RESUMEN
Colorectal Carcinoma (CRC) ranks among the most prevalent cancers globally, with significant variability in incidence rates across different regions. A shift towards a Westernized diet has been implicated in rising cancer rates, particularly in emerging nations. By 2020, CRC is projected to represent a notable proportion of global cancer cases and deaths. In India, CRC primarily affects individuals aged 45 to 84, with a higher incidence in males, commonly occurring in the rectum and sigmoid colon. Risk factors such as obesity, dietary factors, sedentary lifestyle, smoking, and alcohol use contribute to CRC development, especially in aging populations. Diagnosis involves various imaging modalities and histological assessments using Tumour, node and metastasis (TNM) and American Joint Committee on Cancer classifications. Recent advancements in targeted therapies like monoclonal antibodies against HER2 have shown promise in treating metastatic CRC. Immunohistochemistry markers like Ki-67 and HER2 play crucial roles in prognostic assessment and treatment planning. This study aims to investigate Ki-67 and HER2 expression in CRC, correlating with histological characteristics and prognostic factors.
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Biomarcadores de Tumor , Neoplasias Colorrectales , Inmunohistoquímica , Antígeno Ki-67 , Estadificación de Neoplasias , Receptor ErbB-2 , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/diagnóstico , Receptor ErbB-2/metabolismo , Antígeno Ki-67/metabolismo , Biomarcadores de Tumor/metabolismo , Masculino , Persona de Mediana Edad , Femenino , Anciano , Pronóstico , Anciano de 80 o más Años , India , Adulto , Factores de Riesgo , Metástasis LinfáticaRESUMEN
This study examined to evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients, a total of 76 patients diagnosed with glioma by pathology in Tengzhou Central People's Hospital were enrolled. The baseline data and follow ups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Ki-67 negative group showed of a longer OS survival time and a longer PFS survival time with log-rank test (x2 = 16.101, P < 0.001 and x2 = 16.961, P < 0.001). Age older than 50 years (HR = 2.074, 95% CI 1.097-3.923), abnormal treatment (HR = 2.932, 95% CI 1.343-6.403) and Ki-67 positive (HR = 2.722, 95% CI 1.097-6.755) were the independent predictive factors of death. High grade pathology (HR = 2.453, 95% CI 1.010-5.956) and Ki-67 positive (HR = 2.200, 95% CI 1.043-4.639) were the independent predictive factors of recurrence. The C-index for the nomogram of OS and PFS were 0.745 and 0.723, respectively. The calibration results showed that the nomogram could predict the overall and disease-free 1-year survival of glioma patients. In conclusion, the nomograms with Ki-67 as independent risk factor for OS and PFS could provide clinical consultation in the treatment and follow-up of malignant glioma.
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Neoplasias Encefálicas , Glioma , Antígeno Ki-67 , Recurrencia Local de Neoplasia , Nomogramas , Humanos , Glioma/mortalidad , Glioma/cirugía , Glioma/metabolismo , Glioma/patología , Antígeno Ki-67/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Adulto , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Estudios Retrospectivos , Anciano , Pronóstico , Supervivencia sin Enfermedad , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVE: To analyze the expression of SPAG5 in gastric cancer tissues and its regulatory roles in gastric cancer cell growth. METHODS: TCGA analysis, immunohistochemistry, and immunofluorescence staining were used to analyze the expression patterns of SPAG5 and MKi67 in gastric cancer and adjacent tissues. In gastric cancer AGS and MGC803 cells, the effects of lentivirus-mediated SPAG5 knockdown on cell growth and apoptosis were evaluated using Celigo, MTT, clone formation assays and flow cytometry. RESULTS: Proteinatlas and TCGA database analysis suggested that SPAG5 was highly expressed in gastric cancer, and Kaplan-Meier analysis and GEPIA analysis showed high expressions of SPAG 5 in lung adenocarcinoma, breast cancer, hepatocellular carcinoma, pancreatic carcinoma, cervical cancer and bladder carcinoma. Immunohistochemistry revealed that SPAG5 was highly expressed in gastric cancer tissues (P < 0.001), and immunofluorescence colocalization analysis demonstrated a significant correlation between SPAG5 and MKI67 (R=0.393, P < 0.001). RT-qPCR and Western blotting showed that SPAG5 was highly expressed in MKN74, BGC823, MGC803, SGC7901 and AGS cells. In AGS and MGC803 cells, SPAG5 knockdown significantly inhibited proliferation and promoted apoptosis. CONCLUSIONS: The expressions of SPAG5 and MKi67 are correlated in gastric cancer tissues, and SPAG5 knockdown inhibits the proliferation of gastric cancer cells. SPAG5 is associated with the prognosis of gastric cancer patients and may serve as a promising biomarker for gastric cancer.
