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1.
Asian Pac J Cancer Prev ; 22(10): 3267-3286, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34711004

RESUMO

BACKGROUND: Colorectal cancer (CRC) categorized as the most common type of gastrointestinal cancers affected both genders equally. Chemotherapeutic drugs became limited due to their deleterious side effects. Therefore, efficiency of M. oleifera leaves extract increased by incorporating silver nanoparticles (Ag-NPs) then studied against colon cancer induced by azoxymethane (AOM) in rats. METHODS: Different hematological and biochemical measurements in addition to specific tumor and inflammatory markers were quantified. Histopathological examination for Colonic tissues was performed. Native proteins and isoenzyme patterns were electrophoretically detected in addition to assaying expression of Tumor Protein P53 (TP53) and Adenomatous Polyposis Coli (APC) genes in colonic tissues. RESULTS: M. oleifera nano-extract restored levels of the hematological and biochemical measurements in addition to levels of tumor and inflammatory markers to normalcy in both of nano-extract simult- and post-treated groups. Also, it minimized severity of the histopathological alterations in the simult-treated group and prevented it completely in the post-treated group. The lowest similarity index (SI%) values were noticed with electrophoretic protein (SI=61.54%), lipid (SI=0.00%) and calcium (SI=75.00%) moieties of protein patterns, catalase (SI=85.71%), peroxidase (SI=85.71%), α-esterase (SI=50.00%) and ß-esterase (SI=50.00%) isoenzymes in addition to altering the relative quantities of total protein and isoenzyme bands in colon of cancer induced group. Moreover, levels of TP53 and APC gene expression increased significantly (P≤0.05) in colon cancer induced group. The nano-extract prevented the qualitative and quantitative alterations in the different electrophoretic patterns in addition to restoring levels of the gene expressions to normalcy in both of simult- and post-treated groups. CONCLUSION: M. oleifera nano-extract exhibited ameliorative effect against the biochemical, physiological and molecular alterations induced by AOM in nano-extract simult- and post-treated groups.
.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Nanopartículas Metálicas/uso terapêutico , Moringa oleifera , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Animais , Azoximetano , Antígeno CA-19-9/análise , Antígeno Carcinoembrionário/análise , Carcinógenos , Neoplasias do Colo/sangue , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/genética , Eletroforese em Gel de Poliacrilamida , Expressão Gênica , Genes APC , Nanopartículas Metálicas/química , Proteínas de Neoplasias/análise , Estresse Oxidativo , Distribuição Aleatória , Ratos , Prata , Proteína Supressora de Tumor p53/análise
2.
Blood Adv ; 4(2): 367-379, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31985806

RESUMO

Acute myeloid leukemia (AML) is a genetically heterogeneous disease that is characterized by abnormal clonal proliferation of myeloid progenitor cells found predominantly within the bone marrow (BM) and blood. Recent studies suggest that genetic and phenotypic alterations in the BM microenvironment support leukemogenesis and allow leukemic cells to survive and evade chemotherapy-induced death. However, despite substantial evidence indicating the role of tumor-host interactions in AML pathogenesis, little is known about the complex microenvironment of the BM. To address this, we performed novel proteomic profiling of the noncellular compartment of the BM microenvironment in patients with AML (n = 10) and age- and sex-matched healthy control subjects (n = 10) using an aptamer-based, highly multiplexed, affinity proteomics platform (SOMAscan). We show that proteomic assessment of blood or RNA-sequencing of BM are suboptimal alternate screening strategies to determine the true proteomic composition of the extracellular soluble compartment of AML patient BM. Proteomic analysis revealed that 168 proteins significantly differed in abundance, with 91 upregulated and 77 downregulated in leukemic BM. A highly connected signaling network of cytokines and chemokines, including IL-8, was found to be the most prominent proteomic signature associated with AML in the BM microenvironment. We report the first description of significantly elevated levels of the myelosuppressive chemokine CCL23 (myeloid progenitor inhibitory factor-1) in both AML and myelodysplastic syndrome patients and perform functional experiments supportive of a role in the suppression of normal hematopoiesis. This unique paired RNA-sequencing and proteomics data set provides innovative mechanistic insights into AML and healthy aging and should serve as a useful public resource.


