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1.
Medicine (Baltimore) ; 99(14): e19652, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243397

RESUMO

Although serum thyroglobulin (Tg) is a reliable differentiated thyroid carcinoma (DTC) prognostic marker, its cutoff values can be affected by TSH stimulation status. Serum Tg prognostic values measured at different time points before and after radioactive iodine (RAI) therapy prepared with recombinant human TSH (rhTSH) in DTC patients, were investigated.This study included 160 DTC patients who underwent surgery followed by rhTSH-aided RAI therapy. Their serum Tg levels were measured 7 days before (D-7Tg), on the day of (D0Tg), and 2 days after (D2Tg) the RAI therapy. For response evaluation, the patients were classified into 2 groups: acceptable response and non-acceptable response (non-AR). Optimal Tg level cutoff values measured at different time points were evaluated for persistent or recurrent disease (PRD) prediction, as well as therapeutic response.Multivariate analysis showed that D-7Tg, D0Tg, and D2Tg significantly predicted non-AR (P < .05, for all). Optimal Tg level cutoff values for non-AR prediction were 0.6, 2.6, and 3.7 ng/mL for D-7Tg, D0Tg, and D2Tg, respectively. Cox regression analysis showed that Tg levels were significantly associated with PRD free survival with D-7Tg, D0Tg, and D2Tg cutoff values of 0.8, 4.0, and 6.0 ng/mL, respectively (D-7Tg, P = .010; D0Tg, P = .005; D2Tg, P = .011).Serum Tg levels measured at the different time points could predict PRD free survival as well as therapeutic response with different cutoff values in DTC patients who underwent rhTSH-aided RAI therapy.


Assuntos
Carcinoma/sangue , Radioisótopos do Iodo/uso terapêutico , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue , Fatores de Tempo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma/patologia , Carcinoma/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Valores de Referência , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Tireotropina/sangue , Tireotropina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
2.
Ann R Coll Surg Engl ; 102(5): 363-368, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32233846

RESUMO

INTRODUCTION: Hypercalcaemic crisis is a rare manifestation of hyperparathyroidism and occurs in 1.6-6% of patients with primary hyperparathyroidism (pHPT). Although such high serum calcium levels (>14mg/dl) are attributed to malignancy, it is also associated with benign disease of the parathyroid glands. The aim of this study was to evaluate the clinical features and treatment modalities of patients with severe hypercalcaemia who underwent surgery for pHPT. METHODS: The medical records of 537 patients who underwent parathyroidectomy in our department for pHPT between 2005 and 2019 were reviewed retrospectively. Twenty-four (4.4%) of the patients were described as having severe hypercalcaemia. RESULTS: Among 24 patients, 71% were female and the mean age was 55.7 years (range: 40-71 years). The mean serum calcium level at time of diagnosis was 15.9mg/dl (range: 14-22.7mg/dl). According to postoperative pathology reports, solitary adenoma, parathyroid cancer and parathyromatosis were diagnosed with the rates of 87.5%, 8.3% and 4.1% respectively. The mean weight of the solitary parathyroid lesions was 14.9g (standard deviation: 8.9g, range: 4-38g). The mean longest diameter was 2.87cm (standard deviation: 1.4cm, range: 1-5.5cm). Serum calcium levels were within the normal range on the first postoperative day in 75% of the cases. CONCLUSIONS: Severe hypercalcaemia is a rare but urgent condition of pHPT and requires prompt management. Accelerated surgery after adequate medical treatment should be performed. It is important to emphasise that giant adenoma, which is a benign disease, may be a more common cause of severe hypercalcaemia than carcinoma, unlike previously thought.


Assuntos
Adenoma/complicações , Carcinoma/complicações , Hipercalcemia/etiologia , Hiperparatireoidismo Primário/etiologia , Neoplasias das Paratireoides/complicações , Adenoma/sangue , Adenoma/cirurgia , Adulto , Idoso , Cálcio/sangue , Carcinoma/sangue , Carcinoma/cirurgia , Difosfonatos/administração & dosagem , Feminino , Furosemida/administração & dosagem , Humanos , Hipercalcemia/sangue , Hipercalcemia/diagnóstico , Hipercalcemia/terapia , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Neoplasias das Paratireoides/sangue , Paratireoidectomia , Período Pós-Operatório , Diálise Renal , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
3.
J Pak Med Assoc ; 69(9): 1360-1364, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31511725

RESUMO

We report the presentation, management and outcomes of patients operated for hyperparathyroidism at our hospital. Patient sunder going surgery for hyper parathyroidism from 20 05 to 2 015 were retrospectively reviewed. Preoperative biochemistry, diagnostic scans and surgical procedures were studied. Follow up for cure rates, complications and histology were recorded. Out of 72 patients reviewed 54 (75%) were females and the rest males. The mean age was 48.04±15.5 years. Musculoskeletal complains were the most common (76.4%) among the cases reviewed. Asymptomatic hypercalcemia was seen in 13 (18.1%). The mean preoperative PTH level was 658.95 pg/ml and the mean preoperative calcium was 11.9 mg/dl. Bilateral neck exploration was done in 42 (58.3%) while focused unilateral approach was done in 27 (37.5%) cases. Solitary adenoma was the most frequent pathology in 58 (80.5%) patients. Asymptomatic hyperparathyroidism was less frequently detected in our population owing to lack of screening programme. Our patients are younger with a greater severity of the disease both symptomatically and biochemically compared to the West. In almost two decades, preoperative symptoms, calcium and PTH levels have changed marginally. Bilateral explorations are now giving way to focused less invasive procedures.


