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1.
Arkh Patol ; 83(3): 10-18, 2021.
Artigo em Russo | MEDLINE | ID: mdl-33822549

RESUMO

Adrenocortical cancer (ACC) is a rare endocrine malignancy of the adrenal cortex, which has an unfavorable prognosis and extremely aggressive clinical behavior in most cases. Nevertheless, cases of a more favorable disease course with late metastasis and slow progression have been described. In 2017, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) in the 4th edition of the Classification of Tumors of the Endocrine Organs identified histological variants of ACC, such as classical, oncocytic, myxoid, and sarcomatoid ones, indicating the morphological heterogeneity of this tumor. OBJECTIVE: To provide a detailed description of the morphological variants of ACC with an emphasis on their histological characteristics and the expression of immunohistochemical markers. MATERIALS AND METHODS: A total of 75 cases of ACC were analyzed in the adult population diagnosed as having the morphological variants in accordance with the International Histological Classification of Adrenal Tumors (WHO, 2017). Monoclonal antibodies to SF1, Inhibin A, Melan A, Ki-67, p53, and antimitochondrial antibodies were used for immunohistochemical diagnosis. RESULTS: The classic, oncocytic, and myxoid subtypes of ACC were found in 51 (68%), 15 (20%), and 9 (12%) cases, respectively. The functional activity of the tumors was observed in 43% (n=18) in the classic variant of ACC; moreover, the clinical picture was manifested by the symptoms of hypercorticism (38%) and virilization (5%). There were no significant differences in hormonal activity between different morphological variants. The characteristics of the above histological variants of the tumor was determined with a description of growth patterns that can improve the diagnosis of ACC. The diagnosis of ACC can be confirmed by an immunohistochemical study; the required minimum panel of markers should include SF1, Melan A, and Inhibin A. The Ki-67 proliferative activity index showed significant differences (p=0.0056) when it was determined in the morphological variants of ACC. CONCLUSION: Despite the determination of a minimal immunohistochemical panel to confirm the diagnosis of ACC, it is important to remember that each histological variant may be characterized by the different expression of immunohistochemical markers. The identification of morphological variants of ACC and the use of specific, sensitive, and prognostically significant immunohistochemical markers will allow clinicians and pathologists to more accurately judge the biological properties of this tumor and the clinical course of the disease.


Assuntos
Neoplasias do Córtex Suprarrenal , Neoplasias das Glândulas Suprarrenais , Carcinoma Adrenocortical , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/genética , Adulto , Biomarcadores Tumorais/genética , Progressão da Doença , Humanos , Prognóstico
3.
Medicine (Baltimore) ; 100(10): e25031, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725886

RESUMO

ABSTRACT: Adrenocortical carcinoma (ACC) is considered a rare cancer with poor prognosis. We used public datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to assess the relationships between N6-methyladenosine (m6A)-related genes and ACC.We used the Wilcoxon signed-rank test to compare m6A-related gene expression in ACC tissues with that in normal tissues. Then, ACC patients were grouped based on a cluster analysis of m6A-related gene expression. m6A-related genes that were significantly associated with survival were incorporated into a risk signature, and 2 groups were divided according to median risk score. Fisher exact tests were utilized to analyze differences in clinical variables between groups. We compared the overall survival (OS) rates of the groups by means of Kaplan-Meier curves and Cox regression analyses.We found that RBM15, ZC3H3, YTDHF1, YTDHF2, and ALBH5 were overexpressed in ACC and that KIAA1429, YTHDC1, HNRNPC, WTAP, METTL3, and FTO were down regulated in ACC. In addition, membership in cluster 2 or the high-risk group was associated with advanced clinical factors and poor prognosis. The univariable and multivariable Cox regression analyses showed that risk score can be considered an independent prognostic factor for ACC.We found that the expression of m6A-related genes could be used as an independent prognostic factor in ACC. However, the current study has some limitations, and further studies of m6A-related genes in ACC are needed.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Biomarcadores Tumorais/genética , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Adenosina/análogos & derivados , Adenosina/metabolismo , Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/patologia , Biomarcadores Tumorais/metabolismo , Conjuntos de Dados como Assunto , Regulação para Baixo , Feminino , Humanos , Masculino , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Pessoa de Meia-Idade , Oxirredutases N-Desmetilantes/genética , Oxirredutases N-Desmetilantes/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , RNA-Seq , Taxa de Sobrevida , Regulação para Cima
4.
Georgian Med News ; (310): 7-11, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33658401

