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1.
Anticancer Res ; 41(1): 131-136, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419806

RESUMO

AIM: We aimed to develop a rapid, simple procedure and an algorithm for quantitative analysis and classification of the metastatic risk of gastrointestinal stromal tumours (GIST) for clinical use. MATERIALS AND METHODS: Eighteen specimens from laparoscopic local gastrectomy were assessed by flow cytometry. We devised a new risk classification for GIST by combining flow cytometry parameters with tumour size and evaluated whether the combined parameters correlated with the modified Fletcher risk classification. RESULTS: We found a significant correlation between clinical prognostic factors (mitotic count and Ki-67 labelling index) and the flow cytometry parameters DNA ploidy, DNA index and S-phase fraction. The combined parameters established from tumour size and the flow cytometry parameters showed a high correlation with the modified Fletcher risk classification (p=0.0064). Flow cytometry had to be performed for approximately 10 minutes to determine the metastatic risk. CONCLUSION: Rapid flow cytometry parameters can classify risk without the need for histological analysis.


Assuntos
Citometria de Fluxo , Tumores do Estroma Gastrointestinal/diagnóstico , Idoso , Biomarcadores , DNA de Neoplasias , Feminino , Citometria de Fluxo/métodos , Tumores do Estroma Gastrointestinal/etiologia , Tumores do Estroma Gastrointestinal/metabolismo , Humanos , Antígeno Ki-67 , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Ploidias , Prognóstico , Reprodutibilidade dos Testes , Carga Tumoral
2.
Am J Surg Pathol ; 45(1): 25-34, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33177340

RESUMO

Assessment of the Ki67 index is critical for grading well-differentiated neuroendocrine tumors (WD-NETs), which can show a broad range of labeling that defines the WHO grade (G1-G3). Poorly differentiated neuroendocrine carcinomas (PD-NECs) have a relatively high Ki67 index, >20% in all cases and commonly exceeding 50%. After anecdotally observing PD-NECs with an unexpectedly low and heterogeneous Ki67 index following chemotherapy in 5 cases, we identified 15 additional cases of treated high-grade neuroendocrine neoplasms (HG-NENs). The study cohort comprised 20 cases; 11 PD-NECs, 8 mixed adenoneuroendocrine carcinomas, and 1 WD-NET, G3 from various anatomic sites (gastrointestinal tract, pancreas, larynx, lung, and breast). The Ki67 index was evaluated on pretreatment (when available) and posttreatment samples. Topographic heterogeneity in the Ki67 index was expressed using a semi-quantitative score of 0 (no heterogeneity) to 5 (>80% difference between maximal Ki67 and minimal Ki67 indices). Relative to the pretreatment group (n=9, mean Ki67 of 86.3%, range 80% to 100%), the neoplasms in the posttreatment group (n=20, mean Ki67 of 47.7%, range 1% to 90%) showed a significantly lower Ki67 index (18/20 cases). Of the 18 cases with a relatively low Ki67 index, 15 showed heterogeneous labeling (mean heterogeneity score of 2.3, range 1 to 5) and in 3 cases it was a homogeneously low. This phenomenon was observed in all subtypes of HG-NENs. In 6 cases, the alterations in Ki67 index following treatment were sufficient to place these HG-NENs in the WHO G1 or G2 grade, erroneously suggesting a diagnosis of WD-NET, and in 9 cases there was sufficient heterogeneity in the Ki67 index to suggest that a limited biopsy may sample an area of low Ki67, even though hotspot regions with a Ki67 index of >20% persisted. In 7 cases, the alterations in the Ki67 index were accompanied by morphologic features resembling a WD-NET. These observations suggest that there is a potential for misinterpretation of previously treated PD-NECs as WD-NETs, or for assigning a lower grade in G3 WD-NETs. While the prognostic significance of treatment-associated alterations in Ki67 index is unknown, awareness of this phenomenon is important to avoid this diagnostic pitfall when evaluating treated NENs.


