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1.
Medicine (Baltimore) ; 99(39): e22322, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991441

RESUMO

RATIONALE: Bronchiolar adenoma (BA) is a newly designated rare entity of the lung, including both the currently designated ciliated muconodular papillary tumor (CMPT) and so-called non-classic CMPT. The most prominent histological feature of BAs is the bilayered cell structures composed of the continuous basal cell layer and the luminal layer which consists of different proportion of mucinous cells, ciliated cells, Clara cells and/or type II pneumocytes. BA purely covered by mucinous cells without other components in the luminal layer has never been reported. PATIENT CONCERNS: An 82-year-old female patient was detected a 0.8 cm ground glass nodule in the left lower lobe of the lung. DIAGNOSES: The serum levels of tumor markers were normal. INTERVENTIONS: The patient underwent a segmentectomy of the left lower lobe. OUTCOMES: The postoperative pathological diagnosis was BA. Molecular analysis revealed that the tumor harbored ALK rearrangement and BRAF mutations simultaneously. There was no recurrence in 17 months of follow-up. LESSONS: BA can be lined only by mucinous cells, without any cuboidal and/or ciliated cells in the surface layer. This sets a dangerous pitfall in differentiation diagnosis with invasive mucinous adenocarcinoma especially during intraoperative frozen pathological diagnosis.


Assuntos
Adenoma/metabolismo , Bronquíolos/patologia , Neoplasias Pulmonares/patologia , Biologia Molecular/métodos , Adenoma/cirurgia , Assistência ao Convalescente , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/metabolismo , Biomarcadores Tumorais/sangue , Feminino , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Pneumonectomia/métodos , Proteínas Proto-Oncogênicas B-raf/metabolismo , Resultado do Tratamento
2.
Life Sci ; 260: 118416, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926922

RESUMO

BACKGROUND: Non-functioning pituitary adenomas (NFPAs) are common pituitary tumors, and surgery is generally the only treatment option. Few attempts have been made to explore target molecules for the development of NFPA pharmacological treatments. METHOD: We quantitatively assessed the expression profiles of estrogen receptor (ER) transcripts and proteins in NFPA samples, using reverse transcription-digital polymerase chain reaction (RT-dPCR) and immunohistochemistry, and further investigated the correlations between the expression levels of ER and those of downstream responsive genes. All patients had undergone surgery at the same high-volume hospital. A total of 20 patients with NFPAs were included. All patients were new-onset, and none were diagnosed with intratumoral hemorrhages or cysts. RESULTS: NFPA samples exhibited a bimodal ESR1 expression pattern and were categorized into significantly different high- and low-ESR1 expression level groups (P < 0.05). In contrast, expression levels of ESR1 variants and ESR2 could barely be detected. Similar results were obtained through the immunohistochemical staining of NFPAs, using well-validated antibodies against ERs. The expression levels of ESR1 positively correlated with those of GREB1, an estrogen-responsive gene [correlation coefficient (r) = 0.623, P = 0.003]. CONCLUSIONS: ESR1 expression levels in NFPAs exhibited a bimodal pattern and were positively correlated with GREB1 expression levels. The accurate assessment of ER expression levels may further advance future NFPA-related research.


Assuntos
Adenoma/patologia , Biomarcadores Tumorais/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hipofisárias/patologia , Adenoma/genética , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
3.
Cancer Immunol Immunother ; 69(8): 1577-1588, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32306077

RESUMO

HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma-adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15-3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59-4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent non-neoplastic tissues, for both epithelium (n = 63, p = 0.015, HR 3.6, 95% CI 1.279-10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32-19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p < 0.01) and stroma (p < 0.001). HLA-DR was further reduced in late-stage carcinoma (n = 101) compared to early stage (n = 105), in epithelium (p < 0.001) and stroma (p < 0.01). HLA-DR expression was lower (p < 0.05) in the adjacent non-neoplastic epithelium of patients with cancer recurrence. We demonstrate a progressive loss of HLA-DR in epithelial and stromal tissue compartments during CRC development and show prognostic ability in carcinoma-adjacent non-neoplastic tissues, highlighting the importance of this molecule in the anti-cancer immune response. These findings may have wider implications for immunotherapeutic interventions.