Assuntos
Adenoma/cirurgia , Carcinoma/cirurgia , Hiperparatireoidismo Primário/cirurgia , Esvaziamento Cervical/métodos , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/métodos , Adenoma/sangue , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adulto , Doenças Assintomáticas , Cálcio/sangue , Carcinoma/sangue , Carcinoma/diagnóstico por imagem , Carcinoma/patologia , Países em Desenvolvimento , Feminino , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/patologia , Hiperplasia , Hipocalcemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/tendências , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/sangue , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/patologia , Paratireoidectomia/tendências , Complicações Pós-Operatórias/epidemiologia , Centros de Atenção Terciária
4.
Dis Markers ; 2019: 6702964, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534562

RESUMO

Introduction: To investigate the correlation between preoperative De Ritis ratio (aspartate transaminase (AST)/alanine transaminase (ALT)) and postoperative outcome in patients with urothelial cell carcinoma (UC) treated with radical cystectomy. Materials and Methods: We analyzed the clinical and pathological data of 771 patients who underwent radical cystectomy for bladder UC. Patients were divided into two groups according to the optimal value of AST/ALT ratio. The effect of the AST/ALT ratio was analyzed using the Kaplan-Meier method and Cox regression hazard models for patients' cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). In addition, propensity score matching of 1 : 1 was performed between the two groups. Results: Median follow-up was 84.0 (36-275) months. Mean age was 64.8 ± 10.0 years. According to the receiver operating characteristic (ROC) analysis, the optimal threshold of the AST/ALT ratio was 1.1. In Kaplan-Meier analyses, the high AST/ALT group showed worse outcomes in CSS and OS (all P < 0.001). Also, RFS (P = 0.001) in the Cox regression models of clinical and pathological parameters was used to predict CSS, OS, and AST/ALT ratio (HR 2.15, 95% CI 1.23-3.73, P = 0.007) and pathological T stage (HR 4.80, 95% CI 1.19-19.28, P = 0.003). To predict OS and AST/ALT ratio (HR 2.05, 95% CI 1.65-2.56, P < 0.001), pathological T stage (HR 2.96, 95% CI 0.57-17.09, P = 0.037) and positive lymph node (HR 1.71, 95% CI 1.50-1.91, P = 0.021) were determined as independent prognostic factors. Conclusion: Preoperative AST/ALT ratio could be an independent prognostic factor in patients with UC treated with radical cystectomy.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores Tumorais/sangue , Carcinoma/sangue , Neoplasias da Bexiga Urinária/sangue , Idoso , Carcinoma/patologia , Carcinoma/cirurgia , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
5.
Acta Biochim Biophys Sin (Shanghai) ; 51(9): 953-959, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31435668

RESUMO

LncRNA MIR4435-2HG is characterized as an oncogene in lung cancer. However, its role in ovarian carcinoma (OC) is unclear. In this study, we aimed to investigate the role of MIR4435-2HG in OC. We found that both MIR4435-2HG and transforming growth factor beta 1 (TGF-ß1) were upregulated in OC. MIR4435-2HG is associated with tumor metastasis but not with tumor size. Upregulation of MIR4435-2HG distinguished early stage (Stage I and II) OC patients from healthy controls. Correlation analysis showed that plasma levels of MIR4435-2HG and TGF-ß1 were positively correlated only in OC patients. qPCR and western blot analysis results showed that MIR4435-2HG overexpression led to upregulation of TGF-ß1 in OC cells, while TGF-ß1 treatment did not significantly affect MIR4435-2HG expression. Transwell invasion and migration assays showed that MIR4435-2HG and TGF-ß1 promoted the invasion and migration of OC cells while TGF-ß inhibitor suppressed the invasion and migration of these cells. Further analysis of the Transwell invasion and migration assay results showed that TGF-ß inhibitor reduced the effects of MIR4435-2HG overexpression. Therefore, our results suggested that lncRNA MIR4435-2HG may promote OC by upregulating TGF-ß1. Further characterization of the functions of MIR4435-2HG in OC may provide novel targets for cancer therapies.


