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1.
Braz. j. oral sci ; 20: e210298, jan.-dez. 2021. ilus
Article in English | LILACS, BBO | ID: biblio-1252387

ABSTRACT

Oral squamous cell carcinoma (OSCC) is one of the most well-known malignancies that affect the human population worldwide. The early diagnosis and early intervention of OSCC help improve the survival rate of the patients. The tumour free surgical margins are a positive prognostic factor for recurrence-free survival. The molecular markers can be used to detect the tumour free surgical margins. Aim: The aim of the study is to evaluate the expression of p53 & Cyclin D1 marker in resected surgical apparently clear margins and to correlate the p53 & Cyclin D1 expression with clinicopathological characteristics and patient outcome. Methods: The study population included retrospective cases of OSCC with apparently clear margins (2017-18) n=10 and Clinicopathological variables relevant to survival analysis were recorded. Finally, two margins were selected from each case, a total of 20 margins were included in this study. Paraffin-embedded wax blocks retrieved and tissue sections were made. Expression of cyclin D1 and p 53 was assessed by the immunohistochemical staining procedure Results: Positive expressions Cyclin D1 in 40% of mild dysplasia margins and 60% in clearance adequate margins were present. p53 expression was seen in 16% of mild dysplasia margins and 84% in clearance adequate margins. The expression of p53 and Cyclin D1 molecular markers are noted in the basal & parabasal layer of epithelium. Conclusion: Molecular markers could play a more reliable method for the assessment of dysplasia at the margins


Subject(s)
Humans , Male , Female , Carcinoma, Squamous Cell , Tumor Suppressor Protein p53 , Cyclin D1
2.
Braz. dent. j ; 31(3): 290-297, May-June 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1132302

ABSTRACT

Abstract Chloride intracellular channel-4 (CLIC4) is regulated by p53 and tumor necrosis factor-α (TNF-α), it is linked to the increase of transforming growth factor-β (TGF-β), and myofibroblastic differentiation in skin carcinogenesis. This study analyzed the immunoexpression of CLIC4, p53, TGF-β, TNF-α, and α-SMA in 50 actinic cheilitis (AC) and 50 lower lip squamous cell carcinoma (LLSCC). AC and LLSCC immunoexpression were categorized as score 1 (<5% positive cells), 2 (5-50%) or 3 (>50%). For CLIC4, nuclear and cytoplasmic immunostaining of epithelial cells was considered individually. For morphologic analysis, the World Health Organization criteria were used to epithelial dysplasia grade of ACs, and Bryne grading of malignancy system was applied for LLSCC. Higher nuclear CLIC4 (CLIC4n) and TGF-β were observed in ACs with low-risk of transformation, while cytoplasmic CLIC4 (CLIC4c), p53 and TNF-α were higher in the high-risk cases (p<0.05). In LLSCCs, CLIC4c was higher in cases with lymph node metastasis, advanced clinical stages, and histological high-grade malignancy. p53 expression was higher in high-grade LLSCCs, whereas TGF-β decreased as the clinical stage and morphological grade progressed (p<0.05). ACs showed an increased expression of CLIC4n and TGF-β, while CLIC4c and α-SMA were higher in LLSCCs (p<0.0001). Both lesions showed negative correlation between CLIC4n and CLIC4c, while in LLSCCs, negative correlation was also verified between CLIC4c and p53, as well as CLIC4c and TGF-β (p<0.05). Change of CLIC4 from the nucleus to cytoplasm and alterations in p53, TGF-β, TNF-α, and α-SMA expression are involved in lip carcinogenesis.


Resumo O canal intracelular de cloreto 4 (CLIC4) é regulado pela p53 e fator de necrose tumoral α (TNF-α) e está relacionado ao aumento do fator de crescimento transformador β (TGF-β) e na diferenciação miofibroblástica na carcinogênese cutânea. Este estudo analisou a imunoexpressão de CLIC4, p53, TGF-β, TNF-α e α-SMA em 50 queilites actínicas (QA) e 50 carcinomas de células escamosas de lábio inferior (CCELI). A imunoexpressão da QA e CCELI foram categorizadas em escore 1 (<5% de células positivas), 2 (5-50%) ou 3 (>50%). Para CLIC4, a imunomarcação nuclear e citoplasmática das células epiteliais foi considerada separadamente. Para análise morfológica, foram utilizados os critérios da Organização Mundial da Saúde para a gradação das displasias epiteliais nas QAs, e o sistema de gradação de malignidade de Bryne foi utilizado para os casos de CCELIs. Alta imunoexpressão de CLIC4 nuclear (CLIC4n) e TGF-β foi observada em QA de baixo risco de transformação, enquanto CLIC4 citoplasmática (CLIC4c), p53 e TNF-α foram elevadas nos casos de alto risco (p<0.05). No CCELI, a imunoexpressão de CLIC4c foi maior em caos com metástase linfonodal, estágio clínico avançado e alto grau histológico de malignidade. A expressão de p53 foi elevada em CCELI de alto grau, enquanto o TGF-β diminuiu à medida que o estádio clínico e o grau morfológico progrediram (p<0.05). QAs exibiram uma elevada expressão de CLIC4n e TGF-β, enquanto o CLIC4c e α-SMA foram elevados em CCELIs (p<0.0001). Ambas as lesões mostraram correlação negativa entre CLIC4n e CLIC4c, enquanto nos CCELIs, também se verificou correlação negativa entre CLIC4c e p53, assim como entre CLIC4c e TGF-β (p<0.05). Alteração do CLIC4 do núcleo para o citoplasma e alterações na expressão de p53, TGF-β, TNF-α, e α-SMA estão envolvidas na carcinogênese labial.


