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1.
Biosystems ; 198: 104226, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32861800

RESUMO

The goal of the segmentation of brain images is to separate the images in different non-compatible homogenous areas reflecting the numerous anatomical structures. Brain segmentation by magnetic resonance has numerous implications for diagnosing brain disorganizations such as Alzheimer's, Parkinson-related syndrome among others. However, it is not an simple job to automatically segment the MR image. The main motive of this study is to provide a better segmentation approach for the segment of the ROI (Region Of Interest) region from the MRI image by solving the issues that currently exist in the literary works. MRI segmentation is not a trivial task, because acquired MR images are imperfect and are often corrupted by noise and other image artifacts. The variety in technologies for image processing has contributed to the creation in numerous image segmentation techniques. That is because there is no universal approach, nor are all methods necessarily appropriate for a specific form of picture suitable for all pictures. Other approaches still use the gray level histogram, for example, while others integrate detailed spatial picture details for bleeding conditions. Some methods use statistical techniques, but some do incorporate existing information to enhance segmentation efficiency. Some methods utilize probabilistic or fuzzy methods. Yet there are certain inconveniences of all the current processes. Therefore, we have intended to propose a new segmentation approach for the ROI region segmentation. The proposed work comprised of three phases namely preprocessing, edge detection and segmentation. At first, the MRI images are extracted from the database and that each of the input images is enhanced by applying a high pass filter. After completing the preprocessing method, the enhanced canny edge detection (ECED) approach is used to enhance the image. After that, the images are given to the modified watershed segmentation (MWS) algorithm which separates the ROI part from MRI Image. The testing consequences demonstrate that the proposed system accomplishes to give the good result related to the available strategies. Xilinx Virtex-5 FPGA is used to implement in this paper.


Assuntos
Algoritmos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/diagnóstico por imagem , Mapeamento Encefálico/métodos , Lógica Fuzzy , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
2.
Artigo em Inglês | MEDLINE | ID: mdl-30502827

RESUMO

OBJECTIVES: The present study was aimed to find the larvicidal activity of petroleum ether, chloroform, acetone and methanolic extracts of Dichanthium foveolatum (Del.) Roberty, Leptochloa uniflora Hochst, Pancratium triflorum Roxb and Molineria trichocarpa (Wight) N.P.Balakr against Culex quinquefasciatus. METHODS: The larvicidal potential of selected plant extracts were determined against 4th instar larvae of C. quinquefasciatus with various concentrations viz., 50, 100, 150, 200 and 250 mg/ml. The mortality counts were made after 24 h of incubation and LC50 values were calculated. RESULTS: Chloroform extracts of studied plants were showed highest larvicidal activity with remarkable irritant against the larva of C. quinquefasciatus. Highest larvicidal activity was observed in the chloroform extract of D. foveolatum against the larva of C. quinquefasciatus with LC50 = 277.03 mg/ml. The larvicidal activity of the studied plants as follows chloroform extract of D. foveolatum (LC50 = 277.03 mg/ml) >L. uniflora (LC50 = 300.56 mg/ml) >M. trichocarpa (LC50 = 306.60 mg/ml) >P. triflorum (LC50 318.42 mg/ml). The larvicidal potential of P. triflorum was as follows Chloroform > acetone > methanol > petroleum ether. The larvicidal activities of L. uniflora and M. trichocarpa were as follows Chloroform > petroleum ether > acetone > methanol respectively. The larvicidal potentials of D. foveolatum was as follows Chloroform > methanol > acetone > petroleum ether. CONCLUSION: The chloroform extract of D. foveolatum find use as broad-spectrum larvicidal agent in the near future. It is hoped that more work would be undertaken to evaluate the utility of these plant extracts for field applications considering the promising leads given by the present study.


