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1.
Medicine (Baltimore) ; 99(44): e22904, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126344

RESUMO

This study was to investigate clinical features and prognosis of duplex primary malignant neoplasms involving chronic myeloid leukemia (CML-DPMNs). Clinical data of thirteen CML-DPMN patients who were admitted to the First Hospital of Jilin University from May 2008 to December 2018 were collected and retrospectively analyzed. Female patients (9/13) were predominant in this cohort study. Nine patients were metachronous DPMNs (metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia) with 5 years median interval time from primary malignancy to secondary malignancy. The other 4 patients were diagnosed as synchronous CML-DPMNs. Seven of the metachronous duplex primary malignant neoplasms involving chronic myeloid leukemia suffered from CML following many years of comprehensive anti-cancer therapy. Two of CML-MDPMN patients had invasive ductal carcinoma of breast after many years of treatment with imatinib. There was no difference between treatment-related CML group and non-treatment-related CML group in regard as the gender, age, white blood cell count, hemoglobin level, platelet count, and risk level. The median overall survival time of these thirteen patients with CML-DPMNs was not reached. In conclusion, female patients are more likely to suffer from the CML-DPMNs in the present article. Overall survival time of patients with DPMNs involving CML could be promising if timely and effective treatment therapy is adopted.


Assuntos
Neoplasias da Mama , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva , Neoplasias Primárias Múltiplas , Fatores Etários , Anticarcinógenos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , China/epidemiologia , Feminino , Humanos , Incidência , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/sangue , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida , Fatores de Tempo
4.
Toxicol Appl Pharmacol ; 401: 115100, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32512070

RESUMO

(-)-Epigallocatechin-3-gallate (EGCG) is the main bioactive component in tea (Camellia sinensis) catechins, and exhibits potential antitumor activity against colorectal cancer (CRC). However, the underlying mechanisms are largely unclear. We investigated the effects of EGCG on activities of CRC cells and the exact molecular mechanism. We used human colon cancer cells (HT-29) and exposed them to EGCG at various concentrations. The MTT assay, flow cytometry, and TUNEL staining were used to study the underlying mechanisms of EGCG (proliferation, apoptosis, autophagy). Western blotting was used to measure expression of marker proteins of the cell cycle, apoptosis, and autophagy. Using a combined microarray-based transcriptomic and ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomic approach, we investigated the perturbed pathways induced by EGCG treatment at transcript and metabolite levels. Transcriptomic analyses showed that 486 genes were differentially expressed between untreated and EGCG-treated cells. Also, 88 differentially expressed metabolites were identified between untreated and EGCG-treated cells. The altered metabolites were involved in the metabolism of glutathione, glycerophospholipids, starch, sucrose, amino sugars, and nucleotide sugars. There was substantial agreement between the results of transcriptomics and metabolomics analyses. Our data indicate that the anticancer activity of EGCG against HT-29 cells is mediated by induction of cell-cycle arrest, apoptosis, and autophagy. EGCG modulates cancer-cell metabolic pathways. These results provide a platform for future molecular mechanistic studies of EGCG.


Assuntos
Anticarcinógenos/farmacologia , Catequina/análogos & derivados , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Metabolômica/métodos , Transcriptoma/efeitos dos fármacos , Anticarcinógenos/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Neoplasias do Colo/tratamento farmacológico , Células HT29 , Humanos , Transcriptoma/fisiologia
5.
Arch Biochem Biophys ; 689: 108439, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32504553

RESUMO

Chronic obstructive pulmonary disease (COPD) and lung cancer are a major cause of morbidity and mortality worldwide, with cigarette smoking being the single most important risk factor for both. Emerging evidence indicates alterations in reverse cholesterol transport-mediated removal of excess cholesterol from lung, and intracellular cholesterol overload to be involved in smoke-promoted COPD and lung cancer development. Since there are currently few effective treatments for COPD and lung cancer, it is important to identify food-derived, biologically active compounds, which can protect against COPD and lung cancer development. High intake of the carotenoid lycopene, as one of phytochemicals, is associated with a decreased risk of chronic lung lesions. This review article summarizes and discusses epidemiologic evidence, in vitro and in vivo studies regarding the prevention of smoke-promoted COPD and lung carcinogenesis through dietary lycopene as an effective intervention strategy. We focus on the recent research implying that lycopene preventive effect is through targeting the main genes involved in reverse cholesterol transport. This review also indicates gaps in knowledge about the function of lycopene against COPD and lung cancer, offering directions for further research.