Subject(s)
Humans , Lip Neoplasms , Transforming Growth Factor beta , Tumor Suppressor Protein p53 , Tumor Necrosis Factor-alpha , Chloride Channels , Myofibroblasts , Carcinogenesis , Lip
3.
Medicina (B.Aires) ; 80(2): 127-133, abr. 2020. ilus, tab
Article in Spanish | LILACS | ID: biblio-1125052

ABSTRACT

El carcinoma escamoso vulvar puede desarrollarse de manera asociada o independiente a la infección por HPV. La relación entre la patogénesis, la clasificación, el perfil inmunohistoquímico, y el pronóstico ha sido estudiada con algunas discrepancias. El objetivo del trabajo fue observar la concordancia clásicamente descripta que asocia a los carcinomas queratinizantes con la ausencia de infección por HPV y a los carcinomas warty y basaloides con la presencia de dicho virus. Para ello, revisamos la clínica, la morfología y el inmunofenotipo de 39 casos de nuestro hospital. Los tumores fueron clasificados histológicamente en carcinomas escamosos queratinizantes clásicos (30), warty (5) y basaloides (4). En el análisis estadístico la expresión de p16 fue asociada de manera significativa con una edad menor al momento del diagnóstico (p = 0.0025), presencia de lesión intraepitelial escamosa de alto grado (p < 0.0001), coilocitosis (p = 0.02), y subtipo morfológico (p = 0.02); y fue inversamente asociado con la expresión de p53 (p < 0.0001) y con el liquen escleroso (p = 0.0051). Resulta peculiar que, de los casos estudiados, 4 carcinomas queratinizantes coexpresaron p16 y p53. Un solo tumor de tipo warty resultó negativo para p16 y positivo para p53, y 9 queratinizantes resultaron positivos para p16 y negativos para p53. Si bien estos hallazgos indican que con la sola utilización de la hematoxilina y eosina podrían definirse de manera correcta los tumores asociados al HPV, sugerimos fuertemente la realización de inmunohistoquímica, especialmente en carcinomas escamosos queratinizantes en pacientes jóvenes o con historia de HPV.


Squamous cell carcinoma of the vulva may develop in association or independently of HPV infection. The relationship between pathogenesis, classification, immunohistochemical profile and prognosis has been studied in the literature with some discrepancies. The aim of this study was to observe the classical association of keratinizing carcinomas with the absence of HPV infection and warty and basaloid carcinomas with the presence of this virus. Therefore, we reviewed the clinic, morphology, and immunophenotype of 39 cases. The tumors were histologically classified into classic keratinizing squamous carcinoma (30), warty (5) and basaloid (4). In the statistical analysis, diffuse expression with p16 was significantly associated with younger age (p = 0.0025), presence of high-grade intraepithelial lesion (p < 0.0001), koilocytosis (p = 0.02), and morphological subtype (p = 0.02), and was inversely associated with the expression of p53 (p < 0.0001) and the presence of lichen sclerosus (p = 0.0051). It is curious that 4 keratinizing carcinomas of the cases studied presented coexpression of p16 and p53. Only one warty tumor was negative for p16 and positive for p53, and 9 keratinizing tumors were positive for p16 and negative for p53. Although these findings show that the use of hematoxylin and eosin could correctly define tumors associated with HPV, we strongly suggest the performance of immunohistochemistry, especially in squamous keratinizing classic carcinomas in young patients with a history of HPV.


