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1.
Rev. chil. obstet. ginecol. (En línea) ; Rev. chil. obstet. ginecol;89(2): 77-84, abr. 2024. tab
Article in Spanish | LILACS | ID: biblio-1559732

ABSTRACT

Introducción: El cáncer de endometrio ocupa el sexto lugar en incidencia del cáncer en mujeres. La caracterización molecular de este cáncer permite optimizar la estratificación de riesgo para mejorar el tratamiento de las pacientes. Objetivo: Determinar el perfil molecular TCGA de pacientes con cáncer de endometrio en Bogotá, D.C., Colombia. Método: Estudio descriptivo en una cohorte de pacientes con cáncer de endometrio. Las mutaciones en los exones 9 a 14 del gen POLE fueron identificadas mediante amplificación por reacción en cadena de la polimerasa, seguida de secuenciación Sanger y análisis bioinformático. La expresión de las proteínas MMR y p53 se identificó mediante inmunohistoquímica. Resultados: Se incluyeron 40 pacientes con una mediana de edad de 66 años. El 15% presentaron mutaciones en el dominio exonucleasa de POLE. El 32% de las pacientes que no presentaron mutaciones manifestaron deficiencia en el sistema MMR. El 43,47% de las pacientes sin mutaciones en POLE ni alteración del sistema MMR presentaron alteración de la proteína p53. Conclusiones: La población de cáncer de endometrio analizada presenta un perfil molecular TCGA similar a lo reportado para otras poblaciones.


Introduction: Endometrial cancer ranks sixth in cancer incidence among women. Its molecular characterization allows for a more precise risk stratification with the aim of improving patient treatment. Objective: To determine the TCGA molecular profile of patients with endometrial cancer in Bogota, Colombia. Method: A descriptive study of a cohort of patients with endometrial cancer. The expression of MMR proteins and p53 was identified through immunohistochemistry. Mutations in exons 9 to 14 of the POLE gene were identified through polymerase chain reaction amplification, followed by Sanger sequencing and bioinformatic analysis. Results: Forty patients were included in the study, with a median age of 66 years, 15% of them exhibited mutations in the exonuclease domain of POLE, while 32% of patients without mutations showed deficiency in the MMR system. Forty three percent of patients without mutations in POLE or MMR alterations showed aberrant p53 protein expression. Conclusions: The analyzed population of endometrial cancer presents a TCGA molecular profile similar to that reported for other populations.


Subject(s)
Humans , Female , Middle Aged , Aged , Endometrial Neoplasms/genetics , Immunohistochemistry , Polymerase Chain Reaction , Cross-Sectional Studies , Retrospective Studies , Genes, p53/genetics , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/pathology , Sequence Analysis, DNA , Colombia , Risk Assessment , DNA Polymerase II , DNA Mismatch Repair , Poly-ADP-Ribose Binding Proteins , Mutation
2.
Article in Chinese | WPRIM | ID: wpr-1029932

ABSTRACT

Objective:To establish a single-tube, one-step method for detecting and identifying 16 high-risk human papillomavirus (HR-HPV) subtypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, 82) and genotyping p53 (rs1042522) and RB1 (rs3092905) in cervical cells, using high-throughput two-dimensional PCR (2D-PCR) technology. Methods:Applied Research. Specific primers were designed according to the DNA sequences of the 16 different HR-HPV subtypes, p53, and RB1 genes, with the target genes p53 and RB1 serving as internal references to assess the success of sample collection and PCR amplification. In three fluorescent detection channels, upstream primers labeled with corresponding tags were used for different HR-HPV subtypes, p53, and RB1, constructing a comprehensive 2D-PCR detection system. Using this method, 804 cervical brush samples collected from the gynecology outpatient department of Changzhou First People′s Hospital from December 2022 to August 2023 were tested. The test results were compared for consistency with PCR-reverse dot blot assay, flow cytometric fluorescence hybridization assay, and single-plex real-time quantitative PCR assay, respectively. Meanwhile, the genotypes of p53 and RB1 were detected using Sanger sequencing. The Kappa test was applied to determine the consistency between 2D-PCR method and other methods. Results:2D-PCR accurately discriminated and identified the genotypes of 16 HR-HPV types and p53, RB1 through characteristic melting valleys in the FAM, HEX, and Alexa Fluor568 channels. 2D-PCR showed high consistency with PCR-reverse dot blot assay, with a Kappa value of 0.699, even higher consistency with flow cytometric fluorescence hybridization assay, with a Kappa value of 0.793, and the highest consistency with single-plex quantitative PCR, with a Kappa value of 0.880 (95% CI 0.862-0.907). Using Sanger sequencing as the gold standard, the accuracy of 2D-PCR method in detecting p53 and RB1 genotypes is 100%. The distribution frequencies of the three genotypes (G/G, G/C, and C/C) at the p53 rs1042522 locus were 32.09% (258/804), 49.88% (401/804) and 18.03% (145/804), respectively, while all detected genotypes at the RB1 rs3092905 locus were A/A. Conclusion:This study successfully developed a 2D-PCR method for the identification and genotyping of high-risk human papillomavirus types and related tumor suppressor genes p53 and RB1 for cervical cancer.

