopic rotator cuff tear repair and the specimens were histopathologically analysed. RESULTS: Clinically, the shoulder was more painful in females, in the presence of a chronic cuff lesion and a low Goutallier's grade (P < 0.05). No association was found between pain and age of the patient and between pain and tear size. Histologically, hypertrophy and inflammation of the tendon and hypertrophy, inflammation, oedema and necrosis of the subacromial bursa were directly associated with pain (P < 0.05). Pain decreased significantly in the presence of fatty metaplasia and necrosis of the tendon (P < 0.05). CONCLUSIONS: This study defines the main clinical and histopathological features of painful rotator cuff tear. In particular, a greater association of pain was observed with the histopathological changes in the bursa compared with those in the rotator cuff. Considering that the bursa plays also an essential role during the healing process, this "new" role of the subacromial bursa as pain generator has important repercussions in both pharmacological and surgical treatments of rotator cuff tears. LEVEL OF EVIDENCE: IV.


Assuntos
Bolsa Sinovial/diagnóstico por imagem , Lesões do Manguito Rotador/diagnóstico por imagem , Dor de Ombro/diagnóstico por imagem , Traumatismos dos Tendões/diagnóstico por imagem , Idoso , Bolsa Sinovial/patologia , Bolsa Sinovial/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Medição da Dor , Radiografia , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/patologia , Manguito Rotador/fisiopatologia , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/patologia , Lesões do Manguito Rotador/fisiopatologia , Dor de Ombro/etiologia , Dor de Ombro/patologia , Dor de Ombro/fisiopatologia , Traumatismos dos Tendões/complicações , Traumatismos dos Tendões/patologia , Traumatismos dos Tendões/fisiopatologia , Tendões/diagnóstico por imagem , Tendões/patologia , Tendões/fisiopatologia
16.
BMC Cancer ; 15: 120, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25877676

RESUMO

BACKGROUND: This study aimed to evaluate the behavior of non-muscle-invasive bladder cancer (NMIBC) in patients submitted to transurethral bladder resection (TURB) comparing subjects in chronic therapy with aspirin, statins, or both drugs to untreated ones. METHODS: This retrospective study was conducted on 574 patients diagnosed with NMIBC who underwent TURB between March 2008 and April 2013. The study population was divided into two main groups: treated (aspirin and/or statins) and untreated. The treated group was further divided into three therapeutic subgroups: Group A (100 mg of aspirin, daily for at least two years); Group B (20 mg or more of statins, daily for at least two years); and Group C (100 mg of aspirin and 20 mg of statins together). The mean follow-up of patients was 45.06 months. RESULTS: No significant differences were observed among the different groups at baseline. On multivariate analysis, statin treatment, smokers and high stage disease (T1) achieved the level of independent risk factor for the occurrence of a recurrence. When patients were stratified according to the different treatment; patients treated with statins (Group B) presented an higher rate of failure (56/91 patients; 61.5%) when compared to Group A (42/98 patients; 42.9%), Group C (56/98; 57.1%) and (133/287 patients; 46.3%). This difference corresponds to a significant difference in recurrence failure free survival (p = 0.01). CONCLUSIONS: Our results suggest that long-term treatment with aspirin in patients with NMIBC might play a role on reducing the risk of tumor recurrence. In contrast, in our investigation data from statins and combination treatment groups showed increased recurrence rates. A long-term randomized prospective study could definitively assess the possible role of this widely used drugs in NMIBC.


Assuntos
Aspirina/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia
19.
World J Surg ; 39(8): 1936-42, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25862025

