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1.
J Comp Pathol ; 172: 48-52, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31690414

RESUMO

We describe the clinical and histological characteristics of stromal-type nephroblastomas that developed in two hedgehogs (Atelerix albiventris). In case 1, the tumour was composed of a proliferation of anaplastic stromal cells with ductal structures resembling the epithelium of nephroblastoma. In case 2, spindle-shaped cells that were somewhat larger than nephroblasts were frequently seen surrounding the cell cluster, and there was proliferation of stromal cells with collagen fibres at the periphery. Immunohistochemically, the tumour cells labelled weakly to strongly for the nephroblast marker Wilms' tumour-1 and were positive for Ki67 with rates of 5% and 10% for cases 1 and 2, respectively. Based on the above, the diagnosis was of stromal-type nephroblastoma with anaplasia in case 1 and without anaplasia in case 2. Our findings suggest that stromal-type nephroblastomas arise in adult hedgehogs and are clinically benign, and that histological anaplasia does not affect the prognosis.


Assuntos
Ouriços-Cacheiros , Neoplasias Renais/veterinária , Tumor de Wilms/veterinária , Anaplasia , Animais , Biomarcadores Tumorais/metabolismo , Feminino , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Rim/patologia , Neoplasias Renais/patologia , Masculino , Proteínas WT1/metabolismo , Tumor de Wilms/patologia
2.
World Neurosurg ; 132: 282-291, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476452

RESUMO

OBJECTIVE: Atypical and anaplastic meningiomas, unlike their benign counterparts, are highly aggressive, locally destructive, and likely to recur after treatment. These diseases are difficult to definitively treat with traditional radiotherapy without injuring adjacent brain parenchyma. The physical properties of ion radiotherapy allows for treatment plans that avoid damaging critical neural structures. The objectives of this systematic review were to evaluate the use and efficacy of ion radiotherapy in the treatment of atypical and anaplastic meningiomas. METHODS: We performed a systematic review of the literature by querying the PubMed and Ovid databases to identify and examine literature addressing the efficacy of ion radiotherapy in maintaining long-term local tumor control for patients with atypical or anaplastic meningiomas. The outcome of interest was rate of local tumor control at 5 years after ion radiotherapy. RESULTS: Across the included studies, proton therapy delivered a mean local control rate of 59.62% after 5 years. Carbon ion radiotherapy studies showed local control rates of 95% and 63% at 2 years for grade II and III meningiomas, respectively. In contrast, carbon ion radiotherapy studies that failed to differentiate between atypical and anaplastic meningiomas produced a local control rate of 33% at 2 years. CONCLUSIONS: Proton and carbon ion radiotherapy maintain comparable rates of local control to conventional photon therapy and allow for more targeted treatment plans that may limit excess radiation damage. Although additional prospective trials are needed, ion therapy represents a burgeoning field in the treatment of atypical and anaplastic meningiomas.


Assuntos
Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Terapia com Prótons , Anaplasia , Radioterapia com Íons Pesados , Humanos , Neoplasias Meníngeas/patologia , Meningioma/patologia
3.
Breast Cancer Res Treat ; 178(1): 207-219, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31364002

RESUMO

PURPOSE: Transforming growth factor beta (TGFß) has paradoxical effects in breast cancer (BC), inhibiting initial tumors while promoting aggressive ones. A polymorphism on TGFBR2 promoter region (G-875A, rs3087465) increases TGFß type II receptor expression and is protective against cancer. Previously, we have shown that TGFB1 variants have subtype-specific roles in BC. This work sought to investigate the association between TGFBR2 and susceptibility and clinicopathological features in BC subgroups. METHODS: TGFBR2 G-875A was analyzed through PCR-RFLP in 388 BC patients and 405 neoplasia-free women. Case-control analyses as well as interaction with TGFB1 haplotypes previously associated with BC were tested through age-adjusted logistic regression. Correlations between G-875A and clinicopathological parameters were assessed through Kendall's Tau-b test. All statistical tests were two-tailed (α = 0.05). RESULTS: TGFBR2 G-875A was protective against BC in additive, genotypic, and dominant models. In subgroup-stratified analyses, these effects were greater in hormonal receptor-positive and luminal-A tumors, but were not significant in other subgroups. Logistic models including TGFB1 variants showed that in luminal-A tumors, G-875A retained its significance while TGFB1 haplotype showed a trend towards significance; otherwise, in HER2+ tumors TGFB1 variants remained significant while TGFBR2 showed a trend for association. There was no interaction between these genes. In correlation analyses, G-875A positively correlated with histopathological grade in total sample, and a trend towards significance was observed in triple-negative BCs. CONCLUSION: These results indicate that G-875A is a protective factor against BC, especially from luminal-A subtype, but may promote anaplasia in established tumors, consistent with TGFß signaling roles in BC.


