RESUMO
Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina , Imuno-Histoquímica , Mesotelioma , Neoplasias Pleurais , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amiantos Anfibólicos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Deleção de Genes , Homozigoto , Mesotelioma/genética , Mesotelioma/patologia , Mesotelioma/induzido quimicamente , Mesotelioma/metabolismo , Mesotelioma Maligno/patologia , Mesotelioma Maligno/genética , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Neoplasias Pleurais/induzido quimicamente , Neoplasias Pleurais/metabolismo , Purina-Núcleosídeo Fosforilase/genéticaRESUMO
This paper introduces a self-attention Vision Transformer model specifically developed for classifying breast cancer in histology images. We examine various training strategies and configurations, including pretraining, dimension resizing, data augmentation and color normalization strategies, patch overlap, and patch size configurations, in order to evaluate their impact on the effectiveness of the histology image classification. Additionally, we provide evidence for the increase in effectiveness gathered through geometric and color data augmentation techniques. We primarily utilize the BACH dataset to train and validate our methods and models, but we also test them on two additional datasets, BRACS and AIDPATH, to verify their generalization capabilities. Our model, developed from a transformer pretrained on ImageNet, achieves an accuracy rate of 0.91 on the BACH dataset, 0.74 on the BRACS dataset, and 0.92 on the AIDPATH dataset. Using a model based on the prostate small and prostate medium HistoEncoder models, we achieve accuracy rates of 0.89 and 0.86, respectively. Our results suggest that pretraining on large-scale general datasets like ImageNet is advantageous. We also show the potential benefits of using domain-specific pretraining datasets, such as extensive histopathological image collections as in HistoEncoder, though not yet with clear advantages.
RESUMO
Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.
Assuntos
Mesotelioma , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Neoplasias Pleurais , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Humanos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Masculino , Mesotelioma/metabolismo , Mesotelioma/patologia , Mesotelioma/induzido quimicamente , Pessoa de Meia-Idade , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Feminino , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Neoplasias Pleurais/induzido quimicamente , Idoso , Amiantos Anfibólicos/toxicidade , Mesotelioma Maligno/metabolismo , Mesotelioma Maligno/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/induzido quimicamente , Imuno-Histoquímica , Biomarcadores Tumorais/metabolismoRESUMO
Advancements in cutting-edge molecular profiling techniques, such as next-generation sequencing and bioinformatic analytic tools, have allowed researchers to examine tumour biology in detail and stratify patients based on factors linked with clinical outcome and response to therapy. This manuscript highlights the most relevant prognostic and predictive biomarkers in kidney, bladder, prostate and testicular cancers with recognised impact in clinical practice. In bladder and prostate cancer, new genetic acquisitions concerning the biology of tumours have modified the therapeutic scenario and led to the approval of target directed therapies, increasing the quality of patient care. Thus, it has become of paramount importance to choose adequate molecular tests, i.e., FGFR screening for urothelial cancer and BRCA1-2 alterations for prostate cancer, to guide the treatment plan for patients. While no tissue or blood-based biomarkers are currently used in routine clinical practice for renal cell carcinoma and testicular cancers, the field is quickly expanding. In kidney tumours, gene expression signatures might be the key to identify patients who will respond better to immunotherapy or anti-angiogenic drugs. In testicular germ cell tumours, the use of microRNA has outperformed conventional serum biomarkers in the diagnosis of primary tumours, prediction of chemoresistance, follow-up monitoring, and relapse prediction.
Assuntos
Neoplasias Renais , Neoplasias da Próstata , Neoplasias Testiculares , Neoplasias Urológicas , Masculino , Humanos , Prognóstico , Recidiva Local de Neoplasia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Biomarcadores , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/genética , Biomarcadores Tumorais/genéticaRESUMO
Exposure to asbestiform fibers, including chrysotile and amphibole, is carcinogenic, causing malignant pleural mesothelioma (MPM) when inhaled. Some populations globally face Naturally Occurring Asbestos (NOA) exposure, leading to MPM cases like in Biancavilla, Italy, from Fluoro-edenite (FE) contamination. Studies show NOA exposure causes epigenetic changes, focusing on mesothelin methylation, an MPM marker, and altered inflammation, emphasizing the health risks of FE and asbestos. This research, conducted from February 2022 to October 2022, studied 125 construction workers from Biancavilla and 125 controls from 40 km away without Biancavilla work history. With at least ten years in construction and no respiratory conditions, participants underwent medical assessments and gave blood samples for analysis, including inflammation markers, mesothelin methylation, and soluble mesothelin-related protein levels. The results showed similar demographics but differing inflammation and methylation levels in exposed workers, suggesting long-term cellular changes. Pearson correlation showed intricate biomarker relationships. Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.
