RESUMO
Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to evaluate chemopreventive effects of arbutin on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) in rats. Five groups of rats were used: normal control group (rats injected hypodermically with sterile phosphate-buffered saline once per week for two weeks) and groups 2-5, which were subcutaneously inoculated with 15 mg/kg AOM once a week for two weeks. AOM control and 5-fluorouracil (5-FU) control groups were fed 10% Tween orally daily for 8 weeks using a feeding tube. The treated groups were fed 30 and 60 mg/kg arbutin every day for 2 months. ACF from the AOM control group had aberrant nuclei in addition to multilayered cells and an absence of goblet cells. The negative control group displayed spherical cells and nuclei in basal positions. Histological examination revealed a reduced number of AFC cells from colon tissues of the 5-FU reference group. Arbutin-fed animals showed down-regulation of proliferating cell nuclear antigen (PCNA) and up-regulation of Bax protein compared to AOM control. Rats fed with arbutin displayed a significant increase of superoxide dismutase (SOD) and catalase (CAT) activities in colon tissue homogenates compared to the AOM control group. In conclusion, arbutin showed therapeutic effects against colorectal cancer, explained by its ability to significantly decrease ACF, down-regulate PCNA protein, and up-regulate Bax protein. In addition, arbutin significantly increased SOD and CAT, and decreased malondialdehyde (MDA) levels, which might be due to its anti-proliferative and antioxidant properties.
Assuntos
Focos de Criptas Aberrantes , Arbutina , Azoximetano , Antígeno Nuclear de Célula em Proliferação , Proteína X Associada a bcl-2 , Animais , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/patologia , Focos de Criptas Aberrantes/prevenção & controle , Focos de Criptas Aberrantes/tratamento farmacológico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Masculino , Arbutina/farmacologia , Ratos , Proteína X Associada a bcl-2/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Ratos Wistar , Fluoruracila , CarcinógenosRESUMO
Colitis-associated cancer (CAC) is an aggressive subtype of colorectal cancer that can develop in ulcerative colitis patients and is driven by chronic inflammation and oxidative stress. Current chemotherapy for CAC, based on 5-fluorouracil and oxalipltin, is not fully effective and displays severe side effects, prompting the search for alternative therapies. Dimethylfumarate (DMF), an activator of the nuclear factor erythroid 2-related factor 2 (NRF2), is a potent antioxidant and immunomodelatrory drug used in the treatment of multiple sclerosis and showed a strong anti-inflammatory effect on experimental colitis. Here, we investigated the chemotherapeutic effect of DMF on an experimental model of CAC. Male NMRI mice were given two subcutaneous injections of 1,2 Dimethylhydrazine (DMH), followed by three cycles of dextran sulfate sodium (DSS). Low-dose (DMF30) and high-dose of DMF (DMF100) or oxaliplatin (OXA) were administered from the 8th to 12th week of the experiment, and then the colon tissues were analysed histologically and biochemically. DMH/DSS induced dysplastic aberrant crypt foci (ACF), oxidative stress, and severe colonic inflammation, with a predominance of pro-inflammatory M1 macrophages. As OXA, DMF30 reduced ACF multiplicity and crypt dysplasia, but further restored redox status, and reduced colitis severity by shifting macrophages towards the anti-inflammatory M2 phenotype. Surprisingly, DMF100 exacerbated ACF multiplicity, oxidative stress, and colon inflammation, likely through NRF2 and p53 overexpression in colonic inflammatory cells. DMF had a dual effect on CAC. At low dose, DMF is chemotherapeutic and acts as an antioxidant and immunomodulator, whereas at high dose, DMF is pro-oxidant and exacerbates colitis-associated cancer.
Assuntos
Neoplasias Associadas a Colite , Sulfato de Dextrana , Fumarato de Dimetilo , Macrófagos , Estresse Oxidativo , Animais , Fumarato de Dimetilo/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Masculino , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Neoplasias Associadas a Colite/patologia , Neoplasias Associadas a Colite/tratamento farmacológico , Neoplasias Associadas a Colite/prevenção & controle , Sulfato de Dextrana/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/farmacologia , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Modelos Animais de Doenças , Anti-Inflamatórios/farmacologia , Focos de Criptas Aberrantes/patologia , Relação Dose-Resposta a Droga , Antineoplásicos/farmacologia , Antineoplásicos/toxicidadeRESUMO
OBJECTIVE: This study examined the morphological changes in the colonic mucosa and the presence of inflammation in rats induced with 1,2-dimethylhydrazine (DMH) 30 mg/kg BW over 9, 11, and 13 weeks without a latency period. METHODS: Hematoxylin and eosin staining was performed to assess the morphology and characteristic alteration of the epitheliocytes in the colon. Immunohistochemistry was employed to assess the expression of tumor necrosis factor (TNF)-α and cyclooxygenase-2 (COX-2). The difference in the severity of inflammation and COX-2 expression was examined using one-way analysis of variance. The correlation of COX-2 expression with the severity of inflammation was analyzed using Spearman's rank correlation test. RESULT: Until week 13, chronic inflammation and non-hyperplastic and hyperplastic aberrant crypt foci occurred. The severity of inflammation gradually shifted from high moderate to low moderate. TNF-α expression was high in all groups; however, COX-2 expression was gradually lower with longer duration of induction, which corresponded with the severity of inflammation. CONCLUSION: DMH induction until week 13 without a latency period caused chronic inflammation without the formation of adenoma or adenocarcinoma. A very strong correlation was established between COX-2 expression and inflammation.
