Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
1.
Nutrients ; 13(12)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34960072

RESUMO

Erectile dysfunction affects more than 50% of diabetic male patients, with a higher prevalence compared with the general population. Age, clinical factors, and lifestyle habits have been suggested to contribute to the pathophysiology and worsening of erectile dysfunction in diabetic patients. First- and second-line standard treatments are represented by phosphodiesterase type 5 (PDE5) inhibitors and alprostadil, respectively. However, natural compounds have been suggested to ameliorate this clinical condition. This study aims to preclinically characterize the potential synergism among plant-derived products for the improvement of erectile dysfunction in the diabetic condition. The effects of a nutritional supplement composed of Panax ginseng, Moringa oleifera and rutin, as single agents or as a mixture, were evaluated in a streptozotocin (STZ)-induced diabetic rat model with erectile dysfunction. The treatment efficacy was evaluated by measuring sexual-related parameters (i.e., mount and intromission latencies, the mount and intromission frequencies and the ejaculation latency). Results showed that only the mixture was able to significantly reduce the diabetes-related delay in mount latency (p < 0.01). Substantial similar effects were observed by measuring the intromission latency and the mean number of mounts was very similar between rats treated with the mixture and controls. Single agent treatments showed very low effects in terms of intromission frequency, whereas the mixture was able to increase this parameter. Additionally, a statistically significant reduced ejaculation latency was observed in rats treated with the mixture compared with the STZ control. These results are in agreement with the available literature and suggest that the study mixture may ameliorate sexual behavior compared with the administration of the study natural compounds as single agents in diabetic rats. Further preclinical and clinical studies are needed to perform a more comprehensive evaluation of the efficacy and safety of the study mixture.


Assuntos
Produtos Biológicos/farmacologia , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Experimental , Suplementos Nutricionais , Disfunção Erétil/etiologia , Extratos Vegetais/farmacologia , Animais , Produtos Biológicos/química , Humanos , Masculino , Moringa oleifera/química , Panax/química , Ereção Peniana/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/química , Ratos , Rutina/química , Comportamento Sexual Animal
2.
Oncol Res ; 28(6): 631-644, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33208224

RESUMO

The benefit of adjuvant chemotherapy in the early stages of colorectal cancer (CRC) is still disappointing and the prediction of treatment outcome quite difficult. Recently, through a transcriptomic approach, we evidenced a role of PNN and KCNQ1OT1 gene expression in predicting response to fluoropyrimidine-based adjuvant chemotherapy in stage III CRC patients. Thus, the aim of this study was to validate in an independent cohort of stages IIIII CRC patients our previous findings. PNN and KCNQ1OT1 mRNA expression levels were evaluated in 74 formalin-fixed paraffin-embedded tumor and matched normal mucosa samples obtained by stages IIIII CRC patients treated with fluoropyrimidine-based adjuvant chemotherapy. PININ, the protein encoded by PNN, was immunohistochemically evaluated in 15 tumor and corresponding normal mucosa samples, selected on the basis of a low, medium, or high mRNA expression tumor/mucosa ratio. PNN and KCNQ1OT1 mRNA mean expression levels were significantly higher in tumor compared with normal tissues. Patients with high PNN or KCNQ1OT1 tumor mRNA levels according to ROC-based cutoffs showed a shorter disease-free survival (DFS) compared with patients with low tumor mRNA gene expression. Also, patients with tumor mRNA expression values of both genes below the identified cutoffs had a significantly longer DFS compared with patients with the expression of one or both genes above the cutoffs. In a representative large cohort of stages IIIII CRC untreated patients retrieved from GEO datasets, no difference in DFS was observed between patients with high and low PNN or KCNQ1OT1 gene expression levels. These data confirm our previous findings and underscore the relevance of PNN and KCNQ1OT1 expression in predicting DFS in early stages of CRC treated with fluoropyrimidine-based adjuvant chemotherapy. If further validated in a prospective case series, both biomarkers could be used to identify patients who benefit from this treatment and to offer alternative chemotherapy regimens to potential unresponsive patients. In relation to the suggested biological role of PNN and KCNQ1OT1 in CRC, they might also be exploited as potential therapeutic targets.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Moléculas de Adesão Celular/genética , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Proteínas Nucleares/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Moléculas de Adesão Celular/metabolismo , Quimioterapia Adjuvante/métodos , Estudos de Coortes , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Expressão Gênica , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Nucleares/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Prognóstico , Pirimidinas/uso terapêutico , RNA Mensageiro/metabolismo , Resultado do Tratamento
3.
Int J Cancer ; 145(9): 2580-2593, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30973654

RESUMO

Five-year overall survival of stage III colorectal cancer (CRC) patients treated with standard adjuvant chemotherapy (ACHT) is highly variable. Genomic biomarkers and/or transcriptomic profiles identified lack of adequate validation. Aim of our study was to identify and validate molecular biomarkers predictive of ACHT response in stage III CRC patients by a transcriptomic approach. From a series of CRC patients who received ACHT, two stage III extreme cohorts (unfavorable vs. favorable prognosis) were selected. RNA-sequencing was performed from fresh frozen explants. Tumors were characterized for somatic mutations. Validation was performed in stage III CRC patients extracted from two GEO datasets. According to disease-free survival (DFS), 108 differentially expressed genes (104/4 up/downregulated in the unfavorable prognosis group) were identified. Among 104 upregulated genes, 42 belonged to olfactory signaling pathways, 62 were classified as pseudogenes (n = 17), uncharacterized noncoding RNA (n = 10), immune response genes (n = 4), microRNA (n = 1), cancer-related genes (n = 14) and cancer-unrelated genes (n = 16). Three out of four down-regulated genes were cancer-related. Mutational status (i.e., RAS, BRAF, PIK3CA) did not differ among the cohorts. In the validation cohort, multivariate analysis showed high PNN and KCNQ1OT1 expression predictive of shorter DFS in ACHT treated patients (p = 0.018 and p = 0.014, respectively); no difference was observed in untreated patients. This is the first study that identifies by a transcriptomic approach and validates PNN and KCNQ1OT1 as molecular biomarkers predictive of chemotherapy response in stage III CRC patients. After a further validation in an independent cohort, PNN and KCNQ1OT1 evaluation could be proposed to prospectively identify stage III CRC patients benefiting from ACHT.


Assuntos
Biomarcadores Tumorais/genética , Moléculas de Adesão Celular/genética , Neoplasias Colorretais/genética , Proteínas Nucleares/genética , Idoso , Quimioterapia Adjuvante/métodos , Classe I de Fosfatidilinositol 3-Quinases/genética , Estudos de Coortes , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Regulação para Baixo/genética , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estadiamento de Neoplasias/métodos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Prognóstico , Análise de Sequência de RNA/métodos , Transdução de Sinais/genética , Transcriptoma/genética , Regulação para Cima/genética
4.
J Photochem Photobiol B ; 151: 285-96, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26355716

RESUMO

Clinical studies demonstrated the effectiveness of laser therapy in the management of postmastectomy lymphedema, a discomforting disease that can arise after surgery/radiotherapy and gets progressively worse and chronic. However, safety issues restrict the possibility to treat cancer patients with laser therapy, since the effects of laser radiation on cancer cell behavior are not completely known and the possibility of activating postmastectomy residual cancer cells must be considered. This paper reports the results of an in vitro study aimed to investigate the effect of a class IV, dual-wavelength (808 nm and 905 nm), NIR laser system on the behavior of two human breast adenocarcinoma cell lines (namely, MCF7 and MDA-MB361 cell lines), using human dermal fibroblasts as normal control. Cell viability, proliferation, apoptosis, cell cycle and ability to form colonies were analyzed in order to perform a cell-based safety testing of the laser treatment in view of its potential application in the management of postmastectomy lymphedema. The results showed that, limited to the laser source, treatment conditions and experimental models used, laser radiation did not significantly affect the behavior of human breast adenocarcinoma cells, including their clonogenic efficiency. Although these results do not show any significant laser-induced modification of cancer cell behavior, further studies are needed to assess the possibility of safely applying NIR laser therapy for the management of postmastectomy lymphedema.


