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1.
Biochim Biophys Acta ; 1794(1): 61-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18952200

RESUMO

To identify proteins involved in melanoma metastasis mechanisms, comparative proteomic studies were undertaken on B16F10 and B16Bl6 melanoma cell lines and their subsequent syngenic primary tumours as pulmonary metastases were present only in the mice bearing a B16Bl6 tumour. 2DE analyses followed by MALDI-TOF identification showed variations of 6 proteins in vitro and 13 proteins in vivo. Differential expressed proteins in tumours were related to energy production and storage. Two differentially expressed proteins which had not been previously associated to melanoma progression, annexin A1 (ANXA1) and creatine kinase B (CKB), were found both in cells and in tumours. To characterize ANXA1 involvement in melanoma B16 dissemination, we reduced ANXA1 protein level by siRNA and observed a significant decrease of B16Bl6 cell invasion through Matrigel coated chambers. We further demonstrated that the presence of several formyl peptide receptors (FPR1, FPRrs1 and 2) revealed by qRT-PCR, played a role in B16 invasion: incubation of B16Bl6 cells with the FPR agonist (fMLP) or antagonist (tBOC) enhanced or decreased Matrigel coated chamber invasion respectively, with a correlation of ANXA1 levels in both treatments. As ANXA1 could bind to FPRs, this should amplify invasion and enhance melanoma dissemination.


Assuntos
Anexina A1/metabolismo , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Proteômica , Animais , Sequência de Bases , Linhagem Celular Tumoral , Creatina Quinase/metabolismo , Eletroforese em Gel Bidimensional , Camundongos , Metástase Neoplásica , Receptores de Formil Peptídeo/genética , Receptores de Formil Peptídeo/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Células Tumorais Cultivadas
2.
Int J Cancer ; 125(3): 708-16, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19437532

RESUMO

In recent years, there has been dramatic worldwide increase in incidence of malignant melanoma. Although localised disease is often curable by surgical excision, metastatic melanoma is inherently resistant to most treatments. In this context, targeted radionuclide therapy could be an efficient alternative. After pharmacomodulation study, we selected a quinoxaline derivative molecule (ICF01012) for its high, specific and long-lasting uptake in melanoma with rapid clearance from nontarget organs providing suitable dosimetry parameters for targeted radiotherapy. Aim of this study was to investigate, in vivo, efficacy of [(131)I]ICF01012 on nonmetastatic B16F0, metastatic B16Bl6 or human M4Beu melanoma tumours. First, colocalisation of ICF01012 with melanin by SIMS imaging was observed. Second, we showed that treatment drastically inhibited growth of B16F0, B16Bl6 and M4beu tumours whereas [(131)I]NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis and measure of PCNA proliferation marker expression showed that residual B16 tumour cells exhibit a significant loss of aggressiveness after treatment. This effect is associated with a lengthening of the treated-mice survival time. Moreover, with B16Bl6 model, 55% of the untreated mice had lung metastases whereas no metastasis was counted on treated group. Our data demonstrated a strong anti-tumoural effect of [(131)I]ICF01012 for radionuclide therapy on murine and human in vivo pigmented melanoma models, whatever their dissemination profiles and their melanin content be. Further studies will attempt to optimise therapy protocol by increasing the balance between the anti-tumoural effect and the safety on non-target organs.


Assuntos
Antineoplásicos/farmacologia , Radioisótopos do Iodo , Melanoma Experimental/diagnóstico por imagem , Melanoma Experimental/terapia , Quinoxalinas/farmacologia , Animais , Antineoplásicos/uso terapêutico , Western Blotting , Linhagem Celular Tumoral , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/secundário , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Antígeno Nuclear de Célula em Proliferação/sangue , Quinoxalinas/uso terapêutico , Cintilografia , Compostos Radiofarmacêuticos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrometria de Massa de Íon Secundário
3.
Am Heart J ; 157(3): 583.e1-7, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19249433

