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1.
World Neurosurg ; 133: e421-e427, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31526886

RESUMO

BACKGROUND: In the era of integrated genomic-histologic analysis of brain tumors, new biomarkers have been introduced as diagnostic, prognostic, and therapeutic indicators. The analysis of the mutation in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 has provided important diagnostic and prognostic information for patients affected by diffuse glioma (i.e., the presence of the mutation has been related to an increased survival rate). The reference standard of IDH mutation detection has been its assessment in surgical specimens, immunohistochemistry, and/or genetic sequencing. Knowing the IDH status information preoperatively would be of great importance, because it has been related to tumor progression and the response to treatment. The oncometabolite 2-hydroxyglutarate (2HG), accumulated in gliomas with IDH mutation status, can be detected in vivo using magnetic resonance spectroscopy (MRS). METHODS: The 2HG-MRS technique remains technically challenging. We have summarized the results of the first pilot study in Australia, which included 10 patients affected by glioma. The data recorded from May 2017 to November 2018 were analyzed. RESULTS: In our exploratory study, we reached a sensitivity and specificity of 100%, confirming the strong predictive role of 2HG, as detected using MRS, in the diagnosis of glioma. CONCLUSION: In the present study, we have focused on methodological tips and future perspectives of the technique in the neuroimaging and neuro-oncological scenario. We would advocate the integration of 2HG-MRS into standard clinical practice.


Assuntos
Neoplasias Encefálicas/enzimologia , Análise Mutacional de DNA/métodos , Glioma/enzimologia , Isocitrato Desidrogenase/análise , Espectroscopia de Ressonância Magnética/métodos , Proteínas de Neoplasias/análise , Neuroimagem/métodos , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Feminino , Previsões , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/patologia , Humanos , Isocitrato Desidrogenase/genética , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Neuroimagem/tendências , Projetos Piloto , Sensibilidade e Especificidade , Adulto Jovem
2.
Cancer Immunol Immunother ; 68(10): 1597-1603, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31520110

RESUMO

BACKGROUND: Despite the promise of immunotherapy for gastric adenocarcinoma, choices for the selection of effective antigenic targets are very limited. Previously published data and our own in-house computational analysis have suggested that ANTXR1 is a potential target, simultaneously expressed in malignant tumor cells and the endothelial cells of the tumors. However, the expression pattern of ANTXR1 protein in clinical samples of gastric adenocarcinoma has not been fully evaluated. METHODS: Using immunohistochemistry (IHC), we recorded the percentage of ANTXR1 positive cells separately in tumor cells and endothelial cells in the primary tumor, non-tumor gastric tissue adjacent to the primary tumor, and tumor in metastatic sites of 140 gastric adenocarcinoma patients. We also evaluated the association of ANTXR1 expression with the Lauren histological classification of the primary tumors, the patient's history of neoadjuvant chemotherapy and/or radiotherapy, and the patient's overall survival. RESULTS: ANTXR1 was expressed in a mean of 73.89 ± 30.12% of tumor cells and 13.55 ± 20.53% of endothelial cells in the primary tumors. Intestinal adenocarcinomas had lower ANTXR1 expression in the tumor cells and higher ANTXR1 expression in the endothelial cells of the tumor regions, and a history of neoadjuvant therapy was associated with increased ANTXR1 expression in the endothelial cells of the tumor regions. Finally, above median expression of ANTXR1 in the tumor cells of the tumor regions was associated with significantly lower overall patient survival. CONCLUSIONS: Our findings suggest that ANTXR1 is a promising candidate for preclinical and clinical evaluation for gastric adenocarcinoma immunotherapy.


