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1.
Bioelectrochemistry ; 131: 107352, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31494386

RESUMO

The designed synthesis of efficient materials can significantly enhance the performance of electrochemical immunoassay in the detection of diseases, pesticide residues and environmental pollutants. The hollow AgPt@Pt core-shell nanoparticles (AgPt@Pt HNs) have exhibited high catalytic efficiency to the hydrogen peroxide (H2O2) reduction for its high mass activity from their hollow structure. Their limitation of instability can be overcome by loading on polypyrrole nanosheet (PPy NS). Besides, PPy NS exhibits good conductivity, and there exists environmentally-friendly method for its synthetic. Thus, AgPt@Pt HNs loaded on PPy NS (AgPt@Pt HNs/PPy NS) exhibits high catalytic efficiency to the reduction of H2O2 and good stability. Furthermore, the quick electron transfer of AgPt@Pt HNs/PPy NS modified glassy carbon electrode has been evidenced by the finding that the large constant of apparent electron transfer rate has also enlarged the current signal when the amount of electron is invariant. The modified electrode has fabricated a label-free amperometric immunosensor to detect sensitively prostate-specific antigen (PSA) with H2O2 as the electroactive material. The immunosensor in hollow core-shell nanosheet structure exhibiting good detection performance of PSA shows its promising applications in the clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Eletrodos , Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , Platina/química , Polímeros/química , Pirróis/química , Biomarcadores Tumorais/análise , Catálise , Peróxido de Hidrogênio/química , Limite de Detecção , Oxirredução , Antígeno Prostático Específico/análise
2.
J Urol ; 203(1): 62-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31112107

RESUMO

PURPOSE: Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome. MATERIALS AND METHODS: We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications. RESULTS: Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p <0.0001) and overall survival (p=0.01 to <0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively). CONCLUSIONS: Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Transcriptoma
3.
Zhonghua Bing Li Xue Za Zhi ; 48(11): 867-872, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31775436

RESUMO

Objective: To evaluate the concordance of PD-L1 expression in various tissues using antibodies 28-8 and SP263 on their respective detection platforms. Methods: Three hundred seventy four specimens of surgical resection of pulmonary diseases in the First Affiliated Hospital of Nanjing Medical University from January 1, 2012 to January 31, 2017 were collected. Totally 374 cases were tested for PD-L1 expression using the two antibodies, 28-8 and SP263, by respective detection platforms (Dako and Ventana). Finally, 336 cases were used for further evaluation, and the results were statistically analyzed for concordance. Results: For non-small cell lung carcinoma (NSCLC), the positive rate of PD-L1 was 57.5% (177/308) using SP263, and 57.5% (177/308) using 28-8 antibody. The correlation coefficient was 0.97 (P<0.01). The positive rate of both benign lung diseases and paracancerous tissues was about 10.7% (3/28), and the positive concordance rate was 100.0%. The distribution of both antibodies was also relatively consistent. Conclusions: The expression levels of 28-8 and SP263 antibodies in NSCLC and other tissues are relatively consistent, suggesting both antibodies may be complementary and substitute for each other, which may be useful in guiding clinical management.


Assuntos
Antígeno B7-H1/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Anticorpos , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica
4.
Zhonghua Wai Ke Za Zhi ; 57(11): 840-847, 2019 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-31694133