Assuntos
Adenocarcinoma/patologia , Adenoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Antígenos HLA-DR/metabolismo , Recidiva Local de Neoplasia/patologia , Células Estromais/metabolismo , Adenocarcinoma/metabolismo , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Gulf J Oncolog ; 1(32): 66-70, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32342922

RESUMO

Chronic immunosuppression is known to cause an increased risk of cancers in organ transplant recipients leading to the rise in morbidity and mortality among these patients. Recent studies have observed that thyroid lesions are more frequently encountered in kidney transplant recipients. A 45-year-old woman with history of chronic hypertension, kidney transplant and graft failure, was admitted for assessment for a second renal transplant and detected to have a thyroid nodule by ultrasound (US). A fine needle aspirate (FNA) on the nodule was reported as Hurthle cell neoplasm. Histopathology revealed a Hurthle cell adenoma with an incidental micro papillary carcinoma. On follow up a year later, US investigation revealed another nodule in the inferior pole of the remnant lobe of thyroid. FNA showed sheets of uniform small round cells arranged in micro follicles, intermixed with Hurthle-like cells with absence of colloid, raising the possibility of a parathyroid lesion. Biochemical tests, clinical history, cytomorphological, immunocytochemical and biochemical tests supported a parathyroid adenoma. Advancements in diagnostic techniques and management strategies have not only improved survival rates in patients with chronic renal disease but have also identified an increasing number of multiple primary tumors in these patients. Thyroid lesions have cytomorphological similarities and may masquerade parathyroid neoplasms. Regular thyroid screening in post- transplant patients, meticulous pathological examination and parathormone assay are crucial in the early diagnosis, management and prevention of morbidity and mortality in these patients. Keywords: Fine needle aspiration, kidney transplant, Hurthle cell neoplasm, parathyroid adenoma, micropapillary carcinoma.


Assuntos
Adenoma/metabolismo , Carcinoma Papilar/diagnóstico , Células Oxífilas/metabolismo , Neoplasias das Paratireoides/diagnóstico , Disfunção Primária do Enxerto/etiologia , Carcinoma Papilar/complicações , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias das Paratireoides/complicações , Transplantados
5.
Orv Hetil ; 161(12): 474-478, 2020 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-32172585

RESUMO

Thyrotropin-secreting pituitary tumors are rare causes of hyperthyroidism and account for less than 1% of all pituitary adenomas. The number of reported cases increased over the last few years as a consequence of the routine use of ultrasensitive immunometric assays for measuring thyrotropin levels. In the clinical practice, thyrotropin secreting adenomas must be considered in case of inappropriately normal to elevated thyrotropin in the presence of elevated free serum thyroid hormone levels. The authors present the case history of a middle aged female patient, who suffered from hyperthyreodism caused by a thyrotropin-secreting pituitary macroadenoma. After transient thyreostatic treatment, radical neurosurgical removal of the tumor was performed. The pituitary surgery was effective in restoring the patient's euthyreodism. The postoperative pituitary function remained intact. During follow-up, the recurrence of the disease was not detected. In our case report, the difficulties in the differential diagnoses are also discussed. Orv Hetil. 2020; 161(12): 474-478.


Assuntos
Adenoma/metabolismo , Adenoma/cirurgia , Hipertireoidismo/etiologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgia , Tireotropina/metabolismo , Adenoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Hipofisárias/patologia , Testes de Função Tireóidea , Tireotropina/sangue , Resultado do Tratamento
6.
J Endocrinol ; 245(1): 101-113, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32027601

