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Preventive and curative effect of melatonin on mammary carcinogenesis induced by dimethylbenz[a]anthracene in the female Sprague–Dawley rat
Véronique Lenoir, Marianne Yon de Jonage-Canonico, Marie-Hélène Perrin, Antoine Martin, Robert Scholler, Bernard Kerdelhué
Breast Cancer Research , 2005, DOI: 10.1186/bcr1031
Abstract: The aim of this study was to compare the potency of melatonin to limit the frequency of mammary cancer initiation with its potency to inhibit tumor progression once initiation, at 55 days of age, was achieved. The present study compared the effect of preventive treatment with melatonin (10 mg/kg daily) administered for only 15 days before the administration of DMBA with the effect of long-term (6-month) curative treatment with the same dose of melatonin starting the day after DMBA administration. The rats were followed up for a year after the administration of the DMBA.The results clearly showed almost identical preventive and curative effects of melatonin on the growth of DMBA-induced mammary ADK. Many hypotheses have been proposed to explain the inhibitory effects of melatonin. However, the mechanisms responsible for its strong preventive effect are still a matter of debate. At least, it can be envisaged that the artificial amplification of the intensity of the circadian rhythm of melatonin could markedly reduce the DNA damage provoked by DMBA and therefore the frequency of cancer initiation.In view of the present results, obtained in the female Sprague–Dawley rat, it can be envisaged that the long-term inhibition of mammary ADK promotion by a brief, preventive treatment with melatonin could also reduce the risk of breast cancer induced in women by unidentified environmental factors.It has been well documented that the pineal hormone, melatonin, besides its well established circadian rhythm, plays a major role in the control of reproduction in mammals [1,2]. The role of the pineal gland, the major source of melatonin, in the development of breast [3] and mammary [4,5] cancer has been clearly documented. Also, it has been shown that melatonin may exert in vivo [6,7] and in vitro [8-10] an oncostatic activity by at least a direct action on the mammary tissue [11] and on the activation of estrogen receptor (ER) for DNA binding [12], or by modulation of the expression
Inhibition of Bladder Tumor Growth by Chitooligosaccharides in an Experimental Carcinogenesis Model  [PDF]
Jo?o C. Fernandes,José Sereno,Patricia Garrido,Belmiro Parada,Maria F. X. Cunha,Flávio Reis,Manuela E. Pintado,Alice Santos-Silva
Marine Drugs , 2012, DOI: 10.3390/md10122661
Abstract: Urinary bladder cancer is one of the most common cancers worldwide, with the highest incidence in industrialized countries. Patients with cancer commonly use unconventional and complementary therapy including nutraceuticals. In this study we evaluated the efficacy of chitooligosaccharides (in orange juice) in rat bladder cancer chemoprevention and as therapeutic agent, on a rat model of urinary bladder carcinogenesis induced with N-butyl- N-(4-hydroxybutyl) nitrosamine. Results indicate that chitooligosaccharides may have a preventive effect on bladder cancer development and a curative effect upon established bladder tumors, dependent on the concentration ingested 500 mg/kg b.w., every three days, showed capacity to inhibit and prevent the proliferation of bladder cancer; however, this was associated with secondary effects such as hypercholesterolemia and hypertriglyceridemia. The use of lower doses (50 and 250 mg/kg b.w.) showed only therapeutic effects. It is further suggested that this antitumor effect might be due to its expected anti-inflammatory action, as well as by mechanisms not directly dependent of COX-2 inhibition, such as cellular proliferation control and improvement in antioxidant profile.