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Apoptosis , Proliferación Celular , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Antígeno Ki-67/metabolismoRESUMEN
Statins, inhibitors of HMG-CoA reductase, have been shown to have potential anti-carcinogenic effects through the inhibition of the mevalonate pathway and their impact on Ras and RhoGTAases. Prior studies have demonstrated a reduction in breast tumor proliferation, as well as increased apoptosis, among women with early-stage breast cancer who received statins between the time of diagnosis and the time of surgery. The aim of this study was to evaluate the impact of short-term oral high-potency statin therapy on the expression of markers of breast tumor proliferation, apoptosis, and cell cycle arrest in a window-of-opportunity trial. This single-arm study enrolled 24 women with stage 0-II invasive breast cancer who were administered daily simvastatin (20 mg) for 2-4 weeks between diagnosis and surgical resection. Pre- and post-treatment tumor samples were analyzed for fold changes in Ki-67, cyclin D1, p27, and cleaved caspase-3 (CC3) expression. Out of 24 enrolled participants, 18 received statin treatment and 17 were evaluable for changes in marker expression. There was no significant change in Ki-67 expression (fold change = 1.4, p = 0.597). There were, however, significant increases in the expression of cyclin D1 (fold change = 2.8, p = 0.0003), p27 cytoplasmic (fold change = 3.2, p = 0.025), and CC3 (fold change = 2.1, p = 0.016). Statin treatment was well tolerated, with two reported grade-1 adverse events. These results align with previous window-of-opportunity studies suggesting a pro-apoptotic role of statins in breast cancer. The increased expression of markers of cell cycle arrest and apoptosis seen in this window-of-opportunity study supports further investigation into the anti-cancer properties of statins in larger-scale clinical trials.
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Apoptosis , Biomarcadores de Tumor , Neoplasias de la Mama , Proliferación Celular , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Apoptosis/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Persona de Mediana Edad , Proliferación Celular/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Anciano , Adulto , Estadificación de Neoplasias , Simvastatina/farmacología , Simvastatina/uso terapéutico , Antígeno Ki-67/metabolismo , Ciclina D1/metabolismo , Caspasa 3/metabolismoRESUMEN
PURPOSE: To investigate the application value of support vector machine (SVM) model based on diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) and amide proton transfer- weighted (APTW) imaging in predicting isocitrate dehydrogenase 1(IDH-1) mutation and Ki-67 expression in glioma. METHODS: The DWI, DCE and APTW images of 309 patients with glioma confirmed by pathology were retrospectively analyzed and divided into the IDH-1 group (IDH-1(+) group and IDH-1(-) group) and Ki-67 group (low expression group (Ki-67 ≤ 10%) and high expression group (Ki-67 > 10%)). All cases were divided into the training set, and validation set according to the ratio of 7:3. The training set was used to select features and establish machine learning models. The SVM model was established with the data after feature selection. Four single sequence models and one combined model were established in IDH-1 group and Ki-67 group. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic performance of the model. Validation set data was used for further validation. RESULTS: Both in the IDH-1 group and Ki-67 group, the combined model had better predictive efficiency than single sequence model, although the single sequence model had a better predictive efficiency. In the Ki-67 group, the combined model was built from six selected radiomics features, and the AUC were 0.965 and 0.931 in the training and validation sets, respectively. In the IDH-1 group, the combined model was built from four selected radiomics features, and the AUC were 0.997 and 0.967 in the training and validation sets, respectively. CONCLUSION: The radiomics model established by DWI, DCE and APTW images could be used to detect IDH-1 mutation and Ki-67 expression in glioma patients before surgery. The prediction performance of the radiomics model based on the combination sequence was better than that of the single sequence model.
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Neoplasias Encefálicas , Glioma , Isocitrato Deshidrogenasa , Antígeno Ki-67 , Mutación , Máquina de Vectores de Soporte , Humanos , Isocitrato Deshidrogenasa/genética , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/metabolismo , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Persona de Mediana Edad , Femenino , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Masculino , Estudios Retrospectivos , Adulto , Anciano , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Multimodal , Adulto Joven , Imagen por Resonancia Magnética/métodos , Curva ROC , Medios de ContrasteRESUMEN
Objective: To investigate the clinicopathological features and differential diagnosis of breast angiomatosis. Methods: Six cases of breast angiomatosis diagnosed at the Department of Pathology, the Seventh Medical Center, People's Liberation Army General Hospital and the Department of Pathology, Dongzhimen Hospital, Beijing University of Chinese Medicine from January 2011 to December 2023 were evaluated and reviewed. Results: All patients were female with an average age of 46 years at presentation, ranging from 25 to 62 years. The most common clinical presentation was a palpable unilateral breast mass with diameter ranging from 7 to 14 cm, and the average size was 11 cm. Histologically, all cases were composed of variably-sized ectatic, thin-walled blood vessels with minimal to no apparent smooth muscle, lined by flat normochromic endothelium without atypia, and diffusely infiltrating the breast stroma. Where present, the lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Immunohistochemical staining for CD31, CD34, Factor â §, Fli-1 and D2-40 revealed positive expression in vascular and/or lymphatic endothelial cells. Additionally, the Ki-67 proliferation index was found to be less than 1%. Conclusions: Angiomatosis of the breast is a rare benign vascular lesion. Distinguishing it from low-grade angiosarcoma requires careful consideration of the growth pattern, atypical features, and Ki-67 proliferation index.
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Angiomatosis , Antígenos CD34 , Neoplasias de la Mama , Humanos , Femenino , Angiomatosis/patología , Angiomatosis/metabolismo , Persona de Mediana Edad , Adulto , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Antígenos CD34/metabolismo , Diagnóstico Diferencial , Mama/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Enfermedades de la Mama/patología , Enfermedades de la Mama/metabolismo , Enfermedades de la Mama/diagnóstico , Antígeno Ki-67/metabolismo , Inmunohistoquímica , Factor de von Willebrand/metabolismo , Células Endoteliales/patología , Células Endoteliales/metabolismo , Anticuerpos Monoclonales de Origen MurinoAsunto(s)
Carcinoma Mucoepidermoide , Mucina 5AC , Neoplasias Gástricas , Humanos , Masculino , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Carcinoma Mucoepidermoide/patología , Carcinoma Mucoepidermoide/metabolismo , Carcinoma Mucoepidermoide/diagnóstico , Persona de Mediana Edad , Mucina 5AC/metabolismo , Diagnóstico Diferencial , Proteína p53 Supresora de Tumor/metabolismo , Antígeno Ki-67/metabolismoAsunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Biomarcadores de Tumor , Humanos , Carcinoma Corticosuprarrenal/diagnóstico , Carcinoma Corticosuprarrenal/metabolismo , Carcinoma Corticosuprarrenal/patología , Carcinoma Corticosuprarrenal/inmunología , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/patología , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/inmunología , Biomarcadores de Tumor/metabolismo , Antígeno Ki-67/metabolismo , beta Catenina/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Invasividad Neoplásica , Inmunofenotipificación , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Nucleares/metabolismoRESUMEN