Assuntos
Biomarcadores Tumorais/fisiologia , Carcinoma/diagnóstico , MicroRNAs/fisiologia , Neoplasias Ovarianas/diagnóstico , RNA Longo não Codificante/fisiologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma/sangue , Linhagem Celular Tumoral , Feminino , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , RNA Longo não Codificante/sangue , Fator de Crescimento Transformador beta1/sangue
6.
Cells ; 8(7)2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31319587

RESUMO

: Background: Current diagnosis and staging of advanced epithelial ovarian cancer (aEOC) has important limitations and better biomarkers are needed. We investigate the performance of non-haematopoietic circulating cells (CCs) at the time of disease presentation and relapse. Methods: Venous blood was collected prospectively from 37 aEOC patients and 39 volunteers. CCs were evaluated using ImageStream TechnologyTM and specific antibodies to differentiate epithelial cells from haematopoetic cells. qRT-PCR from whole blood of relapsed aEOC patients was carried out for biomarker discovery. Results: Significant numbers of CCs (CK+/WT1+/CD45-) were identified, quantified and characterised from aEOC patients compared to volunteers. CCs are abundant in women with newly diagnosed aEOC, prior to any treatment. Evaluation of RNA from the CCs in relapsed aEOC patients (n = 5) against a 79-gene panel revealed several differentially expressed genes compared to volunteers (n = 14). Size differentiation of CCs versus CD45+ haematopoietic cells was not reliable. Conclusion: CCs of non-haematopoetic origin are prevalent, particularly in patients with newly diagnosed aEOC. Exploiting a CC-rich population in aEOC patients offers insights into a part of the circulating microenvironment.


Assuntos
Carcinoma/sangue , Células Neoplásicas Circulantes/metabolismo , Neoplasias Ovarianas/sangue , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Antígenos Comuns de Leucócito/metabolismo , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/patologia , Proteínas WT1/metabolismo
7.
Dis Markers ; 2019: 8945974, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354892

RESUMO

Integrated device with high purity for circulating tumor cell (CTC) identification has been regarded as a key goal to make CTC analysis a "bench-to-bedside" technology. Here, we have developed a novel integrated microfluidic device that can enrich and identify the CTCs from the blood of patients with colorectal cancer. To enrich CTCs from whole blood, microfabricated trapping chambers were included in the miniaturized device, allowing for the isolation of tumor cells based on differences in size and deformability between tumor and normal blood cells. Microvalves were also introduced sequentially in the device, enabling automatic CTC enrichment as well as immunostaining reagent delivery. Under optimized conditions, the whole blood spiked with caco-2 cells passing through the microfluidic device after leukocyte depletion and approximately 73% of caco-2 cells were identified by epithelial cell adhesion molecule (EpCAM) staining. In clinical samples, CTCs were detectable from all patients with advanced colorectal cancer within 3 h. In contrast, the number of CTCs captured on the device from the blood of healthy donors was significantly lower than that from the patients, suggesting the utilization of the integrated device for further molecular analyses of CTCs.


Assuntos
Carcinoma/sangue , Neoplasias Colorretais/sangue , Microfluídica/métodos , Células Neoplásicas Circulantes/patologia , Células CACO-2 , Carcinoma/patologia , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Humanos , Biópsia Líquida/instrumentação , Biópsia Líquida/métodos , Microfluídica/instrumentação
8.
PLoS One ; 14(6): e0218621, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220149

RESUMO

Clinical utility of new biomarkers often requires the identification of their optimal threshold. This external validation study was conducted to assess the performance of the preoperative plasma tumor markers HE4 and CA125 optimal cut-offs to predict cancer mortality in women with epithelial ovarian cancer (EOC). Participating women had upfront debulking surgery in the University Hospital of Quebec City (Canada) between 1998 and 2013. A total of 136 women participated in the training cohort (cohort 1) and 177 in the validation cohort (cohort 2). Preoperative plasma HE4 and CA125 levels were measured by Elecsys. Optimal thresholds were identified in the cohort 1 using time-dependent receiver operating characteristic (ROC) curves. Multivariate Cox models were used to validate the biomarkers using their optimal cut-offs in the cohort 2. The likelihood ratio (LR) test was done to test whether the biomarkers added prognostic information beyond that provided by standard prognostic factors. The Areas Under the Curves (AUC) for HE4 and CA125 were respectively 64.2 (95% CI: 54.7-73.6) and 63.1 (95%CI: 53.6-72.6). The optimal thresholds were 277 pmol/L for HE4 and 282 U/ml for CA125. Preoperative plasma HE4 (≥277 pmol/L) was significantly associated with EOC mortality (adjusted hazard ratio (aHR): 1.90; 95% CI:1.09-3.29). The prognostic effect of HE4 was strongest in the subgroup of women with serous ovarian cancer (aHR: 2.42; 95% CI: 1.25-4.68). Using a multivariate model including all standard prognostic factors, this association was maintained (aHR: 2.21; 95% CI: 1.15-4.23). In addition, preoperative plasma HE4 added prediction for death over the standard prognostic markers in women with serous tumors (p-value for LR-test: 0.01). Preoperative CA125 was not associated with cancer mortality, both in women with EOC and in those with serous tumors. Preoperative HE4 is a promising prognostic biomarker in EOC, especially in serous tumor.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma/diagnóstico , Proteínas de Membrana/sangue , Neoplasias Ovarianas/diagnóstico , /análise , Idoso , Biomarcadores Tumorais/normas , Carcinoma/sangue , Carcinoma/epidemiologia , Feminino , Humanos , Proteínas de Membrana/normas , Pessoa de Meia-Idade , Mortalidade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/epidemiologia , Valor Preditivo dos Testes , Prognóstico , /normas
9.
J Surg Oncol ; 120(2): 241-248, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31041808

