RESUMO
V(III)(OH)[O(2)C-C(6)H(4)-CO(2)].(HO(2)C-C(6)H(4)-O(2)H)(x)(DMF)(y)(H(2)O)(z) or MIL-68 was solvothermally synthesised in a non-aqueous medium. Its structure, built up from octahedral chains connected by terephthalate linkers, exhibits large hexagonal channels containing different occluded moieties. Their irreversible removal releases a specific surface area of 603(22) m(2).g(-1)(BET).
RESUMO
(V(III)(OH))(2)[C(6)H(2)(CO(2))(4)].4H(2)O (labeled MIL-60) and V(III)(OH)[(2)(O(2)C)C(6)H(2)(COOH)(2)].H(2)O (labeled MIL-61) were hydrothermally synthesized from mixtures of VCl(3), 1,2,4,5-benzenetetracarboxylic acid, and water heated for 3 days at 473 K. The structure of MIL-60 was solved from single-crystal X-ray diffraction data in the triclinic centrosymmetric P1 (No. 2) space group with lattice parameters a = 6.3758(5) A, b = 6.8840(5) A, c = 9.0254(5) A, alpha = 69.010(2) degrees, beta = 85.197(2) degrees, gamma = 79.452(2) degrees, V = 363.53(5) A(3), and Z = 1. The structure of MIL-61 was ab initio determined from an X-ray powder diffraction pattern. MIL-61 crystallizes in the Pnma (No. 62) orthorhombic space group with lattice parameters a = 14.8860(1) A, b = 6.9164(1) A, c = 10.6669(2) A, V = 1098.23(3) A(3), and Z = 4. Both structures contain the same inorganic building block that consists of trans chains of V(III)O(4)(OH)(2) octahedra. The three-dimensional frameworks of MIL-60 and MIL-61 are constituted by the linkage of these chains via the organic molecules so delimiting the channels or cages where the water molecules are encapsulated. The magnetic behavior of these two phases is presented: MIL-60 is paramagnetic, and MIL-61 antiferromagnetically orders below T(N) = 55(5) K.
RESUMO
[V(III)(H2O)]3O(O2CC6H4CO2)3.(Cl, 9H2O) (denoted MIL-59) presents a three-dimensional framework built up from octahedral vanadium trimers joined via the isophthalate anionic linkers to delimit cages where water molecules and chlorine anions are occluded; the frustrated magnetic behaviour of MIL-59 is discussed.
RESUMO
Non-small-cell lung carcinoma (NSCLC) is a particularly serious disease because of its chemoresistance to current treatments. To investigate the nature of his generally innate resistance, we cloned an established cell line (NSCLC-N6) derived from a non-small cell bronchopulmonary carcinoma. Four cell subpopulations (C15, C65, C92 and C98) were isolated from the mother line. These four clones were studied in comparison with each other for cell doubling time in vitro, ploidy, chemosensitivity in vitro, cytogenetic, expression of the oncogene erb-B2 and other tumor markers (Kr, CEA and Chr A). Each clone shows a distinct biologic pattern for various biological parameters. Our results indicated hat cell doubling time (in vitro) increased when the hyperploid population was prevailing. The clones differ in their chemosensitivity to therapeutic agents. This cellular diversity might help to explain why these tumors are chemoresistant. This heterogeneity within NSCLC tumors should be taken into consideration in the choice of treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Aneuploidia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cromogranina A , Cromograninas/metabolismo , Aberrações Cromossômicas/patologia , Transtornos Cromossômicos , Células Clonais , DNA de Neoplasias/metabolismo , Humanos , Cariotipagem , Queratinas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Receptor ErbB-2/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Pachymatismin is a novel glycoprotein extracted from a marine sponge, which has an antiproliferative effect in vitro on cells from a human non-small-cell bronchopulmonary carcinoma (NSCLC-N6). The drug blocks irreversibly the cells in the G0/G1 phase of the cell cycle. Here, we investigate the antitumor activity of pachymatismin against this cell line. Tumor growth was studied after three weeks treatment of nude mice by different doses of pachymatismin. A significant decrease in tumor growth was observed.