Assuntos
Anticarcinógenos/uso terapêutico , Antioxidantes/uso terapêutico , Fumar Cigarros/efeitos adversos , Neoplasias Pulmonares/prevenção & controle , Licopeno/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Animais , Anticarcinógenos/metabolismo , Antioxidantes/metabolismo , Colesterol/metabolismo , Suplementos Nutricionais , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Licopeno/metabolismo , Lycopersicon esculentum/metabolismo , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia
7.
Res Vet Sci ; 131: 87-91, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32311590

RESUMO

Isoflavones, such as genistein, have been proposed to have beneficial effects on health, including preventive or therapeutic actions in carcinogenesis. Their structural similarity to oestrogens allows them to bind at the cellular level with oestrogen receptors. Therefore, this study attempted to determine the antitumoural effects of genistein administered in a canine inflammatory mammary cancer xenograft model, in terms of tumour proliferation, appearance of metastases and steroid hormone regulation. Using histology and immunohistochemical analyses as well as the EIA technique for hormonal determinations, the antitumoural effects of genistein on an inflammatory mammary cancer xenograft model were assessed for 3 weeks. Mice treated with genistein showed higher Ki-67 levels than the control group. There were significantly more distant metastases in the genistein-treated xenografts versus the control group. Intratumoural and serum progesterone, androstenedione and oestrogen levels in treated mice were elevated, whereas intratumoural testosterone levels were decreased compared to the control group. These results revealed that genistein ingestion promotes tumour proliferation and elevates metastatic rates by increasing intratumoural and circulating oestrogen levels in a mammary cancer xenograft model.


Assuntos
Anticarcinógenos/uso terapêutico , Doenças do Cão/metabolismo , Estrogênios/metabolismo , Genisteína/uso terapêutico , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Animais , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Genisteína/farmacologia , Inflamação/metabolismo , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos
8.
Biochem Pharmacol ; 175: 113923, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32217102

RESUMO

Colorectal cancer (CRC) is one of the most common cancers worldwide. Epidemiological studies indicate that consumption of fruits and vegetables containing procyanidins is associated with lower CRC risk. This study investigated the capacity of two dimeric procyanidins composed of epicatechin gallate (ECG) or epigallocatechin gallate (EGCG) isolated from persimmons, to inhibit CRC cell growth and promote apoptosis, characterizing the underlying mechanisms. ECG and EGCG dimers reduced the growth of five human CRC cell lines in a concentration (10-60 µM)- and time (24-72 h)-dependent manner, with a 72 h-IC50 value in Caco-2 cells of 10 and 30 µM, respectively. ECG and EGCG dimers inhibited Caco-2 cell proliferation by arresting the cell cycle in G2/M phase and by inducing apoptosis via the mitochondrial pathway. In addition, ECG and EGCG dimers inhibited cell migration, invasion, and adhesion, decreasing the activity of matrix metalloproteinases (MMP-2/9). Mechanistically, ECG and EGCG dimers inhibited the activation of lipid raft-associated epidermal growth factor (EGF) receptor (EGFR), without affecting its localization at lipid rafts. In particular, ECG and EGCG dimers reduced EGFR phosphorylation at Tyr1068 residue, prevented EGFR dimerization and activation upon stimulation, and induced EGFR internalization both in the absence and presence of EGF. Furthermore, ECG and EGCG dimers increased EGFR phosphorylation at Tyr1045 residue, providing a docking site for ubiquitin ligase c-Cbl and induced EGFR degradation by the proteasome. Downstream of EGFR, ECG and EGCG dimers inhibited the activation of the MEK/ERK1/2 and PI3K/AKT signaling pathways, downregulating proteins involved in the modulation of cell survival. In conclusion, ECG and EGCG dimers reduced CRC cell growth by inhibiting EGFR activation at multiple steps, including the disruption of lipid rafts integrity and promoting EGFR degradation. These results shed light on a potential molecular mechanism on how procyanidins-rich diets may lower CRC risk.