Assuntos
Medula Óssea/patologia , Leucemia Mieloide Aguda/patologia , Proteômica/métodos , Estudos de Casos e Controles , Microambiente Celular , Quimiocinas/análise , Quimiocinas CC/metabolismo , Citocinas/análise , Regulação Leucêmica da Expressão Gênica , Humanos , Interleucina-8/metabolismo , Proteínas de Neoplasias/análise
3.
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 , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Neuroimagem/tendências , Projetos Piloto , Sensibilidade e Especificidade , Adulto Jovem
4.
Mol Oncol ; 12(9): 1415-1428, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30019538

RESUMO

There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and to follow-up personalized cancer therapy. Fine-needle aspiration (FNA) biopsy provides ready access to relevant tissues; however, the minute sample amounts require sensitive multiplex molecular analysis to achieve clinical utility. We have applied proximity extension assays (PEA) and NanoString (NS) technology for analyses of proteins and of RNA, respectively, in FNA samples. Using samples from patients with breast cancer (BC, n = 25) or benign lesions (n = 33), we demonstrate that these FNA-based molecular analyses (a) can offer high sensitivity and reproducibility, (b) may provide correct diagnosis in shorter time and at a lower cost than current practice, (c) correlate with results from routine analysis (i.e., benchmarking against immunohistochemistry tests for ER, PR, HER2, and Ki67), and (d) may also help identify new markers related to immunotherapy. A specific 11-protein signature, including FGF binding protein 1, decorin, and furin, distinguished all cancer patient samples from all benign lesions in our main cohort and in smaller replication cohort. Due to the minimally traumatic sampling and rich molecular information, this combined proteomics and transcriptomic methodology is promising for diagnostics and evaluation of treatment efficacy in BC.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/diagnóstico , Proteínas de Neoplasias/análise , Adulto , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biópsia por Agulha Fina/economia , Mama/patologia , Neoplasias da Mama/terapia , Proteínas de Transporte/análise , Quimiocina CXCL9/análise , Estudos de Coortes , Decorina/análise , Diagnóstico Precoce , Feminino , Furina/análise , Heme Oxigenase-1/análise , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Adulto Jovem
5.
Sci China Life Sci ; 61(4): 492-500, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29556904

RESUMO

Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed in most tumors and is believed to play a key role in the development, invasion and metastasis of tumors. There is an urgent need to develop a simple method to detect the MT1-MMP expression level on cells. In this current study, we demonstrated a red emission Au cluster probes with the specific targeting of MT1-MMP on human dopaminergic neuroblastoma (SH-SY5Y) cells. More importantly, utilizing the intrinsic enzyme-like activity of the Au cluster probes, the expression level of MT1-MMP on the SH-SY5Y cells could be assessed by the naked eye without cell lysis and protein extraction process. Furthermore, SH-SY5Y, human breast cancer (MCF-7), and human bronchial epithelial (16-HBE) cell lines with different MT1-MMP expression level could be distinguished using the Au cluster probes by the naked eye. Meanwhile, fluorescence intensity and Au count determined by inductively coupled plasma mass spectrometry (ICP-MS) were used to verify the feasibility of this simple analytical method. Our proposed method is rapid, convenient, and accurate and could be assessed by the naked eye. This visual assessment method of tumor-associated proteins has immense implications in sorting tumor cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Ouro/química , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 14 da Matriz/metabolismo , Nanopartículas Metálicas/química , Proteínas de Neoplasias/metabolismo , Peptídeos/química , Ligação Competitiva , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Humanos , Células MCF-7 , Nanopartículas Metálicas/ultraestrutura , Microscopia Confocal , Proteínas de Neoplasias/análise , Neoplasias/diagnóstico , Neoplasias/enzimologia , Peptídeos/síntese química , Peptídeos/metabolismo , Ligação Proteica
6.
Cancer ; 123(19): 3807-3815, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28608950