Assuntos
Neoplasias da Mama/genética , Polimorfismo de Nucleotídeo Único , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Fator de Crescimento Transformador beta1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anaplasia , Brasil , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
4.
World Neurosurg ; 131: e321-e328, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31356972

RESUMO

BACKGROUND: Anaplastic meningiomas are rare tumors with a poor prognosis, even after complete surgical resection and radiotherapy. There has been limited evidence with respect to the clinical factors and their effects on the course of the disease. Various retrospective studies have not been able to provide clear evidence of standardized treatment, usually presenting contradictory results. The aim of this study was to evaluate the prognostic factors influencing the progression-free survival (PFS) and overall survival (OS) of anaplastic meningiomas, with a particular focus on the roles of the extent of resection and postoperative adjuvant radiotherapy. METHODS: Between October 2001 and March 2016, 36 patients with anaplastic meningiomas were treated in our Department of Neurosurgery, of whom 11 underwent gross total resection (GTR) and 18 subtotal resection. Twenty-one patients received postoperative adjuvant radiotherapy, and 8 were treated with surgery alone. GTR (Simpson grades I and II) was associated with significantly improved PFS (P = 0.01) and OS (P = 0.004). Furthermore, adjuvant radiotherapy showed an improvement in PFS (P = 0.01) but not in OS (P = 0.16). CONCLUSIONS: The extent of resection in anaplastic meningiomas is correlated with a better outcome. However, resection alone is not sufficient for the long-term control of anaplastic meningiomas. Adjuvant radiotherapy is an essential component in the adjuvant treatment of anaplastic meningiomas, including for patients undergoing GTR. Further investigations through which to improve adjuvant therapy options are necessary to improve meningioma therapy.


Assuntos
Neoplasias Meníngeas/terapia , Meningioma/terapia , Recidiva Local de Neoplasia/epidemiologia , Procedimentos Neurocirúrgicos , Idoso , Anaplasia , Terapia Combinada , Feminino , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida
5.
Brain Tumor Pathol ; 36(2): 40-51, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30859342

RESUMO

Many breakthroughs have been made in the past decade regarding our knowledge of the biological basis of the diffuse gliomas, the most common primary central nervous system (CNS) tumors. These tumors as a group are aggressive, associated with high mortality, and have a predilection for adults. However, a subset of CNS glial and glioneuronal tumors are characterized by a more circumscribed pattern of growth and occur more commonly in children and young adults. They tend to be indolent, but our understanding of anaplastic changes in these tumors continues to improve as diagnostic classifications evolve in the era of molecular pathology and more integrated and easily accessible clinical databases. The presence of anaplasia in pleomorphic xanthoastrocytomas and gangliogliomas is assigned a WHO grade III under the current classification, while the significance of anaplasia in pilocytic astrocytomas remains controversial. Recent data highlight the association of the latter with aggressive clinical behavior, as well as the presence of molecular genetic features of both pilocytic and diffuse gliomas, with the recognition that the precise terminology remains to be defined. We review the current concepts and advances regarding histopathology and molecular understanding of pilocytic astrocytomas, pleomorphic xanthoastrocytomas, and gangliogliomas, with a focus on their anaplastic counterparts.