RESUMO

Pituitary-directed medical treatment for Cushing's disease (CD) is currently represented by membrane receptor targeting drugs (somatostatin analogs and dopamine agonists). Somatostatin and dopamine receptors are regulated by ß-arrestins, which have been shown to be differentially regulated by glucocorticoids in non-neuroendocrine cells. In this study we investigated the effects of glucocorticoids on ß-arrestin expression in corticotroph tumor cells. First, AtT20 cells, a mouse model of CD, were exposed to dexamethasone (Dex) at different time points and ß-arrestin expression was evaluated at mRNA and protein levels. Futhermore, ß-arrestin mRNA expression was evaluated in 17 human corticotroph adenoma samples and correlated to patients' pre-operative cortisol levels. We observed that Dex treatment induced a time-dependent increase in ß-arrestin 1 mRNA expression and a decrease in ß-arrestin 2. The same modulation pattern was observed at protein level. Dex-mediated modulation of ß-arrestins was abolished by co-treatment with mifepristone, and Dex withdrawal restored ß-arrestin expression to basal levels after 72 h. The evaluation of ß-arrestin mRNA in corticotroph adenomas from CD patients with variable disease activity showed a significant positive correlation between ß-arrestin 1 mRNA and urinary cortisol levels. The effect of glucocorticoids on ß-arrestin levels was confirmed by the analysis of two samples from a single patient, which underwent adenomectomy twice, with different pre-operative cortisol levels. In conclusion, glucocorticoids induce an inverse modulation of the two ß-arrestin isofoms in corticotroph tumor cells. Since ß-arrestins regulate membrane receptor functions, this finding may help to better understand the variable response to pituitary-targeting drugs in patients with Cushing's disease.


Assuntos
Adenoma Hipofisário Secretor de ACT/genética , Adenoma/genética , Glucocorticoides/farmacologia , Neoplasias Hipofisárias/genética , beta-Arrestina 1/genética , beta-Arrestina 2/genética , Adenoma Hipofisário Secretor de ACT/metabolismo , Adenoma Hipofisário Secretor de ACT/patologia , Adenoma/metabolismo , Adenoma/patologia , Adulto , Idoso , Animais , Anti-Inflamatórios/farmacologia , Cabergolina/uso terapêutico , Linhagem Celular Tumoral , Dexametasona/farmacologia , Quimioterapia Combinada , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Cetoconazol/uso terapêutico , Masculino , Camundongos , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/genética , Hipersecreção Hipofisária de ACTH/metabolismo , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/patologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , beta-Arrestina 1/metabolismo , beta-Arrestina 2/metabolismo
7.
Ann Endocrinol (Paris) ; 81(1): 11-17, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31982107

RESUMO

OBJECTIVE: The aim of this study was to describe endocrinological outcome in patients operated on for acromegaly. METHODS: A retrospective study included 167 patients. Patients were assessed in the early postoperative period (EPP), at 3 months (M3), at 1 year (Y1), and then annually. They were classified as grade I (IGF-1 level normal-for-age and positive GH response on oral glucose tolerance test [nadir <0.4ng/L]); grade II (discordant); or grade III or IV (acromegaly, controlled or uncontrolled under medical therapy, respectively). RESULTS: Taking all patients with all grades, 35% changed grades between EPP and M3, 26% between M3 and Y1 and 9% after Y1. In grade I, respectively 22%, 15% and 2% of patients changed grades between EPP and M3, between M3 and Y1, and after Y1, compared to 31%, 6% and 6% in grade IV. Respectively 57%, 67%, and 47% of grade II patients changed grades between EPP and M3, between M3 and Y1, and after Y1; between EPP or M3 and last follow-up (>1 year), respectively 74% and 75% of grade II patients changed grades. Knosp category, resection quality and abnormal GH response (vs. abnormal IGF-1) significantly impacted grade II patients' outcome. CONCLUSIONS: Whereas outcome in grades I and III-IV seems to be determined by 1 year, grade II discordant patients' outcome remains uncertain even after 1 year.


Assuntos
Acromegalia/metabolismo , Acromegalia/cirurgia , Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/diagnóstico , Acromegalia/patologia , Adenoma/diagnóstico , Adenoma/metabolismo , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Teste de Tolerância a Glucose , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hormônio do Crescimento Humano/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Recidiva , Estudos Retrospectivos , Via Secretória/fisiologia , Resultado do Tratamento
8.
Clin Transl Gastroenterol ; 11(1): e00089, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31922993