Assuntos
Carcinoma Neuroendócrino/patologia , Antígeno Ki-67/análise , Gradação de Tumores/métodos , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Carcinoma Neuroendócrino/tratamento farmacológico , Humanos , Índice Mitótico
3.
An Bras Dermatol ; 95(6): 691-695, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33008658

RESUMO

BACKGROUND: The mitotic index is no longer used to classify T1 melanoma patients into T1a and T1b, so it should not be used to indicate sentinel node biopsy in these patients. OBJECTIVES: To evaluate patients with T1 melanoma who underwent sentinel lymph node biopsy and to compare those who were classified as T1a with those classified T1b, according to the 7th and 8th Edition of the melanoma staging system, regarding a positive biopsy result. The authors also aimed to assess whether there is any difference in the results in both staging systems. MATERIAL AND METHODS: This was a retrospective analysis of 1213 patients who underwent sentinel lymph node biopsy for melanoma, from 2000 to 2015, in a single institution. RESULTS: Of 399 patients with thin melanomas, 27 (6.7%) presented positive sentinel lymph nodes; there was no difference in positivity for sentinel node biopsy when comparing T1a vs. T1b in both staging systems. Furthermore, the clinical results were also similar between the two groups. However, in the complete cohort analysis, the mitotic index was associated with positivity for sentinel lymph node biopsy (p < 0.0001), positivity for non-sentinel lymph node (p < 0.0001), recurrence-free survival (p < 0.0001), and specific melanoma survival (p = 0.023). STUDY LIMITATION: Unicentric study. CONCLUSION: The mitotic index was shown to be a very important prognostic factor in the present study, but it was not observed in patients classified as T1. The mitotic index should no longer be used as the only reason to refer sentinel lymph node biopsy in patients with thin melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Metástase Linfática , Melanoma/patologia , Índice Mitótico , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Estados Unidos
4.
Georgian Med News ; (303): 178-184, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32841202

RESUMO

Human papilloma virus (HPV) infection, especially with high risk types, represent the major etiological factor for the development of cervical precancerous and cancerous lesions. However, other factors including cell proliferation index, epithelial-mesenchymal transition and the presence of co-infections might also influence the progression of cervical intraepithelial neoplasia (CIN). The aim of our study was to analyse, the expression of cell proliferation markers and epithelial-mesenchymal transition markers during the progression of cervical intraepithelial neoplasia, in cases with and without co-infections. Standard immunohistochemistry was used to detect, Ki67, cyclin D1, phosphohiston-H3, p63, E-cadherin, ß-catenin and vimentin. The results of our study indicated that the expression of Ki67, phosphohiston-H3 and p63 is significantly increased during the progression of CIN disease, whilst the expression of E-cadherin and ß-catenin are progressively lost. The expression of mesenchymal marker vimentin is also increased in CINIII and in invasive carcinoma. Proliferation index based on Ki67 labelling is significantly higher in cases with co-infections and the expression on E-cadherin is significantly lower in cases with co-infections compared to cases without co-infections. In conclusion, the measurement of proliferation index, based on Ki67 labelling, as well as mitotic index based on phosphohiston-H3 detection can reliably indicate high and low risk groups of the progression of CIN. Similarly, higher p63 expression, loss of E-cadherin and ß-catenin and higher vimentin expression can indicate the progression risk of CIN. The presence of co-infections is associated with the increased expression of proliferation marker Ki67 and the loss of E-cadherin and therefore it can be considered as an additional marker of CIN progression.


Assuntos
Neoplasia Intraepitelial Cervical , Coinfecção , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Biomarcadores Tumorais , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Humanos , Índice Mitótico
5.
J Small Anim Pract ; 61(7): 449-457, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32715502