RESUMO

BACKGROUND: Thrombus aspiration devices have been shown to improve reperfusion criteria and to reduce distal embolization in patients treated by percutaneous coronary interventions (PCI) in the acute phase of ST-elevation myocardial infarction (STEMI). There are, however, little data about their efficacy in the reduction of infarct size. METHODS: We sought to assess in a prospective randomized trial the impact of thrombus aspiration on infarct size and severity and on left ventricular function in high-risk patients with a first STEMI. The primary end point was scintigraphic infarct size, and secondary end points were infarct severity and regional and global left ventricular function. Forty-four patients with completely occluded (Thrombolysis in Myocardial Infarction flow 0-1) proximal segments of infarct-related artery were randomly assigned to thrombus aspiration group with the Export catheter (n = 20) (Medtronic, Inc, Minneapolis, MN) or PCI-only group. A rest Tc-99-mibi gated single-photon emission computed tomographic and contrast-enhanced magnetic resonance imaging were performed 6 +/- 2 days later. RESULTS: Infarct size was comparable in patients in the thrombus aspiration group and PCI-only group (30.6% +/- 15.8% vs 28.5% +/- 17.9% of the left ventricle, P = .7) as was infarct severity in infarct-related artery territory (55% +/- 12% vs 55% +/- 14%, P = .9). Transmurality score as assessed by magnetic resonance imaging was similar in both groups (2.03 +/- 1.05 vs 2.16 +/- 1.21, P = .7). There was no impact of thrombus aspiration on other secondary end points. CONCLUSION: In our study, thrombus aspiration with the Export catheter performed as adjunctive therapy in high-risk patients with total occlusion of the proximal part of major coronary arteries does not decrease infarct size or severity and has no effect on left ventricular regional and global function.


Assuntos
Angioplastia Coronária com Balão , Trombose Coronária/cirurgia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Trombectomia , Idoso , Angiografia Coronária , Oclusão Coronária/fisiopatologia , Eletrocardiografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Projetos Piloto , Estudos Prospectivos , Tomografia Computadorizada de Emissão de Fóton Único , Função Ventricular Esquerda
4.
J Nucl Med ; 50(9): 1541-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19690026

RESUMO

UNLABELLED: This study on a rat model of grade II chondrosarcoma aimed to determine whether the radiotracer N-(triethylammonium)-3-propyl-[15]ane-N5 radiolabeled with (99m)Tc ((99m)Tc-NTP 15-5), which binds to cartilage proteoglycans, has pathophysiologic validity for in vivo imaging of cartilage tumoral tissue. METHODS: We used 2 experimental approaches with the Swarm chondrosarcoma rat model: that is, a primary paratibial location and local recurrence after intralesional curettage. (99m)Tc-NTP 15-5 scintigraphy and (99m)Tc-hydroxymethylenediphosphonate ((99m)Tc-HMDP) scanning were performed at regular intervals during 50 d after tumor implantation in a paratibial location (primary model; n = 12 animals) and after intralesional curettage in a femoral condyle location (recurrence model; n = 9 animals). For each animal, positive scans were analyzed at each time point using the target-to-background ratio (TBR), with the target region of interest delineated over the tumor and the background region of interest over muscle. In each model, the TBR time course was followed against primary tumoral growth or recurrence. Tumor volume was monitored for 2 mo by measuring the 2 perpendicular diameters. At study end, animals were sacrificed for histopathologic analysis. RESULTS: For both models, (99m)Tc-NTP 15-5 scans showed tracer accumulation at the site of implantation or curettage. For the primary tumor model, the mean TBR was 1.6 +/- 0.14 by day 4 after implantation and increased over time as the disease progressed, with a mean TBR of 4.25 +/- 0.25 on day 45. For the recurrence model, mean TBR was 3.27 +/- 0.24 by day 4 after curettage and increased with recurrence, with a mean value of 5.25 +/- 0.49 on day 50. (99m)Tc-HMDP bone scans were negative for both models throughout the study; at a later stage of the study, an area of (99m)Tc-HMDP accumulation was seen in the diaphysis of the bone adjacent to the tumor and was attributed to remodeling. CONCLUSION: These experimental results in 2 preclinical models of grade II chondrosarcoma bring forward data in favor of (99m)Tc-NTP 15-5 radiotracer for imaging primary growth of chondrosarcoma and its local recurrence after surgery.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Condrossarcoma/diagnóstico por imagem , Compostos Heterocíclicos com 1 Anel , Recidiva Local de Neoplasia/diagnóstico por imagem , Compostos de Amônio Quaternário , Compostos de Tecnécio , Animais , Avaliação Pré-Clínica de Medicamentos , Masculino , Cintilografia , Compostos Radiofarmacêuticos , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
J Nucl Cardiol ; 16(4): 597-604, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19479315