Assuntos
Adenocarcinoma/terapia , Proteínas de Neoplasias/análise , Receptores de Superfície Celular/análise , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Endoteliais/química , Feminino , Humanos , Imuno-Histoquímica , Imunoterapia , Masculino , Proteínas dos Microfilamentos , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade
3.
Comput Biol Chem ; 83: 107106, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542707

RESUMO

Colorectal cancer is one of the top leading causes of cancer mortality worldwide, especially in China. However, most of the current treatments are invasive and can only be applied to very few cancers. The earlier a malignant tumor is diagnosed, the higher the patient's survival rate. In this study, we proposed a computational framework to identify highly-reliable and easierly-detectable biomarkers capable of secreting into blood, urine and saliva by integrating transcriptomics and proteomics data at the system biology level. First, a large number of transcriptome data were processed to identify candidate biomarkers for colorectal cancer. Second, three classified models are constructed to predict biomarkers for colorectal cancer capable of secreting into blood, urine and saliva, which are effective disease diagnosis media to facilitate clinical screening. Then biological functions and molecular mechanisms of the candidate biomarkers of colorectal cancer are inferred utilizing multi-source biological knowledge and literature mining. Furthermore, the classification power of different combinations of candidate biomarkers is verified by machine learning models. In addition, the targeted drugs of the predicted biomarkers are further analyzed to provide assistance for clinical treatment of colorectal cancer. In this paper, our proposed computational model not only provides the effective candidate biomarkers ESM1, CTHRC1, AZGP1 for colorectal cancer capable of secreting into blood, urine and saliva, but also helps to understand the molecular mechanism of colorectal cancer. This computational framework can span the huge gap between transcriptome and proteomics, which can easily be applied to the biomarker research for other types of tumor.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , Biologia Computacional , Proteínas de Neoplasias/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Bases de Dados de Proteínas , Humanos , Aprendizado de Máquina , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteômica
4.
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
5.
Med Hypotheses ; 131: 109322, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443756

RESUMO

Bladder cancer is one of the most common urogenital tumors. Its prevalence is increasing worldwide, especially men. The cyclooxygenase-2 (COX-2) enzyme has been shown to increase in bladder cancer and has a direct relationship with tumor progression. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the growth of the tumor by inhibiting the COX-2 enzyme. NSAIDs have other effects unrelated to COX that provide anticancer properties. Also, similar to NSAIDs, anticancer effects of paracetamol have been shown in many studies. Therefore we hypothesize intravesical paracetamol application will have beneficial effects in the treatment of non-muscle invasive bladder cancer (NMBIC).


Assuntos
Acetaminofen/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Modelos Biológicos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Vacina BCG/uso terapêutico , Carcinógenos Ambientais/efeitos adversos , Ciclo-Oxigenase 2/análise , Sinergismo Farmacológico , Humanos , Imunoterapia/métodos , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/antagonistas & inibidores , Fumar/efeitos adversos , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/etiologia
6.
J Cancer Res Clin Oncol ; 145(9): 2211-2225, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297606

RESUMO

PURPOSE: To investigate the expression of biological markers in primary vulvar Paget's disease (VPD). METHODS: Forty-one patients referred to a single major Center for Gynecologic Oncology from January 2008 to June 2018 were enrolled retrospectively: 30 non-invasive-VPD and 11 invasive-VPD. A total number of 60 samples, from all the 41 vulvar sites (VS), 8 metastatic lymph node sites (MLS) and 11 successive recurrent disease in vulvar site (RVS), were tested for an immunohistochemical panel, including the following markers: PD-L1, CD3, MSH2, MSH6, MLH1, PMS2, HER2/neu, EGFR, p16, p53, Ki67, ER, PR, AR, VEGF and CD31. RESULTS: We found a positive PD-L1 in 10% of non-invasive-VPD and 27% of invasive-VPD (18% VS; 38% MLS). ER and AR were expressed respectively in more than 70% and 75% of all specimens. HER2/neu amplification was found in 21% of non-invasive-VPD and 45% of invasive-VPD (40% VS; 38% MLS). A machine learning cluster analysis identified three groups among non- invasive-VPD: cluster-1 with higher median ER expression (40%); cluster-3 with more frequent HER2/neu overexpression (46%). Among invasive-VPD, two clusters were found: the second with more frequent HER2/neu overexpression (67% vs. 0%) and nodal metastases (100% vs. 25%). Repeating the IHC panel on the correspondent MLS and RVS, it significantly changed, respectively, in 50% and 27%. CONCLUSIONS: This study reveals the expression of PDL-1 and ER and confirms the expression of HER2/AR in VPD; new bases are provided to design multicenter clinical trials on personalized target therapies.