RESUMO

Objective: To examine the prognostic value of four important driver gene mutations in patients with radical resection of pancreatic cancer. Methods: The clinical data and follow-up data of pancreatic cancer patients undergoing radical pancreatectomy and targeted sequencing from January 2016 to March 2018 at Department of Hepato-Biliary-Pancreatic Surgery, Changhai Hospital were retrospectively analyzed.There were 159 males and 88 females,aged of (60.8±8.7)years(range:33-83 years) and preoperative CA19-9 of (492.4±496.6)kU/L(range: 2-1 200 kU/L). One hundred and fifty nine cases of tumors were located in the head and 88 cases in the body and tail of the pancreas. After univariate analysis of clinical pathological factors (including gender, age, preoperative CA19-9, tumor location, tumor differentiation, pathological T and N stage, Micr. perineural invasion, Micr. lympho-vascular invasion, resection margin), the variable whose P<0.1 was included in COX regression model with four important driver gene mutations to find which mutation was related to prognosis independently. The number of gene mutations and KRAS subgroups were analyzed by Kaplan-Meier curve. Results: Among 247 patients,the number of KRAS,TP53, SMAD4 and CDKN2A mutations was 212 cases(85.8%), 160 cases(64.8%), 66 cases(26.7%) and 44 cases(17.8%),respectively.KRAS mutation was correlated with the tumor differentiation and pathological T stage (χ(2)=24.570/6.690, P=0.000/0.035), TP53 mutation was correlated with the tumor differentiation and the resected margin(χ(2)=5.500/4.620, P=0.019/0.032), and CDKN2A mutation was correlated with gender(χ(2)=16.574, P=0.000).COX regression model analysis showed that only KRAS mutation was an independent risk factor for disease free survival and overall survival(HR=1.776, 95%CI: 1.079-2.923, P=0.024; HR=1.923, 95%CI: 1.016-3.639, P=0.045); KRAS(G12D) mutation was associated with shorter OS(P=0.007). Conclusion: KRAS and its subgroup KRAS(G12D) mutation can be used as a prognostic index for patients with radical resection of pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/análise , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Pancreatectomia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Proteína Smad4/genética , Proteína Supressora de Tumor p53/genética
5.
Medicine (Baltimore) ; 98(45): e17859, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702649

RESUMO

BACKGROUND: To investigate the diagnostic performance of cytology (fine-needle aspiration cytology [FNAC]), thyroglobulin (fine-needle aspiration thyroglobulin [FNA-Tg]), and combination of them in the washout of fine-needle aspiration for those patients who have suspicious metastatic lymph nodes of differentiated thyroid cancer. METHODS: Databases, including PubMed, EMbase, Web of Science and Cochrane Library were searched up to June 2019. The quality assessment of diagnostic accuracy scale-2 was used to conduct quality assessments, and publication bias was evaluated using the Deeks funnel plot. STATA version 14.0 was used to perform the meta-analysis. RESULTS: A total of 2257 patients with 2786 samples of suspicious metastatic lymph nodes of differentiated thyroid cancer were included in the meta-analysis. The results showed that the diagnostic value for detecting lymph node metastasis of differentiated thyroid cancer was as follows: combination of FNAC and FNA-Tg > FNA-Tg > FNAC. All differences of superiority among them are statistically significant. The sensitivity of the combination was 0.968 (95% confidence interval [CI]: 0.942-0.983), the specificity was 0.932 (95% CI: 0.856-0.969), the diagnostic score was 6.036 (95% CI: 4.892-7.181), the diagnostic odds ratio was 418.424 (95% CI: 133.167-1314.729), and the score of summary receiver operating characteristic was 0.99 (95% CI: 0.97-0.99). CONCLUSIONS: The combination of FNAC and FNA-Tg is an excellent procedure in diagnosis of lymph nodes metastasis of patients with differentiated thyroid cancer, which should be highly recommended.


Assuntos
Carcinoma Papilar/patologia , Metástase Linfática/patologia , Tireoglobulina/análise , Neoplasias da Glândula Tireoide/patologia , Área Sob a Curva , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina , Humanos , Metástase Linfática/diagnóstico , Valor Preditivo dos Testes
6.
Anticancer Res ; 39(11): 6241-6247, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704853

RESUMO

BACKGROUND/AIM: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. PATIENTS AND METHODS: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). RESULTS: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. CONCLUSION: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/enzimologia , Mesotelioma/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/análise , Neoplasias Pleurais/enzimologia , Serina-Treonina Quinases TOR/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidade , Mesotelioma/terapia , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Terapia de Alvo Molecular , Pemetrexede/administração & dosagem , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Pneumonectomia , Prognóstico , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo
7.
Georgian Med News ; (294): 123-128, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687963

RESUMO

Microenvironment plays central role in the development of cervical precancerous and cancerous lesions. Cervical intraepithelial neoplasia (CIN) represents a group of precancerous lesions, divided into three degrees. We investigated the distribution of intraepithelial lymphocytes and macrophages in different grades of CIN. We analysed lymphocyte marker CD103, macrophage marker CD68 and proliferation marker Ki67 using standard immunohistochemistry. In addition, we investigated the distribution of lymphocytes using standard haematoxylin and eosin method. The results of our study indicated thatgrade I CIN which subsequently progressed into grade II CIN was characterised with low lymphocytic infiltration, low lympho-epithelial index and low lymphocyte proliferation index. Similar results were seen in cases of CINII which were later progressed into CINIII or in carcinoma. Therefore, we would like to recommend the analysis of microenvironment alterations in CIN lesions, in order to assess their progression potential.


Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/análise , Transformação Celular Neoplásica/patologia , Neoplasia Intraepitelial Cervical/patologia , Linfócitos Intraepiteliais/patologia , Antígeno Ki-67/metabolismo , Macrófagos/patologia , Microambiente Tumoral , Neoplasias do Colo do Útero/patologia , Antígenos CD/análise , Neoplasia Intraepitelial Cervical/metabolismo , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica/métodos , Antígeno Ki-67/análise , Gradação de Tumores , Neoplasias do Colo do Útero/metabolismo
8.
Chem Commun (Camb) ; 55(88): 13235-13238, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31621698

RESUMO

Protein C receptor (PROCR) is a recently discovered transmembrane biomarker for several tissue stem cells and is highly expressed in triple-negative breast cancer (TNBC) patient-derived xenografts. Herein, to enrich the toolbox for the biochemical evaluation of PROCR, we have developed a peptide-functionalized fluorogenic 2D material based on the self-assembly between a fluorescent peptide probe and thin-layer molybdenum disulfide. The material developed was suitable for the sensitive detection of PROCR recombinant protein in buffer solution and the fluorescence imaging of TNBC cells that express high levels of PROCR.


Assuntos
Biomarcadores Tumorais/análise , Receptor de Proteína C Endotelial/análise , Corantes Fluorescentes/química , Imagem Óptica , Peptídeos/química , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Linhagem Celular Tumoral , Feminino , Humanos , Células MCF-7 , Estrutura Molecular , Tamanho da Partícula , Espectrometria de Fluorescência , Propriedades de Superfície
9.
Br J Radiol ; 92(1104): 20190672, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31603350

RESUMO

OBJECTIVE: This paper considers aspects of radiobiology and cell and tissue kinetics applicable to legal disputations concerned with diagnostic and treatment onset delays. METHODS: Various models for tumour volume changes with time are reviewed for estimating volume ranges at earlier times, using ranges of kinetic parameters. Statistical cure probability methods, using Poisson statistics with allowances for parameter heterogeneity, are also described to estimate the significance of treatment delays, as well as biological effective dose (BED) estimations of radiation effectiveness. RESULTS: The use of growth curves, based on parameters in the literature but with extended ranges, can identify a window of earlier times when such tumour volumes would be amenable to a cure based on the literature for curability with stage (and dimensions). Also, where tumour dimensions are not available in a post-operative setting, higher cure probabilities can be achieved if treatment had been given at earlier times. CONCLUSION: The use of radiobiological modelling can provide useful insights, with quantitative assessments of probable prior conditions and future outcomes, and thus be of assistance to a Court in deciding the most correct judgement. ADVANCES IN KNOWLEDGE: This study collates prior knowledge about aspects of radiobiology that can be useful in the accumulation of sufficient proof within medicolegal claims involving diagnostic and treatment days.


Assuntos
Diagnóstico Tardio/legislação & jurisprudência , Neoplasias/diagnóstico , Neoplasias/radioterapia , Radiobiologia/legislação & jurisprudência , Tempo para o Tratamento/legislação & jurisprudência , Algoritmos , Biomarcadores Tumorais/análise , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Estadiamento de Neoplasias , Neoplasias/patologia , Distribuição de Poisson , Resolução de Problemas , Prognóstico , Radioterapia (Especialidade)/legislação & jurisprudência , Radioterapia (Especialidade)/métodos , Radiobiologia/métodos , Eficiência Biológica Relativa , Fatores de Tempo , Carga Tumoral/fisiologia
10.
Zhonghua Bing Li Xue Za Zhi ; 48(10): 779-783, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31594042

RESUMO

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions: ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Mucinas/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/genética
11.
Gene ; 720: 144099, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31479715

