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1.
AJNR Am J Neuroradiol ; 37(2): 342-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26427828

RESUMEN

BACKGROUND AND PURPOSE: For the assessment of the treatment response in non-surgical treatment, tumor blood flow provides the functional information of the tumor which is different from the morphological information such as tumor volume. The purpose of this study was to evaluate the diagnostic value of tumor blood flow values obtained by pseudocontinuous arterial spin-labeling in patients with head and neck squamous cell carcinoma. MATERIALS AND METHODS: Forty-one patients with head and neck squamous cell carcinoma were evaluated by using pseudocontinuous arterial spin-labeling. Quantitative tumor blood flow was calculated at the pretreatment and the early treatment periods in all the patients, and the percentage change of tumor blood flow between the two was calculated. At the early treatment period, based on their tumor volume reduction rate, we divided the patients into stable disease and partial response groups for a subgroup analysis. The local control or failure was confirmed either by histopathology or by radiologic evaluation within the follow-up. RESULTS: Pretreatment tumor blood flow in patients in the failure group was significantly lower than that in patients in the local control group. In the subgroup analysis of patients with stable disease, the percentage change of tumor blood flow was significantly larger (due to the tumor blood flow increase from pretreatment value) in the local control group than in the failure group. In addition, in patients with a partial response, the percentage change of tumor blood flow was significantly smaller (due to the tumor blood flow decrease from the pretreatment value) in the local control group than in the failure group. The accuracy for determination of the local control group or the failure group in pretreatment tumor blood flow was 0.83 and that in the combination use of the percentage change of tumor blood flow and tumor volume in the early treatment period was 0.93. CONCLUSIONS: Tumor blood flow obtained by pseudocontinuous arterial spin-labeling can be useful for the determination of local control. The combined use of the percentage change of tumor blood flow and tumor volume had particularly high diagnostic accuracy.


Asunto(s)
Carcinoma de Células Escamosas/irrigación sanguínea , Espectroscopía de Resonancia por Spin del Electrón/métodos , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Adulto , Carcinoma de Células Escamosas/terapia , Femenino , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Marcadores de Spin , Carcinoma de Células Escamosas de Cabeza y Cuello , Resultado del Tratamiento
2.
Br J Cancer ; 109(12): 2980-6, 2013 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-24196792

RESUMEN

BACKGROUND: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). METHODS: Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg m(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy). RESULTS: One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions. CONCLUSION: We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.


Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias del Seno Maxilar/tratamiento farmacológico , Neoplasias del Seno Maxilar/radioterapia , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Quimioradioterapia , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Recurrencia , Carcinoma de Células Escamosas de Cabeza y Cuello , Análisis de Supervivencia
3.
J Neurooncol ; 100(1): 51-64, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20309720

RESUMEN

Pituitary adenomas produce the chemokine stromal cell-derived factor (SDF-1α/CXCL12) and its receptor, CXCR4. A recent study indicated that CXCL12 and CXCR4 are concomitantly up-regulated in hypoxia. The objective of this study was to analyze the molecular mechanism of hypoxia-mediated CXCR4 up-regulation and assess the effect of pharmacological inhibition of CXCR4 by the receptor blocker, AMD3100, on pituitary function. CXCR4 expression in pituitary adenoma tissues was determined by a tissue microarray analysis of 62 pituitary adenoma samples. CXCR4 expression was significantly elevated and positively correlated with Knosp grade in pituitary adenomas (P < 0.005), and was higher in macroadenoma and growth hormone (GH)-producing adenomas. Pre-operative serum GH levels were significantly correlated with CXCR4 levels in the microarray (P < 0.0001). The relative expression of genes/gene categories that were modulated by up-regulated CXCL12/CXCR4 signaling was determined by a comparative transcriptome analysis of wild-type and CXCR4-knockdown cells in normoxia and hypoxia using the rat GH-producing and prolactin-producing pituitary adenoma cell line, GH3. Real-time reverse transcriptase-polymerase chain reaction analysis (RT-PCR) showed that CXCR4 mRNA expression in GH3 cells was increased by hypoxia (1% oxygen), and a cDNA microarray analysis revealed that inhibin ß-C expression was diminished. siRNA-mediated CXCR4 knockdown blocked the hypoxia-induced decrease in inhibin ß-C mRNA expression, as did inhibition of CXCR4 activity with AMD3100. An ELISA study demonstrated that GH secretion by wild-type GH3 cells was moderately enhanced by hypoxia and further potentiated by exposure to recombinant SDF-1α/CXCL12 protein. Conversely, hypoxia-induced GH secretion was reduced in CXCR4-silenced cells and in cells treated with the CXCR4 antagonist, AMD3100, notwithstanding the presence of SDF-1α/CXCL12 protein. These latter observations reflect the failure of hypoxia to suppress expression of inhibin ß-C in cells deficient in CXCR4 or in which CXCR4 signaling was blocked. Together, these results indicate that the SDF-1α/CXCL12-CXCR4 signaling pathway interfaces with the classical endocrine pathway to up-regulate GH production via suppression of inhibin ß-C. Because it blocks CXCR4 and prevents hypoxia-induced down-regulation of inhibin ß-C expression, AMD3100 has promise as a molecular-targeting agent in the treatment of GH-producing adenomas.


Asunto(s)
Hipoxia de la Célula/efectos de los fármacos , Hipoxia de la Célula/fisiología , Hormona del Crecimiento/metabolismo , Compuestos Heterocíclicos/farmacología , Receptores CXCR4/antagonistas & inhibidores , Adenoma/genética , Adenoma/metabolismo , Adenoma/patología , Animales , Bencilaminas , Línea Celular Tumoral , Quimiocina CXCL12/metabolismo , Ciclamas , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática/métodos , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , ARN Mensajero/metabolismo , ARN Interferente Pequeño/farmacología , Ratas , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Estadística como Asunto , beta Caroteno/metabolismo
4.
J Neuroendocrinol ; 21(5): 481-8, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19302186

RESUMEN

Stromal cell-derived factor (SDF)-1 and its receptor, CXCR4, have been identified in both neurones and glia of many brain areas. Previous studies have mainly focused on the role of SDF-1 and CXCR4 in modulating the hypothalamic-pituitary axis and their possible involvement in the development of pituitary adenomas. An alternative SDF-1 receptor, CXCR7, has recently been identified, but it has not been studied in the context of pituitary adenomas. The present study aimed to investigate the distribution and function of CXCR7 in pituitary adenomas. The expression of CXCR7, normalised to ß-actin, was assessed by tissue microarray analysis of 62 adenomas, including 23 growth hormone (GH)-producing adenomas, 22 nonfunctioning adenomas, seven prolactin (PRL)-producing adenomas, six adrenocorticotrophic hormone-producing adenomas and four thyroid-stimulating hormone-producing adenomas. In vitro functional studies used RNA interference (RNAi) and cDNA microarray analysis to evaluate the CXCR7 signalling pathway in AtT-20 mouse pituitary adenoma cells treated with recombinant mouse SDF-1α and transfected with RNAi against Cxcr7 or control RNAi. In tissue microarray analysis, prominent expression of CXCR7 was observed in GH-producing adenomas and PRL-producing adenomas, and in macroadenomas (P < 0.05). Intracellular signalling via CXCR7 up-regulated Bub1, Cdc29 and Ccnb1, and down-regulated Asns, Gpt, Pycr1, Cars and Dars. The present study demonstrates that the SDF-1α / CXCR7 signalling pathway regulates genes involved in cell cycle control, amino acid metabolism and ligase activity, which comprise targets that are distinct from those of CXCR4.


Asunto(s)
Hormona Adrenocorticotrópica/metabolismo , Quimiocina CXCL12/metabolismo , Neoplasias Hipofisarias/metabolismo , Receptores CXCR/metabolismo , Transducción de Señal/fisiología , Animales , Línea Celular Tumoral , Perfilación de la Expresión Génica , Humanos , Ratones , Análisis por Micromatrices , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Receptores CXCR/genética
5.
Surg Endosc ; 22(4): 985-90, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17710487