Assuntos
Culex , Inseticidas , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Filariose , Concentração Inibidora 50 , Larva , Folhas de Planta/química
3.
Food Chem Toxicol ; 119: 290-295, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29596974

RESUMO

The present investigation was carried out to evaluate the antioxidant and cytotoxic activities of Pancratium triflorum Roxb and Molineria trichocarpa were collected from South Vagaikulam, Tirunelveli district, Tamil Nadu, India. The antioxidant activities of P. triflorum extracts were as follows with the IC50 values methanol (228.13 µg/mL) > chloroform (311.33 µg/mL) > acetone (398.08 µg/mL) > petroleum ether (410.16 µg/mL). The antioxidant activities of P. triflorum and M. trichocarpa extracts were as follows with the IC50 values methanol (80.93 µg/mL) > acetone (98.02 µg/mL) > chloroform (186.84 µg/mL) > petroleum ether (209.64 µg/mL). Among the various extracts of P. triflorum, methanolic extracts showed the strongest phosphomolybdenum reduction (140.56 g AA/100 g). Among the tested extracts, acetone extracts of M. trichocarpa showed maximum inhibition with 71.36 ±â€¯5.86%. In P. triflorum, chloroform extracts showed maximum inhibition (69.51%). The petroleum ether extract of M. trichocarpa was found to be most effective at which 50% mortality (LC50) and 90% mortality (LC90) of brine shrimp nauplii were found to be 29.22 and 184.82 mg/mL. This study results revealed the antioxidant and cytotoxic properties of P. triflorum and M. trichocarpa. Further investigations are needed to isolate and validate the active principles of the extract responsible various pharmacological properties.


Assuntos
Amaryllidaceae/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Hypoxidaceae/química , Extratos Vegetais/farmacologia , Animais , Artemia/efeitos dos fármacos , Flavonoides/análise , Concentração Inibidora 50 , Fenóis/análise
4.
Indian J Nephrol ; 27(6): 468-471, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29217887

RESUMO

We report the development of minimal change disease superimposed on preexisting chronic kidney disease secondary to chronic calcineurin inhibitor nephrotoxicity in a hematopoietic stem cell transplantation (HSCT) recipient and review the renal complications of HSCT.

5.
J Mech Behav Biomed Mater ; 4(7): 1291-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21783138

RESUMO

The critical stress intensity factor, also known as the crack tip toughness K(tip), was determined for three base glasses, which are used in the manufacture of glass-ceramics. The glasses included the base glass for a lithium disilicate glass-ceramic, the base glass for a fluoroapatite glass-ceramic and the base glass for a leucite glass-ceramic. These glass-ceramic are extensively used in the form of biomaterials in restorative dental medicine. The crack tip toughness was established by using crack opening displacement profiles under experimental conditions. The crack was produced by Vickers indentation. The crack tip toughness parameters determined for the three glass-ceramics differed quite significantly. The crack tip parameters of the lithium disilicate base glass and the leucite base glass were higher than that of the fluoroapatite base glass. This last material showed glass-in-glass phase separation. The discussion of the results clearly shows that the droplet glass phase is softer than the glass matrix. Therefore, the authors conclude that a direct relationship exists between the chemical nature of the glasses and the crack tip parameter.


Assuntos
Cerâmica/química , Restauração Dentária Permanente/instrumentação , Vidro/química , Fenômenos Mecânicos , Silicatos de Alumínio/química , Apatitas/química , Porcelana Dentária/química , Nanoestruturas/química
6.
J Biol Eng ; 4: 5, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20398336

