Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
1.
World J Surg Oncol ; 21(1): 287, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37697316

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyze the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma. METHODS: Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates. RESULTS: The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflammatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analyzing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05. CONCLUSIONS: In this study, we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. Our results revealed a high CXCR4 expression in the tumor stroma, which is related to a poor tumor differentiation. On the contrary, we could not find an association between CXCR4 expression and survival and the rest of the clinicopathological variables. Focusing the study on the CXCR4 expression in the tumor stroma could generate more robust results. Therefore, we consider it key to develop more studies to enlighten the role of this receptor in PDAC and its implication as a possible biomarker.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Receptores CXCR4 , Microambiente Tumoral , Biomarcadores Tumorais , Neoplasias Pancreáticas
2.
J Clin Nurs ; 27(7-8): 1464-1474, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29396899

RESUMO

AIMS AND OBJECTIVES: To analyse quality of life and satisfaction after immediate breast reconstruction due to cancer and its determining factors. BACKGROUND: Studying breast reconstruction is important because of its frequency and variability. In addition to the surgical results, it is necessary to analyse the quality of life and patient satisfaction using a specific tool. DESIGN METHODS: An ambispective design was used (n = 101; α = 0.05; precision = 10%), studying anthropometric, sociocultural data, Fagerström test and the BREAST-Q© questionnaire. A logistic regression analysis was performed to identify variables associated with quality of life and satisfaction. RESULTS: Mean age of the patients on diagnosis was 44.87 ± 8.5 years. Forty-one of the patients were carried out a skin-sparing mastectomy (42.7%). Immediate reconstruction was performed with implant in 73 (74.5%). The domains on the BREAST-Q© for quality of life with the lowest scores were physical well-being chest (74) and sexual well-being (61.5). The satisfaction domain with the lowest score was with the breast (59). The variables associated with the worst quality of life in the physical well-being chest domain were the skin-sparing mastectomy (OR, 4.2; 95% confidence interval (CI), 1.2-14.1) and lymphedema (OR, 12.9; 95% CI, 1.0-159.9). Antibody treatment was associated with a worse score on the psychosocial well-being domain (OR, 4.25; 95% CI, 1.0-18.0) and sexual well-being domain (OR, 7.34; 95% CI, 0.9-54.6). Satisfaction was associated with nicotine dependence on the breast and outcome scale. The higher the dependence on nicotine, the greater the dissatisfaction with the breasts (OR, 2.41; 95% CI, 1.1-5.3) and with the result (OR, 2.45; 95% CI, 1.0-5.9). CONCLUSIONS: The type of treatment and lymphedema modify the patients' quality of life. Nicotine dependence is associated with lower satisfaction with the breast and with the outcome. RELEVANCE TO CLINICAL PRACTICE: This study suggests the need for multidisciplinary attention during the first year of adjuvant treatment despite the benefits of immediate reconstruction. It shows the need for preoperative assessment of the level of nicotine dependence, anxiety and depression of smoking patients before preoperative counselling.


Assuntos
Neoplasias da Mama/psicologia , Mamoplastia/psicologia , Mastectomia/psicologia , Satisfação do Paciente/estatística & dados numéricos , Satisfação Pessoal , Qualidade de Vida/psicologia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Espanha , Inquéritos e Questionários
3.
Cancers (Basel) ; 16(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38730669

RESUMO

BACKGROUND: Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer stem cells. MATERIALS AND METHODS: A randomized trial involving 42 patients. All patients were diagnosed with pancreatic ductal adenocarcinoma. Group I: R0 resection. Group II. R0 resection and HIPEC with gemcitabine (120 mg/m2 for 30 min). Effectiveness was measured with analysis of overall survival, disease-free survival, distant recurrence, locoregional recurrence, and measuring of pancreatic cancer stem cells (EpCAM+CXCR4+CD133+). RESULTS: From 2017 to 2023, 63 patients were recruited for our clinical trial; 21 patients were included in each group, and 21 were excluded. Locoregional recurrence, p-value: 0.022, was lower in the experimental group. There were no significant differences between the two groups in hospital mortality, perioperative complications, or hospital costs. We found a significant decrease in pancreatic cancer stem cells in patients in the experimental group after treatment, p -value of 0.018. CONCLUSIONS: The use of HIPEC with gemcitabine after surgery in patients with resectable pancreatic ductal adenocarcinoma reduces locoregional recurrence and may be associated with a significant decrease in pancreatic cancer stem cells.