RESUMO

Emerging evidence demonstrates that circular RNA (circRNA) is a novel class of non-coding RNA that plays a pivotal role in cancer. Recently, circ-PRMT5 was identified as an oncogene in bladder cancer. Nevertheless, its contribution to non-small cell lung cancer (NSCLC) is unknown. Herein, we aimed to clarify the biological role of circ-PRMT5 in NSCLC. High circ-PRMT5 expression was identified in NSCLC tissues and cell lines and positively correlated with larger tumor size, advanced clinic stage, lymph node metastasis as well as worse prognosis. Stable knockdown of circ-PRMT5 dramatically weakened the proliferative capacities of NSCLC cells both in vitro and in vivo. Mechanically, circ-PRMT5 could simultaneously effectively sponge three miRNAs (miR-377, miR-382 and miR-498) and alleviate their repression on the well-known oncogenic EZH2, resulting in increased EZH2 expression, thereby facilitating NSCLC progression. Importantly, a strong positive correlation between circ-PRMT5 and EZH2 expression was observed in NSCLC tissues. Overall, our data indicate that circ-PRMT5 is an oncogenic circRNA in NSCLC that can promote the growth of NSCLC via regulation of miR-377/382/498-EZH2 axis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , MicroRNAs/genética , Proteína-Arginina N-Metiltransferases/genética , RNA/genética , Animais , Apoptose , Biomarcadores Tumorais/análise , Carcinogênese , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células , Progressão da Doença , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Appl Oral Sci ; 27: e20180348, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31508790

RESUMO

SOX2 is a transcription factor related to the maintenance of stem cells in a pluripotent state. Podoplanin is a type of transmembrane sialoglycoprotein, which plays an important role in tumor progression and metastasis. This study aims to determine association of SOX2 and podoplanin expression in the progression of oral squamous cell carcinomas and to elucidate the association between two proteins. Label="METHODOLOGY">The immunohistochemical expression of SOX2 and podoplanin were evaluated in 60 cases of primary oral squamous cell carcinomas. The correlation between the SOX2 and podoplanin expression and the clinicopathological features of the tumors and the patient outcomes were assessed. RESULTS The expression of SOX2 was seen in 38/60 (63%) of the cases and the expression for podoplanin was seen in 45/60 (75%) cases. There was a significant inverse correlation between the expression of SOX2 and podoplanin with the tumor grade (p=0.002 and p=0.017, respectively). There was a high expression of SOX2 in 9/13 cases that presented with disease free survival. Survival analysis showed that a high expression of SOX2 correlated positively (p=0.043) with the disease-free survival. There was a significant positive association between the pattern of SOX2 and podoplanin expression (p=0.002). CONCLUSION A high expression of SOX2 was associated with better disease-free survival. The expression of podoplanin was associated with the degree of differentiation of the tumors. Analysis of these biomarkers can aid in the prognosis and treatment of oral squamous cell carcinomas.


Assuntos
Carcinoma de Células Escamosas/patologia , Glicoproteínas de Membrana/análise , Neoplasias Bucais/patologia , Fatores de Transcrição SOXB1/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Valores de Referência , Estatísticas não Paramétricas , Fatores de Tempo
13.
Anal Bioanal Chem ; 411(26): 6889-6897, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401668

RESUMO

Photoelectrochemical (PEC) sensor for sensitive detection of breast cancer biomarker human epidermal growth factor receptor 2 (HER2) utilizing hexagonal carbon nitride tubes (HCNT) as photoactive material is reported. The detection is based on suppression of the PEC current intensity of the sensor. HCNT were synthesized via a facile hydrothermal method with large specific surface area and low electron-hole recombination. Au nanoparticles (AuNPs) were deposited onto the surface of the HCNT, which enhanced the photocurrent intensity of the HCNT by one time. For HER2 detection, peptide specific to HER2 was immobilized on the AuNPs surface for capturing HER2 molecules. The following binding of HER2 with HER2 aptamer and the reaction of phosphate groups on aptamer with molybdate can form molybdophosphate precipitate, which sticks to the surface of HCNT and impedes electron transport. Thus, photocurrent intensity of the sensor was suppressed. Under optimal conditions, the linear relationship between the PEC intensity and the logarithm of HER2 concentration was from 0.5 to 1 ng mL-1 with low limit of detection (LOD) of 0.08 pg mL-1. Furthermore, the PEC sensor also displayed capability for detecting HER2 in human serum samples. This PEC sensor signal detection strategy can be easily adapted to other PEC sensors involving DNA and find wide applications. Graphical abstract.