RESUMO

BACKGROUND: Left ventricular (LV) remodeling after myocardial infarction (MI) occurs frequently despite successful percutaneaous coronary intervention (PCI) but cannot be predicted by simple clinical parameters. METHODS AND RESULTS: This prospective study tested the value of rest and low-dose dobutamine (LDD) Tc-99m-mibi gated-SPECT for early prediction of LV remodeling in patients treated by PCI in the acute phase of a first MI. Infarct size, infarct severity, regional wall motion abnormality (RWMA), and wall thickening score (WTs) were assessed at rest and on LDD by SPECT 6 +/- 2 days after MI in 40 patients. LV remodeling was defined as 20% increase at 6 months in LV end-diastolic volume assessed by MRI. Infarct severity at rest showed the best predictive values for left remodeling (PPV: 86%, NPV: 88%, accuracy: 88%; AUC: 0.750). Functional parameters at neither rest nor LDD study further improved predictive values of the SPECT imaging. CONCLUSIONS: Infarct severity assessed by Tc-99m-sestamibi gated-SPECT performed in the subacute phase of a first STEMI predicts LV remodeling with high accuracy without incremental value nor of functional parameters nor of LDD. Therefore, our results suggest that LDD should not be used in this setting.


Assuntos
Infarto do Miocárdio/diagnóstico por imagem , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Remodelação Ventricular , Idoso , Dobutamina/metabolismo , Eletrocardiografia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Reperfusão , Reprodutibilidade dos Testes , Fatores de Tempo
6.
J Med Chem ; 51(11): 3133-44, 2008 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-18481842

RESUMO

Targeted radionuclide therapy using radioiodinated compounds with a specific affinity for melanoma tissue is a promising treatment for disseminated melanoma, but the candidate with the ideal kinetic profile remains to be discovered. Targeted radionuclide therapy concentrates the effects on tumor cells, thereby increasing the efficacy and decreasing the morbidity of radiotherapy. In this context, analogues of N-(2-diethylaminoethyl)-4-iodobenzamide (BZA) are of interest. Various (hetero)aromatic analogues 5 of BZA were synthesized and radioiodinated with (125)I, and their biodistribution in melanoma-bearing mice was studied after i.v. administration. Most [ (125)I] 5-labeled compounds appeared to bind specifically and with moderate-to-high affinity to melanoma tumor. Two compounds, 5h and 5k, stood out with high specific and long-lasting uptake in the tumor, with a 7- and 16-fold higher value than BZA at 72 h, respectively, and kinetic profiles that makes them promising agents for internal targeted radionuclide therapy of melanoma.


Assuntos
Benzamidas/síntese química , Melanoma Experimental/diagnóstico por imagem , Quinolinas/síntese química , Quinoxalinas/síntese química , Compostos Radiofarmacêuticos/síntese química , Animais , Benzamidas/química , Benzamidas/farmacocinética , Radioisótopos do Iodo , Masculino , Melaninas/química , Melanoma Experimental/metabolismo , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Quinolinas/química , Quinolinas/farmacocinética , Quinoxalinas/química , Quinoxalinas/farmacocinética , Cintilografia , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Relação Estrutura-Atividade , Distribuição Tecidual
7.
Bioorg Med Chem ; 16(16): 7671-90, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18656367

RESUMO

Various iodo-acridone and acridine carboxamides have been prepared and evaluated as agents for targeted radionuclide and/or chemotherapy for melanoma, due to their structural similarity to benzamides which are known to possess specific affinity for melanin. Three of these carboxamides selected for their in vitro cytotoxic properties were radioiodinated with [(125)I]NaI at high specific activity. Biodistribution studies carried out in B16F0 murine melanoma tumour-bearing mice highlighted that acridone 8f and acridine 9d, presented high, long-lasting tumour concentrations together with an in vivo kinetic profile favourable to application in targeted radionuclide therapy.