RESUMO

OBJECTIVES: To describe the clinicopathological and genetic characteristics of mast cell tumours in dogs less than 12 months old. MATERIALS AND METHODS: Retrospective review of dogs aged less than 12 months when diagnosed with mast cell tumours at three referral hospitals in the UK. RESULTS: Sixteen pure-bred dogs were included, of which 11 were female. The median age at first presentation and diagnosis were 7.6 and 9 months, respectively. In 13 dogs the mast cell tumours were cutaneous and in three they were subcutaneous. Four cutaneous mast cell tumours were described as high-grade (Patnaik or Kiupel) and nine were Patnaik grade II; three had mitotic index of >5 in 10 high-power fields. Of the three subcutaneous tumours, two had an infiltrative growth pattern and one had mitotic index of 10 per 10 high-power fields. Of 10 tested dogs, seven had c-kit mutations in exon 11 and Ki-67 score was above the cut-off value in nine. Four of 12 cases showed evidence of metastasis in the regional lymph nodes. After varying treatment protocols, all patients were alive and disease free at a median of 1115 days after diagnosis. CLINICAL SIGNIFICANCE: The prognosis of mast cell tumours in dogs less than a year old appears better than the adult counterparts, even without extensive treatment.


Assuntos
Doenças do Cão , Neoplasias Cutâneas/veterinária , Animais , Cães , Feminino , Mastócitos , Índice Mitótico/veterinária , Prognóstico , Estudos Retrospectivos
6.
PLoS One ; 15(6): e0233676, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32484812

RESUMO

In urothelial cell type non-muscle invasive urinary bladder carcinoma, TNM stage and WHO grade are widely used to classify patients into low and high­risk groups for prognostic and therapeutic decision-making. However, stage and grade reproducibility and prediction accuracy are wanting. This may lead to suboptimal treatment. We evaluated whether proliferation features, nuclear area of the epithelial cancer cells and the composition of stromal and tumor infiltrating lymphocytes have independent prognostic value. In 183 primary non-muscle invasive bladder cancer patients with long follow-up (median for stage progression cohort: 119 months, range 5-173; median for tumor recurrence cohort: 82, range 3-165) proliferation features Ki67, PPH3 and Mitotic Activity Index (MAI), Mean Nuclear Area (MNA), lymphocyte subsets (CD8+, CD4+, CD25+) and plasma cells (CD138+) were assessed on consecutive sections. Post-resection instillation treatments (none, mitomycin, BCG) were strictly standardized during the intake period. Risk of recurrence was associated with expression of Ki67 (≤ 39 vs. > 39) and Multifocality (p = 0.01). Patients with low Ki67 had a higher recurrence rate than those with high Ki67. Lymphocyte composition did not predict recurrence. Stage progression was strongly associated with high values for MAI (>15) and CD25+ (>0.2%). In a multivariate analysis the combination of MAI and CD25+ was the single most prognostic feature (p<0.001). Validation of these results in additional, independent studies is warranted.


Assuntos
Carcinoma de Células de Transição/patologia , Linfócitos do Interstício Tumoral/imunologia , Índice Mitótico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/imunologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos Testes , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidade
7.
Bull Environ Contam Toxicol ; 105(1): 127-133, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32548730

RESUMO

In this work the toxicity caused by explosive industries effluent (yellow water) at different levels of toxicity (genetic, cellular and organismal level) was evaluated by the Allium cepa test and the Sorghum sudanense germination. The results showed that the effluent paralyze the mitotic process, keeping the cells in the interphase, decreasing the mitotic index in A. cepa. Chromosomal abnormalities such as c-metaphases, adhesions, breaks, early ascending chromosomes and irregular nucleus were observed for this receptor species. The germination of S. sudanense was reduced, and the development of the radicles were affected, showing reduced tolerance index at the highest concentrations of the effluent. Thus, it is concluded that the effluent from the explosive industry is extremely toxic to the tested organisms, both in cellular and chromosomal level and also for seed germination.


Assuntos
Substâncias Explosivas/toxicidade , Germinação/efeitos dos fármacos , Cebolas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Aberrações Cromossômicas , Índice Mitótico , Cebolas/genética , Cebolas/fisiologia , Sorghum
8.
Environ Sci Pollut Res Int ; 27(22): 28066-28076, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32405953