Assuntos
1,2-Dimetilidrazina , Neoplasias Colorretais , Ciclo-Oxigenase 2 , Inflamação , Fator de Necrose Tumoral alfa , Animais , 1,2-Dimetilidrazina/toxicidade , Ratos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inflamação/induzido quimicamente , Inflamação/patologia , Inflamação/metabolismo , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Carcinógenos/toxicidade , Ratos Sprague-Dawley , Focos de Criptas Aberrantes/patologia , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/metabolismo , Colo/patologia , Colo/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/metabolismoRESUMO
BACKGROUND: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls. METHODS: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed. RESULTS: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear ß-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation. CONCLUSIONS: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon.
Assuntos
Focos de Criptas Aberrantes , Neoplasias do Colo , Neoplasias Colorretais , Lesões Pré-Cancerosas , Humanos , Focos de Criptas Aberrantes/genética , Focos de Criptas Aberrantes/diagnóstico , Focos de Criptas Aberrantes/patologia , Neoplasias Colorretais/patologia , Colo/patologia , Hiperplasia/patologia , Metilação , Genes Supressores de Tumor , Lesões Pré-Cancerosas/patologia , Neoplasias do Colo/patologia , Mucosa Intestinal/patologiaRESUMO
Background and Objectives: Aberrant crypt foci (ACF) are one of the earliest putative preneoplastic and, in some cases, neoplastic lesions in human colons. Many studies have confirmed the reduction of ACFs and colorectal adenomas after treatment with acetylsalicylic acid (ASA) commonly referred to as ASA; however, the minimum effective dose of ASA and the duration of use has not been fully elucidated. The objective of our study was to assess the significance of low dose ASA (75-mg internally once daily) to study the chemopreventive effect of ASA in ACF and adenomas development in patients taking this drug for a minimum period of 10 years. Materials and Methods: Colonoscopy, combined with rectal mucosa staining with 0.25% methylene blue, was performed on 131 patients. The number of rectal ACF in the colon was divided into three groups: ACF < 5; ACF 5−10; and ACF > 10. Patients were divided into two groups: the "With ASA" group (the study group subjects taking ASA 75-mg daily for 10 years); and "Without ASA" group (control group subjects not taking ASA chronically). The incidence of different types of rectal ACF and colorectal polyps in both groups of subjects was analysed and ascertained. Results: Normal ACF was found in 12.3% in the study group vs. 87.7% control group, hyperplastic 22.4% vs. 77.6%, dysplastic 25% vs. 75%, mixed 0% vs. 100%. Treatment with ASA affects the occurrence of colorectal adenomas. The amount of dysplastic ACFs was lower in the study group than in the control group. The increase in dysplastic ACFs decreases with age in both groups, with the increase greater in those not taking ASA. Conclusions: Patients who take persistent, chronic (>10 years) low doses of ASA have a lower total number of all types of rectal ACFs and adenomas compared to the control group.
Assuntos
Focos de Criptas Aberrantes , Adenoma , Neoplasias Colorretais , Humanos , Focos de Criptas Aberrantes/tratamento farmacológico , Focos de Criptas Aberrantes/epidemiologia , Focos de Criptas Aberrantes/patologia , Aspirina/uso terapêutico , Reto , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/tratamento farmacológico , Adenoma/prevenção & controle , Adenoma/patologiaRESUMO
The role of chronic inflammation and arachidonic acid (AA) metabolism in tumor progression has been well characterized for variety of cancers, with compelling data for colon cancer. Several preclinical and clinical studies primarily focused on inhibiting the cyclooxygenase pathways using NSAIDs and aspirin for colon cancer prevention. However, emerging evidence clearly supports the pro-tumorigenic role of 5-lipoxygenase and its downstream leukotriene pathway within AA metabolism. As discussed in the current issue, targeting the leukotriene pathway by cysteinyl leukotriene receptor antagonist (LTRA) montelukast suppressed formation of aberrant crypt foci (ACF) and cell proliferation in colonic epithelium, suggesting the potential of LTRAs for colon cancer prevention. Although this is a short clinical chemoprevention trial to explore the effects of LTRAs against ACF development, it is a significant and timely study opening avenues to further explore the possibilities of using LTRAs in other inflammation-associated precancerous lesions as well. In this spotlight commentary, we highlight the implications of their data and the opportunities for developing LTRAs as potential candidates for colorectal cancer interception. See related article by Higurashi et al., p. 661.