RESUMO

OBJECTIVES: Conventional colonoscopy with white light illumination detects colonic adenomas based on structural changes alone and is limited by a high miss rate. We aim to demonstrate an integrated imaging strategy that combines wide-field endoscopy and confocal endomicroscopy in real time to visualize molecular expression patterns in vivo to detect premalignant colonic mucosa. METHODS: A peptide specific for claudin-1 is labeled with Cy5.5 and administrated intravenously in genetically engineered mice that develop adenomas spontaneously in the distal colon. Wide-field endoscopy is used to identify the presence of nonpolypoid and polypoid adenomas. Anatomic landmarks are used to guide placement of a confocal endomicroscope with side-view optics to visualize claudin-1 expression patterns with subcellular resolution. RESULTS: Wide-field fluorescence images show peak uptake in colon adenoma at ∼1 hour after systemic peptide administration, and lesion margins are clearly defined. Further examination of the lesion using a confocal endomicroscope shows dysplastic crypts with large size, elongated shape, distorted architecture, and variable dimension compared with normal. The mean fluorescence intensity is significantly higher for dysplasia than normal. Increased claudin-1 expression in dysplasia vs normal is confirmed ex vivo, and the binding pattern is consistent with the in vivo imaging results. DISCUSSION: Wide-field endoscopy can visualize molecular expression of claudin-1 in vivo to localize premalignant colonic mucosa, and confocal endomicroscopy can identify subcellular feature to distinguish dysplasia from normal.


Assuntos
Adenoma/metabolismo , Claudina-1/metabolismo , Pólipos do Colo/metabolismo , Neoplasias Colorretais/metabolismo , Adenoma/diagnóstico , Adenoma/genética , Adenoma/patologia , Pólipos Adenomatosos/diagnóstico , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/metabolismo , Pólipos Adenomatosos/patologia , Animais , Animais Geneticamente Modificados , Carbocianinas , Claudina-1/genética , Pólipos do Colo/diagnóstico , Pólipos do Colo/genética , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Imunofluorescência , Corantes Fluorescentes , Genes APC , Imuno-Histoquímica , Camundongos , Microscopia Confocal , Peptídeos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
9.
Int J Cancer ; 146(7): 1979-1992, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411736

RESUMO

Removal of colorectal adenomas is an effective strategy to reduce colorectal cancer (CRC) mortality rates. However, as only a minority of adenomas progress to cancer, such strategies may lead to overtreatment. The present study aimed to characterize adenomas by in-depth molecular profiling, to obtain insights into altered biology associated with the colorectal adenoma-to-carcinoma progression. We obtained low-coverage whole genome sequencing, RNA sequencing and tandem mass spectrometry data for 30 CRCs, 30 adenomas and 18 normal adjacent colon samples. These data were used for DNA copy number aberrations profiling, differential expression, gene set enrichment and gene-dosage effect analysis. Protein expression was independently validated by immunohistochemistry on tissue microarrays and in patient-derived colorectal adenoma organoids. Stroma percentage was determined by digital image analysis of tissue sections. Twenty-four out of 30 adenomas could be unambiguously classified as high risk (n = 9) or low risk (n = 15) of progressing to cancer, based on DNA copy number profiles. Biological processes more prevalent in high-risk than low-risk adenomas were related to proliferation, tumor microenvironment and Notch, Wnt, PI3K/AKT/mTOR and Hedgehog signaling, while metabolic processes and protein secretion were enriched in low-risk adenomas. DNA copy number driven gene-dosage effect in high-risk adenomas and cancers was observed for POFUT1, RPRD1B and EIF6. Increased POFUT1 expression in high-risk adenomas was validated in tissue samples and organoids. High POFUT1 expression was also associated with Notch signaling enrichment and with decreased goblet cells differentiation. In-depth molecular characterization of colorectal adenomas revealed POFUT1 and Notch signaling as potential drivers of tumor progression.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fucosiltransferases/genética , Proteínas Oncogênicas/genética , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Biomarcadores Tumorais , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patologia , Neoplasias Colorretais/metabolismo , Progressão da Doença , Fucosiltransferases/metabolismo , Humanos , Proteínas Oncogênicas/metabolismo , Reprodutibilidade dos Testes , Microambiente Tumoral
10.
Aliment Pharmacol Ther ; 51(3): 334-346, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31858615

