RESUMO
Primitive erythropoiesis serves a vital role in embryonic development, generating primitive red blood cells responsible for transportation of oxygen throughout the body. Although diverse niche factors are known to function in definitive hematopoiesis, the microenvironment contributing to primitive hematopoiesis remains largely elusive. Here, we report that platelet-derived growth factor (PDGF) signaling is required for erythroid progenitor differentiation in zebrafish. Ablating pdgfαa (also known as pdgfaa) and pdgfαb (also known as pdgfab) or blocking PDGF signaling with an inhibitor impairs erythroid progenitor differentiation, thus resulting in a significant decrease in the number of erythrocytes. We reveal that pdgfαb is expressed in sclerotomal cells, and that its receptor genes, pdgfra and pdgfrb, are expressed in the adjacent erythroid progenitor cells. Sclerotome-specific overexpression of pdgfαb effectively restores primitive erythropoiesis in pdgfαa-/-;pdgfαb-/- mutant embryos. In addition, we have defined ERK1/2 signaling as a downstream pathway of PDGF signaling during embryonic erythropoiesis. Taken together, our findings indicate that PDGF signaling derived from sclerotome functions as a niche cue for primitive erythropoiesis.
Assuntos
Eritropoese , Fator de Crescimento Derivado de Plaquetas , Animais , Eritropoese/genética , Peixe-Zebra , Sinais (Psicologia) , Diferenciação Celular/genética , Desenvolvimento EmbrionárioRESUMO
In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.
Assuntos
Dendritos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos , Bulbo Olfatório , Olfato , Animais , Feminino , Masculino , Camundongos , Dendritos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Microtúbulos/metabolismo , Morfogênese/genética , Bulbo Olfatório/metabolismo , Olfato/fisiologiaRESUMO
The manchette is a crucial transient structure involved in sperm development, with its composition and regulation still not fully understood. This study focused on investigating the roles of CAMSAP1 and CAMSAP2, microtubule (MT) minus-end binding proteins, in regulating manchette MTs, spermiogenesis, and male fertility. The loss of CAMSAP1, but not CAMSAP2, disrupts the well-orchestrated process of spermiogenesis, leading to abnormal manchette elongation and delayed removal, resulting in deformed sperm nuclei and tails resembling oligoasthenozoospermia symptoms. We investigated the underlying molecular mechanisms by purifying manchette assemblies and comparing them through proteomic analysis, and results showed that the absence of CAMSAP1 disrupted the proper localization of key proteins (CEP170 and KIF2A) at the manchette minus end, compromising its structural integrity and hindering MT depolymerization. These findings highlight the significance of maintaining homeostasis in manchette MT minus-ends for shaping manchette morphology during late spermiogenesis, offering insights into the molecular mechanisms underlying infertility and sperm abnormalities.
Assuntos
Proteômica , Sêmen , Humanos , Masculino , Espermatogênese/fisiologia , Microtúbulos/metabolismo , FertilidadeRESUMO
Natural Nicotinamide Adenine Dinucleotide (NAD+) precursors have attracted much attention due to their positive effects in promoting ovarian health. However, their target tissue, synthesis efficiency, advantages, and disadvantages are still unclear. This review summarizes the distribution of NAD+ at the tissue, cellular and subcellular levels, discusses its biosynthetic pathways and the latest findings in ovary, include: (1) NAD+ plays distinct roles both intracellularly and extracellularly, adapting its distribution in response to requirements. (2) Different precursors differs in target tissues, synthetic efficiency, biological utilization, and adverse effects. Importantly: tryptophan is primarily utilized in the liver and kidneys, posing metabolic risks in excess; nicotinamide (NAM) is indispensable for maintaining NAD+ levels; nicotinic acid (NA) constructs a crucial bridge between intestinal microbiota and the host with diverse functions; nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) increase NAD+ systemically and can be influenced by delivery route, tissue specificity, and transport efficiency. (3) The biosynthetic pathways of NAD+ are intricately intertwined. They provide multiple sources and techniques for NAD+ synthesis, thereby reducing the dependence on a single molecule to maintain cellular NAD+ levels. However, an excess of a specific precursor potentially influencing other pathways. In addition, Protein expression analysis suggest that ovarian tissues may preferentially utilize NAM and NMN. These findings summarize the specific roles and potential of NAD+ precursors in enhancing ovarian health. Future research should delve into the molecular mechanisms and intervention strategies of different precursors, aiming to achieve personalized prevention or treatment of ovarian diseases, and reveal their clinical application value.