Assuntos
Focos de Criptas Aberrantes , Neoplasias do Colo , Focos de Criptas Aberrantes/patologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Araquidonato 5-Lipoxigenase/farmacologia , Ácido Araquidônico/metabolismo , Aspirina/farmacologia , Quimioprevenção , Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/prevenção & controle , Humanos , Inflamação/patologia , Antagonistas de Leucotrienos/farmacologia , Antagonistas de Leucotrienos/uso terapêutico , Leucotrienos/farmacologia , Prostaglandina-Endoperóxido Sintases/farmacologiaRESUMO
BACKGROUND AND AIMS: Several different types of non-conventional dysplasia have been recently described in inflammatory bowel disease [IBD]. Hypermucinous, goblet cell-deficient and crypt cell dysplasias have received most attention, but there is limited information regarding their clinicopathological features and clinical outcomes. METHODS: A total of 126 cases of hypermucinous [n = 55], goblet cell-deficient [n = 26] and crypt cell [n = 45] dysplasias from 97 IBD patients were collected from seven different institutions and analysed. RESULTS: The cohort included 62 [64%] men and 35 [36%] women with a mean age of 49 years [range: 20-78]. The majority of affected patients had longstanding IBD [mean duration: 18 years]. Nineteen [20%] patients had a concurrent history of primary sclerosing cholangitis. As a group, non-conventional dysplasia was predominantly found in patients with ulcerative colitis [UC] [n = 68; 70%] and occurred in the left colon [n = 80; 63%]; however, hypermucinous dysplasia [57%] was the least frequently associated with UC compared with goblet cell-deficient [74%] and crypt cell [89%] dysplasias [p = 0.016]. Fifty [52%] patients had a history of conventional dysplasia, detected in the same colonic segment as non-conventional dysplasia at a rate of 33%. Goblet cell-deficient dysplasia [74%] was more frequently associated with conventional dysplasia than hypermucinous [43%] and crypt cell [48%] dysplasias [p = 0.044]. While hypermucinous dysplasia often had a polypoid appearance [58%], crypt cell [96%] and goblet cell-deficient [65%] dysplasias were more likely to present as flat/invisible lesions [p < 0.001]. Most lesions were low-grade [87%] at diagnosis, but goblet cell-deficient dysplasia [31%] more often showed high-grade dysplasia [HGD] compared with hypermucinous [15%] and crypt cell [0%] dysplasias [p = 0.003]. Hypermucinous dysplasia usually demonstrated a tubulovillous/villous architecture [76%], whereas goblet cell-deficient dysplasia was predominantly tubular [92%]. A flat architecture was exclusively associated with crypt cell dysplasia [100%] [p < 0.001]. Immunohistochemical stain results for p53 were available for 33 lesions; 14 [42%] showed strong [3+] and patchy [10-50%] to diffuse [>50%] nuclear overexpression or null staining pattern, including four [33%] of 12 hypermucinous, two [29%] of seven goblet cell-deficient and eight [57%] of 14 crypt cell dysplastic lesions [p = 0.726]. Follow-up biopsies or resections were available for 92 low-grade lesions from 71 patients; 55 [60%] lesions, including 19 [49%] of 39 hypermucinous, 10 [59%] of 17 goblet cell-deficient and 26 [72%] of 36 crypt cell dysplastic lesions [p = 0.116], were associated with subsequent detection of HGD [n = 34; 37%] or adenocarcinoma [n = 21; 23%] at the site of previous biopsy or in the same colonic segment within a mean follow-up time of 12 months [range: <1-73]. CONCLUSIONS: Hypermucinous, goblet cell-deficient and crypt cell dysplasias have distinct clinicopathological features but appear to have a similar high risk of association with advanced neoplasia [HGD or adenocarcinoma]. More than half of the lesions [66%] presented as flat/invisible dysplasia, suggesting that IBD patients may benefit from random biopsy sampling in addition to targeted biopsies. Although not uncommonly associated with conventional dysplasia, non-conventional dysplasia may be the only dysplastic subtype identified in IBD patients. Therefore, it is important to recognize these non-conventional subtypes and recommend complete removal and/or careful examination and follow-up.