RESUMO

INTRODUCTION: Parathyroid autotransplantation plays an important role in preventing hypoparathyroidism following thyroidectomy. The preferred reimplantation site is still the sternocleidomastoid muscle, but this approach does not permit to check graft vitality postoperatively. The authors report the first prospective evaluation of normal parathyroid gland reimplantation in forearm subcutaneous tissue (using the same technique proposed during parathyroidectomy for hyperplasia) in case of devascularized or inadvertently removed glands during thyroid surgery. MATERIALS AND METHODS: From January 2013 to August 2014, we performed 348 consecutive thyroidectomies for various disease, both benign and malignant. In 25 cases, due to inadvertent parathyroid removal or evidence of insufficient blood supply, we removed and fragmented the gland into 0.5-1 mm slices (one for frozen section) and reimplanted it into two subcutaneous pockets on the non-dominant forearm. After surgery we checked grafted gland function by evaluation of serum parathormone gradient between reimplanted versus non-reimplanted arm (considering significant a ratio of 1.5 or more), at 1 week, 1 and 3 months after surgery. RESULTS: We observed recovery of reimplanted graft function in 48, 88 and 96% of patients respectively at 1 week, 1 and 3 months after surgery. All patients showed normal parathormone levels in peripheral blood (non-reimplanted arm). In one case we observed post-operative wound hematoma on graft-site. This patient showed no graft functionality in post-operative period (even at 3 months follow-up). CONCLUSIONS: Parathyroid gland reimplantation in forearm subcutaneous tissue during thyroid surgery is a safe, easy and effective procedure; furthermore, it allows a good control of graft functionality and would allow an easy grafted gland removal if needed.


Assuntos
Hipoparatireoidismo/prevenção & controle , Glândulas Paratireoides/transplante , Tireoidectomia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Antebraço/cirurgia , Humanos , Hipoparatireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/fisiologia , Hormônio Paratireóideo/sangue , Estudos Prospectivos , Tela Subcutânea/cirurgia , Tireoidectomia/métodos , Transplante Autólogo/métodos , Adulto Jovem
20.
Int J Urol ; 22(11): 1037-42, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26177871

RESUMO

OBJECTIVES: To explore the surgical, oncological and functional outcomes of laparoscopic radical prostatectomy in patients who have undergone transurethral resection of the prostate, using a catheter balloon inflated in the prostatic urethra. METHODS: A total of 25 patients were randomly assigned to the no balloon previous transurethral resection of the prostate laparoscopic radical prostatectomy group (n = 12) and the with balloon previous transurethral resection of the prostate laparoscopic radical prostatectomy group (n = 13). Two matched pairs analyses were carried out to identify the 12 (control A) and 13 (control B) surgery-naïve patients. The outcomes were compared between the groups with previous transurethral resection of the prostate (no balloon previous transurethral resection of the prostate laparoscopic radical prostatectomy and with balloon previous transurethral resection of the prostate laparoscopic radical prostatectomy groups) and the controls. The rate of intra- and postoperative complications was assessed. The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the International Index of Erectile Function 5 were used for symptoms evaluation. RESULTS: The mean blood loss was higher in patients submitted to transurethral resection of the prostate, with statistically insignificant reduced blood loss in the with balloon previous transurethral resection of the prostate laparoscopic radical prostatectomy group. The no balloon previous transurethral resection of the prostate laparoscopic radical prostatectomy group had longer operative time compared with both the with balloon previous transurethral resection of the prostate laparoscopic radical prostatectomy and control A groups (P < 0.05). International Index of Erectile Function 5 showed a significant difference between no balloon previous transurethral resection of the prostate laparoscopic radical prostatectomy and its control group; the International Consultation on Incontinence Questionnaire showed a statistically significant difference (P < 0.05) between the no balloon previous transurethral resection of the prostate laparoscopic radical prostatectomy and control A groups. CONCLUSION: The use of a catheter balloon inflated in the prostatic urethra seems to facilitate laparoscopic radical prostatectomy in patients with previous transurethral resection of the prostate, ultimately reducing the rate of perioperative complications. These findings warrant further investigation on a larger case series with a longer follow up.


Assuntos
Laparoscopia , Complicações Pós-Operatórias , Prostatectomia , Neoplasias da Próstata/cirurgia , Reoperação , Ressecção Transuretral da Próstata , Idoso , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Duração da Cirurgia , Hemorragia Pós-Operatória , Próstata/cirurgia , Glândulas Seminais/cirurgia , Inquéritos e Questionários , Resultado do Tratamento , Uretra/cirurgia
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