RESUMO

BACKGROUND: Systemic inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be prognostic for many types of pancreatic malignancy. The aim of this study was to evaluate the prognostic role of these markers in patients with solid pseudopapillary tumor of the pancreas (SPTP). METHODS: Patients who underwent surgical resection for histologically confirmed SPTP were retrospectively reviewed in our institution. Preoperative NLR and PLR were calculated. Clinicopathologic data were correlated with the presence of malignant potential and recurrence-free survival (RFS). RESULTS: A total of 113 patients with SPTP were included in this study. Of them, 23 were men and 90 were women, with a median age of 35 years (interquartile range, 25-44). The optimal cut-off values for malignant SPTP were 3.22 for NLR, and 75.5 for PLR, respectively. Univariate analysis showed that high NLR (>3.22) and white blood cell count more than 9.96 × 109 /L were predictive of a malignant SPTP. Meanwhile, high NLR (P = 0.001) and age more than 35 years (P = 0.026) were associated with worse RFS. On multivariable analyses, high NLR was the only independent predictor of malignant SPTP (odd ratio 6.871; 95% confidence interval [CI], 1.482-31.864; P = 0.014) and RFS (hazard ratio 12.633; 95% CI, 1.758-90.790; P = 0.012). CONCLUSIONS: This study highlights the supportive role of preoperative NLR in predicting malignancy and RFS of SPTP patients. Further studies including a larger cohort of patients are needed to corroborate our findings.


Assuntos
Carcinoma/sangue , Carcinoma/cirurgia , Contagem de Linfócitos , Neutrófilos , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/cirurgia , Adulto , Biomarcadores Tumorais/sangue , Carcinoma/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Pancreaticoduodenectomia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
10.
APMIS ; 127(8): 561-569, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132191

RESUMO

Toll-like receptors (TLRs) are involved in colorectal cancer (CRC) pathogenesis. However, the significance of serum TLR concentrations in CRC is unknown. We analyzed serum TLR2 and TLR4 concentrations with ELISA in preoperative samples from 118 patients with CRC and 88 matched controls. We also assessed tissue TLR expression with immunohistochemistry and by detecting serum determinants of systemic inflammation. Most participants (>70%) had undetectable serum TLR2. The mean serum TLR4 levels were lower in patients than in controls (1.1 vs 1.8 ng/mL; p = 0.015). Undetectable TLR4 was more common in stage I (39%) than in stages II-IV (11%, p < 0.001). TLR2 or TLR4 expression in tumor cells did not correlate with serum levels, but abundant TLR2 expression in normal colon epithelium was associated with detectable serum TLR2 (p = 0.034). Undetectable serum TLR2 was linked to high modified Glasgow prognostic scores (p = 0.010), high CRP levels (p = 0.013), blood vessel invasion (p = 0.013), and tended to be associated with worse 5-year survival (p = 0.052). In conclusion, serum TLR2 levels were inversely associated with systemic inflammation in patients with CRC. Moreover, serum TLR2 levels might depend more on normal colorectal mucosa contributions than on tumor tissue contributions. Further studies are required to assess the prognostic value of serum TLR2.


Assuntos
Carcinoma/sangue , Neoplasias Colorretais/sangue , Mucosa Intestinal/patologia , Receptor 2 Toll-Like/sangue , Receptor 4 Toll-Like/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma/patologia , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Escala de Resultado de Glasgow , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Análise de Sobrevida
11.
Int Braz J Urol ; 45(3): 541-548, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038863

RESUMO

OBJECTIVES: To investigate whether Glasgow Prognostic Score has prognostic significance in patients with upper urinary urothelial carcinoma. PATIENTS AND METHODS: We retrospectively reviewed the clinical records of 74 patients with upper urinary urothelial carcinoma. We set the cut-off value for C-reactive protein as 1.0mg/dL, and 3.5mg/dL for albumin as Glasgow Prognostic Score. Their blood data including albumin and C-reactive protein for Glasgow Prognostic Score and cytokeratin 19 fragment 21-1 as a tumor marker were measured before starting treatment. The patients were stratified into three groups with Glasgow Prognostic Score: The Group-1, albumin ≥3.5g/dL and C-reactive protein < 1.0mg/dL; Group-2, albumin < 3.5g/dL or C-reactive protein ≥1.0mg/dL; Group-3, albumin < 3.5g/dL and C-reactive protein ≥1.0mg/dL. RESULTS: The median follow-up for all patients was 26.9 months (range: 10.9-91.1 months), during which 37 (50%) patients died. There was a signifi cant difference in the estimated survival rate among the 3 groups stratified by Glasgow Prognostic Score. The estimated survival rate in the Group-1 was significantly higher than those in Groups 2 and 3. In the univariate analysis C-reactive protein, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were significant predictors of overall survival. On the multivariate analysis, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were independently associated with shorter overall survival. CONCLUSION: Our review suggests Glasgow Prognostic Score may play as a prognostic predictor for upper urinary urothelial carcinoma.