RESUMEN

BACKGROUND: The first step toward increasing the level of patient safety in endoscopic surgery is for all endoscopic surgeons to acquire fundamental skills, including psychomotor skills, in the preoperation stage of training. The current study aimed to evaluate the effectiveness of virtual reality (VR) simulator training and box training for training the fundamental skills of endoscopic surgery. METHODS: For this study, 35 medical students at Kyushu University were divided into three groups: simulator (SIM) group (n = 20), box trainer (BOX) group (n = 20), and control group (n = 15). None of the students had any experience assisting with endoscopic surgery or any previous training for endoscopic surgery. The students in the SIM group underwent training using a VR simulator, the Procedicus MIST, 2 h per day for 2 days. The students in the BOX group underwent training using a box trainer 2 h per day for 2 days. The students in the control group watched an educational video for 30 min. The endoscopic surgical skills of all the students were evaluated before and after training with a task of suturing and knot tying using a box trainer. RESULTS: Although no significant differences were found between the three groups in the total time taken to complete the evaluation task before training, there were significant improvements in the SIM and BOX groups after training compared with the control group. Box training increased errors during the task, but simulator training did not. CONCLUSION: The findings showed that box training and VR training have different outcomes. The authors expect that the best curriculum for their training center would involve a combination that uses the merits of both methods.


Asunto(s)
Educación de Pregrado en Medicina , Endoscopía/educación , Interfaz Usuario-Computador , Adulto , Femenino , Humanos , Masculino , Desempeño Psicomotor , Análisis y Desempeño de Tareas
6.
Endoscopy ; 38(9): 886-90, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16981104

RESUMEN

BACKGROUND AND STUDY AIMS: The Confocal Endomicroscopy System (Optiscan Pty Ltd. and Pentax Corp.) is a newly developed imaging tool that uses laser light and optical technology to visualize living tissue at the cellular level. Digital images of cells magnified 1000-fold appear in real time on a computer screen, which enables immediate detection of changes in cellular structure without the need for a biopsy. The aim of this study was to assess the features of the cellular architecture of cancerous tissue that can be used in the differential diagnosis of cancerous tissue and normal mucosa using this system's image-processing software. PATIENTS AND METHODS: A total of 27 gastric cancers were examined ex vivo using confocal endomicroscopy. A fluorescent contrast agent, acriflavine, was applied topically to normal and to cancerous mucosa. In vivo imaging of the gastric mucosa after intravenous injection of fluorescein sodium was also performed in nine patients with gastritis or gastric cancer. RESULTS: The nuclear area in the ex vivo specimens was calculated using Scion Image software. The mean nuclear area of cancer cells was found to be significantly larger than that of normal cells in 18/27 gastric cancers (67 %). The mean nuclear area of the cancers tended to be larger than that of normal mucosa, especially in cases of differentiated adenocarcinoma. In more than half the cases, it was possible to diagnose malignancy automatically using confocal endomicroscopy and image-processing software without the need for biopsy and pathological examination. In vivo imaging of cancerous lesions showed irregularity in cellularity and vascularity. CONCLUSION: The ability of this imaging device to differentiate between normal tissue and cancerous tissues gives it potential value as a new screening tool for early detection of malignancy.


Asunto(s)
Adenocarcinoma/patología , Endoscopía Gastrointestinal/métodos , Microscopía Confocal/métodos , Neoplasias Gástricas/patología , Diferenciación Celular , Diagnóstico Diferencial , Células Endoteliales/patología , Mucosa Gástrica/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Microscopía Confocal/instrumentación , Sensibilidad y Especificidad
7.
J Neurooncol ; 71(2): 169-71, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15690134

RESUMEN

Pleomorphic xanthoastrocytoma has been generally conceived to be in a benign nature, showing a relatively favorable prognosis. Apoplectic attack attributable by massive hemorrhage in this distinct form of the supratentorial glioma is an exceedingly rare event. A 61-year-old female presented with a sudden onset of generalized tonic--clonic convulsion. CT and MRI disclosed the presence of a tumor composing of massive intra-tumoral hemorrhage filling the cyst associated with mural nodule in the left frontotemporal lobe. At surgery, the subpial mass involving hematoma was well marginated and slightly adherent to the dura mater. It could be removed totally and proved to be a pleomorphic xanthoastrocytoma. The unusual hemorrhagic presentation of this typically benign entity is extremely rare and is thought to be intra-tumoral bleeding in this case, since subarachnoid hemorrhage was absent.


Asunto(s)
Astrocitoma/irrigación sanguínea , Astrocitoma/complicaciones , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/complicaciones , Hemorragia Cerebral/etiología , Hematoma/etiología , Astrocitoma/diagnóstico , Astrocitoma/patología , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Femenino , Lóbulo Frontal , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Lóbulo Temporal , Tomografía Computarizada por Rayos X
8.
J Neurooncol ; 52(1): 1-9, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11451198

RESUMEN

Cell invasion is a nature of malignant gliomas, demeriting to many efforts of the treatment. Matrix metalloproteinase (MMP) is acknowledged as a key factor in this complicated process. The aim of this study was to investigate whether inhibition of MMP activity in malignant glioma cells could be achieved by a novel agent, BE16627B (BE). Malignant glioma cell lines, U87MG, U251MG, and U373MG, were employed to evaluate inhibitory effect on zymogram, type IV collagenolysis assay, and haptoinvasion assay for 24 h exposure of BE, following preliminar


Asunto(s)
Antineoplásicos/farmacología , Dipéptidos/farmacología , Glioma/patología , Glioma/fisiopatología , Metaloproteinasa 2 de la Matriz/fisiología , Metaloproteinasa 9 de la Matriz/fisiología , Inhibidores de Proteasas/farmacología , Succinatos/farmacología , Colágeno Tipo IV/metabolismo , Colorantes , Humanos , Invasividad Neoplásica , Sales de Tetrazolio , Tiazoles , Células Tumorales Cultivadas
9.
J Neurooncol ; 52(1): 37-47, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11451201

RESUMEN

Estramustine phosphate (EMP) is an anti-microtubule agent that depolymerizes microtubules and also causes apoptosis of glioma cells. Both of these pharmacological actions have been previously studied within the same cytotoxic range of EMP concentrations. The purpose of this study was to investigate which of these two phenomena occurred before the other. A preliminary MTT assay was done to distinguish non-cytotoxic (0.005-0.1 microM) and cytotoxic (0.5-10 microM) of EMP for BT4C cells. To investigate apoptotic changes, transmission electron microscopy (TEM), DNA laddering, and in situ endo-labeling (TUNEL) method were employed. A chemotaxis assay was used to assess cell motility. Scanning electron microscopy and TEM immunocytochemistry with an anti-beta tubulin antibody were applied to detect morphological changes of the microtubules. Suppression of cell motility by cytotoxic doses of EMP (0.5-10 microM) group was attributed by the cyto-reductive effect, relating to apoptosis. At 0.01-0.1 microM (non-cytotoxic doses), EMP did not indue apoptosis. At these concentrations, TEM and immunohistochemistry revealed the formation of blebs on the tip of the pseudopodia that contained abnormally depolymerized microtubules, a finding that was not observed at a low temperature or during cell migration. Cell chemotaxis was significantly inhibited by cytostatic EMP doses (0.05 and 0.1 microM). Bleb formation of the pseudopodia might be evidence of the abnormal disassembly of microtubules by cytostatic EMP concentrations, prior to the induction of apoptosis. In glioma cells EMP probably initiates apoptosis by causing the depolymerization of microtubules. Inhibition of cell motility by cytostatic doses of EMP could be beneficial to support other therapies.


Asunto(s)
Antineoplásicos Hormonales/farmacología , Estramustina/farmacología , Espacio Extracelular/fisiología , Glioma/metabolismo , Microtúbulos/metabolismo , Polímeros/metabolismo , Seudópodos/fisiología , Animales , Apoptosis , Quimiotaxis , Glioma/patología , Glioma/fisiopatología , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Seudópodos/ultraestructura , Ratas , Células Tumorales Cultivadas
10.
J Magn Reson Imaging ; 13(3): 344-51, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11241805