4.
Front Oncol ; 11: 650316, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268110

RESUMO

Despite current strategies combining surgery, radiation, and chemotherapy, glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Tumor location plays a key role in the prognosis of patients, with GBM tumors located in close proximity to the lateral ventricles (LVs) resulting in worse survival expectancy and higher incidence of distal recurrence. Though the reason for worse prognosis in these patients remains unknown, it may be due to proximity to the subventricular zone (SVZ) neurogenic niche contained within the lateral wall of the LVs. We present a novel rodent model to analyze the bidirectional signaling between GBM tumors and cells contained within the SVZ. Patient-derived GBM cells expressing GFP and luciferase were engrafted at locations proximal, intermediate, and distal to the LVs in immunosuppressed mice. Mice were either sacrificed after 4 weeks for immunohistochemical analysis of the tumor and SVZ or maintained for survival analysis. Analysis of the GFP+ tumor bulk revealed that GBM tumors proximal to the LV show increased levels of proliferation and tumor growth than LV-distal counterparts and is accompanied by decreased median survival. Conversely, numbers of innate proliferative cells, neural stem cells (NSCs), migratory cells and progenitors contained within the SVZ are decreased as a result of GBM proximity to the LV. These results indicate that our rodent model is able to accurately recapitulate several of the clinical aspects of LV-associated GBM, including increased tumor growth and decreased median survival. Additionally, we have found the neurogenic and cell division process of the SVZ in these adult mice is negatively influenced according to the presence and proximity of the tumor mass. This model will be invaluable for further investigation into the bidirectional signaling between GBM and the neurogenic cell populations of the SVZ.

5.
Bioorg Med Chem ; 18(15): 5701-7, 2010 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-20615714

RESUMO

Benzo[b]thiophenesulfonamide 1,1-dioxide derivatives (BTS) were described as candidate antineoplastic drugs. In the hope of finding new compounds with improved antitumour activity and reduced toxicity, we have designed and synthesized a small series of benzo[b]thiophene-6-carboxamide 1,1-dioxide derivatives (BTC) structurally related with the best reported BTS. Growth inhibition of HTB-54, CCRF-CEM and HeLa tumour cells lines at nanomolar concentrations was exhibited by some of the BTC. Hydrophobic substituents on the carboxamide group increased cytotoxicity but substitution by a hydroxy group diminished it, thus pointing to the electronic density on benzo[b]thiophene nucleus as a determinant factor. The process of cell death induced by BTC derivatives was further analyzed in CCRF-CEM cells, where these compounds induced apoptosis in a time and dose-dependent manner and cell cycle arrest at S phase. BTC derivatives also induced a significant increase in intracellular ROS levels in this cell line. Previous treatment of the cells with the antioxidant N-acetyl-cysteine abrogated the induction of apoptosis by BTC indicating that ROS generation is a previous event required to trigger the BTC induced apoptotic process.


Assuntos
Antineoplásicos/química , Tiofenos/química , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Tiofenos/síntese química , Tiofenos/uso terapêutico
6.
Bioorg Med Chem ; 18(7): 2713-9, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20233660

RESUMO

Mycobacterium tuberculosis (M.Tb) is a bacillus capable of causing a chronic and fatal condition in humans known as tuberculosis (TB). It is estimated that there are 8 million new cases of TB per year and 3.1 million infected people die annually. Thirty-six new amide quinoxaline 1,4-di-N-oxide derivatives have been synthesized and evaluated as potential anti-tubercular agents, obtaining biological values similar to the reference compound, Rifampin (RIF).