Assuntos
Metaboloma , Proteínas de Neoplasias/metabolismo , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/metabolismo , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica/métodos , Metástase Linfática , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Doença de Paget Extramamária/patologia , Proteômica/métodos , Estudos Retrospectivos , Neoplasias Vulvares/patologia
8.
Cancer Radiother ; 23(5): 432-438, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31331844

RESUMO

Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (3 to 5% of all non-small cell lung cancers) carries a particularly high risk of central nervous system dissemination (60% to 90%). As the use of ALK inhibitors improves treatment outcomes over chemotherapy, the determent of central nervous system metastases has become an increasingly relevant therapeutic dilemma considering young age and possible extended overall survival. The goal of brain metastases management is to optimize both overall survival and quality of life, with the high priority of neurocognitive function preservation. Unfortunately in the first year on crizotinib, the pioneering ALK inhibitors, approximately one third of these patients fail in the central nervous system, which is explained by an inadequate central nervous system drug penetration through the blood-brain barrier. Central nervous system-directed radiotherapy represents the most important strategy to control intracranial disease burden and extend the survival benefit with crizotinib. The role of whole brain irradiation in the treatment of brain metastases diminishes, as this technique is associated with the risk of neurocognitive decline. Stereotactic radiotherapy represents an alternative technique that delivers ablative doses of ionizing radiation to the limited volume of oligometastatic brain disease, offering sparing of the adjacent brain parenchyma and reduced neurotoxicity. The next generation ALK inhibitors were designed to cross the blood-brain barrier more efficiently than crizotinib and achieve higher concentration in the cerebrospinal fluid, offering prominent ability to control central nervous system spread. In the phase III ALEX trial the intracranial control was significantly better with alectinib as compared to crizotinib and it translated into survival benefit. Other next generation ALK inhibitors (i.e. ceritinib, brigatinib, lorlatinib) also demonstrated promising activity in the central nervous system.


Assuntos
Quinase do Linfoma Anaplásico/antagonistas & inibidores , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares , Neoplasias Meníngeas/secundário , Proteínas de Neoplasias/antagonistas & inibidores , Quinase do Linfoma Anaplásico/análise , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/radioterapia , Carbazóis/farmacocinética , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto , Terapia Combinada , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Crizotinibe/farmacocinética , Crizotinibe/uso terapêutico , Gerenciamento Clínico , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Meníngeas/enzimologia , Neoplasias Meníngeas/radioterapia , Camundongos , Terapia de Alvo Molecular , Proteínas de Neoplasias/análise , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/prevenção & controle , Estudos Observacionais como Assunto , Proteínas de Fusão Oncogênica/análise , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Pemetrexede/administração & dosagem , Piperidinas/farmacocinética , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos
9.
Hematol Oncol ; 37(4): 360-367, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359442

RESUMO

De novo CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is increasingly recognized as a distinct pathologic phenomenon with a specific clinical picture. However, CD5+ DLBCL has not been studied on a large scale in China. In this study, we show that CD5+ DLBCL occurs at a low frequency (9.2%). Comparison of clinical characteristics of CD5+ vs CD5- DLBCL showed that CD5+ DLBCL was more frequently elderly (>60 years) and had B symptoms, high-performance status, stage III-IV, an IPI score >2 and bone marrow involvement. Patients with CD5+ DLBCL had tumours with a higher prevalence of BCL-2 and p53 overexpression than CD5- DLBCL. Patients with CD5+ DLBCL had inferior progression-free survival (PFS) and overall survival (OS) than did patients with CD5- DLBCL. For CD5+ DLBCL, the patients who were treated with rituximab showed significantly better PFS and OS than those treated without rituximab. However, patients treated with RCHOP showed similar PFS and OS when compared with the group treated with intensive therapy. In addition, patients with p53 and CD5 co-expression had the worst PFS and OS. In conclusion, CD5+ DLBCL was associated with unfavorable clinicopathologic variables and with inferior survival. CD5+ DLBCL has a high frequency of p53 overexpression, and CD5 augments the negative effect of p53 overexpression in DLBCL.