AIM: Ki-67 is a marker of cell proliferation and is increasingly being used as a primary outcome measure in preoperative window studies of endometrial cancer (EC). This study explored the feasibility of using apparent diffusion coefficient (ADC) values in noninvasive prediction of Ki-67 expression levels in EC patients before surgery, and constructs a nomogram by combining clinical data. MATERIAL AND METHODS: This study retrospectively analyzed 280 EC patients who underwent preoperative magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in our hospital from January 2017 to February 2023. Evaluate the potential nonlinear relationship between ADC values and Ki-67 expression using the nomogram. The included patients were randomized into a training set (n = 186) and a validation set (n = 84). Using a combination of logistic regression and LASSO regression results, from which the four best predictors were identified for the construction of the nomogram. The accuracy and clinical applicability of the nomogram were assessed using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: The results of this study showed a nonlinear correlation between ADCmin and Ki-67 expression (nonlinear P = 0.019), and the nonlinear correlation between ADCmean and Ki-67 expression (nonlinear P = 0.019). In addition, this study constructed the nomogram by incorporating ADCmax, International Federation of Gynecology and Obstetrics (FIGO), and chemotherapy. The area under the curve (AUC) values of the ROC for nomogram, ADCmax, FIGO, chemotherapy and grade in the training set were 0.783, 0.718, 0.579, 0.636, and 0.654, respectively. In the validation set, the AUC values for nomogram, ADCmax, FIGO, chemotherapy, and grade were 0.820, 0.746, 0.558, 0.542, and 0.738, respectively. In addition, the calibration curves and the DCA curves suggested a better predictive efficacy of the model. CONCLUSION: A nomogram prediction model constructed on the basis of ADCmax values combined with clinical data can be used as an effective method to noninvasively assess Ki-67 expression in EC patients before surgery.
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Imagen de Difusión por Resonancia Magnética , Neoplasias Endometriales , Antígeno Ki-67 , Nomogramas , Humanos , Femenino , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Imagen de Difusión por Resonancia Magnética/métodos , Anciano , Valor Predictivo de las Pruebas , Adulto , Cuidados Preoperatorios/métodos , Estudios de Factibilidad , Biomarcadores de Tumor/metabolismoRESUMEN
OBJECTIVE: To assess whether diffusion and perfusion MRI derived parameters could non-invasively predict PD-L1 and Ki-67 status in primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). METHODS: We retrospectively analyzed DWI, DSC-PWI, and morphological MRI (mMRI) in 88 patients with PCNS-DLBCL. The mMRI features were compared using chi-square tests or Fisher exact test. Minimum ADC (ADCmin), mean ADC(ADCmean), relative minimum ADC (rADCmin), relative mean ADC (rADCmean), and relative maximum CBV (rCBVmax) values were compared in PCNS-DLBCL with different molecular status by using the Mann-Whitney U test. The diagnostic performances were evaluated by receiver operating characteristic curves. RESULTS: PCNS-DLBCL with high PD-L1 expression demonstrated a significantly higher ADCmin value than those with low PD-L1. The ADCmean and rADCmean values were significantly lower in PCNS-DLBCL with high Ki-67 status compared with those in low Ki-67 status. Other ADC, CBV parameters, and mMRI features did not show any association with these molecular statuses The diagnostic efficacy of ADC values in assessing PD-L1 and Ki-67 status was relatively low, with area under the curves (AUCs) values less than 0.7. CONCLUSIONS: DWI-derived ADC values can provide some relevant information about PD-L1 and Ki-67 status in PCNS-DLBCL, but may not be sufficient to predict their expression due to the rather low diagnostic performance.
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Antígeno B7-H1 , Neoplasias del Sistema Nervioso Central , Imagen de Difusión por Resonancia Magnética , Antígeno Ki-67 , Linfoma de Células B Grandes Difuso , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Antígeno Ki-67/metabolismo , Antígeno B7-H1/metabolismo , Imagen de Difusión por Resonancia Magnética/métodos , Anciano , Adulto , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Neoplasias del Sistema Nervioso Central/metabolismo , Anciano de 80 o más Años , Angiografía por Resonancia Magnética/métodos , Curva ROCRESUMEN
BACKGROUND: Pathologists commonly employ the Ki67 immunohistochemistry labelling index (LI) when deciding appropriate therapeutic strategies for patients with breast cancer. However, despite several attempts at standardizing the Ki67 LI, inter-observer and inter-laboratory bias remain problematic. We developed a flow cytometric assay that employed tissue dissociation, enzymatic treatment and a gating process to analyse Ki67 in formalin-fixed paraffin-embedded (FFPE) breast cancer tissue. RESULTS: We demonstrated that mechanical homogenizations combined with thrombin treatment can be used to recover efficiently intact single-cell nuclei from FFPE breast cancer tissue. Ki67 in the recovered cell nuclei retained reactivity against the MIB-1 antibody, which has been widely used in clinical settings. Additionally, since the method did not alter the nucleoskeletal structure of tissues, the nuclei of cancer cells can be enriched in data analysis based on differences in size and complexity of nuclei of lymphocytes and normal mammary cells. In a clinical study using the developed protocol, Ki67 positivity was correlated with the Ki67 LI obtained by hot spot analysis by a pathologist in Japan (rho = 0.756, P < 0.0001). The number of cancer cell nuclei subjected to the analysis in our assay was more than twice the number routinely checked by pathologists in clinical settings. CONCLUSIONS: The findings of this study showed the application of this new flow cytometry method could potentially be used to standardize Ki67 assessments in breast cancer.
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Neoplasias de la Mama , Citometría de Flujo , Antígeno Ki-67 , Adhesión en Parafina , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análisis , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Humanos , Citometría de Flujo/métodos , Femenino , Adhesión en Parafina/métodos , Formaldehído , Fijación del Tejido/métodosRESUMEN
OBJECTIVES: To develop and validate a radiomics nomogram combining radiomics features and clinical factors for preoperative evaluation of Ki-67 expression status and prognostic prediction in clear cell renal cell carcinoma (ccRCC). METHODS: Two medical centers of 185 ccRCC patients were included, and each of them formed a training group (n = 130) and a validation group (n = 55). The independent predictor of Ki-67 expression status was identified by univariate and multivariate regression, and radiomics features were extracted from the preoperative CT images. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) were used to identify the radiomics features that were most relevant for high Ki-67 expression. Subsequently, clinical model, radiomics signature (RS), and radiomics nomogram were established. The performance for prediction of Ki-67 expression status was validated using area under curve (AUC), calibration curve, Delong test, decision curve analysis (DCA). Prognostic prediction was assessed by survival curve and concordance index (C-index). RESULTS: Tumour size was the only independent predictor of Ki-67 expression status. Five radiomics features were finally identified to construct the RS (AUC: training group, 0.821; validation group, 0.799). The radiomics nomogram achieved a higher AUC (training group, 0.841; validation group, 0.814) and clinical net benefit. Besides, the radiomics nomogram provided a highest C-index (training group, 0.841; validation group, 0.820) in predicting prognosis for ccRCC patients. CONCLUSIONS: The radiomics nomogram can accurately predict the Ki-67 expression status and exhibit a great capacity for prognostic prediction in patients with ccRCC and may provide value for tailoring personalized treatment strategies and facilitating comprehensive clinical monitoring for ccRCC patients.
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Carcinoma de Células Renales , Antígeno Ki-67 , Neoplasias Renales , Nomogramas , Radiómica , Tomografía Computarizada por Rayos X , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
This study investigates the carcinogenic potential of chronic dermal exposure (16 weeks) to sulfuric acid (SA) in immunocompetent mice. Clinical assessments, histopathological analyses, immunohistochemical analyses and biochemical assays were conducted to evaluate skin irritation, oxidative stress biomarkers and the potential carcinogenic effect of SA. Results indicated that prolonged exposure to SA leads to various alterations in skin structure, notably inflammation, preneoplastic and neoplastic proliferation in hair follicles, as well as hyperkeratosis and acanthosis, resulting in an increased epidermal thickness of 98.50 ± 21.6 µm. Immunohistochemistry analysis further corroborates these observations, showcasing elevated nuclear expression of p53 and Ki-67, with a significant mitotic index of (57.5% ± 2.5%). Moreover, biochemical analyses demonstrate that SA induces lipid peroxidation in the skin, evidenced by a high level of Malondialdehyde and a consequential reduction in catalase activity. These findings suggest that prolonged exposure to SA can induce skin neoplasms, highlighting the need for stringent safety measures in environments where SA is frequently used. This study underscores the potential occupational health risks associated with SA exposure.
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Neoplasias Cutáneas , Ácidos Sulfúricos , Animales , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Ratones , Ácidos Sulfúricos/efectos adversos , Ácidos Sulfúricos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Femenino , Malondialdehído/metabolismo , Inmunocompetencia , Catalasa/metabolismo , Piel/patología , Piel/metabolismo , Piel/efectos de los fármacos , Antígeno Ki-67/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
To determine if fluoride's established negative impact on adult kidney health begins during gestation, an intergenerational model of Wistar rats was exposed to two doses of fluoride (2.5 or 5.0â¯mg/kg/day via gavage) 20 days before mating and during gestation (20 days). The results revealed that fluoride was distributed to the amniotic fluid and fetus, resulting in lower weight, more pronounced fetal restriction, and decreased creatinine, osmolarity, and amniotic fluid volume. At the kidney level, less development in the nephrogenic and cortical zones was observed in the fluoride treatment groups, with an imbalance in the number of glomeruli and "S" shaped bodies, an increase in the immunoexpression of the marker of proliferation Ki-67 in the nephrogenic zone, an increase in the expression of Wnt4 and more maturation of the renal tubules, indicating that fluoride exposure during pregnancy alters kidney development and promotes early maturation of tubular segments.
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Fluoruros , Riñón , Ratas Wistar , Animales , Femenino , Embarazo , Riñón/efectos de los fármacos , Riñón/metabolismo , Fluoruros/toxicidad , Proteína Wnt4/genética , Proteína Wnt4/metabolismo , Líquido Amniótico/metabolismo , Ratas , Antígeno Ki-67/metabolismo , Masculino , Feto/efectos de los fármacos , Exposición Materna/efectos adversosRESUMEN
The individualization of chromosomes during early mitosis and their clustering upon exit from cell division are two key transitions that ensure efficient segregation of eukaryotic chromosomes. Both processes are regulated by the surfactant-like protein Ki-67, but how Ki-67 achieves these diametric functions has remained unknown. Here, we report that Ki-67 radically switches from a chromosome repellent to a chromosome attractant during anaphase in human cells. We show that Ki-67 dephosphorylation during mitotic exit and the simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface. Experiments and coarse-grained simulations support a model in which the coalescence of chromosome surfaces, driven by co-condensation of Ki-67 and RNA, promotes clustering of chromosomes. Our study reveals how the switch of Ki-67 from a surfactant to a liquid-like condensed phase can generate mechanical forces during genome segregation that are required for re-establishing nuclear-cytoplasmic compartmentalization after mitosis.
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Segregación Cromosómica , Cromosomas Humanos , Antígeno Ki-67 , Mitosis , Humanos , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Células HeLa , Cromosomas Humanos/metabolismo , Cromosomas Humanos/genética , Fosforilación , AnafaseRESUMEN
During the aging process, elastin is degraded and the level of elastin-derived peptides (EDPs) successively increases. The main peptide released from elastin during its degradation is a peptide with the VGVAPG sequence. To date, several papers have described that EDPs or elastin-like peptides (ELPs) affect human mesenchymal stem cells (hMSCs) derived from different tissues. Unfortunately, despite the described effect of EDPs or ELPs on the hMSC differentiation process, the mechanism of action of these peptides has not been elucidated. Therefore, the aim of the present study was to evaluate the impact of the VGVAPG and VVGPGA peptides on the hMSC stemness marker and elucidation of the mechanism of action of these peptides. Our data show that both studied peptides (VGVAPG and VVGPGA) act with the involvement of ERK1/2 and c-SRC kinases. However, their mechanism of activation is probably different in hMSCs derived from adipose tissue. Both studied peptides increase the KI67 protein level in hMSCs, but this is not accompanied with cell proliferation. Moreover, the changes in the NANOG and c-MYC protein expression and in the SOX2 and POU5F1 mRNA expression suggest that EDPs reduced the hMSC stemness properties and could initiate cell differentiation. The initiation of differentiation was evidenced by changes in the expression of AhR and PPARγ protein as well as specific genes (ACTB, TUBB3) and proteins (ß-actin, RhoA) involved in cytoskeleton remodeling. Our data suggest that the presence of EDPs in tissue can initiate hMSC differentiation into more tissue-specific cells.
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Diferenciación Celular , Elastina , Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/metabolismo , Elastina/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/citología , Antígeno Ki-67/metabolismo , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción SOXB1/genética , Péptidos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Proteína Homeótica Nanog/metabolismo , Proteína Homeótica Nanog/genética , Células Cultivadas , Oligopéptidos/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Proliferación Celular , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismoAsunto(s)
Neoplasias Encefálicas , Proteínas de Unión al ARN , Humanos , Masculino , Femenino , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Preescolar , Estudios Retrospectivos , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteína Ácida Fibrilar de la Glía/genética , Nestina/metabolismo , Nestina/genética , Lóbulo Parietal/patología , Lóbulo Parietal/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Neoplasias del Tronco Encefálico/patología , Neoplasias del Tronco Encefálico/genética , Neoplasias del Tronco Encefálico/metabolismo , Neoplasias del Tronco Encefálico/cirugía , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteína SMARCB1/metabolismo , Proteína SMARCB1/genética , Lóbulo Frontal/patología , Lóbulo Frontal/metabolismo , Formación de Roseta , Estudios de Seguimiento , Antígeno Ki-67/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genéticaRESUMEN
Most mesenchymal tumors found in the uterine corpus are benign tumors; however, uterine leiomyosarcoma is a malignant tumor with unknown risk factors that repeatedly recurs and metastasizes. In some cases, the histopathologic findings of uterine leiomyoma and uterine leiomyosarcoma are similar and surgical pathological diagnosis using excised tissue samples is difficult. It is necessary to analyze the risk factors for human uterine leiomyosarcoma and establish diagnostic biomarkers and treatments. Female mice deficient in the proteasome subunit low molecular mass peptide 2 (LMP2)/ß1i develop uterine leiomyosarcoma spontaneously. MATERIAL AND METHODS: Out of 334 patients with suspected uterine mesenchymal tumors, patients diagnosed with smooth muscle tumors of the uterus were selected from the pathological file. To investigate the expression status of biomarker candidate factors, immunohistochemical staining was performed with antibodies of biomarker candidate factors on thin-cut slides of human uterine leiomyosarcoma, uterine leiomyoma, and other uterine mesenchymal tumors. RESULTS AND DISCUSSION: In human uterine leiomyosarcoma, there was a loss of LMP2/ß1i expression and enhanced cyclin E1 and Ki-67/MIB1 expression. In human uterine leiomyomas and normal uterine smooth muscle layers, enhanced LMP2/ß1i expression and the disappearance of the expression of E1 and Ki-67/MIB1 were noted. The pattern of expression of each factor in other uterine mesenchymal tumors was different from that of uterine leiomyosarcoma. CONCLUSIONS: LMP2/ß1i, cyclin E1, and Ki-67/MIB1 may be candidate factors for biomarkers of human uterine leiomyosarcoma. Further large-cohort clinical trials should be conducted to establish treatments and diagnostics for uterine mesenchymal tumors.
Asunto(s)
Biomarcadores de Tumor , Ciclina E , Leiomioma , Leiomiosarcoma , Proteínas Oncogénicas , Neoplasias Uterinas , Humanos , Femenino , Neoplasias Uterinas/patología , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Leiomiosarcoma/genética , Leiomiosarcoma/metabolismo , Leiomiosarcoma/patología , Leiomiosarcoma/diagnóstico , Leiomioma/metabolismo , Leiomioma/patología , Leiomioma/diagnóstico , Leiomioma/genética , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo , Ciclina E/metabolismo , Ciclina E/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Complejo de la Endopetidasa Proteasomal/genética , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Adulto , Cisteína EndopeptidasasRESUMEN
The association of clinical, pathological, and immunohistochemical characteristics of papillary thyroid cancer with cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center. According to multivariate analysis, the independent predictors of fatal outcome within 10 years after surgery in patients living in Altai region are nuclear pattern of Hsp70 expression, thyroid capsular invasion, Ki-67 expression index >7%, and patient's age >45 years for men and >50 years for women. The prognostic model based on these features contributes to a significant improvement in the individual prognostic performance for papillary thyroid cancer in the modeling sample. The model has high statistical significance (χ2=64.73; p<0.001) and discriminative power (AUC=0.950, prediction accuracy 88.5%).
Asunto(s)
Antígeno Ki-67 , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Femenino , Masculino , Persona de Mediana Edad , Cáncer Papilar Tiroideo/mortalidad , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/cirugía , Estudios de Casos y Controles , Adulto , Antígeno Ki-67/metabolismo , Antígeno Ki-67/genética , Pronóstico , Análisis Multivariante , Proteínas HSP70 de Choque Térmico/metabolismo , Carcinoma Papilar/patología , Carcinoma Papilar/mortalidad , Carcinoma Papilar/cirugía , Carcinoma Papilar/metabolismo , Inmunohistoquímica , Anciano , Biomarcadores de Tumor/metabolismoRESUMEN
BACKGROUND/AIMS: Incidence of colorectal cancer is rapidly increasing worldwide. Extracellular superoxide dismutase (EcSOD; SOD3) is an antioxidant enzyme. However, SOD3 roles in colorectal cancer progression remain uncertain. MATERIALS AND METHODS: Superoxide dismutase 3 expression was evaluated, and we analyzed clinical relevance of SOD3 expression in colorectal cancer. Subsequently, SOD3 roles in colorectal cancer progression were detected by gain of function experiments. Changes in subcutaneous tumor and liver nodule size after SOD3 overexpression were examined in nude mice. The expression of proliferation marker Ki67 was assessed by immunohistochemical staining. RESULTS: Supperoxide dismutase 3 was downregulated in colorectal cancer (P <.01). Downregulation of SOD3 was correlated with unfavorable outcomes (P < .05). Superoxide dismutase 3 upregulation limited the proliferative (P <.05), migrative (P <.01) and invasive actions of colorectal cancer cells (P <.01) by suppressing epithelial-mesenchymal transition. Moreover, SOD3 overexpression reduced Ki67 expression (P <.01) and blocked tumor growth (P <01) and liver metastasis (P <.001) in mouse tumor model. CONCLUSION: Superoxide dismutase 3 upregulation attenuates tumor growth and liver metastasis in colorectal cancer, suggesting that SOD3 has potential diagnostic and prognostic values regarding colorectal cancer treatment.