Assuntos
Antituberculosos/síntese química , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Quinoxalinas/síntese química , Quinoxalinas/farmacologia , Animais , Chlorocebus aethiops , Cromatografia em Camada Fina , Humanos , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/crescimento & desenvolvimento , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Relação Estrutura-Atividade , Tuberculose/epidemiologia , Células Vero
7.
Bioorg Med Chem ; 18(9): 3125-32, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-20371184

RESUMO

The heterocyclic N-oxide, 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine, 1), shows promising antitumor activity in preclinical studies, but there is a continuing need to explore new compounds in this general structural category. In the work described here, we examined the properties of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide (9h). We find that 9h causes redox-activated, hypoxia-selective DNA cleavage that mirrors the lead compound, tirapazamine, in both mechanism and potency. Furthermore, we find that 9h displays hypoxia-selective cytotoxicity against human cancer cell lines.


Assuntos
DNA/química , DNA/efeitos dos fármacos , Hipóxia , Quinoxalinas/química , Quinoxalinas/farmacologia , Antineoplásicos/farmacologia , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/química , DNA/metabolismo , Clivagem do DNA , Humanos , Estrutura Molecular , NADP/química , Oxirredução , Tirapazamina , Triazinas/farmacologia
8.
Bioorg Med Chem ; 17(1): 385-9, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19058970

RESUMO

New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 microg/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivatives showed a good in vitro activity/toxicity ratio. The most active and selective compounds carry a fluorine atom in the quinoxaline 7-position or in the phenyl substituent para-position. In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new analogues, particularly compound 7-methyl-3-(4'-fluoro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide (MIC <0.2 microg/mL and SI > 500).


Assuntos
Antituberculosos/síntese química , Mycobacterium tuberculosis/efeitos dos fármacos , Quinoxalinas/farmacologia , Antituberculosos/farmacologia , Flúor , Humanos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
9.
Molecules ; 14(6): 2256-72, 2009 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-19553897

RESUMO

Neglected diseases represent a major health problem. It is estimated that one third of the world population is infected with tuberculosis (TB). Besides TB, Chagas disease, affects approximately 20 million people. Quinoxalines display great activities against TB and Chagas. Forty new quinoxaline 1,4-di-N-oxide derivatives have been prepared and tested against M. tuberculosis and T. cruzi. Carboxylic acid quinoxaline 1,4-di-N-oxides (CAQDOs) 5 and 17 showed MIC values on the same order as the reference antituberculosis drug, rifampicin. Meanwhile, CAQDOs 12 and 22 presented IC(50) values in the same order as the anti-chagasic drug, nifurtimox.


Assuntos
Antituberculosos/química , Antituberculosos/farmacologia , Quinoxalinas/química , Quinoxalinas/farmacologia , Animais , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina , Trypanosoma/efeitos dos fármacos
10.
Antimicrob Agents Chemother ; 52(9): 3321-6, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18625764

RESUMO

This study extends earlier reports regarding the in vitro efficacies of the 1,4-di-N-oxide quinoxaline derivatives against Mycobacterium tuberculosis and has led to the discovery of a derivative with in vivo efficacy in the mouse model of tuberculosis. Quinoxaline-2-carboxylate 1,4-di-N-oxide derivatives were tested in vitro against a broad panel of single-drug-resistant M. tuberculosis strains. The susceptibilities of these strains to some compounds were comparable to those of strain H(37)Rv, as indicated by the ratios of MICs for resistant and nonresistant strains, supporting the premise that 1,4-di-N-oxide quinoxaline derivatives have a novel mode of action unrelated to those of the currently used antitubercular drugs. Specific derivatives were further evaluated in a series of in vivo assays, including evaluations of the maximum tolerated doses, the levels of oral bioavailability, and the efficacies in a low-dose aerosol model of tuberculosis in mice. One compound, ethyl 7-chloro-3-methylquinoxaline-2-carboxylate 1,4-dioxide, was found to be (i) active in reducing CFU counts in both the lungs and spleens of infected mice following oral administration, (ii) active against PA-824-resistant Mycobacterium bovis, indicating that the pathway of bioreduction/activation is different from that of PA-824 (a bioreduced nitroimidazole that is in clinical trials), and (iii) very active against nonreplicating bacteria adapted to low-oxygen conditions. These data indicate that 1,4-di-N-oxide quinoxalines hold promise for the treatment of tuberculosis.


