ABSTRACT
BACKGROUND: Current data indicate that supplements such as folic acid and vitamin B may be beneficial in halting and even reversing atrophic gastritis, intestinal metaplasia and intraepithelial neoplasia, generally referred to as gastric precancerous conditions(GPC). However, there is no Meta-analysis article to evaluate the prevention and treatment of folic acid in the gastric precancerous conditions. We therefore conducted a meta-analysis to confirm the efficacy of folic acid in treating GPC. METHODS: Using a systematic review method, consider randomized controlled trials (RCT), including clinical trial reports, unpublished clinical trial data, and conference papers. The search time was been set from the database's establishment to June 2, 2021. The language was not limited, using PubMed, SinoMed, Lancet, Web of Science, CNKI, Cochrane, Ovid, Science Direct, Embase, and EBSCO databases. Data were extracted using a pre-designed extraction tool and analysis was undertaken using RevMan5.2.Besides,we use Origin software to construct the Time-dose interval analysis. RESULTS: Of the 225 records identified, 13 studies involving 1252 patients (including 11 clinical controlled trials, 1 conference paper report and 1 unpublished research report) met the inclusion conditions. Folic acid dose maintained at 20-30 mg / d for 3-6 months may be beneficial to pathological changes of GPC. Moreover, in the 3 month treatment of 5 trials, the effect was more obvious when the folic acid dose was maintained at 30 mg / d. In the 7 trials, the symptom ineffective rate of GPC treated with folic acid was 32% (RR:0.32, 95% confidence interval CI:0.21-0.48), which was combined using a fixed analysis model; The effect of folic acid on gastric mucosal atrophy in 5 trials (RR: 1.61, 95%CI 1.07-2.41). The changes of folic acid on intestinal metaplasia in the 2 experiments (RR: 1.77, 95% CI: 1.32-2.37).The 2 results are combined using a fixed analytical model. However, the subgroup analysis of 9 trials revealed no significant effectiveness of symptom. CONCLUSIONS: Our research showed that folic acid supplementation brings benefits in preventing and even reversing the progression of GPC in the stomach, and provided evidence for its potential clinical use in management of GPC. REGISTRATION: The logn number of our Meta-anlysis on PROSPERO is CRD420223062.
Subject(s)
Folic Acid , Precancerous Conditions , Dietary Supplements , Folic Acid/therapeutic use , Humans , Metaplasia , Precancerous Conditions/drug therapy , Precancerous Conditions/pathology , Precancerous Conditions/prevention & control , Randomized Controlled Trials as Topic , Stomach/pathologyABSTRACT
Retinoic acid (RA) is the most biologically active metabolite of vitamin A and is important for stomach physiological function. However, little is known about the metabolic status of RA in human gastric lesions. From 2015 to 2018, 1,392 local residents in Lujiang County were recruited into a cross-sectional survey program, which included a questionnaire interview and blood collection. We detected the mRNA and protein expression of RA metabolism-relevant factors in gastric tissues from 68 local patients with gastric lesions. The effects of all-trans retinoic acid (ATRA) supplementation were investigated in a gastric precancerous lesions (GPLs) rat model. In the cross-sectional survey, no significant differences in the level of RA precursor (P > 0.05) between the H. pylori seronegative and seropositive residents were observed. However, the mRNA and protein expression of RA synthesizing enzymes (RDH10 and ALDH1A1) were significantly decreased and catabolic enzyme (CYP26B1) was significantly increased in the patients (P < 0.05). Consistently, in the GPL rat model, we observed a similar disorder; however, ATRA supplementation significantly not only corrected the disorder by increasing Rdh10, Aldh1a1 and decreasing Cyp26b1, but also reduced claudin-18 (P < 0.05). Our study suggested that RA metabolism is disrupted in individuals with gastric lesions, while ATRA supplementation can prevent GPL from progressing to gastric cancer.
Subject(s)
Precancerous Conditions , Tretinoin , Animals , Cross-Sectional Studies , Humans , Precancerous Conditions/prevention & control , RNA, Messenger/genetics , Rats , Retinoic Acid 4-Hydroxylase , Stomach , Tretinoin/pharmacologyABSTRACT
BACKGROUND & AIMS: Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50. METHODS: We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratios (ORs) and 95% CIs for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model. RESULTS: We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend = .01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n = 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n = 1,878). CONCLUSIONS: In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.