RESUMO
Primary Sjögren's syndrome (pSS) is a chronic, systemic, inflammatory autoimmune disease characterised by lymphocyte proliferation and progressive damage to exocrine glands. Salivary gland histopathology based on salivary gland biopsy is relevant for the diagnosis of pSS and therefore broadly applied in clinical practice. Tissue can be obtained from labial salivary glands (LSG) biopsy or from major salivary glands (MSG) biopsy, namely the parotid; in this latter scenario, the procedure can be either an open surgical biopsy or a US guided core needle biopsy.In this review we will: i) present the histopathological findings that may be encountered by pathologists on biopsies from pSS patients; ii) discuss the advantages and disadvantages of the surgical and/or imaging guided procedures to obtain tissues from LSG or MSG; iii) describe the histopathological features of lymphoma of MSG in pSS patients.
Assuntos
Linfoma , Síndrome de Sjogren , Humanos , Glândulas Salivares , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Glândulas Salivares Menores/patologia , Linfoma/patologia , BiópsiaRESUMO
OBJECTIVES: The aim of the study was to culture vital salivary gland organoids obtained through labial or parotid biopsy of primary Sjögren's syndrome (pSS) patients in order to evaluate their morphological and functional features in basal condition and after stimulation with Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activator forskolin and phosphodiesterase 4 (PDE4) inhibitor apremilast, their in vitro regenerative capacity and the immune-histological resemblance with original tissue. METHODS: Salivary gland tissues from five pSS patients were processed to obtain vital organoids; swelling assay and cell proliferation tests were performed after forskolin and apremilast application. Immunochemistry evaluation on original salivary gland tissue and corresponding organoids was performed, and secretomics analysis was conducted to assess their functional status. REULTS: After application of forskolin and apremilast, we observed organoid swelling after 30 minutes, compatible with a positive functional status and enhancement of saliva production. In 3 cases, apremilast induced organoid proliferation. All cases were positive for cytokeratin 14 (CK14) and most for cytokeratin 5 (CK5). All the cases were positive for amylase; its secretion, and thus functional status of organoids, was confirmed by its high concentration in the culture medium. A focal ductal differentiation was found in some cases, highlighted by epithelial membrane antigen (EMA) positivity. The more differentiated EMA positive areas were negative for the staminal marker CK14, showing a sort of "complementary staining". CONCLUSIONS: Our data highlighted that differentiated cells and vital functional organoids that recapitulate the development of original salivary glands can be obtained from pSS epithelium. For the first time, the direct stimulating effect of PDE4 inhibitor apremilast on pSS human salivary gland organoids is reported, opening new perspectives on targeting oral dryness with drugs that combine secretagogue and immunomodulatory effects.
Assuntos
Inibidores da Fosfodiesterase 4 , Síndrome de Sjogren , Humanos , Inibidores da Fosfodiesterase 4/farmacologia , Secretagogos , Colforsina , Glândulas Salivares , Organoides/metabolismo , Organoides/patologiaRESUMO
BACKGROUND: Mesothelioma is strongly associated with exposure to asbestos fibers, however, recent studies have also linked exposure to "naturally occurring asbestos" fibers with this disease. Fluoro-edenite, a silicate mineral found in the southeast of Biancavilla (Sicily, Italy), has been identified as a potential risk factor for mesothelioma. Unfortunately, this cancer often has a poor prognosis, and current diagnostic and prognostic biomarkers are inadequate. Histological subtype, gender, and age at diagnosis are the most significant parameters for mesothelioma. Stathmin, a cytosolic protein that regulates cell growth and migration and is overexpressed in many human malignancies, has not yet been linked to mesothelioma survival or clinical-pathological variables. AIM: The aim of this study was to investigate the immunohistochemical expression of stathmin in ten mesothelioma tissue samples with available clinical and follow-up data. MATERIAL AND METHODS: Paraffin-embedded tissue samples from ten mesothelioma patients were processed for immunohistochemical analyses to evaluate stathmin expression. RESULTS: Our findings suggest that stathmin overexpression is associated with shorter overall survival in patients with mesothelioma. Furthermore, stathmin expression was significantly correlated with the survival time of mesothelioma patients. CONCLUSION: Our results suggest that stathmin expression may serve as a potential prognostic biomarker for mesothelioma. This biomarker could be used to promptly identify patients with poor prognosis and to guide clinicians in the selection of treatment options.