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Vulvar Neoplasms/metabolism , Immunohistochemistry , Carcinoma, Squamous Cell/metabolism , Tumor Suppressor Protein p53/metabolism , Papillomaviridae , Vulvar Neoplasms/diagnosis , Warts , Carcinoma, Squamous Cell/diagnosis , Biomarkers, Tumor , Papillomavirus Infections , Carcinogenesis
4.
Rev. bras. anal. clin ; 52(1): 18-26, 20200330. ilus, tab
Article in Portuguese | LILACS | ID: biblio-1104126

ABSTRACT

A maioria das neoplasias na bexiga tem início no urotélio. O carcinoma das células de transição é o mais comum. A citologia urinária juntamente com a cistoscopia, permanece como ferramenta de diagnóstico e monitoração. Alguns marcadores potenciais foram reconhecidos em espécimes de citologia urinária, incluindo a proteína p53. O objetivo desta pesquisa foi descrever os marcadores moleculares para diferenciação diagnóstica do carcinoma urotelial. Foi realizado um estudo de revisão de literatura. Quando observamos o carcinoma urotelial, notamos que há dissensões resultantes em variantes histológicas; sendo assim, utilizamos a imuno-histoquímica para confirmar sua origem. O urotelioma apresenta microhematúria, macrohematúria indolor. As células apresentam ocasionalmente um arranjo "semelhante a janela". Os biomarcadores baseiam-se na expressão diferencial das proteínas, DNA, RNA ou marcadores relacionados ao câncer. Observou-se que a citologia apresenta uma baixa sensibilidade, porém, em concentrações mais altas, a sua especificidade é >90%. A sensibilidade combinada da maioria dos marcadores variou e a especificidade da maioria variou entre 70% a 90%, menor que a citologia urinária. Nisso, os marcadores passam por estudos constantes para melhorar as tecnologias atuais. Embora a técnica seja de alto custo, a utilização e combinação de biomarcadores juntamente com a citologia urinária tem resultado na alta sensibilidade e especificidade.


The majority of neoplasms in the bladder have no onset urothelium. Transitional cell carcinoma is the most common. A urinary cytology together with cystoscopy remain as a diagnostic and monitoring toll. Some potential molecular markers were recognized in urinary cytology specimens, including the p53 protein. The objective of this research was to describe the molecular markers for diagnostic differentiation of urothelial carcinoma. A review of the literature was performed. When we observe the urothelial carcinoma, we notice that there are dissensions resulting in histological variants, and, therefore, it uses immunohistochemistry to confirm your origin. Urotelioma presents microhematúria, painless macrohematúria. As cells do not urotelioma occasionally transformed a "window-like" arrangement. The biomarkers are based on the differential expression of proteins, DNA, RNA or cancer-related markers. It was observed that cytology has a low sensitivity, but at higher concentrations its specificity (>90%). A combined sensitivity of most markers ranged and the specificity of the majority varied from 70% to 90%, lower than urinary cytology. In this, the markers go through constant studies to improve it as current technologies. Although a high-cost technique, a use and combination of biomarkers with urinary cytology results in high sensitivity and specificity.


Subject(s)
Urinary Bladder Neoplasms , Immunohistochemistry , Biomarkers, Tumor , Tumor Suppressor Protein p53 , Diagnosis, Differential
5.
Article in Chinese | WPRIM | ID: wpr-880803

ABSTRACT

OBJECTIVE@#To investigate the effect of palbociclib on cell cycle progression and proliferation of human renal tubular epithelial cells.@*METHODS@#Human renal tubular epithelial cell line HK-2 was treated with 1, 5, 10, and 20 μmol/L of palbociclib, and the changes in cell proliferation and viability were examined by cell counting and CCK8 assay. EDU staining was used to assess the proliferation of HK-2 cells following palbiciclib treatment at different concentrations for 5 days. The effect of palbociclib on cell cycle distribution of HK-2 cells was evaluated using flow cytometry. SA-β-Gal staining and C12FDG senescence staining were used to detect senescence phenotypes of HK-2 cells after palbociclib treatment at different concentrations for 5 days. The relative mRNA expression levels of P16, P21, and P53 and the genes associated with senescence-related secretion phenotypes were detected by RT-PCR, and the protein expressions of P16, P21 and P53 were detected by Western blotting.@*RESULTS@#Palbociclib inhibited HK-2 cell proliferation and induced cell cycle arrest in G1 phase. Compared with the control cells, HK-2 cells treated with high-dose (10 μmol/L) palbociclib exhibited significantly suppressed cell proliferation activity, and the inhibitory effect was the most obvious on day 5 (@*CONCLUSIONS@#Palbociclib induces HK-2 cell senescence by causing cell growth arrest and delaying cell cycle progression.


Subject(s)
Cell Cycle , Cell Cycle Checkpoints , Cellular Senescence , Epithelial Cells , Humans , Piperazines/pharmacology , Pyridines/pharmacology , Tumor Suppressor Protein p53/genetics
6.
Article in English | WPRIM | ID: wpr-811139

ABSTRACT

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.METHODS: Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.RESULTS: DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).CONCLUSION: FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.


