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1.
Int J Cancer ; 153(7): 1406-1412, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37265033

RESUMO

Identifying risk factors for fracture occurrence in breast cancer (BC) skeletal metastases (SM) may guide the management of such bone deposits. There is sparse evidence regarding receptor status in SM and their relationship to fracture occurrence. Our study aimed to determine the relationship between estrogen (ER), progesterone (PR) and HER2 receptor status and Ki-67 index and fracture occurrence in SM of BC. Exactly 152 samples of SM of BC obtained from individual patients were evaluated. The status of the aforementioned receptors and Ki67 index were determined in SMs samples. Their expression was compared between SM that did and did not develop a fracture. Ninety-one cases sustained a pathological fracture at the SM site, and 61 did not. Patients who sustained a pathological fracture had a higher rate of PR positivity at their SMs as compared to those with no fracture. There was no significant difference between the two groups concerning ER, HER2+ or Ki67 status. SMs secondary to BC with a fracture are more likely to be PR positive than those with no fracture. Determining the receptor status in SMs may identify high-risk groups for fracture occurrence, and determining the PR status may also guide surgical and hormonal therapy.


Assuntos
Neoplasias da Mama , Fraturas Ósseas , Fraturas Espontâneas , Humanos , Feminino , Neoplasias da Mama/patologia , Receptores de Progesterona/metabolismo , Receptor ErbB-2/metabolismo , Antígeno Ki-67/metabolismo , Receptores de Estrogênio/metabolismo , Estrogênios , Progesterona , Biomarcadores Tumorais/metabolismo
2.
Biol Trace Elem Res ; 201(7): 3225-3232, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36156766

RESUMO

Medullary Thyroid Carcinoma (MTC) constitutes around 5% of all thyroid cancers. Trace elements assessment has emerged as a useful strategy in the diagnostics of MTC combined with Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) analysis. The aim of this study was to compare the presence and content of trace elements (i.e., Copper (Cu), Zinc (Zn), Iron (Fe), and Manganese (Mn)) in MTC with respect to control samples and their potential relationship with markers of MTC in tissues. The study included 26 patients who had undergone thyroidectomy, due to the diagnosis of MTC and 17 patients as control. We combined tumour pathology and staging, immunohistochemical analysis of calcitonin, MMPs, and TIMPs, with analytical biochemistry using Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) to determine the levels of trace elements. No differences by MTC type for MMPs and their TIPMs, although strong TIMP-1 and TIMP-2 immunohistochemical expression of MTC were unveiled. Additionally, Zn, Fe, and Mn tended to be decreased, and Cu to be increased in samples presenting MTC with respect to controls. Moreover, Zn was the unique trace element which seemed to be correlated with MMPs and TIMPs. Trace elements such as Zn, Fe, and Mn are decreased in tissues affected by MTC. In addition, Zn may be the trace element which saves more relationship with the proportion and intensity of MMPs, being considered altogether useful biomarkers of MTC. We therefore suggest the analysis of novel and traditional markers of MTC as a novel approach in this pathology.


Assuntos
Neoplasias da Glândula Tireoide , Oligoelementos , Humanos , Oligoelementos/análise , Zinco , Manganês , Metaloproteinase 2 da Matriz , Neoplasias da Glândula Tireoide/patologia
3.
J Clin Endocrinol Metab ; 105(12)2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32901291