Assuntos
Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Humanos , Amianto/toxicidade , Amianto/análise , Biomarcadores/análise , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/metabolismo , Sicília , EstatminaRESUMO
BACKGROUND: Glioma grade 4 (GG4) tumors, including astrocytoma IDH-mutant grade 4 and the astrocytoma IDH wt are the most common and aggressive primary tumors of the central nervous system. Surgery followed by Stupp protocol still remains the first-line treatment in GG4 tumors. Although Stupp combination can prolong survival, prognosis of treated adult patients with GG4 still remains unfavorable. The introduction of innovative multi-parametric prognostic models may allow refinement of prognosis of these patients. Here, Machine Learning (ML) was applied to investigate the contribution in predicting overall survival (OS) of different available data (e.g. clinical data, radiological data, or panel-based sequencing data such as presence of somatic mutations and amplification) in a mono-institutional GG4 cohort. METHODS: By next-generation sequencing, using a panel of 523 genes, we performed analysis of copy number variations and of types and distribution of nonsynonymous mutations in 102 cases including 39 carmustine wafer (CW) treated cases. We also calculated tumor mutational burden (TMB). ML was applied using eXtreme Gradient Boosting for survival (XGBoost-Surv) to integrate clinical and radiological information with genomic data. RESULTS: By ML modeling (concordance (c)- index = 0.682 for the best model), the role of predicting OS of radiological parameters including extent of resection, preoperative volume and residual volume was confirmed. An association between CW application and longer OS was also showed. Regarding gene mutations, a role in predicting OS was defined for mutations of BRAF and of other genes involved in the PI3K-AKT-mTOR signaling pathway. Moreover, an association between high TMB and shorter OS was suggested. Consistently, when a cutoff of 1.7 mutations/megabase was applied, cases with higher TMB showed significantly shorter OS than cases with lower TMB. CONCLUSIONS: The contribution of tumor volumetric data, somatic gene mutations and TBM in predicting OS of GG4 patients was defined by ML modeling.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Adulto , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Variações do Número de Cópias de DNA/genética , Fosfatidilinositol 3-Quinases/genética , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/cirurgia , Prognóstico , Biomarcadores Tumorais/genética , Genômica , Mutação/genéticaRESUMO
Despite advances in understanding of the biology of malignant pleural mesothelioma (MPM), the prognosis of this malignancy remains poor. Although asbestos still remains the main pathogenic agent of MPM, other asbestoslike fibers such as fluoroedenite (FE) fibers, induce MPM. Notable incidence and mortality rates of MPM have been found in Biancavilla, Italy, where FE fibers have been extracted from building materials for >50 years. Cyclic adenosine monophosphate (cAMP) is a secondary messenger that plays a key role in several physiological and pathological mechanisms regulating protein kinase A (PKA) and the CREB pathway. Hyperactivation of the cAMP/PKA/CREB pathway is involved in many neoplastic processes, including tumor cell proliferation, invasion and metastatic spread. The present study investigated immunohistochemical expression of cAMP in patients with FEinduced MPM, which included six males and four females with an age range of 5093 years. There was high immunoexpression of cAMP in 5 out of 10 tumors while the remaining 5 cases showed low immunoexpression. In addition, there was a correlation between cAMP overexpression and decreased survival times (mean overall survival times, 7.5 months in high expression group vs. 18 months in low expression group).
Assuntos
Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Mesotelioma/induzido quimicamente , Mesotelioma/metabolismo , Neoplasias Pulmonares/patologiaRESUMO
PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen, first isolated in tumor-reactive T-cell clones from a metastatic melanoma patient. It has been widely studied in skin pathology as an immunohistochemical marker capable of distinguishing between benign nevi and malignant melanomas. PRAME has been found to be also expressed in non-melanocytic tumors, including lung, breast, kidney and ovarian cancer. However, less is known about the diagnostic and/or prognostic role of this protein in uveal melanoma (UM); few studies have reported that PRAME expression seems to give to UM patients an additional metastatic risk beyond the other already-known prognostic parameters. In the present retrospective study, we aimed to correlate PRAME immunoreactivity to other clinico-pathologic features and follow-up data on a large series of 85 cases (45 non-metastasizing and 40 metastasizing tumors) of primary UM. A statistically significant correlation was found between PRAME expression and higher metastatic risk and lower metastasis-free survival. We propose to include PRAME in the immunohistochemical panel of UM as an easily usable marker capable of predicting higher metastatic risk and stratifying patients' outcome.