RESUMO

BACKGROUND: Programmed death 1 (PD-1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD-1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death-ligand 1 (PD-L1) expression in common childhood cancers. The authors characterized PD-L1 expression and tumor-associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers. METHODS: Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD-L1 expression and for the presence of TAICs. TAICs were also screened for PD-L1 expression. RESULTS: Thirty-nine of 451 evaluable tumors (9%) expressed PD-L1 in at least 1% of tumor cells. The highest frequency histotypes comprised Burkitt lymphoma (80%; 8 of 10 tumors), glioblastoma multiforme (36%; 5 of 14 tumors), and neuroblastoma (14%; 17 of 118 tumors). PD-L1 staining was associated with inferior survival among patients with neuroblastoma (P = .004). Seventy-four percent of tumors contained lymphocytes and/or macrophages. Macrophages were significantly more likely to be identified in PD-L1-positive versus PD-L1-negative tumors (P < .001). CONCLUSIONS: A subset of diagnostic pediatric cancers exhibit PD-L1 expression, whereas a much larger fraction demonstrates infiltration with tumor-associated lymphocytes. PD-L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD-L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy. Cancer 2017;123:3807-3815. © 2017 American Cancer Society.


Assuntos
Antígeno B7-H1/análise , Linfócitos do Interstício Tumoral , Macrófagos , Proteínas de Neoplasias/análise , Neoplasias/química , Neoplasias Ósseas/química , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Linfoma de Burkitt/química , Linfoma de Burkitt/imunologia , Linfoma de Burkitt/patologia , Criança , Glioblastoma/química , Glioblastoma/imunologia , Glioblastoma/patologia , Humanos , Imuno-Histoquímica , Neoplasias/imunologia , Neoplasias/mortalidade , Neoplasias/patologia , Neuroblastoma/química , Neuroblastoma/imunologia , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Osteossarcoma/química , Osteossarcoma/imunologia , Osteossarcoma/patologia , Rabdomiossarcoma/química , Rabdomiossarcoma/imunologia , Rabdomiossarcoma/patologia , Sarcoma de Ewing/química , Sarcoma de Ewing/imunologia , Sarcoma de Ewing/patologia , Análise Serial de Tecidos
7.
Cir Cir ; 85(6): 504-509, 2017.
Artigo em Espanhol | MEDLINE | ID: mdl-28069112

RESUMO

BACKGROUND: Gastric cancer in Mexico is ranked third in both males and females. Most patients present clinically with advanced disease and treatment options are sparse. HER2 overexpression in gastric cancer is related to poor outcome. Immunohistochemical testing for HER2 is becoming the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab. OBJECTIVES: To determine the frequency of HER2 overexpression in patients with gastric cancer in the Hospital de Oncología del Centro Médico Nacional, Siglo XXI and its association with other histopathological findings. MATERIAL AND METHODS: Patients with gastric cancer who underwent surgery between March 12, 2006-August 31, 2011, were enrolled in this retrospective study. Diagnosis was confirmed by review of slides and immunohistochemistry with anti-HER2 antibody was performed. Scoring was done by Hoffman scoring system. Medical records were evaluated. RESULTS: Ninety-three patients were included in the study, with 43 (46.2%) male and 50 (53.7%) female patients. The median age was 64 years. HER2-positive tumours were identified in 6 patients (6.45%) and located most frequently in the proximal stomach. There was no difference in HER2 overexpression in relation to age, gender or histologic type. CONCLUSION: In our study, about 7% of patients with gastric cancer were HER2-positive on immunohistochemistry.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Proteínas de Neoplasias/análise , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Adenocarcinoma/patologia , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Diferenciação Celular , Estudos Transversais , Feminino , Gastrectomia , Humanos , Técnicas Imunoenzimáticas , Masculino , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Receptor ErbB-2/imunologia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Análise Serial de Tecidos
8.
J Proteomics ; 154: 59-68, 2017 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-27986506