3.
Int. j. morphol ; 41(2): 491-500, abr. 2023. ilus, tab
Article in Spanish | LILACS | ID: biblio-1440341

ABSTRACT

Siendo el cáncer gástrico la 3ª causa de muerte por cáncer en Chile, y existiendo estrategias de tamizaje consistentes en pesquisa de lesiones preneoplásicas de la mucosa gástrica, es relevante conocer los aspectos genéticos y moleculares que puedan ser aplicados, en la optimización de dichas estrategias a grupos de mayor riesgo. El objetivo de este manuscrito fue revisar la evidencia actual en los aspectos señalados, y de la inmunohistoquímica de 4 marcadores (p53, CDX2, MUC2 y S100A9) en la mucosa gástrica normal y en las lesiones preneoplásicas de la misma.


SUMMARY: Since gastric cancer is the 3rd leading cause of death from cancer in Chile, and there are screening strategies consisting of screening for preneoplastic lesions of the gastric mucosa, it is important to know certain genetic and molecular aspects that can be applied in optimizing these strategies for higher risk groups. The aim of this manuscript was to review the current evidence on the aforementioned aspects, and on the immunohistochemistry of 4 markers (p53, CDX2, MUC2 and S100A9) in normal gastric mucosa and in its preneoplastic lesions.


Subject(s)
Humans , Precancerous Conditions/pathology , Stomach Neoplasms/pathology , Gastric Mucosa/pathology , Precancerous Conditions/genetics , Precancerous Conditions/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Immunohistochemistry , Biomarkers, Tumor , Mass Screening , Risk Factors , Genes, p53 , Mucin-2 , CDX2 Transcription Factor , Gastric Mucosa/metabolism , Metaplasia
4.
Article in Chinese | WPRIM | ID: wpr-1027555

ABSTRACT

Liver cancer is one of the most common and fatal malignancies worldwide, with high mortality and morbidity. As an important tumor suppressor gene, p53 gene plays a key role in cell cycle regulation, cell growth and apoptosis of tumor cells. P53 gene mutations are closely related to the occurrence of liver cancer. At present, the treatment of liver cancer includes surgery, local treatment and systemic treatment. However, since most liver cancer patients are in advanced stages at the time of diagnosis, non-surgical treatment has become the best choice for the treatment of patients with intermediate and advanced liver cancer. But patients still have problems such as short survival and easy drug resistance. Therefore, the development of new treatment options is essential to improve the treatment outcomes of liver cancer patients. P53-related gene therapy products have great potential as drugs for the treatment of liver cancer. This article will briefly review the relationship between p53 gene and primary liver cancer, and explore its role in diagnosis and treatment, in order to provide a new direction for future clinical treatment.

5.
Cancer Research and Clinic ; (6): 521-525, 2023.
Article in Chinese | WPRIM | ID: wpr-996268

ABSTRACT

Objective:To explore the status of microsatellite instability (MSI) and its relationship with clinicopathological characteristics of patients with endometrial carcinoma.Methods:The clinical data of 365 patients with endometrial carcinoma who received surgery in Shanxi Province Cancer Hospital between January 2020 and December 2021 were retrospectively analyzed. Immunohistochemistry was used to detect the expressions of 4 DNA mismatch repair (MMR) proteins (MLH1, MSH2, MHS6, and PMS2), estrogen receptor (ER), progesterone receptor (PR), and p53 mutant protein in postoperative cancer tissue samples from 365 patients with endometrial carcinoma. All patients were divided into MSI group (1 or more non-expression of MMR protein) and microsatellite stability (MSS) group (4 proteins were all expressed), and the clinicopathological characteristics of patients in both groups were compared. φ efficient was used to analyze the correlation of MSI with ER, PR, p53 mutant protein expressions. Results:There were 72 cases (19.7%) in MSI group and 293 cases (80.3%) in MSS group; and the age of all patients was (53±19) years (21-83 years). There were statistically significant differences in the proportion of MSI patients in endometrial carcinoma patients with different age [>50 years vs. ≤50 years: 22.1% (61/276) vs. 12.4% (11/89)], tumor diameter [≤2 cm vs. > 2 cm: 25.9% (30/116) vs. 16.8% (42/249)], International Federation of Gynecology and Obstetrics (FIGO) staging [stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 31.1% (14/45) vs. 18.1% (58/320)], histological type [type Ⅰ vs. type Ⅱ: 21.7% (71/327) vs. 2.6% (1/38)] (all P < 0.05). There were no statistically significant differences in the proportion of MSI patients with different depth of invasion, degree of differentiation, lymph node metastasis, vascular involvement, and lesion location (all P > 0.05). Among 327 cases of type Ⅰendometrial carcinoma, 1 case was mucinous adenocarcinoma (MSS status), and the other 326 cases were endometrioid adenocarcinoma. Of the 72 patients with MSI, 71 cases were endometrioid carcinoma and the other was 1 of 3 mixed carcinomas in type Ⅱ endometrial carcinoma. There was a negative correlation between MSI and mutant p53 ( φ coefficient was -0.11, P = 0.031), and φ coefficient of the correlation of MSI with ER and PR was -0.03 and -0.06, while there were no statistically significant differences ( P value was 0.578 and 0.255, respectively). Conclusions:Endometrioid adenocarcinoma is the main type of endometrial cancer patients with MSI. MSI in endometrial cancer is correlated with age, FIGO staging, tumor diameter and histological type of patients, while negatively correlated with mutant p53.