RESUMO

BACKGROUND: A polarized light scattering technique was used to monitor the performance of a continuously operated foam fractionation process. The S11 and S12 parameters, elements of the light scattering matrix, combined together (S11+S12) have been correlated with the bubble size and liquid content for the case of a freely draining foam. The performance of a foam fractionation column is known to have a strong dependence on the bubble size distribution and liquid hold up in foam. In this study the enrichment is used as a metric, representative of foam properties and column performance, and correlated to the S11+S12 parameter. RESULTS: Three different superficial gas velocities (6.9, 7.5, and 10.6 cm/min) and four different pH values (4.8, 5.5, 6.5, and 7.5) are tested for the foam fractionation of a dilute solution of bovine serum albumin (0.1 mg/ml). As a result, at scattering angle of 125 degrees the magnitude of S11+S12 is higher as the pH increases. When the bubble sizes are small with a larger liquid content, the foam is strongly back scattering resulting in lower values of S11+S12 (at 125 degrees ) at pH = 4.8. The light scattering data and the enrichment values are measured over a period of 90 minutes and correlated using a linear model. The predictive power of the model was found to be statistically significant. CONCLUSION: The time average S11+S12 shows a direct proportionality with the enrichment value, indicating that polarized light should be a valuable technique for monitoring foam fractionation columns. Additional knowledge of the nature of dependence between foam properties and S11+S12 combined with models relating the enrichment to the bubble size and liquid hold up is needed to develop an accurate diagnostics tool for monitoring enrichment utilizing S11+S12 measurements.

7.
Bone Marrow Transplant ; 43(11): 845-51, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19139731

RESUMO

To study the impact of auto-SCT on the outcomes in African Americans (AA) with multiple myeloma (MM), we evaluated 101 consecutive AA patients who underwent auto-SCT. The median PFS and OS were 15.6 and 50.8 months, respectively. The median OS from diagnosis was 60 months. Traditional pre and post transplant prognostic variables earlier examined in Caucasian Americans (CA), including beta-2 microglobulin (B2M), chromosome 13 deletion, CR status after auto-SCT, gender, stage, Ig subtype, time to transplant, number of prior regimens and presence of lytic lesions, were not predictive of improved PFS or OS on univariate analysis. Age, lower CD34 cell dose infused, history of palliative radiation therapy (XRT) prior to auto-SCT and refractory disease at the time of auto-SCT were predictive of inferior PFS. History of palliative XRT was the only predictive factor of inferior PFS and OS after auto-SCT on multivariate analysis. In conclusion, MM in AA tends to relapse early after auto-SCT. It is unclear whether early relapses impact OS. Common prognostic peritransplant variables known in CA with MM may not be applicable to AA with MM.


Assuntos
Afro-Americanos , Mieloma Múltiplo/terapia , Transplante de Células-Tronco , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/cirurgia , Prognóstico , Recidiva , Transplante Homólogo , Resultado do Tratamento
9.
Neurology ; 59(4): 514-23, 2002 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-12196642

RESUMO

OBJECTIVE: To test the effect of i.v.-injected human bone marrow stromal cells (hMSC) on neurologic functional deficits after stroke in rats. METHODS: Rats were subjected to transient middle cerebral artery occlusion and IV injected with 3 x 10(6) hMSC 1 day after stroke. Functional outcome was measured before and 1, 7, and 14 days after stroke. Mixed lymphocyte reaction and the development of cytotoxic T lymphocytes measured the immune rejection of hMSC. A monoclonal antibody specific to human cellular nuclei (mAb1281) was used to identify hMSC and to measure neural phenotype. ELISA analyzed neurotrophin levels in cerebral tissue from hMSC-treated or nontreated rats. Bromodeoxyuridine injections were used to identify newly formed cells. RESULTS: Significant recovery of function was found in rats treated with hMSC at 14 days compared with control rats with ischemia. Few (1 to 5%) hMSC expressed proteins phenotypic of brain parenchymal cells. Brain-derived neurotrophic factor and nerve growth factor significantly increased, and apoptotic cells significantly decreased in the ischemic boundary zone; significantly more bromodeoxyuridine-reactive cells were detected in the subventricular zone of the ischemic hemisphere of rats treated with hMSC. hMSC induced proliferation of lymphocytes without the induction of cytotoxic T lymphocytes. CONCLUSION: Neurologic benefit resulting from hMSC treatment of stroke in rats may derive from the increase of growth factors in the ischemic tissue, the reduction of apoptosis in the penumbral zone of the lesion, and the proliferation of endogenous cells in the subventricular zone.