Assuntos
Linfedema Relacionado a Câncer de Mama/cirurgia , Neoplasias da Mama/patologia , Terapia a Laser/métodos , Apoptose , Linfedema Relacionado a Câncer de Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Fibroblastos , Humanos , Terapia com Luz de Baixa Intensidade/métodos , Células MCF-7 , Mastectomia/efeitos adversos
5.
J Nanobiotechnology ; 12: 55, 2014 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-25477237

RESUMO

BACKGROUND: The interest for gold nanorods in biomedical optics is driven by their intense absorbance of near infrared light, their biocompatibility and their potential to reach tumors after systemic administration. Examples of applications include the photoacoustic imaging and the photothermal ablation of cancer. In spite of great current efforts, the selective delivery of gold nanorods to tumors through the bloodstream remains a formidable challenge. Their bio-conjugation with targeting units, and in particular with antibodies, is perceived as a hopeful solution, but the complexity of living organisms complicates the identification of possible obstacles along the way to tumors. RESULTS: Here, we present a new model of gold nanorods conjugated with anti-cancer antigen 125 (CA125) antibodies, which exhibit high specificity for ovarian cancer cells. We implement a battery of tests in vitro, in order to simulate major nuisances and predict the feasibility of these particles for intravenous injections. We show that parameters like the competition of free CA125 in the bloodstream, which could saturate the probe before arriving at the tumors, the matrix effect and the interference with erythrocytes and phagocytes are uncritical. CONCLUSIONS: Although some deterioration is detectable, anti-CA125-conjugated gold nanorods retain their functional features after interaction with blood tissue and so represent a powerful candidate to hit ovarian cancer cells.


Assuntos
Anticorpos/administração & dosagem , Antineoplásicos/administração & dosagem , Antígeno Ca-125/imunologia , Ouro/administração & dosagem , Proteínas de Membrana/imunologia , Nanotubos/química , Animais , Anticorpos/química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antígeno Ca-125/administração & dosagem , Antígeno Ca-125/química , Linhagem Celular Tumoral , Cetrimônio , Compostos de Cetrimônio/química , Avaliação Pré-Clínica de Medicamentos/métodos , Eritrócitos/efeitos dos fármacos , Feminino , Ouro/química , Humanos , Immunoblotting , Injeções Intravenosas , Macrófagos/efeitos dos fármacos , Proteínas de Membrana/administração & dosagem , Proteínas de Membrana/química , Camundongos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia
6.
Dalton Trans ; 40(9): 2006-16, 2011 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-21212880

RESUMO

Twelve Pt(II) complexes with cis-PtP(2)S(2) pharmacophores (where P(2) refers to two monodentate or one bidentate phosphane ligand and S(2) is a dithiolato ligand) were prepared, characterized and evaluated as potential antiproliferative agents. The various compounds were first studied from the structural point of view; afterward, their solubility properties as well as their solution behaviour were analyzed in detail. Antiproliferative properties were specifically evaluated against A2780 human ovarian carcinoma cells, either resistant or sensitive to cisplatin. For comparison purposes similar studies were carried out on four parent cis-dichloro bisphosphane Pt(II)complexes. On the whole, the cis-PtP(2)S(2) compounds displayed significant antiproliferative properties while the cis-PtP(2)Cl(2) (cis-dichloro bisphosphane Pt(II)) compounds revealed quite poor biological performances. To gain further insight into the molecular mechanisms of these bisphosphane Pt(II) compounds, the reactions of selected complexes against the model protein cytochrome c were investigated by ESI-MS and their adduct formation explored. A relevant reactivity with cyt c was obtained only for cis-PtP(2)Cl(2) compounds, whereas cis-PtP(2)S(2) compounds turned out to be nearly unreactive. The obtained results are interpreted and discussed in the frame of the current knowledge of anticancer platinum compounds and their structure-activity-relationships. The observation of appreciable antiproliferative effects for the relatively inert cis-PtP(2)S(2) compounds strongly suggests that these compounds will undergo specific activation within the cellular environment.


Assuntos
Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Compostos de Platina/química , Compostos de Platina/síntese química , Enxofre/química , Linhagem Celular Tumoral , Cisplatino/química , Cisplatino/toxicidade , Citocromos c/química , Feminino , Humanos , Ligantes , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/toxicidade , Neoplasias Ovarianas/tratamento farmacológico , Fosfinas/química , Fósforo/química , Ligação Proteica , Espectrofotometria Ultravioleta/métodos , Relação Estrutura-Atividade
7.
Int J Cancer ; 128(8): 1935-45, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20560137

RESUMO

Although adjuvant chemotherapy has significantly increased overall survival in resected Stage III colorectal cancer, disease recurrence is still high (30-40%). 20-25% of Stage II patients also develop recurrent disease. Thus, high-risk patients may benefit from chemotherapy. As patient response to standard chemotherapy varies, the study of molecular differences in the expression of pharmacologically relevant genes may help clinicians to understand variability and tailor therapy. The expression of 5-fluorouracil (5-FU) pathway genes in tumors from 53 Stages II-III colorectal cancer patients who underwent 5-FU adjuvant chemotherapy was investigated by reverse transcription quantitative real-time polymerase chain reaction. Patients were dichotomized into high- and low-mRNA expression level groups using median values of gene mRNA levels. Then, a threshold analysis to identify a cut-off distinguishing recurrent- or nonrecurrent-disease was used. A high degree of interpatient variation in relative tumor expression of study genes was observed. Multiple gene correlations were found, which suggest possible coregulation mechanisms. No statistically significant relationship between experimental data and baseline clinical/pathological characteristics or clinical outcome was observed using gene expression median values. Threshold analysis indicated significant inverse relationships between deoxyuridine triphosphatase (DUT), ferrodoxin reductase (FDXR) or tumor protein p53 (TP53) and disease-free survival (DFS) in the entire case series and between DUT or NM23-H1 and DFS in Stage III patients: higher gene expression was associated with shorter DFS. This study provides data on relationships between expression of 5-FU pathway genes and clinical outcome of colorectal cancer patients undergoing 5-FU adjuvant chemotherapy and underscores the predictive role of specific genes. Validation in an independent case series is warranted.


Assuntos
Adenocarcinoma/genética , Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Fluoruracila/uso terapêutico , Recidiva Local de Neoplasia/genética , Farmacogenética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Nucleosídeo NM23 Difosfato Quinases/genética , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Pirofosfatases/genética , Pirofosfatases/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
8.
Pharmacol Res ; 59(6): 365-78, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19429468

RESUMO

We describe here the main natural compounds used in cancer therapy and prevention, the historical aspects of their application and pharmacognosy. Two major applications of these compounds are described: as cancer therapeutics and as chemopreventive compounds. Both natural compounds, extracted from plants or animals or produced by microbes (antibiotics), and synthetic compounds, derived from natural prototype structures, are being used. We also focus on the molecular aspects of interactions with their recognized cellular targets, from DNA to microtubules. Some critical aspects of current cancer chemotherapy are also discussed, focusing on genetics and genomics, and the recent revolutionary theory of cancer: aneuploidy as the primum movens of cancer.


Assuntos
Anticarcinógenos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/uso terapêutico , Produtos Biológicos/uso terapêutico , Suplementos Nutricionais , Neoplasias/tratamento farmacológico , Animais , Humanos , Neoplasias/prevenção & controle , Farmacognosia , Fitoterapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA