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1.
Radiología (Madr., Ed. impr.) ; 65(1): 22-31, ene.-feb. 2023. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-ADZ-594

RESUMO

Introducción y objetivosLos nódulos tiroideos requieren con frecuencia evaluación mediante ecografía y biopsia por aspiración con aguja fina (BAAF). No obstante, la BAAF no permite la diferenciación entre adenoma y carcinoma folicular en lesiones de tipo IV según la clasificación de Bethesda. Esto provoca numerosas intervenciones quirúrgicas innecesarias porque no es posible garantizar el carácter benigno de las lesiones, ni siquiera cuando la mayoría de las muestras corresponden a adenomas o incluso a otras lesiones benignas. El objetivo de este estudio es establecer si hay características ecográficas que nos ayudarían a pronosticar el riesgo de malignidad de los nódulos con un diagnóstico anatomopatológico de neoplasia folicular para conseguir un abordaje más conservador de los nódulos sin sospecha de malignidad.Material y métodosEstudiamos 61 nódulos en 61 pacientes (51 mujeres y 10 varones) que se habían sometido a intervención quirúrgica de la glándula tiroides y tenían resultados histopatológicos de adenoma o carcinoma folicular. Se analizaron diversas características ecográficas de los nódulos (composición, ecogenicidad, borde, estado de calcificación, presencia de halo y sospecha general de malignidad según el observador) y se estableció su correlación con el análisis histopatológico.ResultadosObservamos una relación estadísticamente significativa entre el carcinoma folicular y la presencia de calcificaciones, bordes mal definidos y la sospecha o impresión general del observador (definida por sospecha clara de signos ecográficos de malignidad, como calcificación, borde mal definido y un nódulo sólido marcadamente hipoecoico; y signos ecográficos de benignidad, como composición ecogénica predominantemente quística y presencia de halo hipoecogénico perinodular). Sin embargo, todas estas características han mostrado una sensibilidad baja en el estudio que nos ocupa (30%, 30% y 50%, respectivamente)...(AU)


Introduction and objectivesThyroid nodules frequently require ultrasound and Fine Needle Aspiration Cytology (FNAC) evaluation. However, FNA cytology does not allow differentiation between follicular adenoma and carcinoma on Bethesda type IV lesions. This situation leads to many unnecessary surgical procedures because it is not possible to assure the benignity of the lesions, even when most of the specimens correspond to adenomas or even other benign lesions.The objective is this study is to establish if there are any US characteristics that would help us to predict the risk of malignancy of nodules with a pathological diagnosis of follicular neoplasm in order to achieve a more conservative management for non-suspicious nodules.Material and methodsWe studied 61 nodules in 61 patients (51 women and 10 men) that underwent thyroid surgery and had histopathological results of either follicular adenoma or carcinoma.Different US characteristics of the nodules were analysed (composition, echogenicity, margin, calcification status, the presence of halo and overall observer suspicion of malignancy) and were correlated with the histopathological analysis.ResultsWe have found a statistically significant association between the presence of calcifications, ill-defined borders and overall observer suspicion or impression (defined by well-known suspicious for malignancy ultrasonographic features, such as calcification, poorly defined margin, and a markedly hypoechoic solid nodule; and benign ultrasonographic features, such as predominantly cystic echogenic composition and the presence of a perinodular hypoechogenic halo) with follicular carcinoma. However all those features have shown low sensitivities in the present study (30%, 30% and 50%, respectively). On the other hand, the absence of halo sign has shown a sensitivity of 100% and a negative predictive value (NPV) of 100% in our study... (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adenoma/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Estudos Retrospectivos , Diagnóstico Diferencial , Ultrassonografia/métodos
2.
Cells ; 12(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36611973