RESUMEN

The purpose of this study was to examine which physiological factors affect cerebral T2* signal intensity (SI) during breath holding (BH) (apnea after inspiration and breathing after expiration) in normal volunteers. We examined SI changes caused by anoxic gas inhalation, by respiratory movements, and by BH. High-speed echo planar images (EPI) showed changes in SI that could be divided into five phases. Reports indicate that SI changes induced by BH are due to the effects on the magnetic susceptibility of deoxygenated hemoglobin (deoxyhemoglobin (dHb)) and to hypercapnia, but these reports could not fully explain the observed five phases. In addition to deoxyhemoglobin susceptibility and hypercapnia, we found that respiratory movements play a third critical role in modifying SI by affecting blood flow into the region of interest (ROI), as judged from right carotid artery flow. Consequently, we propose that the physiological SI changes induced by BH are derived from blood oxygenation, hypercapnia, and respiratory movements.


Asunto(s)
Hipoxia Encefálica/diagnóstico , Imagen por Resonancia Magnética , Ventilación Pulmonar/fisiología , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/patología , Femenino , Hemoglobinas/metabolismo , Humanos , Hipercapnia/diagnóstico , Hipercapnia/fisiopatología , Hipoxia Encefálica/fisiopatología , Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador , Masculino , Valores de Referencia , Flujo Sanguíneo Regional/fisiología
11.
Abdom Imaging ; 26(2): 184-90, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11178697

RESUMEN

BACKGROUND: The purpose of this study was to compare the ability of Lipiodol-computed tomography (CT), power Doppler (PD) sonography, and dynamic magnetic resonance imaging (MRI) in evaluating the therapeutic effect of transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma (HCC). METHODS: TACE was performed by injecting an emulsion consisting of Lipiodol and a chemotherapeutic drug, followed by gelatin sponge particles, into 54 patients with 84 HCC lesions. Five to 7 days later, Lipiodol-CT, PD sonography, and dynamic MRI were performed. Findings from the three modalities were correlated with relapse within 1 year after TACE. RESULTS: All lesions with blood flow on PD sonography or intratumoral enhancement on dynamic MRI relapsed regardless of the findings with Lipiodol-CT. None of the negatively enhanced lesions on dynamic MRI relapsed regardless of the Lipiodol-CT findings. However, the readers could not evaluate the contrast uptake in 14 lesions that were already hyperintense on the precontrast images. These cases were considered unsuitable for qualitative assessment and reduced the applicability of MRI to 83% of the examined lesions (70 of 84). Although PD sonography perfectly predicted relapse in superficial (0-5 cm from abdominal surface) lesions of the right hepatic lobe, blood flow in deep (>5 cm) or left lobe lesions was undetectable regardless of the occurrence of relapse. As a result, Lipiodol-CT displayed 76.0% sensitivity, 67.6% specificity, and 72.6% accuracy. The sensitivity, specificity, and accuracy of PD sonography were 34.0%, 100%, and 60.7%, respectively. In the 70 lesions in which evaluation was possible, dynamic MRI achieved 100% sensitivity, 100% specificity, and 100% accuracy. CONCLUSION: Of the three modalities, dynamic MRI was the best for evaluating the efficacy of TACE in the treatment of HCC. We also found that superficial lesions of the right lobe are good candidates for PD sonography. However, high signals on precontrast MR images, motion artifacts, and ultrasonic attenuation remain key limitations.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Quimioembolización Terapéutica , Medios de Contraste , Aceite Yodado , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/terapia , Femenino , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
13.
Brain Tumor Pathol ; 18(2): 89-100, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11908879

RESUMEN

Degradation of basement membrane by metalloproteinases (MMP) is a critical step in tumor angiogenesis. To evaluate in vitro angiogenesis, several models have been employed, including bovine cornea, fenestrated rat brain, Matrigel, and others. These models did not provide quantitative analysis of capillary formation. The current study aimed for a novel approach to in vitro assay of angiogenesis with a "wet scanning electron microscope (SEM)" to investigate suppression of tumor angiogenesis by the MMP inhibitor, SI-27. The effects of noncytotoxic concentrations of SI-27 (1-100 microM) were determined on nonmitogenic vascular endothelial growth factor (VEGF) (10 ng/ml)-mediated cell motility and in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). Activities of MMP and tissue inhibitor of metalloproteinase (TIMP) were determined by enzyme-linked immunosorbent assay (ELISA). Subsequently, the inhibitory effect of SI-27 was examined on in vitro angiogenesis stimulated by supernatants of human glioma cell lines (U87MG, U251MG, or U373MG). In vitro angiogenesis was quantitatively analyzed with a variable-pressure SEM. Cell motility and in vitro angiogenesis by HUVECs were significantly increased by VEGF along with elevated MMP-1 and -2 activity, whereas SI-27 significantly suppressed VEGF-mediated in vitro angiogenesis and inactivated both MMP-1 and MMP-2, but not inhibited cell motility. The angiogenesis promoted by glioma supernatants showed a significant reduction in the presence of SI-27. SI-27, a novel MMP inhibitor, inhibited tumor angiogenesis in vitro. It can be anticipated to prevent tumor growth through its angiosuppressive effect. Quantitative analysis with a variable-pressure SEM is a novel approach to in vitro angiogenesis assay.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Metaloproteinasa de la Matriz , Microscopía Electrónica/métodos , Proteínas de Neoplasias/antagonistas & inhibidores , Neovascularización Patológica/patología , Oligopéptidos/farmacología , Inhibidores de Proteasas/farmacología , Quimiotaxis/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Endotelio Vascular/efectos de los fármacos , Humanos , Metaloproteinasas de la Matriz/análisis , Metaloproteinasas de la Matriz/fisiología , Estructura Molecular , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/fisiología , Oligopéptidos/química , Proteínas Recombinantes/farmacología , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/ultraestructura , Inhibidores Tisulares de Metaloproteinasas/análisis , Células Tumorales Cultivadas/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/farmacología
14.
J Neurooncol ; 54(1): 23-9, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11763419

RESUMEN

Estramustine phosphate (EMP) is an anti-microtubule agent that induces apoptosis of glioma cells. We investigated whether EMP caused apoptosis through the alkylating effect of its nitrogen mustard component or by phosphorylation of bcl-2 like other anti-microtubule agents in normal human astrocyte and human malignant glioma cell lines. Apoptosis was seen in glioma cells treated either with nitrogen mustard or EMP and expression of bcl-2 mRNA was not changed by exposure to the drug. An immunoprecipitation study only found phosphorylation bcl-2 in glioma cells exposed to EMP and not in cells exposed to nitrogen mustard. These results indicate that induction of apoptosis in glioma cells by EMP is mediated by phosphorylation of bcl-2.


Asunto(s)
Antineoplásicos Hormonales/farmacología , Estramustina/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Antineoplásicos Alquilantes/farmacología , Astrocitos/efectos de los fármacos , Astrocitos/ultraestructura , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/ultraestructura , Electroforesis en Gel de Agar , Glioma/patología , Glioma/ultraestructura , Humanos , Mecloretamina/farmacología , Microscopía Electrónica , Microtúbulos/efectos de los fármacos , Fosforilación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas
15.
J Neurooncol ; 48(3): 217-23, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11100819

RESUMEN

Matrix metalloproteinase (MMP) has come to be highlighted by its close relation to the cell invasion of gliomas. Suppression of MMP activity in malignant glioma cells would be meriting to local delivery of genes or chemotherapeutic agents. In this study, we employed a novel MMP inhibitor, SI-27 to investigate inhibition of cell invasiveness in human malignant glioma cell lines, U87MG, U251MG, and U373MG. We evaluated with zymogram, reverse zymogram, and cell invasion assay after exposure of SI-27 for 24 h followed by preliminary MTT assay to find non-cytotoxic dose range, 5, 10, 50, 100 microg/ml compared with non-treatment group as the control. Common to three glioma cell lines, zymogram disclosed that expressions of MMP-2 and -9 were suppressed in a dose-dependent fashion, meanwhile those of tissue inhibitor of MMP (TIMMP) in reverse zymogram were not. The numbers of invading cells through Boyden chamber were significantly reduced in a dose-dependent manner, while those with 5 microg/ml were not diminished common to those three lines. In conclusion, dose concentration ranging 10-100 microg/ml of SI-27 inhibited MMP-2 and -9 mediated cell invasiveness in malignant glioma cell lines. This is the first report for chemotherapeutic effect of SI-27 on glioma cells.