Subject(s)
Adenoma/prevention & control , Colonic Polyps/prevention & control , Colorectal Neoplasms/prevention & control , Precancerous Conditions/prevention & control , Vitamin D/administration & dosage , Vitamins/administration & dosage , Adenoma/diagnosis , Adenoma/epidemiology , Adult , Age of Onset , Colonic Polyps/diagnosis , Colonic Polyps/epidemiology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Female , Humans , Incidence , Middle Aged , Nurses , Precancerous Conditions/diagnosis , Precancerous Conditions/epidemiology , Prospective Studies , Protective Factors , Risk Assessment , Risk Factors , Sex Factors , Time Factors , United States/epidemiologyABSTRACT
CONTEXT: Observational studies suggest that low vitamin D status may be a risk factor for cancer. OBJECTIVE: In a population with prediabetes and overweight/obesity that is at higher risk of cancer than the general population, we sought to determine if vitamin D supplementation lowers the risk of cancer and precancers. METHODS: The Vitamin D and type 2 diabetes (D2d) cancer outcomes study (D2dCA) is an ancillary study to the D2d study, which was conducted at 22 academic medical centers in the United States. Participants had prediabetes and overweight/obesity and were free of cancer for the previous 5 years. Participants were randomized to receive vitamin D3 4000 IU daily or placebo. At scheduled study visits (4 times/year), cancer and precancer events were identified by questionnaires. Clinical data were collected and adjudicated for all reported events. Cox proportional hazard models compared the hazard ratio (HR) of incident cancers and precancers between groups. RESULTS: Over a median follow-up period of 2.9 years, among 2385 participants (mean age 60 years and 25-hydroxyvitamin D 28 ng/mL), there were 89 cases of cancer. The HR of incident cancer for vitamin D vs placebo was 1.07 (95% CI 0.70, 1.62). Of 241 participants with incident precancers, 239 had colorectal adenomatous polyps. The HR for colorectal polyps for vitamin D vs placebo was 0.83 (95% CI 0.64, 1.07). CONCLUSION: In the D2d population of participants with prediabetes and overweight/obesity, not selected for vitamin D insufficiency, vitamin D supplementation did not have a significant effect on risk of incident cancer or colorectal polyps.
Subject(s)
Neoplasms/prevention & control , Obesity/complications , Overweight/complications , Prediabetic State/complications , Vitamin D/administration & dosage , Aged , Dietary Supplements , Female , Humans , Male , Middle Aged , Precancerous Conditions/prevention & control , Proportional Hazards ModelsABSTRACT
Nonalcoholic steatohepatitis (NASH) is considered growing risk factor for hepatocellular carcinoma development in high-income countries. Diet- and chemically induced rodent models have been applied for the translational study of NASH-associated hepatocarcinogenesis due to their morphological and molecular similarities to the corresponding human disease. Arctium lappa L. (burdock) root tea has been extensively consumed in Traditional Chinese Medicine due to its potential therapeutic properties. Indeed, the bioactive compounds of A. lappa root, as the polyphenols, have already showed antioxidant and anti-inflammatory properties in different in vivo and in vitro bioassays. In this study, we investigated whether burdock root ethanolic extract (BRE) administration attenuates NASH-associated hepatocarcinogenesis. Eight-week-old male Wistar rats received choline-deficient high-fat diet for 8 weeks and multiple thioacetamide doses for 4 weeks in order to induce NASH and preneoplastic glutathione-S-transferase pi (GST-P)+ preneoplastic foci. Subsequently, rats were treated with BRE (100 or 200 mg/kg body weight) or vehicle by oral gavage for 2 weeks. BRE displayed high levels of chlorogenic and caffeic acids and BRE administration reduced total fatty acid and lipid hydroperoxide levels, while increasing the activities of antioxidant superoxide dismutase and catalase enzymes in the liver. Furthermore, burdock intervention diminished the size of GST-P+ remodeling preneoplastic lesions (PNLs) and displayed a trend on reducing hepatocyte proliferation (Ki-67) inside them. These findings suggest that short-term exposure to BRE alleviated remodeling PNL development in NASH-associated hepatocarcinogenesis.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Arctium/chemistry , Liver Neoplasms/prevention & control , Non-alcoholic Fatty Liver Disease/drug therapy , Plant Extracts/therapeutic use , Precancerous Conditions/prevention & control , Animals , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Antioxidants/metabolism , Caffeic Acids , Diet, High-Fat/adverse effects , Humans , Liver Neoplasms/pathology , Male , Medicine, Chinese Traditional , Non-alcoholic Fatty Liver Disease/pathology , Plant Extracts/isolation & purification , Plant Roots/chemistry , Precancerous Conditions/pathology , Rats , Rats, Wistar , Thioacetamide/toxicityABSTRACT