Assuntos
Catequina/análogos & derivados , Neoplasias Colorretais/metabolismo , Inibidores do Crescimento/farmacologia , Microdomínios da Membrana/metabolismo , Proantocianidinas/farmacologia , Anticarcinógenos/farmacologia , Anticarcinógenos/uso terapêutico , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Células CACO-2 , Catequina/farmacologia , Catequina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Relação Dose-Resposta a Droga , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Inibidores do Crescimento/uso terapêutico , Células HCT116 , Células HT29 , Humanos , Microdomínios da Membrana/efeitos dos fármacos , Proantocianidinas/uso terapêutico , Multimerização Proteica/efeitos dos fármacos , Multimerização Proteica/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
10.
Sci Rep ; 10(1): 2444, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051483

RESUMO

Cancer stem cells (H1299-sdCSCs) were obtained from tumour spheres of H1299 human lung cancer cells. We studied low stiffness, a unique biophysical property of cancer cells, in H1299-sdCSCs and parental H1299. Atomic force microscopy revealed an average Young's modulus value of 1.52 kPa for H1299-sdCSCs, which showed low stiffness compared with that of H1299 cells, with a Young's modulus value of 2.24 kPa. (-)-Epigallocatechin gallate (EGCG) reversed the average Young's modulus value of H1299-sdCSCs to that of H1299 cells. EGCG treatment inhibited tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. AXL receptor tyrosine kinase is highly expressed in H1299-sdCSCs and AXL knockdown with siAXLs significantly reduced tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. An AXL-high population of H1299-sdCSCs was similarly reduced by treatment with EGCG and siAXLs. Transplantation of an AXL-high clone isolated from H1299 cells into SCID/Beige mice induced faster development of bigger tumour than bulk H1299 cells, whereas transplantation of the AXL-low clone yielded no tumours. Oral administration of EGCG and green tea extract (GTE) inhibited tumour growth in mice and reduced p-AXL, ALDH1A1, and SLUG in tumours. Thus, EGCG inhibits the stemness and tumourigenicity of human lung cancer cells by inhibiting AXL.


Assuntos
Anticarcinógenos/farmacologia , Carcinogênese/efeitos dos fármacos , Catequina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Animais , Anticarcinógenos/uso terapêutico , Carcinogênese/metabolismo , Carcinogênese/patologia , Catequina/farmacologia , Catequina/uso terapêutico , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/antagonistas & inibidores
11.
Phytother Res ; 34(8): 1812-1828, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32059077

RESUMO

Apigenin is an edible plant-derived flavonoid that has been reported as an anticancer agent in several experimental and biological studies. It exhibits cell growth arrest and apoptosis in different types of tumors such as breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach, by modulating several signaling pathways. Apigenin induces apoptosis by the activation of extrinsic caspase-dependent pathway by upregulating the mRNA expressions of caspase-3, caspase-8, and TNF-α. It induces intrinsic apoptosis pathway as evidenced by the induction of cytochrome c, Bax, and caspase-3, while caspase-8, TNF-α, and B-cell lymphoma 2 levels remained unchanged in human prostate cancer PC-3 cells. Apigenin treatment leads to significant downregulation of matrix metallopeptidases-2, -9, Snail, and Slug, suppressing invasion. The expressions of NF-κB p105/p50, PI3K, Akt, and the phosphorylation of p-Akt decreases after treatment with apigenin. However, apigenin-mediated treatment significantly reduces pluripotency marker Oct3/4 protein expression which might be associated with the downregulation of PI3K/Akt/NF-κB signaling.