Assuntos
Antígenos CD5/análise , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas de Neoplasias/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Prednisona/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Fatores de Risco , Rituximab/administração & dosagem , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética , Regulação para Cima , Vincristina/administração & dosagem , Adulto Jovem
10.
J Clin Pathol ; 72(11): 762-770, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31256008

RESUMO

AIMS: Knowledge regarding the genetic features of ampullary carcinoma (AC) in European patients is limited. The utility of tumour markers for the establishment of a malignant diagnosis in biopsies from the ampullary region has not been fully elucidated. We aimed to describe the clinical, pathological, immunohistochemical (IHC) and genetic features of a Danish series of surgically resected ACs. METHODS: Surgically resected ACs (n=59) were examined regarding (1) clinicopathological features, (2) histological subtypes, (3) expression of IMP3, maspin, MUC5AC and S100P and (4) next-generation sequencing using a hybrid capture-based platform (Illumina HiSeq2500), including 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. Tumour mutational burden (TMB) and microsatellite instability (MSI) were also evaluated. RESULTS: Pancreatobiliary adenocarcinomas (PB-AC), intestinal adenocarcinomas (INT-AC), other ampullary tumours and mixed adenocarcinomas represented 45.8%, 23.7%, 16.9% and 13.6%. The proportion of IHC-positive ACs (score ≥2) was: Maspin (94.9%), IMP3 (67.8%), S100P (39.0%) and MUC5AC (18.6%). Most frequently altered genes were TP53 (59.3%), KRAS (40.7%), APC (27.8%), SMAD4 (20.4%), CDKN2A (16.7%) and ARID2/PIK3CA (each 11.1%). MUC5AC and S100P were frequently expressed in PB-AC, APC alterations frequent in INT-AC, SOX9 alterations were exclusive in INT-AC and MDM2 and FRS2 alterations in PB-AC. Four of 49 ACs (8.2%) were TMB-high/MSI-high and showed loss of MLH1 and PMS2. CONCLUSIONS: PB-AC was the most frequent histological subtype of AC. Maspin and IMP3 were the IHC tumour markers with the highest sensitivity. Adenocarcinoma subtypes differed regarding several genetic alterations, whose predictive value remains to be evaluated.


Assuntos
Adenocarcinoma/química , Adenocarcinoma/genética , Ampola Hepatopancreática/química , Biomarcadores Tumorais , Neoplasias do Sistema Digestório/química , Neoplasias do Sistema Digestório/genética , Perfilação da Expressão Gênica , Imuno-Histoquímica , Mutação , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/análise , Proteínas de Ligação ao Cálcio/genética , Dinamarca , Neoplasias do Sistema Digestório/patologia , Neoplasias do Sistema Digestório/cirurgia , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mucina-5AC/análise , Mucina-5AC/genética , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Fenótipo , Valor Preditivo dos Testes , Sistema de Registros , Ribonucleoproteínas Nucleolares Pequenas/análise , Ribonucleoproteínas Nucleolares Pequenas/genética , Serpinas/análise , Serpinas/genética
12.
Cell Prolif ; 52(3): e12589, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30873683

RESUMO

In recent years, with the increase in cancer mortality caused by metastasis, and with the development of individualized and precise medical treatment, early diagnosis with precision becomes the key to decrease the death rate. Since detecting tumour biomarkers in body fluids is the most non-invasive way to identify the status of tumour development, it has been widely investigated for the usage in clinic. These biomarkers include different expression or mutation in microRNAs (miRNAs), circulating tumour DNAs (ctDNAs), proteins, exosomes and circulating tumour cells (CTCs). In the present article, we summarized and discussed some updated research on these biomarkers. We overviewed their biological functions and evaluated their multiple roles in human and small animal clinical treatment, including diagnosis of cancers, classification of cancers, prognostic and predictive values for therapy response, monitors for therapy efficacy, and anti-cancer therapeutics. Biomarkers including different expression or mutation in miRNAs, ctDNAs, proteins, exosomes and CTCs provide more choice for early diagnosis of tumour detection at early stage before metastasis. Combination detection of these tumour biomarkers may provide higher accuracy at the lowest molecule combination number for tumour early detection. Moreover, tumour biomarkers can provide valuable suggestions for clinical anti-cancer treatment and execute monitoring of treatment efficiency.


