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1.
Nat Commun ; 12(1): 1999, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790276

RESUMO

Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. The membrane coating provides a means of enhancing interactions with the tumor microenvironment, thereby maximizing the activity of R848. Intratumoral administration of PNP-R848 strongly enhances local immune activation and leads to complete tumor regression in a colorectal tumor model, while providing protection against repeated tumor re-challenges. Moreover, treatment of an aggressive breast cancer model with intratumoral PNP-R848 delays tumor growth and inhibits lung metastasis. Our findings highlight the promise of locally delivering immunostimulatory payloads using biomimetic nanocarriers, which possess advantages such as enhanced biocompatibility and natural targeting affinities.


Assuntos
Imidazóis/uso terapêutico , Imunoterapia/métodos , Nanopartículas/uso terapêutico , Neoplasias/terapia , Microambiente Tumoral/efeitos dos fármacos , Animais , Plaquetas/química , Plaquetas/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Membrana Celular/química , Membrana Celular/metabolismo , Células Cultivadas , Feminino , Células HT29 , Humanos , Imidazóis/química , Imidazóis/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Camundongos Endogâmicos C57BL , Nanopartículas/química , Neoplasias/imunologia , Neoplasias/patologia , Resultado do Tratamento , Microambiente Tumoral/imunologia
2.
JAMA ; 325(10): 988-997, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687469

RESUMO

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2013 lung cancer screening guidelines, which recommend annual screening for adults aged 55 through 80 years who have a smoking history of at least 30 pack-years and currently smoke or have quit within the past 15 years. Objective: To inform the USPSTF guidelines by estimating the benefits and harms associated with various low-dose computed tomography (LDCT) screening strategies. Design, Setting, and Participants: Comparative simulation modeling with 4 lung cancer natural history models for individuals from the 1950 and 1960 US birth cohorts who were followed up from aged 45 through 90 years. Exposures: Screening with varying starting ages, stopping ages, and screening frequency. Eligibility criteria based on age, cumulative pack-years, and years since quitting smoking (risk factor-based) or on age and individual lung cancer risk estimation using risk prediction models with varying eligibility thresholds (risk model-based). A total of 1092 LDCT screening strategies were modeled. Full uptake and adherence were assumed for all scenarios. Main Outcomes and Measures: Estimated lung cancer deaths averted and life-years gained (benefits) compared with no screening. Estimated lifetime number of LDCT screenings, false-positive results, biopsies, overdiagnosed cases, and radiation-related lung cancer deaths (harms). Results: Efficient screening programs estimated to yield the most benefits for a given number of screenings were identified. Most of the efficient risk factor-based strategies started screening at aged 50 or 55 years and stopped at aged 80 years. The 2013 USPSTF-recommended criteria were not among the efficient strategies for the 1960 US birth cohort. Annual strategies with a minimum criterion of 20 pack-years of smoking were efficient and, compared with the 2013 USPSTF-recommended criteria, were estimated to increase screening eligibility (20.6%-23.6% vs 14.1% of the population ever eligible), lung cancer deaths averted (469-558 per 100 000 vs 381 per 100 000), and life-years gained (6018-7596 per 100 000 vs 4882 per 100 000). However, these strategies were estimated to result in more false-positive test results (1.9-2.5 per person screened vs 1.9 per person screened with the USPSTF strategy), overdiagnosed lung cancer cases (83-94 per 100 000 vs 69 per 100 000), and radiation-related lung cancer deaths (29.0-42.5 per 100 000 vs 20.6 per 100 000). Risk model-based vs risk factor-based strategies were estimated to be associated with more benefits and fewer radiation-related deaths but more overdiagnosed cases. Conclusions and Relevance: Microsimulation modeling studies suggested that LDCT screening for lung cancer compared with no screening may increase lung cancer deaths averted and life-years gained when optimally targeted and implemented. Screening individuals at aged 50 or 55 years through aged 80 years with 20 pack-years or more of smoking exposure was estimated to result in more benefits than the 2013 USPSTF-recommended criteria and less disparity in screening eligibility by sex and race/ethnicity.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Tomografia Computadorizada por Raios X , Idoso , Detecção Precoce de Câncer/efeitos adversos , Detecção Precoce de Câncer/normas , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/prevenção & controle , Pessoa de Meia-Idade , Modelos Teóricos , Medição de Risco , Sensibilidade e Especificidade , Fumar , Abandono do Hábito de Fumar , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/métodos
3.
Am J Nurs ; 121(3): 21, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625004