RESUMO

Clear cell renal cell carcinoma (ccRCC) has a high metastatic rate, and its incidence and mortality are still rising. The aim of this study was to identify the key tumor-infiltrating immune cells (TIICs) affecting the distant metastasis and prognosis of patients with ccRCC and to construct a relevant prognostic panel to predict immunotherapy response. Based on ccRCC bulk RNA sequencing data, resting mast cells (RMCs) were screened and verified using the CIBERSORT algorithm, survival analysis, and expression analysis. Distant metastasis-associated genes were identified using single-cell RNA sequencing data. Subsequently, a three-gene (CFB, PPP1R18, and TOM1L1) panel with superior distant metastatic and prognostic performance was established and validated, which stratified patients into high- and low-risk groups. The high-risk group exhibited lower infiltration of RMCs, higher tumor mutation burden (TMB), and worse prognosis. Therapeutically, the high-risk group was more sensitive to anti-PD-1 and anti-CTLA-4 immunotherapy, whereas the low-risk group displayed a better response to anti-PD-L1 immunotherapy. Furthermore, two immune clusters revealing distinct immune, clinical, and prognosis heterogeneity were distinguished. Immunohistochemistry of ccRCC samples verified the expression patterns of the three key genes. Collectively, the prognostic panel based on RMCs is able to predict distant metastasis and immunotherapy response in patients with ccRCC, providing new insight for the treatment of advanced ccRCC.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Mastócitos , Prognóstico , Imunoterapia , Neoplasias Renais/genética , Neoplasias Renais/terapia , Proteínas Adaptadoras de Transdução de Sinal
3.
Cells ; 12(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36611995

RESUMO

Therapy resistance is still a major reason for treatment failure in colorectal cancer (CRC). Previously, we identified the E3 ubiquitin ligase TRIM25 as a novel suppressor of caspase-2 translation which contributes to the apoptosis resistance of CRC cells towards chemotherapeutic drugs. Here, we report the executioner caspase-7 as being a further target of TRIM25. The results from the gain- and loss-of-function approaches and the actinomycin D experiments indicate that TRIM25 attenuates caspase-7 expression mainly through a decrease in mRNA stability. The data from the RNA pulldown assays with immunoprecipitated TRIM25 truncations indicate a direct TRIM25 binding to caspase-7 mRNA, which is mediated by the PRY/SPRY domain, which is also known to be highly relevant for protein-protein interactions. By employing TRIM25 immunoprecipitation, we identified the heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) as a novel TRIM25 binding protein with a functional impact on caspase-7 mRNA stability. Notably, the interaction of both proteins was highly sensitive to RNase A treatment and again depended on the PRY/SPRY domain, thus indicating an indirect interaction of both proteins which is achieved through a common RNA binding. Ubiquitin affinity chromatography showed that both proteins are targets of ubiquitin modification. Functionally, the ectopic expression of caspase-7 in CRC cells caused an increase in poly ADP-ribose polymerase (PARP) cleavage concomitant with a significant increase in apoptosis. Collectively, the negative regulation of caspase-7 by TRIM25, which is possibly executed by hnRNPH1, implies a novel survival mechanism underlying the chemotherapeutic drug resistance of CRC cells. The targeting of TRIM25 could therefore offer a promising strategy for the reduction in therapy resistance in CRC patients.


Assuntos
Carcinoma , Neoplasias do Colo , Humanos , RNA Mensageiro/genética , Caspase 7 , Ubiquitina-Proteína Ligases/metabolismo , RNA , Neoplasias do Colo/genética , Linhagem Celular Tumoral , Ubiquitina , Apoptose/genética , Proteínas com Motivo Tripartido/genética , Fatores de Transcrição/genética
4.
Sci Rep ; 13(1): 345, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611038

RESUMO

Pulmonary lymphangitic carcinomatosis (PLC) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to determine prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC with radiologically diagnosed PLC. We retrospectively reviewed 50 NSCLC patients with radiologically diagnosed PLC. Among eight clinical variables and five imaging parameters, metabolic PLC burden, which represents the overall tumor burden of PLC, and cPLC, which represents the location and extent of PLC in a three-grade system, were used. In multivariate analyses for progression-free survival, metabolic PLC burden (P = 0.0181), cPLC (P = 0.0401), and clinical stage (P = 0.0284) were identified as independent prognostic factors. High metabolic PLC burden had a worse prognosis, and the prognosis of cPLC3 was significantly worse than that of cPLC1 or cPLC2. In univariate analyses for overall survival, only age (P = 0.0073) was identified a prognostic factor. In conclusion, FDG PET/CT parameters were identified as independent prognostic factors in NSCLC with radiologically diagnosed PLC. Furthermore, a combination of anatomical and metabolic information about PLC obtained using FDG PET/CT provides insight into the overall tumor burden of PLC and is useful in predicting prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18/metabolismo , Prognóstico , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Compostos Radiofarmacêuticos , Estadiamento de Neoplasias , Carcinoma/patologia , Carga Tumoral
5.
Anal Sci ; 39(1): 5-11, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596957