Subject(s)
Animals , Connective Tissue Growth Factor , Diabetes Mellitus, Type 1 , Diabetic Nephropathies , Epithelial-Mesenchymal Transition , Fibroblast Growth Factors , Fibroblasts , Fibrosis , Hypertrophy , Injections, Intraperitoneal , Kidney , Mice , Phosphorylation , Streptozocin , Transforming Growth Factor beta , Tumor Suppressor Protein p53
7.
Journal of Experimental Hematology ; (6): 1221-1227, 2020.
Article in Chinese | WPRIM | ID: wpr-827136

ABSTRACT

OBJECTIVE@#To investigate the clinical efficacy and prognosis of double-hit multiple myeloma patients with deletion P53 treated with regimen based on bortezomib.@*METHODS@#The ethnical data from 186 newly diagnosed MM patients hospitalized in the Department of Hematology of Harrison International Peace hospital from January 2012 to January 2019 were analyzed retrospectively. The fluorescent in situ hybridization (FISH) and G-binding staining were used to detect cytogenetic abnormalities (P53 deletion, lq21 amplification and IgH rearranagement) for analyses of complete remission (CR), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) of patients treated with bortezomib for 4 circles.@*RESULTS@#In 186 patients, simple P53 deletion was 14 cases, 1q21 amplification and P53 deletion were found in 11 cases (A group), t (14;16) and P53 deletion in 7 cases (B group), t (4;14) and P53 deletion in 9 cases (C group). The complete remission rate (CR%) of above-mentioned three groups was 27.27%, 28.57% and 33.33% respectively, and the ORR of the three groups was 54.54%, 57.14% and 55.56%, respectively, there was no statistically significant difference between the three groups (P>0.05). The patients with 1q21 amplification and P53 deletion had shorter OS and PFS time (P=0.041, P=0.046). The double-hit patients with 1q21 amplification showed shorter OS time, compared with the patients with P53 deletion (P=0.027). The double-hit patients with t(14;16) and t(4;14) showed shorter OS time (P=0.871, P=0.276) and PFS time (P=0.955, P=0.379) than those of the patients with P53 deletion.@*CONCLUSION@#P53 deletion and 1q21 amplification are an adverse prognostic factor of early recurrence and short lifetime in patients with newly diagnosed double-hit MM.


Subject(s)
Bortezomib , Chromosome Aberrations , Humans , In Situ Hybridization, Fluorescence , Multiple Myeloma , Prognosis , Retrospective Studies , Treatment Outcome , Tumor Suppressor Protein p53
8.
Biol. Res ; 53: 13, 2020. tab, graf
Article in English | LILACS | ID: biblio-1100919

ABSTRACT

BACKGROUND: Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. RESULTS: After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. CONCLUSIONS: The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.


Subject(s)
Humans , Animals , Male , Middle Aged , Antigens, Tumor-Associated, Carbohydrate/genetics , Indians, South American/genetics , Gallbladder Neoplasms/genetics , Ascitic Fluid/metabolism , Tumor Cells, Cultured , Carcinogenicity Tests , Chile , DNA Fingerprinting , Tumor Suppressor Protein p53/genetics , Cisplatin/pharmacology , Mice, Inbred NOD , Clone Cells/drug effects , Clone Cells/metabolism , Sequence Analysis, RNA , Receptor, ErbB-2/genetics , Genes, erbB-2/genetics , Gene Expression Profiling , Cell Line, Tumor/drug effects , Cell Line, Tumor/metabolism , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Epithelial Cells/metabolism , Keratin-19/genetics , Keratin-7/genetics , Carcinogenesis/genetics , Gallbladder Neoplasms/metabolism , Antineoplastic Agents/pharmacology
9.
Article in Chinese | WPRIM | ID: wpr-828235

ABSTRACT

OBJECTIVE@#To observe effects of (, TLZT) gel preparation on p53, miR-502-5p, NF-κBp65 in synovial tissue of knee osteoarthritis (KOA), and to explore mechanism of TLZT gel preparation in treating KOA.@*METHODS@#Thirthy-six Wistar rats aged 8 weeks and weighed 200 to 220 g (meaned 208 g) were randomly divided into normal group, model group and traditional Chinese medicine (TCM) group, 12 rats in each group. KOA model was established by modified Hulth method. After 4 weeks of modeling, TCM group treated with TLZT gel preparation for external use, 3 times daily for 2 weeks;normal group and model group were fed normally without intervention. After treatment, morphological changes of specimens in each group were observed, changes of miR-502-5p in synovial tissue were detected by qPCR, and contents of p53, NF-κBp65, IL-1β, TNF-α, MMP-13 in synovial tissue were detected by qPCR and Western Blot respectively.@*RESULTS@#(1)Morphological observation of specimens showed that the articular cartilage in model group was hyaline and uneven, the synovial membranes were hypertrophic and proliferative with a large number of inflammatory cells infiltrating, the joint fluid was thicker in texture;the articular cartilage in TCM group was more transparent and smooth, synovial hyperplasia was mild with a small amount of inflammatory cell infiltration, the texture of articular fluid was clear and sparse. (2) Compared with normal group, content of miR-502-5p of synovial tissue in model and TCM group were increased, mRNA and expression of p53 decreased, expression of NF-κBp65, IL-1β, TNF-α, MMP-13 increased. (3)Compared with model group, content of miR-502-5p in synovial tissue of TCM group decreased (<0.05), mRNA and protein expression of p53 increased (<0.05), mRNA and protein expression of NF-κBp65, IL-1β, TNF-α, MMP-13 decreased (<0.05).@*CONCLUSION@#Expression of p53, miR-502 -5p, NF -κBp65 in synovial tissue is closely related to synovial hyperplasia and inflammatory reaction, TLZT gel preparation may reduce proliferation and inflammatory reaction of KOA synovium by regulating the expression of p53, miR- 502-5p, NF-κBp65 in synovial tissues.