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer diagnosis in the Western world. AIM: To evaluate exhaled volatile organic compounds (VOCs) as a non-invasive biomarker for the detection of CRC and precursor lesions using an electronic nose. METHODS: In this multicentre study adult colonoscopy patients, without inflammatory bowel disease or (previous) malignancy, were invited for breath analysis. Two-thirds of the breath tests were randomly assigned to develop training models which were used to predict the diagnosis of the remaining patients (external validation). In the end, all data were used to develop final-disease models to further improve the discriminatory power of the algorithms. RESULTS: Five hundred and eleven breath samples were collected. Sixty-four patients were excluded due to an inadequate breath test (n = 51), incomplete colonoscopy (n = 8) or colitis (n = 5). Classification was based on the most advanced lesion found; CRC (n = 70), advanced adenomas (AAs) (n = 117), non-advanced adenoma (n = 117), hyperplastic polyp (n = 15), normal colonoscopy (n = 125). Training models for CRC and AAs had an area under the curve (AUC) of 0.76 and 0.71 and blind validation resulted in an AUC of 0.74 and 0.61 respectively. Final models for CRC and AAs yielded an AUC of 0.84 (sensitivity 95% and specificity 64%) and 0.73 (sensitivity and specificity 79% and 59%) respectively. CONCLUSIONS: This study suggests that exhaled VOCs could potentially serve as a non-invasive biomarker for the detection of CRC and AAs. Future studies including more patients could further improve the discriminatory potential of VOC analysis for the detection of (pre-)malignant colorectal lesions. (https://clinicaltrials.gov Identifier NCT03488537).


Assuntos
Adenoma/diagnóstico , Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Expiração , Compostos Orgânicos Voláteis/análise , Adenoma/metabolismo , Adenoma/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Testes Respiratórios/instrumentação , Testes Respiratórios/métodos , Estudos de Casos e Controles , Colonoscopia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Estudos Transversais , Progressão da Doença , Detecção Precoce de Câncer/instrumentação , Detecção Precoce de Câncer/métodos , Nariz Eletrônico/normas , Expiração/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estadiamento de Neoplasias , Países Baixos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Sensibilidade e Especificidade , Compostos Orgânicos Voláteis/metabolismo
12.
In Vivo ; 34(1): 213-223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882481

RESUMO

BACKGROUND/AIM: Mammary neoplasms are very common tumours in female dogs. Cancer-associated fibroblasts (CAFs) play an important role in the oncogenesis process. One of the useful proteins used in the diagnostics of CAFs cells is podoplanin (PDPN). The aim of our study was to assess the expression of PDPN in mammary cancer in female dogs. MATERIALS AND METHODS: Our study cohort included 61 cancers and 21 adenomas of the mammary tumour in bitches. Expression of podoplanin, Ki-67 and HER2 was determined using the Immunohistochemical (IHC) method. PDPN expression at the mRNA level was determined using real-time PCR. RESULTS: Expression of PDPN in CAFs was observed in 22.9% of cases of mammary cancers in bitches, with no PDPN expression in adenomas. A positive correlation was found between the expression of PDPN in CAFs and the grade of histological malignancy and expression of Ki-67. CONCLUSION: PDPN plays a significant role during the process of carcinogenesis of mammary tumours in female dogs.


Assuntos
Adenoma/metabolismo , Biomarcadores Tumorais/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Mamárias Animais/metabolismo , Glicoproteínas de Membrana/metabolismo , Adenoma/patologia , Animais , Biomarcadores Tumorais/genética , Fibroblastos Associados a Câncer/patologia , Cães , Feminino , Neoplasias Mamárias Animais/patologia , Glicoproteínas de Membrana/genética , Células Tumorais Cultivadas
13.
Anticancer Res ; 39(12): 6711-6722, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810936

RESUMO

BACKGROUND/AIM: Autophagy is a cellular mechanism that recycles cellular components to maintain homeostasis. To investigate the clinical implication of autophagy in gastric cancer, the autophagy markers with autophagosome formation, LC3B and selective autophagy substrate p62/SQSTM1 (P62) were validated. MATERIALS AND METHODS: LC3B and p62 expression was examined using immunohistochemistry, western blot assays, and reverse-transcription polymerase chain reaction (RT-PCR). The relationship of LC3B and p62 expression in gastric adenocarcinomas with clinicopathological parameters, including patient survival, were analyzed. RESULTS: Normal gastric mucosae exhibit no LC3B and p62 expression, while tubular adenoma and gastric adenocarcinomas exhibit variable nuclear or cytoplasmic p62 expression. High LC3B, high cytoplasmic p62, and low nuclear p62 protein expression in gastric adenocarcinomas is positively correlated with poor prognostic factors including survival. CONCLUSION: Dynamic LC3B and p62 changes are suggested to be involved in gastric tumorigenesis and cancer progression. LC3B and p62 could be used as prognostic biomarkers and potential therapeutic targets for gastric adenocarcinomas.