Assuntos
Transplante de Medula Óssea/métodos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator de Crescimento Neural/metabolismo , Acidente Vascular Cerebral/terapia , Células Estromais/transplante , Animais , Comportamento Animal , Transplante de Medula Óssea/imunologia , Fator Neurotrófico Derivado do Encéfalo/análise , Divisão Celular , Movimento Celular/fisiologia , Células Cultivadas , Testes Imunológicos de Citotoxicidade , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Sobrevivência de Enxerto , Humanos , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/terapia , Teste de Cultura Mista de Linfócitos , Masculino , Atividade Motora , Fator de Crescimento Neural/análise , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Baço/citologia , Baço/imunologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Células Estromais/imunologia , Transplante Heterólogo , Resultado do Tratamento
10.
Biochem Pharmacol ; 62(9): 1299-308, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11705464

RESUMO

trans-Resveratrol, a phytoalexin found in grapes, wine, and other plant products, has been shown to have anti-inflammatory, antioxidant, and antitumor activities. Many of these beneficial effects of resveratrol require participation of the cells of the immune system; however, the effect of resveratrol on the development of immunological responses remains unknown. We have investigated the effect of resveratrol on mitogen/antigen-induced proliferation of splenic lymphocytes, induction of cytotoxic T lymphocytes (CTLs) and lymphokine activated killer (LAK) cells, and the production of the cytokines interferon (IFN)-gamma, interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, and IL-12. We found that mitogen-, IL-2-, or alloantigen-induced proliferation of splenic lymphocytes and the development of antigen-specific CTLs were suppressed significantly at 25-50 microM resveratrol. The generation of LAK cells at similar concentrations was less sensitive to the suppressive effect of resveratrol. The suppression of cell proliferation and CTL generation by resveratrol was not only reversible, but in some cases the response (mitogen/IL-2-induced proliferation and CTL generation) was actually enhanced following pretreatment of cells with resveratrol. Resveratrol also inhibited the production of IFN-gamma and IL-2 by splenic lymphocytes, and the production of TNF-alpha and IL-12 by peritoneal macrophages. The inhibition of cytokine production by resveratrol was irreversible. Further, resveratrol blocked the activation of the transcription factor NF-kappaB without affecting basal NF-kappaB activity. The latter result suggests that resveratrol inhibits cell proliferation, cell-mediated cytotoxicity, and cytokine production, at least in part through the inhibition of NF-kappaB activation.


Assuntos
Adjuvantes Imunológicos/farmacologia , Citocinas/metabolismo , Linfócitos/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Interleucina-2/genética , Interleucina-2/metabolismo , Linfócitos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Resveratrol
11.
J Neurooncol ; 53(1): 55-9, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11678432

RESUMO

OBJECTIVE: and importance Therapy-related myelodysplastic syndrome (t-MDS) is a rare and typically fatal complication of therapy for cancer, including brain tumors. We report successful therapy of t-MDS that developed after treatment for an anaplastic astrocytoma. CLINICAL PRESENTATION: t-MDS developed four and one-half years after successful therapy (resection, radiation and chemotherapy) administered for a cerebral anaplastic astrocytoma in a 34-year-old patient. INTERVENTION: The patient was treated with allogeneic bone marrow transplant (BMT) for t-MDS. CONCLUSION: She is alive three years after BMT with no evidence of brain tumor and in complete remission from t-MDS. To our knowledge, this is the first report of allogeneic BMT administered for t-MDS in an adult brain tumor patient. Clinicians must be alert to the development of t-MDS following chemotherapy for brain tumors and initiate appropriate treatment promptly.