Assuntos
Focos de Criptas Aberrantes/patologia , Neoplasias Colorretais/patologia , Células Caliciformes/patologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Adulto , Idoso , Feminino , Humanos , Hiperplasia/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta reflexa Roxb. (C. reflexa) is a well-known traditional herbal plant, with numerous inherent therapeutic potentials including anticancer, antitumor, antibacterial, analgesic, anthelmintic, laxative and others. Moreover, the anticancer and antitumor potentials of this herb are ongoing with several trails, thus an attempt was made to assess the anticancer and hepatoprotective potentials of traditional C. reflexa herbs. METHOD: The dried ethanolic extract of C. reflexa was tested for acute oral toxicity in the treated animals subsequently their behavioral, neurological, and autonomic profiles changes were observed. The preliminary anti-cancer effects of extracts against 1, 2- Dimethyl hydrazine (DMH) induced animals were assessed through barium enema X-ray, colonoscopy, and Aberrant crypt foci (ACF) studies. The blood samples of the animals (treated and untreated) were collected and their in-vitro histological parameters were evaluated by the experienced technician. RESULTS: It was observed that C. reflexa significantly reduced Disease activity indexing (DAI) level and ACF counting, as well as demonstrated similar activity as of the standard drug 5-Fluorouracil (5-FU). Histopathological results revealed that the apoptotic bodies decreased in the DMH-induced group (group II) during cancer progression while in 5-FU treated (group III) and C. reflexa treated (group IV and V) animals the apoptotic bodies were increased. Inversely, the mitotic bodies increased in group II animals and reduced in group III, IV, and V animals. In the colonic section, DMH-induced cancer assay exhibited significant effects on the levels of hemoglobin, Packed cell volume (PCV), Red blood cell (RBC) counts, Mean corpuscular hemoglobin concentration (MCHC), Mean corpuscular volume (MCV), and Mean cell hemoglobin (MCH), and was found to be less in group II animals whereas administration of C. reflexa efficiently recovered back the loss probably by healing the colon damage/depletion of cancer progression. Moreover, compared to the group II animals, the neutrophil count was within the normal range in C. reflexa administered group. CONCLUSIONS: In the present study, the major hematological parameters significantly increased within DMH treated animals and exhibited extensive damage in the hepatic regions. Moreover, the histopathological findings demonstrated that the C. reflexa extracts potentially reduced the cell proliferation, with no toxicity. The C. reflexa extracts exhibited impending anti-cancer activity as well as protected the hepatic cells and thus could be potentially used in the management of colon or colorectal cancer and hepatic impairments.
Assuntos
Focos de Criptas Aberrantes , Neoplasias do Colo , Cuscuta , Testes de Toxicidade/métodos , Focos de Criptas Aberrantes/tratamento farmacológico , Focos de Criptas Aberrantes/patologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Monitoramento de Medicamentos/métodos , Medicamentos de Ervas Chinesas/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Camundongos , Extratos Vegetais/farmacologiaRESUMO
Colorectal cancer (CRC) is the third leading type of adult cancer in both genders with high morbidity and mortality worldwide. Even though the discovery of many antineoplastic drugs for CRC, the current therapy is not adequately efficient.This study was designed to investigate the effect and mechanism of Piclamilast (PIC), a selective PDE4 inhibitor, on a DMH-induced colorectal cancer (CRC) rat model. The rats were grouped (n = 10) into group 1 (control), group 2 (PIC 3 mg/kg, p.o.), groups 3-5 received DMH (20 mg/kg/week, S.C.), and groups 4 and 5 received PIC (1 and 3 mg/kg/day, p.o.) for 15 weeks. The DMH treatment increased aberrant crypt foci (ACF), Proliferating cell nuclear antigen (PCNA), and TBARS levels, along with decreased antioxidant defenses (GSH, GSH-Px, and catalase). Increased NF-κß expression and inflammatory cytokines were also evident. PIC dose-dependently reduced ACF and restored oxidative stress and inflammatory markers favorably. Moreover, PIC in its large, tested dose only significantly increased the intracellular level of cAMP and suppressed the activation of Ras and PI3K and its downstream Akt/mTOR signaling. Furthermore, PIC promoted CRC apoptosis, and increased the gene expression of the apoptotic factors, caspase-3 and Bax, and decreased the anti-apoptotic factor Bcl-2. The results of this study show that PIC may be a promising therapeutic agent for the treatment of CRC. PIC might inhibit the proliferation of CRC cells and induce apoptosis via multiple mechanisms that involve its antioxidant effect and inhibition of NF-κß and Ras/PI3K/Akt/mTOR signaling.