Gastric cancer is recognized as one of the most common cancer. In-depth research of gastric precancerous lesions (GPL) plays an important role in preventing the occurrence of gastric cancer. Meanwhile, traditional treatment provides a novel sight in the prevention of occurrence and development of gastric cancer. The current study was designed to assess the effects of therapy with Weipixiao (WPX) decoction on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL rats and the underlying molecular mechanisms. After 10-weeks treatment, all rats were sacrificed. Histopathological changes of gastric tissue were assessed via hematoxylin-eosin (HE) and High-iron diamine-Alcian blue-Periodic acid-Schiff (HID-AB-PAS) staining. To be fully evidenced, RT-qPCR, Western blot and immunohistochemistry were used to detect the expressions of LDHA, CD147, HIF-1α, MCT4, PI3K, AKT, mTOR and miRNA-34a, which were crucial factors for evaluating GPL in the aspect of glycolysis pathogenesis. According to the results of HE and HID-AB-PAS staining, it could be confirmed that MNNG-induced GPL rats were obviously reversed by WPX decoction. Additionally, the increased gene levels of LDHA, CD147, MCT4, PI3K, AKT, mTOR and HIF-1α in model group were down-regulated by WPX decoction, while miRNA-34a expression was decreased and up-regulated by WPX decoction. The significantly increased protein levels of LDHA, CD147, MCT4, PI3K, AKT, mTOR and HIF-1α induced by MNNG were attenuated in rats treated with WPX decoction. In brief, the findings of this study imply that abnormal glycolysis in MNNG-induced GPL rats was relieved by WPX decoction via regulation of the expressions of LDHA, CD147, HIF-1α, MCT4, PI3K, AKT, mTOR and miRNA-34a.
Subject(s)
Anticarcinogenic Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Glycolysis/drug effects , Methylnitronitrosoguanidine , Precancerous Conditions/prevention & control , Stomach Neoplasms/prevention & control , Stomach/drug effects , Animals , Cytoprotection , Disease Models, Animal , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Male , Precancerous Conditions/chemically induced , Precancerous Conditions/enzymology , Precancerous Conditions/pathology , Rats, Sprague-Dawley , Signal Transduction , Stomach/enzymology , Stomach/pathology , Stomach Neoplasms/chemically induced , Stomach Neoplasms/enzymology , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy. METHODS/DESIGN: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy. TRIAL REGISTRATION: NCT03616444.
Subject(s)
Adenomatous Polyps/prevention & control , Colorectal Neoplasms/prevention & control , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Precancerous Conditions/prevention & control , Double-Blind Method , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as TopicABSTRACT
Dendrobium officinale is a herb in traditional Chinese medicine where D. officinale polysaccharides (DOP) are the main active ingredient. This study aimed at evaluating DOP efficiency at inhibiting 1-Methyl-2-nitro-1-nitrosoguanidine (MNNG) induced precancerous lesions of gastric cancer (PLGC) in rats through the Wnt/b-catenin pathway and analyzing the variations of serum endogenous metabolites. PLGC was established in male Sprague-Dawley (SD) rats by administering 150 µg/mL MNNG in drinking water for 7 months and giving 0.1 mL of 10% NaCl once weekly during the initial 20 weeks. Treatment with DOP inhibited the progress of PLGC through decreasing the expression of ß-catenin by immunohistochemical analysis. The futher study indicated DOP downregulated gene expression of Wnt2ß, Gsk3ß, PCNA, CyclinD1, and ß-catenin, as well as protein expression of Wnt2ß, PCNA, and ß-catenin. On the other hand, there were nine endogenous metabolites identified after the DOP treatment. Among these, the most significant one is betaine because of its strong antioxidant activity, leading to an anti-tumor effect. DOP can inhibit MNNG-induced PLGC models via regulating Wnt/ß-catenin pathway and by changing endogenous metabolites.