RESUMO

Editor's note: The mission of Cochrane Nursing is to provide an international evidence base for nurses involved in delivering, leading, or researching nursing care. Cochrane Corner provides summaries of recent systematic reviews from the Cochrane Library. For more information, see https://nursing.cochrane.org.


Assuntos
Suplementos Nutricionais , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/prevenção & controle , Vitaminas/administração & dosagem , Humanos , Neoplasias Pulmonares/mortalidade , Pesquisa em Enfermagem , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Nat Cell Biol ; 23(1): 75-86, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33420490

RESUMO

Nutrient availability is central for T-cell functions and immune responses. Here we report that CD8+ T-cell activation and anti-tumour responses are strongly potentiated by the non-essential amino acid Asn. Increased Asn levels enhance CD8+ T-cell activation and effector functions against tumour cells in vitro and in vivo. Conversely, restriction of dietary Asn, ASNase administration or inhibition of the Asn transporter SLC1A5 impairs the activity and responses of CD8+ T cells. Mechanistically, Asn does not directly alter cellular metabolic fluxes; it instead binds the SRC-family protein tyrosine kinase LCK and orchestrates LCK phosphorylation at Tyr 394 and 505, thereby leading to enhanced LCK activity and T-cell-receptor signalling. Thus, our findings reveal a critical and metabolism-independent role for Asn in the direct modulation of the adaptive immune response by controlling T-cell activation and efficacy, and further uncover that LCK is a natural Asn sensor signalling Asn sufficiency to T-cell functions.


Assuntos
Asparagina/farmacologia , Linfócitos T CD8-Positivos/imunologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/prevenção & controle , Ativação Linfocitária , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/imunologia , Melanoma Experimental/prevenção & controle , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Melanoma Experimental/imunologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Transdução de Sinais , Células Tumorais Cultivadas , Tirosina/metabolismo , Quinases da Família src/metabolismo
5.
Zhongguo Fei Ai Za Zhi ; 24(1): 31-35, 2021 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-33478188

RESUMO

Lung cancer is the malignant tumor with the highest incidence in China. Early detection and identification of symptomatic lung cancer patients and timely screen out asymptomatic patients from high-risk groups require multiple cooperation. At present, although combined imaging, serology, genomics, proteomics and other methods have been combined to screen for suspected lung cancer, there are still problems such as missed diagnosis and misdiagnosis. Meanwhile, the spread of the corona virus disease 2019 (COVID-19) epidemic has brought new challenges to early lung cancer screening. Under the normalization of epidemic prevention and control, the work of early lung cancer screening should be changed accordingly: improve the population's awareness of cancer prevention and control, strengthen the management of medical procedures, improve the efficiency of tumor detection, optimize detection technology, and utilize internet and big data platforms rationally. We should establish an ideal model, combining multiple screening methods, which is streamlined and efficient for early lung cancer screening under normal epidemic prevention and control.
.


Assuntos
/epidemiologia , Neoplasias Pulmonares/diagnóstico , China/epidemiologia , Detecção Precoce de Câncer , Epidemias , Humanos , Neoplasias Pulmonares/prevenção & controle
6.
Med Clin North Am ; 104(6): 1037-1050, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33099449

RESUMO

Lung cancer screening with low-dose computed tomography provides an opportunity to save lives by early detection of the deadliest cancer in the United States. Uptake of lung cancer screening has been quite low but may be improving. Clinician and patient education, integration of lung cancer screening protocols into electronic medical records, support for shared decision making and tobacco cessation, and improved communication between referral centers and clinicians are all important areas for improvement for lung cancer screening to reach its potential in improving morbidity and mortality from lung cancer.


