RESUMO
The burden of cervical cancer remains greater among minority women. The purpose of this study was to evaluate racial/ethnic disparities in cervical cancer screening among minority women in Michigan. Data from 8,023 women (≥ 40 years) surveyed in the 2004-2008 Michigan Special Cancer Behavioral Risk Factor Survey were used to assess racial/ethnic differences in cervical cancer screening, knowledge and beliefs. Unexpectedly, African-American and Hispanic women reported being screened for cervical cancer at rates similar to, or higher than, Whites. Women demonstrated limited knowledge of cervical cancer risk factors and its signs/symptoms. Most minority women were more likely than Whites to believe in the importance of cervical screening, with Hispanic women more likely to support HPV vaccination. Differential utilisation of screening does not explain the disproportionately high rates of cervical cancer among minorities. Future research should examine disparities in the follow-up of abnormal cervical results and receipt of treatment.
Assuntos
Programas de Rastreamento/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Adulto , População Negra/estatística & dados numéricos , Feminino , Comportamentos Relacionados com a Saúde , Hispânico ou Latino/estatística & dados numéricos , Humanos , Michigan , Pessoa de Meia-IdadeRESUMO
We describe the case of a patient presenting with an atrial flutter mechanically induced by a stent migration from the superior vena cava to the right atrium.
Assuntos
Flutter Atrial , Veia Cava Superior , Humanos , Flutter Atrial/etiologia , Átrios do Coração , Stents/efeitos adversosRESUMO
Left ventricular assist devices are used for severe chronic heart failure management. Many of these patients have an implantable cardioverter defibrillator (ICD). However electromagnetic interferences are possible between the 2 devices. We report here a case of an interference in a 77 years-old patient. This was associated with an impossibility to communicate with the ICD. We discuss how to manage this situation.
Assuntos
Desfibriladores Implantáveis , Falha de Equipamento , Coração Auxiliar , Idoso , Fenômenos Eletromagnéticos , Humanos , MasculinoRESUMO
BACKGROUND: Therapeutic drug monitoring may optimize therapy for Crohn's disease (CD). AIM: To use a population pharmacokinetic model that accounts for the time-varying nature of covariates to simulate certolizumab pegol (CZP) concentrations to evaluate the exposure-response relationship for CZP in Crohn's disease. METHODS: Adults (N = 2157) with Crohn's disease were treated with CZP in nine clinical trials. Simulated CZP concentrations were compared to outcomes at weeks 6 and 26, including Crohn's disease activity index (CDAI) response (decrease from baseline ≥ 100 points), remission (CDAI ≤ 150), C-reactive protein (CRP) ≤ 5 mg/L, faecal calprotectin (FC) ≤ 250 µg/g, and a composite endpoint of CDAI ≤ 150 and FC ≤ 250 µg/g. Multivariable analyses identified covariates associated with outcomes and receiver operating characteristic analyses determined optimal CZP concentrations. RESULTS: CZP concentrations at weeks 2, 4 and 6 were higher in patients with clinical response, remission, CRP ≤ 5 mg/L or FC ≤ 250 µg/g at week 6 than without. In multivariable analyses, higher CZP concentrations at week 6 were associated with the composite outcome at weeks 6 and 26 (P < .001). Although the exposure-response relationship varied among patients, approximate CZP concentrations of at least 36.1 µg/mL (positive predictive value [PPV] 22.8% and negative predictive value [NPV] 92.7%) and at least 14.8 µg/mL (PPV 28.0% and NPV 90.4%) at weeks 6 and 12 were associated with weeks 6 and 26 outcomes. CONCLUSIONS: An exposure-response relationship was apparent for CZP in Crohn's disease and achieving higher CZP concentrations may increase the likelihood of attaining efficacy outcomes, but this remains to be evaluated prospectively.