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Dendrobium/chemistry , Gene Expression Regulation, Neoplastic , Polysaccharides/pharmacology , Precancerous Conditions/prevention & control , Stomach Neoplasms/prevention & control , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Betaine/blood , Cyclin D1/genetics , Cyclin D1/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Male , Metabolome/genetics , Methylnitronitrosoguanidine/toxicity , Plant Extracts/chemistry , Polysaccharides/isolation & purification , Precancerous Conditions/chemically induced , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Proliferating Cell Nuclear Antigen/genetics , Proliferating Cell Nuclear Antigen/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Stomach Neoplasms/chemically induced , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Wnt Proteins/genetics , Wnt Proteins/metabolism , beta Catenin/genetics , beta Catenin/metabolismABSTRACT
Maslinic acid triggers compelling antiproliferative and pro-apoptotic effects in different human cancer cell lines. Hence, the chemopreventive activity was investigated on early stages of carcinogenesis induced by 1,2-dimethylhydrazine (DMH) which is a model that mimics human sporadic colorectal cancer. Male Sprague-Dawley rats were orally administered either maslinic acid at 5, 10 or 25 mg/kg dissolved in (2-hydroxypropyl)-ß-cyclodextrin 20% (w/v) or the solvent for 49 days. After one week of treatment, animals received three weekly intraperitoneal injections of DMH at the dose of 20 mg/kg. Maslinic acid reduced the preneoplastic biomarkers, aberrant crypt foci (ACF) and mucin-depleted foci (MDF), already at 5 mg/kg in a 15% and 27%, respectively. The decline was significant at 25 mg/kg with decreases of 33% and 51%, respectively. Correlation analysis showed a significant association between the concentrations of maslinic acid found in the colon and the reduction of ACF (r = 0.999, P = 0.019) and MDF (r = 0.997, P = 0.049). The present findings demonstrate that maslinic acid induced an inhibition of the initiation stages of carcinogenesis. The assessment of this pentacyclic triterpene at the colon sheds light for designing diets with foods rich in maslinic acid to exert a chemopreventive activity in colorectal cancer.
Subject(s)
1,2-Dimethylhydrazine/toxicity , Aberrant Crypt Foci/prevention & control , Colonic Neoplasms/prevention & control , Olea/chemistry , Plant Extracts/pharmacology , Precancerous Conditions/prevention & control , Triterpenes/pharmacology , Aberrant Crypt Foci/chemically induced , Aberrant Crypt Foci/pathology , Animals , Carcinogens/toxicity , Colonic Neoplasms/chemically induced , Colonic Neoplasms/pathology , Male , Precancerous Conditions/chemically induced , Precancerous Conditions/pathology , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Cancer is the second leading cause of death worldwide next to cardiovascular diseases. Despite the advancement in screening, early diagnosis, and development in treatment technology in last several decades, cancer incidence overall, particularly that of gastrointestinal (GI) cancers, is far from being controlled, and is expected to increase worldwide. SUMMARY: Although numerous preclinical and population-based clinical studies have already made important progress in restraining the overall cancer incidence and mortality, the full potential of preventive strategy is still far from being realized, and remains at an early stage. There are several major challenges regarding this issue, and one of the crucial challenges is to maintain the balance between risks and benefits. As a result of past investments, primary prevention nowadays include the integration of various activities such as lifestyle changes to reduce risk, screening to detect early lesions, vaccines and preventive therapies aimed to actively interrupt the carcinogenic pathway. Long-term aspirin use seems to have the largest potential effect on the general population on cancer incidence and mortality overall, especially GI cancers. Helicobacter pylori eradication reduces the risk for gastric cancer and is advocated regardless of the symptoms and stage of disease. Metformin and statins are promising in cancer prevention in patients with type 2 diabetes. Vitamin D supplementation is promising in the prevention of colorectal adenoma recurrence. Key Message: However, additional studies are warranted to establish the potential of various agents and to identify more specific and highly targeted new agents for chemoprevention in digestive oncology.