Assuntos
Neoplasias Pulmonares/prevenção & controle , Atenção Primária à Saúde , Detecção Precoce de Câncer , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Padrões de Prática Médica/estatística & dados numéricos , Abandono do Hábito de Fumar , Tomografia Computadorizada por Raios X , Estados Unidos
7.
Anticancer Res ; 40(9): 4869-4874, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878774

RESUMO

BACKGROUND/AIM: In the present study, we evaluated the efficacy of adjuvant administration of oral recombinant methioninase (o-rMETase) against recurrence and metastasis in a 4T1 murine breast-cancer syngeneic model. MATERIALS AND METHODS: 4T1 cells were orthotopically implanted into the 2nd mammary fat pad of BALB/c mice. The 4T1 orthotopic syngeneic models were randomized into 2 groups after primary tumor resection: untreated control and o-rMETase (100 units, oral, daily, 2 weeks). RESULTS: The frequency and extent of local recurrence were reduced by o-rMETase. The number of individual cancer cells and metastatic nodules on the lung surface was significantly lower in the o-rMETase-treated mice than the untreated control mice. CONCLUSION: Adjuvant o-rMETase inhibited local recurrence and lung metastasis after primary tumor resection.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Liases de Carbono-Enxofre/administração & dosagem , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/tratamento farmacológico , Administração Oral , Animais , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/cirurgia , Camundongos , Camundongos Endogâmicos BALB C , Recidiva Local de Neoplasia/prevenção & controle , Proteínas Recombinantes/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
8.
PLoS One ; 15(9): e0239088, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32977329

RESUMO

Previously, we demonstrated the in vitro anti-tumor effects of desethylamiodarone (DEA) in bladder and cervix cancer cell lines. In the present study, we intended to establish its potentiality in B16-F10 metastatic melanoma cells in vitro and in vivo. We assessed cell proliferation, apoptosis and cell cycle by using sulforhodamine B assay, Muse™ Annexin V & Dead Cell and Muse® Cell Cycle assays, respectively. We determined colony formation after crystal violet staining. For studying mechanistic aspects, immunoblotting analysis was performed. We used a C57BL/6 experimental lung metastasis model for demonstrating in vivo anti-metastatic potential of DEA. DEA inhibited in vitro proliferation and colony formation, and in vivo lung metastasizing properties of B16-F10 cells. It arrested the cells in G0/G1 phase of their cycle likely via p21 in a p53-dependent fashion, and induced caspase mediated apoptosis likely via inversely regulating Bcl-2 and Bax levels, and reducing Akt and ERK1/2 activation. In this study, we provided in vitro and in vivo experimental evidences for DEA's potentiality in the therapy of metastatic melanomas. Since DEA is the major metabolite of amiodarone, a worldwide used antiarrhythmic drug, safety concerns could be resolved more easily for it than for a novel pharmacological agent.


Assuntos
Amiodarona/análogos & derivados , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Melanoma Experimental/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Amiodarona/uso terapêutico , Animais , Antiarrítmicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Cutâneas/patologia
9.
Life Sci ; 260: 118384, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32898529