RESUMO

We present a case of androgen and glucocorticoid secreting adrenocortical carcinoma with concomitant myelolipoma. A giant adrenal tumor which was initially nonfunctional was reassessed four years later due to the patient's refusal to treat. The patient was a 48-year-old woman with hypertension and acne lesions on the face. Laboratory findings were consistent with glucocorticoid and androgen hypersecretion. Computed tomography revealed a heterogeneously contrasting mass of 145x118x100 mm with lobular contour and soft tissue areas. The patient underwent left laparoscopic transperitoneal adrenalectomy with three port technique. There were no complications in the perioperative period. The resected specimen weighed 850 grams. Pathological findings showed a combination of myelolipoma-adrenal cortical cancer. In the postoperative period, hypertension improved and the hormone panel was normalized. Postoperative computed tomography and PET-CT showed no residual mass and metastasis. Although imaging is compatible with benign masses such as myelolipoma, coexistence of ACC-myelolipoma should be kept in mind and functional evaluation should be performed.


Assuntos
Neoplasias do Córtex Suprarrenal , Neoplasias das Glândulas Suprarrenais , Carcinoma Adrenocortical , Mielolipoma , Neoplasias do Córtex Suprarrenal/complicações , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Carcinoma Adrenocortical/complicações , Carcinoma Adrenocortical/diagnóstico por imagem , Carcinoma Adrenocortical/cirurgia , Androgênios , Feminino , Glucocorticoides , Humanos , Pessoa de Meia-Idade , Mielolipoma/complicações , Mielolipoma/diagnóstico , Mielolipoma/cirurgia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
5.
J Surg Oncol ; 123(5): 1238-1245, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33577722

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is often a contraindication to minimally invasive adrenalectomy (MIA). We used an administrative data set to analyze postoperative outcomes. We hypothesized that small tumors would have better short- and long-term outcomes, independent of the operative approach. METHODS: The National Cancer Database (2010-2016) identified patients with ACC who underwent adrenalectomy. Tumors were grouped: <5 cm (n = 125), 5-10 cm (n = 431), and >10 cm (n = 443). The primary and secondary outcomes were margin positivity and overall survival, respectively. RESULTS: Nine hundred and ninety-nine patients were analyzed: 37% MIA and 63% open adrenalectomy (OA). As the size increased, the rate of attempted MIA decreased. Larger tumors were associated with conversion to open. Although tumors with local invasion and those which required conversion to open were associated with an increased likelihood of a positive margin, tumor size was not. Although "complete" MIA (vs. OA) and tumor size were not associated with differences in survival, conversion (HR = 1.83, p = .02), positive margins (HR = 1.54, p = .01), and local invasion (HR = 1.84, p < .001) were associated with poor survival. CONCLUSION: Positive margins are associated with poor survival in ACC. Tumors ≥ 5 cm were associated with an increased conversion rate and subsequent increase in margin positivity. MIA may be considered for select patients with small tumors but adequate oncologic resection is critical.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Adrenalectomia/mortalidade , Carcinoma Adrenocortical/patologia , Laparoscopia/mortalidade , Margens de Excisão , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
6.
BMJ Case Rep ; 14(2)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568404

RESUMO

We present a case of a 19-year-old man with right shoulder pain lasting for several months. Abdominal imaging revealed a right adrenal mass directly invading vascular structures into the right atrium. Widespread metastatic adrenocortical carcinoma was confirmed on biopsy. He opted for palliative mitotane treatment with home hospice care. This case emphasises the importance of considering abdominal masses in the differential diagnosis of persistent right shoulder pain after common causes have been ruled out. Early diagnosis could be potentially life-saving.