Assuntos
Acridinas/síntese química , Antineoplásicos/síntese química , Radioisótopos do Iodo/administração & dosagem , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/radioterapia , Compostos Radiofarmacêuticos/síntese química , Acridinas/química , Acridinas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Desenho de Fármacos , Humanos , Concentração Inibidora 50 , Células Jurkat , Espectroscopia de Ressonância Magnética , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Cintilografia , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Distribuição Tecidual
8.
Chemotherapy ; 54(5): 336-42, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18714154

RESUMO

BACKGROUND: Cancer patients can be exposed to drug interactions during treatment with toxic anticancer drugs. The peripheral nervous system is a target for neurotoxic anticancer drugs. P-glycoprotein is essential for the functional integrity of blood-tissue barriers, and P-glycoprotein inhibition due to possible drug interactions could lead to adverse neurotoxic reactions. METHODS: In a rat model of vincristine-induced neuropathy, we assessed the consequences of potential drug interactions of vincristine with some P-glycoprotein-inhibiting drugs, chosen because of their potency to increase the incorporation of (99m)Tc-sestamibi in nervous tissue. RESULTS: Quinidine (30 mg/kg) increased (99m)Tc-sestamibi incorporation in dorsal root ganglia (DRG) but was toxic for rats. Verapamil (30 mg/kg) increased the tracer incorporation in the spinal cord, DRG and sciatic nerve. Combination treatment with the verapamil-vincristine regimen had a tendency to lower weight gain and altered nociceptive thresholds of neuropathic animals. CONCLUSION: Behavioral pain tests did not reveal an increase in vincristine neurotoxicity following combination treatment with verapamil and vincristine. This regimen only led to a slight increase in general toxicity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Doenças do Sistema Nervoso/induzido quimicamente , Vincristina/efeitos adversos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Interações Medicamentosas , Masculino , Ratos , Ratos Sprague-Dawley , Verapamil/efeitos adversos
9.
Eur J Pharmacol ; 544(1-3): 49-57, 2006 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-16859677

RESUMO

It has recently been suggested that P-glycoprotein is involved in the genesis and the treatment of the neurotoxic adverse events of anticancer drugs, including vincristine. A lower activity of P-glycoprotein in the peripheral nervous system (PNS) than in the central nervous system could contribute to the neurotoxicity of vincristine. Vincristine treatment is responsible for the induction of multidrug resistance (MDR) gene expression and transporter activity, with deleterious consequences, including a potential decrease in the efficiency of opioid analgesics, antidepressants or antiepileptics. Concerning cisplatin, which is also a strong neurotoxic drug but only an multidrug resistance protein 2 (MRP2) substrate, the same assumption could be suggested for MRP2 nervous function. The aim of this study was to assess MDR gene and protein activity in a rat model of cisplatin-induced neuropathy compared with different peripheral nerve injury models, i.e. mononeuropathy and inflammatory pain (monoarthritis). First, in cisplatin-induced neuropathy, this study demonstrated low MRP2 gene expression in dorsal root ganglia compared with the brain and spinal cord, which could contribute to the strong neurotoxicity of cisplatin in the PNS and particularly the dorsal root ganglia. Thus, gene expression increased in cisplatin-induced neuropathy but decreased in mononeuropathy and remained unchanged in monoarthritis models. Transporter activity of nervous tissues increased in the cisplatin-induced neuropathy, mononeuropathy and monoarthritis to different intensities (3.7-, 1.8- and 1.8-fold, respectively). The development of a MDR in the cisplatin-induced neuropathy is a striking difference with mononeuropathy and monoarthritis models, and characterizes the neuropathies induced by this anticancer drug.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Transportadores de Cassetes de Ligação de ATP/fisiologia , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Animais , Artrite/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Sistema Nervoso Central , Modelos Animais de Doenças , Resistência a Múltiplos Medicamentos , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Doenças do Sistema Nervoso/patologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacos , Vincristina/farmacologia
10.
J Nucl Med ; 44(10): 1625-32, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14530477