6.
Dement. neuropsychol ; 16(2): 228-236, Apr.-June 2022. tab, graf, il. color
Article in English | LILACS | ID: biblio-1384665

ABSTRACT

ABSTRACT. Alzheimer's dementia (AD) is a neurodegenerative disease. The mechanism of oxidative stress in AD is due to amyloid beta (Aβ) protein that aggregates to form plaques, which further triggers chronic inflammation and neuronal apoptosis. Purple sweet potato extract with the main content of anthocyanins is a potential antioxidant with a direct target on the amyloid cascade hypothesis. Objective: The research objective was to determine the role of purple sweet potato water extract as an antioxidant and anti-inflammatory in preventing apoptosis in order to provide a neuroprotective effect in d-galactose-induced rats. Methods: A total of 100 male Wistar rats with randomized posttest-only control group design that met the eligibility criteria were included in this study. The treatment group was given 200 mg/kg BW/day of purple sweet potato water extract on days 1-70. d-galactose induction was administered in the treatment and control groups on days 15-70. Results: The independent t-test showed that the mean tumor necrosis factor-α (TNF-α) levels in the treatment group (735.36±139.74) was significantly lower than that in the control group (896.77±152.52). The p53 and glial fibrillary acidic protein (GFAP) expressions of astrocyte cells in the treatment group were significantly lower than that in the control group. The brain-derived neurotrophic factor (BDNF) levels in the treatment group (498.13±121.47) were higher than that in the control (391.93±140.28), and there was a significant increase in spatial working memory in the treatment group (72.01±10.22) than the control (59.77±11.87). Conclusions: The neuroprotective effect of purple sweet potato extract is due to d-galactose induction resulting from decrease in TNF-α levels, p53 expression, and GFAP expression and increase in BDNF levels and spatial working memory.


RESUMO. A doença de Alzheimer (DA) é uma doença neurodegenerativa. O mecanismo de estresse oxidativo na DA ocorre devido à proteína beta amilóide que se agrega para formar placas que desencadeiam inflamação crônica e apoptose neuronal. O extrato de batata-doce roxa composto principalmente por antocianinas é um potencial antioxidante com efeito direto sobre a hipótese da cascata amilóide. Objetivo: O objetivo da pesquisa foi determinar o papel do extrato aquoso de batata-doce roxa como antioxidante e anti-inflamatório na prevenção da apoptose, para proporcionar um efeito neuroprotetor em ratos induzidos por D-galactose. Métodos: Grupo controle randomizado pós-teste com 100 ratos Wistar machos que preencheram os critérios de elegibilidade. O grupo de tratamento recebeu 200mg/kg de peso corporal/dia de extrato aquoso de batata-doce roxa nos dias 1-70. A indução de D-galactose foi testada nos grupos de tratamento e controle nos dias 15-70. Resultados: O teste t independente mostrou que a média dos níveis de TNF-α no grupo de tratamento (735,36±139,74) foi significativamente menor do que no grupo controle (896,77±152,52). A expressão de p53 e a expressão de GFAP de células de astrócitos foram significativamente menores no grupo de tratamento do que no grupo controle. Os níveis de BDNF no grupo de tratamento (498,13±121,47) foram maiores que no grupo controle (391,93±140,28) e houve um aumento significativo da memória de trabalho espacial no grupo de tratamento (72,01±10,22) em relação ao controle (59,77±11,87). Conclusões: O efeito neuroprotetor do extrato de batata-doce roxa é devido à indução de D-galactose pela diminuição dos níveis de TNF-α, expressão de p53 e expressão de GFAP, aumentando assim os níveis de BDNF e memória espacial.


Subject(s)
Animals , Rats , Inhibitor of Apoptosis Proteins , Ipomoea batatas
7.
Article in Chinese | WPRIM | ID: wpr-955845

ABSTRACT

Objective:To investigate the expression and clinical significance of estrogen receptor (ER), progesterone receptor (PR), p53 and p16 protein in endometrial carcinoma.Methods:The endometrial tissue of 57 patients with endometrial carcinoma who received surgery in The First People's Hospital of Chuzhou between January 2017 and May 2021 was harvested as the study group. The normal endometrial tissue of 30 patients with endometrial hyperplasia was selected as the control group. Envision immunohistochemical staining was performed to determine the expression of ER, PR, p53 and p16 protein in endometrial tissue and analyze their expression with clinical pathological characteristics.Results:ER, PR, p16 protein expression rates in the endometrial tissue in the study group were 70.2%, 61.4%, 38.6%, respectively, which were significantly lower than 90.0%, 86.7%, 93.3% in the control group ( χ2 = 4.36, 5.98, 24.09, all P < 0.05). p53 expression rate in the endometrial tissue was significantly higher in the study group than that in the control group (52.6% vs. 13.3%, χ2 = 12.75, P < 0.001). ER and PR expression were significantly different between endometrial carcinoma patients with lymph node metastasis and those without and among those with different histological grades and those at different pathological stages (all P < 0.05). There was no significant difference in p53 protein expression among patients with different pathological stages of endometrial carcinoma, between patients who suffered endometrial carcinoma at different ages, and between patients with different degrees of myometrial invasion (all P > 0.05). p16 protein expression rate differed among patients with different pathological stages of endometrial carcinoma, among those with different histological grades and between patients with different degrees of myometrial invasion (all P < 0.05). There was no significant difference in p16 protein expression rate between endometrial carcinoma patients with lymph node metastasis and those without ( P > 0.05). Conclusion:Abnormal expressions of ER, PR, p53 and p16 protein in endometrial tissue may be related to the occurrence, development and transformation of the disease. Combined detection of ER, PR, p53 and p16 protein is helpful for the clinical diagnosis, treatment and prognosis assessment of endometrial carcinoma.