Subject(s)
Neoplasms/prevention & control , Primary Prevention , Chemoprevention , Diet , Humans , Life Style , Precancerous Conditions/prevention & control , Risk Reduction BehaviorABSTRACT
Diets high in fruits and vegetables may help prevent colorectal cancer (CRC). Watermelon consumption may reduce CRC risk due to its concentration of l-citrulline and its role in endothelial nitric oxide (NO) production. Research suggests that increased NO levels have tumoricidal effects. The purpose of this study was to determine the effects of watermelon powder supplementation on aberrant crypt foci (ACF) formation, precancerous lesions, and expression of genes associated with colon carcinogenesis. Thirty-two male Sprague-Dawley rats were assigned into three groups: control, 0.36% l-arginine, or 0.5% watermelon powder and injected with azoxymethane (15 mg/kg body weight). Both l-arginine and watermelon powder groups exhibited lower total numbers of ACF and high multiplicity ACF (P < 0.01). The watermelon powder group exhibited higher NO levels and lower 8-hydroxyguanosine DNA damage (P < 0.05). Watermelon powder and l-arginine downregulated 8-oxoguanine DNA glycosylase gene expression and upregulated O6-methylguanine DNA methyltransferase gene expression (P < 0.05). Cyclooxgenase-2 gene expression was lower for rats fed with watermelon powder (P < 0.05). These results suggest that watermelon powder or l-arginine supplementation may reduce the risk of colon cancer by suppressing ACF formation through lowering oxidative DNA damage and inflammation, modulating DNA repair enzyme expression, and/or enhancing NO production.
Subject(s)
Arginine/administration & dosage , Citrullus , Colonic Neoplasms/prevention & control , 8-Hydroxy-2'-Deoxyguanosine , Aberrant Crypt Foci/prevention & control , Animals , Azoxymethane , Cyclooxygenase 2/genetics , DNA Damage , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Dietary Supplements , Male , Nitric Oxide/biosynthesis , Powders , Precancerous Conditions/prevention & control , Rats , Rats, Sprague-DawleyABSTRACT
p-Hydroxylcinnamaldehyde isolated from the Cochinchina momordica seed (CMSP) has been identified to inhibit growth and metastasis in oesophageal squamous cell carcinoma (ESCC) by inducing differentiation. The aim of the present study was to evaluate the effect and underlying mechanism of CMSP on 4-nitroquinoline 1-oxide (4NQO)-induced oesophageal tumourigenesis. In the present study, a mouse model of oesophageal preneoplastic lesions was established by providing 4NQO-containing drinking water to C57BL/6 mice. The effect of CMSP on tumourigenesis induced by the chemical mutagen and the effect of CMSP on immune function were investigated. The results showed that the incidence and pathological stage of atypical hyperplasia in oesophageal tissues were significantly reduced in CMSP-treated mice compared with untreated mice. Immunohistochemistry and pull-down assay results revealed that the expression levels of p-ERK1/2, p-SAPK/JNK, and GTP-RhoA were significantly decreased in the oesophageal tissue of CMSP-treated mice. In addition, the proportions of CD4+ T cells, CD8+ T cells, and NK cells were increased, while the proportion of CD4+ CD25+ regulatory T cells (Tregs) was decreased, in the peripheral blood of CMSP-treated mice. These results indicated that CMSP could hamper 4NQO-induced oesophageal tumourigenesis by regulating the RhoA-ERK/JNK signaling pathway and promoting immune system function, thus providing a new potential strategy for treating preneoplastic lesions of the oesophagus.
Subject(s)
Carcinogenesis/drug effects , Cinnamates/pharmacology , Esophageal Neoplasms/prevention & control , Esophageal Squamous Cell Carcinoma/prevention & control , MAP Kinase Signaling System/drug effects , rhoA GTP-Binding Protein/metabolism , 4-Nitroquinoline-1-oxide , Animals , Carcinogenesis/chemically induced , Carcinogenesis/metabolism , Disease Progression , Esophageal Neoplasms/chemically induced , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/chemically induced , Esophageal Squamous Cell Carcinoma/metabolism , Esophagus/drug effects , Esophagus/metabolism , Esophagus/pathology , Mice, Inbred C57BL , Momordica/chemistry , Plant Extracts/pharmacology , Precancerous Conditions/chemically induced , Precancerous Conditions/metabolism , Precancerous Conditions/prevention & control , Seeds/chemistryABSTRACT
OBJECTIVES: Ankaferd BloodStopper® (ABS) is an herbal extract which has been used historically as a hemostatic agent in traditional Turkish medicine. ABS comprises of standardized mixture of herbs Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. In addition to its hemostatic effects, the herb ABS contains some other biological effects including antioxidant and antitumoral properties. The aim of this study is to investigate the chemopreventive effects of ABS in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral epithelial dysplasia. MATERIALS AND METHODS: A total of 40 Sprague Dawley rats were randomly divided into four groups. Group 1 animals received DMBA alone, and group 2 animals received both DMBA and Ankaferd. Group 3 animals received ABS alone while group 4 animals served as control group and received only liquid paraffine. All animals were sacrificed, and tissue samples were analyzed histologically at the end of the experimental period (14 weeks). RESULTS: Histological studies have shown that the buccal pouches of animals treated with DMBA alone revealed severe dysplasia while only mild or no dysplasia were noticed in DMBA + ABS group. Ankaferd were administered to animals and control group showed no dysplasia or other oral lesions. CONCLUSION: The results suggest that Ankaferd Bloodstopper® has chemopreventive effect against DMBA-induced oral epithelial dysplasia. CLINICAL RELEVANCE: Ankaferd Bloodstopper® could be used as a supportive treatment option of cancer in oral and maxillofacial surgery since it possesses chemopreventive effect.