Assuntos
Melanoma , Neoplasias Cutâneas , Masculino , Humanos , Estudos Retrospectivos , Antígenos de Neoplasias/metabolismo , Melanoma/patologia , Prognóstico , Fatores de Transcrição , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Val804Met RET is one of the most common genetic alterations in Multiple Endocrine Neoplasia 2 and is considered to confer only a moderate risk for familial medullary thyroid carcinoma (MTC). The associated phenotype can however be much more complex in some cases. METHODS: A clinical, genetic, and pathological analysis was conducted on a family cluster of thyroid neoplasms associated with Val804Met RET mutation. RESULTS: All the kindreds who are carriers of the mutated RET received total thyroidectomy + /- VI level dissection. The proband presented with a pT1bN0 MTC, her 29-yo brother showed a concomitant papillary thyroid carcinoma (PTC) and MTC, their father had a pT1a PTC plus a follicular adenoma, while the uncle of the proband showed C-cell hyperplasia. None had clinical or biochemical evidence of parathyroid disorders or pheochromocytoma. CONCLUSIONS: In the presence of Val804Met RET several types of thyroid premalignant and malignant should be screened for, and without limiting to MTC.
Assuntos
Neoplasias das Glândulas Suprarrenais , Neoplasia Endócrina Múltipla Tipo 2a , Neoplasias da Glândula Tireoide , Masculino , Feminino , Humanos , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasia Endócrina Múltipla Tipo 2a/genética , Neoplasia Endócrina Múltipla Tipo 2a/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Mutação/genéticaRESUMO
Environmental exposure to fibers of respirable size has been identified as a risk for public health. Experimental evidence has revealed that a variety of fibers, including fluoro-edenite, can develop chronic respiratory diseases and elicit carcinogenic effects in humans. Fluoro-edenite (FE) is a silicate mineral first found in Biancavilla (Sicily, Italy) in 1997. Environmental exposure to its fibers has been correlated with a cluster of malignant pleural mesotheliomas. This neoplasm represents a public health problem due to its long latency and to its aggression not alerted by specific symptoms. Having several biomarkers providing us with data on the health state of those exposed to FE fibers or allowing an early diagnosis on malignant pleural mesothelioma, still asymptomatic patients, would be a remarkable goal. To these purposes, we reported the miRNA transcriptome in human normal mesothelial cell line (MeT-5A) and in the human malignant mesothelioma cell line (JU77) exposed and not exposed to FE fibers. The results showed a difference in the number of deregulated miRNAs between tumor and nontumor samples both exposed and not exposed to FE fibers. As a matter of fact, the effect of exposure to FE fibers is more evident in the expression of miRNA in the tumor samples than in the nontumor samples. In the present paper, several pathways involved in the pathogenesis of malignant pleural mesothelioma have been analyzed. We especially noticed the involvement of pathways that have important functions in inflammatory processes, angiogenesis, apoptosis, and necrosis. Besides this amount of data, further studies will be designed for the selection of the most significant miRNAs to test and validate their diagnostic potential, alone or in combination with other protein biomarkers, in high-risk individuals' liquid biopsy to have a noninvasive tool of diagnosis for this neoplasm.
RESUMO
OBJECTIVES: The diagnosis and classification of primary Sjögren's syndrome (pSS) relies on labial biopsy, whereas the role of open parotid biopsy is mainly reserved to evaluate the lymphoproliferative complications. Recently ultrasound-guided core needle biopsy (US-guided CNB) appeared as a novel and safe technique useful in lymphoma assessment, however, its potential role in the diagnosis of pSS has never been assessed.The main aim of this study was to evaluate the diagnostic value of US-guided CNB of the parotid glands in patients affected by pSS. METHODS: Patients affected by pSS who underwent US-guided CNB for a suspected glandular lymphoma were included. Adequacy of the samples and histopathological features related to pSS were analysed. RESULTS: US-guided CNB was performed on 29 parotid glands. The biopsied samples were adequate for diagnosis in 28/29 (96.5%) cases. Fifteen patients showed pathologic features of parotid lymphoma. Among the remaining patients, 9/13 presented focus score≥1; LELs were present in 8/13 patients, and GCs in 11/13. In 8 cases the histological features were coherent with MESA/LESA. Acinar atrophy, fibrosis and duct dilatation were also evaluated. CONCLUSIONS: This preliminary study suggests the possible usefulness of US-guided CNB for the diagnosis of pSS by enabling the collection of adequate salivary gland tissue to assess the FS, GCs, LELs, and other histopathologic features also useful in the management of pSS patients.