Assuntos
Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Mitotano/uso terapêutico , Dor de Ombro/diagnóstico , Dor de Ombro/tratamento farmacológico , Adulto , Evolução Fatal , Humanos , Masculino , Doenças Raras/diagnóstico , Doenças Raras/tratamento farmacológico , Adulto Jovem
7.
Int J Mol Sci ; 22(3)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513905

RESUMO

Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expression of ATRX and ZNRF3 in a cohort of 82 adults with ACC and to establish their prognostic value. Two pathologists analyzed immuno-stained slides of a tissue microarray. The low protein expression of ATRX and ZNRF3 was associated with a decrease in overall survival (OS) (p = 0.045, p = 0.012, respectively). The Cox regression for ATRX protein expression of >1.5 showed a hazard ratio (HR) for OS of 0.521 (95% CI 0.273-0.997; p = 0.049) when compared with ≤1.5; for ZNRF3 expression >2, the HR for OS was 0.441 (95% CI, 0.229-0.852; p = 0.015) when compared with ≤2. High ATRX and ZNRF3 protein expressions were associated with optimistic recurrence-free survival (RFS) (p = 0.027 and p = 0.005, respectively). The Cox regression of RFS showed an HR of 0.332 (95%CI, 0.111-0.932) for ATRX expression >2.7 (p = 0.037), and an HR of 0.333 (95%CI, 0.140-0.790) for ZNRF3 expression >2 (p = 0.013). In conclusion, low protein expression of ATRX and ZNRF3 are negative prognostic markers of ACC; however, different cohorts should be evaluated to validate these findings.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/mortalidade , Recidiva Local de Neoplasia/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteína Nuclear Ligada ao X/metabolismo , Adolescente , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Análise de Regressão , Análise Serial de Tecidos
10.
Medicine (Baltimore) ; 99(40): e22620, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019484

RESUMO

RATIONALE: Low-dose mitotane has been widely used for many decades in patients with advanced adrenocortical carcinoma (ACC), which exhibited good safety profiles compared with the high-dose regimen. The clinical efficacy and toxicity of mitotane are closely related to its plasma concentration, and therapeutic drug monitoring (TDM) is recommended. Until now, no severe adverse drug reaction (ADR) related to the toxic plasma level after a short-term treatment of low-dose mitotane has been published. PATIENT CONCERNS: A 50-year-old Chinese female presented with severe neurological adverse events related to a toxic plasma levels of 42.8 mg/L after 4 months treatment of low-dose mitotane. DIAGNOSES: During the course of therapy, no other medication could cause neurological adverse events. Therefore, we suspected a high sensitivity to the side effect of mitotane related to a toxic plasma level. INTERVENTIONS: Treatment of mitotane was stopped. OUTCOMES: The trough plasma concentration of mitotane decreased to 18.7 mg/mL after one and a half months, and the neurological symptoms gradually improved after drug discontinuance. LESSONS: The present case provides the first report of severe neurological adverse events induced by the short-term use of low-dose mitotane for adjuvant treatment in a patient with ACC, indicating that potentially severe ADR can also occur when using low-dose regimen in the early stage of treatment. TDM and early recognition could result in a favorable outcome.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/toxicidade , Mitotano/toxicidade , Doenças do Sistema Nervoso/induzido quimicamente , Antineoplásicos Hormonais/sangue , Antineoplásicos Hormonais/uso terapêutico , Grupo com Ancestrais do Continente Asiático/etnologia , Monitoramento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Mitotano/sangue , Mitotano/uso terapêutico , Síndromes Neurotóxicas , Resultado do Tratamento , Suspensão de Tratamento
12.
Oncogene ; 39(30): 5282-5291, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32561853