Assuntos
Adenocarcinoma/metabolismo , Adenoma/metabolismo , Morte Celular Autofágica/fisiologia , Biomarcadores Tumorais/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Sequestossoma-1/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adulto Jovem
14.
Int J Mol Sci ; 20(23)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795192

RESUMO

Colorectal cancer (CRC) is a kind of solid tumor and the third most common cancer type in the world. It is a heterogeneous disease characterized by genetic and epigenetic aberrations. The TP53 mutation is the key step driving the transition from adenoma to adenocarcinoma. The functional roles of TP53 mutation in tumor development have been comprehensively investigated. In CRC, TP53 mutation was associated with poor prognosis and chemoresistance. A gain of function (GOF) of p53 mutants promotes cell proliferation, migration and invasion through multiple mechanisms. Restoring wild type p53 function, depleting p53 mutants, or intervention by targeting the oncogenic downstreams provides potential therapeutic strategies. In this review, we comprehensively summarize the GOF of p53 mutants in CRC progression as well as in some other solid tumors, and discuss the current strategies targeting p53 mutants in malignancies.


Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , Mutação , Proteína Supressora de Tumor p53/genética , Adenoma/tratamento farmacológico , Adenoma/metabolismo , Animais , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Humanos , Proteína Supressora de Tumor p53/metabolismo
15.
Int J Mol Sci ; 20(23)2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31783512

RESUMO

The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient's cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen (T-Ag), Viral Protein 1 (Vp1), and miR-J1-5p in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region (NCCR) DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp NCCR DNA rearrangement was detected. T-Ag levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, miR-J1-5p expression decreased with CRC progression. Vp1 expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.


Assuntos
Neoplasias do Colo/virologia , Neoplasias Colorretais/virologia , Mucosa Intestinal/virologia , Vírus JC/patogenicidade , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/virologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Adenoma/metabolismo , Adenoma/patologia , Adenoma/virologia , Idoso , Antígenos Virais de Tumores/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , DNA Viral/genética , Progressão da Doença , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/metabolismo , Infecções por Polyomavirus/patologia , Infecções Tumorais por Vírus/metabolismo , Infecções Tumorais por Vírus/patologia
16.
PLoS One ; 14(12): e0226033, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830115

RESUMO

INTRODUCTION: Cushing's disease (CD) is a rare cause of hypercortisolemia presenting a major diagnostic and therapeutic challenge. Data on pituitary function in long-term follow-up after CD treatment in childhood is limited. AIM: Long-term assessment of patients of the Children's Memorial Health Institute (CMHI) after CD treatment in childhood. MATERIALS AND METHODS: Retrospective analysis of 29 CD patients, mean age at the time of diagnosis 13.46 yrs. The long-term follow-up (FU) was done by: 1) obtaining the data from a patient's questionnaire (75% of adult patients); 2) using the data from the last clinic visit for patients who did not respond to the questionnaire and for current CMHI patients. The average long-term FU from transsphenoidal pituitary surgery (TSS) was 10.23 yrs. RESULTS: At the latest FU: 18 patients (62%) had long-term disease remission after TSS1, 2 patients (6.9%) after TSS2, 1 patient (3.4%) after the post-TSS radiotherapy (XRT) cycle and 3 patients (10.3%) after bilateral adrenalectomy (BA). One patient (3.4%) died after TSS2 due to postoperative complications, 1 patient (3.4%) had persistent disease at latest FU, in 1 patient (3.4%) the long-term FU was not possible to perform. CD recurrence occurred in 4 out of 28 patients (14%) at an average time 3.6 yrs. from definitive treatment. One patient (3.4%) after BA was operated because of Nelson's syndrome. Two patients (6.9%) were suspected of relapse at latest assessment. At the time of the last evaluation, 17 patients (63%) were on levothyroxine therapy since definitive treatment, 16 patients (59%) were on hydrocortisone treatment, 10 patients (37%) were taking sex hormones replacement, 4 patients (15%)-antidiuretic hormone. CONCLUSIONS: Relatively large number of patients after CD treatment in childhood have hormonal pituitary deficits as well as mood and cognitive disorders. CD recurrence can occur even after a long time post effective treatment.