RESUMO

UNLABELLED: This study validates a new quantitative myocardial perfusion SPECT software. METHODS: The processing starts with the extraction of the morphologic skeleton of the left ventricular myocardium from reconstructed transverse sections. Fuzzy logic is used to decide whether a pixel belongs to the myocardium and any perfusion defect is filled according to a truncated bullet model. The resulting image is partitioned in 18 isovolumetric sectors. Sex-matched normal limits, criteria of abnormality for rest (201)Tl and (99m)Tc-labeled perfusion tracers, reproducibility studies, and detection of coronary artery disease were developed and validated in an overall population of 343 patients. The sex- and tracer-matched means and SDs of a normal response were calculated in 93 male and 93 female patients with a <5% likelihood of coronary artery disease. Reproducibility measurements and assignment of different sectors of the myocardium to a specific coronary were performed from data collected in 49 and 60 patients, respectively. The accuracy of the detection of a coronary artery occlusion was assessed in 48 patients who also underwent coronary angiography. RESULTS: The intra- and interoperator reproducibility of the sectorial activity was high with a linear regression coefficient of 0.97 and a SD of the difference measurement at 4.4% and 3.8%, respectively. Overall sensitivity and specificity for the detection of occluded coronary artery were 90% and 80%, respectively. For the detection of left anterior descending, left circumflex, and right artery coronary occlusion, sensitivity was 92%, 75%, and 92.5%, respectively, and specificity was 75%, 78%, and 90%, respectively. CONCLUSION: The new quantitative myocardial perfusion SPECT software appears to be a very helpful program for the objective analysis of perfusion tracer distribution in myocardial SPECT and a very accurate tool in the detection and localization of coronary artery occlusion.


Assuntos
Algoritmos , Doença da Artéria Coronariana/diagnóstico por imagem , Lógica Fuzzy , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Doença da Artéria Coronariana/complicações , Estudos de Viabilidade , Feminino , Humanos , Masculino , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Software , Interface Usuário-Computador , Disfunção Ventricular Esquerda/etiologia
11.
Int J Oncol ; 20(5): 1049-55, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11956603

RESUMO

We examined the relevance of a pre-treatment single static view 99mTc-sestamibi scintimammography and expression of multidrug resistance proteins as predictors of response to neoadjuvant chemotherapy for invasive breast cancer. Forty-five patients affected by primary breast cancer underwent clinical examination, mammography, sonography, 99mTc-sestamibi scintimammography, and biopsy for histopathological diagnosis before neoadjuvant chemotherapy. Expression of MDR1 and MRP mRNA were determined by RT-PCR on fine-needle aspirations. Following completion of anthracycline-based chemotherapy, clinical, mammographic, sonographic and pathological responses were determined. 99mTc-sestamibi scintimammography predicted the reduction of tumor size measured by sonography and the pathological response according to Sataloff classification (p<0.05) and tend to predict pathological response according to Chevallier (p<0.1). A negative 99mTc-sestamibi scintimammography predicted chemoresistance with a specificity of 100%. Uptake of 99mTc-sestamibi was inversely correlated to the expression of MDR1 (p<0.05) in invasive ductal carcinoma. A pre-treatment single-view 99mTc-sestamibi scintimammography is an excellent predictor of MDR1 chemoresistance and was highly specific of a lack of pathological response to chemotherapy.