Assuntos
Carcinoma/sangue , Neoplasias Urológicas/sangue , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Proteína C-Reativa/análise , Carcinoma/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Queratina-19/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Albumina Sérica/análise , Estatísticas não Paramétricas , Neoplasias Urológicas/patologia , Urotélio/patologia
12.
Glycoconj J ; 36(3): 219-226, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31098851

RESUMO

Humanized monoclonal antibody HMMC-1 established by immunizing transchromosomal mice with a human uterine endometrial cancer cell line has been found to react with the H-antigen carried on core l O-glycans through cotransfection of glycosyltransferases for O-glycans and inhibition of antibody-binding with synthetic oligosaccharides. However, direct binding analysis of an antibody against glycosphingolipids from human erythrocytes with different ABO blood groups revealed that it was able to bind selectively with polar glycolipids in blood group O, but not blood group A, B and AB erythrocytes. Unexpectedly, typical monofucosylated H-glycolipids, IV2Fucα-nLc4Cer and VI2Fucα-nLc6Cer, which are the precursors for A and B-glycolipids, and were present not only in blood group O, but also A, B and AB-erythrocytes, were not the antigens for the HMMC-1 antibody. The antigen comprised less than 0.001% of the total glycolipids in blood group O-erythrocytes, and was purified by conventional silica gel column chromatography. Structural determination by permethylation, GC-MS, and ESI-TOFMS demonstrated that the structure was a novel glycolipid with a difucosylated H-antigen, Fucα1-2Galß1-4GlcNAcß1-3Gal(2-1αFuc)ß1-4GlcNAcß1-3Galß1-4GlcNAcß1-3Galß1-4Glcß1-1'Cer, VI2,VIII2(Fucα)2-nLc8Cer, whose terminal difucosylated structure was the epitope of the HMMC-1 antibody. The HMMC-1 glycolipid was detected in five out of 29 tissues from patients suffering from uterine cervical carcinomas, irrespective of their ABO-blood groups.


Assuntos
Sistema ABO de Grupos Sanguíneos/química , Carcinoma/sangue , Eritrócitos/imunologia , Neoplasias do Colo do Útero/sangue , Sistema ABO de Grupos Sanguíneos/imunologia , Anticorpos Monoclonais/imunologia , Carcinoma/imunologia , Colo do Útero/imunologia , Feminino , Fucose/análogos & derivados , Glicolipídeos/química , Glicolipídeos/imunologia , Humanos , Neoplasias do Colo do Útero/imunologia
13.
Biomed Res Int ; 2019: 9681863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984788

RESUMO

Abnormal expression of noncoding RNA molecules such as circRNA plays an important role in the development of malignant tumors. circRNAs are stable in structure and can be useful as ideal tumor markers. Advanced bladder cancer has poor treatment options and prognosis. Thus, we examined circRNAs to further understand the pathogenesis and development of bladder cancer and to identify molecular markers for the early diagnosis of bladder carcinoma. We found that hsa_circ_0018069 was differentially expressed in our RNA sequencing data. We used qRT-PCR to detect its expression in T24 and Biu-87 cell lines and in 41 paired samples of bladder cancer and adjacent normal tissue and analyzed the correlation between expression of hsa_circ_0018069 and the clinical characteristics of patients with bladder cancer. We then performed a bioinformatics analysis to reveal the mechanism of hsa_circ_0018069 in tumorigenesis of bladder cancer. The expression of hsa_circ_0018069 was significantly reduced in T24 and Biu-87 cells and was also significantly downregulated in bladder cancer tissues. Decreased expression of hsa_circ_0018069 was related to the grade stage (P=0.024), T stage (P=0.027), and muscular invasion depth (P=0.022) of bladder cancer. Bioinformatics analysis showed that hsa_circ_0018069 was coexpressed with protein-coding mRNAs that participate in cytoskeletal protein binding and cell-substrate junction assembly and play an anticancer role through focal adhesion and calcium signaling pathways. ceRNA analysis showed that hsa_circ_0018069 functions in ErbB, Ras, FoxO, and the focal adhesion signaling pathway by harboring miR-23c, miR-34a-5p, miR-181b-5p, miR-454-3p, and miR-3666. hsa_circ_0018069 may thus play an important role in the occurrence and progression of bladder cancer and serve as a valuable biomarker for the early diagnosis of this disease.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma/sangue , RNA/genética , Neoplasias da Bexiga Urinária/sangue , Idoso , Biomarcadores Tumorais/genética , Sinalização do Cálcio , Carcinoma/genética , Carcinoma/patologia , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , RNA/sangue , RNA Mensageiro/sangue , Análise de Sequência de RNA , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
14.
Am J Physiol Renal Physiol ; 316(6): F1094-F1102, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30892932