8.
Cancer Research and Clinic ; (6): 807-811, 2022.
Article in Chinese | WPRIM | ID: wpr-958940

ABSTRACT

Objective:To investigate the expression of miRNA-221-3p (miR-221-3p) in pancreatic cancer cells and its effect on apoptosis of pancreatic cancer cells, and the possible related mechanisms.Methods:Pancreatic cancer cell line PATU8988T was selected and transfected with miR-221-3p mimics, miR-221-3p inhibitors and their corresponding negative control sequences using Lipofectamine 3000. PATU8988T cells were divided into negative control group (without any treatment), miR-221-3p mimics negative control group, miR-221-3p mimics group, miR-221-3p inhibitors negative control group, and miR-221-3p inhibitors group. Real-time quantitative fluorescence polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of miR-221-3p, flow cytometry was used to detect the influence of miR-221-3p on apoptosis of pancreatic cancer cells, and Western blotting was used to detect the expressions of P53 and PTEN proteins in PATU8988T cell line.Results:The relative expression levels of miR-221-3p in negative control group, miR-221-3p mimics negative control group, miR-221-3p mimics group, miR-221-3p inhibitors negative control group and miR-221-3p inhibitors group were 1.02±0.18, 1.50±0.33, 2.96±0.70, 1.62±0.30, and 0.36±0.05, respectively, and the difference was statistically significant ( F = 12.61, P < 0.05); the relative expression level of miR-221-3p in miR-221-3p mimics group was higher than that in negative control group and miR-221-3p mimics negative control group ( t = 1.94, P < 0.05; t = 1.45, P < 0.05); the relative expression level of miR-221-3p in miR-221-3p inhibitors group was lower than that in negative control group and miR-221-3p inhibitors negative control group ( t = -0.65, P < 0.05; t = -1.26, P < 0.05). The apoptosis rates in negative control group, miR-221-3p mimics negative control group, miR-221-3p mimics group, miR-221-3p inhibitors negative control group and miR-221-3p inhibitors group were (8.60±0.20)%, (8.60±0.26)%, (4.27±0.31)%, (8.83±0.29)%, and (13.63±0.60)%, respectively, and the difference was statistically significant ( F = 253.80, P < 0.01); the apoptosis rates in miR-221-3p mimics group was lower than that in negative control group and miR-221-3p mimics negative control group ( t = -4.33, P < 0.05; t = 4.33, P < 0.05); the apoptosis rate in miR-221-3p inhibitors group was higher than that in negative control group and miR-221-3p inhibitors negative control group ( t = 5.03, P < 0.05; t = 4.80, P < 0.05). There was no statistical difference in expression levels of P53 and PTEN proteins between miR-221-3p mimics negative control group and miR-221-3p inhibitors negative control group (P53: t = 0.22, P > 0.05; PTEN: t = 0.33, P > 0.05); the expression levels of P53 and PTEN proteins in miR-221-3p mimics group were decreased compared with the miR-221-3p mimics negative control group (P53: t = 4.31, P < 0.05; PTEN: t = 8.49, P < 0.05); the expression levels of P53 and PTEN proteins in miR-221-3p inhibitors group were increased compared with the miR-221-3p inhibitors negative control group (P53: t = 5.17, P < 0.05; PTEN: t = 6.21, P < 0.05). Conclusions:miR-221-3p is highly expressed in pancreatic cancer PATU8988T cells, which can inhibit the apoptosis of pancreatic cancer cells. miR-221-3p may regulate the progression of pancreatic cancer through P53 and PTEN.

9.
Cancer Research and Clinic ; (6): 260-265, 2022.
Article in Chinese | WPRIM | ID: wpr-934668

ABSTRACT

Objective:To investigate the expression levels of silent information regulator 1 (SIRT1), hypoxia-inducible factor-1α (HIF-1α) and mutant P53 proteins in colorectal adenocarcinoma tissues and their clinical significances.Methods:The data of 68 cases of colorectal adenocarcinoma confirmed by pathology in Shanxi Traditional Chinese Medical Hospital from March 2015 to October 2021 were collected. The expressions of SIRT1, HIF-1α and mutant P53 proteins in colorectal adenocarcinoma tissues and paracancerous tissues were determined by immunohistochemistry. The correlation among SIRT1, HIF-1α and mutant P53 proteins and their relationship with clinicopathological features of patients were analyzed.Results:Among 68 colorectal adenocarcinoma tissues and paracancerous tissues, SIRT1 protein was positive in 38 cases (55.88%) and 11 cases (16.18%) ( χ2 = 23.25, P < 0.001), HIF-1α protein was positive in 47 cases (69.12%) and 5 cases (7.35%) ( χ2 =54.92, P < 0.001), and mutant P53 protein was positive in 41 cases (60.29%) and 0 cases (0) ( P < 0.001). The positive expression rate of SIRT1 protein was high in patients with high clinical stage and lymph node metastasis (both P < 0.05); the positive expression rate of HIF-1α protein was high in patients with poor differentiation ( P < 0.05); the positive expression rate of mutant P53 protein was high in patients with poor differentiation and lymph node metastasis (both P < 0.05). There was a negative correlation between expressions of SIRT1 and mutant P53 proteins ( rs = -0.38, P = 0.001); there was a positive correlation between expressions of HIF-1α and mutant P53 proteins ( rs = 0.56, P < 0.001); there was a negative correlation between expressions of SIRT1 and HIF-1α proteins ( rs = -0.40, P = 0.001). Conclusions:SIRT1, HIF-1α and mutant P53 proteins are highly expressed in colorectal adenocarcinoma and are correlated with clinicopathological features suggesting poor prognosis. Combined detection of the three proteins may be used for the diagnosis and prognosis of colorectal adenocarcinoma and serve as a new target for treatment.