Assuntos
Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante , Mamografia/métodos , Glicoproteínas de Membrana , Tecnécio Tc 99m Sestamibi/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Adulto , Idoso , Antígenos CD/biossíntese , Neoplasias da Mama/mortalidade , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Fenótipo , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Tetraspanina 29
12.
Bull Cancer ; 89(7-8): 671-80, 2002.
Artigo em Francês | MEDLINE | ID: mdl-12206980

RESUMO

The isotopic detection of the sentinel node is undergoing a fast development in breast cancer and melanoma. It requires a good collaboration between a surgeon and a nuclear medicine specialist. Although the method is now well defined for melanoma, several options remain possible for breast cancer. The injected dose and volume can differ between centers, as well as the sites of injection in terms of their number, anatomical location and depth. However, since all options seem to provide equivalent results, a single intradermal periareolar injection could be the preferred choice. The role of imaging remains controversial, but it provides a definite complementary information, in particular in case of an unusual location of the sentinel node. The addition of dye injection also adds to the results. The optimal use of a peroperative hand-held gamma probe requires some training for the surgeon. A good selection of the indications is essential for a successful detection. Other fields of application are under investigation such as colon cancer, head and neck tumors, lung and prostate cancers. By avoiding a majority of the routine axillary lymph nodes dissections in small breast cancer, the isotopic detection of the sentinel node should dramatically decrease the morbidity of axillary staging and the duration of hospital stay for the patients.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Melanoma/secundário , Neoplasias Cutâneas/diagnóstico por imagem , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Doses de Radiação , Radioisótopos/administração & dosagem , Cintilografia , Biópsia de Linfonodo Sentinela , Coloração e Rotulagem
14.
J Proteome Res ; 8(5): 2594-600, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19323466

RESUMO

This study assessed the 1H HRMAS NMR spectroscopic profile of articular cartilage in both physiological and osteoarthitic situations. One-dimensional and two-dimensional 1H HRMAS NMR spectra were obtained from the tibial plateau cartilage of healthy and operated (unilateral medial meniscectomy and sham surgery) guinea pigs at different stages of disease, over a 6-month period. The major osteoarthritis-induced 1H HRMAS NMR changes were an increase of the N-acetyl peak of proteoglycans (at day 20 after meniscectomy) and a decrease after day 60 as the pathology evolved. These proteoglycan changes revealed by 1H HRMAS NMR analysis were validated by proteoglycan biochemistry assays. 1H HRMAS NMR analysis also evidenced a sharp increase in methylene resonances of chondrocyte membrane lipids from day 90 as a marker of apoptosis. There was an increase of the mobile methyl group of collagen at day 120, which was associated with collagen breakdown. 1H HRMAS NMR analysis provided a multifactorial and sequential picture of cartilage degradation at the extracellular matrix and chondrocyte levels.


Assuntos
Cartilagem Articular/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Metaboloma , Osteoartrite/metabolismo , Aminoácidos/análise , Animais , Cartilagem Articular/patologia , Condrócitos/metabolismo , Condrócitos/patologia , Modelos Animais de Doenças , Cobaias , Lipídeos/análise , Masculino , Meniscos Tibiais/cirurgia , Metabolômica/métodos , Osteoartrite/cirurgia , Proteoglicanas/análise , Fatores de Tempo
15.
Neurosci Lett ; 465(1): 108-12, 2009 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-19733628

RESUMO

Pain from anticancer drugs-induced neuropathies is difficult to treat and can significantly alter the patient's quality of life. These neuropathies are considered relatively resistant to conventional analgesic drugs (opioids). Opioids are also P-glycoprotein substrates and it has been demonstrated that the P-glycoprotein is linked to the integrity of blood-brain barrier protecting the nervous system. Previous works presented an increase of P-glycoprotein in vincristine- and cisplatin-induced neuropathy which could potentially decrease opioid efficiency. To test this hypothesis, the efflux inhibition of P-glycoprotein and the antinociceptive effect of morphine were assessed in normal and cisplatin-induced neuropathic rats after the administration of the P-glycoprotein inhibitor (R101933). R101933 (20 mg/kg) inhibited significantly the efflux transporter under the condition of the study and had no analgesic effect. Nociceptive thresholds were measured by the paw pressure test. R101933 (20 mg/kg) enhanced antinociceptive activity of morphine (0.5 mg/kg) to a maximum of +58% and +35%, respectively compared with control animals and animals treated by morphine alone (0.5 mg/kg). R101933 increased morphine (2 mg/kg) antinociceptive activity to a maximum of +105% compared with control animals and to a maximum of +41% compared with morphine alone (2 mg/kg). This study demonstrated that cisplatin-induced neuropathy may present a particular pathophysiology with a multidrug resistance, of the central nervous system, to analgesics. This resistance can be blocked by a P-glycoprotein inhibitor which may enhance analgesia of low doses of morphine.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Analgésicos Opioides/farmacologia , Benzazepinas/farmacologia , Morfina/farmacologia , Dor/tratamento farmacológico , Quinolinas/farmacologia , Analgésicos Opioides/administração & dosagem , Animais , Benzazepinas/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cisplatino , Sinergismo Farmacológico , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Masculino , Morfina/administração & dosagem , Dor/induzido quimicamente , Medição da Dor , Pressão , Quinolinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Tecnécio Tc 99m Sestamibi
16.
Cancer Biother Radiopharm ; 24(5): 629-36, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19877894

RESUMO

INTRODUCTION: The use of radiolabeled molecules allows the study of in vivo biodistribution, target organs, and kinetic profile after systemic administration by 1) radioactive organ counting and 2) quantitative autoradiographic analysis of whole-body slices (WBA). However, these techniques are time- and animal consuming for several times studied. So, in vivo scintigraphic imaging should appear of interest for a first screening of compounds, as it is able to rapidly demonstrate tumoral uptake and kinetics by serial examinations in the same mice. MATERIALS AND METHODS: In this study, the tumoral distribution and kinetics of six molecules considered as potential melanoma tracers radiolabeled with (125)I were analyzed by gamma-scintigraphy comparatively to the results obtained by WBA. Tumoral uptake has been quantified and expressed by: 1) tumor-to-background ratios and 2) standardized tumoral uptake (STU) in percent injected dose per gram, with tumor weight being extrapolated from the measurement of the two diameters. RESULTS: Results from STU analysis showed good agreement (correlation coefficient = 0.92) with those of WBA, and the same classification of compounds (on the basis of their melanoma affinity) was obtained, with two compounds (of six) being rejected. CONCLUSIONS: [(125)I] scintigraphic imaging appeared as a relevant, easy-going method for a first pharmacologic selection in mice.


Assuntos
Radioisótopos do Iodo/farmacologia , Melanoma/diagnóstico por imagem , Cintilografia/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Vetores Genéticos , Cinética , Masculino , Melanoma/tratamento farmacológico , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , Modelos Químicos , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Imagens de Fantasmas , Neoplasias Cutâneas/tratamento farmacológico , Imagem Corporal Total
17.
Mol Imaging ; 7(6): 263-71, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19123996

RESUMO

This study aimed to report the first single-photon emission computed tomographic (SPECT) imaging of articular cartilage in mice using 99mTc-NTP 15-5 radiotracer. Mice intravenously injected with 99mTc-NTP 15-5 were submitted to (1) dynamic planar imaging, (2) static planar imaging, (3) 1 mm pinhole SPECT acquisition, and (4) dissection. Tomographic reconstruction of SPECT data was performed with a three-dimensional ordered subset expectation maximization algorithm, and slices were reconstructed in three axes. 99mTc-NTP 15-5 rapidly accumulated in the joint, with a peak of radioactivity being reached from 5 minutes postinjection and maintained for at least 90 minutes. Given that bone and muscle did not show any accumulation of the tracer, highly contrasted joint imaging was obtained from 15 minutes postinjection. When 1 mm pinhole SPECT acquisition was focused on the knee, the medial and lateral compartments of both the femoral condyle and tibial plateau were highly delineated, allowing a separate quantitation of tracer accumulation within each component of the femorotibial joint. A good correlation was found between tracer uptake determined by region of interest analysis of both planar and SPECT scans and dissection. This new approach to imaging of cartilage in mice provides joint functionality assessment in vivo, giving a unique opportunity to achieve a greater understanding of cartilage physiology in health and disease.