Assuntos
Biomarcadores Tumorais , Neoplasias/diagnóstico , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Metilação de DNA , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Detecção Precoce de Câncer/métodos , Exossomos/química , Humanos , MicroRNAs/sangue , MicroRNAs/genética , Mutação , Proteínas de Neoplasias/análise , Neoplasias/sangue , Neoplasias/genética , Células Neoplásicas Circulantes/patologia , Valor Preditivo dos Testes , Prognóstico
13.
J Cancer Res Ther ; 15(1): 138-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880769

RESUMO

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT) but have a low incidence. Arising from the interstitial cells of Cajal, GISTs occur at different sites in the GIT with stomach being the most common. They can rarely be seen at sites outside the GIT such as omentum, retroperitoneum and are called as extraintestinal GISTs (EGIST). They have a spindle or epithelioid cell morphology and show positivity by immunohistochemistry (IHC) for CD117. Our aim was to study the clinicopathological and immunohistochemical profile of our cases of EGISTs. Materials and Methods: A cross-sectional study of EGISTs received from 2010 to 2015 was done. IHC with CD117 and discovered on GIST1 (DOG1) was performed and tumors were scored based on the percentage of cells that stained positive. Thirteen abdominal non-GIST spindle cell tumors were included in the study as controls. Results: Seven cases of EGIST were included (four-omental, three-retroperitoneal). All cases stained positive for CD117 and DOG1. One case of epithelioid EGIST scored 4 + with DOG1 and 2 + with CD117. Another case with mixed morphology scored 2 + with DOG1 and 4 + with CD117. All controls were negative for both markers. Conclusion: EGISTs are one of the rare differentials for spindle cell lesions outside the GIT. Although both markers stain positive, DOG1 showed higher score with epithelioid GISTs.


Assuntos
Neoplasias Abdominais/diagnóstico , Anoctamina-1/análise , Biomarcadores Tumorais/análise , Tumores do Estroma Gastrointestinal/diagnóstico , Proteínas de Neoplasias/análise , Neoplasias Abdominais/patologia , Adulto , Anoctamina-1/metabolismo , Biomarcadores Tumorais/metabolismo , Estudos Transversais , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-kit/análise , Proteínas Proto-Oncogênicas c-kit/metabolismo
15.
Zhonghua Bing Li Xue Za Zhi ; 48(3): 215-219, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-30831648

RESUMO

Objective: To investigate the clinicopathologic features and prognosis of ALK-positive Spitz tumors. Methods: Thirteen patients with ALK-positive Spitz tumors diagnosed at Shanghai Cancer Center, Fudan University from October 2016 to December 2017 were collected. All cases were routinely evaluated histopathological features in HE staining and detected ALK protein expression by immunohistochemistry. The ALK fusions of 7 cases were confirmed by fluorescence in situ hybridization (FISH).Follow-up data was collected. Results: The age of patients including 2 males and 11 females ranged from 4 to 47 years (mean 25 years). 12 patients were diagnosed with atypical Spitz tumors and 1 patient was diagnosed with Spitz nevus. Clinically, most lesions presented as papules or nodules, while a few lesions presented as plaques. Histologically, most tumors were exophytic (9/13). More than half of the tumors were amelanotic and the junctional component was mainly composed of melanocytic nests. Kamino bodies were not found. The bases of the tumors were mainly wedge-shaped (5/13) and flat (7/13). Eight tumors displayed mixed cell types, while 5 tumors were composed of only spindle cells. All the tumors showed a plexiform and/or intersecting fascicular growth pattern, and perineural extension was observed in 3 tumors. ALK immunohistochemistry showed diffuse and intense cytoplasmic staining in 13 cases, and 7 of them were detected by FISH to confirm the presence of ALK fusions. All patients were followed up for 7 to 21 months (median=12), with no recurrence or lymph node dissemination. Conclusions: Spitz tumors with ALK fusions have their special histopathologic features.ALK fusions mainly occur in Spitz nevi and atypical Spitz tumors. The follow-up data of the existing literatures and our research indicates that the prognosis of ALK-positive Spitz tumors may be good.