Assuntos
Linfoma , Neoplasias Parotídeas , Síndrome de Sjogren , Humanos , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Síndrome de Sjogren/diagnóstico por imagem , Síndrome de Sjogren/patologia , Biópsia com Agulha de Grande Calibre , Linfoma/diagnóstico por imagem , Linfoma/patologia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Biópsia , Ultrassonografia de IntervençãoRESUMO
Despite the state-of-the-art treatment, patients diagnosed with glioblastoma (GBM) have a median overall survival (OS) of 14 months. The insertion of carmustine wafers (CWs) into the resection cavity as adjuvant treatment represents a promising option, although its use has been limited due to contrasting clinical results. Our retrospective evaluation of CW efficacy showed a significant improvement in terms of OS in a subgroup of patients. Given the crucial role of the tumor microenvironment (TME) in GBM progression and response to therapy, we hypothesized that the TME of patients who benefited from CW could have different properties compared to that of patients who did not show any advantage. Using an in vitro model of the glioma microenvironment, represented by glioma-associated-stem cells (GASC), we performed a transcriptomic analysis of GASC isolated from tumors of patients responsive and not responsive to CW to identify differentially expressed genes. We found different transcriptomic profiles, and we identified four genes, specifically down-regulated in GASC isolated from long-term survivors, correlated with clinical data deposited in the TCGA-GBM dataset. Our results highlight that studying the in vitro properties of patient-specific glioma microenvironments can help to identify molecular determinants potentially prognostic for patients treated with CW.
RESUMO
Experimental evidence demonstrated that fluoro-edenite (FE) can develop chronic respiratory diseases and elicit carcinogenic effects. Environmental exposure to FE fibers is correlated with malignant pleural mesothelioma (MPM). An early diagnosis of MPM, and a comprehensive health monitoring of the patients exposed to FE fibers are two clinical issues that may be solved by the identification of specific biomarkers. We reported the microRNA (miRNA) and transfer RNA-derived non coding RNA (tRNA-derived ncRNA) transcriptome in human normal mesothelial and malignant mesothelioma cell lines exposed or not exposed to several concentration FE fibers. Furthermore, an interactive mesothelioma-based network was derived by using NetME tool. In untreated condition, the expression of miRNAs and tRNA-derived ncRNAs in tumor cells was significantly different with respect to non-tumor samples. Moreover, interesting and significant changes were found after the exposure of both cells lines to FE fibers. The network-based pathway analysis showed several signaling and metabolic pathways potentially involved in the pathogenesis of MPM. From papers analyzed by NetME, it is clear that many miRNAs can positively or negatively influence various pathways involved in MPM. For the first time, the analysis of tRNA-derived ncRNAs molecules in the context of mesothelioma has been made by using in vitro systems. Further studies will be designed to test and validate their diagnostic potential in high-risk individuals' liquid biopsies.
Assuntos
Mesotelioma Maligno , Mesotelioma , MicroRNAs , Linhagem Celular , Fibras na Dieta , Humanos , Mesotelioma/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA de Transferência/genética , RNA não Traduzido/genéticaRESUMO
Nevoid basal cell carcinoma syndrome (NBCCS) associated odontogenic keratocysts (OKCs) show more aggressive behavior and it has a higher frequency of relapse than non-syndromic OKCs. Stromal myofibroblasts (MFs), characterized by α-smooth muscle actin (αSMA), desmin and caldesmon expression, and metalloproteinases (MMPs) have an essential role in the remodeling of the extracellular matrix (ECM). The aim of the study is to analyze the immunohistochemical expression of MMP-7, MMP-9, αSMA and other new markers in the study of OKCs MFs such as desmin and caldesmon in NBCCS-associated OKCs compared to recurrent and sporadic keratocysts. Fourty 40 patients (23 M and 17 F) underwent surgery to remove the OKCs. The histological sections in paraffin were incubated with markers antibodies and a semi-quantitative score was used to evaluate the immunoreactivity. Densitometric analysis showed a very significantly increased expression of αSMA, caldesmon, MMP-7 and MMP-9 in NBCCS-OKCs compared to non-syndromic OKCs (p < 0.001). However, desmin showed a not significant increased expression in non-syndromic OKC compared to NBCCS-OKCs specimens in which desmin was slightly or not at all expressed. NBCSS-OKCs showed a greater distribution of MFs compared to the other OKCs subtypes. Further studies will be needed to evaluate whether the different expressions of these markers can be correlated to a different clinical behavior.
