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1.
BMJ Open ; 14(2): e081379, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316601

RESUMO

INTRODUCTION: Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC). METHODS/DESIGN: This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1-3 and one meal/day in months 4-6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1-2 pounds per week. ETHICS AND DISSEMINATION: The National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563). TRIAL REGISTRATION NUMBER: NCT04780477.


Assuntos
Pólipos Adenomatosos , Neoplasias do Colo , Fabaceae , Microbioma Gastrointestinal , Adulto , Humanos , Sobrepeso/complicações , Sobrepeso/terapia , Obesidade/complicações , Obesidade/terapia , Neoplasias do Colo/prevenção & controle , Pólipos Adenomatosos/complicações , Verduras , Metaboloma , Biomarcadores , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Food Funct ; 15(1): 183-195, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38019686

RESUMO

Anticancer effects of vitamin E (tocopherols) have been studied extensively. While in vitro and animal studies showed promising results regarding anticancer effects of tocopherols, human intervention studies failed to reproduce these results. In vivo, α-tocopherol (α-TOH) is metabolized to the long-chain metabolites (LCM) 13'-hydroxychromanol (α-13'-OH) and 13'-carboxychromanol (α-13'-COOH), which likely reach the large intestine. The LCM showed antiproliferative effects in different colon cancer cell lines, but the exact mechanism of action remains unclear. To further clarify the chemopreventive action of the LCM, premalignant LT97 colon adenoma cells were treated with α-TOH, α-13'-OH and α-13'-COOH to study their impact on growth, apoptosis, antigenotoxicity, and ROS-scavenging capacity as well as expression of selected genes involved in detoxification and the cell cycle. Growth inhibitory potential was observed for α-13'-OH (IC50: 37.4 µM) and α-13'-COOH (IC50: 5.8 µM) but not for α-TOH in the tested concentrations. Levels of caspase-3 activity and expression of genes regulating the cell cycle and detoxification remained unchanged. However, α-TOH, α-13'-OH and α-13'-COOH exhibited antigenotoxic and partly ROS-scavenging capacity. The results indicate that the LCM exert chemopreventive effects via ROS-scavenging capacity, the protection against DNA damage and the induction of cell death via caspase-independent mechanisms in premalignant colon cells.


Assuntos
Adenoma , Neoplasias do Colo , Animais , Humanos , alfa-Tocoferol/farmacologia , alfa-Tocoferol/metabolismo , Espécies Reativas de Oxigênio , Tocoferóis , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/prevenção & controle , Adenoma/tratamento farmacológico , Adenoma/prevenção & controle
3.
Oncoimmunology ; 12(1): 2260620, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781234

RESUMO

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality despite efforts to improve standard interventions. As CRC patients can benefit from immunotherapeutic strategies that incite effector T cell action, cancer vaccines represent a safe and promising therapeutic approach to elicit protective and durable immune responses against components of the tumor microenvironment (TME). In this study, we investigate the pre-clinical potential of a Listeria monocytogenes (Lm)-based vaccine targeting the CRC-associated vasculature. CRC survival and progression are reliant on functioning blood vessels to effectively mediate various metabolic processes and oxygenate underlying tissues. We, therefore, advance the strategy of initiating immunity in syngeneic mouse models against the endogenous pericyte antigen RGS5, which is a critical mediator of pathological vascularization. Overall, Lm-based vaccination safely induced potent anti-tumor effects that consisted of recruiting functional Type-1-associated T cells into the TME and reducing tumor blood vessel content. This study underscores the promising clinical potential of targeting RGS5 against vascularized tumors like CRC.