RESUMO

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited therapeutic options. The lack of mouse models that recapitulate the genetics of ACC has hampered progress in the field. We analyzed The Cancer Genome Atlas (TCGA) dataset for ACC and found that patients harboring alterations in both p53/Rb and Wnt/ß-catenin signaling pathways show a worse prognosis compared with patients that harbored alterations in only one. To model this, we utilized the Cyp11b2(AS)Cre mouse line to generate mice with adrenocortical-specific Wnt/ß-catenin activation, Trp53 deletion, or the combination of both. Mice with targeted Wnt/ß-catenin activation or Trp53 deletion showed no changes associated with tumor formation. In contrast, alterations in both pathways led to ACC with pulmonary metastases. Similar to ACCs in humans, these tumors produced increased levels of corticosterone and aldosterone and showed a high proliferation index. Gene expression analysis revealed that mouse tumors exhibited downregulation of Star and Cyp11b1 and upregulation of Ezh2, similar to ACC patients with a poor prognosis. Altogether, these data show that altering both Wnt/ß-catenin and p53/Rb signaling is sufficient to drive ACC in mouse. This autochthonous model of ACC represents a new tool to investigate the biology of ACC and to identify new treatment strategies.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Modelos Animais de Doenças , Proteína Supressora de Tumor p53/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/patologia , Animais , Proliferação de Células/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Camundongos Knockout , Camundongos Transgênicos , Prognóstico
13.
Mol Cancer Ther ; 19(9): 1909-1921, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32546662

RESUMO

Mitotane causes hypercholesterolemia in patients with adrenocortical carcinoma (ACC). We suppose that cholesterol increases within the tumor and can be used to activate proliferative pathways. In this study, we used statins to decrease intratumor cholesterol and investigated the effects on ACC growth related to estrogen receptor α (ERα) action at the nuclear and mitochondrial levels. We first used microarray to investigate mitotane effect on genes involved in cholesterol homeostasis and evaluated their relationship with patients' survival in ACC TCGA. We then blocked cholesterol synthesis with simvastatin and determined the effects on H295R cell proliferation, estradiol production, and ERα activity in vitro and in xenograft tumors. We found that mitotane increases intratumor cholesterol content and expression of genes involved in cholesterol homeostasis, among them INSIG, whose expression affects patients' survival. Treatment of H295R cells with simvastatin to block cholesterol synthesis decreased cellular cholesterol content, and this affected cell viability. Simvastatin reduced estradiol production and decreased nuclear and mitochondrial ERα function. A mitochondrial target of ERα, the respiratory complex IV (COXIV), was reduced after simvastatin treatment, which profoundly affected mitochondrial respiration activating apoptosis. Additionally, simvastatin reduced tumor volume and weight of grafted H295R cells, intratumor cholesterol content, Ki-67 and ERα, COXIV expression and activity and increase terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Collectively, these data demonstrate that a reduction in intratumor cholesterol content prevents estradiol production and inhibits mitochondrial respiratory chain-inducing apoptosis in ACC cells. Inhibition of mitochondrial respiration by simvastatin represents a novel strategy to counteract ACC growth.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Colesterol/química , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mitotano/uso terapêutico , Animais , Antineoplásicos Hormonais/farmacologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Camundongos , Mitotano/farmacologia
14.
Tech Vasc Interv Radiol ; 23(2): 100676, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32591192

RESUMO

Incidental adrenal masses are common and are found in 4% of the CT scans.1 While clinical history, laboratory results, and imaging characteristics are typically sufficient for diagnosis of an adrenal lesion, a biopsy is sometimes warranted. In some cases, adrenal mass ablation is subsequently indicated. This article serves as a brief but comprehensive review of preprocedural work-up and planning before an adrenal mass ablation, as well as a discussion on ablation techniques, associated challenges and solutions, and management of expected and unexpected outcomes.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adenoma Adrenocortical/cirurgia , Carcinoma Adrenocortical/cirurgia , Criocirurgia , Micro-Ondas/uso terapêutico , Feocromocitoma/cirurgia , Ablação por Radiofrequência , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/diagnóstico por imagem , Adenoma Adrenocortical/patologia , Carcinoma Adrenocortical/diagnóstico por imagem , Carcinoma Adrenocortical/patologia , Tomada de Decisão Clínica , Criocirurgia/efeitos adversos , Humanos , Micro-Ondas/efeitos adversos , Seleção de Pacientes , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/patologia , Complicações Pós-Operatórias/etiologia , Ablação por Radiofrequência/efeitos adversos , Fatores de Risco , Resultado do Tratamento
15.
Sci Rep ; 10(1): 8846, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483162