Assuntos
Carcinoma/patologia , Ganglioglioma/patologia , Glioma/patologia , Anaplasia/patologia , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Neoplasias do Sistema Nervoso Central/patologia , Humanos , Neuroglia/patologia , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas B-raf/fisiologia
6.
World Neurosurg ; 131: e1-e11, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30500581

RESUMO

OBJECTIVE: Lateral intraventricular anaplastic meningiomas (LIAMs) are rare lesions. The aim of this study is to clarify clinical and radiologic characteristics and the optimal treatment strategies of LIAMs with long-term follow-up. METHODS: From September 2008 to September 2017, 5 patients with LIAM were enrolled in our study. The clinical profiles, radiologic features, treatment strategies, and outcomes were retrospectively analyzed. RESULTS: Five patients (all female; mean age, 48.8 years; range, 33-61 years) were included in this study. The most frequent symptoms were those related to increased intracranial pressure. Mean duration of symptoms was 6.7 months (range, 2 weeks-2 years). The average tumor size was 4.98 cm at the maximal diameter (range, 3.0-6.2 cm). All were confirmed with a diagnosis of anaplastic meningioma. Gross total resection was achieved in all 5 patients. All patients experienced improvement of symptoms. Recurrence and progression were identified in only 2 patients. At the last follow-up, the mean recurrence-free survival was 13 months (range, 7-21 months) and the mean overall survival was 16.25 months (range, 8-21 months). One patient was lost to follow-up. CONCLUSIONS: Female and right trigone area predominance were found in our case series. Shorter duration of symptoms, irregular tumor shape, peritumoral edema, and heterogeneous enhancement may indicate an aggressive feature. Maximal safe resection followed by radiation therapy may be the best strategy for patients with LIAM. Long-term clinical follow-up and serial imaging are recommended.


Assuntos
Neoplasias do Ventrículo Cerebral/cirurgia , Ventrículos Laterais/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Adulto , Anaplasia , Neoplasias do Ventrículo Cerebral/diagnóstico por imagem , Neoplasias do Ventrículo Cerebral/patologia , Intervalo Livre de Doença , Feminino , Humanos , Ventrículos Laterais/diagnóstico por imagem , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Radioterapia Adjuvante , Fatores de Tempo , Carga Tumoral
7.
Brain Pathol ; 29(1): 126-140, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30192422

RESUMO

Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fifty-seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3-75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomere-specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3-K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRX- (20/24, 83%) or ALT-/ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3-K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PA-A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3-K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.


Assuntos
Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Adolescente , Adulto , Idoso , Anaplasia/patologia , Biomarcadores Tumorais/genética , Encéfalo/patologia , Criança , Pré-Escolar , Feminino , Glioma/patologia , Histonas/genética , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/genética , Telômero/genética , Telômero/fisiologia , Homeostase do Telômero/genética , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/fisiologia
8.
J Comp Pathol ; 165: 45-51, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30502795

RESUMO

Feline injection site sarcomas (FISSs) are mesenchymal neoplasms that develop at the sites of delivery of vaccines or other injectable products. Vaccine adjuvants can trigger an intense and persistent inflammatory response that may lead to neoplastic transformation. The proinflammatory role of cyclo-oxygenase (COX)-2 is well known and its overexpression has prognostic value in multiple neoplastic processes. One hundred and seventeen FISSs were evaluated for the degree of inflammation and anaplasia. Immunohistochemistry was used to determine the expression of COX-2 in these sarcomas. There was a significant association between the degree of inflammation and the expression of COX-2 by neoplastic cells. COX-2 expression was lower in tumours with higher degrees of anaplasia. These findings may be useful in predicting the sensitivity of FISSs to treatment with COX-2 inhibitors. The potential therapeutic use of such agents could then be restricted to tumours with lower degrees of anaplasia.