Assuntos
Anticarcinógenos/envenenamento , Anticarcinógenos/uso terapêutico , Apigenina/uso terapêutico , Neoplasias/tratamento farmacológico , Plantas/química , Anticarcinógenos/farmacologia , Apigenina/farmacologia , Feminino , Humanos , Masculino
12.
Gastroenterology ; 158(2): 368-388, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563626

RESUMO

Although colorectal cancer (CRC) screening has reduced the incidence of and mortality from CRC, chemoprevention strategies have the potential to further reduce CRC incidence and mortality. Chemoprevention agents might be used for average-risk as well as high-risk groups, and to prevent CRC recurrence after therapy. CRC chemoprevention agents that have been studied include aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, statins, agents that target metabolic pathways, and vitamins and minerals. We review the prospect of chemoprevention of CRC, results from preclinical and human studies, challenges, and future directions.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticarcinógenos/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Vitaminas/uso terapêutico , Animais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Modelos Animais de Doenças , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Detecção Precoce de Câncer/estatística & dados numéricos , Humanos , Incidência , Programas de Rastreamento/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Estados Unidos/epidemiologia , United States Food and Drug Administration/legislação & jurisprudência
13.
Acta Clin Belg ; 75(1): 49-56, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31671027

RESUMO

Objective: To give a brief literature overview of current knowledge regarding FGFR inhibition in bladder cancer.Background: The deeper molecular understanding of bladder urothelial carcinoma (UC) has reshaped the diagnostic and therapeutic landscape of this malignancy. Rapid technological development, including the frequent use of next-generation sequencing (NGS) in clinical practice, has boosted identification and development of potential biomarkers and targeted therapies. Genetic aberrations in the fibroblast growth factor receptor (FGFR)-pathway may drive tumorigenesis and are considered as attractive drug targets in advanced and/or metastatic UC. Several clinical trials have been performed or are ongoing to assess the safety and efficacy of (non-)selective FGFR inhibitors in patients with advanced or metatastic UC.Results: While non-selective FGFR inhibitors have shown limited clinical response with unacceptable toxicity, selective 'pan'-FGFR inhibitors had favourable response rates with manageable toxicity. To predict response, patients were screened for FGFR aberrations using NGS after DNA/RNA extraction of UC tissue specimen or collection of ctDNA or cfDNA.Conclusion: Early clinical trials have shown promising results for targeting FGFR in advanced or metastatic UC, though these findings need to be validated in phase III trials. It seems that FGFR aberrations can be detected in ctDNA and cfDNA as efficiently as in tumour tissue, showing their potential as predictive, non-invasive liquid biomarkers.


Assuntos
Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/terapia , Receptores de Fatores de Crescimento de Fibroblastos/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Anticarcinógenos/uso terapêutico , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/diagnóstico , Humanos , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Mutação , Valor Preditivo dos Testes , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Neoplasias da Bexiga Urinária/diagnóstico
14.
Recent Pat Anticancer Drug Discov ; 14(4): 298-311, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31746310

RESUMO

BACKGROUND: Cancer is a global health problem and the continuous rise in incidence and mortality due to cancer carries a real economic burden to all countries. Accumulation of genetic mutation, exposure of environmental carcinogens and food habits due to change in lifestyles are the key reasons for cancer. Targeting cancer cells, we need a multitargeting molecule with low/no toxicity. OBJECTIVE: To review the current update of the research status of chemopreventive/therapeutic molecule, Apigenin. METHODS: Compare the results of the published articles and granted patents on this compound. We also discuss the pros and cons of the present research and future direction. RESULTS: Cancer cells have characteristic alterations and dysregulation of various cell signaling pathways that control cell homeostasis, proliferation, motility, and survival in normal cells. Natural flavonoids are the compounds well known for their anti-inflammatory, anti-oxidant, and anti-cancerous properties. Apigenin, along with several other physiological effects, has a very low intrinsic toxicity and striking effects on the proliferation of cancer cells. Interestingly, this multitargeting molecule is getting wide acceptance among researchers. It is evident from the recent patents filed in this compound. At present, three patents have been granted only on the anticancer properties of apigenin. CONCLUSION: This mini-review will explain the present research status of apigenin and will further shine some light on how apigenin performs its anti-cancerous actions by interfering with the key cellsignaling pathways.