Subject(s)
9,10-Dimethyl-1,2-benzanthracene , Mouth Mucosa , Plant Extracts , Precancerous Conditions , Animals , Male , Rats , Mouth Mucosa/drug effects , Mouth Mucosa/pathology , Plant Extracts/pharmacology , Precancerous Conditions/prevention & control , Random Allocation , Rats, Sprague-DawleyABSTRACT
Colon cancer is a world-wide health problem and one of the most dangerous type of cancer, affecting both men and women. Naringenin (4, 5, 7-trihydroxyflavanone) is one of the major flavone glycoside present in citrus fruits. Naringenin has long been used in Chinese's traditional medicine because of its exceptional pharmacological properties and non-toxic nature. In the present study, we investigated the chemopreventive potential of Naringenin against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions, that is, aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the oxidative stress, inflammation and hyperproliferation, in the colon of Wistar rats. Animals were divided into five groups. In groups 3-5, Naringenin was administered at the dose of 50 mg/kg b. wt. orally while in groups 2-4, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b. wt. once a week for first 5 weeks and animals were euthanized after 10 weeks. Administration of Naringenin ameliorated the development of DMH-induced lipid peroxidation, ROS formation, precancerous lesions (ACF and MDF) and it also reduced the infiltration of mast cells, suppressed the immunostaining of NF-κB-p65, COX-2, i-NOS PCNA and Ki 67 Naringenin treatment significantly attenuated the level of TNF-α and it also prevented the depletion of the mucous layer. Our findings suggest that Naringenin has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of Naringenin.
Subject(s)
Anticarcinogenic Agents/therapeutic use , Colonic Neoplasms/prevention & control , Flavanones/therapeutic use , Precancerous Conditions/prevention & control , Aberrant Crypt Foci/pathology , Aberrant Crypt Foci/prevention & control , Animals , Carcinogenesis/metabolism , Carcinogenesis/pathology , Cell Proliferation/drug effects , Colonic Neoplasms/pathology , Inflammation/metabolism , Inflammation/prevention & control , Lipid Peroxidation , Male , Mucins/metabolism , NF-kappa B/metabolism , Oxidative Stress , Precancerous Conditions/metabolism , Precancerous Conditions/pathology , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolismABSTRACT
PURPOSE: Glycerol usage is increasing in food industry for human and animal nutrition. This study analyzed the impact of glycerol metabolism when orally supplemented during the early stage of rat liver carcinogenesis. METHODS: Wistar rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP group). IP animals also received glycerol by gavage (200 mg/kg body weight, IPGly group). RESULTS: Glycerol treatment reduced the volume of preneoplastic lesions by decreasing the proliferative status of liver foci, increasing the expression of p53 and p21 proteins and reducing the expression of cyclin D1 and cyclin-dependent kinase 1. Besides, apoptosis was enhanced in IPGly animals, given by an increment of Bax/Bcl-2 ratio, Bad and PUMA mitochondrial expression, a concomitant increase in cytochrome c release and caspase-3 activation. Furthermore, hepatic levels of glycerol phosphate and markers of oxidative stress were increased in IPGly rats. Oxidative stress intermediates act as intracellular messengers, inducing p53 activation and changes in JNK and Erk signaling pathways, with JNK activation and Erk inhibition. CONCLUSION: The present work provides novel data concerning the preventive actions of glycerol during the development of liver cancer and represents an economically feasible intervention to treat high-risk individuals.