RESUMO

Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is referred to as the resection margin. Our analysis employed an 8-plex iTRAQ to label four adenocarcinoma biopsies and their corresponding resection margins at 5cm; our results disclose fifty-six proteins as being differentially abundant. These proteins are mainly involved in energetic metabolism (e.g. S100 calcium binding protein A11), cell migration (e.g. transgelin), formation of the cytoskeleton (e.g. profilin 1) and degradation of extracellular matrix (e.g. carbonic anhydrase 2). A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell. Taken together, our results highlight proteins related to invasion, cell proliferation, and linked to the metastasis of colorectal cancer in tumor tissue. Finally, we argue that the expression patterns revealed in our comparison helps shed light on the development of more effective surgical strategies and add to the comprehension of this disease. BIOLOGICAL SIGNIFICANCE: Colorectal cancer (CRC) is the third most common type of cancer in the world with a low survival rate and therapeutic efficiency. Tumor surgery implies the removal of an apparently non-tumorous tissue around the tumor in an attempt to reduce recurrence chances; this tissue is also referred to as the resection margin. In this regard, resection margins pose as a treasure trove for investigating the molecular characteristics of the tumorigenesis process. While most studies focus on comparing cancer versus control tissue, this study contrasts the proteomic profiles of colorectal cancer biopsies with their corresponding resection margin at 5cm apart. Our analysis employed an 8-plex iTRAQ labeling and a 4-step offline MudPIT online with a Velos. A gene ontology enrichment analysis revealed several proteins related to adhesion, invasion, metastasis, death, and recognition cell.


Assuntos
Neoplasias Colorretais/patologia , Margens de Excisão , Proteínas de Neoplasias/análise , Idoso , Biópsia , Brasil , Adesão Celular , Neoplasias Colorretais/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteômica/métodos
9.
Bull Cancer ; 103(4): 368-80, 2016 Apr.
Artigo em Francês | MEDLINE | ID: mdl-26920041

RESUMO

Immunotherapy targeting the PD-L1/PD-1 axis has shown recently some promising results in metastatic lung cancer patients. This treatment seems to be more effective when a high expression of PD-L1 is detected by immunohistochemistry in bronchial biopsies. In this regard, this targeted therapy will be proposed soon in metastatic lung cancer patients. This immunotherapy could be dependent to the immunohistochemical (IHC) assessment of PD-L1 expression, thus considered as a companion diagnostic test. This near perspective poses challenges with regard to the positivity threshold value for PD-L1 expression before therapy administration, the positive cellular compartment (tumour cells and/or immune cells), the percentage of positive cells and the clone which is used. A couple of patients have a good response to treatment targeting the PD-1/PD-L1 axis despite the absence or a weak PD-L1 expression. However the assessment of PD-L1 expression by immunohistochemistry will be the only mandatory approach before therapeutic strategies targeting the PD1/PD-L1 axis for lung cancer patients. In this review, the main challenges of using PD-L1 immunohistochemistry as a potential companion diagnostic tool for metastatic lung cancer patient immunotherapy will be discussed.


Assuntos
Antígenos de Neoplasias/análise , Antígeno B7-H1/análise , Carcinoma Pulmonar de Células não Pequenas/química , Neoplasias Pulmonares/química , Pulmão/química , Antígeno B7-H1/antagonistas & inibidores , Biópsia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Imuno-Histoquímica , Imunoterapia , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/antagonistas & inibidores
10.
Biomed Khim ; 61(4): 462-7, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26350736

RESUMO

The nanowire (NW) detection is one of fast-acting and high-sensitive methods allowing to reveal potentially relevant protein molecules. A NW biosensor based on the silicon-on-insulator (SOI)-structures was used for biospecific label-free detection of NFAT 1 (D-NFAT 1) oncomarker in real time. For this purpose, SOI-nanowires (NWs) were modified with aptamers against NFAT 1 used as molecular probes. It was shown that using this biosensor it is possible to reach the sensitivity of ~10(-15) M. This sensitivity was comparable with that of the NW biosensor with immobilized antibodies used as macromolecular probes. The results demonstrate promising approaches used to form the sensor elements for high-sensitive disease diagnostics.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/instrumentação , Fatores de Transcrição NFATC/análise , Nanofios/química , Proteínas de Neoplasias/análise , Anticorpos Monoclonais/química , Aptâmeros de Nucleotídeos/síntese química , Técnicas Biossensoriais/economia , Técnicas Eletroquímicas , Humanos , Limite de Detecção , Dióxido de Silício/química , Soluções , Succinimidas/química
12.
Diagn Cytopathol ; 43(10): 802-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26223029