Assuntos
Cartilagem/diagnóstico por imagem , Fêmur/diagnóstico por imagem , Compostos Heterocíclicos com 1 Anel , Compostos de Amônio Quaternário , Tecnécio , Tíbia/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Algoritmos , Animais , Câmaras gama , Compostos Heterocíclicos com 1 Anel/farmacocinética , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Compostos de Amônio Quaternário/farmacocinética , Tecnécio/farmacocinética , Distribuição Tecidual
19.
Respiration ; 73(5): 634-41, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16679755

RESUMO

BACKGROUND: The diagnosis of malignancy may be difficult to establish in solitary pulmonary nodules (SPNs). OBJECTIVES: It was the aim of this study to assess diagnostic performances of technetium-99m ((99m)Tc)-depreotide in differentiating benign from malignant SPNs and compare its diagnostic accuracy with fluor-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) in a subgroup of patients. METHODS: One hundred and eighteen patients presenting with an SPN < or =3 cm suspected of malignancy on CT were included in a prospective, open-label, European multicentre trial. Single photon emission computed tomography (SPECT) images were acquired 1.1-4.5 h after injection of 459-770 MBq of (99m)Tc-depreotide. A subset of 29 patients also underwent FDG-PET imaging. Images were interpreted blindly and correlated with histopathology. RESULTS: (99m)Tc-depreotide was positive in 65 of 73 patients with a malignant lesion and negative in 30 of 45 patients with a benign lesion, resulting in a sensitivity, specificity and diagnostic accuracy of 89, 67 and 81%, respectively. In 40 patients with SPN < or =1.5 cm, diagnostic accuracy was 88, sensitivity 75 and specificity 96%. In the subset of 29 patients who underwent both (99m)Tc-depreotide SPECT and FDG-PET imaging, sensitivity, specificity and diagnostic accuracy were identical for both modalities, i.e. 90, 67 and 83%, respectively. CONCLUSIONS: The diagnostic accuracy of (99m)Tc-depreotide SPECT is good and comparable with FDG-PET imaging in SPN of indeterminate origin.


Assuntos
Compostos de Organotecnécio , Nódulo Pulmonar Solitário/diagnóstico por imagem , Somatostatina/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Bull Cancer ; 93(12): 1191-9, 2006 Dec.
Artigo em Francês | MEDLINE | ID: mdl-17182375

RESUMO

In comparison with conventional imaging, nuclear medicine offers an original metabolic approach for the assessment of the therapeutic response. Gallium 67, thallium 201, technetium 99m-labeled sestamibi and diphosphonates can be performed for therapeutic response assessment in lymphoma, brain and breast tumours, sarcoma, or bone metastasis. PET-CT facilities are now easily available in France and are ready to provide a new and accurate tool in oncology, specially for therapeutic evaluation. The procedure consists in the injection of fluor-18-fluoro-déoxyglucose (18FDG), an analogue of glucose, followed by a PET then a CT acquisition for FDG uptake abnormalities location. Therapeutic response is assessed by a decrease of 18FDG tumoral uptake between two consecutive studies. Methodology and interpretation criteria have been recently defined in international guidelines. 18FDG-PET-CT seems to be a valuable tool for therapeutic response assessment of patients with Hodgkin or non Hodgkin malignant lymphoma. Promising preliminary results have been recently published for lung, gastro-intestinal and head and neck cancers. PET-CT could also be able to predict the therapeutic response after the first courses of chemotherapy, allowing an early treatment optimization. Finally, new PET agents pave the way for molecular imaging with promising results in gene therapy and targeted treatment in oncology.


Assuntos
Monitorização Fisiológica/métodos , Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Difosfonatos , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Compostos Radiofarmacêuticos , Compostos de Tecnécio , Tecnécio Tc 99m Sestamibi , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão , Resultado do Tratamento
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