Assuntos
Hipersecreção Hipofisária de ACTH/epidemiologia , Hipersecreção Hipofisária de ACTH/terapia , Adenoma/complicações , Adenoma/epidemiologia , Adenoma/metabolismo , Adenoma/terapia , Adolescente , Adulto , Idade de Início , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Testes de Função Hipofisária , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/terapia , Polônia/epidemiologia , Puberdade/fisiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Ann Clin Lab Sci ; 49(6): 699-702, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31882419

RESUMO

OBJECTIVE: CpG island methylator phenotype (CIMP)-positive colorectal cancers (CRC) and CRC with microsatellite instability (MSI) were reported to have a decreased expression of estrogen receptor, beta1 (ER-ß1), and methylation accompanied by decreased expression for the caudal-related homeobox, transcription factor 2 (CDX2). While precursor lesions of these cancers, known as sessile serrated adenomas (SSA), were found to have decreased CDX2 expression, the status of ER-ß1 expression in SSA is unknown. The aim of this study is to determine ER-ß1 expression in SSA and its relation to CDX2 expression. METHODS: Sections of formalin fixed and paraffin embedded tissue from 62 consecutive cases of SSA were stained by immunohistochemistry for ER-ß1 and CDX2. SSA with ER-ß1 or CDX2 expression similar to that of a normal colon were scored as 0, while those with a loss of expression in <10% of SSA crypts as 1, 11-25% as 2, 26-50% as 3, 51-75% as 4, and CDX2 loss in >75% of the SSA crypts scored as 5. RESULTS: There is a significant correlation between a loss of CDX2 and the loss of ER-ß1 scores in SSA (p<0.001). The downregulation of CDX2 was greater in SSA arising from the right colon compared to the left colon and rectum (p=0.012). Similarly, downregulation of ER-ß1 was greater in SSA arising in the right colon compared to the left colon and rectum (p=0.014). CONCLUSIONS: Our findings show significant downregulation of both ER-ß1 and CDX2 expression in SSA, especially in the right colon. These findings suggest that ER-ß1 downregulation plays a significant role in the malignant progression of SSA.


Assuntos
Adenoma/metabolismo , Fator de Transcrição CDX2/metabolismo , Neoplasias Colorretais/patologia , Receptor beta de Estrogênio/metabolismo , Adenoma/patologia , Adulto , Idoso , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Clin Lab ; 65(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31721543

RESUMO

BACKGROUND: The expression and significance of small nucleolar RNA host gene 7 (SNHG7) in early-stage colon carcinogenesis remains unclear. METHODS: The level of SNHG7 and microRNA-193b (miR-193b) was detected by qRT-PCR in colon tumor tissues and cells. The interaction of SNHG7 and miR-193b and the influence of SNHG7 silencing on colon tumor cells was evaluated. RESULTS: Stepwise upregulated SNHG7 in colon advanced adenomas and early-stage cancer negatively correlates with miR-193b level, the direct interaction was confirmed in vitro. SNHG7 silencing in HT29 cells decreased proliferation and promoted apoptosis by inhibiting K-ras/ERK/cyclinD1. CONCLUSIONS: SNHG7 is an oncogenic biomarker in colon carcinogenesis. The effect may be mediated by interaction with miR-193b.