Subject(s)
Anticarcinogenic Agents/therapeutic use , Apoptosis , Dietary Supplements , Glycerol/therapeutic use , Liver Neoplasms, Experimental/prevention & control , Oxidative Stress , Precancerous Conditions/prevention & control , Animals , Anticarcinogenic Agents/blood , Anticarcinogenic Agents/metabolism , Biomarkers/blood , Carcinogenesis , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glycerol/blood , Glycerol/metabolism , Lipid Peroxidation , Liver/enzymology , Liver/metabolism , Liver/pathology , Liver Neoplasms, Experimental/blood , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms, Experimental/pathology , MAP Kinase Signaling System , Male , Mitochondria, Liver/enzymology , Mitochondria, Liver/metabolism , Mitochondria, Liver/pathology , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Phosphorylation , Precancerous Conditions/blood , Precancerous Conditions/metabolism , Precancerous Conditions/pathology , Rats, Wistar , Tumor BurdenABSTRACT
Ku-jin tea (KJT) is a health beverage prepared from the leaves of the plant Acer tataricum subsp. ginnala that has been consumed in some regions of China for thousands of years. KJT contains high levels of anti-inflammatory and antioxidative compounds such as ginnalins, but little is known about the chemopreventive effect of KJT on colon cancer. In this study, we investigated the preventive effects of KJT on colon carcinogenesis using the azoxymethane (AOM)-induced precancerous colorectal lesion model in rats. The results showed that the number of aberrant crypts, aberrant crypt foci (ACF) and crypts/focus in rats of the KJT + AOM group were significantly decreased compared with rats of the AOM group (p < 0.01). Further exploration of the prevention mechanism of KJT by UPLC-QTOF/MS-based urinary metabolomics showed that 5 metabolic pathways were modulated, including purine metabolism and amino acid metabolism, in the group with KJT. In addition, the levels of the immunomodulatory cytokines IL-1α and IL-10 were significantly decreased, and the levels of IL-2 in the serum of AOM rats increased after KJT treatment. Our present data suggest that KJT can inhibit AOM-induced colonic ACF formation and might be a useful chemopreventive agent against colorectal carcinogenesis.
Subject(s)
Chemoprevention , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/prevention & control , Metabolomics , Precancerous Conditions/metabolism , Precancerous Conditions/prevention & control , Tea/chemistry , Animals , Azoxymethane , Body Weight/drug effects , Colon/drug effects , Colon/pathology , Colorectal Neoplasms/blood , Cytokines/blood , Discriminant Analysis , Immunologic Factors/pharmacology , Least-Squares Analysis , Male , Metabolic Networks and Pathways/drug effects , Precancerous Conditions/blood , Precancerous Conditions/pathology , Rats, WistarABSTRACT
The potential utilization of Demodex mites as delivery vectors for cytotoxic medications directed to early skin cancer is proposed. Potential benefits, proof of concept, and limitations are discussed.
Subject(s)
Antineoplastic Agents/administration & dosage , Drug Delivery Systems , Melanoma/drug therapy , Mites/physiology , Models, Biological , Skin Neoplasms/drug therapy , Administration, Topical , Animals , Antineoplastic Agents/therapeutic use , Arachnid Vectors/physiology , Biological Therapy , Drugs, Investigational/administration & dosage , Drugs, Investigational/therapeutic use , Humans , Melanoma/prevention & control , Mite Infestations , Precancerous Conditions/drug therapy , Precancerous Conditions/prevention & control , Skin/drug effects , Skin Neoplasms/prevention & control , Therapies, InvestigationalABSTRACT
Hericium erinaceus is typically used in traditional Chinese medicine for mucosal protection, healing of gastric ulcers, and treatment of gastritis. We purified from the cultured mycelia of H. erinaceus a polysaccharide with anti-gastric ulcer and antigastritis activity, but its effects on gastric malignancy have not been elucidated. We examined the differential effects of this purified polysaccharide, named EP-1, on the human gastric (GES-1) cell line and a precancerous cell line (MC) that was transformed from GES-1 using N-methyl-N'-nitro-N-nitrosoguanidine. We observed that the polysaccharide potently induced cell apoptosis and cell cycle arrest at the G0/G1 phase in the MC cell line but did not have any effect on the GES-1 cell line at the same doses. Further mechanistic studies revealed that the polysaccharide exerted its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. Differential effects of the polysaccharide on the GES-1 and MC cell lines indicate that the polysaccharide was effective in preventing gastric cancer progression.