RESUMO

BACKGROUND: The objective of this study was to investigate the performance of the Fournier(®) self-sampled device in the cytological diagnosis of cervical precursor or neoplastic lesions. The colposcopy and cervical biopsy were used as the gold standard evaluation. METHOD: This was a case-control study performed at a cervical pathology outpatient clinic from January 2008 to October 2009. Samples were obtained through physician-collected mode before a colposcopic evaluation. Liquid-based cytology slides obtained with the device in question were stained using the Papanicolaou method and anti-p16 immunocytochemistry and were analyzed by two pathologists blind to the histological and colposcopic diagnoses. RESULTS: Diagnostic performance for Fournier device using Papanicolaou technique was sensitivity 41.1% (Pathologist 1-P1) and 52.9% (Pathologist 2-P2) for diagnosing low-grade intraepithelial lesions; for high-grade lesions and cervical cancer, sensitivity was 68.7% (P1) and 75.0% (P2) and specificity was 81.8% (P1) and 73.8% (P2). When using the anti-p16 immunocytochemistry, the sensitivity for diagnosing low-grade intraepithelial lesions was 57.1% (P1) and 62.9% (P2), and the sensitivity was 87.5% (P1) and 93.8% (P2) for high-grade lesions and cancer. The specificity was 75.0% (P1) and 54.4% (P2). CONCLUSIONS: These results show that when used with "blind" physician-collected cytology in an outpatient setting, the Fournier(®) device achieved a sensitivity and specificity comparable to those obtained by the Pap test traditionally collected during a speculum examination.


Assuntos
Biópsia/instrumentação , Colo do Útero/patologia , Colposcopia/instrumentação , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Instituições de Assistência Ambulatorial , Biópsia/métodos , Estudos de Casos e Controles , Colo do Útero/citologia , Colposcopia/métodos , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Humanos , Programas de Rastreamento/métodos , Proteínas de Neoplasias/análise , Teste de Papanicolaou/métodos , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/métodos , Displasia do Colo do Útero/patologia
13.
G Ital Dermatol Venereol ; 150(3): 283-91, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25946671

RESUMO

AIM: Endothelin-1 is an autocrine growth factor for keratinocytes, an effect controlled by its A and B receptors, with no previous comparison of endothelin axis expression in inflammatory and neoplastic skin diseases showing keratinocyte proliferation. The aim of the study was to investigate endothelin-1 axis expression in skin lesions of psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). METHODS: This study included 40 subjects (8 patients with SCC, 12 patients with BCC, 10 patients with psoriasis, and 10 healthy controls). Biopsies from lesional skin of patients and normal skin of controls were examined immunohistochemically for endothelin-1 and its receptors A and B frequency and grade of expression. RESULTS: Endothelin-1 and receptor A were detected in all patients with SCC and psoriasis, with a higher frequency and grade of expression than controls and BCC. The frequency of receptor B expression was significantly lower while higher staining grade was found in BCC (8.3%) rather than other studied groups. CONCLUSION: A comparable higher frequency and grade of expression of endothelin-1 and its receptor A are documented in psoriasis and SCC than in BCC and controls denoting their involvement in keratinocyte proliferation in both diseases. Receptor A is the predominately expressed receptor in psoriasis and SCC.