RESUMO

Effects of imidacloprid and iprodione, isolated and in mixture, were assessed by using seed germination and root growth test, flow cytometry, and chromosomal aberrations test on Allium cepa root meristem. The highest concentrations of imidacloprid, including field concentration, increased the frequency of sub-G1 particles, decreased the frequency of nuclei in G2/M, increased the coefficient of variation of G1 (CVG1) and the frequency of aberrant cells, and inhibited the mitotic index culminating in the reduction in root length. All doses of iprodione also presented cytogenotoxic action. The highest concentration of the fungicide affected the growth of A. cepa roots. In response to exposure to pesticide mixtures, the cell cycle of A. cepa was blocked in the G1 phase. The mixtures with low doses of the pesticides significantly decreased the mitotic index, and as a consequence, the genotoxicity was reduced. In the mixtures with the highest doses of the agrochemicals, the blockage of the cell cycle was insufficient for damage repair, resulting in a significant increase of chromosomal aberrations. The results suggest caution in the use of pesticides doses that induce cytological abnormalities in non-target organisms.


Assuntos
Cebolas , Praguicidas , Aminoimidazol Carboxamida/análogos & derivados , Aberrações Cromossômicas , Dano ao DNA , Humanos , Hidantoínas , Meristema , Índice Mitótico , Neonicotinoides , Nitrocompostos , Raízes de Plantas
9.
Am J Surg Pathol ; 44(10): 1419-1428, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32452872

RESUMO

We investigated the prognostic value of a range of histologic parameters in medullary thyroid carcinoma (MTC) to design a grading system to predict overall survival. We assessed 76 patients with MTCs undergoing primary tumor resection for age, sex, tumor size, vascular space invasion, lymph node metastasis, multiple endocrine neoplasia type 2 (MEN2) status, mitotic count, Ki-67 proliferative index, spindled morphology, sheet-like growth pattern, coagulative necrosis, incipient necrosis, nuclear grade, multinucleation, prominent nucleoli, fibrosis, and amyloid deposition. In addition to the clinical features of age and the diagnosis of MEN2, the only histologic features that significantly predicted reduced overall survival were Ki-67 proliferative index, mitotic count, and the presence of coagulative necrosis. Using a combination of these 3 variables, we propose a 3-tiered grading system based solely on proliferative activity (Ki-67 proliferative index and mitotic count) and necrosis. There were 62 (82%) low-grade MTCs (low proliferative activity, no necrosis), 9 (12%) intermediate grade (low proliferative activity and necrosis present, or intermediate proliferative activity and no necrosis), and 5 (7%) high grade (intermediate proliferative activity and necrosis present, or high proliferative activity with or without necrosis). The mean overall survival was 193, 146, and 45 months, respectively (P=0.0001) for the 3 grades. The grading system remained prognostic when controlled for other factors associated with survival including age and known MEN2 syndrome. We conclude that this proposed grading system, which uses only a combination of proliferative activity (Ki-67 index, mitotic count) and coagulative necrosis, is a strong predictor of overall survival in MTC.


Assuntos
Carcinoma Neuroendócrino/patologia , Gradação de Tumores/métodos , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/mortalidade , Feminino , Humanos , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Necrose/patologia , Prognóstico , Análise de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Adulto Jovem
10.
Life Sci ; 254: 117812, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32428596

RESUMO

AIMS: Since the role of the major mitochondrial NAD+-dependent deacetylase, sirtuin 3 (Sirt3), is differential in cancer, opposite to the well-known tumor-suppressing effect of hyperoxia, this study aimed to investigate the role of Sirt3 in triple-negative breast cancer (TNBC) cell line MDA-MB-231 upon hyperoxic (95% O2) conditions. MAIN METHODS: MDA-MB-231 cells were stably transfected with Flag-tagged Sirt-3 or empty plasmid. Western blot and real-time PCR were used to monitor the expression of proteins or genes involved in mitochondrial biogenesis, metabolic regulation and antioxidant defense. Immunocytochemistry and confocal microscopy were used to confirm the cellular localization and abundance of proteins. Flow cytometry was used to analyze mitochondrial mass, potential and ROS production, and MTT test as a measure of metabolic activity. Mitotic index analysis, colony-forming unit assay, DNA damage and Annexin V-FITC analyses were used to assess the differences in the growth and apoptosis rate. KEY FINDINGS: Although Sirt3 seemed to improve mitochondrial properties by increasing mitochondrial mass and potential, metabolic activity (Warburg effect) and antioxidative defense (SOD2, Cat), it also increased mitochondrial ROS, induced DNA damage, timp-1 expression, formation of multinucleated cells and apoptosis, and finally markedly reduced the proliferation of MDA-MB-231 cells. All these effects were even more evident upon the hyperoxic treatment, thus pointing towards combined negative effect of Sirt3 and hyperoxia on MDA-MB-231 cells. SIGNIFICANCE: Both Sirt3 and hyperoxia, alone or in combination, have the potential to negatively affect the malignant properties of the MDA-MB-231 cells and should be further explored as a possible therapy for TNBC.