Assuntos
Aptâmeros de Nucleotídeos/química , Neoplasias da Mama/sangue , Nitrilos/química , Receptor ErbB-2/sangue , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Técnicas Biossensoriais/métodos , Neoplasias da Mama/diagnóstico , Técnicas Eletroquímicas/métodos , Feminino , Ouro/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Peptídeos/química , Receptor ErbB-2/análise
16.
JAMA ; 322(8): 764-774, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454018

RESUMO

Importance: Non-small cell lung cancer remains the leading cause of cancer death in the United States. Until the last decade, the 5-year overall survival rate for patients with metastatic non-small cell lung cancer was less than 5%. Improved understanding of the biology of lung cancer has resulted in the development of new biomarker-targeted therapies and led to improvements in overall survival for patients with advanced or metastatic disease. Observations: Systemic therapy for metastatic non-small cell lung cancer is selected according to the presence of specific biomarkers. Therefore, all patients with metastatic non-small cell lung cancer should undergo molecular testing for relevant mutations and expression of the protein PD-L1 (programmed death ligand 1). Molecular alterations that predict response to treatment (eg, EGFR mutations, ALK rearrangements, ROS1 rearrangements, and BRAF V600E mutations) are present in approximately 30% of patients with non-small cell lung cancer. Targeted therapy for these alterations improves progression-free survival compared with cytotoxic chemotherapy. For example, somatic activating mutations in the EGFR gene are present in approximately 20% of patients with advanced non-small cell lung cancer. Tyrosine kinase inhibitors such as gefitinib, erlotinib, and afatinib improve progression-free survival in patients with susceptible EGFR mutations. In patients with overexpression of ALK protein, the response rate was significantly better with crizotinib (a tyrosine kinase inhibitor) than with the combination of pemetrexed and either cisplatin or carboplatin (platinum-based chemotherapy) (74% vs 45%, respectively; P < .001) and progression-free survival (median, 10.9 months vs 7.0 months; P < .001). Subsequent generations of tyrosine kinase inhibitors have improved these agents. For patients without biomarkers indicating susceptibility to specific targeted treatments, immune checkpoint inhibitor-containing regimens either as monotherapy or in combination with chemotherapy are superior vs chemotherapy alone. These advances in biomarker-directed therapy have led to improvements in overall survival. For example, the 5-year overall survival rate currently exceeds 25% among patients whose tumors have high PD-L1 expression (tumor proportion score of ≥50%) and 40% among patients with ALK-positive tumors. Conclusions and Relevance: Improved understanding of the biology and molecular subtypes of non-small cell lung cancer have led to more biomarker-directed therapies for patients with metastatic disease. These biomarker-directed therapies and newer empirical treatment regimens have improved overall survival for patients with metastatic non-small cell lung cancer.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Pontos de Checagem do Ciclo Celular , Genes erbB-1 , Humanos , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Intervalo Livre de Progressão , Taxa de Sobrevida
17.
Virchows Arch ; 475(4): 479-488, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31451895

RESUMO

Recent studies have shown that re-expression of stem cell factors contribute to pathogenesis, therapy resistance, and recurrent disease in ovarian carcinomas. In this study, we compare the expression and co-expression of stem cell markers ALDH1 and SOX2 in different types of serous ovarian tumors. A total of 215 serous ovarian tumors (161 high-grade serous carcinomas (HGSC), 17 low-grade serous carcinomas (LGSC), 37 atypical proliferative serous tumors (APST)), and 10 cases of serous tubal intraepithelial carcinoma (STIC) were analyzed. Double immunostaining experiments addressed the association of cell proliferation (Ki67) with ALDH1 and the potential co-expression of SOX2 and ALDH1. The prognostic effect was analyzed in the cohort of HGSC. Expression of ALDH1and/or SOX2 was detected with increased frequency in HGSC (88.8%), compared with LGSC (70.5%) and APST (36.4%), while ALDH1 alone was significantly more frequently expressed in LGSC. The majority of all tumor types showed expression of ALDH1 and SOX2 in different cells. Only a minority of HGSC (4.6%) and STIC (20%) showed SOX2/ALDH1 co-expression in > 10% of tumor cells. Double staining also revealed that ALDH1 is associated with the non-proliferating Ki67-negative fraction consistent with a stem cell phenotype. Co-expression of ALDH1 and SOX2 or ALDH1 and Ki67 has no effect on survival. Expression of stem cell factors ALDH1 and/or SOX2 shows increased frequency in high-grade serous ovarian carcinomas compared to low-grade carcinomas and borderline tumors, supporting the concept that stem cell markers play different biological roles in low-grade versus high-grade serous neoplasia of the ovary.