RESUMO

In the present work, a highly sensitive sandwich-type electrochemical immunosensor of carcinoembryonic antigen (CEA) was developed by preparing N-doped hollow mesoporous nanocarbon spheres/gold hybrids (NHMN/Au) hybridsas sensing platformand Au/ferrocene (Au/Fc) as signal amplifiers. The large surface area and high conductivity as well as good biocompatibility of NHMN/Au can increase the loading of primary antibody (Ab1) and accelerate the electron transport rate of the electrode surface, while Au can carry immobilized secondary antibodies (Ab2) and Fc derivative (Fc-SH).By using Fc-SH as response probe, the experiments show that the peak current of probe could increase after occurring the specific recognition of Ab1-CEA-Ab2, thus a novel sandwich-type immunosensor of CEA was developed. Finally, the proposed method for CEA detection was applied in human serum and the obtained results are satisfactory, indicating the developed method has important clinical applications for CEA determination.


Assuntos
Técnicas Biossensoriais , Carcinoma , Grafite , Nanopartículas Metálicas , Humanos , Antígeno Carcinoembrionário , Imunoensaio , Ouro , Metalocenos , Técnicas Eletroquímicas/métodos , Limite de Detecção , Anticorpos Imobilizados
6.
Artigo em Chinês | MEDLINE | ID: mdl-36597369

RESUMO

Objective:To analyze the clinical effect of free posterior lateral peroneal artery perforator flap of lower leg in repairing postoperative defect of oropharyngeal carcinoma. Methods:Thirty-six patients with oropharyngeal carcinoma admitted to the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Bengbu Medical College from June 2016 to June 2019 were analyzed and followed up, eighteen patients were treated with free posterior lateral peroneal artery perforator flap of the lower leg to repair the postoperative defects(experimental group), and eighteen patients were treated with free forearm flap(control group). The survival rate of the transplanted flap, the wound stageⅠhealing rate and average hospitalization time were compared between the two groups. Kaplan-Meier method was used to calculate the 1-year and 3-year survival rates of patients after operation, and log-rank test was used to compare the difference between the survival curves of the two groups; The recovery of swallowing and palatopharyngeal closure function of patients in the two groups at 3, 6, 12 and 18 months after operation was calculated and statistically analyzed through the water swallow test and the air blowing method. Results:There was one case of skin flap necrosis in both the experimental group and the control group, and the survival rate was 94.4%. The wound stageⅠhealing rate in the surgical area was 94.4% in both groups. The wound healing rates of the donor area in the experimental group and the control group were 100.0% and 94.4% respectively. The average hospitalization time of the experimental group and the control group was 16.9 days and 17.2 days, respectively, with no significant difference (P>0.05). The overall survival rates of all patients at 1-year and 3-year were 91.2% and 66.5% respectively; The 1-year and 3-year survival rates of the experimental group and the control group were 94.1%, 69.3% and 88.2%, 63.7%, respectively, and there was no significant difference between the two groups (P>0.05). The 1-year and 3-year survival rates of P16+ and P16 - patients were 100.0%, 80.0% and 85.7%, 64.3%, respectively, and there was no significant difference between the two groups (P>0.05). There was no significant difference in the evaluation of swallowing and velopharyngeal closure function between the two groups at 3 and 6 months after operation (P>0.05), but there was a significant difference at 12 and 18 months after operation (P<0.05). Conclusion:The anatomic position of the perforating vessels of the free posterior lateral peroneal artery perforator flap of the lower leg is constant, and it can be prepared into single leaf, multi leaf, chimeric and other flaps according to the tissue defect space. And the concealed supply area can be directly drawn to suture. At the same time, the skin flap has strong plasticity. Therefore, the skin flap can be used as a common skin flap to repair the defects after the operation of oropharyngeal carcinoma.