Assuntos
Síndrome do Nevo Basocelular , Cistos Odontogênicos , Actinas/metabolismo , Síndrome do Nevo Basocelular/metabolismo , Síndrome do Nevo Basocelular/patologia , Proteínas de Ligação a Calmodulina , Desmina/metabolismo , Humanos , Metaloproteinase 7 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Músculo Liso/metabolismo , Cistos Odontogênicos/metabolismo , Cistos Odontogênicos/patologiaRESUMO
Background and Objectives: The type of instrumentation used during laparoscopic surgery might impact on the learning curve of resident surgeons. The aim of this study was to investigate differences in operator satisfaction and surgical outcomes between tissue sealers and classic bipolar instruments during gynecological laparoscopies performed by residents. Materials and Methods: A prospective cohort study conducted at two tertiary university hospitals between March 2019 and March 2021, on consecutive procedures: salpingo-oophorectomies (Group 1) and salpingectomies (Group 2), subdivided according to the utilized device: radiofrequency tissue sealers (Groups A1 and A2) or bipolar forceps (Groups B1 and B2). Results: 80 procedures were included. Concerning salpingo-oophorectomies, better visibility (8.4 ± 0.8 vs. 7.3 ± 0.9; p = 0.03), reduced difficulty (5.4 ± 1.2 vs. 7.0 ± 1.4; p = 0.02), improved overall satisfaction (9.2 ± 0.4 vs. 7.6 ± 1.0; p = 0.02) and reduced procedure time (7.8 ± 3.4 vs. 12.6 ± 3.1; p = 0.01) were reported by residents using tissue sealers. Intraoperative blood loss (12.2 ± 4.7 mL vs. 33.2 ± 9.7 mL; p = 0.01) and 24 h postoperative pain (4.5 ± 1.1 vs. 5.7 ± 1.8; p = 0.03) were lower in group A1 than B1. For salpingectomies, a significant reduction in duration was found in A2 compared to B2 (7.2 ± 3.4 min vs. 13.8 ± 2.2 min; p = 0.02). Tissue sealers enhanced visibility (8.1 ± 1.1 vs. 6.7 ± 1.4; p = 0.01), difficulty (6.5 ± 1.1 vs. 7.5 ± 0.9; p = 0.04) and improved satisfaction (9.3 ± 0.5 vs. 7.5 ± 0.6; p = 0.01). Moreover, hemoglobin loss and postoperative pain were reduced in A2 relative to B2 [(8.1 ± 4.2 % vs. 4.5 ± 1.1%; p = 0.02) and (5.1 ± 0.9 vs. 4.1 ± 0.8; p = 0.03), respectively] Conclusions: The use of sealing devices by residents was related to reduced difficulty as well improved visibility and overall satisfaction, with improved surgical outcomes.
Assuntos
Ginecologia , Laparoscopia , Obstetrícia , Humanos , Laparoscopia/efeitos adversos , Dor Pós-Operatória , Estudos ProspectivosRESUMO
Background and Objectives: Since the Food and Drug Administration's (FDA) approval in 2005, the application of robotic surgery (RS) in gynecology has been adopted all over the world. This study aimed to provide an update on RS in benign gynecological pathology by reporting the scientific recommendations and high-value scientific literature available to date. Materials and Methods: A systematic review of the literature was performed. Prospective randomized clinical trials (RCT) and large retrospective trials were included in the present review. Results: Twenty-two studies were considered eligible for the review: eight studies regarding robotic myomectomy, five studies on robotic hysterectomy, five studies about RS in endometriosis treatment, and four studies on robotic pelvic organ prolapse (POP) treatment. Overall, 12 RCT and 10 retrospective studies were included in the analysis. In total 269,728 patients were enrolled, 1721 in the myomectomy group, 265,100 in the hysterectomy group, 1527 in the endometriosis surgical treatment group, and 1380 patients received treatment for POP. Conclusions: Currently, a minimally invasive approach is suggested in benign gynecological pathologies. According to the available evidence, RS has comparable clinical outcomes compared to laparoscopy (LPS). RS allowed a growing number of patients to gain access to MIS and benefit from a minimally invasive treatment, due to a flattened learning curve and enhanced dexterity and visualization.