Assuntos
Quinase do Linfoma Anaplásico/análise , Proteínas de Neoplasias/análise , Nevo de Células Epitelioides e Fusiformes/química , Nevo de Células Epitelioides e Fusiformes/patologia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Criança , Pré-Escolar , China , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/mortalidade , Prognóstico , Neoplasias Cutâneas/mortalidade , Adulto Jovem
16.
Org Biomol Chem ; 17(11): 3010-3017, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30816385

RESUMO

"Minimalist" small molecule tagging (MSMT) is a promising approach that easily converts bioactive compounds into affinity-based probes (AfBPs) for proteomic studies. In this work, seven bioactive compounds targeting diversified protein classes were installed with "minimalist" linkers through common reactions to generate the corresponding AfBPs. These probes were evaluated for cell-based protein profiling and target validation. Among them, the entinostat-derived probe EN and the camptothecin-derived probe CA were further utilized in cellular imaging and SILAC-based large-scale target identification. Our extensive studies suggest that the "minimalist" small molecule tagging approach could be expanded to different classes of bioactive compounds for modification into AfBPs as a dual functional tool for both proteomics and cellular imaging.


Assuntos
Camptotecina/análise , Camptotecina/química , Proteínas de Neoplasias/análise , Imagem Óptica , Proteômica , Bibliotecas de Moléculas Pequenas/análise , Bibliotecas de Moléculas Pequenas/química , Camptotecina/síntese química , Células Hep G2 , Humanos , Proteínas Recombinantes/análise , Bibliotecas de Moléculas Pequenas/síntese química
17.
Ginekol Pol ; 90(2): 86-92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30860275

RESUMO

OBJECTIVES: This study Aims to explore the role of placental Cripto-1 in the incidence of an adherent placenta. MATERIAL AND METHODS: Ten pregnant women with placenta increta, 20 pregnant women with placenta previa and 30 women with normal pregnant were enrolled in this study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of Cripto-1 in the placenta while as the analysis of placental Cripto-1 was performed by Western blotting RESULTS: The placenta increta group showed higher levels of Cripto-1 in the center of the increta as compared to the non-implantation area. The level of placental Cripto-1 in the placenta increta was higher than that of the placenta accrete. The expression of placental Cripto-1 in the placenta increta and placenta previa groups was higher than that of control. CONCLUSIONS: Placental Cripto-1 is involved in the regulation of placental tissue invasion. Additionally, excessive placental growth or penetration into the myometrium are likely to be involved in the development of placenta increta.


Assuntos
Proteínas Ligadas por GPI/análise , Proteínas Ligadas por GPI/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/metabolismo , Placenta Acreta/metabolismo , Placenta Prévia/metabolismo , Placenta/metabolismo , Adulto , Feminino , Proteínas Ligadas por GPI/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Neoplasias/genética , Placenta/química , Placenta/fisiopatologia , Placenta Acreta/epidemiologia , Placenta Acreta/fisiopatologia , Placenta Prévia/epidemiologia , Placenta Prévia/fisiopatologia , Gravidez
18.
World Neurosurg ; 127: e212-e220, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30880197