Assuntos
Carcinoma de Células Escamosas/química , Endotelina-1/análise , Queratinócitos/metabolismo , Proteínas de Neoplasias/análise , Neoplasia de Células Basais/química , Psoríase/metabolismo , Receptor de Endotelina A/análise , Receptor de Endotelina B/análise , Neoplasias Cutâneas/química , Adolescente , Adulto , Idoso , Biópsia , Carcinoma de Células Escamosas/patologia , Endotelina-1/biossíntese , Endotelina-1/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasia de Células Basais/patologia , Psoríase/patologia , Receptor de Endotelina A/biossíntese , Receptor de Endotelina A/genética , Receptor de Endotelina B/biossíntese , Receptor de Endotelina B/genética , Estudos de Amostragem , Neoplasias Cutâneas/patologia , Adulto Jovem
14.
Biomed Res Int ; 2014: 860241, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25247190

RESUMO

Glioma of infiltrative nature is challenging for surgeons to achieve tumor-specific and maximal resection. Raman spectroscopy provides structural information on the targeted materials as vibrational shifts. We utilized Raman spectroscopy to distinguish invasive tumors from normal tissues. Spectra obtained from replication-competent avian sarcoma-(RCAS-) based infiltrative glioma cells and glioma tissues (resembling low-grade human glioma) were compared with those obtained from normal mouse astrocytes and normal tissues. In cell analysis, the spectra at 950-1000, 1030, 1050-1100, 1120-1130, 1120-1200, 1200-1300, 1300-1350, and 1450 cm(-1) were significantly higher in infiltrative glioma cells than in normal astrocytes. In brain tissue analysis, the spectra at 1030, 1050-1100, and 1200-1300 cm(-1) were significantly higher in infiltrative glioma tissues than in normal brain tissues. These spectra reflect the structures of proteins, lipids, and DNA content. The sensitivity and specificity to predict glioma cells by distinguishing normal cells were 98.3% and 75.0%, respectively. Principal component analysis elucidated the significance of spectral difference between tumor tissues and normal tissues. It is possible to distinguish invasive tumors from normal tissues by using Raman spectroscopy.


Assuntos
Astrócitos/química , Neoplasias Encefálicas/química , DNA/análise , Glioma/química , Lipídeos/análise , Proteínas de Neoplasias/análise , Análise Espectral Raman/métodos , Animais , Camundongos , Camundongos Endogâmicos ICR , Células Tumorais Cultivadas
15.
Anal Bioanal Chem ; 405(27): 8719-28, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23934397

RESUMO

Hyperspectral unmixing is an unsupervised algorithm to calculate a bilinear model of spectral endmembers and abundances of components from Raman images. Thirty-nine Raman images were collected from six glioma brain tumor specimens. The tumor grades ranged from astrocytoma WHO II to glioblastoma multiforme WHO IV. The abundance plots of the cell nuclei were processed by an image segmentation procedure to determine the average nuclei size, the number of nuclei, and the fraction of nuclei area. The latter two morphological parameters correlated with the malignancy. A combination of spectral unmixing and non-negativity constrained linear least squares fitting is introduced to assess chemical parameters. First, endmembers of the most abundant and most dissimilar components were defined that represent all data sets. Second, the content of the obtained components' proteins, nucleic acids, lipids, and lipid to protein ratios were determined in all Raman images. Except for the protein content, all chemical parameters correlated with the malignancy. We conclude that the morphological and chemical information offer new ways to develop Raman-based classification approaches that can complement diagnosis of brain tumors. The role of non-linear Raman modalities to speed-up image acquisition is discussed.


Assuntos
Algoritmos , Astrocitoma/diagnóstico , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Análise Espectral Raman , Astrocitoma/química , Astrocitoma/patologia , Neoplasias Encefálicas/química , Neoplasias Encefálicas/patologia , Núcleo Celular/ultraestrutura , Glioblastoma/química , Glioblastoma/patologia , Humanos , Processamento de Imagem Assistida por Computador , Análise dos Mínimos Quadrados , Lipídeos/análise , Gradação de Tumores , Proteínas de Neoplasias/análise , Ácidos Nucleicos/análise , Tamanho das Organelas
16.
Intern Med J ; 42(11): 1229-35, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21981464