Assuntos
Neoplasias do Colo , Listeria monocytogenes , Listeria , Proteínas RGS , Camundongos , Animais , Humanos , Pericitos , Neoplasias do Colo/prevenção & controle , Listeria monocytogenes/metabolismo , Vacinação , Microambiente Tumoral , Proteínas RGS/genética , Proteínas RGS/metabolismo
4.
Food Funct ; 14(21): 9617-9634, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37814914

RESUMO

We previously found greater reduction of colon cancer (CC) biomarkers for red wheat compared to white wheat regardless of refinement state. In the present study we examined whether the phenolic-rich aleurone and testa layers are drivers of chemoprevention by red wheat and their influence on gut microbiota composition using a 1,2-dimethylhydrazine-induced CC rat model. Rats were fed a low-fat diet (16% of energy as fat), high-fat diet (50% of energy as fat), or high-fat diet containing whole red wheat, refined red wheat, refined white wheat, or aleurone- or testa-enriched fractions for 12 weeks. Morphological markers (aberrant crypt foci, ACF) were assessed after methylene blue staining and biochemical markers (3-nitrotyrosine [3-NT], Dclk1) by immunohistochemical determination of staining positivity within aberrant crypts. Gut microbiota composition was evaluated from 16S rRNA gene sequencing of DNA extracted from cecal contents. Relative to the high-fat diet, the whole and refined red wheat, refined white wheat, and testa-enriched fraction decreased ACF, while only the refined red wheat and aleurone-enriched fraction decreased 3-NT. No significant differences were observed for Dclk1. An increase in microbial diversity was observed for the aleurone-enriched fraction (ACE index) and whole red wheat (Inverse Simpson Index). The diet groups significantly modified overall microbiome composition, including altered abundances of Lactobacillus, Mucispirillum, Phascolarctobacterium, and Blautia coccoides. These results suggest that red wheat may reduce CC risk through modifications to the gut microbiota and nitrosative stress, which may be due, in part, to the influence of dietary fiber and the phenolic-rich aleurone layer.


Assuntos
Neoplasias do Colo , Microbioma Gastrointestinal , Ratos , Animais , Biomarcadores Tumorais , Triticum , Estresse Nitrosativo , RNA Ribossômico 16S , Neoplasias do Colo/prevenção & controle , Dieta Hiperlipídica/efeitos adversos
5.
Int J Mol Sci ; 24(11)2023 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-37298349

RESUMO

Phosphodiesterase-5 inhibitors (PDE5i) are under investigation for repurposing for colon cancer prevention. A drawback to conventional PDE5i are their side-effects and drug-drug interactions. We designed an analog of the prototypical PDE5i sildenafil by replacing the methyl group on the piperazine ring with malonic acid to reduce lipophilicity, and measured its entry into the circulation and effects on colon epithelium. This modification did not affect pharmacology as malonyl-sildenafil had a similar IC50 to sildenafil but exhibited an almost 20-fold reduced EC50 for increasing cellular cGMP. Using an LC-MS/MS approach, malonyl-sildenafil was negligible in mouse plasma after oral administration but was detected at high levels in the feces. No bioactive metabolites of malonyl-sildenafil were detected in the circulation by measuring interactions with isosorbide mononitrate. The treatment of mice with malonyl-sildenafil in the drinking water resulted in a suppression of proliferation in the colon epithelium that is consistent with results previously published for mice treated with PDE5i. A carboxylic-acid-containing analog of sildenafil prohibits the systemic delivery of the compound but maintains sufficient penetration into the colon epithelium to suppress proliferation. This highlights a novel approach to generating a first-in-class drug for colon cancer chemoprevention.


Assuntos
Neoplasias do Colo , Inibidores da Fosfodiesterase 5 , Camundongos , Animais , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Cromatografia Líquida , Espectrometria de Massas em Tandem , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/prevenção & controle , Proliferação de Células , GMP Cíclico/metabolismo
7.
Phytochemistry ; 211: 113706, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37149122

RESUMO

In this manuscript the biomolecular mechanism of action of the natural colon cancer chemopreventive agent 4'-geranyloxyferulic acid in cultured Caco-2 cells has been investigated. It was first demonstrated how the application of this phytochemical led to a time- and dose-dependent decrease of cell viability and in parallel to a massive generation of reactive oxygen species and induction of caspases 3 and 9, finally providing apoptosis. This event is accompanied by deep modifications in key pro-apoptotic targets like CD95, DR4 and 5, cytochrome c, Apaf-1, Bcl-2, and Bax. Such effects can explain the large apoptosis recorded in Caco-2 cells treated with 4'-geranyloxyferulic acid.