Assuntos
Antituberculosos , Óxidos N-Cíclicos , Modelos Animais de Doenças , Mycobacterium tuberculosis/efeitos dos fármacos , Quinoxalinas , Tuberculose Pulmonar/tratamento farmacológico , Animais , Antituberculosos/química , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/farmacologia , Óxidos N-Cíclicos/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Humanos , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana/normas , Mycobacterium tuberculosis/isolamento & purificação , Quinoxalinas/química , Quinoxalinas/farmacologia , Quinoxalinas/uso terapêutico , Organismos Livres de Patógenos Específicos , Baço/microbiologia , Relação Estrutura-Atividade , Resultado do Tratamento , Tuberculose Pulmonar/microbiologia
11.
J Antimicrob Chemother ; 62(3): 547-54, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18502817

RESUMO

OBJECTIVES: To evaluate a novel series of quinoxaline 1,4-di-N-oxides for in vitro activity against Mycobacterium tuberculosis and for efficacy in a mouse model of tuberculosis (TB). METHODS: Ketone and amide derivatives of quinoxaline 1,4-di-N-oxide were evaluated in in vitro and in vivo tests including: (i) activity against M. tuberculosis resistant to currently used antitubercular drugs including multidrug-resistant strains (MDR-TB resistant to isoniazid and rifampicin); (ii) activity against non-replicating persistent (NRP) bacteria; (iii) MBC; (iv) maximum tolerated dose, oral bioavailability and in vivo efficacy in mice; and (v) potential for cross-resistance with another bioreduced drug, PA-824. RESULTS: Ten compounds were tested on single drug-resistant M. tuberculosis. In general, all compounds were active with ratios of MICs against resistant and non-resistant strains of

Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Quinoxalinas/farmacologia , Tuberculose/tratamento farmacológico , Administração Oral , Animais , Antituberculosos/metabolismo , Biotransformação , Farmacorresistência Bacteriana Múltipla , Feminino , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana , Estrutura Molecular , Quinoxalinas/metabolismo , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
12.
Eur J Med Chem ; 43(9): 1903-10, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18215443

RESUMO

As a continuation of our research and with the aim of obtaining new antimalarial agents, new series of 3-phenylquinoxaline 1,4-di-N-oxide derivatives have been synthesized following the classical Beirut reaction. Antiplasmodial activity was evaluated in vitro against Plasmodium falciparum by the incorporation of [3H]-hypoxanthine. Cytotoxicity was tested in KB cells by AlamarBlue assay. Twenty-one of the 60 compounds that were assayed against 3D7 (CQ-sensitive) showed enough activity to be also evaluated against K1 (CQ-resistant) strain. Ten of them were shown to be more active than chloroquine in the resistant strain. The most interesting compounds are 7-(methyl or methoxy)-3-(4'-fluoro or chloro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxides because of their low IC50 and their high SI shown for the K1 strain, making them valid new leads.


Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacocinética , Quinoxalinas/síntese química , Quinoxalinas/farmacologia , Animais , Antimaláricos/química , Antimaláricos/toxicidade , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Humanos , Células KB , Plasmodium falciparum/efeitos dos fármacos , Quinoxalinas/química , Quinoxalinas/toxicidade , Relação Estrutura-Atividade
13.
Mem Inst Oswaldo Cruz ; 103(8): 778-80, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19148416

RESUMO

A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E)-3-(3,4,5-trimethoxy-phenyl)-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl)-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.


Assuntos
Antiprotozoários/química , Óxidos N-Cíclicos/química , Leishmania mexicana/efeitos dos fármacos , Quinoxalinas/química , Animais , Antiprotozoários/farmacologia , Antiprotozoários/toxicidade , Óxidos N-Cíclicos/farmacologia , Óxidos N-Cíclicos/toxicidade , Feminino , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Parasitária , Quinoxalinas/farmacologia , Quinoxalinas/toxicidade , Relação Estrutura-Atividade
14.
Molecules ; 13(1): 86-95, 2008 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-18259132

RESUMO

The unexpected substitution of fluorine atoms and phenoxy groups attached to quinoxaline or benzofuroxan rings is described. The synthesis of 2-benzyl- and 2-phenoxy-3-methylquinoxaline 1,4-di-N-oxide derivatives was based on the classical Beirut reaction. The tendency of fluorine atoms linked to quinoxaline or benzofuroxan rings to be replaced by a methoxy group when dissolved in an ammonia saturated solution of methanol was clearly demonstrated. In addition, 2-phenoxyquinoxaline 1,4-di-N-oxide derivatives became 2-aminoquinoxaline 1,4-di-N-oxide derivatives in the presence of gaseous ammonia.


Assuntos
Flúor/química , Fenóis/química , Quinoxalinas/síntese química , Antituberculosos/química , Espectrometria de Massas , Quinoxalinas/química
15.
Molecules ; 13(1): 69-77, 2008 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-18259130

RESUMO

The aim of this study was to identify new compounds active against Plasmodium falciparum based on our previous research carried out on 3-phenyl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives. Twelve compounds were synthesized and evaluated for antimalarial activity. Eight of them showed an IC(50) less than 1 microM against the 3D7 strain. Derivative 1 demonstrated high potency (IC(50)= 0.63 microM) and good selectivity (SI=10.35), thereby becoming a new lead-compound.


Assuntos
Antimaláricos/síntese química , Antimaláricos/farmacologia , Óxidos N-Cíclicos/síntese química , Óxidos N-Cíclicos/farmacologia , Nitrilas/síntese química , Nitrilas/farmacologia , Óxidos/síntese química , Óxidos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Quinoxalinas/síntese química , Quinoxalinas/farmacologia , Animais , Antimaláricos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular , Óxidos N-Cíclicos/química , Resistência a Medicamentos/efeitos dos fármacos , Nitrilas/química , Óxidos/química , Testes de Sensibilidade Parasitária , Quinoxalinas/química
16.
J Med Chem ; 50(22): 5485-92, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17910426

RESUMO

As a continuation of our research in the quinoxaline 1,4-di-N-oxide new series of 2-arylcarbonyl-3-trifluoromethylquinoxaline, 1,4-di-N-oxide derivatives have been synthesized and evaluated in a full panel of 60 human tumor cell lines. Selective reductions were carried out on two compounds which allowed us to determine the compound structures by comparison of the 1H NMR spectra. In general, all the di-N-oxidized compounds showed good cytotoxic parameters. The best activity was observed in derivatives with electron-withdrawing groups in position 6 or 7 on the quinoxaline ring and in the unsubstituted analogues, whereas loss of one or two oxygens reduced the cytotoxicity. The best five compounds were selected for evaluation for the in vivo hollow fiber assays. In vitro studies reveal that compound 5h efficiently generates reactive oxygen species via redox cycling in the presence of the NADPH/cytochrome P450 enzyme system, providing a plausible molecular mechanism for the observed aerobic cytotoxicity of these quinoxaline N-oxides.


Assuntos
Antineoplásicos/síntese química , Óxidos N-Cíclicos/síntese química , Quinoxalinas/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Dano ao DNA , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , NAD/metabolismo , Oxirredução , Quinoxalinas/química , Quinoxalinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
17.
Bioorg Med Chem Lett ; 17(23): 6439-43, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17942306

RESUMO

We report the synthesis, anti-inflammatory and antioxidant activities of novel ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4,5-dihydro-(1H)-pyrazole analogues. The tested compounds inhibit the carrageenin-induced rat paw edema (4.5-56.1%) and present important scavenging activities. Compound 2a is the most potent (56.1%) in the in vivo experiment and exhibits promising in vitro inhibition of soybean lipoxygenase (IC(50)<1microM).


Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Antioxidantes/síntese química , Pirazóis/síntese química , Quinoxalinas/síntese química , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Edema/tratamento farmacológico , Pirazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Ratos
18.
Rev Lat Am Enfermagem ; 25: e2958, 2017 Dec 21.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-29267541

RESUMO

OBJECTIVES: to determine the quality of life and anxiety in patients with breast cancer and the changes they experience after treatments. METHOD: prospective study. Breast cancer statistics (n=339, confidence=95%, accuracy= ± 5.32%). The quality of life questionnaires (QLQ) used were QLQ C-30 and QLQ Br23, and the State-Trait Anxiety Inventory (STAI) was used for anxiety. A multivariate analysis was performed to identify variables associated with baseline quality of life and anxiety as well as pre- and post-treatment differences. Authorization was obtained from the Ethics Committee, and informed consent was provided by all patients. RESULTS: the baseline quality of life dimensions with the lowest score were future prospects (46.0/100) and sexual enjoyment (55.7/100). The dimensions with the highest score were body image (94.2/100) and role (93.3/100). The most disturbing symptoms were insomnia, fatigue and concern about hair loss. After treatment, the dimensions of physical function, role, body image, financial concerns and symptomatology worsened, whereas emotional function and future prospects improved. Severe anxiety presented as a state (48.6%) and as a trait (18.2%). The highest baseline state anxiety was associated with married-widowed status and anxiolytic medication. The greatest trait anxiety was associated with an inactive work situation, anxiolytic medication, breast swelling and advanced stage at diagnosis. After treatment, anxiety significantly decreased. CONCLUSIONS: After treatment, the quality of life score was positively modified, while state and trait anxiety decreased.


Assuntos
Ansiedade/etiologia , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Qualidade de Vida , Neoplasias da Mama/terapia , Autoavaliação Diagnóstica , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Oral Maxillofac Surg ; 17(2): 155-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22899469

RESUMO

BACKGROUND: Adenocarcinomas arising from the nasal cavity and paranasal sinus are malignant tumours that are not of minor salivary gland origin, and they do not demonstrate histopathological features of sinonasal intestinal-type adenocarcinoma. These adenocarcinomas are divided into low- and high-grade subtypes. We herein present a case to highlight the significance of a correct histological diagnosis for treatment and follow-up. CASE REPORT: We report a case of a recurrent low-grade adenocarcinoma arising in the left nasal cavity and extending to the ethmoid, maxillary sinus and orbital floor. No facial deformity or proptosis was present. The diagnosis was made by analysis of a sample taken by biopsy and CT-MRI. We performed a radical maxillectomy and reconstruction with a temporalis muscle flap and a titanium mesh for the orbital floor. DISCUSSION: Low-grade adenocarcinomas of the sinonasal tract are a challenge for the pathologist to differentiate from benign adenomas and high-grade adenocarcinomas, but the distinction is important because the treatment and prognosis differ. Treatment success is determined by complete surgical excision. We also suggest the usefulness of PET to detect recurrence during follow-up.


Assuntos
Adenocarcinoma/diagnóstico , Cavidade Nasal , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Nasais/diagnóstico , Neoplasias dos Seios Paranasais/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Maxila/cirurgia , Cavidade Nasal/patologia , Cavidade Nasal/cirurgia , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Nasais/patologia , Neoplasias Nasais/cirurgia , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/cirurgia , Seios Paranasais/patologia , Seios Paranasais/cirurgia , Reoperação/métodos , Retalhos Cirúrgicos/cirurgia , Telas Cirúrgicas , Tomografia Computadorizada por Raios X , Conchas Nasais/patologia , Conchas Nasais/cirurgia
20.
Rev. latinoam. enferm. (Online) ; 25: e2958, 2017. tab
Artigo em Inglês | LILACS, BDENF | ID: biblio-961129

RESUMO

ABSTRACT Objectives: to determine the quality of life and anxiety in patients with breast cancer and the changes they experience after treatments. Method: prospective study. Breast cancer statistics (n=339, confidence=95%, accuracy= ± 5.32%). The quality of life questionnaires (QLQ) used were QLQ C-30 and QLQ Br23, and the State-Trait Anxiety Inventory (STAI) was used for anxiety. A multivariate analysis was performed to identify variables associated with baseline quality of life and anxiety as well as pre- and post-treatment differences. Authorization was obtained from the Ethics Committee, and informed consent was provided by all patients. Results: the baseline quality of life dimensions with the lowest score were future prospects (46.0/100) and sexual enjoyment (55.7/100). The dimensions with the highest score were body image (94.2/100) and role (93.3/100). The most disturbing symptoms were insomnia, fatigue and concern about hair loss. After treatment, the dimensions of physical function, role, body image, financial concerns and symptomatology worsened, whereas emotional function and future prospects improved. Severe anxiety presented as a state (48.6%) and as a trait (18.2%). The highest baseline state anxiety was associated with married-widowed status and anxiolytic medication. The greatest trait anxiety was associated with an inactive work situation, anxiolytic medication, breast swelling and advanced stage at diagnosis. After treatment, anxiety significantly decreased. Conclusions: After treatment, the quality of life score was positively modified, while state and trait anxiety decreased.


RESUMO Objetivos: determinar a qualidade de vida e a ansiedade de pacientes com câncer de mama e as mudanças sofridas após os tratamentos. Método: estudo prospectivo. Incidentes de câncer de mama (n = 339, nível de confiança = 95%, precisão = ± 5,32%). Os questionários de qualidade de vida foram o QLQC-30 e o QLQBr23 e o de ansiedade, o Inventário de Ansiedade Traço Estado (IDATE; em inglês: State-Trait Anxiety Inventory - STAI). Foi feita uma análise multivariada para identificar as variáveis associadas à qualidade de vida e à ansiedade iniciais e as diferenças entre os períodos pré e pós tratamento. Foi obtido consentimento informado e uma autorização do Comitê de Ética. Resultados: as dimensões iniciais da qualidade de vida com as menores pontuações foram: perspectivas futuras (46,0/100) e prazer sexual (55,7/100). Dimensões com as pontuações mais altas: imagem corporal (94,2/100) e funcional (93,3/100). Os sintomas mais perturbadores foram: insônia, fadiga e preocupação com a queda de cabelo. Após os tratamentos, pioraram: função física, funcional, imagem corporal, preocupações financeiras e sintomatologia. A função emocional e as perspectivas futuras melhoraram. A ansiedade grave foi apresentada como estado (48,6%) e como traço (18,2%). A maior ansiedade inicial como estado estava associada ao estado civil de casada ou viúva e ao uso de medicamentos ansiolíticos. A maior ansiedade como traço estava associada a: situação inativa no trabalho, medicamentos ansiolíticos, inchaço nas mamas e estágios avançados no momento do diagnóstico. Após os tratamentos, a ansiedade diminui significativamente. Conclusões: após os tratamentos, a pontuação da qualidade de vida é modificada positivamente e a ansiedade como estado e traço diminui.


RESUMEN Objetivos: determinar calidad de vida y ansiedad en pacientes con cáncer de mama y cambios experimentados tras tratamientos. Método: estudio prospectivo. Casos incidentes de cáncer de mama(n=339;seguridad=95%;precisión=±5,32%). Los cuestionarios de calidad de vida fueron: QLQC-30, QLQBr23, y ansiedad: STAI. Se realizó análisis multivariado para identificar variables asociadas a calidad de vida y ansiedad basales y las diferencias pre y post tratamiento. Se obtuvo autorización del comité de ética y consentimiento informado. Resultados: las dimensiones de calidad de vida basales con menor puntuación son: perspectivas de futuro(46,0/100), disfrute sexual(55,7/100). Dimensiones con mayor puntuación: imagen corporal(94,2/100), funcionalidad del rol(93,3/100). Los síntomas más perturbadores fueron: insomnio, fatiga, preocupación por pérdida del cabello. Tras tratamientos, empeoraron: función física, del rol, imagen corporal, dificultades financieras y sintomatología. Mejoraron la función emocional y perspectivas de futuro. Presentaron ansiedad severa como estado 48,6% y como rasgo 18,2%. La mayor ansiedad estado basal se asoció con estado civil casadas-viudas y medicación ansiolítica. La mayor ansiedad rasgo con: situación laboral inactiva, medicación ansiolítica, hinchazón mamaria y estadios avanzados al diagnóstico. Tras los tratamientos, disminuye significativamente la ansiedad. Conclusiones: tras los tratamientos, la puntuación de calidad de vida se modifica positivamente y la ansiedad como estado y como rasgo disminuye.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Ansiedade/etiologia , Qualidade de Vida , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Estudos Prospectivos , Autoavaliação Diagnóstica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA