RESUMO
Breast cancer (BC) is the most frequent malignant neoplasia and leading cause of cancer mortality for women. A timely diagnosis of BC is crucial to ensure the best chances of survival. Among the various screening tools for BC, antibodies directed towards self-antigens or tumor-associated antigens (autoantibodies) have emerged as an alternative to image-based screening modalities. However, little attention has been paid to the global diversity of autoantibodies. This work aimed to analyze the diversity of autoantibodies reactive to antigens expressed by the BC cell line T47D in the sera of Mexican women with BC, benign breast pathology (BBP), or without breast pathology (WBP). We found that the diversity of antibodies in the sera was higher in the BC and BBP groups than in the WBP group. Likewise, the diversity changed with the progression of BC. Our results show and measure the complexity of the antibody response in breast health and disease.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/patologia , Autoanticorpos , Antígenos de NeoplasiasRESUMO
Breast cancer (BC) is a leading cause of women's morbimortality worldwide. Unfortunately, attempts to predict women's susceptibility to developing BC well before it becomes symptomatic, based on their genetic, family, and reproductive background have proved unsatisfactory. Here we analyze the matching of personality traits and protein serum profiles to predict women's susceptibility to developing cancer. We conducted a prospective study among 150 women (aged 18-70 years), who were distributed into three groups (n = 50): women without breast pathology and women diagnosed with BC or benign breast pathology. Psychological data were obtained through standardized psychological tests and serum protein samples were analyzed through semiquantitative protein immunoblotting. The matching for psychological and immunological profiles was constructed from these data using a mathematical generalized linear model.The model predicted that women who have stronger associations between high-intensity stress responses, emotional containment, and an increased number and reduced variability of serum proteins (detected by IgG autoantibodies) have the greatest susceptibility to develop BC before the disease has manifested clinically. Hence, the present study endorses the possibility of using psychological and biochemical tests in combination to increase the possibility of identifying women at risk of developing BC before the disease shows clinical manifestations. A longitudinal study must be instrumented to test the prediction ability of the instrument in real scenarios. Trial registration: Committee of Ethical Research of the Hospital General de México "Dr. Eduardo Liceaga," Ministry of Health (DI/12/111/03/064).
RESUMO
BACKGROUND AND AIMS: Tuberculosis remains a worldwide health problem and requires long-term treatment with several antibiotics; therefore, compliance problems and the emergence of multidrug resistance (MDR) are involved. (-)-Licarin A (LA) was isolated from diverse plants such as Aristolochia taliscana and possesses antimycobacterial, antiinflammatory, trypanocidal, and neuroprotective activities. The aim of the study was to determine the antitubercular and subacute toxicity of LA isolated from A. taliscana in BALB/c mice. METHODS: The antitubercular activity of LA was tested in a TB murine model inducing disease with M. tuberculosis H37Rv or MDR. Mice were treated with LA (5 mg/kg) for 30 and 60 days; post/treatment, lung bacilli loads and pneumonia percentage were determined. The subacute toxicity of LA (21 days) was evaluated in healthy mice. After treatment, biochemical and hematological parameters were determined and main organs were analyzed histologically. RESULTS: In animals infected with drug-sensitive or MDR strains, LA produced a significant decrease of pulmonary bacillary burdens at day 30 of treatment, and a significant pneumonia reduction at days 30 and 60 of treatment. Regarding subacute toxicity, LA administration during 21 days showed no abnormalities in main-organ macro- and microarchitecture. Biochemical and hematological parameters analyzed showed no statistical differences between control and treated groups. CONCLUSIONS: (-)-Licarin A reduces pneumonia of mice infected with both mycobacterium strains. Also, subacute toxicity of LA exhibits no major signs of damage. Biochemical and hematological parameters and histological analyses indicate that LA caused no significant changes at the doses assayed.
Assuntos
Antituberculosos/administração & dosagem , Aristolochia/química , Lignanas/administração & dosagem , Animais , Antituberculosos/efeitos adversos , Farmacorresistência Bacteriana Múltipla , Lignanas/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
We analyzed the antimycobacterial activity of the hexane extract of rhizomes from Aristolochia elegans. Some compounds of this extract were purified and tested against a group of drug-resistant Mycobacterium tuberculosis strains. We also evaluated their antiprotozoal activities. The hexane extract was active against M. tuberculosis H37Rv at a MIC = 100 µg mL(-1); the pure compounds eupomatenoid-1, fargesin, and (8R,8'R,9R)-cubebin were active against M. tuberculosis H37Rv (MIC = 50 µg mL(-1)), while fargesin presented activity against three monoresistant strains of M. tuberculosis H37Rv and a MDR clinical isolate of M. tuberculosis (MIC < 50 µg mL(-1)). Both the extract and eupomatenoid-1 were very active against E. histolytica and G. lamblia (IC(50) < 0.624 µg mL(-1)); in contrast, fargesin and (8R,8'R,9R)-cubebin were moderately active (IC(50) < 275 µg mL(-1)). In this context, two compounds responsible for the antimycobacterial presented by A. elegans are fargesin and cubebin, although others may exert this activity also. In addition to the antimycobacterial activity, the hexane extract has important activity against E. histolytica and G. lamblia, and eupomatenoid-1 is one of the compounds responsible for the antiparasite activity.
RESUMO
Tuberculosis (TB - Mycobacterium tuberculosis) is an ancient infectious disease that has appeared once again as a serious worldwide health problem and now comprises the second leading cause of death resulting from a single infection. The prevalence of multidrug resistance (MDR) TB is increasing and therapeutic options for treatment are not always accessible; in fact, some patients do not respond to the available drugs. Therefore, there is an urgent need to develop novel anti-TB agents. The aim of the present study was to screen extracts of Aristolochia taliscana, a plant used in traditional Mexican medicine to treat cough and snake bites, for antimycobacterial activity. The hexanic extract of A. taliscana was tested by microdilution alamar blue assay against Mycobacterium strains and bioguided fractionation led to the isolation of the neolignans licarin A, licarin B and eupomatenoid-7, all of which had antimycobacterial activity. Licarin A was the most active compound, with minimum inhibitory concentrations of 3.12-12.5 microg/mL against the following M. tuberculosis strains: H37Rv, four mono-resistant H37Rv variants and 12 clinical MDR isolates, as well as against five non-tuberculous mycobacteria (NTM) strains. In conclusion, licarin A represents a potentially active anti-TB agent to treat MDR M. tuberculosis and NTM strains.
Assuntos
Antibacterianos/farmacologia , Aristolochia/química , Lignanas/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Farmacorresistência Bacteriana Múltipla , Humanos , Lignanas/isolamento & purificação , México , Testes de Sensibilidade Microbiana , Mycobacterium/classificação , Mycobacterium/efeitos dos fármacos , Extratos Vegetais/químicaRESUMO
Tuberculosis (TB - Mycobacterium tuberculosis) is an ancient infectious disease that has appeared once again as a serious worldwide health problem and now comprises the second leading cause of death resulting from a single infection. The prevalence of multidrug resistance (MDR) TB is increasing and therapeutic options for treatment are not always accessible; in fact, some patients do not respond to the available drugs. Therefore, there is an urgent need to develop novel anti-TB agents. The aim of the present study was to screen extracts of Aristolochia taliscana, a plant used in traditional Mexican medicine to treat cough and snake bites, for antimycobacterial activity. The hexanic extract of A. taliscana was tested by microdilution alamar blue assay against Mycobacterium strains and bioguided fractionation led to the isolation of the neolignans licarin A, licarin B and eupomatenoid-7, all of which had antimycobacterial activity. Licarin A was the most active compound, with minimum inhibitory concentrations of 3.12-12.5 ìg/mL against the following M. tuberculosis strains: H37Rv, four mono-resistant H37Rv variants and 12 clinical MDR isolates, as well as against five non-tuberculous mycobacteria (NTM) strains. In conclusion, licarin A represents a potentially active anti-TB agent to treat MDR M. tuberculosis and NTM strains.