Subject(s)
Agaricales/chemistry , Apoptosis/drug effects , Mycelium/chemistry , Polysaccharides/pharmacology , Precancerous Conditions/prevention & control , Stomach Neoplasms/prevention & control , Apoptosis/genetics , Caspase 3/drug effects , Caspase 3/genetics , Cell Cycle/drug effects , Cell Line , Cell Line, Transformed , Drugs, Chinese Herbal/chemical synthesis , Drugs, Chinese Herbal/pharmacology , Fruiting Bodies, Fungal , Gastritis/drug therapy , Genes, bcl-2/drug effects , Humans , Medicine, Chinese Traditional , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Precancerous Conditions/pathology , Stomach Neoplasms/pathology , Stomach Ulcer/drug therapy , bcl-2-Associated X Protein/drug effects , bcl-2-Associated X Protein/geneticsABSTRACT
Asiatic acid (AA), a pentacyclic triterpenoid, derived from the tropical medicinal plant Centella asiatica is known to exhibit numerous pharmacological properties. We hypothesized that AA will have chemopreventive potential against 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis in male Wistar rats. Rats were arbitrarily divided into six groups. Group I rats were processed as control. Group II rats received AA (8 mg/kg b.w., p.o.) and groups III-VI rats received subcutaneous injections of DMH (20 mg/kg b.w.) once a week, for the first four weeks. In addition, groups IV-VI rats received AA at the doses of 2, 4 and 8 mg/kg b.w., respectively, for 16 weeks. Our results discovered that supplementation with AA to the DMH-exposed rats significantly decreased the incidence of polyps and Aberrant crypt foci (ACF) as compared to the DMH-alone-exposed rats. Moreover, in the AA-supplemented DMH-exposed rats, we ascertained increased activities of the antioxidants and decreased levels of lipid peroxidation (LPO) in the liver and circulation and enhanced levels of both LPO and antioxidants in the colon, which were altered in the DMH-alone-exposed rats. Furthermore, we also observed altered activities of vitamins C and E and biotransforming enzymes in DMH-alone-exposed rats, which were reversed on AA supplementation. All the observations were supported by our histological findings. Thus, we can conclude that, AA could be used as an effective chemopreventive agent against DMH-induced colon carcinogenesis.
Subject(s)
Anticarcinogenic Agents/therapeutic use , Colon/drug effects , Colonic Neoplasms/prevention & control , Oxidative Stress/drug effects , Pentacyclic Triterpenes/therapeutic use , Precancerous Conditions/prevention & control , 1,2-Dimethylhydrazine/pharmacokinetics , Animals , Anticarcinogenic Agents/administration & dosage , Ascorbic Acid/metabolism , Biotransformation , Catalase/metabolism , Colon/enzymology , Colon/pathology , Colonic Neoplasms/chemically induced , Colonic Neoplasms/enzymology , Colonic Neoplasms/pathology , Dose-Response Relationship, Drug , Male , Pentacyclic Triterpenes/administration & dosage , Precancerous Conditions/chemically induced , Precancerous Conditions/enzymology , Precancerous Conditions/pathology , Rats, Wistar , Superoxide Dismutase/metabolism , Vitamin E/metabolismABSTRACT
Se realizó un estudio experimental de intervención educativa del tipo antes-después con pacientes de 35-60 años. El universo estuvo constituido por 120 pacientes, con una muestra no probabilística intencional de 80 expuestos a factores de riesgo, con el objetivo de elevar los conocimientos sobre factores de riesgo para lesiones premalignas de la cavidad bucal, consultorio médico de la familia No. 26, Roberto Reyes, Bayamo, Granma, Cuba de enero a marzo 2016. La aplicación de la intervención educativa demostró ser un instrumento práctico para elevar el nivel de conocimiento de la población. Al evaluar el nivel de conocimientos sobre lesiones premalignas antes de la intervención la calificación de bien fue en un bajo por ciento y después se logró aumentar, con diferencias estadísticamente significativas entre ambos momentos(AU)
An experimental study of before-after educational intervention with patients aged 35-60 years was carried out. The universe consisted of 120 patients, with an intentional non-probabilistic sample of 80 exposed to risk factors, aiming to increase knowledge on risk factors for premalignant lesions of the oral cavity, doctor's office No. 26, Roberto Reyes, Bayamo city, Granma province, Cuba; from January to March 2016. The application of the educational intervention proved to be a practical instrument to raise the level of knowledge of the population. When assessing the level of knowledge about premalignant lesions before the intervention, the qualification of good was in a low percentile and then it was possible to increase, with statistically significant differences between both moments(EU)