Assuntos
Caspases , Neoplasias do Colo , Humanos , Células CACO-2 , Apoptose , Neoplasias do Colo/prevenção & controle , Espécies Reativas de Oxigênio
8.
Multimedia | Recursos Multimídia | ID: multimedia-10273

RESUMO

Olá! Eu sou o Luciano Duro, médico de família e comunidade, mestre e doutor em epidemiologia e no oitavo episódio da terceira temporada, vou falar sobre um estudo publicado em outubro de 2022 no New England Journal of Medicine, comparando os efeitos da colonoscopia na redução da incidência de câncer de cólon, na mortalidade por este câncer e na mortalidade por todas as causas. Vou realizar uma análise à luz deste artigo, mas com o viés das interpretações que devemos tecer em termos de efetividade para saúde pública, pois o tema gera discussões.


Assuntos
Webcast , Medicina Baseada em Evidências , Colonoscopia , Neoplasias do Colo/prevenção & controle
9.
Cancer Prev Res (Phila) ; 16(8): 429-438, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37012205

RESUMO

Colorectal cancer represents the third most common cancer type worldwide and is a leading cause of cancer-related mortality in the United States and Western countries. Rodent models have been invaluable to study the etiology of colorectal cancer and to test novel chemoprevention avenues. In the past, the laboratory mouse has become one of the best preclinical models for these studies due to the availability of genetic information for commonly used mouse strains with well-established and precise gene targeting and transgenic techniques. Well-established chemical mutagenesis technologies are also being used to develop mouse and rat models of colorectal cancer for prevention and treatment studies. In addition, xenotransplantation of cancer cell lines and patient-derived xenografts has been useful for preclinical prevention studies and drug development. This review focuses on the recent use of rodent models to evaluate the utility of novel strategies in the prevention of colon cancers including immune prevention approaches and the manipulation of the intestinal microbiota.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Microbiota , Humanos , Camundongos , Ratos , Animais , Roedores , Neoplasias do Colo/prevenção & controle , Neoplasias do Colo/genética , Vacinação , Neoplasias Colorretais/prevenção & controle
10.
Eur J Pharmacol ; 946: 175656, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-36921708

RESUMO

Despite being shown to be effective for chemoprevention of colorectal cancer, aspirin has limitations including adverse effects and inability to block colitis-associated colon cancer (CAC). γ-Tocopherol (γT), a vitamin E form, has been reported to mitigate experimental colitis and CAC, prolong the anti-inflammatory activity of aspirin and alleviate aspirin-induced adverse effect. We therefore hypothesize that combining γT and aspirin is better than either compound singly for suppressing CAC. This hypothesis was tested in the murine azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CAC model and with human HCT116 colon cancer cells. Compared to the control, combining aspirin (250 ppm) and γT (500 ppm) but not either compound alone significantly reduced AOM/DSS-induced tumor area and multiplicity of large-size tumors by 60% and 50%, respectively. Meanwhile, γT mitigated aspirin-promoted inflammation and stomach lesions in mice. Moreover, the combination appeared to cause favorable changes of gut microbiota compared to the control and synergistically suppressed the growth of HCT116 cells. Our study demonstrates that combining aspirin and γT improves anticancer effects and counteracts side effects compared to aspirin and may therefore be a novel combinatory chemopreventive agent against CAC.


Assuntos
Colite , Neoplasias do Colo , Microbioma Gastrointestinal , Humanos , Camundongos , Animais , gama-Tocoferol/efeitos adversos , Aspirina/efeitos adversos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , Neoplasias do Colo/patologia , Colite/induzido quimicamente , Colite/complicações , Colite/tratamento farmacológico , Carcinogênese , Transformação Celular Neoplásica , Sulfato de Dextrana/efeitos adversos , Azoximetano/toxicidade , Camundongos Endogâmicos C57BL
11.
Eur J Pharmacol ; 947: 175680, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36990263