RESUMO

The incidence of urothelial carcinoma (UC) is higher in patients undergoing chronic dialysis than in the general population. This study investigated plasma miRNA profiling as the ancillary diagnosis biomarker associated with UC in patients undergoing chronic hemodialysis. We successfully screened out and detected miRNA expression from plasma in eight patients undergoing dialysis through quantitative real-time PCR array analysis and identified eight candidate miRNAs. The candidate miRNAs were then validated using single quantitative RT-PCR assays from 52 plasma samples. The miRNA classifier for ancillary UC detection was developed by multiple logistic regression analyses. Moreover, we validated the classifier by testing another nine samples. Expression levels of miR-150-5p, miR-150-5p/miR-155-5p, miR-378a-3p/miR-150-5p, miR-636/miR-150-5p, miR-150-5p/miR-210-3p, and miR-19b-1-5p/miR-378a-3p were shown to be significantly different between UC and non-UC samples (P = 0.035, 0.0048, 0.016, 0.024, 0.038, and 0.048). Kaplan-Meier curve analysis also showed that low miR-19b-1-5p expression was associated with a worse prognosis (P = 0.0382). We also developed a miRNA classifier based on five miRNA expression levels to predict UC and found that the area under curve was 0.882. The classifier had a sensitivity of 80% (95% confidence interval: 0.5191% to 0.9567%) and a specificity of 83.7% (95% confidence interval: 0.6799% to 0.9381%). This classifier was tested by nine samples with 100% accuracy. The miRNA classifier offers higher sensitivity and specificity than the existing makers. Thus, this approach will improve the prospective diagnosis of UC in patients undergoing chronic hemodialysis.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma/sangue , MicroRNA Circulante/sangue , Detecção Precoce de Câncer/métodos , Perfilação da Expressão Gênica , Diálise Renal/efeitos adversos , Neoplasias Urológicas/sangue , Idoso , Biomarcadores Tumorais/genética , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Carcinoma/genética , MicroRNA Circulante/genética , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Taiwan/epidemiologia , Transcriptoma , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/genética , Urotélio/patologia
15.
Int J Radiat Oncol Biol Phys ; 104(4): 801-808, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30890448

RESUMO

PURPOSE: The purpose of this study is to assess the utility of 68Gallium prostate-specific membrane antigen (PSMA) Division of Radiopharmaceutical Chemistry (DKFZ)-PSMA-11 positron emission tomography (PET)-computed tomography (CT), compared with standard imaging, in the detection of recurrent prostate carcinoma in patients with biochemical relapse to determine the prevalence of oligometastatic disease recurrence and its distribution. METHODS AND MATERIALS: This is a prospective, multicenter clinical trial of PSMA-HBED PET/CT imaging in patients with early biochemical relapse of prostate carcinoma (median prostate-specific antigen [PSA], 2.55 ng/mL) after definitive prostatectomy (152 patients) or radiation therapy (86 patients) with either no lesions or oligometastatic disease on abdominopelvic CT and bone scan (BS). PSMA-HBED PET/CT scan was performed within 8 weeks of restaging imaging, and all sites of abnormal PSMA-HBED binding determined as probable or definite for prostate carcinoma were included in the analysis. PSMA positivity was assessed for correlation with Gleason Score, PSA level, and PSA doubling time. RESULTS: Two hundred thirty-eight patients underwent PSMA-HBED PET/CT imaging. In 199 patients with no lesions on restaging CT and BS, 148 patients (74%) demonstrated PSMA-positive lesions, with 113 patients (57%) being oligometastatic. In 39 patients with oligometastatic lesions on restaging CT and BS, 19 patients (49%) were confirmed as oligometastatic on PSMA PET/CT and 16 patients (41%) were upstaged to polymetastatic. The 4 remaining patients (10%) with sites of possible metastatic disease were not confirmed as having prostate carcinoma. Combining the overall group, there were 183 patients (77%) with PSMA-HBED-positive lesions (682 lesions), suggesting prostate carcinoma, of whom 132 patients (55%) were oligometastatic. In the oligometastatic group, PSMA positivity was limited to the pelvis in 65% of patients, involving either the prostate or nodes (American Joint Committee on Cancer stage N1). This study found a positive correlation between PSMA-HBED positivity and PSA levels; no other factors were statistically significant. CONCLUSIONS: For patients with biochemical relapse with BS and CT demonstrating either no disease or low-volume disease, there is a high overall prevalence of PSMA PET/CT-positive disease. More than half of the patients were oligometastatic, and of those, disease was confined to the pelvis in nearly two-thirds of patients. This result confirms that PSMA PET/CT is significantly more sensitive than standard restaging imaging, and it may be useful in identifying patients for subsequent targeted therapy.