RESUMO

AIMS: The major cause behind lung cancer development is exposure to various polycyclic aromatic hydrocarbons like benzo(a)pyrene (BaP) present in tobacco smoke, motor vehicle, and industrial exhaust. BaP is reported to induce the expression of various pro-inflammatory cytokines and matrix remodeling proteins. It is also responsible for dysfunction and exhaustion of the killing capacity of CD8+ T lymphocytes, one of the important components of the immune system which can kill tumor cells. We tried to evaluate the synergistic role of IL-27 and IL-28B in modulation of BaP-induced lung carcinogenesis associated with various hallmarks like pulmonary redox imbalance, angiogenesis, inflammation and cell proliferation in lung tissue. MAIN METHOD: BaP was treated to Swiss albino mice to develop lung tumor. After the confirmation of lung tumor development Swiss albino mice were treated with IL-27 and IL-28B alone or in combination intraperitoneally. Histological analysis, immunohistochemistry, biochemical assay, western blot analysis, cell cytotoxicity assay, real-time PCR assay etc. were performed to evaluate the modulatory role of IL-27 and IL-28B. KEY FINDINGS: We observed that IL-27 and IL-28B were able to suppress the expression of lung cancer-associated NFkB, COX-2, and iNOS. The expression of TNF-α, PCNA and some matrix remodeling enzymes were also modulated upon IL-27 and IL-28B treatment. Although the population of lung residing CD8+ T cells in tumor bearing lung tissue were unresponsive but the activity of systemic CD8+ cells was increased. SIGNIFICANCE: Results hinted that IL-27 along with IL-28B were able to ameliorate various hallmarks ranging from angiogenesis to inflammation associated with the BaP-induced lung carcinogenesis. From this study, we propose that IL-27 and IL28B can be used as immunotherapeutic agent to regulate lung cancer.


Assuntos
Benzo(a)pireno/toxicidade , Citocinas/metabolismo , Imunossupressão , Inflamação/prevenção & controle , Interleucina-27/metabolismo , Neoplasias Pulmonares/prevenção & controle , Estresse Oxidativo , Animais , Citocinas/genética , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Interleucina-27/genética , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Oxirredução
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(7): 1076-1080, 2020 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-32741174

RESUMO

Objective: To evaluate the compliance of low-dose computed tomography (LDCT) screening for high-risk groups of lung cancer and influencing factors in urban area of Henan province during 2013-2017. Methods: Cluster sampling method was used to select the residents of 40-74 years old in Henan for cancer risk factor investigation and lung cancer risk assessment. Subjects with high risk of lung cancer received LDCT screening. The differences of LDCT receiving rates between groups were compared with χ(2) tests, and the time trend of rates were tested with the Cochran- Armitage trend test. The potential factors correlating to the compliance of LDCT screening were identified with multivariate logistic regression models. Results: Overall, 35 672 participants who met the inclusion criteria were included in this analysis, and 13 383 of them received LDCT screening, the receiving rate was 37.52%. The receiving rate varied greatly across cities, ranging from 38.47% to 26.73% (P<0.05). Moreover, the receiving rate varied greatly across periods, ranging from 29.22% during 2013-2014 to 43.30% during 2014-2015, and the receiving rate increases gradually as the screening year increases (P<0.001). The multivariate logistic regression analyses showed that: being female, age 45-69 years, with education level of junior high school/high school, previous smoking, drinking or previous drinking, infrequent physical exercise, history of tuberculosis, history of chronic bronchitis, history of emphysema, history of asthma bronchiectasis and family history of lung cancer were positive factors for receiving LDCT screening (All P<0.05). Conclusions: The overall compliance of LDCT screening in high-risk population of lung cancer was still not high in urban area of Henan. Implementation of effective interventions targeting the specific high-risk populations might improve the overall compliance of LDCT screening in the future.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias Pulmonares/prevenção & controle , Cooperação do Paciente/estatística & dados numéricos , Tomografia Computadorizada por Raios X/métodos , População Urbana , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores Socioeconômicos , População Urbana/estatística & dados numéricos
11.
J Environ Pathol Toxicol Oncol ; 39(2): 137-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749123

RESUMO

Lung carcinogenesis is one of the main sources of cancer-related mortality globally and it is estimated that nearly 1 million people die from it every year. The 5-year survival rate of lung carcinogenesis is reported at just 15%. The aim of the current research was to investigate the immunomodulatory effect of eriocitrin against benzo(a)pyrene [B(a) P]-induced lung tumorigenesis in Swiss albino mice. The lung sarcoma was provoked through oral gavage of B(a)P (50 mg/kg body weight) two times/week for four weeks. CEA, lung weight, lipid peroxidation (LPO), body weight, immuno-globulin (IgG, IgA, and IgM), tumor incidence, serum marker enzymes (LDH, AHH, λ-GT, and 5'-NTs), hematological counts (leucocytes, lymphocytes, neutrophils, absolute numbers of lymphocytes and neutrophils), antioxidants (SOD and CAT), inflammatory modulators (IL-1ß, IL-6, and TNF-α), immune complexes (avidity index, phagocyte index, NBT reduction, and SIC) and histopathological changes were analyzed. Moreover, the status of apoptosis proteins (Bax, caspase-9, and caspase-3) and cell proliferative protein (cyclin D1 and cyclin A) expression was determined by Western blot and PCNA by immunohistochemical analysis. B(a)P-challenged cancer-bearing mice exhibited augmented levels of lipid peroxidation, tumor incidence, lung weight, CEA, serum marker enzymes, IgA, SIC, cell proliferative markers, and inflammatory cytokines with concurrent decrease in body weight, antioxidant levels, hematological counts, immunoglobulins, immune complexes, and apoptotic protein expression. The eriocitrin treatments caused significant reversion of all these marker to previous levels. Overall, the results propose the immunomodulatory prospective of eriocitrin against B(a) P-induced lung carcinogenesis on Swiss albino mice.


Assuntos
Flavanonas/farmacologia , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/prevenção & controle , Animais , Anticarcinógenos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Imunoglobulinas/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Fagócitos/efeitos dos fármacos
12.
Int J Nanomedicine ; 15: 6019-6032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848399

RESUMO

Purpose: To evaluate the antitumor efficacy of Ag3Au1Trp1:2NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor's metastatic potential and the underlying molecular mechanism. Subjects and Methods: Ag3Au1Trp1:2NPs were radiolabeled with Gallium-68 and the biodistribution was studied in Swiss mice without tumors and in SCID mice bearing tumors. SCID mice received intratumoral Ag3Au1Trp1:2NPs and tumor size was measured using calipers. Lung and liver tissues were extracted and studied microscopically for the detection of any metastatic sites. Changes in the Caspase-3 and TNF-related apoptosis-inducing ligand (TRAIL) were also investigated using real-time PCR and Western blot techniques, respectively. Results: In the 4T1 tumor-bearing SCID mice, Ag3Au1Trp1:2NPs showed quick passive accumulation at tumor sites at 30 mins post-injection. Mice that received the highest dose of NPs (5.6mg/mL) demonstrated a 1.9-fold lower tumor volume compared to that of the control group at 11 days post-injection, while mice that did not receive NPs showed metastatic sites in liver and lung. Extracted tumor tissue of treated mice revealed increased Casp-3 mRNA levels as well as elevated TRAIL protein levels. Conclusion: Based on our results, Ag3Au1Trp1:2NPs express anti-tumor and anti-metastatic effects in vivo. Ag3Au1Trp1:2NPs also reach tumor site via the enhancement and retention effect which results in the apoptotic death of cancerous cells selectively via the extrinsic TRAIL-dependent pathway.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Nanopartículas Metálicas/uso terapêutico , Neoplasias Experimentais/patologia , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Feminino , Radioisótopos de Gálio/química , Ouro/química , Ouro/farmacologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Nanopartículas Metálicas/química , Camundongos SCID , Neoplasias Experimentais/tratamento farmacológico , Prata/química , Prata/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Distribuição Tecidual , Carga Tumoral
14.
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
15.
Cancer Res ; 80(14): 3009-3022, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32366477

RESUMO

HACE1 is an E3 ubiquitin ligase with important roles in tumor biology and tissue homeostasis. Loss or mutation of HACE1 has been associated with the occurrence of a variety of neoplasms, but the underlying mechanisms have not been defined yet. Here, we report that HACE1 is frequently mutated in human lung cancer. In mice, loss of Hace1 led to enhanced progression of KRasG12D -driven lung tumors. Additional ablation of the oncogenic GTPase Rac1 partially reduced progression of Hace1-/- lung tumors. RAC2, a novel ubiquitylation target of HACE1, could compensate for the absence of its homolog RAC1 in Hace1-deficient, but not in HACE1-sufficient tumors. Accordingly, ablation of both Rac1 and Rac2 fully averted the increased progression of KRasG12D -driven lung tumors in Hace1-/- mice. In patients with lung cancer, increased expression of HACE1 correlated with reduced levels of RAC1 and RAC2 and prolonged survival, whereas elevated expression of RAC1 and RAC2 was associated with poor prognosis. This work defines HACE1 as a crucial regulator of the oncogenic activity of RAC-family GTPases in lung cancer development. SIGNIFICANCE: These findings reveal that mutation of the tumor suppressor HACE1 disrupts its role as a regulator of the oncogenic activity of RAC-family GTPases in human and murine lung cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/14/3009/F1.large.jpg.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinogênese/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/prevenção & controle , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas rac de Ligação ao GTP/antagonistas & inibidores , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinogênese/patologia , Proliferação de Células , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Prognóstico , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
16.
Int J Exp Pathol ; 101(3-4): 106-121, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32452573

RESUMO

Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluated 196 extracts prepared by maceration of Brazilian Atlantic Forest trees with organic solvents and distilled water for cytotoxic and antimetastatic activity. The MTT assay was used to screen the extract activity in MCF-7, HepG2 and B16F10 cancer cells. The highest cytotoxic extract had antimetastatic activity, as determined in in vitro assays and melanoma murine model. The organic extract of the leaves of Athenaea velutina (EAv) significantly inhibited migration, adhesion, invasion and cell colony formation in B16F10 cells. The phenolic compounds and flavonoids in EAv were identified for the first time, using flow injection with electrospray negative ionization-ion trap tandem mass spectrometry analysis (FIA-ESI-IT-MSn ). EAv markedly suppressed the development of pulmonary melanomas following the intravenous injection of melanoma cells to C57BL/6 mice. Stereological analysis of the spleen cross-sections showed enlargement of the red pulp area after EAv treatment, which indicated the activation of the haematopoietic system. The treatment of melanoma-bearing mice with EAv did not result in liver damage. In conclusion, these findings suggest that A velutina is a source of natural products with potent antimetastatic activity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Florestas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/prevenção & controle , Melanoma Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Solanaceae/química , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias da Mama/patologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/secundário , Células MCF-7 , Melanoma Experimental/secundário , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Metástase Neoplásica , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química
19.
Am J Physiol Lung Cell Mol Physiol ; 318(5): L1004-L1007, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32233791
20.
Cochrane Database Syst Rev ; 3: CD005004, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32118296