Assuntos
Carcinoma , Neoplasias Orofaríngeas , Retalho Perfurante , Lesões dos Tecidos Moles , Humanos , Transplante de Pele/métodos , Perna (Membro)/cirurgia , Retalho Perfurante/cirurgia , Retalho Perfurante/transplante , Neoplasias Orofaríngeas/cirurgia , Artérias/cirurgia , Carcinoma/cirurgia , Lesões dos Tecidos Moles/cirurgia , Resultado do Tratamento
7.
Saudi Med J ; 44(1): 19-28, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36634939

RESUMO

OBJECTIVES: To explore the expression and significance of long non-coding RNA ITGB2-AS1 in kidney renal clear cell carcinoma (KIRC). METHODS: The expression of ITGB2-AS1 in KIRC tissues of 45 KIRC patients in the first affiliated hospital of Henan University, Henan, China, from September 2018 to December 2020, KIRC cells were detected and the relationship of ITGB2-AS1 and overall survival of KIRC patients were analyzed. The expression of ITGB2-AS1 in KIRC cells Caki-1 and ACHN was interfered, and the changes of cell proliferation, invasion, migration, and apoptosis were detected. Dual luciferase reporter gene assay and RNA pull-down assay were carried out to verify the relationship between ITGB2-AS1 and miR-338-3p or miR-338-3p and epidermal growth factor receptor (EGFR). The expression of miR-338-3p and EGFR were detected after the interference of ITGB2-AS1. RESULTS: The expression of ITGB2-AS1 was expressed highly in KIRC tissues and cells (p<0.05). The overall survival of KIRC patients with high ITGB2-AS1 was poorer than those with low ITGB2-AS1. In Caki-1 cell, downregulation of ITGB2-AS1 suppressed the cell proliferation, invasion and migration, promoted the cell apoptosis (p<0.05). In ACHN cell, upregulation of ITGB2-AS1 promoted the cell proliferation, invasion and migration and inhibited the apoptosis (p<0.05). The ITGB2-AS1 targeted and regulated the expression of miR-338-3p/EGFR. CONCLUSION: The ITGB2-AS1 is expressed highly in KIRC and affects the survival of patients by regulating cell proliferation, invasion, and apoptosis.


Assuntos
Carcinoma , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Receptores ErbB
8.
PLoS One ; 18(1): e0279224, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36626395

RESUMO

OBJECTIVES: To investigate whether the pretreatment hemogram parameters and their ratios can be used in predicting the endometrial transformation in patients with abnormal uterine bleeding. MATERIAL AND METHODS: Records of all patients who underwent an endometrial histopathological evaluation between 2011 and 2021 were investigated. Hemogram, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were analyzed. Chi square and Mann Whitney U tests were used for analysis. P<0.05 was considered statistically significant. RESULTS: 427 patients were included, of whom 117 were presented with endometrial hyperplasia without atypia (27.4%; mean age, 42±9.7; Group II), 70 with atypia (16.3%; mean age, 53.4±9; Group III), 102 with early endometrial cancer (EC) (23.8%; mean age, 63±7.8; Group IV) and 38 with advanced disease (8.8%; mean age, 63.3±10.5; Group V). Patients without pathology constituted the control group (23.4%; mean age, 42.2±9.5; Group I). Risk factors for atypia and carcinoma were determined as age, postmenopausal state, obesity, diabetes, and increased estrogen exposure (each, p<0.05). There was no significant difference in NLR and PLR (p>0.05). However, hemoglobin and hematocrit levels were higher in Groups IV and V (13.9 vs 13.1 mg/dL, and 39.1 vs 38.8%, respectively; p<0.01). Platelet value was significantly higher in Groups III to V (282x109/L, 283x109/L and 295x109/L; p<0.05, p<0.05 and p<0.01, respectively). CONCLUSIONS: Our findings support the impact of inflammation on malign transformation from normal endometrial mucosa to atypia and carcinoma. NLR and PLR values showed no statistical difference. Instead, thrombocytosis may have a predictive role in EC.


Assuntos
Carcinoma , Neoplasias do Endométrio , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Prognóstico , Estudos Retrospectivos , Endométrio/patologia , Linfócitos/patologia , Neoplasias do Endométrio/patologia , Neutrófilos/patologia , Fatores de Risco , Carcinoma/patologia
9.
BMC Urol ; 23(1): 8, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627638