Assuntos
Antígenos de Superfície/sangue , Carcinoma/diagnóstico por imagem , Ácido Edético/análogos & derivados , Radioisótopos de Gálio , Glutamato Carboxipeptidase II/sangue , Recidiva Local de Neoplasia/diagnóstico por imagem , Oligopeptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/diagnóstico por imagem , Carcinoma/sangue , Carcinoma/secundário , Estudos Transversais , Ácido Edético/sangue , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Pelve , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia
16.
Cancer Biother Radiopharm ; 34(4): 218-223, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30810349

RESUMO

Background: The treatment of abdominal wall metastasis presents a challenge, because resection can be followed by poor healing and external radiotherapy is associated with serious adverse events. This study aimed to evaluate the efficacy and safety of interstitial 125I seed implantation under ultrasound (US) guidance for treating abdominal wall metastasis. Materials and Methods: The cases of 21 patients with 28 abdominal wall metastases who received brachytherapy with 125I seeds at the department from August 2010 to March 2015 were retrospectively reviewed. 125I seeds were implanted in the abdominal wall lesions under US guidance and with the help of a treatment planning system. Follow-up was performed using computed tomography at 1 d and at 3, 6, and 12 months after implantation. The lymphocyte count before the surgery was compared with the 3-month postoperative count. The main indicators observed were changes in tumor size, side effects, and complications. Results: All 21 patients were successfully treated with 125I seed implantation under US guidance. The median follow-up since 125I seed implantation was 15 months (range 6-23 months). The response rates and local tumor control after 3, 6, and 12 months were 78.6% and 89.3%, 64.3% and 85.7%, and 52.4% and 71.4%, respectively. The mean preoperative lymphocyte count was 0.262 ± 0.117 × 109/L, which did not differ significantly from the postoperative count, which was 0.259 ± 0.094 × 109/L (p = 0.122). Procedure-related complications included fever, bleeding, and pain, but all these were Grade 1-2. No severe side effects or complications were noted. Conclusions: Percutaneous interstitial implantation of 125I seeds under US guidance is safe and feasible for abdominal wall metastases. However, its long-term efficacy requires further investigation.


Assuntos
Neoplasias Abdominais/radioterapia , Braquiterapia/métodos , Carcinoma/radioterapia , Radioisótopos do Iodo/administração & dosagem , Lesões por Radiação/epidemiologia , Neoplasias Abdominais/sangue , Neoplasias Abdominais/diagnóstico por imagem , Neoplasias Abdominais/secundário , Parede Abdominal/diagnóstico por imagem , Parede Abdominal/patologia , Parede Abdominal/efeitos da radiação , Adulto , Idoso , Braquiterapia/efeitos adversos , Carcinoma/sangue , Carcinoma/diagnóstico por imagem , Carcinoma/secundário , Estudos de Viabilidade , Feminino , Febre/epidemiologia , Febre/etiologia , Seguimentos , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Radioisótopos do Iodo/efeitos adversos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Dor/epidemiologia , Dor/etiologia , Lesões por Radiação/etiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral/efeitos da radiação , Ultrassonografia de Intervenção/métodos
17.
Int Urol Nephrol ; 51(3): 443-451, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30739268

RESUMO

PURPOSE: To identify a novel biomarker that can predict biochemical recurrence (BCR) after radical prostatectomy. METHODS: The gene expression profile of SAMD5 in prostate cancer was explored based on the oncomine database and The Cancer Genomic Atlas (TCGA). The follow-up information and clinical pathologic variables were extracted from the following cohort study: TCGA_prostate carcinoma. And then, survival analysis was conducted using the Kaplan-Meier plot and Cox's proportional hazard regression model. Furthermore, another independent cohort study: Taylor prostate, was also acquired to validate the predictive effect of SAMD5 on BCR. In addition, the expression profile of SAMD5 in other cancer types was investigated using TCGA dataset. RESULTS: SAMD5 mRNA was shown to be up-regulated in multiple microarray datasets of prostate cancer with the strict statistic criteria: p < 0.01 and fold change ≥ 2. In TCGA_PCa cohort study, high expression of SAMD5 was a risk factor for patients on post-operative BCR (HR 2.181, 95%CI 1.199-3.966, p = 0.011) and this predictive ability was independent of Gleason score and pathologic T stage (HR 2.018, 95%CI 1.102-3.698, p = 0.023). In another validating cohort study, the statistic trend was similar, and the pooled analysis by combining the two cohort study further confirmed its prognostic effect. CONCLUSION: SAMD5 mRNA was overexpressed in prostate cancer and had powerful prognostic ability on predicting post-operative BCR, independent of Gleason score and pathologic T stage. Its high expression was associated with poor prognosis after RP.