Assuntos
Antineoplásicos/farmacologia , Fatores Biológicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glicoproteínas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Poríferos/química , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Camundongos Nus , Transplante Heterólogo , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/transplanteRESUMO
We studied the pharmacomodulating effects of a marine substance, bistramide D, which is capable of inducing terminal differentiation on the expression of the c-erb-B1, ras, src, myc and p53 genes in the NSCLC-N6 cell line established from a non-small cell lung carcinoma. Analysis (subsequent to treatment) demonstrated that among the genes for which it was possible to detect expression, namely c-erb-B1, c-myc and p53, only the expression of the p53 gene varied significantly. The increase of the expression rate of the p53 gene underlines its prominent role in the control of cell proliferation and differentiation.
Assuntos
Neoplasias Brônquicas/metabolismo , Neoplasias Brônquicas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteína Supressora de Tumor p53/biossíntese , Antineoplásicos/farmacologia , Northern Blotting , Neoplasias Brônquicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Receptores ErbB/biossíntese , Receptores ErbB/genética , Éteres Cíclicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes p53 , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Oncogenes , Proteínas Proto-Oncogênicas c-myc/biossíntese , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas pp60(c-src)/biossíntese , Proteínas Proto-Oncogênicas pp60(c-src)/genética , RNA Neoplásico/análise , RNA Neoplásico/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Proteínas ras/biossíntese , Proteínas ras/genéticaRESUMO
Fucans, sulfated polysaccharides extracted from brown seaweeds, have been shown to be endowed with inhibitory effects cell growth in various experimental models. We studied both the antiproliferative and antitumor properties of a fucoidan extract (HF) obtained from the brown seaweed Ascophyllum nodosum on a cell line derived from a non-small-cell human bronchopulmonary carcinoma (NSCLC-N6), this type of carcinoma is particularly chemo-resistant. HF exerts in vitro a reversible antiproliferative activity with a block observed in the G1 phase the cell cycle. Studies performed with the NSCLC-bearing nude mice show antitumor activity at subtoxic doses. These preliminary results indicate that HF exhibits inhibitory effect both in vitro and in vivo and is very potent antitumor agent in cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Brônquicas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Phaeophyceae/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Neoplasias Brônquicas/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
The inhibitory effect of natural substances of marine origin on the erb-B2 oncogene of a human NSCLC-N6 line was demonstrated in vitro by simultaneous study of the expression of the gene and its product, using respectively an erb-B2 specific probe and an anti-c-erb-B2 polyclonal antibody. Preliminary results indicate inhibition ranging from 17-77% of oncogene expression and from 77-90% of product expression. The fact that substances of this type, with different chemical structures, have the common ability to induce terminal differentiation in an experimental model after irreversible blockade in G1 phase suggests a relationship between the inhibition of certain oncogenes and terminal differentiation.
Assuntos
Acetamidas , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/biossíntese , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Oncogenes/efeitos dos fármacos , Proteínas Proto-Oncogênicas/biossíntese , Piranos , Diferenciação Celular/efeitos dos fármacos , Diterpenos/farmacologia , Éteres Cíclicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptor ErbB-2 , Compostos de Espiro , Succinimidas/farmacologia , Células Tumorais CultivadasRESUMO
Bistramides A, D and K are substances extracted from the marine ascidian Lissoclinum bistratum Sluiter that are capable of inducing in vitro terminal differentiation (G1DT) of cells from a non-small cell broncho-pulmonary carcinoma (NSCLCN6), but present different in vitro toxicities. This study shows that only the least toxic bistramides D and K possess an antitumor activity. These two substances could be administered as a continuous treatment which would induce terminal differentiation of stem cells at their entry into the cell cycle, thereby causing their destruction.