Assuntos
Anemia Refratária com Excesso de Blastos/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Astrocitoma/terapia , Neoplasias Encefálicas/terapia , Adulto , Anemia Refratária com Excesso de Blastos/induzido quimicamente , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Radioterapia Adjuvante , Transplante Homólogo
12.
Clin Immunol ; 98(2): 180-9, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11161974

RESUMO

We have previously shown that the myeloid progenitor cell line 32Dc13 transduced with mIL-12 cDNAs (32DIL-12 cells) induces IFN-gamma and NK-cell-mediated cytotoxicity in vivo. Since systemic therapy with recombinant IL-12 protein has been shown to produce moderate to severe toxic side effects we examined whether IL-12 gene therapy with hematopoietic progenitor cells also induces systemic toxicities that are commonly associated with the administration of rIL-12 protein. Injection of large doses of IL-12 secreting 32DIL-12 cells (5 to 6 x 10(7) cells) significantly reduced mortality in mice injected with a lethal dose of 32Dp210 myeloid leukemia cells. More importantly, injection of similar doses of transduced cells failed to reduce body weight significantly or produce other visible signs of toxicity, i.e., fur ruffling or lethargy. There was no evidence of hematologic or hematopoietic toxicity resulting from the injection of transduced cells. In addition, microscopic examination of liver, kidney, lung, and intestine of mice injected with transduced cells revealed the absence of tissue necrosis or inflammatory response in any of these organs. Finally, 32DIL-12 cells were not found to interfere with the engraftment of syngeneic bone marrow transplant or the hematopoietic reconstitution of irradiated mice. These results demonstrate that IL-12 gene therapy with hematopoietic progenitor cells is nontoxic and provide a rationale for exploring the feasibility of treating minimal residual leukemia with IL-12 gene therapy.


Assuntos
Terapia Genética , Transplante de Células-Tronco Hematopoéticas , Interleucina-12/genética , Leucemia Experimental/terapia , Animais , Contagem de Células Sanguíneas , Doenças da Medula Óssea/induzido quimicamente , Doenças da Medula Óssea/prevenção & controle , Transplante de Medula Óssea , Células Cultivadas/metabolismo , Células Cultivadas/transplante , Ensaio de Unidades Formadoras de Colônias , Estudos de Viabilidade , Sobrevivência de Enxerto , Células-Tronco Hematopoéticas/metabolismo , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Interferon gama/metabolismo , Interleucina-12/metabolismo , Interleucina-12/uso terapêutico , Interleucina-12/toxicidade , Leucemia Mieloide/terapia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Necrose , Neoplasia Residual , Quimera por Radiação , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/toxicidade , Transfecção , Vísceras/patologia
13.
Cancer Gene Ther ; 7(7): 1060-8, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10917209

RESUMO

Recombinant interleukin-12 (rlL-12) is a potent immunomodulatory cytokine that has been shown to exert strong antitumoral and antimetastatic activity against several mouse tumors grown as solid lesions. The therapeutic efficacy of rIL-12 against hematological tumors and the transfer of IL-12 genes into hematopoietic progenitor cells to deliver IL-12 to the bone marrow (BM) to treat residual leukemia has not been studied adequately. We have investigated the retroviral-mediated transduction of hematopoietic progenitor cells with IL-12 genes and the in vivo anti-leukemic activity of transduced cells against the murine myeloid leukemia cell line 32Dp210. We were able to efficiently transduce the IL-3-dependent 32Dc13 myeloid progenitor cell line and primary hematopoietic progenitor cells using an MFG-based polycistronic retroviral vector containing the cDNAs of p35 and p40 murine IL-12 genes. 32Dc13 myeloid progenitor cells expressing IL-12 genes (32DIL-12 cells) have stably secreted biologically active murine IL-12 for >9 months. Mice transplanted with 32DIL-12 cells transiently express the transgene in the BM and spleen, which is associated with a rapid elevation of interferon-gamma (IFN-gamma) in the circulation and with secretion of IFN-gamma by spleen cells in vitro. In addition, spleen and BM cells of mice injected with 32DIL-12 cells readily acquire the capacity to lyse natural killer cell-sensitive YAC-1 target cells and 32Dp210 myeloid leukemia cells. Furthermore, whereas mice challenged with leukemia cells suffered 100% mortality within 14 days, approximately 40% of mice coinjected with 32Dp210 leukemia cells and 32DIL-12 progenitor cells exhibited long-term, leukemia-free survival (>60 days). This study demonstrates that IL-12 can be stably expressed in hematopoietic cells; in addition, when transplanted, transduced cells induce IFN-gamma production and activation of natural killer cells, both of which may be involved in inhibiting the progression of leukemia in vivo.


Assuntos
Terapia Genética , Células-Tronco Hematopoéticas/imunologia , Interleucina-12/genética , Leucemia Experimental/terapia , Animais , Citotoxicidade Imunológica , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Vetores Genéticos , Interferon gama/biossíntese , Células Matadoras Naturais/imunologia , Leucemia Experimental/imunologia , Leucemia Experimental/patologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Reação em Cadeia da Polimerase , Proteínas Recombinantes/genética , Retroviridae/genética , Baço/citologia , Baço/imunologia , Transfecção
14.
Bone Marrow Transplant ; 25(6): 639-45, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10734298

RESUMO

Ex vivo purging of contaminating tumor cells may reduce the incidence of relapse in patients undergoing bone marrow transplantation. In this study we demonstrate that resveratrol, a phytoalexin with anti-oxidant and chemopreventive activity, exhibits anti-leukemic activity against mouse (32Dp210, L1210) and human (U937, HL-60) leukemic cell lines by inhibiting cell proliferation. Long-term exposure to resveratrol also inhibits the clonal growth of normal hematopoietic progenitor cells but at a higher IC50 of resveratrol than that for most of the leukemia cell lines tested. The inhibitory effect of resveratrol on hematopoietic progenitors is partially reversible, whereas the effect on leukemia cells is largely irreversible. The inhibition of leukemia cells by resveratrol involves nucleosomal DNA fragmentation (apoptosis). On the other hand, resveratrol does not induce or enhance spontaneously occurring apoptotic death in normal hematopoietic progenitor cells. In vivo experiments performed with untreated and resveratrol-treated bone marrow showed comparable hematopoietic reconstitution in lethally irradiated mice (10 Gy) as determined by survival, hematologic recovery, and the number of hematopoietic progenitor cells present in the marrow of reconstituted animals. Taken together, these results indicate the potential use of resveratrol for ex vivo pharmacological purging of leukemia cells from bone marrow autografts without significant loss in the hematopoietic activity of progenitor cells.


Assuntos
Leucemia Experimental/tratamento farmacológico , Estilbenos/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Purging da Medula Óssea , Transplante de Medula Óssea , Divisão Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sobrevivência de Enxerto/efeitos dos fármacos , Células HL-60/efeitos dos fármacos , Humanos , Leucemia Experimental/genética , Leucemia Experimental/patologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Resveratrol , Células Tumorais Cultivadas/efeitos dos fármacos , Células U937/efeitos dos fármacos , Irradiação Corporal Total
15.
J Clin Oncol ; 17(12): 3793-803, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10577851

RESUMO

PURPOSE: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy. PATIENTS AND METHODS: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20(+) B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass > or = 5 cm. RESULTS: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/microL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (> or = 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody). CONCLUSION: These phase I/II data demonstrate that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma não Hodgkin/radioterapia , Adolescente , Adulto , Anticorpos Monoclonais Murinos , Antígenos CD20/efeitos dos fármacos , Antígenos CD20/imunologia , Linfócitos B/patologia , Feminino , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Radioimunoterapia , Recidiva , Rituximab , Radioisótopos de Ítrio/uso terapêutico
16.
Clin Cancer Res ; 5(10 Suppl): 3281s-3286s, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10541376

RESUMO

Approximately 55,400 new cases of non-Hodgkin's lymphoma (NHL) are diagnosed each year, with the overall prevalence of the disease now estimated to be 243,000. Until recently, treatment alternatives for advanced disease included chemotherapy with or without external beam radiation. Based on the results of several clinical trials, the chimeric monoclonal antibody Rituximab has now been approved by the United States Food and Drug Administration as a treatment for patients with relapsed or refractory, low-grade or follicular, B-cell NHL. Several other monoclonal antibodies in conjugated and unconjugated forms have been evaluated in the treatment of NHL. Ibritumomab, the murine counterpart to Rituximab, radiolabeled with 90Y (Zevalin), is presently being evaluated in clinical trials. The success of radioimmunotherapy is dependent upon the appropriate choice of antibody, isotope, and chelator-linker. The Ibritumomab antibody targets the CD20 antigen. The antibody is covalently bound to the chelator-linker tiuxetan (MX-DTPA), which tightly chelates the isotope 90Y. To date, two Phase I/II Zevalin clinical trials have been completed in patients with low-grade, intermediate-grade, and mantle cell NHL. The overall response rate was 64% in the first trial and 67% in the later trial. Phase II and III trials are ongoing.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Linfoma não Hodgkin/radioterapia , Radioimunoterapia , Radioisótopos de Ítrio/uso terapêutico , Humanos , Ácido Pentético , Recidiva
17.
Ann Oncol ; 10(6): 655-61, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10442187

RESUMO

BACKGROUND: Rituximab is a chimeric monoclonal antibody directed against the B-cell CD20 antigen which has been utilized for therapy of B-cell non-Hodgkin's lymphoma (NHL). A previous clinical trial demonstrated that treatment with four weekly doses of 375 mg/m2 of Rituximab in patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma was well tolerated and had significant clinical activity. PATIENTS AND METHODS: To assess the safety and efficacy of Rituximab treatment, an open-label, single-arm, multi-center, phase II study of eight consecutive weekly infusions of 375 mg/m2 Rituximab in patients with low-grade or follicular B-cell NHL who had relapsed or had failed primary therapy was conducted. Thirty-seven patients with a median age of 55 years were treated. RESULTS: Grade 1 or 2 adverse events were the majority of reported toxicities and occurred most frequently with the first infusion, decreasing with subsequent infusions. No patients developed a host antibody response (HACA) to Rituximab. The mean serum immunoglobulin levels for IgG, IgA, and IgM stayed within the normal range throughout the study. The majority of patients who were bcl-2 positive at baseline in peripheral blood became bcl-2 negative during treatment and remained negative at the time of B-cell recovery. In the 37 intent-to-treat patients, 5 (14%) had a complete response and 16 (43%) had a partial response for an overall response rate of 57%. Of 35 evaluable patients, 21 (60%) responded to treatment (14% CR and 46% PR). In responders, the median time to progression (TTP) and the median response duration have not been reached after 19.4+ months and 13.4+ months, respectively. CONCLUSIONS: The safety profile and efficacy achieved in this pilot study of extended treatment with Rituximab compares favorably with those seen with four weekly doses. Further studies are warranted to investigate whether this or other extended Rituximab schedules will result in increased efficacy in all or in certain subgroups of patients with low-grade or follicular NHL.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma de Células B/terapia , Linfoma Folicular/terapia , Linfoma não Hodgkin/terapia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Murinos , Antígenos CD20/imunologia , Antineoplásicos/administração & dosagem , Antineoplásicos/imunologia , Progressão da Doença , Feminino , Humanos , Imunoglobulinas/análise , Imunoglobulinas/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Rituximab , Resultado do Tratamento
18.
J Hematother ; 8(3): 237-45, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10417046

RESUMO

We examined the antileukemic activity and the toxicity of HPC transduced with human tumor necrosis factor (TNF) cDNA. Both clonal (32Dcl3) and BM-derived primary hematopoietic progenitors (BM-Prog) expressing hTNF-alpha gene (32DTNF-alpha and BMTNF-alpha cells, respectively) inhibited the development of leukemia in mice with a small dose of 32Dp210 cells, a myeloid leukemia cell line. Whether the trans-gene expressing 32DTNF-alpha cells produce toxicities commonly associated with systemic TNF-alpha therapy was determined by examining the effect of TNF-alpha-secreting progenitor cells on body weight, tissue histology, growth of HPC, and engraftment of BMT. Administration of a low or high dose of TNF-alpha-secreting 32DTNF-alpha cells to mice failed to produce loss in body weight, a measure of TNF-alpha-related cachexia. There was also no evidence of tissue necrosis or mononuclear cell (MNC) infiltration in lung, liver, kidney, or intestine of mice injected with transduced progenitor cells. Furthermore, 32DTNF-alpha cells showed no effect on the clonal growth of HPC in colony-forming assays or loss of cellularity in BM, spleen, or blood. Finally, TNF-alpha-secreting cells were found not to interfere with the engraftment of BM transplant and hematopoietic reconstitution thereafter. We conclude from these findings that unlike systemic administration of TNF-alpha, TNF-alpha gene therapy with transduced HPC is nontoxic and may have a role in eradicating residual leukemia after BMT.