Assuntos
Carcinoma/genética , Carcinoma/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Proteína Smad5/genética , Adulto , Idoso , Carcinoma/sangue , Carcinoma/cirurgia , Bases de Dados Genéticas , Expressão Gênica , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/cirurgia , RNA Mensageiro/metabolismo , Recidiva , Regulação para Cima
18.
Gynecol Endocrinol ; 35(5): 370-375, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30668178

RESUMO

Endometrial carcinoma (EC) often expresses estrogen receptors (ER), and the growth of EC is stimulated by estrogen. Therefore, EC is considered to be an estrogen-dependent tumor. However, the role of estrogen in endometrial carcinogenesis is somewhat unclear because the majority of EC occurs at peri- or post menopause when serum estrogen levels are generally decreased. In this article, we describe the double-edged role of estrogen in the genesis of EC, especially in terms of mismatch repair functions in vitro and in vivo, i.e. when serum estradiol (E2) levels are relatively low (approximately less than 90 pg/ml), and E2 enhance the carcinogenesis, whereas high E2 levels may suppress the carcinogenesis. This will deepen mechanistic insight into unopposed estrogen.


Assuntos
Carcinogênese/patologia , Carcinoma/patologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Estrogênios/sangue , Carcinoma/sangue , Neoplasias do Endométrio/sangue , Feminino , Humanos
19.
J Am Vet Med Assoc ; 254(2): 226-235, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30605380

RESUMO

OBJECTIVE To identify minimally invasive biomarkers to help differentiate dogs with gastric carcinoma from those with chronic gastritis. DESIGN Prospective study. ANIMALS 15 dogs with gastric carcinoma, 29 dogs with chronic gastritis, and 7 healthy dogs. PROCEDURES Dogs with clinical signs of upper gastrointestinal tract disease for > 14 days that underwent gastroscopy or necropsy for collection of gastric biopsy specimens for histologic evaluation were prospectively enrolled. Gastric carcinoma and chronic gastritis were diagnosed on the basis of histologic findings. Additionally, gastric biopsy specimens were collected endoscopically from 7 healthy (control) dogs while they were anesthetized for a routine neutering procedure. Prior to being anesthetized for gastroscopy or euthanized, all dogs underwent a physical examination, and a blood sample was collected for quantification of select serum biomarker concentrations. Histologic findings, body condition score (BCS), and serum biomarker concentrations were compared among the 3 groups. RESULTS Dogs with gastric carcinoma were significantly older and had a significantly lower BCS, lower serum folate concentration, and greater serum C-reactive protein (CRP) concentration, compared with dogs with chronic gastritis and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age > 8 years, BCS < 4, serum CRP concentration > 25 mg/L, and an abnormally low serum folate concentration might be useful noninvasive biomarkers for identification of dogs with gastric carcinoma. For underweight older dogs with signs of upper gastrointestinal tract disease and high serum CRP and low serum folate concentrations, gastric biopsy specimens should be obtained and evaluated so that a prompt definitive diagnosis can be made and appropriate treatment initiated.


Assuntos
Carcinoma/veterinária , Doenças do Cão/diagnóstico , Gastrite/veterinária , Neoplasias Gástricas/veterinária , Envelhecimento , Animais , Biomarcadores/sangue , Contagem de Células Sanguíneas/veterinária , Composição Corporal , Carcinoma/sangue , Carcinoma/diagnóstico , Citocinas/sangue , Citocinas/metabolismo , Doenças do Cão/sangue , Cães , Feminino , Ácido Fólico/sangue , Gastrite/sangue , Gastrite/diagnóstico , Masculino , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Vitamina B 12/sangue
20.
Oncol Rep ; 41(2): 863-874, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30535507

RESUMO

Laryngeal carcinoma is one of the most common tumors concerning otorhinolaryngology head and neck surgery, however, the pathogenesis of laryngeal carcinoma remains unclear. MicroRNAs (miRNAs) have been reported to play vital roles in the pathogenesis of laryngeal carcinoma Herein, the present study was designed to explore the function and mechanism of miRNA­98 in hypopharyngeal carcinoma. In brief, qRT­PCR, MTT assay, western blot analysis, Transwell assay and luciferase reporter assay were performed. Based on the results, miRNA­98 expression was downregulated in patients with hypopharyngeal carcinoma. Downregulation of miRNA­98 promoted cell growth and migration, and decreased the apoptotic rate of hypopharyngeal carcinoma cells. Overexpression of miRNA­98 increased the apoptotic rate, and inhibited cell growth and migration of hypopharyngeal carcinoma cells. Moreover, luciferase reporter assays revealed that MTDH is a direct target of miRNA­98 and overexpression of miRNA­98 induced the protein expression of PTEN and suppressed that of PI3K and p­Akt. si­MTDH attenuated the anticancer effects of miRNA­98 on hypopharyngeal carcinoma via the PTEN/AKT pathway. To the best of our knowledge, the present study confirmed for the first time that miRNA­98 inhibits hypopharyngeal carcinoma cell proliferation and induces apoptosis via the PTEN/AKT pathway by MTDH.


Assuntos
Carcinoma/genética , Moléculas de Adesão Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hipofaríngeas/genética , MicroRNAs/metabolismo , Transdução de Sinais/genética , Apoptose/genética , Carcinoma/sangue , Carcinoma/patologia , Estudos de Casos e Controles , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Voluntários Saudáveis , Humanos , Neoplasias Hipofaríngeas/sangue , Neoplasias Hipofaríngeas/patologia , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Invasividade Neoplásica/patologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
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