RESUMO

Colon cancer was the second leading cause of cancer-related death in 2019. We herein investigated the effects of acertannin containing Acer species on azoxymethane (AOM)/dextran sulfate sodium (DDS)-induced colon cancer growth and changes in the colonic levels of interleukin (IL)-1ß, monocyte chemoattractant protein (MCP)-1, IL-10, and programmed cell death-1 (PD-1). Colorectal carcinogenesis was induced by an intraperitoneal injection of AOM (10 mg/kg) on days 0 and 27. Mice were given 1% (w/v) DSS drinking water ad libitum on days 7-14, 32-33, and 35-38. Acertannin (30 and 100 mg/kg) was orally administered on days 1-16, discontinued for 11 days (days 16-26), and then administered again on days 27-41. The colonic levels of cytokines, a chemokine, and PD-1 were measured using the respective ELISA kits. The number and area of tumors in mice treated with acertannin (100 mg/kg) decreased by 53.9 and 63.1%, respectively. Furthermore, the colonic levels of IL-1ß, MCP-1, IL-10, and PD-1 showed reductions of 57.3, 62.9, 62.8, and 100%, respectively, while the numbers of cyclooxygenase-2 (COX-2)-, thymocyte selection-associated high mobility group box proteins (TOX)/TOX2-, PD-1-, and signal transducer and activator of transcription 3 (STAT3) phosphorylation-positive numbers decreased by 79.6, 77.9, 93.8, and 100%, respectively. In conclusion, the inhibitory effects of acertannin on AOM/DSS-induced colon tumor growth appear to be associated with reductions in the colonic levels of IL-1ß, MCP-1, IL-10, and PD-1 through the down-regulated expression of COX-2 and TOX/TOX2 in the tumor microenvironment.


Assuntos
Neoplasias do Colo , Taninos , Animais , Camundongos , Azoximetano/toxicidade , Quimiocina CCL2/metabolismo , Colo , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , Neoplasias do Colo/metabolismo , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana/toxicidade , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral , Taninos/farmacologia
12.
Int J Mol Sci ; 24(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36982300

RESUMO

Colorectal cancer (CRC) is responsible for a notable rise in the overall mortality rate. Obesity is found to be one of the main factors behind CRC development. Andrographis paniculata is a herbaceous plant famous for its medicinal properties, particularly in Southeast Asia for its anti-cancer properties. This study examines the chemopreventive impact of A. paniculata ethanolic extract (APEE) against a high-fat diet and 1,2-dimethylhydrazine-induced colon cancer in Sprague Dawley rats. Sprague Dawley rats were administered 1,2-dimethylhydrazine (40 mg/kg, i.p. once a week for 10 weeks) and a high-fat diet (HFD) for 20 weeks to induce colorectal cancer. APEE was administered at 125 mg/kg, 250 mg/kg, and 500 mg/kg for 20 weeks. At the end of the experiment, blood serum and organs were collected. DMH/HFD-induced rats had abnormal crypts and more aberrant crypt foci (ACF). APEE at a dose of 500 mg/kg improved the dysplastic state of the colon tissue and caused a 32% reduction in the total ACF. HFD increased adipocyte cell size, while 500 mg/kg APEE reduced it. HFD and DMH/HFD rats had elevated serum insulin and leptin levels. Moreover, UHPLC-QTOF-MS analysis revealed that APEE was rich in anti-cancer phytochemicals. This finding suggests that APEE has anti-cancer potential against HFD/DMH-induced CRC and anti-adipogenic and anti-obesity properties.


Assuntos
Focos de Criptas Aberrantes , Anticarcinógenos , Neoplasias do Colo , Ratos , Animais , Ratos Sprague-Dawley , Andrographis paniculata , 1,2-Dimetilidrazina/toxicidade , Dieta Hiperlipídica/efeitos adversos , Extratos Vegetais/efeitos adversos , Neoplasias do Colo/prevenção & controle , Anticarcinógenos/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/etiologia , Carcinógenos
13.
Br J Nutr ; 130(6): 1047-1055, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36620946

RESUMO

According to the World Cancer Research Fund International, vitamin D might decrease the risk of colorectal cancer (CRC). However, less is known about the association with cancers in different subsites of the colon and in the rectum. The aim of this study was to examine associations between pre-diagnostic intake of vitamin D and risk of CRC by anatomical subsites. Data from 95 416 participants in the Norwegian Women and Cancer Cohort Study was included, and vitamin D intake was estimated from two repeated FFQ. Associations between vitamin D intake and incidence of CRC were assessed using multivariable Cox regression. During follow-up, there were 1774 incident cases of CRC. A small but borderline significant inverse association was found for a 5-µg increase in vitamin D intake and risk of CRC (hazard ratio (HR) = 0·97; 95 % CI 0·93, 1·01) and colon cancer (HR = 0·96; 95 % CI 0·91, 1·01). High (≥ 20 µg) compared with low (< 10 µg) vitamin D intake was associated with 17 % borderline significant reduced risk of CRC (HR = 0·83; 95 % CI 0·68, 1·02). Medium (10-19 µg) v. low intake (< 10 µg) was associated with 27 % reduced risk of proximal colon cancer (HR = 0·73; 95 % CI 0·57, 0·94). No significant associations were observed between vitamin D intake and risk of distal colon or rectal cancer. Our study indicates that vitamin D may be differently associated with subsites of the colon. The association between vitamin D intake and proximal colon cancer is novel.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Feminino , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Estudos de Coortes , Vitamina D , Incidência , Fatores de Risco , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/etiologia , Neoplasias do Colo/prevenção & controle , Noruega/epidemiologia
14.
Eur J Cancer Prev ; 32(2): 103-112, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579178

RESUMO

PURPOSE: Colorectal cancer is one of the most commonly diagnosed and deadly cancers worldwide. Epidemiological studies on the relationship between folate intake and the risk of colorectal cancer have reported inconsistent findings since folate fortification in the USA. For this situation, we conducted a large number of data analyses to study the relationship between folate intake and colorectal cancer risk. METHODS: PubMed and EMBASE databases were used to search the literature systematically. Eligible studies were reviewed and meta-analyzed to assess the relationship. RESULTS: A total of 24 cohort studies involving 37 280 patients and 6 165 894 individuals were included. The results showed that high folate intake was associated with a reduced risk of colorectal cancer. The combined relative risk (RR) for the highest intake compared with the lowest was 0.88 [95% confidence interval (CI), 0.83-0.92, P = 10 -4 ). Further studies indicated that the increase of folate intake may decrease the risk of colorectal cancer in people with medium or high alcohol consumption (RR = 0.97, 95% CI: 0.96-0.99, P = 0.008; RR = 0.95, 95% CI: 0.92-0.98, P = 0.003), but not in non-drinkers (RR = 1.00, 95% CI: 0.98-1.02, P = 0.827). Next, high folate intake may decrease the risk of colon cancer (RR = 0.86, 95% CI: 0.81-0.92, P = 10 -4 ) but not rectal cancer (RR = 0.92, 95% CI: 0.84-1.02, P = 0.112). Additionally, the result that high folate intake may decrease the risk of colorectal cancer was observed in the USA and Europe but not in other regions. CONCLUSION: High folate intake may be protective against colon cancer, particularly in people with middle or high alcohol consumption, but it still needs to be further confirmed.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Ácido Fólico , Estudos Prospectivos , Dieta , Neoplasias do Colo/prevenção & controle , Risco , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Fatores de Risco
15.
Br J Nutr ; 129(3): 395-405, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35506448

RESUMO

Colorectal cancer is the third most diagnosed cancer worldwide and linked to dietary/lifestyle factors. Arthrospira (Spirulina) platensis (AP) contains bioactive compounds with beneficial effects in vivo/in vitro. We evaluated the effects of AP feeding against 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male Sprague Dawley rats were given subcutaneous injections of DMH (4 × 40 mg/kg body weight) (G1-G3) or vehicle (G4-G5) twice a week (weeks 3-4). During weeks 1-4, animals were fed a diet containing 1 % (G2) or 2 % (G3-G4) AP powder (w/w). After this period, all groups received a balanced diet until week 12. Some animals were euthanised after the last DMH injection (week 4) for histological, immunohistochemical (Ki-67, γ-H2AX and caspase-3) and molecular analyses (real time-PCR for 91 genes), while other animals were euthanised at week 12 for preneoplastic aberrant crypt foci (ACF) analysis. Both AP treatments (G2-G3) significantly decreased the DMH-induced increase in γ-H2AX (DNA damage) and caspase 3 (DNA damage-induced cell death) in colonic crypts at week 4. In addition, Cyp2e1 (Drug metabolism), Notch1, Notch2 and Jag1 genes (Notch pathway) and Atm, Wee1, Chek2, Mgmt, Ogg1 and Xrcc6 genes (DNA repair) were also down-regulated by 2 % AP feeding (G3) at week 4. A significant reduction in ACF development was observed in both AP-treated groups (G2-G3) at week 12. In conclusion, findings indicate that AP feeding reduced acute colonic damage after DMH, resulting in fewer preneoplastic lesions. Our study provided mechanistic insights on dietary AP-preventive effects against early colon carcinogenesis.


Assuntos
Focos de Criptas Aberrantes , Neoplasias do Colo , Lesões Pré-Cancerosas , Spirulina , Ratos , Animais , Masculino , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , 1,2-Dimetilidrazina/toxicidade , Ratos Sprague-Dawley , Carcinogênese/patologia , Colo , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/prevenção & controle , Carcinógenos/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/prevenção & controle
16.
Cancer Epidemiol Biomarkers Prev ; 32(1): 30-36, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36306403

RESUMO

BACKGROUND: Moderate-vigorous physical activity (MVPA) reduces colon cancer risk; however, it is unclear how the timing of MVPA throughout the adult life course impacts colon cancer risk. We evaluated whether maintenance and changes in MVPA levels over time are associated with colon cancer risk. METHODS: We assessed 293,198 adults ages 50 to 71 years in the NIH-AARP Diet and Health Study. Participants completed baseline health and physical activity questionnaires between 1995 and 1997 and were followed through 2011, (average follow-up of 13.1 years). There were 5,072 colon cancer cases over the study period. Using latent class trajectory models, we identified seven distinct MVPA trajectories across the adult life course (15-18, 19-29, 30-35, and past 10-years) and ran Cox proportional hazards regression models. RESULTS: Compared with those who maintained low MVPA levels, those who maintained high and moderate levels of MVPA had a lower risk of colon cancer [HR, 0.85; confidence interval (CI), 0.78-0.93; HR = 0.87; CI, 0.76-1.00)], and those who increased MVPA levels early and later during adulthood had a lower colon cancer risk (HR, 0.90; CI, 0.80-1.01) and (HR, 0.92; CI, 0.80-1.06), respectively. Those who decreased MVPA early in adulthood had an increased risk of colon cancer (HR, 1.12; CI, 1.02-1.23). These associations were stronger in adults ages <65 years at baseline and in men (P < 0.001). CONCLUSIONS: Consistent participation in MVPA throughout life may reduce colon cancer risk. IMPACT: These findings emphasize that engaging in MVPA throughout adulthood lowers risk of colon cancer.


Assuntos
Neoplasias do Colo , Exercício Físico , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Acontecimentos que Mudam a Vida , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/prevenção & controle , Dieta , Modelos de Riscos Proporcionais
17.
Eur J Cancer Prev ; 32(1): 30-47, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36134612

RESUMO

The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.


Assuntos
Neoplasias do Colo , Gastroenteropatias , Probióticos , Humanos , Dieta de Imunonutrição , Probióticos/uso terapêutico , Neoplasias do Colo/prevenção & controle
18.
Clin Nutr ; 42(2): 61-75, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36502573

RESUMO

Butyrate is a key energy source for colonocytes and is produced by the gut microbiota through fermentation of dietary fiber. Butyrate is a histone deacetylase inhibitor and also signals through three G-protein coupled receptors. It is clear that butyrate has an important role in gastrointestinal health and that butyrate levels can impact both host and microbial functions that are intimately coupled with each other. Maintaining optimal butyrate levels improves gastrointestinal health in animal models by supporting colonocyte function, decreasing inflammation, maintaining the gut barrier, and promoting a healthy microbiome. Butyrate has also shown protective actions in the context of intestinal diseases such as inflammatory bowel disease, graft-versus-host disease of the gastrointestinal tract, and colon cancer, whereas lower levels of butyrate and/or the microbes which are responsible for producing this metabolite are associated with disease and poorer health outcomes. However, clinical efforts to increase butyrate levels in humans and reverse these negative outcomes have generated mixed results. This article discusses our current understanding of the molecular mechanisms of butyrate action with a focus on the gastrointestinal system, the links between host and microbial factors, and the efforts that are currently underway to apply the knowledge gained from the bench to bedside.


Assuntos
Butiratos , Fibras na Dieta , Gastroenteropatias , Microbioma Gastrointestinal , Animais , Humanos , Butiratos/farmacologia , Neoplasias do Colo/prevenção & controle , Fibras na Dieta/metabolismo , Fibras na Dieta/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/metabolismo , Gastroenteropatias/prevenção & controle , Receptores Acoplados a Proteínas G/metabolismo , Microbioma Gastrointestinal/fisiologia
19.
Gastroenterol. latinoam ; 34(1): 15-21, 2023. tab
Artigo em Espanhol | LILACS | ID: biblio-1524560

RESUMO

Colorectal Cancer (CRC) is the third most frequent neoplasia worldwide. Despite the significant advances in surgical techniques and the development of new targeted antineoplastic therapies for this type of tumor, primary prevention and early diagnosis of malignant precursor lesions will continue to be the best strategies to reduce their incidence, morbidity, and mortality. Technologies for CRC screening can be classified into two groups, those of an invasive nature, such as colonoscopy and all its different modalities of use, and those of a non-invasive nature, such as laboratory tests and imaging. This review, will focus exclusively on non-invasive screening tests, excluding imaging. Specifically, it will address those that use depositions as a sample. This review will approach the latest international recommendations, regarding the age at which they should be used, their technical-biological bases, the two main types currently used (biochemical and immunological), and we will put into perspective their advantages and their possible disadvantages. Towards the end of this article, the most recent biotechnological developments in relation to molecular tests based on the study of blood samples, will be discussed. Although these tests are not yet in routine clinical use given their high costs, they are promising for the early detection of CRC.


El cáncer colorrectal (CCR) es la tercera neoplasia más común en todo el mundo. A pesar de los avances significativos en las técnicas quirúrgicas y en el desarrollo de nuevas terapias antineoplásicas para este tipo de tumor, la prevención primaria y el diagnóstico precoz de lesiones precursoras malignas siguen siendo las mejores estrategias para reducir la incidencia, morbilidad y mortalidad asociadas al CCR. Existen dos tipos de tecnologías para el tamizaje del CCR: las invasivas, como la colonoscopia, y las no invasivas, como los ensayos de laboratorio y la imagenología. Esta revisión, se centrará exclusivamente en las pruebas de tamizaje no invasivas que utilizan muestras de deposiciones, excluyendo las imágenes. Se abordarán las últimas recomendaciones internacionales sobre el momento etario en que se deben utilizar, sus bases técnico-biológicas, los dos principales tipos utilizados en la actualidad (bioquímico e inmunológico) y pondremos en perspectiva sus ventajas y posibles desventajas. Al final de esta revisión, se discutirá brevemente los últimos avances biotecnológicos relacionados con pruebas moleculares basadas en el estudio de muestras sanguíneas. Aunque estas pruebas aún no son de uso clínico habitual debido a sus altos costos, representan una prometedora innovación para la detección temprana del CCR.


Assuntos
Humanos , Programas de Rastreamento/métodos , Neoplasias do Colo/diagnóstico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Neoplasias do Colo/prevenção & controle , Sangue Oculto
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