Assuntos
Anticarcinógenos/farmacologia , Anticarcinógenos/uso terapêutico , Apigenina/farmacologia , Apigenina/uso terapêutico , Neoplasias/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Humanos , Neoplasias/metabolismo
15.
Life Sci ; 239: 117032, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31704450

RESUMO

Colorectal cancer remains to be the most prevalent malignancy in humans and 1.5 million men and women living in the United States are diagnosed with colorectal cancer, with a predicted 145,600 new cases to be diagnosed in 2019. Curcuminoids and its synthetic analogs are now of interest due to their bioactive attributes, especially their action as anticancer activity in various cancer cell line models. Several in vivo and in vitro studies have substantially proved their anticancer activities against colon cancer cell lines. Curcumin analogues like IND-4, FLLL, GO-Y030 and C086 have demonstrated to produce greater cytotoxicity when experimentally studied and study results from many have been suggested to be the same. Combination of curcumin with therapeutic cancer agents like tolfenamic acid, 5-fluorouracil, resveratrol and dasatinib showed improved cytotoxicity and chemotherapeutic effect. The results propose that employment of curcumin with novel drug delivery systems like liposome, micelles and nanoparticle have been performed which could improve the therapeutic efficacy against colon cancer. The present review highlights the mechanism of action, synergistic effect and novel delivery methods to improve the therapeutic potential of curcumin.


Assuntos
Anticarcinógenos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/prevenção & controle , Curcumina/análogos & derivados , Curcumina/uso terapêutico , Humanos
16.
J Biochem Mol Toxicol ; 33(12): e22374, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31702096

RESUMO

The main purpose of the current study is to reveal the anticancer action of limonin against benzo(a)pyrene [B(a)P]-treated lung carcinogenesis in Swiss albino mice and A549 lung cancer cells. B(a)P was orally supplemented (50 mg/kg body weight) twice a week for four weeks induction of lung cancer in mice. The lung weight, body weight, incidence of tumor, lipid peroxidation, carcinoembryonic antigen (CEA), enzymatic and nonenzymatic antioxidants (superoxide dismutase, GPx, glutathione, glutathione reductase, catalase, and glutathione S-transferase), serum marker enzymes (aryl hydroxylase, lactate dehydrogenase, 5'-nucleotidases, and γ-glutamyl transpeptidase), and inflammatory mediators (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) were estimated. Moreover, a histopathological study of lung tissues was supported by the biochemical analysis. Furthermore, the anticancer activity of limonin on A549 cells was measured by cell viability, production of reactive oxygen species (ROS), apoptotic morphological changes by AO/EtBr staining. Additionally, the status of apoptosis protein (caspase-9 and -3) expressions was analyzed by the colorimetric analysis. B(a)P-induced mice showed increased lipid peroxidation, CEA, serum marker enzymes and inflammatory cytokines levels with simultaneously decreased in the nonenzymatic and enzymatic antioxidants levels. Limonin supplements significantly reverted back to all these changes in this manner, showing the efficiency of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of limonin-enhanced apoptosis by loss of cell viability, improved ROS production, apoptotic morphological changes, and apoptosis protein expression were analyzed. Overall, these results suggest the anticancer potential of limonin against B(a)P-induced lung cancer in Swiss albino mice and A549 lung cancer cells.


Assuntos
Anticarcinógenos/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Benzo(a)pireno/farmacologia , Carcinogênese/induzido quimicamente , Carcinogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Limoninas/uso terapêutico , Neoplasias Pulmonares/prevenção & controle , Células A549 , Animais , Benzo(a)pireno/administração & dosagem , Antígeno Carcinoembrionário/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Carga Tumoral
17.
Oxid Med Cell Longev ; 2019: 2716870, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737167

RESUMO

A growing awareness of the mechanisms by which phytochemicals can influence upstream endogenous cellular defence processes has led to intensified research into their potential relevance in the prevention and treatment of disease. Pharmaceutical medicine has historically looked to plants as sources of the starting materials for drug development; however, the focus of nutraceutical medicine is to retain the plant bioactive in as close to its native state as possible. As a consequence, the potency of a nutraceutical concentrate or an extract may be lower than required for significant gene expression. The molecular structure of bioactive phytochemicals to a large extent determines the molecule's bioavailability. Polyphenols are abundant in dietary phytochemicals, and extensive in vitro research has established many of the signalling mechanisms involved in favourably modulating human biochemical pathways. Such pathways are associated with core processes such as redox modulation and immune modulation for infection control and for downregulating the synthesis of inflammatory cytokines. Although the relationship between oxidative stress and chronic disease continues to be affirmed, direct-acting antioxidants such as vitamins A, C, and E, beta-carotene, and others have not yielded the expected preventive or therapeutic responses, even though several large meta-analyses have sought to evaluate the potential benefit of such supplements. Because polyphenols exhibit poor bioavailability, few of their impressive in vitro findings have been replicated in vivo. SFN, an aliphatic isothiocyanate, emerges as a phytochemical with comparatively high bioavailability. A number of clinical trials have demonstrated its ability to produce favourable outcomes in conditions for which there are few satisfactory pharmaceutical solutions, foreshadowing the potential for SFN as a clinically relevant nutraceutical. Although myrosinase-inert broccoli sprout extracts are widely available, there now exist myrosinase-active broccoli sprout supplements that yield sufficient SFN to match the doses used in clinical trials.


Assuntos
Anticarcinógenos/uso terapêutico , Suplementos Nutricionais , Isotiocianatos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/uso terapêutico , Animais , Disponibilidade Biológica , Brassica , Doença Crônica , Ensaios Clínicos como Assunto , Humanos , Prevenção Primária
18.
Int J Mol Sci ; 20(17)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480481

RESUMO

The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (Bifidobacterium longum, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13-38%) and adenocarcinoma (13-14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and ß-glucuronidase (ß-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.


Assuntos
Anticarcinógenos/uso terapêutico , Bifidobacterium longum , Neoplasias Colorretais/terapia , Licopeno/uso terapêutico , Probióticos/uso terapêutico , Administração Oral , Animais , Anticarcinógenos/administração & dosagem , Bifidobacterium longum/fisiologia , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Fator de Crescimento Insulin-Like I/análise , Licopeno/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Probióticos/administração & dosagem , Receptor IGF Tipo 1/análise
19.
Can J Surg ; 62(5): 358-360, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31550104

RESUMO

Summary: The management of high-risk benign breast disease (BBD) is changing because of improvements in radiological and pathological analysis. We sought to determine the current practice recommendations of breast health professionals in managing patients with high-risk BBD. We surveyed members of the Canadian Society of Surgical Oncology, Canadian Association of General Surgeons and Canadian Association of Radiologists. The survey contained demographic and case-based questions concerning management of high-risk benign breast lesions. Participants were asked for their recommendations and opinions regarding future risk of breast cancer as well as the role of chemoprevention. There was no consistency among the 41 respondents in the treatment recommendations for any of the high-risk benign conditions, and the lifetime risk associated with classic lobular carcinoma in situ was vastly underestimated. Education and evidenced-based guidelines are urgently needed to ensure more uniform practice nationally.


Assuntos
Neoplasias da Mama/prevenção & controle , Oncologia/normas , Médicos/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Lesões Pré-Cancerosas/terapia , Anticarcinógenos/normas , Anticarcinógenos/uso terapêutico , Biópsia/normas , Mama/diagnóstico por imagem , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Canadá , Feminino , Humanos , Mamografia/normas , Mastectomia Segmentar/métodos , Mastectomia Segmentar/normas , Oncologia/métodos , Médicos/normas , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Inquéritos e Questionários/estatística & dados numéricos
20.
Eur J Med Chem ; 181: 111579, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398616

RESUMO

Many bioactive agents have been extracted from plants or belong to functional foods and have been considered in the treatment of serious and multifactorial diseases, such as cancer. In particular, this review is focused on the anti-cancer properties owned by several natural products typically from the Mediterranean area. In some regions of the South of Italy, a lower cancer incidence has been observed. There is increasing evidence that adherence to a Mediterranean dietary pattern correlates with reduced risk of several cancer types. This could be mainly attributed to the typical lifestyle aspects of the Mediterranean diet, such as high consumption of fruit and vegetables. In this review, the main natural products of the Mediterranean area are discussed, with particular attention on their anti-cancer properties endowed with multi-target profiles.


Assuntos
Dieta Mediterrânea , Neoplasias/prevenção & controle , Anticarcinógenos/análise , Anticarcinógenos/uso terapêutico , Antioxidantes/análise , Antioxidantes/uso terapêutico , Frutas/química , Humanos , Neoplasias/dietoterapia , Azeite de Oliva/análise , Azeite de Oliva/uso terapêutico , Verduras/química , Vinho/análise
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