Asunto(s)
Neoplasias Encefálicas/patología , Glioma/patología , Inhibidores de la Metaloproteinasa de la Matriz , Invasividad Neoplásica/prevención & control , Oligopéptidos/farmacología , Inhibidores de Proteasas/farmacología , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Inhibidores Tisulares de Metaloproteinasas/análisis , Células Tumorales Cultivadas
16.
J Neurooncol ; 47(2): 133-40, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10982154

RESUMEN

The drug effect of estramustine phosphate (EMP), an anti-microtubule agent on human glioma cells has been studied with the focus being mainly its cytotoxity or its targeting of organelles. However, the pharmacological knowledge of estramustine with respect to its cytotoxity and mechanism is limited. To acquire such knowledge, the present study investigates the ability of EMP to induce apoptosis in a human malignant glioma cell line. Transmission electron microscope (TEM) images were examined to monitor periodic changes. Agarose gel electrophoresis was also examined. Cellular DNA fragmentation ELISA was performed to investigate the DNA fragmentation rates and an MTT assay was studied to evaluate the ID50. A TEM study revealed condensing and fragmentation of the chromatin. Laddering of the bands was observed in all EMP exposure groups in agarose gel electrophoresis. DNA fragmentation in all EMP groups began at 0.5 h following an exposure with EMP and increased in a dose- and time-dependent manner as revealed by DNA ELISA fragmentation. ID50 at 24 h was 5.0 microM according to the MTT assay, a value close to 4.8 microM of ID50 was revealed by the DNA fragmentation assay. None of the above mentioned changes was observed in the control group. These results indicated that EMP caused a drug-induced apoptosis in the human malignant glioma cell line, U87MG.


Asunto(s)
Antineoplásicos Alquilantes/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/patología , Estramustina/farmacología , Glioma/patología , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Fragmentación del ADN , ADN de Neoplasias/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Agar , Ensayo de Inmunoadsorción Enzimática , Estramustina/uso terapéutico , Glioma/tratamiento farmacológico , Glioma/genética , Humanos , Técnicas In Vitro , Microscopía Electrónica , Microtúbulos/efectos de los fármacos , Orgánulos/ultraestructura , Análisis de Supervivencia , Células Tumorales Cultivadas
17.
J Neurooncol ; 47(1): 51-8, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10930100

RESUMEN

A thirty-year-old male with an intracranial malignant meningioma, first diagnosed 9 years ago, with three recurrences was admitted with a hypoglycemic shock. The blood glucose level was 17 mg/dl, requiring treatment with high doses of intravenous and oral dextrose for improvement. A large metastatic tumor in the liver was noted. All hormones and peptides influencing blood glucose levels were in their normal levels. Chemo-embolization and injection of anti-cancer drugs was employed in the management of the metastatic tumor. Positron emission tomography was performed to measure the glucose metabolism of the abdominal tumor and it indicated that glucose consumption within the tumor was much elevated than the surrounding abdominal organs. Hypoglycemia secondary to primary hepatoma or islet-cell cancer has been frequently described, but a complication of metastatic meningioma is an exceedingly rare event. Elevated glucose consumption within the tumor might be addressed as one of the reasons for hypoglycemia, not due to the elevated serum levels of insulin or IGF, but due to the closely related blood glucose level.


Asunto(s)
Neoplasias Abdominales/complicaciones , Neoplasias Abdominales/secundario , Hipoglucemia/etiología , Neoplasias Meníngeas/patología , Meningioma/complicaciones , Meningioma/secundario , Neoplasias Abdominales/diagnóstico por imagen , Adulto , Biopsia , Resultado Fatal , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Factor II del Crecimiento Similar a la Insulina/análisis , Neoplasias Pulmonares/secundario , Masculino , Meningioma/diagnóstico por imagen , Tomografía Computarizada de Emisión
18.
Abdom Imaging ; 25(2): 172-8, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10675460

RESUMEN

BACKGROUND: To determine whether a difference exists in the relative ability of power Doppler sonography and conventional color Doppler sonography to detect the intratumoral vasculature of hepatocellular carcinoma based on lesion size and location. METHODS: Sixty patients with 88 hepatocellular carcinoma lesions that showed tumor staining on angiography and were enhanced on dynamic computed tomography were evaluated. Power Doppler sonography and color Doppler sonography were used to detect the intratumoral vasculature, and their sensitivity to blood flow was evaluated. RESULTS: Power Doppler sonography showed a superior detection rate for lesions smaller than 2 cm and located 4-8 cm from the abdominal surface in the right hepatic lobe as compared with color Doppler sonography (p < 0.01). Neither power Doppler sonography nor color Doppler sonography depicted the intratumoral vasculature of lesions located more than 8 cm from the abdominal surface (n = 14). Both color Doppler imagings exhibited a low detection rate for lesions in the left hepatic lobe (n = 31, p < 0.01). CONCLUSIONS: Power Doppler sonography should be applied in the evaluation of small or intermediate depth lesions because it is more sensitive to these lesions than color Doppler sonography, but it is not useful for left lobe and deep lesions.


Asunto(s)
Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/diagnóstico por imagen , Ultrasonografía Doppler , Anciano , Anciano de 80 o más Años , Angiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler en Color
19.
Nihon Igaku Hoshasen Gakkai Zasshi ; 60(1): 42-4, 2000 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-10689889

RESUMEN

To assess whether cerebral arterial blood oxygen saturation (SaO2) can be calculated by EPI, we examined the relationship between peripheral SaO2 and T2+ signal intensity (SI) changes in the brain in three normal subjects, using 1.5 Tesla MRI. To decrease SaO2, hypoxia was induced by 100% helium-gas inhalation (60 sec). SI declined as SaO2 decreased during helium inhalation, while rapid recovery of SI to the baseline was noted with recovery from hypoxia. The differential effective transverse relaxation rate was closely correlated with SaO2 (r > 0.94). Consequently, using MRI, we were able to calculate arterial SaO2.


Asunto(s)
Arterias Cerebrales , Imagen por Resonancia Magnética , Oximetría/métodos , Oxígeno/sangre , Arterias Cerebrales/patología , Humanos , Hipoxia/sangre
20.
Cancer ; 86(8): 1470-9, 1999 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-10526275

RESUMEN

BACKGROUND: Various prognostic markers for lung carcinoma have been proposed, but to the authors' knowledge none is noninvasive and convenient for clinical use. The current study examined the utility of several radiotracers for the prediction of multidrug resistance (MDR) and radioresistance in patients with lung carcinoma. METHODS: Thirty patients with untreated lung carcinoma underwent a dual isotope single photon emission computed tomography (SPECT) scan at 10 minutes and 120 minutes after the injection of technetium-99m ((99m)Tc)-tetrofosmin ((99m)Tc-TF) (370 megabecquerels [MBq]) and thallium-201 ((201)TlCl) (111 MBq). Retention of each tracer was evaluated semiquantitatively. Using radiation and chemotherapy (cisplatin plus etoposide), the patients either were treated sequentially (n = 12) or concurrently (n = 18). The relation between therapeutic response and retention of each tracer was analyzed. The detectability of radioresistance was examined. RESULTS: In patients treated with sequential therapy, the response to radiation was predicted by (99m)Tc-TF retention, whereas (201)Tl retention was found not to be predictive. Regardless of whether the sequential or concurrent protocol was applied, 14 of 18 tumors with high (99m)Tc-TF retention (>/= 15%) exhibited a favorable response to chemoradiotherapy whereas all 12 tumors with low (99m)Tc-TF retention (

Asunto(s)
Carcinoma de Células Pequeñas/diagnóstico por imagen , Resistencia a Múltiples Medicamentos , Neoplasias Pulmonares/diagnóstico por imagen , Tolerancia a Radiación , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Antineoplásicos/uso terapéutico , Carcinoma de Células Pequeñas/terapia , Cisplatino/uso terapéutico , Terapia Combinada , Quimioterapia , Femenino , Humanos , Cinética , Neoplasias Pulmonares/terapia , Masculino , Compuestos Organofosforados , Compuestos de Organotecnecio , Pronóstico , Radioterapia , Radioisótopos de Talio , Resultado del Tratamiento
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