10.
Iatreia ; Iatreia;34(4): 370-374, oct.-dic. 2021. graf
Article in Spanish | LILACS | ID: biblio-1350837

ABSTRACT

RESUMEN Las alteraciones genéticas en el gen TP53 están presentes entre el 5 al 8 % de los pacientes de leucemia linfocítica crónica (LLC) en el momento del diagnóstico. Estos casos se relacionan con un mal pronóstico debido a su resistencia al tratamiento estándar. Presentamos el caso de un paciente masculino de 52 años diagnosticado con LLC, expresión del marcador CD38 y una deleción en el gen TP53 (17p13.1). Tras la evaluación posterior del tratamiento, se observó enfermedad mínima residual lo que llevó a un trasplante haploidéntico de progenitores hematopoyéticos. Debido al alto riesgo de recaída, su edad y la ausencia de comorbilidades, era la única opción curativa hasta la fecha para la LLC. El objetivo de este trabajo es realizar una revisión de la literatura que sirva como base para analizar el caso clínico presentado, en el marco de las implicaciones clínicas, pronóstico y respuesta al tratamiento en los individuos con LLC que presentan alteraciones en el gen TP53.


SUMMARY Genetic alterations in the TP53 gene are present in 5 to 8% of chronic lymphocytic leukemia (CLL) cases at the time of diagnosis. These cases are typically associated with poor prognosis due to their resistance against standard CLL treatment. In our report a 52-yearold male patient was diagnosed with CLL, CD38 expression and a deletion in the TP53 gene (17p13.1). Upon evaluation post-treatment, minimal residual disease (MDR) was observed, and a haploidentical stem cell transplant was performed. Because of the high risk of relapse, his age, and the absence of comorbidities it was the only curative option to date for CLL. The purpose of this article is to complete a literature review that will give a basis to analyze the clinical case presented, within the framework of the clinical implications, prognosis, and response to treatment in patients with CLL who present with aberrations of the TP53 gene.


Subject(s)
Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Genes, p53 , Research Report
11.
Rev. colomb. obstet. ginecol ; 72(3): 307-318, July-Sept. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1351955

ABSTRACT

Objetivo: describir el caso de una paciente con Síndrome de Li-Fraumeni (SLF) y cáncer de mama, en quien se cuestionó el beneficio en la supervivencia de la mastectomía profiláctica contralateral (MPC); asimismo, se pretende hacer una discusión crítica acerca de la evidencia que soporta este procedimiento en esta población. Presentación del caso: mujer de 37 años con cáncer de mama y múltiples antecedentes familiares de cánceres de temprana aparición del espectro del SLF, en quien, durante la adyuvancia hormonal, se confirmó una variante patogénica en el gen TP53. La paciente fue presentada en la Junta Multidisciplinaria del Servicio de Mama de un Centro Oncológico de referencia en Colombia, con el fin de discutir el beneficio de la MPC. La decisión de la junta fue no realizar la MPC. Después de 30 meses de seguimiento la paciente se encuentra libre de enfermedad. Conclusión: no existe evidencia que analice, de forma particular, el impacto de la MPC en la supervivencia de las pacientes con SLF y cáncer de mama. Sin embargo, a la luz del conocimiento actual no es posible generalizar la conducta de omitir esta cirugía profiláctica. Es importante reportar los casos en los que se decida realizar u omitir este procedimiento con el fin de incrementar el cuerpo de la evidencia, dado que existen limitaciones para construir grandes cohortes o estudios experimentales exclusivos para esta alteración genética.


Objective: To describe the case of a patient with Li-Fraumeni syndrome (LFS) and breast cancer in whom the benefit of contralateral prophylactic mastectomy (CPM) was challenged; and to offer a critical discussion regarding the evidence supporting this procedure in this patient population. Case presentation: A 37-year-old woman with breast cancer and a family history of multiple early onset cancer of the LFS spectrum in whom a pathogenic variant of the TP53 gene was confirmed during adjuvant hormonal therapy. The case was presented during the multidisciplinary meeting of the Breast Service of a referral oncology center in Colombia, in order to discuss the benefit of CPM. The decision of the board meeting was not to perform CPM. After 30 months of follow-up, the patient is disease-free. Conclusion: There is no evidence on the impact of CPM on survival of patients with LFS and breast cancer in particular. However, in light of the current knowledge, it is not possible to generalize the approach of withholding this prophylactic surgery. It is important to report those cases in which the decision is made to either perform or omit this procedure in order to increase the body of evidence, considering the limitations that make it difficult to build large cohorts or conduct trials exclusively for this genetic disorder.


Subject(s)
Female , Adult , Breast Neoplasms , Li-Fraumeni Syndrome , Genes, p53 , Prophylactic Mastectomy
12.
REVISA (Online) ; 9(1): 89-96, jan-mar.2020.
Article in English, Portuguese | LILACS | ID: biblio-1050902

ABSTRACT

Objetivo: investigar a associação entre o polimorfismo TP53 Arg72Pro em pacientes diagnosticados com acidente vascular encefálico hemorrágico (AVEH) ou aneurisma intracerebral em uma amostra do Distrito Federal. Método: Tratou-se de um estudo caso-controle, com 162 indivíduos equitativamente divididos nos grupos, com anotações das características clínicas do prontuário e análise da genotipagem por meio da estratégia de PCR. As frequências genotípicas foram estimadas por contagem direta. O nível de significância adotado foi de 5%. Resultados: Foi verificado que a presença do alelo Arg do polimorfismo do TP53 Arg72Pro atuou como fator do risco para a ocorrência do AVEH/aneurisma intracerebral. A presença do genótipo Arg/Arg aumentou o risco para o prognóstico ruim (ERM >3) em pacientes portadores do AVEH/aneurisma (P<0,01; OR= 6,07). Não houve associação estatística entre HAS, diabetes, tabagismo e etilismo e a presença do polimorfismo TP53 Arg72Pro no grupo estudado. Conclusão: Concluiu-se que a presença do alelo Arg do polimorfismo do TP53 Arg72Pro está associada ao aumento do risco de ocorrência do AVEH/aneurisma intracerebral.


Objective: to investigate the association between the TP53 Arg72Pro polymorphism in patients diagnosed with hemorrhagic stroke (HS) or intracerebral aneurysm in a sample from Distrito Federal. Method: This was a case-control study, with 162 individuals equally divided into groups, with notes on the clinical characteristics of the medical record and analysis of genotyping using the PCR strategy. Genotype frequencies were estimated by direct counting. The level of significance adopted was 5%.Results: we found that the presence of the Arg allele of the TP53 Arg72Pro polymorphism acted as a risk factor for the occurrence of HS/intracerebral aneurysm. The presence of the Arg/Arg genotype increased the risk for poor prognosis (ERM> 3) in patients with HS/aneurysm (P <0.01; OR = 6.07). There was no statistical association between SAH, diabetes, smoking and alcohol consumption and the presence of the TP53 Arg72Pro polymorphism in the studied group. Conclusion: It was concluded that the presence of the Arg allele of the TP53 Arg72Pro polymorphism is associated with an increased risk of occurring HS/intracerebral aneurysm.


Objetivo: investigar la asociación entre el polimorfismo TP53 Arg72Pro en pacientes diagnosticados de accidente cerebrovascular hemorrágico (AVEH) o aneurisma intracerebral en una muestra del Distrito Federal. Método: Este fue un estudio de casos y controles, con 162 individuos igualmente divididos en grupos, con notas sobre las características clínicas de la historia clínica y el análisis de genotipado utilizando la estrategia de PCR. Las frecuencias de genotipo se estimaron por conteo directo. El nivel de significación adoptado fue del 5%. Resultados: Se encontró que la presencia del alelo Arg del polimorfismo TP53 Arg72Pro actuó como un factor de riesgo para la aparición de AVEH/aneurisma intracerebral. La presencia del genotipo Arg / Arg aumentó el riesgo de mal pronóstico (ERM> 3) en pacientes con AVEH/aneurisma (P <0.01; OR = 6.07). No hubo asociación estadística entre SAH, diabetes, tabaquismo y consumo de alcohol y la presencia del polimorfismo TP53 Arg72Pro en el grupo estudiado. Conclusión: se concluyó que la presencia del alelo Arg del polimorfismo TP53 Arg72Pro se asocia con un mayor riesgo de aparición de AVEH/aneurisma intracerebral.


Subject(s)
Polymorphism, Genetic
13.
Repert. med. cir ; 28(2): 105-110, 2019. ilus., tab.
Article in English, Spanish | LILACS, COLNAL | ID: biblio-1009958

ABSTRACT

Introducción: la mutación en el gen TP53 se ha asociado con la oncogénesis de los tumores de ovario tipo II. Se ha propuesto que las mutaciones de p53 se inician en las células de la trompa uterina y después migran al ovario. El objetivo de este estudio es establecer la frecuencia de la expresión de p53 en ovario y trompa uterina en carcinoma epitelial primario de ovario. Materiales y métodos: estudio de corte transversal en tumores primarios epiteliales de ovario. Se evaluó la expresión de p53 por inmunohistoquímica en el ovario y en las trompas uterinas. Resultados: se incluyeron 45 pacientes con edad media de 55 años. Se estudiaron 24 casos de carcinomas serosos, 6 endometrioides, 5 mixtos, 3 de células claras, 3 carcinosarcomas, 2 carcinomas mucinosos y 2 indiferenciados. Se observó positividad fuerte y difusa en 68% de los tumores tipo II. En 52 hubo positividad en trompa uterina y ovario, 92% con compromiso bilateral. En 3 de estos casos se reconoció carcinoma intraepitelial tubárico con positividad de p53 en el área tumoral, no tumoral y en el carcinoma seroso. Conclusión: como se ha observado en estudios previos, el gen TP53 está involucrado en la oncogénesis de los tumores tipo II y se ha demostrado que existe una relación entre una mutación inicial de p53, seguida por STIL, STIC, evolucionando a un carcinoma seroso de ovario.


Introduction: a TP53 gene mutation has been associated with the oncogenesis of type II ovary tumors. Mutations of the p53 gene in the fallopian tube cells which migrate to the ovary have been proposed as an alternative origin. This study focuses on establishing the frequency of p53 ovary and uterine tube expression in primary epithelial ovarian cancer. Materials and Methods: a cross-sectional study on primary epithelial ovarian tumors. Expression of p53 in the ovary and uterine tubes was assessed using immunohistochemistry. Results: 45 patients, median age 55 years, were included. Twenty-four (24) cases of serous carcinomas, 6 endometrioid carcinomas, 5 mixed carcinomas, 3 clear-cell carcinomas, 3 carcinosarcomas, 2 mucinous carcinomas and 2 undifferenciated tumors were studied. Positivity was strong and diffuse in 68% of type II tumors. Positivity was detected in the tubes and ovaries in 52 cases, 92% with bilateral compromise. Intraepithelial tube carcinoma was recognized in 3 cases with p53 positivity in the tumor, outside the tumor and in the serous carcinoma. Conclusion: as observed in previous studies, TP53 gene is involved in the oncogenesis of type II tumors and a correlation between the initial p53 mutations followed by STIL, STIC progressing to an ovary serous carcinoma has been demonstrated.


Subject(s)
Humans , Female , Middle Aged , Carcinoma, Ovarian Epithelial , Genes, p53 , Fallopian Tubes , Neoplasms
14.
Article in Chinese | WPRIM | ID: wpr-743098

ABSTRACT

The development of non-small cell lung cancer (NSCLC) is a complex process which referring to multi-factor interaction.In this process,p53 gene regulates the normal growth of cells,but p53 gene after mutation can induce the occurrence of NSCLC,promote tumor distant metastasis,induce chemotherapy resistance,and cause poor prognosis of patients.Therefore,the restoration of normal expression of p53 gene is very significant for the treatment of NSCLC.In recent years,the rapid progress of p53 gene therapy has opened up a new way for the treatment of NSCLC.

15.
Journal of Breast Cancer ; : 172-184, 2019.
Article in English | WPRIM | ID: wpr-764271

ABSTRACT

PURPOSE: Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) functions in various cancers. We studied the effect and molecular mechanism of TP53AIP1 in breast cancer. METHODS: The degree of correlation between TP53AIP1 expression and overall survival in patients with breast cancer was obtained from the online The Cancer Genome Atlas database. Six of the TP53AIP1 levels in the tumor and adjacent non-tumor tissues randomly selected from 38 breast cancer patients were determined. Transgenic technology was used to enhance the expression of TP53AIP1 in breast cancer cell lines, MDA-MB-415 and MDA-MB-468, and to observe the effects of gene overexpression on the proliferation, cell cycle, and apoptosis of breast cancer cells. The molecular mechanism of association between cell cycle- and apoptosis-related factors and the phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) pathway was also studied. RESULTS: The messenger RNA and protein expression levels of TP53AIP1 in cancer tissues were significantly lower than those in the control group. TP53AIP1 overexpression inhibits cell viability. The mechanism of TP53AIP1 inhibition of proliferation and growth of breast cancer cells includes cell cycle arrest, apoptosis promotion (p < 0.01), promotion of the expression of cleaved-caspase-3 (p < 0.01), cleaved-caspase-9 (p < 0.01), B cell lymphoma/leukemia-2 (Bcl-2)-associated X protein, and p53 (p < 0.01), and the inhibition of Bcl-2, Ki67, and PI3K/Akt pathways (p < 0.01). CONCLUSION: TP53AIP1 may be a novel tumor suppressor gene in breast cancer and can potentially be used as an effective target gene for the treatment of breast cancer.


Subject(s)
Humans , Apoptosis , Breast Neoplasms , Breast , Cell Cycle Checkpoints , Cell Line , Cell Proliferation , Cell Survival , Genes, p53 , Genes, Tumor Suppressor , Genome , Phosphotransferases , RNA, Messenger
16.
Journal of Chinese Physician ; (12): 373-378, 2019.
Article in Chinese | WPRIM | ID: wpr-744880

ABSTRACT

Objective APOBEC3B (A3B) is an important member of the apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) family.This study aimed to investigate its important role in the metastasis of small cell lung cancer (NSCLC).Methods The statistical relationship between A3 B and clinicopathological data was analyzed in 249 cases of NSCLC.Sanger sequencing was used to detect mutations in exon 5,6,7 and 8 of P53 in 74 cases of lung cancer.A3B overexpression cell line was constructed in human lung adenocarcinoma cells HCC827 to observe the change of cell migration and metastasis capacity.Results A3B was highly expressed in NSCLC tissues compared with normal lung tissues.The expression of A3B was closely related to the lymph node metastasis of NSCLC and the mutation rate of p53 was positively correlated with the expression of A3B.In vitro experiment,it showed enhanced migration and increased metastatic potential in cells after overexpression of A3B.Conclusions A3B-mediated mutations in P53 may play a key role in the metastasis of NSCLC.

17.
Journal of Clinical Hepatology ; (12): 1373-1376, 2017.
Article in Chinese | WPRIM | ID: wpr-621051

ABSTRACT

P53 abnormality or mutation is commonly seen in patients with hepatocellular carcinoma (HCC), and therefore, restoration of P53 function has become a research hotspot in the treatment of HCC.This article reviews the association of P53 with Bcl-2 protein family, microRNA, TGFβ, HBV, HCV, and AKT and the role of P53 in regulating cell apoptosis, in order to provide clues for improving the therapeutic outcome of HCC.

18.
Military Medical Sciences ; (12): 342-345, 2017.
Article in Chinese | WPRIM | ID: wpr-612729

ABSTRACT

Objective To explore whether PERK is involved in the regulation of arsenite-induced autophagy.Methods Human hepatoma cells HepG2 were cultured and treated with arsenite.The expression level of autophagic hallmarks and the activation status of PERK were detected by Western blotting.The transactivation of p53 and the induction of its downstream target genes expression were also detected by Western blotting after knockdown of PERK expression.Transactivity of p53 was detected by dual luciferase reporter assay after knockdown of PERK expression.Results An increase in the LC3BII:I ratio,the induction of Beclin-1 expression and the degradation of p62 were readily observed in arsenite-treated HepG2 cells,but the effects were abolished after knockdown of PERK expression.Furthermore,phosphorylation of p53 at Ser15 and Ser392,transactivation of p53 and the induction of its downstream target gene DAPK1 expression were effectively inhibited under the same PERK knockdown conditions.Conclusion PERK regulates arsenite-induced autophagy by activating p53-dependent DAPK1 upregulation.

19.
Article in Chinese | WPRIM | ID: wpr-668792

ABSTRACT

Objective To investigate the effect of transcatheter arterial chemoembolization combined with radiofrequency ablation in the treatment of primary hepatocellular carcinoma (HCC) and its influence on the levels of nuclear factor kappa B (NF-B) and p53.Methods 90 patients with primary HCC were selected,and they were randomly divided into control group (n =45) and observation group (n =45) according to the digital table.The control group received chemoembolization treatment,the observation group was given combined radiofrequency ablation treatment.The patients were continuously treated for 6 months.Immunohistochemical assay was used to detect the expression of NF-B and p53 in two groups.The clinical curative effect and influence on the expression of NF-B and p53 were compared between the two groups.Results After 6 months of treatment,the Karnofsky score of the observation group was (84.32 ± 12.31)points,which was higher than (64.32 ± 11.24) points of the control group (t =21.295,P < 0.05).After treatment for 6 months,the AFP level of the observation group was (121.23 ± 1.43) μg/L,which was lower than (189.44 ± 36.42) μg/L of the control group (t =19.853,P < 0.05).After treatment,the positive expression rates of NF-B and p53 of the observation group were 24.44% and 20.00%,respectively,which were lower than 40% and 33.33 % of the control group (x2 =6.597,5.784,all P < 0.05).The recurrence rate of the observation group was 15.56%,which was lower than 28.89% of the control group (x2 =6.126,P < 0.05).The 6-month and 12-month survival rates of the observation group were 86.67% and 82.22%,respectively,which were higher than 75.56% and 64.44% of the control group (x2 =4.927,7.192%,all P<0.05).Conclusion The effect of radiofrequency ablation combined with radiofrequency ablation for patients with primary liver cancer is satisfactory,which is worthy of popularization and application.

20.
Tumor ; (12): 1017-1023, 2017.
Article in Chinese | WPRIM | ID: wpr-848471

ABSTRACT

Objective: To study the correlation between the expressions of p53 and histone deacetylase 2 (HDAC2) in colorectal cancer, and to explore their regulative relationship. Methods: The association between p53 and HDAC2 mRNAs was explored by the Cancer Genome Atlas (TCGA) clinical colorectal cancer data analysis. The expression of HDAC2 in wide-type (WT) and p53-knockout (p53-/-) colorectal HCT116 cell lines was detected by Western blotting. After p53 expression in HCT116 p53-/- cells was recovered by adenovirus infection method, the expression of HDAC2 was detected by Western blotting again. Then TCGA colorectal cancer data were further used to analyze the relationship between HDAC2 and p53 signaling pathway-related genes. Results: TCGA data analysis showed that the transcriptional level of p53 was positively correlated with HDAC2 in 382 RNA-sequencing specimens of colorectal cancer (r = 0.198, P = 0.000 1). As compared with HCT116 WT cells, the expression level of HDAC2 protein was significantly reduced in HCT116 p53-/- cells (P < 0.000 1). After infection with Ad-p53 adenovirus, the expression levels of p53 and HDAC2 proteins in HCT116 p53-/- cells were recovered (both P < 0.000 1). Further analysis of TCGA colorectal cancer data showed that there was significant co-occurrence (all P < 0.05) and positive association (all P < 0.01) between the expressions of HDAC2 and nine p53 signaling pathway-related genes. Conclusion: P53 may play an important role in regulating HDAC2 expression in colorectal cancer. HDAC2 may act as a down-stream regulator of p53, participate in p53 signal transduction, and modulate tumorigenesis and progression.

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