RESUMO

Rare or orphan diseases affect only small populations, thereby limiting the economic incentive for the drug development process, often resulting in a lack of progress towards treatment. Drug repositioning is a promising approach in these cases, due to its low cost. In this approach, one attempts to identify new purposes for existing drugs that have already been developed and approved for use. By applying the process of drug repositioning to identify novel treatments for rare diseases, we can overcome the lack of economic incentives and make concrete progress towards new therapies. Adrenocortical Carcinoma (ACC) is a rare disease with no practical and definitive therapeutic approach. We apply Heter-LP, a new method of drug repositioning, to suggest novel therapeutic avenues for ACC. Our analysis identifies innovative putative drug-disease, drug-target, and disease-target relationships for ACC, which include Cosyntropin (drug) and DHCR7, IGF1R, MC1R, MAP3K3, TOP2A (protein targets). When results are analyzed using all available information, a number of novel predicted associations related to ACC appear to be valid according to current knowledge. We expect the predicted relations will be useful for drug repositioning in ACC since the resulting ranked lists of drugs and protein targets can be used to expedite the necessary clinical processes.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Reposicionamento de Medicamentos/métodos , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/patologia , Biologia Computacional , Cosintropina/uso terapêutico , DNA Topoisomerases Tipo II/metabolismo , Humanos , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/antagonistas & inibidores , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/metabolismo
17.
Nucleic Acids Res ; 48(W1): W252-W261, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32319523

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the regulation of major pathways in eukaryotic cells through their binding to and repression of multiple mRNAs. With high-throughput methodologies, various outcomes can be measured that produce long lists of miRNAs that are often difficult to interpret. A common question is: after differential expression or phenotypic screening of miRNA mimics, which miRNA should be chosen for further investigation? Here, we present miRViz (http://mirviz.prabi.fr/), a webserver application designed to visualize and interpret large miRNA datasets, with no need for programming skills. MiRViz has two main goals: (i) to help biologists to raise data-driven hypotheses and (ii) to share miRNA datasets in a straightforward way through publishable quality data representation, with emphasis on relevant groups of miRNAs. MiRViz can currently handle datasets from 11 eukaryotic species. We present real-case applications of miRViz, and provide both datasets and procedures to reproduce the corresponding figures. MiRViz offers rapid identification of miRNA families, as demonstrated here for the miRNA-320 family, which is significantly exported in exosomes of colon cancer cells. We also visually highlight a group of miRNAs associated with pluripotency that is particularly active in control of a breast cancer stem-cell population in culture.


Assuntos
MicroRNAs/metabolismo , Software , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/mortalidade , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Conjuntos de Dados como Assunto , Exossomos/metabolismo , Feminino , Humanos , Internet , Camundongos , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo
18.
Curr Opin Endocrinol Diabetes Obes ; 27(3): 177-186, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32304390