Assuntos
Terapia Genética , Células-Tronco Hematopoéticas/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Caquexia/induzido quimicamente , Linhagem Celular , Sobrevivência de Enxerto/efeitos dos fármacos , Doenças Hematológicas/induzido quimicamente , Humanos , Imunoterapia Adotiva , Leucemia Mieloide/terapia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Transdução Genética , Células Tumorais Cultivadas
19.
Hematology ; 4(4): 345-356, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-11399575

RESUMO

Recombinant chemotactic cytokines (chemokines) have been shown to modulate in vitro proliferation of hematopoietic progenitor cells. Whether bone marrow stromal cells produce chemokines and the physiological role they may have in the regulation of hematopoiesis has largely remained unexamined. We have examined the expression of monocyte chemoattractant protein-1 (MCP-1/JE) in bone marrow stromal cells and its effect on the migration and proliferation of murine hematopoietic progenitor cells. Freshly derived murine bone marrow stromal cells were found to secrete abundant amounts of MCP-1/JE, which was further increased upon stimulation of stromal cells with pro-inflammatory agents LPS, IL1-alpha, IFN-gamma, or TNF-alpha. Although culture supernatant conditioned by stromal cells exhibited chemotactic activity toward hematopoietic progenitor cells, the chemotactic activity was not due to MCP-1/JE. Furthermore, rMCP-1/JE also failed to induce migration of progenitor cells. MCP-1/JE, however, caused 20 to 30% increase in the clonal expansion of progenitor cells. Thus, although MCP-1/JE does not chemoattract hematopoietic progenitor cells it may have a role in their proliferation and clonal expansion.

20.
Bone Marrow Transplant ; 24(11): 1235-41, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10642814

RESUMO

Traditional qualitative gel electrophoresis approaches lack accurate' and quantitative assessment of mixed chimerism in BMT patients. The likelihood of informative markers is greatly increased using simultaneous amplification of 10 highly polymorphic loci with fluorescent-labeled primers in an automated DNA sequencer. This allows for more precise interpretation of mixed chimerism with a detection level approximating 1%. To evaluate this approach to quantitative assessment of chimeric populations we mixed varying proportions of samples from two unrelated donors, by either mixing aliquots of DNA isolated from whole blood, or by first counting the white blood cells and mixing varying proportions of cells together prior to DNA isolation. The allelic-peak area ratios were identical to allelic-peak height ratios and corresponded to the proportion of mixed DNA, regardless of the method used to create the mixture. Formulas to provide routine, consistent and quantitative interpretation of mixed chimerism are presented. We analyzed 14 allograft recipients and one autologous BMT patient with transfusion-induced GVHD. In all cases, at least four out of nine markers were informative. Inter-laboratory concordance of results was also obtained with an eight marker panel using an automated Alf-Express. In conclusion, the automated DNA fluorescent-labeled primer approach using an eight to 10 marker panel is quantitative and informative in assessing chimerism.


Assuntos
Transplante de Medula Óssea , Sobrevivência de Enxerto/genética , Análise de Sequência de DNA/métodos , Alelos , Doadores de Sangue , Células da Medula Óssea , DNA/sangue , Primers do DNA , Processamento Eletrônico de Dados , Feminino , Corantes Fluorescentes , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Polimorfismo Genético , Sensibilidade e Especificidade , Quimeras de Transplante , Transplante Homólogo
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