Assuntos
Certolizumab Pegol/uso terapêutico , Doença de Crohn/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Quimioterapia de Indução , Quimioterapia de Manutenção , Adulto , Certolizumab Pegol/farmacocinética , Ensaios Clínicos como Assunto/estatística & dados numéricos , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Doença de Crohn/metabolismo , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Manutenção/efeitos adversos , Masculino , Prognóstico , Resultado do TratamentoRESUMO
OBJECTIVE: To determine if nephropathy in NIDDM is associated with cellular markers for hypertension. RESEARCH DESIGN AND METHODS: We compared 11 patients with clinical diabetic nephropathy with 15 control subjects with no diabetic nephropathy. The patients were white and had had NIDDM for > or = 9 yr and serum creatinine levels < or = 177 M (2.0 mg/dl). RESULTS: Patients with nephropathy were more obese and had higher blood pressures and triglyceride levels, and lower high-density lipoprotein cholesterol levels than control subjects. Erythrocyte sodium lithium countertransport activity, erythrocyte sodium content, and platelet sodium-proton exchange were higher in patients with nephropathy than in control subjects. CONCLUSIONS: The results of this small study suggest that in white patients with long-standing NIDDM, diabetic nephropathy is associated with cellular markers for hypertension. Measurement of cellular markers for hypertension may be useful to identify patients who are at risk for developing nephropathy.
Assuntos
Antiporters , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/fisiopatologia , Hipertensão/sangue , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Proteínas de Transporte/sangue , Colesterol/sangue , HDL-Colesterol/sangue , Eritrócitos/metabolismo , Feminino , Humanos , Hipertensão/fisiopatologia , Insulina/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Valores de Referência , Sódio/sangue , Trocadores de Sódio-Hidrogênio , Triglicerídeos/sangueRESUMO
A comparative analysis of methanol extracts from fruit and leaves of Lycium intricatum Boiss., a Solanaceous shrubbery with the potential to become a high-value crop, was performed by means of liquid chromatography with photodiode array and electrospray ionisation mass spectrometric detection (LC/PDA/ESI-MS). The total phenolic (TPC), anthocyanin (TAC) and flavonoid (TFC) contents as well as the antioxidant capacity measured by four complementary methods were performed for each sample. The results showed the tested extracts to be rich sources of phenolics; in leaves polyphenols and flavonoids dominate, while in fruit anthocyanins dominate. Nineteen phenolic compounds were detected and fifteen were identified or tentatively characterised based on Photodiode-array ultraviolet visible (PDA) UV-Vis spectra, ESI-MS spectrometric data and spiking experiments with authentic standards. Rutin and chlorogenic acid are the major constituents of the leaves and fruit, respectively. Results obtained in this study have revealed that leaves exhibit better performance in all antioxidant assays. From these results it has been shown that extracts of L. intricatum have great potential as a source of phenolics for natural health products.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Lycium/química , Metanol/análise , Extratos Vegetais/química , Compostos Fitoquímicos , PolifenóisRESUMO
Allogeneic stem cell transplantation is increasingly considered as a curative though risky treatment option for adults with sickle cell disease. Little is known about attitudes of adult patients and their health care providers regarding the risks and benefits of transplantation. A survey of 100 patients and their health care providers was undertaken. Assessment of risk was by a reference gamble paradigm. Comparison was made of the characteristics of those accepting substantial risk vs those not accepting risk, as well as assessment of agreement on risks recommended by health care providers and accepted by patients. Sixty-three of 100 patients were willing to accept some short-term risk of mortality in exchange for the certainty of cure. Fifteen patients were willing to accept more than 35% mortality risk. No differences in patient or disease-related variables were identified between those accepting risk and those not accepting risk. There was no agreement between the recommendations of health care providers and the risk accepted by patients. A substantial proportion of adults with sickle cell disease are interested in curative treatment, at the expense of considerable risk. The decision to accept risk is influenced by individual patient values that cannot be easily quantified and that do not correlate with the assessment of the health care provider. Given the substantial interest in curative therapy, education about and consultation for allogeneic stem cell transplantation in sickle cell patients should be encouraged.
Assuntos
Anemia Falciforme/terapia , Transplante de Células-Tronco Hematopoéticas/psicologia , Adulto , Anemia Falciforme/mortalidade , Anemia Falciforme/psicologia , Transplante de Medula Óssea/mortalidade , Transplante de Medula Óssea/psicologia , Coleta de Dados , Tomada de Decisões , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Medição de Risco , Transplante Homólogo/mortalidade , Transplante Homólogo/psicologiaRESUMO
A total of 31 consecutive patients with hematologic malignancies who were considered poor candidates for TBI underwent allogeneic stem cell transplantation after conditioning with fludarabine and melphalan. A total of 25 matched sibling recipients received fludarabine 25 mg/m(2) x 5 days and melphalan 70 mg/m(2) x 2 days. For unrelated and haploidentical donor recipients, fludarabine was increased to 30 mg/m(2) and ATG 30 mg/kg x 4 days was added. Graft-versus-host disease prophylaxis consisted of tacrolimus and mini methotrexate. All patients engrafted. Regimen-related toxicity was considerable and included mainly renal, hepatic and mucosal toxicity. There were seven regimen-related-deaths including two VOD, two pulmonary, one renal, one cardiac and one mucosal toxicity. One case of fatal pulmonary toxicity death could be attributed to pre-existing pulmonary damage. Progression-free survival at 12 months was 44% (90% CI: 30-58%) for recipients of HLA-identical sibling transplants and 33% (90% CI: 21-45%) for all patients. In conclusion, the fludarabine-melphalan regimen leads to consistent engraftment. The regimen-related toxicity is considerable and cannot be explained solely by patient selection. Cardiac toxicity is emerging as a unique toxicity of this regimen. Despite toxicity, fludarabine-melphalan has considerable activity and leads to durable remission in a proportion of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Neoplasias Hematológicas/terapia , Condicionamento Pré-Transplante/efeitos adversos , Vidarabina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Intervalo Livre de Doença , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Melfalan/administração & dosagem , Melfalan/toxicidade , Irmãos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/toxicidadeRESUMO
Fludarabine, thiotepa and total body irradiation (TBI) has been used as conditioning in haplo-identical transplantation. We studied this conditioning regimen in adults undergoing matched sibling transplantation and alternative donor transplantation. A total of 30 consecutive patients underwent matched related, haplo-identical related or matched unrelated donor transplantation with fludarabine, thiotepa and TBI conditioning. All but four had advanced hematologic malignancies. For haplo-identical transplant, ATG was added to the regimen. All patients received peripheral blood stem cells; these were T-cell depleted for 2-antigen or 3-antigen mismatched related transplantation. Additional graft-versus-host disease prophylaxis consisted of tacrolimus and mini-methotrexate. One recipient of haplo-identical transplant failed to engraft; all other evaluable patients had prompt engraftment. Four patients died of regimen-related toxicity. In all, 14 additional patients died of regimen-related causes including four from failure to thrive with persistent thrombocytopenia and four from delayed pulmonary toxicity. Six patients relapsed. Progression-free survival at 12 months was 47% (90% CI: 25-69%) for recipients of HLA-identical sibling transplants and 30% (90% CI: 14-46%) for all patients. Five of six long-term survivors have extensive chronic GVHD. As a result of the delayed complications and a relatively high recurrence rate, we abandoned this regimen.
Assuntos
Antineoplásicos Alquilantes/toxicidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Irradiação Corporal Total/efeitos adversos , Adolescente , Adulto , Antineoplásicos Alquilantes/administração & dosagem , Criança , Terapia Combinada , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/imunologia , Haplótipos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Histocompatibilidade , Humanos , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Análise de Sobrevida , Tiotepa/administração & dosagem , Tiotepa/toxicidade , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo/imunologia , Falha de Tratamento , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/toxicidade , Irradiação Corporal Total/métodosRESUMO
Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete remission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mismatched transplants received antithymocyte globulin in addition to fludarabine and melphalan as part of the conditioning regimen. All 11 patients received acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to absolute neutrophil count >0.5 x 10(9)/l and to platelet count of >20 x 10(9)/l of 14 and 19 days, respectively. All engrafting patients achieved 100% donor chimerism on initial analysis, except for one with persistent leukemia at day +19. Two patients experienced grade 3 regimen-related toxicity, manifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two recipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) after the second transplant. The causes of death included relapse (n = 5), sepsis (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludarabine- and melphalan-based conditioning promotes full donor chimerism, even following HLA-mismatched transplants. However, the regimen may be more beneficial when applied to patients undergoing allogeneic HSC transplantation earlier in their disease course.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Causas de Morte , Feminino , Sobrevivência de Enxerto/imunologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Recidiva , Terapia de Salvação , Taxa de Sobrevida , Quimeras de Transplante , Condicionamento Pré-Transplante/mortalidade , Condicionamento Pré-Transplante/normas , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
To establish the incidence of CMV viremia after allogeneic blood stem cell transplantation, we studied 51 consecutive allogeneic peripheral blood stem cell (PBSC) transplant recipients. A total of 12 recipients were at moderate risk for CMV disease and 39 were at high risk. Conditioning regimens varied, but GvHD prophylaxis consisted of tacrolimus and mini-methotrexate in all patients. All patients received prophylactic ganciclovir from admission until day -2 and prophylactic acyclovir from day -1 until day 180 after transplantation. CMV viremia was treated with ganciclovir. Using a PCR-based technique, the cumulative incidence of CMV viremia was 31+/-14% by day 100 and 35+/-14% by day 150. Donor type, CMV risk group, underlying disorder, conditioning regimen, GvHD, and steroid use were not associated with the risk for CMV viremia. No cases of CMV disease occurred. We hypothesize that the low rate of CMV viremia and the absence of CMV disease in this cohort of PBSCT transplant recipients, which contrasts with other reports, may be related to the prophylactic use of high-dose acyclovir and possibly to pretransplant use of ganciclovir.
Assuntos
Aciclovir/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Pré-Medicação , Aciclovir/administração & dosagem , Adolescente , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Ganciclovir/administração & dosagem , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Reação em Cadeia da Polimerase , Fatores de Risco , Transplante Homólogo , Viremia/diagnóstico , Viremia/tratamento farmacológico , Viremia/prevenção & controleRESUMO
3,4,5,6,16,17-Hexadehydro-16-(methoxycarbonyl)-19 alpha-methyl-20 alpha-oxayohimbanium (Alstonine) is a fluorescent alcaloid which has been known to stain tumour cells more efficiently than normal ones. In this paper the spectral properties of Alstonine were first investigated and its capability for preferential staining of tumour cells verified in culture using SK-OV-3 cells as tumour cells and Mouse 3T3 fibroblasts as controls. Then interactions between Alstonine and biological macromolecules were investigated to provide the rationale for preferential labelling. Molecular filtration techniques have demonstrated that binding occurs only with RNA molecules. Similar experiments were performed with different isopolynucleotides to find an explanation for that specificity. They provide evidence that binding occurs only in the presence of a uridyl ring. This is consistent with the specificity of the linkage to RNA. As the linkage of Alstonine with RNA did not induce any shift or obvious change in the intensity of its fluorescence spectrum, it is concluded that the binding might involve the side chain of the fluorescent compound.
Assuntos
Corantes Fluorescentes , Neoplasias/patologia , RNA Neoplásico/análise , RNA/análise , Alcaloides de Triptamina e Secologanina , Uracila , Células 3T3 , Adenocarcinoma , Animais , Antineoplásicos Fitogênicos , Linhagem Celular , Linhagem Celular Transformada , Corantes , Feminino , Humanos , Camundongos , Microscopia de Fluorescência/métodos , Microscopia de Vídeo/métodos , Neoplasias Ovarianas , Valores de Referência , Células Tumorais CultivadasRESUMO
Patients with a history of myocardial infarction and complete bundle branch block with syncopal episodes have a high risk of sudden death: the identification of the cause of the syncope is therefore essential. The aim of the study was to assess the diagnostic value of non-invasive techniques used in the investigations of syncope: 24 hour Holter recording, high amplification ECG and measurement of left ventricular ejection fraction. The results of these investigations were compared with those of complete electrophysiological investigation evaluating atrioventricular conduction and the inducibility of tachycardia. The patient population was 134 patients, 83 with right bundle branch block and 51 with left bundle branch block. Ninety one patients had inducible sustained ventricular tachycardia and 24 had atrioventricular conduction defects: of these, 14 also had ventricular tachycardia. During follow-up, there were 12 sudden deaths and 13 deaths from cardiac failure. Uni- and multivariate analysis showed induction of ventricular tachycardia to be a significant risk factor for global mortality and sudden death but prolongation of the averaged QRS complex (> 165 msec) was also an independent risk factor of global cardiac mortality. The authors conclude that simple prolongation of the averaged QRS duration > 160 ms in patients with right bundle branch block and > 170 ms in patients with left bundle branch block after myocardial infarction and syncope is a significant poor prognostic factor. However, this sign is not predictive of sudden death.
Assuntos
Bloqueio de Ramo/diagnóstico , Infarto do Miocárdio/complicações , Síncope/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Bloqueio de Ramo/patologia , Eletrocardiografia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Função Ventricular EsquerdaRESUMO
The authors report the case of a 28 year old woman admitted as an emergency at 15 weeks' amenorrhea for malaise with transient aphasia and orthopnoea due to massive thrombosis of a St Jude aortic valve prosthesis implanted two years previously. This complication occurred after relay of oral anticoagulants with subcutaneous heparin therapy. After a medico-surgical and obstetrical discussion, the indication for thrombolytic therapy with 50 mg of rt-PA over two hours was decided with an excellent clinical and echocardiographic, immediate and lasting result, without any maternal or foetal complication. This enabled pregnancy to be continued to term under oral anti-coagulant therapy. Caesarean section was performed at 8 months leading to the birth of a healthy child. Echocardiographic and radioscopic parameters in the post-partum period showed good prosthetic valve function with no indication for reoperation. This case is original by the absence of neurological and obstetrical complications of thrombolysis, the continuation of pregnancy to term and complete lysis of the thrombus without replacement of the valvular prosthesis.
Assuntos
Fibrinolíticos/uso terapêutico , Próteses Valvulares Cardíacas/efeitos adversos , Ativadores de Plasminogênio/uso terapêutico , Complicações Cardiovasculares na Gravidez/cirurgia , Trombose/etiologia , Ativador de Plasminogênio Tecidual/uso terapêutico , Adulto , Estenose da Valva Aórtica/cirurgia , Cesárea , Ecocardiografia , Feminino , Heparina/efeitos adversos , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Resultado da Gravidez , Falha de Prótese , Proteínas Recombinantes/uso terapêutico , Trombose/tratamento farmacológicoRESUMO
Due to their electrophysiological characteristics, class 1 antiarrhythmic drugs can induce an auricular flutter with a 1/1 response. In addition to antiarrhythmic treatment, several authors have therefore considered using drugs capable of slowing auriculoventricular nodal conduction and preventing the 1/1 response. Beta-blockers have been proposed as candidate drugs. In this study, two patients were treated with an association of class 1 antiarrhythmic drugs (cibenzoline in one case, flecainide in the other) and beta-blockers. The administration of these drugs resulted in an atrial proarrhythmic response, and wide QRS tachycardia. Although both subjects had underlying heart disease, the tachycardia was relatively well tolerated in both instances. It was concluded that although beta-blockers may not suppress the risk of atrial proarrhythmia, they at least permit an improved tolerance to this complication.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antiarrítmicos/efeitos adversos , Flutter Atrial/induzido quimicamente , Flutter Atrial/prevenção & controle , Flecainida/efeitos adversos , Imidazóis/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Neoplasias das Glândulas Suprarrenais/complicações , Feocromocitoma/complicações , Oclusão da Artéria Retiniana/etiologia , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Oclusão da Artéria Retiniana/tratamento farmacológico , Tomografia de Coerência Óptica , Baixa Visão/tratamento farmacológico , Baixa Visão/etiologia , Acuidade VisualRESUMO
The growing number of studies suggested that inhibition of autophagy enhances the efficacy of Akt kinase inhibitors in cancer therapy. Here, we provide evidence that ML-9, a widely used inhibitor of Akt kinase, myosin light-chain kinase (MLCK) and stromal interaction molecule 1 (STIM1), represents the 'two-in-one' compound that stimulates autophagosome formation (by downregulating Akt/mammalian target of rapamycin (mTOR) pathway) and inhibits their degradation (by acting like a lysosomotropic agent and increasing lysosomal pH). We show that ML-9 as a monotherapy effectively induces prostate cancer cell death associated with the accumulation of autophagic vacuoles. Further, ML-9 enhances the anticancer activity of docetaxel, suggesting its potential application as an adjuvant to existing anticancer chemotherapy. Altogether, our results revealed the complex effect of ML-9 on autophagy and indentified ML-9 as an attractive tool for targeting autophagy in cancer therapy through dual inhibition of both the Akt pathway and the autophagy.