Assuntos
Doenças do Gato/etiologia , Doenças do Gato/patologia , Reação no Local da Injeção/veterinária , Sarcoma/veterinária , Neoplasias de Tecidos Moles/veterinária , Anaplasia/veterinária , Animais , Doenças do Gato/metabolismo , Gatos , Ciclo-Oxigenase 2/metabolismo , Inflamação/veterinária
9.
PLoS One ; 13(12): e0208936, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30543698

RESUMO

This study explores the genomic alterations that contribute to the formation of a unique subset of low-risk, epithelial differentiated, favorable histology Wilms tumors (WT), tumors that have been characterized by their expression of post-induction renal developmental genes (Subset 1 WT). We demonstrate copy neutral loss of heterozygosity involving 19q13.32-q13.43, unaccompanied by evidence for imprinting by DNA methylation. We further identified loss-of-function somatic mutations in TRIM28 (also known as KAP1), located at 19q13, in 8/9 Subset 1 tumors analyzed. An additional germline TRIM28 mutation was identified in one patient. Retrospective evaluation of previously analyzed WT outside of Subset 1 identified an additional tumor with anaplasia and both TRIM28 and TP53 mutations. A major function of TRIM28 is the repression of endogenous retroviruses early in development. We depleted TRIM28 in HEK293 cells, which resulted in increased expression of endogenous retroviruses, a finding also demonstrated in TRIM28-mutant WT. TRIM28 has been shown by others to be active during early renal development, and to interact with WTX, another gene recurrently mutated in WT. Our findings suggest that inactivation of TRIM28 early in renal development contributes to the formation of this unique subset of FHWTs, although the precise manner in which TRIM28 impacts both normal renal development and oncogenesis remains elusive.


Assuntos
Carcinogênese/genética , Neoplasias Renais/genética , Proteína 28 com Motivo Tripartido/genética , Tumor de Wilms/genética , Anaplasia/genética , Anaplasia/patologia , Metilação de DNA/genética , Feminino , Mutação em Linhagem Germinativa/genética , Células HEK293 , Humanos , Lactente , Recém-Nascido , Rim/crescimento & desenvolvimento , Rim/metabolismo , Rim/patologia , Neoplasias Renais/patologia , Mutação com Perda de Função/genética , Masculino , Fatores de Risco , Tumor de Wilms/patologia
10.
Am J Pathol ; 188(10): 2328-2338, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30036517

RESUMO

Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part owing to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to assess tumor samples easily for the degree of anaplasia. Instead, identification of genetic signatures that are able to distinguish among anaplastic grades and thus predict high- versus low-risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia also would yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes also are able to predict severe anaplasia accurately in our data set. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.


Assuntos
Genes do Retinoblastoma/genética , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Anaplasia/genética , Anaplasia/patologia , Pré-Escolar , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica , Marcadores Genéticos/genética , Humanos , Lactente , Masculino , Gradação de Tumores , Neoplasias da Retina/genética , Retinoblastoma/genética , Fatores de Risco
13.
Artigo em Inglês | MEDLINE | ID: mdl-29610389

RESUMO

We report the case of a 27-yr-old male with visual field loss who had a 4.9-cm complex cystic mass in the right occipital lobe. Histologic examination showed pilocytic astrocytoma (PA) with anaplasia, and molecular characterization revealed FGFR1 duplication with additional variants of unknown significance in several genes (ARID1A, ARID1B, CHEK2, EPHA5, and MLL2). This is one of only a very few reported cases of anaplastic PA with characterization of molecular alterations.


Assuntos
Astrocitoma/diagnóstico , Astrocitoma/genética , Duplicação Gênica , Domínios e Motivos de Interação entre Proteínas/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adulto , Anaplasia , Biópsia , Humanos , Imuno-Histoquímica , Imagem por Ressonância Magnética , Masculino , Gradação de Tumores , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/química , Tomografia Computadorizada por Raios X
14.
J Pediatr Hematol Oncol ; 40(4): 331-333, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28859044