RESUMO

OBJECTIVE: This study explored the differences between the immune microenvironments of primary and recurrent craniopharyngiomas (CPs). In addition, we investigated the relationship between the immune microenvironment and clinical characteristics of CP. METHODS: We collected 52 specimens from 26 patients with CPs. For each patient, specimens for both primary and recurrent CPs were obtained. We performed an immunohistochemical analysis of these specimens to determine the distributions of M2 macrophages, CD8+ T cells, programmed cell death 1 ligand 1 (PD-L1), and Ki67. RESULTS: In recurrent CP specimens, the distributions of M2 macrophages, Ki67, and PD-L1 increased compared with primary CP specimens (P = 0.019, P = 0.0084, and P = 0.0319, respectively). Moreover, the distributions of M2 macrophages, CD8+ T cells, and PD-L1 in papillary CPs were higher than those observed in adamantinomatous craniopharyngiomas (ACPs) (P = 0.0317, P = 0.0359, and P < 0.0001, respectively). In the adult ACP group, M2 macrophages, CD8+ T cells, and PD-L1 were more abundant/expressed than in the child ACP group (P = 0.0159, P = 0.0215, and P < 0.0088, respectively). A positive correlation was found between M2 macrophages and CD8+ T cells (r = 0.4079; P = 0.0027). Correspondingly, M2 macrophages and CD8+ T cells were both positively correlated with PD-L1 (r = 0.4564; P = 0.0007 and r = 0.3987; P = 0.0034, respectively). The observed high expression of M2 macrophages in primary CPs suggests a shortened time for tumor recurrence (P = 0.0131). CONCLUSIONS: The microenvironment of recurrent CP varies from that of primary CP. The abundance of M2 macrophages in primary CP may indicate a risk of early recurrence. Therefore, it is recommended to increase the frequency of follow-up examinations in these patients.


Assuntos
Craniofaringioma/imunologia , Neoplasias Hipofisárias/imunologia , Microambiente Tumoral/imunologia , Adulto , Antígenos de Neoplasias/análise , Antígeno B7-H1/análise , Linfócitos T CD8-Positivos/patologia , Criança , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/patologia , Craniofaringioma/cirurgia , Feminino , Humanos , Antígeno Ki-67/análise , Linfócitos do Interstício Tumoral/patologia , Macrófagos/patologia , Masculino , Proteínas de Neoplasias/análise , Recidiva Local de Neoplasia/química , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Risco , Subpopulações de Linfócitos T/patologia , Adulto Jovem
20.
Clin Transl Oncol ; 21(10): 1312-1318, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30759304

RESUMO

PURPOSE: Phosphoinositide-dependent kinase 1 (PDK1) is highly expressed in many solid tumors. And several studies have demonstrated that PDK1 has been an emerging and promising target for anti-cancer therapies. However, the role of PDK1 has not been studied so far in malignant pheochromocytoma (PCC). METHODS: In this study, immunohistochemical staining was performed to investigate the protein level of PDK1 in 63 PCC tissue samples, of which 49 were benign and 14 were malignant. In addition, we evaluated the effect of inhibition of PDK1 with siRNA on cell growth, apoptosis and invasive capacity in PC12 cells and identified the underlying mechanisms. RESULTS: We found that PDK1 was overexpressed in malignant PCC tissues, and knockdown of PDK1 with siRNA significantly inhibited cell proliferation, increased apoptosis induction, and attenuated cell migration and invasive capacity in PC12 cells. We also showed that knockdown of PDK1 significantly reduced the phosphorylation of Akt at threonine 308 (p-Akt T308) but did not alter the serine phosphorylation of Akt on the S473 site (p-Akt S473). Furthermore, we found that the p-Akt expression was noticeably decreased after knockdown of PDK1, but the t-Akt expression did not show a significant decrease. CONCLUSION: We have demonstrated for the first time that PDK1 is overexpressed in human malignant PCC and plays an important role in the malignant biological behaviors of PC12 cell. Specifically, we have revealed that knockdown of PDK1 could attenuate activation of the Akt signaling. These data suggest that PDK1 could be a new promising potential therapeutic target in human cancer treatment for malignant PCC.


Assuntos
Proteínas Quinases Dependentes de 3-Fosfoinositídeo/análise , Neoplasias das Glândulas Suprarrenais/enzimologia , Proteínas de Neoplasias/análise , Feocromocitoma/enzimologia , Glândulas Suprarrenais/química , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Técnicas de Silenciamento de Genes , Humanos , RNA Interferente Pequeno , Transfecção
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