RESUMO

BACKGROUND: Cardiotoxicity is a concern in patients on trastuzumab therapy, and cardiac function assessment is a recommended practice. In 2006, trastuzumab was publically subsidised for human epidermal growth factor receptor-2 early stage breast cancer with a requirement for cardiac testing prior to and during treatment. AIM: To investigate the spillover effects of this requirement on testing rates in metastatic patients treated with trastuzumab where no monitoring requirements are applied. METHODS: We examined cardiac testing (echocardiography or multiple-gated acquisition scan) in 3779 women with metastatic breast cancer receiving trastuzumab between December 2001 and February 2010 and used interrupted time-series analyses to estimate changes in testing rates. The main outcome measures were the proportion of eligible patients, by quarter, receiving a cardiac function test pretreatment and during trastuzumab therapy. RESULTS: Only 21% of women had a cardiac function test pretreatment, and 47% were tested at some point during the first year of trastuzumab therapy. The introduction of mandatory cardiac testing for early breast cancer was associated with an immediate 8% increase (95% confidence interval, 2-14%) in pretreatment cardiac testing and an immediate 7% increase (95% confidence interval, 4-10%) in testing during therapy in metastatic patients. Testing rates during therapy increased steadily from early 2005, coinciding with the release of interim results from several trastuzumab trials reporting cardiac-safety outcomes. CONCLUSION: The introduction of mandatory cardiac testing for early stage disease spilled over to the metastatic setting. While deviation from guidelines may be warranted in some cases, this study suggests underutilisation of cardiac testing among patients treated with trastuzumab in the metastatic setting.


Assuntos
Adenocarcinoma/secundário , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiomiopatias/induzido quimicamente , Testes de Função Cardíaca/estatística & dados numéricos , Seguro de Serviços Farmacêuticos/legislação & jurisprudência , Programas Nacionais de Saúde/legislação & jurisprudência , Adenocarcinoma/química , Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Austrália , Neoplasias da Mama/química , Institutos de Câncer/estatística & dados numéricos , Cardiomiopatias/diagnóstico , Cardiomiopatias/prevenção & controle , Quimioterapia Adjuvante , Monitoramento de Medicamentos/métodos , Ecocardiografia/estatística & dados numéricos , Feminino , Imagem do Acúmulo Cardíaco de Comporta/estatística & dados numéricos , Fidelidade a Diretrizes , Humanos , Terapia de Alvo Molecular/efeitos adversos , Proteínas de Neoplasias/análise , Receptor ErbB-2/análise , Trastuzumab
17.
Pancreas ; 41(2): 169-74, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22076567

RESUMO

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas evolve from dysplasia to invasive adenocarcinoma. The aims of this study were to look for candidate protein profiles in IPMN mucus according to histological grade, using a differential proteomic technique, and to highlight protein peaks associated with malignant transformation. METHODS: Forty-three mucus samples obtained from surgically resected IPMN and categorized as benign (low/moderate dysplasia) or malignant (severe dysplasia/invasive adenocarcinoma) in 21 and 22 patients, respectively. A surface-enhanced laser desorption ionization time-of-flight mass spectrometry was used to determine candidate protein expression profiles. Protein peaks that significantly differed between benign/malignant IPMN (area under curve > 0.88; P < 10; high intensity) were identified using adapted software. RESULTS: Among 952 protein peaks, 31 were differentially expressed in benign/malignant IPMN (P < 0.001). Among them, 5 candidate proteins of interest (mass-to-charge ratio [m/z]: 5217, 6326, 6719, 10,453, and 10,849 d) were selected by their high diagnostic accuracy and ability to distinguish between malignant and benign tumors. No correlation was found between peak profiles and duct involvement. CONCLUSIONS: Carcinogenic process in IPMN is associated with changes in mucus proteome with characteristic peaks that could be potential candidate biomarkers of malignancy. ABBREVIATIONS: IPMN - intraductal papillary mucinous neoplasm, EPC - extrapancreatic cancer, MRI - magnetic resonance imaging, ERCP - endoscopic retrograde cholangiopancreatography.


Assuntos
Adenocarcinoma Mucinoso/química , Adenocarcinoma Papilar/química , Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/química , Muco/química , Proteínas de Neoplasias/análise , Neoplasias Pancreáticas/química , Proteômica , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Papilar/patologia , Adenocarcinoma Papilar/cirurgia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Detecção Precoce de Câncer , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Prognóstico , Análise Serial de Proteínas , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
18.
PLoS One ; 6(9): e24632, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21935432

RESUMO

PURPOSE: To assess the prognostic value of FDG PET/CT compared to the tumor markers S100B and melanoma inhibitory activity (MIA) in patients with high risk melanoma. METHODS: Retrospective study in 125 consecutive patients with high risk melanoma that underwent FDG PET/CT for re-staging. Diagnostic accuracy and prognostic value was determined for FDG PET/CT as well as for S100B and MIA. As standard of reference, cytological, histological, PET/CT or MRI follow-up findings as well as clinical follow-up were used. RESULTS: Of 125 patients, FDG PET/CT was positive in 62 patients. 37 (29.6%) patients had elevated S100B (>100 pg/ml) and 24 (20.2%) had elevated MIA (>10 pg/ml) values. Overall specificities for FDG PET/CT, S100B and MIA were 96.8% (95% CI, 89.1% to 99.1%), 85.7% (75.0% to 92.3%), and 95.2% (86.9% to 98.4%), corresponding sensitivities were 96.8% (89.0% to 99.1%), 45.2% (33.4% to 55.5%), and 36.1% (25.2% to 48.6%), respectively. The negative predictive values (NPV) for PET/CT, S100B, and MIA were 96.8% (89.1% to 99.1%), 61.4% (50.9% to 70.9%), and 60.6% (50.8% to 69.7%). The positive predictive values (PPV) were 96.7% (89.0% to 99.1%), 75.7% (59.9% to 86.6%), and 88.0% (70.0% to 95.8%). Patients with elevated S100B- or MIA values or PET/CT positive findings showed a significantly (p<0.001 each, univariate Cox regression models) higher risk of melanoma associated death which was increased 4.2-, 6.5- or 17.2-fold, respectively. CONCLUSION: PET/CT has a higher prognostic power in the assessment of cancer-associated mortality in melanoma patients compared with S100 and MIA.


Assuntos
Proteínas da Matriz Extracelular/análise , Fluordesoxiglucose F18 , Melanoma/metabolismo , Melanoma/mortalidade , Proteínas de Neoplasias/análise , Tomografia por Emissão de Pósitrons/métodos , Proteínas S100/análise , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
Anticancer Res ; 31(7): 2553-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21873174

RESUMO

BACKGROUND: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a rational target for ovarian cancer therapy. The aim of this study was to examine HB-EGF levels in the peritoneal fluid and serum of ovarian cancer (OVCA) patients. PATIENTS AND METHODS: Samples were collected from six healthy women, 21 OVCA patients, and 21 ovarian cyst patients. HB-EGF levels were measured using a sandwich ELISA kit and calculated using a parallel line assay. RESULTS: No significant difference between the slopes of the standard and sample curves was observed at an anti-HB-EGF antibody concentration of 1.6 µg/ml. HB-EGF levels in the peritoneal fluid and serum of OVCA patients were significantly higher than those in patients with ovarian cysts or controls. Serum HB-EGF levels were also significantly correlated with levels in peritoneal fluid in OVCA patients. CONCLUSION: We developed an assay for the exact measurement of HB-EGF levels in peritoneal fluid and serum.


Assuntos
Líquido Ascítico/química , Ensaio de Imunoadsorção Enzimática , Peptídeos e Proteínas de Sinalização Intercelular/análise , Proteínas de Neoplasias/análise , Neoplasias Ovarianas/metabolismo , Adulto , Idoso , Anticorpos/imunologia , Afinidade de Anticorpos , Especificidade de Anticorpos , Artefatos , Ligação Competitiva , Biomarcadores Tumorais , Feminino , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/imunologia , Cistos Ovarianos/sangue , Cistos Ovarianos/metabolismo , Neoplasias Ovarianas/sangue , Ligação Proteica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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