RESUMO

The prognosis of relapsed Wilms tumor (WT) with diffuse anaplasia is dismal, therefore, novel therapeutic strategies need to be explored. We reported on 2 consecutive cases with relapsed anaplastic WT who presented a partial response after 2 courses of vincristine, irinotecan, and bevacizumab association. This regimen may have a role in the treatment of patients with anaplastic advanced WT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Tumor de Wilms/tratamento farmacológico , Anaplasia , Bevacizumab/administração & dosagem , Criança , Pré-Escolar , Feminino , Humanos , Irinotecano/administração & dosagem , Neoplasias Renais/patologia , Masculino , Vincristina/administração & dosagem , Tumor de Wilms/patologia
15.
Int Immunol ; 29(8): 385-390, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28992076

RESUMO

Autoimmune and inflammatory conditions are frequent complications in patients with reduced numbers of T cells. Here, we describe a mouse model of thymic stromal dysplasia resulting in peripheral T-cell lymphopenia. In Foxn1:CFP-NTR transgenic mice, the bacterial nitroreductase enzyme is expressed in thymic epithelial cells and converts the prodrug CB1954 into a cytotoxic agent. This strategy enables titratable and durable destruction of thymopoietic tissue in early embryogenesis. Our results indicate that the resulting low levels of thymic capacity for T-cell production create a predisposition for the development of a complex autoimmune syndrome, chiefly characterized by inflammatory bowel disease and lymphocytic organ infiltrations. We conclude that the Foxn1:CFP-NTR transgenic mouse strain represents a suitable animal model to optimize established clinical protocols, such as thymus transplantation, to correct various forms of thymic dysplasia and to explore novel treatment options.


Assuntos
Doenças Inflamatórias Intestinais/imunologia , Linfócitos T/fisiologia , Timo/patologia , Anaplasia , Animais , Antineoplásicos/farmacologia , Apoptose , Autoimunidade , Aziridinas/farmacologia , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Humanos , Linfopenia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
17.
Oncotarget ; 8(16): 27075-27092, 2017 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-28404918

RESUMO

Glycans containing α-L-fucose participate in diverse interactions between cells and extracellular matrix. High glycan expression on cell surface is often associated with neoplastic progression. The lysosomal exoenzyme, α-L-fucosidase-1 (FUCA-1) removes fucose residues from glycans. The FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors. However, the role of FUCA-1 in tumor progression remains unclear. It is speculated that its inactivation perturbs glycosylation of proteins involved in cell adhesion and promotes cancer. FUCA-1 expression of various thyroid normal and cancer tissues assayed by immunohistochemical (IHC) staining was high in normal thyroids and papillary thyroid carcinomas (PTC), whereas it progressively decreased in poorly differentiated, metastatic and anaplastic thyroid carcinomas (ATC). FUCA-1 mRNA expression from tissue samples and cell lines and protein expression levels and enzyme activity in thyroid cancer cell lines paralleled those of IHC staining. Furthermore, ATC-derived 8505C cells adhesion to human E-selectin and HUVEC cells was inhibited by bovine α-L-fucosidase or Lewis antigens, thus pointing to an essential role of fucose residues in the adhesive phenotype of this cancer cell line. Finally, 8505C cells transfected with a FUCA-1 containing plasmid displayed a less invasive phenotype versus the parental 8505C. These results demonstrate that FUCA-1 is down-regulated in ATC compared to PTC and normal thyroid tissues and cell lines. As shown for other human cancers, the down-regulation of FUCA-1 correlates with increased aggressiveness of the cancer type. This is the first report indicating that the down-regulation of FUCA-1 is related to the increased aggressiveness of thyroid cancer.


Assuntos
Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , alfa-L-Fucosidase/genética , Anaplasia , Animais , Bovinos , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular , Selectina E/metabolismo , Ativação Enzimática , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Invasividade Neoplásica , Metástase Neoplásica , Ligação Proteica , alfa-L-Fucosidase/metabolismo , alfa-L-Fucosidase/farmacologia
18.
Mod Pathol ; 30(1): 52-59, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27658478

RESUMO

The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well-established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (≥90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high-grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated.


Assuntos
Neoplasias Ósseas/patologia , Mitose/fisiologia , Osteossarcoma/patologia , Adolescente , Adulto , Anaplasia/genética , Anaplasia/patologia , Biópsia , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Necrose/genética , Necrose/patologia , Osteossarcoma/genética , Osteossarcoma/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
19.
Acta Biochim Pol ; 64(1): 25-33, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27741326

RESUMO

Hepatocellular carcinoma (HCC) is one of the deadliest primary cancers, with a 5-year survival rate of 10% or less. This study was undertaken to elucidate the underlying biochemical and molecular mechanisms in favor of N-nitrosodiethylamine-induced hepatocellular carcinoma. Furthermore, the aim of this work was extended to explore the efficacy of Ginkgo biloba leaves extract in deterioration of HCC in rats. In the current study, HCC group experienced significant downregulation of ING-3 gene expression and upregulation of Foxp-1 gene expression in liver. Treatment of HCC groups with Ginkgo biloba leaves extract resulted in upregulation of ING-3 and downregulation of Foxp-1 gene expression in liver. In addition, there was significant increase in serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and glypican-3 (GPC-3) levels in HCC group versus the negative control group. In contrast, the groups with HCC subjected to either high or low dose of Ginkgo biloba leaves extract elicited significant reduction (P<0.05) of AFP, CEA and GPC-3 in serum compared to the untreated HCC rats. Besides, histological examination of liver tissue sections of rats in HCC group revealed typical anaplasia. Interestingly, treatment with Ginkgo biloba leaves extract elicited marked improvement in the histological feature of liver tissue in HCC groups. In conclusion, this research indicated that the carcinogenic potency of N-nitrosodiethylamine targeted multiple systems on the cellular and molecular levels. In addition, the results of the current study shed light on the promising anticancer activity of Ginkgo biloba leaves extract in treatment of hepatocellular carcinoma induced chemically in the experimental model through its apoptotic and antiproliferative properties.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Ginkgo biloba , Extratos Vegetais/farmacologia , Anaplasia/tratamento farmacológico , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Dietilnitrosamina , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas , Metabolismo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Ratos
20.
Clin Cancer Res ; 22(22): 5582-5591, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27702824

RESUMO

PURPOSE: To investigate the role and significance of TP53 mutation in diffusely anaplastic Wilms tumors (DAWTs). EXPERIMENTAL DESIGN: All DAWTs registered on National Wilms Tumor Study-5 (n = 118) with available samples were analyzed for TP53 mutations and copy loss. Integrative genomic analysis was performed on 39 selected DAWTs. RESULTS: Following analysis of a single random sample, 57 DAWTs (48%) demonstrated TP53 mutations, 13 (11%) copy loss without mutation, and 48 (41%) lacked both [defined as TP53-wild-type (wt)]. Patients with stage III/IV TP53-wt DAWTs (but not those with stage I/II disease) had significantly lower relapse and death rates than those with TP53 abnormalities. In-depth analysis of a subset of 39 DAWTs showed seven (18%) to be TP53-wt: These demonstrated gene expression evidence of an active p53 pathway. Retrospective pathology review of TP53-wt DAWT revealed no or very low volume of anaplasia in six of seven tumors. When samples from TP53-wt tumors known to contain anaplasia histologically were available, abnormal p53 protein accumulation was observed by immunohistochemistry. CONCLUSIONS: These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery. These data also suggest that most DAWTs will show evidence of TP53 mutation when samples selected for the presence of anaplasia are analyzed. This suggests that modifications of the current criteria to also consider volume of anaplasia and documentation of TP53 aberrations may better reflect the risk of relapse and death and enable optimization of therapeutic stratification. Clin Cancer Res; 22(22); 5582-91. ©2016 AACR.


Assuntos
Anaplasia/genética , Neoplasias Renais/genética , Mutação/genética , Rádio (Anatomia)/anormalidades , Proteína Supressora de Tumor p53/genética , Tumor de Wilms/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Expressão Gênica/genética , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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