RESUMO

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2009, Issue 3).Tea is one of the most commonly consumed beverages worldwide. Teas from the plant Camellia sinensis can be grouped into green, black and oolong tea, and drinking habits vary cross-culturally. C sinensis contains polyphenols, one subgroup being catechins. Catechins are powerful antioxidants, and laboratory studies have suggested that these compounds may inhibit cancer cell proliferation. Some experimental and nonexperimental epidemiological studies have suggested that green tea may have cancer-preventative effects. OBJECTIVES: To assess possible associations between green tea consumption and the risk of cancer incidence and mortality as primary outcomes, and safety data and quality of life as secondary outcomes. SEARCH METHODS: We searched eligible studies up to January 2019 in CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and reference lists of previous reviews and included studies. SELECTION CRITERIA: We included all epidemiological studies, experimental (i.e. randomised controlled trials (RCTs)) and nonexperimental (non-randomised studies, i.e. observational studies with both cohort and case-control design) that investigated the association of green tea consumption with cancer risk or quality of life, or both. DATA COLLECTION AND ANALYSIS: Two or more review authors independently applied the study criteria, extracted data and assessed methodological quality of studies. We summarised the results according to diagnosis of cancer type. MAIN RESULTS: In this review update, we included in total 142 completed studies (11 experimental and 131 nonexperimental) and two ongoing studies. This is an additional 10 experimental and 85 nonexperimental studies from those included in the previous version of the review. Eleven experimental studies allocated a total of 1795 participants to either green tea extract or placebo, all demonstrating an overall high methodological quality based on 'Risk of bias' assessment. For incident prostate cancer, the summary risk ratio (RR) in the green tea-supplemented participants was 0.50 (95% confidence interval (CI) 0.18 to 1.36), based on three studies and involving 201 participants (low-certainty evidence). The summary RR for gynaecological cancer was 1.50 (95% CI 0.41 to 5.48; 2 studies, 1157 participants; low-certainty evidence). No evidence of effect of non-melanoma skin cancer emerged (summary RR 1.00, 95% CI 0.06 to 15.92; 1 study, 1075 participants; low-certainty evidence). In addition, adverse effects of green tea extract intake were reported, including gastrointestinal disorders, elevation of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin/subcutaneous reactions. Consumption of green tea extracts induced a slight improvement in quality of life, compared with placebo, based on three experimental studies. In nonexperimental studies, we included over 1,100,000 participants from 46 cohort studies and 85 case-control studies, which were on average of intermediate to high methodological quality based on Newcastle-Ottawa Scale 'Risk of bias' assessment. When comparing the highest intake of green tea with the lowest, we found a lower overall cancer incidence (summary RR 0.83, 95% CI 0.65 to 1.07), based on three studies, involving 52,479 participants (low-certainty evidence). Conversely, we found no association between green tea consumption and cancer-related mortality (summary RR 0.99, 95% CI 0.91 to 1.07), based on eight studies and 504,366 participants (low-certainty evidence). For most of the site-specific cancers we observed a decreased RR in the highest category of green tea consumption compared with the lowest one. After stratifying the analysis according to study design, we found strongly conflicting results for some cancer sites: oesophageal, prostate and urinary tract cancer, and leukaemia showed an increased RR in cohort studies and a decreased RR or no difference in case-control studies. AUTHORS' CONCLUSIONS: Overall, findings from experimental and nonexperimental epidemiological studies yielded inconsistent results, thus providing limited evidence for the beneficial effect of green tea consumption on the overall risk of cancer or on specific cancer sites. Some evidence of a beneficial effect of green tea at some cancer sites emerged from the RCTs and from case-control studies, but their methodological limitations, such as the low number and size of the studies, and the inconsistencies with the results of cohort studies, limit the interpretability of the RR estimates. The studies also indicated the occurrence of several side effects associated with high intakes of green tea. In addition, the majority of included studies were carried out in Asian populations characterised by a high intake of green tea, thus limiting the generalisability of the findings to other populations. Well conducted and adequately powered RCTs would be needed to draw conclusions on the possible beneficial effects of green tea consumption on cancer risk.


Assuntos
Camellia sinensis , Neoplasias/prevenção & controle , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Chá , Neoplasias da Mama/prevenção & controle , Camellia sinensis/química , Estudos de Casos e Controles , Feminino , Flavonoides/farmacologia , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/prevenção & controle , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/prevenção & controle , Masculino , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/prevenção & controle , Neoplasias/epidemiologia , Neoplasias/mortalidade , Fenóis/farmacologia , Extratos Vegetais/efeitos adversos , Polifenóis , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controle , Chá/efeitos adversos , Neoplasias Urogenitais/epidemiologia , Neoplasias Urogenitais/prevenção & controle
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