Subject(s)
Animals , Drugs, Chinese Herbal , MicroRNAs , Osteoarthritis, Knee , Rats , Rats, Wistar , Synovial Membrane , Tumor Suppressor Protein p53
10.
Int. braz. j. urol ; 45(4): 671-678, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019884

ABSTRACT

ABSTRACT Introduction Penile cancer (PC) occurs less frequently in Europe and in the United States than in South America and parts of Africa. Lymph node (LN) involvement is the most important prognostic factor, and inguinal LN (ILN) dissection can be curative; however, ILN dissection has high morbidity. A nomogram was previously developed based on clinicopathological features of PC to predict ILN metastases. Our objective was to conduct an external validation of the previously developed nomogram based on our population. Materials and methods We included men with cN0 ILNs who underwent ILN dissection for penile carcinoma between 2000 and 2014. We performed external validation of the nomogram considering three different external validation methods: k-fold, leave-one-out, and bootstrap. We also analyzed prognostic variables. Performance was quantified in terms of calibration and discrimination (receiver operator characteristic curve). A logistic regression model for positive ILNs was developed based on clinicopathological features of PC. Results We analyzed 65 men who underwent ILN dissection (cN0). The mean age was 56.8 years. Of 65 men, 24 (36.9%) presented with positive LNs. A median 21 ILNs were removed. Considering the three different methods used, we concluded that the previously developed nomogram was not suitable for our sample. Conclusions In our study, the previously developed nomogram that was applied to our population had low accuracy and low precision for correctly identifying patients with PC who have positive ILNs.


Subject(s)
Humans , Male , Adult , Aged , Aged, 80 and over , Penile Neoplasms/pathology , Carcinoma/pathology , Nomograms , Inguinal Canal/pathology , Lymph Nodes/pathology , Lymphatic Metastasis/diagnosis , Reference Values , Logistic Models , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Risk Factors , ROC Curve , Tumor Suppressor Protein p53/analysis , Statistics, Nonparametric , Neoplasm Grading , Lymph Node Excision , Middle Aged , Neoplasm Staging
11.
Säo Paulo med. j ; 137(1): 33-38, Jan.-Feb. 2019. tab
Article in English | LILACS | ID: biblio-1004740

ABSTRACT

ABSTRACT BACKGROUND: There are cases of colorectal tumors that, although small, show more aggressive evolution than large tumors. This motivated us to study whether there are any proteins capable of alerting about these changes. The aim here was to correlate the immunoexpression of the TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers in tumors in patients with colorectal adenocarcinoma, with the degree of cell differentiation, tumor staging and clinical-pathological prognostic factors. DESIGN AND SETTING: Retrospective observational study at a public tertiary-level hospital. METHODS: We analyzed tissue-microarray paraffin blocks of tumor tissues that had been resected from 107 patients. We used Fisher's exact test to study associations between tumor differentiation/staging and the immunoexpression of biomarkers. We also used Kaplan-Meier estimation, the log-rank test and the adjusted Cox regression model to investigate the patients' overall survival (in months) according to biomarkers and disease-free interval. RESULTS: The degree of tumor differentiation and tumor staging were not associated with the biomarkers, except in cases of patients in stages III or IV, in which there was a correlation with MLH1 expression (P=0.021). Patient survival and disease-free interval were not associated with the biomarkers. CONCLUSION: There were no associations between the degree of tumor differentiation, staging, length of survival or disease-free interval and the immunoexpression of the TS, p53, COX2, EGFR or MSH6 tumor markers. In advanced cases of colorectal adenocarcinoma (stages III and IV), there was a higher percentage of MLH1-negative results.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Adenocarcinoma/pathology , Biomarkers, Tumor/analysis , Reference Values , Thymidylate Synthase/analysis , Immunohistochemistry , Adenocarcinoma/mortality , Proportional Hazards Models , Retrospective Studies , Longitudinal Studies , Tumor Suppressor Protein p53/analysis , Tissue Array Analysis , DNA-Binding Proteins/analysis , Cyclooxygenase 2/analysis , Kaplan-Meier Estimate , ErbB Receptors/analysis , MutL Protein Homolog 1/analysis , Neoplasm Staging
13.
Chinese Medical Journal ; (24): 525-533, 2019.
Article in English | WPRIM | ID: wpr-774810

ABSTRACT

BACKGROUND@#Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL.@*METHODS@#This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS). Receiver operator characteristic curves and area under the curve (AUC) were utilized to assess the predictive accuracy of ANAs together with other independent factors for OS.@*RESULTS@#The incidence of ANAs abnormality at diagnosis was 13.9%. ANAs positivity and TP53 disruption were independent prognostic indicators for OS. The AUC of positive ANAs together with TP53 disruption was 0.766 (95% confidence interval [CI]: 0.697-0.826), which was significantly larger than that of either TP53 disruption (AUC: 0.706, 95% CI: 0.634-0.772, P = 0.034) or positive ANAs (AUC: 0.595, 95% CI: 0.520-0.668, P < 0.001) in OS prediction. Besides, serum positive ANAs as one additional parameter to CLL-international prognostic index (IPI) obtained superior AUCs in predicting CLL OS than CLL-IPI alone.@*CONCLUSION@#This study identified ANAs as an independent prognostic factor for CLL, and further investigations are needed to validate this finding.


Subject(s)
ADP-ribosyl Cyclase 1 , Blood , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Antinuclear , Blood , Autoimmunity , Physiology , Female , Humans , Kaplan-Meier Estimate , Leukemia, Lymphocytic, Chronic, B-Cell , Blood , Mortality , Male , Middle Aged , Multivariate Analysis , Mutation , Genetics , Proportional Hazards Models , Retrospective Studies , Survival Analysis , Tumor Suppressor Protein p53 , Blood , Young Adult , ZAP-70 Protein-Tyrosine Kinase , Blood
14.
Article in Chinese | WPRIM | ID: wpr-771869

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics of myelodysplastic syndrome (MDS) with TP53 mutant and the relationship between TP53 mutation and monosomal karyotype in MDS patients.@*METHODS@#The TP53 mutations in 102 patients with de nove MDS were retrospectively analyzed, and the clinical features of the TP53 mutation group and the non-mutation group were compared. The relationship between TP53 mutation and karyotype, especially monosomal karyotype was analyzed.@*RESULTS@#Fifty-two out of the 102 MDS patients were male and 50 were female, the median age was 59.5 (23-83) years old. The mutational frequency of TP53 was 12.7%, which mostly occurred in patients with MDS-EB. As compared with non-mutation group, the hemoglobin level and platelet count were lower (P=0.001, P=0.033), the LDH level and bone marrow blast ratio were higher in TP53 mutation group (P=0.002, P<0.001), but the statistical difference of alsolute count of neutrophils and levels of serum ferritin and β2-microglobulin between 2 groups was not found. The karyotype abnormality frequency of patients with TP53 mutation was 90.9%, among them 72.7% was monosomal karyotype. The incidence of monosomal karyotype in the TP53 mutation group was very significantly higher than that in the non-mutation group (P<0.001). MDS with TP53 mutation and monosomal karyotype appeared in the groups with high and very high IPSS-R risk.@*CONCLUSION@#MDS patients with TP53 mutation have unique clinical features and high incidence of monosomal karyotype, and their overall prognosis is poor.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Karyotype , Karyotyping , Male , Middle Aged , Mutation , Myelodysplastic Syndromes , Genetics , Prognosis , Retrospective Studies , Tumor Suppressor Protein p53 , Genetics , Young Adult
15.
Journal of Experimental Hematology ; (6): 1001-1007, 2019.
Article in Chinese | WPRIM | ID: wpr-771848

ABSTRACT

OBJECTIVE@#To investigate the methylation status of CHD5 gene promoter in bone marrow from acute myeloid leukemia (AML) patients, and the underlying mechanism for initiating the pathogenesis of AML via p19/p53/p21 pathway.@*METHODS@#Methylation status of the CHD5 gene promoter was detected by using methylation-specific polymerase chain reaction (MSPCR) in bone marrow from AML patients, and the iron-deficiency anemia (IDA) samples were served as control. The expression of CHD5, p19, p53 and p21 was determined by real-time quantitative reverse transcriptase PCR and Western blot.@*RESULTS@#The methylation of CHD5 gene in bone marrow from AML patients increased significantly (39.06%) as compared with control group (6.67%). The methylation of CHD5 gene significantly correlated with chromosome karyotype differentiation (P<0.01), but did not correlate with the patient's sex, age and clinical classification (P>0.05). The mRNA expression of CHD5 gene in AML decreased, compared with control group, the mRNA and protein expression of p19, p53 and p21 in AML with CHD5 methylation promoter decreased.@*CONCLUSION@#The hypermeltylation of CHD5 gene promoter in AML patients can lead to decrease of CHD5, p19, p53 and p21 expression levels which may reduce the inhibitory effect on proliferation of leukemia cells through the regulation of p19, p53 and p21 pathway, thus promotes the occurence of AML.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p16 , Cyclin-Dependent Kinase Inhibitor p21 , DNA Helicases , DNA Methylation , Humans , Leukemia, Myeloid, Acute , Nerve Tissue Proteins , Promoter Regions, Genetic , Tumor Suppressor Protein p53
16.
Article in English | WPRIM | ID: wpr-771436

ABSTRACT

OBJECTIVE@#To investigate the effect of a modified Wuzi Yanzong Pill (, WZYZP) on the male rats' testis after microwave radiation, as well as its potential mechanism.@*METHODS@#Forty-five male rats were randomly assigned to three groups: the control group, the radiation group, and the WZYZP group. The rats in the radiation group and WZYZP group were exposed to microwave radiation for 15 min once, while the rats in the control group were not exposed to any radiation. The rats in the WZYZP group were given a modified of WZYZP by gavage daily for 7 days. Apoptosis in the testis was evaluated using terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. Histopathological alterations of the testis were observed by haematoxylin-eosin (HE) staining. Tat-interactive protein, 60kD (Tip60) and p53 expressions were determined by Western blotting.@*RESULTS@#The apoptosis index (AI) in the radiation group was higher than that of the WZYZP group and control group on day 1 (D1), day 7 (D7) day 14 (D14) after radiation (P<0.05). The seminiferous tubules were of normal morphology in the control group. In the radiation group, the partial seminiferous tubules were collapsed, basement membranes of the seminiferous epithelia became detached. WZYZP could restore the morphological changes. There was no expression of Tip60 among the three groups on D7 and D14. The expression of p53 was higher in the radiation group than in the control group (P<0.05). WZYZP could down-regulate the rising p53 induced by radiation on D7 and D14 (P<0.05).@*CONCLUSION@#A modified WZYZP may affect germ cells, and its protective effects may partly result from its ability to intervene in Tip60 mediated apoptosis.


Subject(s)
Animals , Apoptosis , Drugs, Chinese Herbal , Pharmacology , Male , Microwaves , Rats, Wistar , Testis , Metabolism , Pathology , Radiation Effects , Trans-Activators , Metabolism , Tumor Suppressor Protein p53 , Metabolism
17.
Article in Chinese | WPRIM | ID: wpr-776769

ABSTRACT

OBJECTIVE@#To explore the correlation of genetic mutations and clinical features of myelodysplastic syndromes (MDS) with scores of Revised International Prognostic Scoring System (IPSS-R).@*METHODS@#Eighty-seven patients with de novo MDS were enrolled. Mutations of MDS-related genes and clinical features were used to determine the incidence and subtype of mutations. Clinical features and IPSS-R scores of the patients with high frequency mutations involving TET2, TP53, ASXL1, RUNX1 and SF3B1 genes were compared.@*RESULTS@#Fifty-four patients (62.1%) harbored at least one point mutation. The incidences of various mutations were significantly different, with the incidence of MDS-EB-2 being 100% and MDS-SLD being only 38.9%. Compared with the wild types, patients harboring mutations had higher lactate dehydrogenase, higher β2 microglobulin, higher percentage of bone marrow blast cells and lower hemoglobin levels (P=0.027, 0.05).@*CONCLUSION@#Genetic mutations are commonly found in MDS. MDS patients with mutations have unique clinical laboratory characteristics. Although the prognostic value of most genes is controversial, TP53 is an definite indicator of poor prognosis.


Subject(s)
DNA Mutational Analysis , Humans , Incidence , Mutation , Myelodysplastic Syndromes , Genetics , Prognosis , Tumor Suppressor Protein p53 , Genetics
18.
Article in English | WPRIM | ID: wpr-776717

ABSTRACT

DNA double-stranded break (DSB) is one of the most catastrophic damages of genotoxic insult. Inappropriate repair of DNA DSBs results in the loss of genetic information, mutation, and the generation of harmful genomic rearrangements, which predisposes an organism to immunodeficiency, neurological damage, and cancer. The tumor repressor p53 plays a key role in DNA damage response, and has been found to be mutated in 50% of human cancer. p53, p63, and p73 are three members of the p53 gene family. Recent discoveries have shown that human p53 gene encodes at least 12 isoforms. Different p53 members and isoforms play various roles in orchestrating DNA damage response to maintain genomic integrity. This review briefly explores the functions of p53 and its isoforms in DNA DSB repair.


Subject(s)
Animals , DNA Breaks, Double-Stranded , DNA Repair , Humans , Mice , Protein Isoforms , Physiology , Tumor Protein p73 , Physiology , Tumor Suppressor Protein p53 , Genetics , Physiology
19.
Article in Chinese | WPRIM | ID: wpr-776233

ABSTRACT

OBJECTIVE@#To explore the protective effect and apoptosis-related mechanism of electroacupuncture (EA) preconditioning in the rats with cerebral ischemia-reperfusion injury.@*METHODS@#Sixty male SD rats, 3 months old, at SPF grade were randomized into a sham-operation group, an ischemia-reperfusion group and an EA preconditioning group, 20 rats in each one. In the ischemia-reperfusion group and EA preconditioning group, the modified MCAO suture-occlusion method was adopted to exert ischemia for 2 h and reperfusion for 3 h, and thus, the models of focal cerebral ischemia-reperfusion injury were prepared on the right side. In the sham-operation group, the right common carotid artery was separated and no more management was given. In the EA preconditioning group, EA at "Baihui" (GV 20), "Shenshu" (BL 23) and "Sanyinjiao" (SP 6) was provided before modeling, with disperse-dense wave, at 2 Hz/100 Hz, 1 mA in intensity. The stimulation for 15 min was taken as one unit (meaning electric stimulation for 10 min and needle retaining for 5 min without electric stimulation). Such preconditioning was repeated continuously for 4 times, totally for 1 h. The neuroethologic condition was assessed in 3 h of reperfusion in each group. TTC staining method was used to determine the percentage of cerebral infarction zone, TUNEL method was to determine the apoptosis index (AI) in hippocampal neuron and the immunohistochemical method (IHC) was to determine the protein expression of p53 and caspase-3.@*RESULTS@#Compared with the sham-operation group, the neuroethologic score, the percentage of cerebral infarction zone and neuronal AI were all increased obviously in the ischemia-reperfusion group (all <0.01). Compared with the ischemia-reperfusion group, the neuroethologic score, the percentage of cerebral infarction zone and neuronal AI were all reduced obviously in the EA preconditioning group (all <0.01). p53's nuclei and caspase-3's cytoplasms were stained. The positive cells of both of them were brown-yellow in color. In the sham-operation group, the structure of the right hippocampal CA3 neurons of rats was clear, with few positive cells. In the ischemia-perfusion group, the positive expressions of p53 and caspase-3 in the right hippocampal CA3 were increased obviously (<0.01). Compared with the ischemia-reperfusion group, the positive expressions of caspase-3 and p53 in the right hippocampal CA3 were significantly reduced in the EA preconditioning group (<0.01).@*CONCLUSION@#Electroacupuncture preconditioning relieves ischemic injury in brain tissue of rats probably through inhibiting the expressions of p53 and caspase-3 to resisting neuronal apoptosis.


Subject(s)
Acupuncture Points , Animals , Brain Ischemia , Caspase 3 , Physiology , Electroacupuncture , Hippocampus , Humans , Male , Neurons , Random Allocation , Rats , Rats, Sprague-Dawley , Reperfusion Injury , Tumor Suppressor Protein p53 , Physiology
20.
Article in Chinese | WPRIM | ID: wpr-775977

ABSTRACT

Objective To approach the discordance of estrogen receptor(ER),progesterone receptor(PR),Cerb-B2,Ki-67 index and P53 expressions between primary and regional or distant recurrent lesions in recurrent or metastatic breast cancer patients.Methods Clinical and pathological data of 56 recurrent or metastatic breast cancer patients who were treated in Peking Union Medical College Hospital from January 2001 to February 2015 were retrospectively analyzed.The changes in the expressions of ER,PR,Cerb-B2,Ki-67 index,and P53 status were analyzed.Results The hormone receptor positive rate between primary tumor and recurrent or metastatic sites decreased from 60.7% to 57.1% for ER and from 55.4% to 44.6% for PR,respectively.Changes in hormone receptor status were seen at the rate of 12.5%(7/56)and 16.1%(9/56)for ER and PR,respectively.Cerb-B2 receptor positive rate increased from 19.1% to 29.5% and the discordance rate was 9.1%(4/44).The discordance rate of Ki-67 index was 24.5%(12/49).The P53 receptor positive rate increased from 37.5% to 55.6% and the discordance rate was 13.3%(6/45).Conclusion Although the relevant rules of above changes are still controversial,these findings still have great clinical significance for making effective treatment decisions of recurrent or metastatic breast cancer.


Subject(s)
Breast Neoplasms , Genetics , Humans , Ki-67 Antigen , Genetics , Receptor, ErbB-2 , Genetics , Receptors, Estrogen , Genetics , Receptors, Progesterone , Genetics , Retrospective Studies , Tumor Suppressor Protein p53 , Genetics
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