Assuntos
Adenoma/genética , Biomarcadores Tumorais/genética , Carcinogênese/genética , Colo/metabolismo , Neoplasias do Colo/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Regiões 3' não Traduzidas/genética , Adenoma/metabolismo , Adenoma/patologia , Apoptose/genética , Sequência de Bases , Carcinogênese/metabolismo , Proliferação de Células/genética , Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Células HT29 , Humanos , Interferência de RNA , RNA Longo não Codificante/metabolismo , Homologia de Sequência do Ácido Nucleico
19.
BMC Med Genet ; 20(1): 185, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747893

RESUMO

BACKGROUND: Our purpose was to determine if SIRT1 (rs4746720, rs3740051) genotypes have an influence on the development of pituitary adenoma (PA). METHODS: The study group included 142 patients with pituitary adenoma (PA) and the control group consisted of 826 healthy people. The genotyping of SIRT1 (rs4746720, rs3740051) was carried out using the real-time polymerase chain reaction method. RESULTS: Statistically significant results were obtained in the analysis of SIRT1 rs3740051. Significant differences in genotype (G/G, G/A, A/A) distribution were obtained comparing patients with PA without recurrence and PA with recurrence (0, 17.9, 82.1% vs. 6.7, 6.7, 86.7%, respectively, p = 0.022). Also, statistically significant differences were observed when comparing the genotype (G/G, G/A, A/A) distribution in the non-invasive PA group and the invasive PA group (3.4, 25.9, 70.7% vs. 0, 8.3, 91.7%, respectively, p = 0.003), and allele G was less frequently observed in invasive PA, than in non-invasive PA (4.2% vs. 16.4%, p < 0,001). Further analysis revealed that G/A (OR = 0.261; 95% CI:0.099-0.689; p = 0.007) and each allele A (OR = 0.229; 95% CI:0.091-0.575; p = 0.002) were associated with lower odds of occurring an invasive PA. CONCLUSIONS: Our study revealed that SIRT1 rs3740051 is associated with PA recurrence and invasiveness. The haplotype containing alleles C-A in rs12778366-rs3740051 was found to be associated with increased odds of PA development as well.


Assuntos
Adenoma/genética , Neoplasias Hipofisárias/genética , Sirtuína 1/genética , Adenoma/metabolismo , Adenoma/patologia , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Hormônios Hipofisários/metabolismo , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Recidiva
20.
Endocr Regul ; 53(4): 263-267, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31734654

RESUMO

OBJECTIVES: Pituicytomas are rare, solid, well-circumscribed, low grade (grade I), non-neuroendocrine, and noninfiltrative tumors of the neurohypophysis or infundibulum, which appear in the sellar/suprasellar regions. Herein, we present a case with Cushing's disease (CD) caused by an ACTH-secreting pituitary adenoma in association with an infundibular pituicytoma. Subject and Results. A 37-year-old male patient presented to the hospital with a six-month history of blurry vision. Physical examination demonstrated plethora, excessive sweating, weight gain, moon facies, and acne. Basal serum cortisol and ACTH levels were 16 µg/dl and 32 pg/ml, respectively. The results of screening tests were suggestive of Cushing syndrome. It was also 1.97 µg/dl following 8 mg dexamethasone suppression test which was consistent with CD. Pituitary MR imaging revealed a single lesion measuring 6x6.5 mm on the pituitary stalk. Infundibular mass excision and pituitary exploration by extended endoscopic endonasal approach were applied. On immunohistochemistry, strong diffuse immunolabeling for both S100 and TTF-1 was noted for the cells of infundibular mass, diagnosed as pituicytoma. Because the developed panhypopituitarism postoperatively, patient was discharged with daily desmopressin, levothyroxine, hydrocortisone, and intramuscular testosterone, once a month. CONCLUSIONS: Pituicytoma is an uncommon noninvasive tumor of the sellar and suprasellar regions. In this case report, we described a patient with Cushing's disease to whom MRI displayed only an infundibular well-circumscribed lesion, but not any pituitary adenoma. Despite the absence of any sellar lesion, awareness of other undetected possible lesion and exploring hypophysis during the transsphenoidal surgery is mandatory for the correct diagnosis.


Assuntos
Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipófise/patologia , Neoplasias Hipofisárias/diagnóstico , Adenoma Hipofisário Secretor de ACT/metabolismo , Adenoma Hipofisário Secretor de ACT/patologia , Adenoma/metabolismo , Adenoma/patologia , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Humanos , Masculino , Neoplasias Primárias Múltiplas/complicações , Neoplasias Primárias Múltiplas/metabolismo , Hipersecreção Hipofisária de ACTH/metabolismo , Hipersecreção Hipofisária de ACTH/patologia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia
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