RESUMO

CONTEXT: Adrenal lesions are frequent among patients with sporadic neuroendocrine tumors (spNETs) or multiple endocrine neoplasia type 1 (MEN1). Armadillo repeat-containing 5 (ARMC5)-inactivating variants cause adrenal tumors and possibly other neoplasms. OBJECTIVE: The objective of this work is to investigate a large cohort spNETs or MEN1 patients for changes in the ARMC5 gene. PATIENTS AND METHODS: A total of 111 patients, 94 with spNET and 17 with MEN1, were screened for ARMC5 germline alterations. Thirty-six tumors (18 spNETs and 18 MEN1 related) were collected from 20 patients. Blood and tumor DNA samples were genotyped using Sanger sequencing and microsatellite markers for chromosomes. ARMC5 and MEN1 expression were assessed by immunohistochemistry. RESULTS: In 76 of 111 (68.4%) patients, we identified 16 different ARMC5 germline variants, 2 predicted as damaging. There were no differences in the prevalence of ARMC5 variants depending on the presence of MEN1-related adrenal lesions. Loss of heterozygosity (LOH) at chromosome 16p and ARMC5 germline variants were present together in 23 or 34 (67.6%) tumors; in 7 of 23 (30.4%) their presence led to biallelic inactivation of the ARMC5 gene. The latter was more prevalent in MEN1-related tumors than in spNETs (88.9% vs 38.9%; P = .005). LOH at the chromosome 16p (ARMC5) and 11q (MEN1) loci coexisted in 16/18 MEN1-related tumors, which also expressed lower ARMC5 (P = .02) and MEN1 (P = .01) proteins compared to peritumorous tissues. CONCLUSION: Germline ARMC5 variants are common among spNET and MEN1 patients. ARMC5 haploinsufficiency or biallelic inactivation in spNETs and MEN1-related tumors suggests that ARMC5 may have a role in modifying the phenotype of patients with spNETs and/or MEN1 beyond its known role in macronodular adrenocortical hyperplasia.


Assuntos
Proteínas do Domínio Armadillo/genética , Neoplasia Endócrina Múltipla Tipo 1/genética , Tumores Neuroendócrinos/genética , Adenoma/epidemiologia , Adenoma/genética , Adolescente , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/genética , Adulto , Idoso , Criança , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/epidemiologia , Tumores Neuroendócrinos/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Paraganglioma/epidemiologia , Paraganglioma/genética , Neoplasias das Paratireoides/epidemiologia , Neoplasias das Paratireoides/genética , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/genética , Análise de Sequência de DNA , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genética , Adulto Jovem
4.
Acta Chir Iugosl ; 60(1): 95-7, 2013.
Artigo em Sérvio | MEDLINE | ID: mdl-24669571

RESUMO

Among neuroendocrine tumors of the urinary bladder, small cell carcinoma (SCCB) is the most common one. Less frequent is carcinoid tumour and very rare is a large-cell neuroendocrine carcinoma. Small cell neuroendocrine carcinoma is a very aggressive tumour, with major frequency in the seventh decade. In 95% of patients it presents with hematuria and muscle invasive disease. A case of a patient with the urinary bladder tumour, which had muscle invasion and extension in perivesical tissue, was presented. The patient was diagnosed with combined form of the tumour, consisting of small cell and squamous cell patterns. Some of the imunochistochemical markers used in diagnosis were chromogranin A, synaptophysin, cytokeratins, LCA and Ki-67. Consequently, neuroendocrine differentiation of small cell patterns of the tumour was proven. Neoadjuvant cisplatin- based chemotherapy followed by radical resection should be considered as the treatment of choice in surgically resectabile SCCB. Because of that it is essential to make histopathologic diagnosis of SCCB in transuretral tumour samples using, chromogranin A or synapthysin.


Assuntos
Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/patologia , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais/análise , Carcinoma Neuroendócrino/química , Carcinoma de Células Pequenas/química , Cromogranina A/análise , Feminino , Humanos , Sinaptofisina/análise , Neoplasias da Bexiga Urinária/química
5.
Acta Chir Iugosl ; 59(1): 39-44, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22924301

RESUMO

Neural cell adhesion molecule (NCAM) is important for cell migration and it could be expressed in some renal cell carcinoma (RCC). In recent decades, the incidence of RCC has been steadily rising by 2-4% each year. In this study NCAM expression and correlation with nuclear grade in different RCC were analyzed. We analyzed NCAM expression on 7 different RCC cell lines and 32 different RCC by immunohistochemistry, immunofluorescence, Western blot and FACS analysis. NCAM expression is detected in 6 cell lines and 16 RCC cases. NCAM-140 kDa isoform is expressed in different RCC and RCC cell lines. NCAM expression in non-invasive clear cell RCC is lower than in clear cell RCC with high nuclear grade. Expression of NCAM is not exclusive for specific RCC type, so NCAM can not be used as a specific diagnostic marker for RCC. NCAM expression is in correlation with nuclear grade in clear cell RCC, suggesting that NCAM expression is involved in aggressive behavior and metastatic potential in RCC.


Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Renais/patologia
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