Assuntos
NAD , Niacinamida , Ovário , Humanos , NAD/metabolismo , NAD/biossíntese , Ovário/metabolismo , Feminino , Animais , Niacinamida/metabolismo , Niacinamida/biossíntese , Vias Biossintéticas , Mononucleotídeo de Nicotinamida/metabolismoRESUMO
OBJECTIVES: To identify prognostic CT features that predict recurrence in patients with resectable pancreatic body/tail adenocarcinoma (PBTA) and construct a CT-based nomogram for preoperative risk stratification. METHODS: A total of 258 patients with resectable PBTA who underwent upfront surgery were retrospectively enrolled (development cohort, n = 172; validation cohort, n = 86), and their clinical and CT features were analyzed. Stepwise Cox proportional hazard analysis was performed to identify prognostic features and construct a predictive nomogram for recurrence-free survival (RFS). The prognostic performance of the CT-based nomogram was validated and compared to the 8th American Joint Committee on Cancer (AJCC) pathological staging system. RESULTS: In the development cohort, the following five CT features for predicting recurrence were identified to construct the nomogram: tumor density in the venous phase, tumor necrosis, adjacent organ invasion, splenic vein invasion, and superior mesenteric vein/portal vein abutment. In the validation cohort, the CT-based nomogram showed a concordance index of 0.65 (95% confidence interval: 0.58-0.73), which was higher than the 8th AJCC staging system. The area under the curves of the nomogram for predicting recurrence at 0.5, 1, and 2 years were 0.66, 0.71, and 0.72, respectively. Patients were categorized into high- and low-risk groups with 1-year recurrence probabilities of 0.73 and 0.43, respectively. CONCLUSIONS: The proposed nomogram provided accurate recurrence risk stratification for patients with resectable PBTA in a preoperative setting and may be used to facilitate clinical decision-making. CLINICAL RELEVANCE STATEMENT: The proposed CT-based nomogram, based on easily available CT features, may serve as an effective and convenient tool for stratifying further the recurrence risk of patients with pancreatic body/tail adenocarcinoma. KEY POINTS: ⢠The CT-based nomogram, incorporating five commonly used CT features, successfully preoperatively stratified patients with resectable PBTA into distinct prognosis groups. ⢠Tumor density in the venous phase, tumor necrosis, splenic vein invasion, adjacent organ invasion, and superior mesenteric vein/portal vein abutment were associated with RFS in patients with resectable PBTA. ⢠The CT-based nomogram exhibited better predictive performance for recurrence than the 8th AJCC staging system.
Assuntos
Adenocarcinoma , Nomogramas , Humanos , Estudos Retrospectivos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Prognóstico , Veia Porta/patologia , Medição de Risco , Tomografia Computadorizada por Raios X , Necrose/patologia , Neoplasias PancreáticasRESUMO
The establishment of axon/dendrite polarity is fundamental for neurons to integrate into functional circuits, and this process is critically dependent on microtubules (MTs). In the early stages of the establishment process, MTs in axons change dramatically with the morphological building of neurons; however, how the MT network changes are triggered is unclear. Here we show that CAMSAP1 plays a decisive role in the neuronal axon identification process by regulating the number of MTs. Neurons lacking CAMSAP1 form a multiple axon phenotype in vitro, while the multipolar-bipolar transition and radial migration are blocked in vivo. We demonstrate that the polarity regulator MARK2 kinase phosphorylates CAMSAP1 and affects its ability to bind to MTs, which in turn changes the protection of MT minus-ends and also triggers asymmetric distribution of MTs. Our results indicate that the polarized MT network in neurons is a decisive factor in establishing axon/dendritic polarity and is initially triggered by polarized signals.
Assuntos
Polaridade Celular/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/fisiologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Imunoprecipitação , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Neurônios , Paclitaxel , Ligação ProteicaRESUMO
BACKGROUND: This study investigated the efficacy of radiomics to predict survival outcome for locally advanced breast cancer (LABC) patients and the association of radiomics with tumor heterogeneity and microenvironment. METHODS: Patients with LABC from 2010 to 2015 were retrospectively reviewed. Radiomics features were extracted from enhanced MRI. We constructed the radiomics score using lasso and assessed its prognostic value. An external validation cohort from The Cancer Imaging Archive was used to assess phenotype reproducibility. Sequencing data from TCGA and our center were applied to reveal genomic landscape of different radiomics score groups. Tumor infiltrating lymphocytes map and bioinformatics methods were applied to evaluate the heterogeneity of tumor microenvironment. Computational histopathology was also applied. RESULTS: A total of 278 patients were divided into training cohort and validation cohort. Radiomics score was constructed and significantly associated with disease-free survival (DFS) of the patients in training cohort, validation cohort and external validation cohort (p < 0.001, p = 0.014 and p = 0.041, respectively). The radiomics-based nomogram showed better predictive performance of DFS compared with TNM model. Distinct gene expression patterns were identified. Immunophenotype and immune cell composition was different in each radiomics score group. The link between radiomics and computational histopathology was revealed. CONCLUSIONS: The radiomics score could effectively predict prognosis of LABC after neoadjuvant chemotherapy and radiotherapy. Radiomics revealed heterogeneity of tumor cell and tumor microenvironment and holds great potential to facilitate individualized DFS estimation and guide personalized care.
Assuntos
Neoplasias da Mama , Microambiente Tumoral , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Humanos , Prognóstico , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Peripheral nerve regeneration is a coordinated process of Schwann cell (SC) reprogramming and intrinsic neuronal growth program activation. Panaxydol (PND) is a strong biologically active traditional Chinese medicine monomer extracted from Panax notoginseng rhizomes. In vitro, PND protects neurons and SCs from injury and stimulates the expression and secretion of neurotrophic factors (NTFs) by SCs. We hypothesized that PND may also promote peripheral nerve regeneration in adult animals. METHODS: PND (10 mg/kg body weight) was injected intraperitoneally into the Sprague-Dawley (SD) rats for two consecutive weeks after sciatic nerve transection. The morphology of the repaired sciatic nerve was evaluated after 16 weeks, and sensory and motor function recovery was evaluated using functional and behavioral techniques. RESULTS: PND was biologically safe at an injection dose of 10 mg/kg/day. After 14 days, it significantly increased the myelination of regenerated nerve fibers, and promoted sensory and motor function recovery. In the early stage of injury, PND significantly upregulated the mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptors in distal injured nerves, which may represent a possible mechanism by which PND promotes nerve regeneration in vivo. CONCLUSIONS: Our study demonstrated that PND leads to sensory and motor recovery in a sciatic nerve transection model rat. Furthermore, we showed that BDNF mRNA level was significantly increased in the injured distal nerve, potentially contributing to the functional recovery. Further research is warrantied to examine whether direct injection is a more efficient method to increase BDNF expression compared to an exogenous BDNF administration.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Panax notoginseng , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Di-Inos , Álcoois Graxos , Regeneração Nervosa/fisiologia , Panax notoginseng/genética , Panax notoginseng/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Células de Schwann/metabolismo , Nervo Isquiático/lesõesRESUMO
OBJECTIVE: The aim of the study was to construct and validate a nomogram for differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA). METHODS: Two hundred patients with pathologically confirmed thyroid follicular neoplasms were retrospectively analyzed. The patients were randomly divided into a training set (n = 140) and validation set (n = 60). Baseline data including demographics, CT (computed tomography) signs, and radiomic features were analyzed. Predictive models were developed and compared to build a nomogram. The predictive effectiveness of it was evaluated by the area under receiver operating characteristic curve (AUC). RESULTS: The CT model, radiomic model and combination model showed excellent discrimination (AUCs [95% confidence interval] = 0.847 [0.766-0.928], 0.863 [0.746-0.932], 0.913 [0.850-0.975]). The nomogram based on the combination model showed remarkable discrimination in the training and validation sets. The calibration curves suggested good consistency between actual observation and prediction. CONCLUSIONS: This study proposed a nomogram that can accurately and intuitively predict the malignancy potential of follicular thyroid neoplasms.
Assuntos
Adenocarcinoma Folicular/diagnóstico por imagem , Nomogramas , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Distribuição Aleatória , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Machine learning has been widely used in the characterization of tumors recently. This article aims to explore the feasibility of the whole tumor fat-suppressed (FS) T2WI and ADC features-based least absolute shrinkage and selection operator (LASSO)-logistic predictive models in the differentiation of soft tissue neoplasms (STN). The clinical and MR findings of 160 cases with 161 histologically proven STN were reviewed, retrospectively, 75 with diffusion-weighted imaging (DWI with b values of 50, 400, and 800 s/mm2). They were divided into benign and malignant groups and further divided into training (70%) and validation (30%) cohorts. The MR FS T2WI and ADC features-based LASSO-logistic models were built and compared. The AUC of the FS T2WI features-based LASSO-logistic regression model for benign and malignant prediction was 0.65 and 0.75 for the training and validation cohorts. The model's sensitivity, specificity, and accuracy of the validation cohort were 55%, 96%, and 76.6%. While the AUC of the ADC features-based model was 0.932 and 0.955 for the training and validation cohorts. The model's sensitivity, specificity, and accuracy were 83.3%, 100%, and 91.7%. The performances of these models were also validated by decision curve analysis (DCA). The AUC of the whole tumor ADC features-based LASSO-logistic regression predictive model was larger than that of FS T2WI features (p = 0.017). The whole tumor fat-suppressed T2WI and ADC features-based LASSO-logistic predictive models both can serve as useful tools in the differentiation of STN. ADC features-based LASSO-logistic regression predictive model did better than that of FS T2WI features.
Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias de Tecidos Moles , Estudos de Coortes , Humanos , Aprendizado de Máquina , Estudos Retrospectivos , Neoplasias de Tecidos Moles/diagnóstico por imagemRESUMO
Protein arginine methyltransferase 5 (PRMT5) has been implicated in the development and progression of human cancers. However, few studies reveal its role in epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. In this study, we find that PRMT5 is up-regulated in pancreatic cancer, and promotes proliferation, migration and invasion in pancreatic cancer cells, and promotes tumorigenesis. Silencing PRMT5 induces epithelial marker E-cadherin expression and down-regulates expression of mesenchymal markers including Vimentin, collagen I and ß-catenin in PaTu8988 and SW1990 cells, whereas ectopic PRMT5 re-expression partially reverses these changes, indicating that PRMT5 promotes EMT in pancreatic cancer. More importantly, we find that PRMT5 knockdown decreases the phosphorylation level of EGFR at Y1068 and Y1172 and its downstream p-AKT and p-GSK3ß, and then results in down-regulation of ß-catenin. Expectedly, ectopic PRMT5 re-expression also reverses the above changes. It is suggested that PRMT5 promotes EMT probably via EGFR/AKT/ß-catenin pathway. Taken together, our study demonstrates that PRMT5 plays oncogenic roles in the growth of pancreatic cancer cell and provides a potential candidate for pancreatic cancer treatment.
Assuntos
Transição Epitelial-Mesenquimal , Receptores ErbB/metabolismo , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/patologia , Proteína-Arginina N-Metiltransferases/metabolismo , Transdução de Sinais , beta Catenina/metabolismo , Animais , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neoplasias Pancreáticas/genética , Proteína-Arginina N-Metiltransferases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias PancreáticasRESUMO
OBJECTIVES: To identify a CT-based radiomics nomogram for survival prediction in patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: A total of 220 patients (training cohort n = 147; validation cohort n = 73) with PDAC were enrolled. A total of 300 radiomics features were extracted from CT images. And the least absolute shrinkage and selection operator algorithm were applied to select features and develop a radiomics score (Rad-score). The radiomics nomogram was constructed by multivariate regression analysis. Nomogram discrimination, calibration, and clinical usefulness were evaluated. The association of the Rad-score and recurrence pattern in PDAC was evaluated. RESULTS: The Rad-score was significantly associated with PDAC patient's disease-free survival (DFS) and overall survival (OS) (both p < 0.001 in two cohorts). Incorporating the Rad-score into the radiomics nomogram resulted in better performance of the survival prediction than that of the clinical model and TNM staging system. In addition, the radiomics nomogram exhibited good discrimination, calibration, and clinical usefulness in both the training and validation cohorts. There was no association between the Rad-score and recurrence pattern. CONCLUSIONS: The radiomics nomogram integrating the Rad-score and clinical data provided better prognostic prediction in resected PDAC patients, which may hold great potential for guiding personalized care for these patients. The Rad-score was not a predictor of the recurrence pattern in resected PDAC patients. KEY POINTS: ⢠The Rad-score developed by CT radiomics features was significantly associated with PDAC patients' prognosis. ⢠The radiomics nomogram integrating the Rad-score and clinical data has value to permit non-invasive, low-cost, and personalized evaluation of prognosis in PDAC patients. ⢠The radiomics nomogram outperformed clinical model and the TNM staging system in terms of survival estimation.
Assuntos
Algoritmos , Carcinoma Ductal Pancreático/diagnóstico , Estadiamento de Neoplasias/métodos , Nomogramas , Neoplasias Pancreáticas/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Nodular fasciitis rarely occurs in young adults and children; it usually resembles other tumors, even malignancy. PURPOSE: To review the imaging findings of six cases of nodular fasciitis misdiagnosed radiologically. MATERIAL AND METHODS: The clinical and radiologic features of six cases of histologically proven but radiologically misdiagnosed nodular fasciitis were reviewed retrospectively. Two cases underwent both plain and enhanced computed tomography (CT) scans and the other four had both regular and enhanced magnetic resonance (MR) scans. RESULTS: All six patients were young (five children and one young adult). A rapid growing mass, pain or painless, was the most frequent presentation. Most masses were oval, well-defined, and homogeneous, with an average diameter of 2.2 cm. Five were found in superficial fascia with a broad base. Two cyst-like masses showed hypodensity relative to muscle on plain CT and without enhancement. Compared to muscle, these masses showed isointensity (n = 3) or slight hyperintensity (n = 1) on T1-weighted imaging, hyperintensity on T2-weighted imaging (n = 4), with homogeneous notable enhancement (n = 3) or mild enhancement (n = 1). Five (83.3%) were found with a "fascial tail" sign characterized as thickening of adjacent fascial layer with notable enhancement. One mass showed an "inverted target" sign. CONCLUSION: Nodular fasciitis in young adults and children is usually superficial, rapid growing, well-defined, and homogeneous, frequently with a "fascial tail" sign. Radiologically, it can resemble a benign cyst and might be easily misdiagnosed. Therefore, nodular fasciitis should be remembered in the differential diagnosis for superficial soft tissue tumor found in young adult and children.
Assuntos
Erros de Diagnóstico , Fasciite/diagnóstico , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
DNA methylation is an important form of epigenetic regulation in mammalian development. Methyl-CpG-binding domain protein 1 (MBD1) and methyl-CpG-binding domain protein 2 (MeCP2) are two members of the MBD subfamily of proteins that bind methylated CpG to maintain the silencing effect of DNA methylation. Given their important roles in linking DNA methylation with gene silencing, this study characterized the coordinated mRNA expression and protein localization of MBD1 and MeCP2 in embryos and placentas and aimed to analysis the effects of MBD1 and MeCP2 on transgenic cloned goats. Our result showed that MBD1 expression of transgenic cloned embryo increased significantly at the 2-4-cell and 8-16-cell stages (P < 0.05), then decreased at the morula and blastocyst stages (P < 0.05); MeCP2 expression in transgenic cloned embryo was significant decreased at the 2-4-cell stage and increased at the 8-16-cell stage (P < 0.05). Placenta morphology analysis showed that the cotyledon number of deceased transgenic cloned group (DTCG) was significantly lower than that the normal goats (NG) and in the live transgenic cloned goats (LTCG) (P < 0.05). MBD1 and MeCP2 were clearly detectable in the placental trophoblastic binucleate cells by immunohistochemical staining. Moreover, MBD1 and MeCP2 expression in DTCG was significant higher than in the NG and the LTCG (P < 0.05). In summary, aberrant expression of methylation CpG binding proteins MBD1 and MeCP2 was detected in embryonic and placental development, which reflected abnormal transcription regulation and DNA methylation involved in MBD1 and MeCP2. These findings have implications in understanding the low efficiency of transgenic cloning.
Assuntos
Blastocisto/fisiologia , Proteína 2 de Ligação a Metil-CpG/metabolismo , Placenta/fisiologia , Fatores de Transcrição/metabolismo , Animais , Animais Geneticamente Modificados , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Cabras , Proteína 2 de Ligação a Metil-CpG/genética , Mórula/fisiologia , Gravidez , Fatores de Transcrição/genéticaRESUMO
PURPOSE: The aim of this study was to discuss the correlation between diffusion-weighted imaging (DWI) at 3.0-T magnetic resonance and histopathology for pancreatic ductal adenocarcinoma (PDA). MATERIALS AND METHODS: Twenty-eight patients with histopathologically proven PDA were included in this study after 108 cases of suspected pancreatic tumors had been performed with DWI. The sequences of DWI included respiratory-triggered DWI and breath-hold DWI, which were performed with 2 b values (0 and 500 s/mm; 0 and 1000 s/mm), respectively. According to magnetic resonance images, wax blocks and slices were selected and stained with hematoxylin-eosin for anti-vascular endothelial growth factor (VEGF), anti-CD34, and anti-Ki-67 (Mib-1). The relationship between tumor apparent diffusion coefficient (ADC) and tumor fibrosis, as well as the expression of tumor VEGF, Ki-67, and multivessel density (MVD), were studied. RESULTS: The ADC values of PDA of different grades of differentiation and fibrosis grade did not show statistically significant difference. The ADC values of PDA did not show the statistically significant correlation with the grades of differentiation, fibrosis grade, Ki-67 expression, and expression of VEGF and MVD. CONCLUSIONS: The ADC of PDA cannot be used to reflect grades of differentiation, degree of tumor fibrosis, the expression of VEGF, the expression of Ki-67, and the tumor MVD.
Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico , Imagem de Difusão por Ressonância Magnética , Humanos , Pâncreas/patologia , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: The aim of this study was to discuss the correlation of quantitative dynamic contrast-enhanced magnetic resonance imaging (QDCE-MRI) at 3.0-T magnetic resonance and histopathology for pancreatic ductal adenocarcinoma (PDA). METHODS: Twenty-three patients with histopathologically proven PDA were included in this study after 75 cases of suspected pancreatic tumors had been performed by QDCE-MRI. The quantitative kinetic parameters analyzed by 2-compartment and 3-compartment models were calculated automatically, which included the volume transfer constant of the contrast agent, the rate constant (Kep), the volume as a percentage of the extravascular extracellular leakage space, the time of arrival of contrast agent, the time of peaking of contrast agent, the maximum slope of signal intensity ascent, and the contrast enhancement ratio. According to magnetic resonance images, tissue section were selected and stained for evaluating tumor differentiation, tumor fibrosis, tumor microvessel density, the expression of tumor vascular endothelial growth factor (VEGF) and Ki67. Subsequently, the relationship between the parameters of QDCE-MRI and histopathology of PDA was analyzed. RESULTS: The tumor Kep and extravascular extracellular leakage space showed a statistically significant correlation with tumor fibrosis; the tumor volume transfer constant of the contrast agent 2-compartment showed a statistically significant correlation with the expressions of tumor VEGF; and the tumor Kep, maximum slope of signal intensity ascent, and contrast enhancement ratio showed a statistically significant correlation with the expression of tumor Ki67. CONCLUSIONS: The parameters of QDCE-MRI of PDA can be used to evaluate the degrees of tumor fibrosis and the expressions of VEGF and Ki67.
Assuntos
Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Gadolínio DTPA/farmacocinética , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Simulação por Computador , Meios de Contraste/farmacocinética , Humanos , Aumento da Imagem/métodos , Modelos Biológicos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
PURPOSE: To retrospectively analyze MRI and computed tomographic (CT) findings from renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions (Xp11-RCC). MATERIALS AND METHODS: Institutional review board permission was obtained to review patient medical records, and the requirement for informed consent was waved . The clinical and MRI/CT features of five cases with Xp11-RCC that were confirmed by pathology were analyzed retrospectively. The image characteristics included the lesion location and size, contribution of cystic and solid components, intratumoral necrosis or hemorrhage, invasion of perinephric tissue and renal sinus, lymphadenopathy, major venous or arterial vascular invasion, pattern of the tumor growth, intratumor calcification and lipids, homogeneity of SI on T2-weighted images, attenuation and SI of the mass with respect to the normal renal cortex on precontrast and contrasted CT/MRI images, tumor SIs, tumor attenuations and tumor-to-cortex indices, homogeneity of enhancement on the contrasted images. RESULTS: The mean age was 32 years (range, 15-47 years). Most patients (4/5) were women. All tumors showed a cortical location. The average tumor size was 9 cm (range, 4-18 cm). Four tumors comprised a predominantly solid lesion with focal necrosis, and one tumor comprised a solid lesion with significant necrosis. All tumors showed intertumor hemorrhage, infiltrative growth and invasion of the perirenal adipose/renal sinus. Four cases showed retroperitoneal lymphadenopathy, of which one case showed simultaneous mediastinal and supraclavicular lymphadenopathy. All tumors from four cases showed mild hyperintensity on T1-weighted MRI images, and three tumors showed hypointensity on T2-weighted MRI images relative to the renal cortex except for 1 tumor that showed significant hemorrhage and a relative hyperintensity. For 3 cases who were imaged with CT, two tumors imaged using nonenhanced CT images showed mild hyperdensity relative to the renal cortex. Calcification was noted in all three tumors. All tumors showed mild, persistent enhancement. CONCLUSION: Typical Xp11-RCC manifests as an advanced, solid renal mass with mild persistent enhancement, a prevalence of intertumor hemorrhage/calcification, and a cortical epicenter location. The predilection for children and young adults is a useful clinical feature when confirming a diagnosis of Xp11-RCC.
Assuntos
Cromossomos Humanos X/genética , Proteínas de Ligação a DNA/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Imageamento por Ressonância Magnética , Proteínas Musculares/genética , Tomografia Computadorizada por Raios X , Fatores de Transcrição/genética , Adolescente , Adulto , Feminino , Fusão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição de Domínio TEA , Translocação Genética/genética , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to investigate the diagnostic value of quantitative dynamic contrast-enhanced magnetic resonance imaging (QDCE-MRI) of pancreatic ductal adenocarcinoma (PDA) on a 3.0-T magnetic resonance. MATERIALS AND METHODS: The study was approved by the local institutional review board, and all subjects provided written informed consent. Seventy-five patients with suspected pancreatic tumors underwent QDCE-MRI, in which 33 patients with cases of pancreatic solid lesions (23 patients with PDA, 3 patients with solid pseudopapillary tumor, 3 patients with neuroendocrine tumor, 2 patients with mass-forming pancreatitis, 2 patients with ampullary adenocarcinoma) proven through histopathologic diagnosis were included in this study. The parameters of QDCE-MRI were recorded and compared. RESULTS: The parameters of QDCE-MRI of PDA tissue and non-cancer tissue did not show significant difference between 2-compartment model (2C) and 3-compartment model (3C). The contrast enhancement ratio of non-cancer tissue with dilatation of pancreatic duct was significantly higher than that of non-cancer tissue without dilatation of pancreatic duct, whereas the rate constant (Kep) of 2C was significantly lower. The maximun slope of signal intensity ascent (MxSIp), the volume transfer constant (Ktrans), and the Kep of PDA tissue were significantly lower than those of the non-cancer tissue, but the time of peaking of contrast agent (PeakT) was significantly longer. Receiver operating characteristic curves showed that the areas under the curve of differentiating PDA tissue from the non-cancer tissue were 0.82, 0.79, 0.91, 0.94, 0.88, and 0.89 for PeakT, MxSIp, Ktrans-2C, Kep-2C, Ktrans-3C, and Kep-3C, respectively. The PDA tissue showed lower MxSIp and Kep as well as longer PeakT than those of the non-PDA lesions. The receiver operating characteristic curves showed that the areas under the curve of differentiating the PDA from the non-PDA tumor were 0.73, 0.72, 0.79, and 0.72 for PeakT, MxSIp, Kep-2C, and Kep-3C, respectively CONCLUSIONS: The parameters of QDCE-MRI are useful for the diagnosis of PDA.
Assuntos
Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/patologia , Gadolínio DTPA , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: The aim of this study is to analyse the computed tomographic (CT) findings of pulmonary epithelioid haemangioendothelioma (EHE). MATERIALS AND METHODS: The CT features and clinical presentations of six patients (five women, one man; mean age, 53 years) with pathology-proven pulmonary EHE were reviewed. Noncontrast CT images were available for three patients and enhanced CT images for three patients. The image characteristics included the number of tumours, tumour location and size, tumour margins, the presence of calcification/necrosis/cavity, the presence of perivascular location, the presence of pleural lesions, tumour homogeneity at contrast-enhanced CT, tumour enhancement relative to the adjacent muscle and the presence of extrapulmonary lesions. RESULTS: Multiple nodules/masses with irregular margin were shown in all cases, and reticulonodular opacities and ground-glass opacities were found in one case. Overall, the six cases showed 178 nodules/masses, 90 % (160/178) of which were <1 cm in diameter. The average size of the largest nodules/masses in each case was 2.7 cm. The nodules/masses were mostly (93 %, 166/178) located in the subpleural region (<2 cm from the pleura). A total of 48 % (86/178) of nodules/masses showed punctate calcification in four of six cases. All nodules/masses showed perivascular location. Pleural indentation was shown in all cases, as well as pleural-thickening in five cases and pleural effusion in two cases. On contrast-enhanced CT, EHE showed a mildly heterogeneous hyperdense appearance. CONCLUSIONS: With predilection for subpleural and perivascular location, typical pulmonary EHE appears as multiple irregular nodules with punctate calcification and pleural indentation.
Assuntos
Hemangioendotelioma Epitelioide/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico por imagemRESUMO
Mitophagy, the cellular process that removes damaged mitochondria, plays a crucial role in maintaining normal cell functions. It is deeply involved in the entire process of follicle development and is associated with various ovarian diseases. This review aims to provide a comprehensive overview of mitophagy regulation, emphasizing its role at different stages of follicular development. Additionally, the study illuminates the relationship between mitophagy and ovarian diseases, including ovary aging (OA), primary ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS). A detailed understanding of mitophagy could reveal valuable insights and novel strategies for managing female ovarian reproductive health.