Assuntos
Cistadenocarcinoma Seroso/patologia , Isoenzimas/análise , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/patologia , Retinal Desidrogenase/análise , Fatores de Transcrição SOXB1/análise , Adulto , Biomarcadores Tumorais/análise , Feminino , Humanos , Isoenzimas/biossíntese , Pessoa de Meia-Idade , Retinal Desidrogenase/biossíntese , Fatores de Transcrição SOXB1/biossíntese
18.
Medicine (Baltimore) ; 98(31): e16511, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374012

RESUMO

Blood-based biomarkers, such as carcinoembryonic antigen (CEA), and saliva-based biomarkers, such as mRNA, have emerged as potential liquid biopsies for non-invasive detection of many cancers. However, current tests typically use single type of biomarkers, and their sensitivity and specificity is often unsatisfactory.In this study, we developed a novel biomarker panel that measures both CEA level in blood and GREB1 and FRS2 levels in saliva to achieve high sensitivity and high specificity in detecting Non-Small Cell Lung Cancer (NSCLC).In the discovery phase, we achieved sensitivity of 96.67% and specificity of 93.33% for 30 NSCLC patients and 30 healthy controls. To further evaluate the prediction performance of our biomarker panel, we applied it to an independent set of 15 NSCLC cancer patients and 25 healthy controls. The sensitivity and specificity of our test reached 93.33% and 80.00% respectively.Our study discovered that the combined analysis of CEA and mRNA can be a novel liquid-biopsy technology for non-invasive detection of NSCLC.


Assuntos
Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Proteínas Adaptadoras de Transdução de Sinal/análise , Idoso , Área Sob a Curva , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Feminino , Humanos , Masculino , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Curva ROC , Saliva/enzimologia
19.
Adv Exp Med Biol ; 1140: 451-467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347064

RESUMO

Innovations in approaches for early detection and individual risk assessment of different cancers, including breast cancer (BC), are needed to reduce cancer morbidity and associated mortality. The assessment of potential cancer biomarkers in accessible bodily fluids provides a novel approach to identify the risk and/or onset of cancer. Biomarkers are biomolecules, such as proteins, that are indicative of an abnormality or a disease. Human milk is vastly underutilized biospecimen that offers the opportunity to investigate potential protein BC-biomarkers in young, reproductively active women. As a first step, we have examined the entire protein pattern in human milk samples from breastfeeding mothers with cancer, who were diagnosed either before or after milk donation, and from women without cancer, using mass spectrometry (MS)-based proteomics.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico , Eletroforese , Leite Humano/química , Proteômica , Animais , Detecção Precoce de Câncer , Feminino , Humanos , Espectrometria de Massas
20.
Rev Assoc Med Bras (1992) ; 65(6): 893-901, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31340322

RESUMO

Breast cancer (BC) is one of the primary health problems worldwide. As the most common cancer in women in the world and in Brasil, behind only non-melanoma skin cancer, this neoplasm corresponds to approximately 28% of new cases per year in the country. BC also affects men, although the incidence corresponds to only 1% of total cases. Currently, most of the chemotherapeutic agents used in BC treatment are extremely toxic and cause long-term side effects. There is also a need to obtain earlier diagnoses, more accurate prognoses and make new therapies available that are more selective and effective in order to improve the current scenario. Therefore, this work sought to evaluate the importance of the biomarker survivin (Sur) in relation to BC, through the detailing of the role of Sur as a biomarker, the correlation between this protein and the prognosis of BC patients, and a summary of therapeutic strategies that target Sur for the development of new anticancer therapies.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma/diagnóstico , Carcinoma/patologia , Survivina/análise , Apoptose , Biomarcadores Tumorais/análise , Feminino , Humanos , Prognóstico
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