Assuntos
Acetamidas , Antineoplásicos/uso terapêutico , Carcinoma Broncogênico/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Éteres Cíclicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Piranos , Animais , Carcinoma Broncogênico/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos , Camundongos Nus , Estrutura Molecular , Análise de Regressão , Compostos de Espiro , Relação Estrutura-Atividade , Transplante HeterólogoRESUMO
Vinorelbine (NavelbineR) is a new antitumor agent chemically related to the Vinca alkaloid group, but differentiated by its in vivo activity relative to non-small-cell lung carcinoma (NSCLC). Studies in the NSCLC-bearing nude mouse of vinorelbine associations with drugs currently used clinically in phase III (cisplatin, 5-fluorouracil and actinomycin D) showed that such associations are ineffective or even of negative value and that it would be preferable to use vinorelbine alone in a single dose at the maximum tolerated concentration.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Cisplatino/administração & dosagem , Dactinomicina/administração & dosagem , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/administração & dosagem , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
Bistramide A, a new toxin isolated from a New Caledonian Urochordata, shows an antiproliferative effect on a non-small-cell lung carcinoma line in vitro and G1-blockade. In this work, the growth arrest induced by bistramide A was shown to be irreversible as assessed by growth kinetics of pretreated cells. Furthermore, the drug caused an underexpression of the nuclear antigen Ki67. These events are similar to a G1-differentiation cell cycle step blockage and a terminal maturation induction.
Assuntos
Acetamidas , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Éteres Cíclicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Piranos , Ciclo Celular/imunologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Humanos , Antígeno Ki-67 , Proteínas de Neoplasias/análise , Proteínas Nucleares/análise , Compostos de Espiro , Células Tumorais CultivadasRESUMO
The antiproliferative activity of two nitrogenous labdane cytotoxic substances from Lissoclinum voeltzkowi Michaelson (Urochordata), dichlorolissoclimide (P2) and chlorolissoclimide (P1), was studied in vitro on a continuous human non-small-cell bronchopulmonary carcinoma line (NSCLC-N6) at the cell cycle level. This antiproliferative effect resulted from a blockade of G1 phase cells. Mortality occurred, regardless of the degree of cell ploidy, with cell transition to an out-of-cycle situation characteristic of a G1D terminal maturation state.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diterpenos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Succinimidas/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Citometria de Fluxo , Fase G1/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Células Tumorais CultivadasRESUMO
The antiproliferative effects of bistramide A, a nitrogenous dilactam polyether from Lissoclinum bistratum Sluiter (Urochordata), were studied at the level of the cell cycle in asynchronous cells of the NSCLCN6-L16 line. Bistramide A has a dual mechanism that induces blockade in the G1 phase (compatible with differentiation properties reported elsewhere) and causes polyploidy that is suggestive of inaptitude for cytokinesis. These effects confirm the results of cytomorphology studies in electron microscopy.
Assuntos
Acetamidas , Antineoplásicos/uso terapêutico , Carcinoma Broncogênico/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Éteres Cíclicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Piranos , Animais , Antineoplásicos/toxicidade , Carcinoma Broncogênico/ultraestrutura , Carcinoma Pulmonar de Células não Pequenas/ultraestrutura , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Ensaios de Seleção de Medicamentos Antitumorais , Éteres Cíclicos/toxicidade , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/ultraestrutura , Camundongos , Camundongos Nus , Microscopia Eletrônica , Transplante de Neoplasias , Compostos de Espiro , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/ultraestruturaRESUMO
Three personal cases, and the cases of literature of congenital adrenal hypoplasia with cytomegaly allow an histological definition. Clinical and biological findings are described. In 2 cases, a diffused hypertrophy of the cells responsible for corticotrope or melanotrope secretion was discovered; it confirmed the peripheral adrenal origin of the condition, as well as high plasmatic level of ACTH, in the third case. Sex-bound cytomegalic adrenal hypoplasia is differenciated from other cortico-adrenal insufficiencies with cytomegaly.