RESUMO

BACKGROUND: The high incidence of Gleason score upgrading (GSU) made urologists underestimate the disease, leading to the inaccurate therapeutic decision. The study aimed to explore relevant laboratory examination evidence associated with GSU. METHODS: Patients diagnosed with prostate carcinoma undergoing radical prostatectomy in our center between January 2015 and December 2019 were included in this retrospective study. Patients were divided into GSU and NGSU groups according to the occurrence of GSU. Medical records were reviewed and analyzed between groups. RESULTS: A total of 130 patients were enrolled, including 52 patients diagnosed with GS = 6 (20 NGSU and 32 GSU) and 78 patients with GS = 7 (36 NGSU and 42 GSU). No significant differences in demographic characteristics were found between groups. An increased neutrophil count (OR = 1.326, 95% CI = 1.005-1.748) and a decreased percentage of lymphocytes (OR = 0.951, 95% CI = 0.904-1) were associated with GSU in the GS = 6 group, whereas a high HDL level (OR = 7.735, 95% CI = 0.998-59.957) was associated with GSU in GS = 7 group. Preoperative high neutrophile count and low lymphocyte percentage were correlated with GSU in patients with low-grade prostate cancer. In contrast, high HDL level was associated with GSU in patients with high-grade prostate cancer. CONCLUSIONS: These laboratory examination data could provide urologists with information before making a therapeutic protocol.


Assuntos
Carcinoma , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Gradação de Tumores , Estudos Retrospectivos , Antígeno Prostático Específico , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Prostatectomia , Lipoproteínas HDL , Carcinoma/patologia
10.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614304

RESUMO

Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinß6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.


Assuntos
Carcinoma , Neoplasias do Colo do Útero , Humanos , Feminino , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Cisplatino , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo do Útero/patologia , Proliferação de Células/genética , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Ubiquitina-Proteína Ligases/metabolismo
11.
Korean J Gastroenterol ; 81(1): 40-45, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695066

RESUMO

An undifferentiated carcinoma (UC) of the gall bladder behaves aggressively and has a grave prognosis. Small cell type undifferentiated carcinoma of the gall bladder is a rare variant. This paper reports a case of UC of gall bladder with PAS-positive diastase- resistant eosinophilic hyaline globules present as liver mass (on imaging) in a male patient. The microscopic findings of the liver and gall bladder after a right tri-segmentectomy showed an un-differentiated malignant neoplasm composed of cells with round to oval nuclei, prominent nucleoli, and scanty neoplasm. No definite cell pattern was identified with these neoplastic cells. A section from the gall bladder revealed a tumor arising from the lining epithelium and infiltrating through the muscularis. This tumor was infiltrating the adherent liver tissue directly and forming a mass of undifferentiated malignant cells. The focal area within the tumor mass showed the presence of PAS-positive, diastase-resistant, eosinophilic hyaline globules within the neoplastic cells. The immunohistochemistry test was diffusely positive for perinuclear anti-neutrophil cytoplasmic antibodies and negative for chromogranin, vimentin, Desmin, alpha-fetoprotein, leukocyte common antigen, CD34, and bcl2. When the clinical and radiological data are inconclusive, careful analysis of the histological and immunophenotypic features is needed to make the final diagnosis of UC of the gall bladder. The biological behavior and prognosis of this tumor remain unclear because of its rarity. Further studies will be needed to understand the characteristics of this deadly tumor and to establish an effective therapy for it.


Assuntos
Carcinoma , Neoplasias da Vesícula Biliar , Humanos , Masculino , Hialina/metabolismo , Carcinoma/patologia , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , Fígado/patologia
12.
Rev Esp Patol ; 56(1): 69-72, 2023.
Artigo em Espanhol | MEDLINE | ID: mdl-36599602

RESUMO

Well Differentiated Papillary Mesothelioma (MPBD) is a very rare neoplasm that mainly affects women of reproductive age. The most common location is the peritoneum and it is an incidental finding, with a generally favorable prognosis. We present three cases diagnosed incidentally, in the course of a surgical intervention of various causes, which presented as peritoneal exophytic lesions not detected in the pre-surgical imaging study. It is important to keep this entity in mind, to differentiate it from other neoplasms with an unfavorable prognosis and evolution, such as Malignant Mesothelioma or primary and metastatic carcinomas. Recent studies give the MPBD a specific immunohistochemical and molecular profile that allow a greater diagnostic precision of the entity.


Assuntos
Carcinoma , Mesotelioma , Neoplasias Peritoneais , Humanos , Feminino , Neoplasias Peritoneais/patologia , Mesotelioma/diagnóstico , Mesotelioma/patologia , Mesotelioma/cirurgia , Peritônio/patologia , Prognóstico , Carcinoma/patologia
13.
Nat Commun ; 14(1): 378, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36690674

RESUMO

BRD4-NUT, a driver fusion mutant in rare and highly aggressive NUT carcinoma, acts in aberrant transcription of anti-differentiation genes by recruiting histone acetyltransferase (HAT) p300 and promoting p300-driven histone hyperacetylation and nuclear condensation in chromatin. However, the molecular basis of how BRD4-NUT recruits and activates p300 remains elusive. Here, we report that BRD4-NUT contains two transactivation domains (TADs) in NUT that bind to the TAZ2 domain in p300. Our NMR structures reveal that NUT TADs adopt amphipathic helices when bound to the four-helical bundle TAZ2 domain. The NUT protein forms liquid-like droplets in-vitro that are enhanced by TAZ2 binding in 1:2 stoichiometry. The TAD/TAZ2 bipartite binding in BRD4-NUT/p300 triggers allosteric activation of p300 and acetylation-driven liquid-like condensation on chromatin that comprise histone H3 lysine 27 and 18 acetylation and transcription proteins BRD4L/S, CDK9, MED1, and RNA polymerase II. The BRD4-NUT/p300 chromatin condensation is key for activating transcription of pro-proliferation genes such as ALX1, resulting ALX1/Snail signaling and epithelial-to-mesenchymal transition. Our study provides a previously underappreciated structural mechanism illuminating BRD4-NUT's bipartite p300 recruitment and activation in NUT carcinoma that nucleates a feed-forward loop for propagating histone hyperacetylation and chromatin condensation to sustain aberrant anti-differentiation gene transcription and perpetual tumor cell growth.


Assuntos
Carcinoma , Proteínas de Ciclo Celular , Cromatina , Proteínas de Neoplasias , Proteínas Nucleares , Humanos , Acetilação , Carcinoma/metabolismo , Carcinoma/patologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Histonas/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Genética , Proteínas de Neoplasias/metabolismo
14.
Aging (Albany NY) ; 15(1): 148-163, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36602525

RESUMO

BACKGROUND: Shaoyao-Gancao Decoction (SG-D) is a famous classical Chinese prescription that has been used in the treatment of numerous kinds of diseases. However, its mechanism of action in the treatment of Gastric carcinoma (GC) is not clear. METHODS: The active ingredients and targets of SG-D were screened using network pharmacology, and GC-related targets were retrieved through several databases. The protein-protein interaction network was then further constructed and GO and KEGG enrichment analysis were performed. Subsequently, molecular docking was carried out. Finally, we validated the results of the network pharmacology by performing in vitro cell experiments on CCK-8, apoptosis, cell cycle, platelet clone formation, and Western blotting with AGS cells. RESULTS: Three key active ingredients and 8 core targets were screened through a network pharmacological analysis, and the results of the KEGG indicated that the PI3K/Akt and MAPK signaling pathways are critical signaling pathways for SG-D to treat GC. Experimental results revealed that SG-D was able to inhibit AGS cells proliferation, induce apoptosis and arrest the cell cycle, and reduce the ability of cell clone formation by regulating the PI3K/Akt and MAPK signaling pathways. CONCLUSIONS: Network pharmacology has shown that SG-D can act on multiple targets through multiple ingredients and treat GC by regulating multiple signaling pathways. In vitro cell experiments have also confirmed this, so as to provide a reference for subsequent related research.


Assuntos
Carcinoma , Farmacologia em Rede , Humanos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
15.
Oral Oncol ; 137: 106304, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608459

RESUMO

OBJECTIVES: In head and neck squamous cell carcinoma (HNSCC), poor prognosis and low survival rates are associated with downregulated calprotectin. Calprotectin (S100A8/A9) inhibits cancer cell migration and invasion and facilitates G2/M cell cycle arrest. We investigated whether S100A8/A9 regulates DNA damage responses (DDR) and apoptosis in HNSCC after chemoradiation. MATERIALS AND METHODS: Human HNSCC cases in TCGA were analyzed for relationships between S100A8/A9 and expression of apoptosis-related genes. Next, S100A8/A9-expressing and non-expressing carcinoma lines (two different lineages) were exposed to genotoxic agents and assessed for 53BP1 and γH2AX expression and percent of viable/dead cells. Finally, S100A8/A9-wild-type and S100A8/A9null C57BL/6j mice were treated with 4-NQO to induce oral dysplastic and carcinomatous lesions, which were compared for levels of 53BP1. RESULTS: In S100A8/A9-high HNSCC tumors, apoptosis-related caspase family member genes were upregulated, whereas genes limiting apoptosis were significantly downregulated based on TCGA analyses. After X-irradiation or camptothecin treatment, S100A8/A9-expressing carcinoma cells (i.e., TR146 and KB-S100A8/A9) showed significantly higher 53BP1 and γH2AX expression, DNA fragmentation, proportions of dead cells, and greater sensitivity to cisplatin than wild-type KB or TR146-S100A8/A9-KD cells. Interestingly, KB-S100A8/A9Δ113-114 cells showed similar 53BP1 and γH2AX levels to S100A8/A9-negative KB and KB-EGFP cells. After 4-NQO treatment, 53BP1 expression in oral lesions was significantly greater in calprotectin+/+ than S100A8/A9null mice. CONCLUSIONS: In HNSCC cells, intracellular calprotectin is strongly suggested to potentiate DDR and promote apoptosis in response to genotoxic agents. Hence, patients with S100A8/A9-high HNSCC may encounter more favorable outcomes because more tumor cells enter apoptosis with increased sensitivity to chemoradiation therapy.


Assuntos
Carcinoma , Neoplasias de Cabeça e Pescoço , Animais , Camundongos , Humanos , Complexo Antígeno L1 Leucocitário/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Calgranulina B/metabolismo , Camundongos Endogâmicos C57BL , Calgranulina A/genética , Calgranulina A/metabolismo , Apoptose , Neoplasias de Cabeça e Pescoço/genética
16.
Oral Oncol ; 137: 106297, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36610231

RESUMO

The use of anticancer drugs targeting specific molecular tumor characteristics is rapidly increasing in clinical practice, but selecting patients to benefit from these remains a challenge. It has been suggested that organoid cultures would be ideally suited to test drug responses in vitro. Here we describe and characterize in depth a case of ETV6-NTRK3 gene fusion-positive secretory carcinoma of the salivary glands and corresponding organoid cultures that responded and subsequently acquired resistance to TRK targeting therapy with larotrectinib. This case-culture-characterization illustrates the advances made in precision oncology, but also exposes important caveats in using organoids to predict treatment response.


Assuntos
Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/tratamento farmacológico , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Proteínas de Fusão Oncogênica/genética , Imuno-Histoquímica , Medicina de Precisão , Glândulas Salivares/patologia , Carcinoma/patologia , Biomarcadores Tumorais/genética
17.
PLoS One ; 18(1): e0280735, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36696374

RESUMO

Lesions diagnosed as gastric low-grade dysplasia (LGD) may be pathologically upgraded to early gastric cancer (EGC) or high-grade dysplasia (HGD) after endoscopic resection (ER). In this study, we investigated the risk factors for pathological upgrades after ER and assessed the reason for these upgrades by retrospectively analyzing ER data between January 1999 and December 2019. We enrolled patients with LGD confirmed by forceps biopsy; the patients were classified into pathologically concordant (LGD) and upgraded (HGD and EGC) groups according to the pathology of their resected specimen. To determine the risk factors for upgrade, we compared the endoscopic findings of the concordant and upgraded groups via 1:1 matched case-control design. To find the reasons for discordance, all upgraded cases were pathologically re-evaluated. Among 1,643 cases of LGD, pathological upgrades were observed in 423 (25.7%) resected specimens and EGC was found in 111 (6.7%) lesions. After matching the upgraded and concordant cases, lesion sizes exceeding 1.5 cm (odds ratio (OR): 1.8; 95% CI: 1.1-3.0), mucosal nodularity (OR: 10.8; 95% CI: 5.6-21.0), heterogeneous color (OR: 3.0; 95% CI: 1.7-5.3), presence of erosion (OR: 2.7; 95% CI: 1.8-5.3), and open-type gastric atrophy (OR: 2.9; 95% CI: 1.7-4.9) were noted to be significantly associated with upgraded pathology to EGC. Among the EGC cases, 99 (89.2%) were found to have pre-existing dysplasia. In conclusion, endoscopic evaluations should be performed because of possible pathological upgrades and co-existence of carcinomas in LGDs, especially when they exhibit surface nodularity, erosion, heterogeneous color, and large size.