Assuntos
1,2-Dimetilidrazina/antagonistas & inibidores , 1,2-Dimetilidrazina/toxicidade , Benzamidas/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Piridinas/farmacologia , Focos de Criptas Aberrantes/tratamento farmacológico , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/induzido quimicamente , Modelos Animais de Doenças , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteínas ras/metabolismoRESUMO
BACKGROUND: Colorectal cancer is a highly prevalent disease, requiring effective strategies for prevention and treatment. The present research aimed to formulate a natural fiber-rich food product (NFRFP) and to evaluate its safety, toxicogenetics, and effects on aberrant crypt foci induced by 1,2-dimethyl-hydrazine in a preclinical model. METHODS: A total of 78 male Wistar rats were distributed in six experimental groups: negative control, positive control (1,2-Dimethylhydrazine-40 mg/Kg), and four groups fed with 10% NFRFP: NFRFP, pre-treatment protocol, simultaneous treatment, and post-treatment protocol. RESULTS: The NFRFP was shown to be a good source of fibers and did not change biometric, biochemical, hematological, and inflammatory parameters, and did not induce signs of toxicity and genotoxicity/carcinogenicity. NFRFP exhibited a chemopreventive effect, in all protocols, with damage reduction (% DR) of 75% in the comet test. NFRFP reduced the incidence of aberrant crypt outbreaks by 49.36% in the post-treatment protocol. CONCLUSIONS: The results suggest the applicability of NFRFP in the human diet due to potential production at an industrial scale and easy technological application in different products, since it could be incorporated in food without altering or causing small changes in final product sensory characteristics.
Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Colo/patologia , Neoplasias Colorretais/prevenção & controle , Fibras na Dieta/administração & dosagem , 1,2-Dimetilidrazina , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patologia , Ração Animal , Animais , Colo/metabolismo , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Citocinas/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Masculino , Ratos WistarRESUMO
Polyphenon E (Poly E) is a green tea polyphenol preparation whose most active component is epigallocatechin gallate (EGCG). We studied the cancer preventive efficacy and safety of Poly E in subjects with rectal aberrant crypt foci (ACF), which represent putative precursors of colorectal cancers. Eligible subjects had prior colorectal advanced adenomas or cancers, and had ≥5 rectal ACF at a preregistration chromoendoscopy. Subjects (N = 39) were randomized to 6 months of oral Poly E (780 mg EGCG) daily or placebo. Baseline characteristics were similar by treatment arm (all P >0.41); 32 of 39 (82%) subjects completed 6 months of treatment. The primary endpoint was percent reduction in rectal ACF at chromoendoscopy comparing before and after treatment. Among 32 subjects (15 Poly E, 17 placebo), percent change in rectal ACF number (baseline vs. 6 months) did not differ significantly between study arms (3.7% difference of means; P = 0.28); total ACF burden was also similar (-2.3% difference of means; P = 0.83). Adenoma recurrence rates at 6 months were similar by arm (P > 0.35). Total drug received did not differ significantly by study arm; 31 (79%) subjects received ≥70% of prescribed Poly E. Poly E was well tolerated and adverse events (AE) did not differ significantly by arm. One subject on placebo had two grade 3 AEs; one subject had grade 2 hepatic transaminase elevations attributed to treatment. In conclusion, Poly E for 6 months did not significantly reduce rectal ACF number relative to placebo. Poly E was well tolerated and without significant toxicity at the dose studied. PREVENTION RELEVANCE: We report a chemoprevention trial of polyphenon E in subjects at high risk of colorectal cancer. The results show that polyphenon E was well tolerated, but did not significantly reduce the number of rectal aberrant crypt foci, a surrogate endpoint biomarker of colorectal cancer.
Assuntos
Focos de Criptas Aberrantes/tratamento farmacológico , Catequina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Focos de Criptas Aberrantes/diagnóstico , Focos de Criptas Aberrantes/patologia , Idoso , Catequina/administração & dosagem , Catequina/efeitos adversos , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Placebos/administração & dosagem , Placebos/efeitos adversos , Reto/diagnóstico por imagem , Reto/efeitos dos fármacos , Reto/patologia , Resultado do TratamentoRESUMO
BACKGROUND: The incidence and mortality rates of colorectal cancer (CRC) continue to increase worldwide. Therefore, new preventive strategies are needed to lower the burden of this disease. Previous studies reported that aspirin could suppress the development of sporadic colorectal adenoma. In addition, metformin is a biguanide derivative that is long widely used for the treatment of diabetes mellitus and has recently been suggested to have a suppressive effect on carcinogenesis and cancer cell growth. Both drugs exhibit a chemopreventive effect, but their efficacy is limited. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are more prevalent in patients with cancer and adenomas, and considered a reliable surrogate biomarker of CRC. Thus, we designed a prospective trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of aspirin combined with metformin on colorectal ACF formation in patients scheduled for polypectomy. METHODS: This study is a double-blind randomized controlled trial that will be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients will be recruited for the study and the number of ACF in the rectum will be counted at the baseline colonoscopy. Then, the participants will be allocated to one of the following two groups; the aspirin plus placebo group or the aspirin plus metformin group. Patients in the aspirin plus placebo group will receive oral aspirin (100 mg) and placebo for 8 weeks, and those in the aspirin plus metformin group will receive oral aspirin (100 mg) and metformin (250 mg) for 8 weeks. After 8 weeks of administration, polypectomy will be performed to evaluate changes in the number of ACF, and the cell-proliferative activity in the normal colorectal mucosa and colorectal polyps. DISCUSSION: This is the first study proposed that will explore the effect of aspirin combined with metformin on the formation of colorectal ACF in humans. TRIAL REGISTRATION: This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000028259 . Registered 17 July 2017.