RESUMO

PURPOSE OF REVIEW: Adrenocortical tumor (ACT) is a rare disease with an annual worldwide incidence of 0.3-0.38/million children below 15 years old, and Brazilian population presents the highest incidence because of germline mutation in the TP53. Pediatric ACT is associated with virilizing features and hypercortisolism in most cases. Malignancy is defined when local invasion or metastasis is found, and it is associated with a poor prognosis. However, the correct and early diagnosis and treatment may impact on overall and disease-free survival. RECENT FINDINGS: A complete understanding of the disease and its singularities facilitates the assistance to the pediatric patient with ACT. The new insights about adrenal tumorigenesis have provided a better understanding of this disease. In this scenario, the era of molecular studies is leading to the refinement of the taxonomy, and it is offering the opportunity to discover new biomarkers and pathways of tumorigenesis, beyond the knowing ß-catenin, Insulin-like growth factor-II/IGF-IR, and the p53/Rb signaling. SUMMARY: The rarity of this disease makes it a real challenge. Here, we present a review focusing on clinical practice. A methodic approach aiming to clarify the diagnosis and a follow-up are suggested to guide physicians in the assistance of pediatrics patients, improving the prognosis.


Assuntos
Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/terapia , Carcinoma Adrenocortical/epidemiologia , Carcinoma Adrenocortical/terapia , Adolescente , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/genética , Idade de Início , Transformação Celular Neoplásica/genética , Criança , Pré-Escolar , Endocrinologia/métodos , Endocrinologia/tendências , Mutação em Linhagem Germinativa , Humanos , Lactente , Recém-Nascido , Oncologia/métodos , Oncologia/tendências , Pediatria/métodos , Pediatria/tendências
19.
Curr Opin Endocrinol Diabetes Obes ; 27(3): 170-176, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32304391

RESUMO

PURPOSE OF REVIEW: The aim of this review is to summarize recent advances on development of in vivo preclinical models of adrenocortical carcinoma (ACC). RECENT FINDINGS: Significant progress has been achieved in the underlying molecular mechanisms of adrenocortical tumorigenesis over the last decade, and recent comprehensive profiling analysis of ACC tumors identified several genetic and molecular drivers of this disease. Therapeutic breakthroughs, however, have been limited because of the lack of preclinical models recapitulating the molecular features and heterogeneity of the tumors. Recent publications on genetically engineered mouse models and development of patient-derived ACC xenografts in both nude mice and humanized mice now provide researchers with novel tools to explore therapeutic targets in the context of heterogeneity and tumor microenvironment in human ACC. SUMMARY: We review current in-vivo models of ACC and discuss potential therapeutic opportunities that have emerged from these studies.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais/tendências , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Animais , Transformação Celular Neoplásica/patologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Camundongos , Camundongos Nus , Microambiente Tumoral/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
20.
Acta Obstet Gynecol Scand ; 99(10): 1297-1302, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32282928

RESUMO

INTRODUCTION: Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery. MATERIAL AND METHODS: Five women presented with stage III-IV adrenocortical carcinoma and ovarian cyst formation during mitotane treatment. The clinical course of the disease was followed during and after treatment. The effects of mitotane on progesterone production and cell proliferation were studied in cultured human ovarian granulosa cells. RESULTS: Computed tomography and vaginal ultrasonography during mitotane treatment repeatedly demonstrated ovarian cysts of varying size without solid intralocular structures. Two women became amenorrheic during the treatment period. After mitotane cessation, the ovarian cysts disappeared and normal menstrual cycles resumed. One woman had an uncomplicated pregnancy two years after mitotane treatment. In one woman, who underwent salpingo-oophorectomy, histological analysis demonstrated benign ovarian cysts. Mitotane impeded the synthesis of progesterone, reduced the stimulatory effect of gonadotropins on progesterone formation, and reduced labeling with [3 H]thymidine in cultured granulosa cells. CONCLUSIONS: Therapeutic concentrations of mitotane are associated with the formation of benign ovarian cysts and amenorrhea. Mitotane-induced suppression of ovarian steroidogenesis and impediment of the proliferative capacity of steroid-producing cells are suggested potential pathogenetic mechanisms underlying mitotane-induced ovarian dysfunction and cyst development. Mitotane treatment does not compromise future ovarian function.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Mitotano/efeitos adversos , Cistos Ovarianos/induzido quimicamente , Adulto , Amenorreia/induzido quimicamente , Antineoplásicos Hormonais/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Mitotano/administração & dosagem , Cistos Ovarianos/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia , Adulto Jovem
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