Assuntos
Sobrevivência Celular/fisiologia , Hiperóxia/fisiopatologia , Mitocôndrias/fisiologia , Sirtuína 3/fisiologia , Neoplasias de Mama Triplo Negativas/fisiopatologia , Anexinas/metabolismo , Apoptose/fisiologia , Carcinogênese , Linhagem Celular Tumoral , Dano ao DNA , Regulação Neoplásica da Expressão Gênica , Humanos , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/metabolismo , Índice Mitótico , Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 3/genética , Células-Tronco , Transfecção , Neoplasias de Mama Triplo Negativas/metabolismo
11.
Hum Pathol ; 100: 38-44, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32334830

RESUMO

A subset of endometrial polyps recurs after resection. The clinicopathologic significance of the phenomenon is evaluated herein. Consecutive cases of recurrent polyps (index polyp removed by hysteroscopy-directed polypectomy or by curettage; at least one more polyp diagnosed ≤12 months after) were compared with an age-matched control group of nonrecurrent polyps regarding 15 clinicopathologic features. A total of 107 (5.6%) of the 1908 polyps diagnosed in a sampling specimen during the study period was a recurrence, and 102 (6.9%) of the 1478 patients who were diagnosed with an endometrial polyp in a sampling specimen had at least 1 recurrence. Eighty-six percent of patients with any recurrences had only one recurrence, with a mean duration between the index polyp and the first recurrence of 4.36 months. On univariate analyses, the recurrent polyps were, compared with controls, significantly larger, had a higher stromal mitotic index, and more frequently displayed prominent thick-walled vessels in most fragments of the polyp. However, on Cox regression multivariate analyses, no single clinicopathologic feature was significantly associated with a recurrence. No malignancies were diagnosed during the follow-up of the study and control group patients at median follow-up durations of 23 and 34 months, respectively. In conclusion, the recurrence of an endometrial polyp is relatively uncommon (5.6% of polyps) and does not portend an increased risk of malignancy. We could not identify any clinicopathologic features that conclusively predict a recurrence.


Assuntos
Proliferação de Células , Pólipos/patologia , Células Estromais/patologia , Doenças Uterinas/patologia , Estudos de Casos e Controles , Curetagem , Bases de Dados Factuais , Feminino , Humanos , Histeroscopia , Índice Mitótico , Pólipos/cirurgia , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Doenças Uterinas/cirurgia
12.
Environ Sci Pollut Res Int ; 27(16): 20335-20343, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32242316

RESUMO

Imazalil (IMZ), a fungicide containing imidazole group, is extensively used for the prevention and treatment of fungal diseases in plants. Current study was performed to examine cyto-genotoxic potential of IMZ on Allium cepa roots by following Allium ana-telophase and single cell gel electrophoresis (comet) assays. The concentration which reduced the growth of the root tips of IMZ by 50% compared to the negative control group (EC50) was found to be 1 µg/mL by Allium root growth inhibition test. 0.5, 1, and 2 µg/mL concentrations of IMZ were exposed to Allium roots for intervals of 24, 48, 72, and 96 h. 10 µg/mL of methyl methane sulfonate (MMS) and distilled water were used as control groups, both positive and negative. Statistical analysis was performed by using one-way ANOVA with Duncan's multiple comparison tests at p ≤ 0.05 and Pearson correlation test at p = 0.01. IMZ showed cytotoxic effect by statistically decreasing root growth and mitotic index (MI) and also genotoxic effect by statistically increasing chromosomal aberrations (CAs) and DNA damage compared to the negative control group. With these cyto-genotoxic effects, it should be used carefully and further cyto-genotoxic mechanisms should be investigated along with other toxicity tests.


Assuntos
Fungicidas Industriais/farmacologia , Cebolas/genética , Aberrações Cromossômicas , Análise Citogenética , Dano ao DNA , Humanos , Imidazóis/farmacologia , Meristema/efeitos dos fármacos , Índice Mitótico , Raízes de Plantas/efeitos dos fármacos
13.
PLoS One ; 15(4): e0231082, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240261

RESUMO

Increased periods of prolonged droughts followed by severe precipitation events are expected throughout South America due to climate change. Freshwater sediments are especially sensitive to these changing climate conditions. The increased oscillation of water levels in aquatic ecosystems causes enhanced cycles of sediment drying and rewetting. Here we experimentally evaluate the effects of induced drought followed by a rewetting event on the release of carbon dioxide (CO2), methane (CH4), nutrients (nitrogen and phosphorus), and trace elements (iron, manganese, and zinc) from the sediment of a tropical reservoir in southeastern Brazil. Furthermore, we used bulb onions (Allium cepa) to assess the potential cytogenotoxicity of the water overlying sediments after rewetting. We found peaks in CO2 and CH4 emissions when sediments first transitioned from wet to dry, with fluxes declining as sediments dried out. CO2 emissions peaked again upon rewetting, whereas CH4 emissions remained unaltered. Our experiment also revealed average increases by up to a factor of ~5000 in the release rates of nutrients and trace elements in water overlying sediments after rewetting. These increased release rates of potentially toxic compounds likely explain the lower replication of Allium cepa cells (up to 22% reduction) exposed to water overlying sediments after rewetting. Our findings suggest that increased events of drought followed by rewetting may lead to a range of changes in freshwater ecosystems, including nutrient enrichment, increased toxicity following resuspension of contaminants, and higher emission of greenhouse gases to the atmosphere.


Assuntos
Dessecação , Sedimentos Geológicos/química , Gases de Efeito Estufa/análise , Mutagênicos/toxicidade , Oligoelementos/análise , Água/química , Dióxido de Carbono/análise , Morte Celular/efeitos dos fármacos , Difusão , Metano/análise , Índice Mitótico , Nitrogênio/análise , Cebolas/citologia , Fósforo/análise
14.
Hum Pathol ; 98: 98-109, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32145220

RESUMO

We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcomes. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2 mm2, necrosis, lymphatic invasion, and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlated with clinical outcomes. Based on our analysis, we consider that the separation of low- and intermediate-grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of overgrading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcomes.


Assuntos
Tumor Carcinoide/patologia , Neoplasias Pulmonares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/mortalidade , Tumor Carcinoide/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Gradação de Tumores , Estadiamento de Neoplasias , Pneumonectomia , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
15.
Plant Physiol Biochem ; 149: 170-177, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32070910

RESUMO

With the aim to investigate the mechanisms of action of nano plastics (nano PS) on plants, seeds of Allium cepa were germinated for 72 h in the presence of polystyrene nano PS (50 nm size, at concentrations of 0.01, 0.1 and 1 g L-1) and, subsequently, roots were analysed by a multifaceted approach. No effect was induced by any concentration of nano PS on the percentage of seed germination while root growth was inhibited by 0.1 and 1 g L-1 nano PS. Cytological analysis of the root meristems indicated cytotoxicity (reduction of mitotic index) and genotoxicity (induction of cytogenetic anomalies and micronuclei) starting from the lowest dose. Moreover, the biochemical and histochemical analysis of oxidative stress markers gave evidence of stress induction, especially at the highest doses. Damages reported could be due to mechanical surface contact in root external layers, as evidenced by histological localization, and to the internalization of nano PS in different cellular compartments, observed under TEM. The present research underlines the hazardous nature of nano PS, that for their ability to be internalized into crop plants, can enter into different trophic levels of the food chain.


Assuntos
Allium , Germinação , Cebolas , Estresse Oxidativo , Raízes de Plantas , Plásticos , Poliestirenos , Germinação/efeitos dos fármacos , Índice Mitótico , Cebolas/efeitos dos fármacos , Cebolas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plásticos/metabolismo , Plásticos/toxicidade , Poliestirenos/metabolismo , Poliestirenos/toxicidade
16.
Chemosphere ; 249: 126193, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32086064

RESUMO

Propanil can produce methemoglobinemia, hemolytic anemia, hepatotoxicity, metabolic disorder and nephrotoxicity. It also has a genotoxic effect, although it is not listed as a carcinogen and it continues to be applied excessively throughout the world. Consequently, in this study the cytogenotoxic effect of propanil was evaluated, using apical root cells of Allium cepa and Lens culinaris. In which, L. culinaris seeds and A. cepa bulbs were subjected to 6 treatments with propanil (2, 4, 6, 8, 10 and 12 mg L-1) and to distilled water as control treatment. Subsequently, the root growth was measured every 24 h for 3 days. Next, the mitotic index and cellular anomalies were determined. Whereby, decreased root development was observed in all treatments. Likewise, greater inhibition of mitosis was evidenced in L. culinaris compared to A. cepa. In addition, chromosomal abnormalities, such as nucleus absence, sticky chromosomes in metaphase and binucleated cells, were present in most of the treatments. Thus, the presence of micronuclei and the results of L. culinaris, indicate the high cytogenotoxicity of propanil and the feasibility of this species as bioindicator.


Assuntos
Herbicidas/toxicidade , Lens (Planta)/efeitos dos fármacos , Cebolas/efeitos dos fármacos , Propanil/toxicidade , Allium , Núcleo Celular , Aberrações Cromossômicas , Dano ao DNA , Biomarcadores Ambientais , Mitose , Índice Mitótico , Raízes de Plantas/efeitos dos fármacos , Testes de Toxicidade
17.
Mutat Res ; 849: 503142, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32087856

RESUMO

E171 (titanium dioxide, TiO2), an authorized foods and beverage additive, is also used in food packaging and in pharmaceutical and cosmetic preparations. E171 is considered to be an inert and non-digestible material, not storable in animal tissues, but the possible presence of TiO2 nanoparticles (NP) may present a risk to human health and the environment. We determined the presence of 15% TiO2 NP in a commercial E171 food additive product, by electron microscopy. The biological effects of E171 were assessed in Lens culinaris and Allium cepa for the following endpoints: percentage of germination, root elongation, mitotic index, presence of chromosomal abnormalities, and micronuclei. The results indicated low phytotoxicity but dose-dependent genotoxicity. We also observed internalization of TiO2 NP and ultrastructural alterations in the root systems.


Assuntos
Aditivos Alimentares/toxicidade , Lens (Planta)/efeitos dos fármacos , Mutagênicos/toxicidade , Nanopartículas/toxicidade , Cebolas/efeitos dos fármacos , Titânio/toxicidade , Animais , Aberrações Cromossômicas/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Germinação/efeitos dos fármacos , Humanos , Lens (Planta)/metabolismo , Lens (Planta)/ultraestrutura , Micronúcleos com Defeito Cromossômico , Microscopia Eletrônica , Índice Mitótico/estatística & dados numéricos , Cebolas/metabolismo , Cebolas/ultraestrutura , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/ultraestrutura
18.
Radiol Med ; 125(5): 465-473, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32048155

RESUMO

PURPOSE: The pathological risk degree of gastrointestinal stromal tumors (GISTs) has become an issue of great concern. Computed tomography (CT) is beneficial for showing adjacent tissues in detail and determining metastasis or recurrence of GISTs, but its function is still limited. Radiomics has recently shown a great potential in aiding clinical decision-making. The purpose of our study is to develop and validate CT-based radiomics models for GIST risk stratification. METHODS: Three hundred and sixty-six patients clinically suspected of primary GISTs from January 2013 to February 2018 were retrospectively enrolled, among which data from 140 patients were eventually analyzed after exclusion. Data from patient CT images were partitioned based on the National Institutes of Health Consensus Classification, including tumor segmentation, radiomics feature extraction and selection. A radiomics model was then proposed and validated. RESULTS: The radiomics signature demonstrated discriminative performance for advanced and nonadvanced GISTs with an area under the curve (AUC) of 0.935 [95% confidence interval (CI) 0.870-1.000] and an accuracy of 90.2% for validation cohort. The radiomics signature demonstrated favorable performance for the risk stratification of GISTs with an AUC of 0.809 (95% CI 0.777-0.841) and an accuracy of 67.5% for the validation cohort. Radiomics analysis could capture features of the four risk categories of GISTs. Meanwhile, this CT-based radiomics signature showed good diagnostic accuracy to distinguish between nonadvanced and advanced GISTs, as well as the four risk stratifications of GISTs. CONCLUSION: Our findings highlight the potential of a quantitative radiomics analysis as a complementary tool to achieve an accurate diagnosis for GISTs.


Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Intervalos de Confiança , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Estudos Retrospectivos , Medição de Risco/métodos , Carga Tumoral
19.
Ecotoxicol Environ Saf ; 192: 110328, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32078840

RESUMO

In this study pillar[5]arene (P5) and a quinoline-functionalized pillar[5]arene (P5-6Q) which is used for detecting radioactive element, gas adsorption and toxic ions were synthesized. These materials were characterized by Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared (FTIR), elemental analysis, melting point, Mass Spectroscopy, Scanning Electron Microscopy (SEM) and Zeta Potential. The cytotoxic and genotoxic potential of P5 and P5-6Q at distinct concentrations of 12.5, 25, 50, and 100 µg/mL were also investigated by Allium ana-telophase and comet assays on Allium cepa roots and Drosophila melanogaster haemocytes. P5 and P5-6Q showed dose dependent cytotoxic effect by decreasing mitotic index (MI) and genotoxic effect by increasing chromosomal aberrations (CAs such as disturbed anaphase-telophase, polyploidy, stickiness, chromosome laggards and bridges) and DNA damage at the exposed concentrations. These changes in P5-6Q were lower than P5. Further research is necessary to clarify the cytotoxic and genotoxic action mechanisms of P5 and P5-6Q at molecular levels.


Assuntos
Calixarenos/toxicidade , Dano ao DNA , Drosophila melanogaster/efeitos dos fármacos , Cebolas/efeitos dos fármacos , Anáfase/efeitos dos fármacos , Animais , Calixarenos/química , Aberrações Cromossômicas , Ensaio Cometa , Citotoxinas/química , Citotoxinas/toxicidade , Drosophila melanogaster/genética , Hemócitos/efeitos dos fármacos , Índice Mitótico , Cebolas/genética , Raízes de Plantas/efeitos dos fármacos , Quinolinas/síntese química , Quinolinas/química , Quinolinas/toxicidade , Telófase/efeitos dos fármacos
20.
Asian Pac J Cancer Prev ; 21(1): 63-66, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31983165

RESUMO

BACKGROUND: Mitotic activity index is considered as the most important grading component to predict prognosis in invasive breast carcinoma. But it is believed that it is also the cause of discordance in grade estimation based on Bloom-Richardson system. Thus, reproducible methods such as immunohistochemistry (IHC) based analysis methods appears to be of great value in facilitating mitotic count. MATERIALS AND METHODS: In the present study, we examined the utility of Phosphohistone H3 by IHC in various grades of breast carcinoma and compared it with traditional mitotic count by hematoxylin and eosin (H and E) staining and probable changes in tumor grading. RESULTS: Total 90 cases of invasive breast carcinoma were evaluated. Mean mitotic count were 8.6 and 6.4/10HPF in IHC and HandE groups, respectively. Although , mean average count was higher by IHC method , good correlation was observed(R=0.914). Using PHH3 IHC, two out of 33 cases of grade I tumors were upgraded in to grade II and three cases of grade II were upgraded in to grade III. None of the tumors were down graded. CONCLUSION: Similar to some other previous studies, we found PHH3 a robust sensitive and practical marker for mitotic count in breast carcinoma. Especially it is helpful to identify the most proliferating area. However, further studies are required to confirm the superiority of this biomarker for including in grading system.
.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Histonas/genética , Mitose/genética , Fosforilação/genética , Biomarcadores Tumorais/genética , Feminino , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Índice Mitótico/métodos , Gradação de Tumores , Prognóstico
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