Assuntos
Focos de Criptas Aberrantes/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Focos de Criptas Aberrantes/patologia , Neoplasias Colorretais/patologia , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Prognóstico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Leukotriene receptor antagonists (LTRAs) are broadly used for the management of allergic asthma and have recently been indicated to inhibit carcinogenesis and cancer cell growth. In colorectal cancer (CRC) chemoprevention studies, the occurrence of adenoma or CRC itself is generally set as the trial endpoint. Although the occurrence rate of CRC is the most confident endpoint, it is inappropriate for chemoprevention studies because CRC incidence rate is low in the general population and needed for long-term monitoring. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and darker in methylene blue staining than normal crypts, are regarded to be a fine surrogate biomarker of CRC. Therefore, this prospective study was designed to explore the chemopreventive effect of LTRA on colonic ACF formation and the safety of the medicine in patients scheduled for a poly resection as a pilot trial leading the CRC chemoprevention trial. METHODS: This study is a nonrandomized, open-label, controlled trial in patients with colorectal ACF and polyps scheduled for a polypectomy. Participants meet the inclusion criteria will be recruited, and the number of ACF in the rectum will be counted at the baseline colonoscopic examination. Next, the participants will be assigned to the LTRA or no treatment group. Participants in the LTRA group will continue 10 mg of oral montelukast for 8 weeks, and those in the no treatment group will be observed without the administration of any additional drugs. At the end of the 8-week LTRA intervention period, a polypectomy will be conducted to evaluate the changes in the number of ACF, and cell proliferation in the normal colorectal epithelium will be analyzed. DISCUSSION: This will be the first study to investigate the effect of LTRAs on colorectal ACF formation in humans. TRIAL REGISTRATION: This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000029926 . Registered 10 November 2017.
Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Acetatos/administração & dosagem , Pólipos do Colo/terapia , Ciclopropanos/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , Antagonistas de Leucotrienos/administração & dosagem , Quinolinas/administração & dosagem , Sulfetos/administração & dosagem , Focos de Criptas Aberrantes/diagnóstico , Focos de Criptas Aberrantes/patologia , Focos de Criptas Aberrantes/cirurgia , Acetatos/efeitos adversos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Proliferação de Células/efeitos dos fármacos , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Colo/cirurgia , Pólipos do Colo/patologia , Colonoscopia , Ensaios Clínicos Controlados como Assunto , Ciclopropanos/efeitos adversos , Feminino , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Antagonistas de Leucotrienos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Quinolinas/efeitos adversos , Reto/diagnóstico por imagem , Reto/efeitos dos fármacos , Reto/patologia , Reto/cirurgia , Sulfetos/efeitos adversos , Resultado do TratamentoRESUMO
Glucosylceramide (GlcCer), a major sphingolipid in plants and fungi, is known to have food functions, such as preventing intestinal impairment and enhancing the moisture content of skin. This study investigated the influence of fermentation on the composition and function of lipophilic components containing GlcCer in plant-based foods; we compared the effects of ethanol extracts from sake rice (SR) and sake lees (SL) on colon impairment in mice. GlcCer and ceramide (Cer) levels in SL were much higher than those in SR, and GlcCer in SL contained 9-methyl-trans-4,trans-8-sphingadienine as a fungi-specific sphingoid base. 1,2-dimethylhydrazine (DMH) treatment markedly increased the formation of aberrant crypt foci (ACF) and the levels of TNF-α and lipid oxidation in mice colons. However, dietary SR or SL significantly suppressed these DMH-induced changes, and SR demonstrated stronger effects than SL. In addition, dietary SR or SL suppressed the expression of apoptotic and anti-apoptotic proteins induced by DMH treatment. This study suggests that SR or SL intake could reduce colon ACF formation via the suppression of inflammation and oxidation-induced cell cycle disturbances. When compared to SR, the weaked effects of SL rich in GlcCer may be the result of the changes in sphingolipid composition (sphingoid base and Cer) and differences in the concentration of other bioactive compounds produced or digested during fermentation.
Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Neoplasias do Colo/prevenção & controle , Glucosilceramidas/análise , Glucosilceramidas/farmacologia , Oryza/química , Fitoterapia , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Vinho/análise , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patologia , Administração Oral , Animais , Apoptose , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Etanol , Feminino , Fermentação , Glucosilceramidas/administração & dosagem , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION: Aberrant Crypt (AC) and Aberrant Crypt Focus (ACF) are considered pre-neoplasic lesions, ranging from hyperplasia to different degrees of dysplasia in the colon. This work aimed to evaluate and quantify the chemopreventive activity of Zingiber officinale essential oil in the colorectal region of Wistar rats. MATERIALS AND METHODS: We extracted the essential oil from ginger rhizomes and carried out ACF induction, in rats, with 1.2 Dimethylhydrazine (DMH) at a 20 mg/kg dose. The experimental groups were GI (negative control); GII (positive induction control); GIII (DMH + essential oil); GIV (DMH +5-Florouracil) and GV (essential oil). The histological techniques used were methylene blue, hematoxylin-eosin (HE) dyeing, and immunohistochemistry (IHQ). RESULTS: The major essential oil compounds were citral (17.25%), δ-citral (10.25%), camphene (9.55%), α-zingiberene (7.57%), nerol (6.37%) and plelandrene (6.83%). For the presence of AC or ACF, we did not observe them in GI and GV, while in GII and GIII, they were observed, in high values, in both regions, but only in the distal region, there was a significant difference between them. For GIV, for both regions, there were significant lower numbers of AC when compared to GIII. As observed, with HE, there were hyperplastic and dysplastic ACF in the proximal and distal portions of the colon. For IHQ analyses, there were positively PCNA antibody marked cells in all experimental groups. Yet, there was no significant correlation of mitotic index among them. Moreover, the results of GIII compared to GIV were very similar. CONCLUSION: In this sense, the Zingiber officinale essential oil has good antioxidant potential because it presents a mixture of monoterpene and sesquiterpene compounds. Thus, it is able to develop a chemoprotective effect, as it presented similar results to the standard drug, showing cell proliferation control.
Assuntos
1,2-Dimetilidrazina/toxicidade , Focos de Criptas Aberrantes/tratamento farmacológico , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Óleos Voláteis/farmacologia , Zingiber officinale/química , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/patologia , Animais , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Masculino , Ratos , Ratos WistarRESUMO
To explore fresh strategies in colorectal cancer (CRC) chemotherapy, we evaluated the capability of the ruthenium-phloretin complex in exterminating colon cancer by effectively addressing multiple apoptotic mechanisms on HT-29 cancer cells together with an animal model of colorectal cancer activated by 1,2-dimethylhydrazine and dextran sulfate sodium. Our current approach offers tangible evidence of the application of the ruthenium-phloretin complex in future chemotherapy. The complex triggers intrinsic apoptosis triggered by p53 and modulates the Akt/mTOR pathway along with other inflammatory biomarkers. The ruthenium-phloretin complex has been synthesized and successfully characterized by numerous spectroscopic methodologies accompanied by DPPH, FRAP, and ABTS assays assessing its antioxidant potential. Studies conducted in human cell lines revealed that the complex improved levels of p53 and caspase-3 while diminishing the activities of VEGF and mTOR, triggers apoptosis, and induces fragmentation of DNA in the HT-29 cells. Toxicity studies were conducted to identify the therapeutic doses of the novel complex in animal models. The outcomes of the in vivo report suggest that the complex was beneficial in repressing multiplicity of aberrant crypt foci as well as hyperplastic lesions and also promoted increased levels of CAT, SOD, and glutathione. In addition, the ruthenium-phloretin complex was able to control cell proliferation and boosted apoptotic outbursts in cancer cells associated with the increase in cellular response towards Bax while diminishing responses towards Bcl-2, NF-κB, and MMP-9. Our observations from the experiments deliver testament that the ruthenium-phloretin complex has the potential to act as a promising chemotherapeutic agent in colorectal cancer because it can affect the growth of ACF and hyperplastic abrasions in the colon tissues by evoking cell death.
Assuntos
Apoptose , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Floretina/uso terapêutico , Rutênio/uso terapêutico , Focos de Criptas Aberrantes/patologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Benzotiazóis/química , Compostos de Bifenilo/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias do Colo/sangue , DNA/metabolismo , Feminino , Sequestradores de Radicais Livres/farmacologia , Células HT29 , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Oxirredução , Floretina/química , Floretina/farmacologia , Picratos/química , Rutênio/química , Rutênio/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Sulfônicos/química , Testes de Toxicidade , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC. AIM: To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis. METHODS: DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG. RESULTS: At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively. CONCLUSION: EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.
Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Anticarcinógenos/farmacologia , Catequina/análogos & derivados , Neoplasias Colorretais/prevenção & controle , Neoplasias Experimentais/prevenção & controle , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/genética , Focos de Criptas Aberrantes/patologia , Animais , Anticarcinógenos/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Catequina/farmacologia , Catequina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Dimetilidrazinas/toxicidade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , Ratos , Reto/efeitos dos fármacos , Reto/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
BACKGROUND AND PURPOSE: This study subjected a rat model to the extracts of muscle and shell tissues from Portunus segnis to assess their therapeutic effects on the HT-29 colon cancer cells as well as on colonic Aberrant Crypt Foci (ACF) induced by Azoxymethane (AOM). METHODS: The cell line was exposed to the extracts to compare the cytotoxicity of hexane, butanol, ethyl acetate, and water extract of muscle and ethanolic extract of the shell. Male rats (n=40) were assigned into control, positive, negative, and treatment groups. The animals were injected with AOM, except the control group, and then exposed to 250 and 500mg/kg of the crude extracts. Immunohistochemical localization of Bax and Bcl-2, as well as ACF and antioxidant enzymes, were evaluated in the rat colon. RESULTS: The butanolic muscle extract and ethanolic shell one demonstrated an IC50 of 9.02±0.19µg/ml and 20.23±0.27µg/ml towards the cell line, respectively. Dietary exposure inhibited the ACF formation and crypt multiplicity in the colon compared to the cancer control group. The activity of SOD and CAT increased, while that of MDA decreased. The expression of Bax and Bcl-2 increased and decreased, respectively. CONCLUSION: Taken together, the results show that both extractions were suggested to be suppressive to AOMinduced colon cancer.
Assuntos
Focos de Criptas Aberrantes/tratamento farmacológico , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Braquiúros/química , Neoplasias Colorretais/tratamento farmacológico , Músculos/química , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/patologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Azoximetano/administração & dosagem , Compostos de Bifenilo/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Injeções Intradérmicas , Masculino , Estrutura Molecular , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Picratos/antagonistas & inibidores , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
The discovery of aberrant crypt foci (ACF) more than three decades ago not only enhanced our understanding of how colorectal tumors form, but provided new opportunities to detect lesions prior to adenoma development and intervene in the colorectal carcinogenesis process even earlier. Because not all ACF progress to neoplasia, it is important to stratify these lesions based on the presence of dysplasia and establish early detection methods and interventions that specifically target dysplastic ACF (microadenomas). Significant progress has been made in characterizing the morphology and genetics of dysplastic ACF in both preclinical models and humans. Image-based methods have been established and new techniques that utilize bioactivatable probes and capture histologic abnormalities in vivo are emerging for lesion detection. Successful identification of agents that target dysplastic ACF holds great promise for intervening even earlier in the carcinogenesis process to maximize tumor inhibition. Future preclinical and clinical prevention studies should give significant attention to assessing the utility of dysplastic ACF as the earliest identifiable biomarker of colorectal neoplasia and response to therapy.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.
Assuntos
Focos de Criptas Aberrantes/terapia , Adenoma/prevenção & controle , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Suplementos Nutricionais , Focos de Criptas Aberrantes/diagnóstico , Focos de Criptas Aberrantes/genética , Focos de Criptas Aberrantes/patologia , Adenoma/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Animais , Antineoplásicos/farmacologia , Aspirina/farmacologia , Aspirina/uso terapêutico , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Carcinogênese/efeitos dos fármacos , Catequina/administração & dosagem , Catequina/análogos & derivados , Ensaios Clínicos como Assunto , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Licopeno/administração & dosagem , Camundongos , Mutação , Resultado do TratamentoRESUMO
BACKGROUND: The importance of ACF is not fully explained, however, their number may be a good predictor of synchronous and metachronic adenoma or other polyps whose removal reduces the risk of CRC. Due to the epidemiological and genetic association of ACF with pre-cancer lesions, they may be a potential CRC biomarker. The aim of our study was to show that the number and type of rectal ACF may be a good predictive factor for the presence of polyps located proximally from the splenic flexure and that the type and number of ACF can correlate with the number and specific types of polyps in the large intestine. METHODS: The study included 131 patients who underwent colonoscopy combined with rectal mucosa staining with 0.25% methylene blue. The number of rectal ACF was determined and bioptats were sampled for histopathological examination to assess the type of ACF. Endoscopic ACF assessment criteria given by L. Roncucci were used. The obtained material was subjected to statistical analysis using probability distribution, U-test, t-student test, and chi 2 as well as the Statistica 7.1 software package. RESULTS: The study population was divided into three subgroups according to the number of ACF observed, i.e. ACF < 5, 5-10 and > 10. ACF < 5 were found in 35 patients (29.41%), 5-10 ACF in 70 (58.82%) and ACF > 10 in 14 individuals (11.76%). The study revealed the presence of normal ACF (p = 0.49), hyperplastic ACF (p = 0.34), dysplastic ACF (p = 0.11), and mixed ACF (p = 0.06). A single type of ACF was most commonly observed (n = 88, p = 0.74). In the researched group a larger number of ACF is concurrent with adenomas and hyperplastic polyps. The number of ACF clearly correlates with the dysplasia advancement in the adenoma and the number of polyps found. CONCLUSIONS: Rectal ACF are a useful marker for the presence of cancerous lesions in the proximal and distal sections of the large intestine.