Assuntos
Carcinoma , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Gastroscopia , Neoplasias Gástricas/patologia , Biópsia , Hiperplasia
18.
Int J Mol Sci ; 24(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36675253

RESUMO

Over the years, increasing evidence has shown that copy number variations (CNVs) play an important role in the pathogenesis and prognosis of Colorectal Cancer (CRC). Colorectal adenomas are highly prevalent lesions, but only 5% of these adenomas ever progress to carcinoma. This review summarizes the different CNVs associated with adenoma-carcinoma CRC progression and with CRC staging. Characterization of CNVs in circulating free-RNA and in blood-derived exosomes augers well with the potential of using such assays for patient management and early detection of metastasis. To overcome the limitations related to tissue biopsies and tumor heterogeneity, using CNVs to characterize tumor-derived materials in biofluids provides less invasive sampling methods and a sample that collectively represents multiple tumor sites in heterogeneous samples. Liquid biopsies provide a source of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), tumor-derived exosomes (TDE), circulating free RNA, and non-coding RNA. This review provides an overview of the current diagnostic and predictive models from liquid biopsies.


Assuntos
Adenoma , Carcinoma , Ácidos Nucleicos Livres , Neoplasias Colorretais , Células Neoplásicas Circulantes , Humanos , Variações do Número de Cópias de DNA/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Biópsia Líquida/métodos , Ácidos Nucleicos Livres/genética , Células Neoplásicas Circulantes/patologia , RNA , Biomarcadores Tumorais/genética , Adenoma/diagnóstico , Adenoma/genética
19.
Cancer Lett ; 555: 216057, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36627048

RESUMO

Ovarian carcinoma (OC) is an umbrella term for multiple distinct diseases (histotypes), each with their own developmental origins, clinical behaviour and molecular profile. Accordingly, OC management is progressing away from a one-size-fits all approach, toward more molecularly-driven, histotype-specific management strategies. Our knowledge of driver events in high grade serous OC, the most common histotype, has led to major advances in treatments, including PARP inhibitor use. However, these agents are not suitable for all patients, most notably for many of those with rare OC histotypes. Identification of additional targeted therapeutic strategies will require a detailed understanding of the molecular landscape in each OC histotype. Until recently, tumour profiling studies in rare histotypes were sparse; however, significant advances have been made over the last decade. In particular, reports of genomic characterisation in endometrioid, clear cell, mucinous and low grade serous OC have significantly expanded our understanding of mutational events in these tumour types. Nonetheless, substantial knowledge gaps remain. This review summarises our current understanding of each histotype, highlighting recent advances in these unique diseases and outlining immediate research priorities for accelerating progress toward improving patient outcomes.


Assuntos
Carcinoma , Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Epitelial do Ovário/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/metabolismo , Cistadenocarcinoma Seroso/patologia , Mutação
20.
Curr Oncol ; 30(1): 1000-1009, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36661725

RESUMO

(1) Background: Prophylactic percutaneous endoscopic gastrostomy (PEG) maintained nutritional status and improved survival of patients with locally advanced nasopharyngeal carcinoma (LA-NPC). However, the role of PEG in patients' quality of life (QoL) is still controversial. We aimed to investigate the effect of PEG on the QoL of patients with LA-NPC without progression. (2) Methods: Patients with LA-NPC between 1 June 2010 and 30 June 2014 in Fujian Cancer Hospital were divided into PEG and non-PEG groups. The QoL Questionnaire core 30 (QLQ-C30), incidence of adverse effects, weight, and xerostomia recovery were compared between the two groups of patients without progression as of 30 June 2020. (3) Results: No statistically significant difference in the scores of each QLQ-C30 scale between the two groups (p > 0.05). The incidence of xerostomia was higher in the PEG group than in the non-PEG group (p = 0.044), but the association was not seen after adjusting for gender, age, T, and N stage (OR: 0.902, 95%CI: 0.485-1.680). No significant difference in the incidence of other adverse effects as well as in weight and dry mouth recovery (p > 0.05). (4) Conclusion: PEG seems not to have a detrimental effect on long-term Qol, including the self-reported swallowing function of NPC patients without progressive disease.


Assuntos
Carcinoma , Neoplasias Nasofaríngeas , Xerostomia , Humanos , Carcinoma Nasofaríngeo , Qualidade de Vida , Estudos Transversais , Gastrostomia/efeitos adversos , Xerostomia/etiologia , Neoplasias Nasofaríngeas/terapia
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