Short-term Celecoxib intervention is a safe and effective chemopreventive for gastric carcinogenesis based on a Mongolian gerbil model  [cached]
Chao-Hung Kuo, Huang-Ming Hu, Pei-Yun Tsai, I-Chen Wu, Sheau-Fang Yang, Lin-Li Chang, Jaw-Yuan Wang, Chang-Ming Jan, Wen-Ming Wang, Deng-Chyang Wu
World Journal of Gastroenterology , 2009,
Abstract: AIM: To evaluate the optimal intervention point of a selective cyclooxygenase-2 (COX-2) inhibitor, Celecoxib, for inhibiting Helicobacter pylori (H pylori)-associated gastric carcinogenesis in Mongolian gerbils (MGs).METHODS: One hundred and twelve MGs were divided into six groups (A-F). One hundred gerbils were inoculated with H pylori (groups A-E). Twelve gerbils were inoculated with vehicle broth only (group F). After 4 wk, they were given N’-methyl-N’-nitro-N-nitroso-guanidine (MNNG) (50 μg/mL) in the drinking water for 20 wk. In groups B-E, the animals were given the stock Celecoxib (10 mg/kg per day) diet from the 21st, 31st, 21st and 41st week respectively. The periods of administering Celecoxib were 30, 20, 20, and 15 wk respectively. On the 51st week, the animals were sacrificed for histological examination. Local PCNA expression was examined by the immunohistochemistry method. The expression of COX-2 protein was assessed by Western Blot. Analysis used the χ2 test. The difference was regarded as significant when P value was less than 0.05.RESULTS: Seventeen percent (17/100) of H pylori-infected MGs developed gastric cancer. All of these lesions were well-differentiated adenocarcinoma. The incidence rates of adenocarcinoma in groups A-F were 40%, 0%, 0%, 20%, 25%, and 0% respectively. The inflammatory scores were higher in group B than in other groups. There was no inflammatory response noted in group F. Celecoxib treatment resulted in a significant reduction in the proliferation of H pylori-infected mucosal cells (groups B, C and D) (P < 0.01).The expression of COX-2 protein was significantly attenuated in the groups which were Celecoxib-treated for more than 20 wk (groups B, C, D). The groups treated with Celecoxib had a significantly lower rate of advanced gastric cancer (34% vs 75%, P < 0.001) There were no sudden deaths in any of the groups.CONCLUSION: Short-term treatment with Celecoxib has an anti-carcinogenic effect, and resulted in less severe inflammation and inhibited the invasive degree of gastric cancer.
Utilization Of Preventive And Curative Services In A Semi- Urban Area In Tamilnadu  [cached]
Kachirayan M,Radhakrishna S,Selvaraj V,Pushparaj Veena
Indian Journal of Community Medicine , 1988,
Abstract: Using a cluster sampling procedure, 2,248 semi- urban households comprising of 10,326 persons were chosen and surveyed to determine the extent of utilization of curative and preventive health services. Each household was visited by graduate interviewers on two occasions, a fortnight apart, and information collected over a reference period of 4 weeks. In all, 3,324 episodes were reported. A physician was consulted and treatment taken for 56.5 per cent of the episodes, Self- treatment or treatment on the advice of a lay person was resorted to for 22.7 per cent. For the remaining 20.8 per cent, no action was taken. Immunization coverage in children under 5 years was very poor, namely, 26 per cent for DPT and 15 per cent for OPV. Only a third of the pregnant women had visited a prenatal clinic during the reference period. Family planning, invariably sterilization, was practiced by 20 per cent of the eligible couples. The health utilization practices in this area are contrasted with those in nearby Madras City, and other urban areas, and the implications are discussed.
Role of Urinary Tract Bacterial Infection in the Process of Bladder Carcinogenesis (Molecular and Biochemical Studies)  [PDF]
Abeer Mostafa Ashmawey, Waleed S Mohamed, Ibrahim M Abdel-Salam, Saad M El-Gendy, Ali I Ali, Abdelbaset A El-Aaser
Asian Journal of Medical Sciences , 2011, DOI: 10.3126/ajms.v2i1.3542
Abstract: Objective: This work is designed to study the possible role of chronic inflammation induced by E. coli in the urinary bladder of rats, the protective role of soybean flour, in addition to the role of oxidative and nitrosative stresses during bladder carcinogenesis.
Effect of removing user fees on attendance for curative and preventive primary health care services in rural South Africa
Wilkinson,David; Gouws,Eleanor; Sach,Marlene; Karim,Salim S. Abdool;
Bulletin of the World Health Organization , 2001, DOI: 10.1590/S0042-96862001000700012
Abstract: user fees are used to recover costs and discourage unnecessary attendance at primary care clinics in many developing countries. in south africa, user fees for children aged under 6 years and pregnant women were removed in 1994, and in 1997 all user fees at all primary health care clinics were abolished. the intention of these policy changes was to improve access to health services for previously disadvantaged communities. we investigated the impact of these changes on clinic attendance patterns in hlabisa health district. average quarterly new registrations and total attendances for preventive services (antenatal care, immunization, growth monitoring) and curative services (treatment of ailments) at a mobile primary health care unit were studied from 1992 to 1998. regression analysis was undertaken to assess whether trends were statistically significant. there was a sustained increase in new registrations (p = 0.0001) and total attendances (p = 0.0001) for curative services, and a fall in new registrations (p = 0.01) and total attendances for immunization and growth monitoring (p = 0.0002) over the study period. the upturn in demand for curative services started at the time of the first policy change. the decreases in antenatal registrations (p = 0.07) and attendances (p = 0.09) were not statistically significant. the number of new registrations for immunization and growth monitoring increased following the first policy change but declined thereafter. we found no evidence that the second policy change influenced underlying trends. the removal of user fees improved access to curative services but this may have happened at the expense of some preventive services. governments should remain vigilant about the effects of new health policies in order to ensure that objectives are being met.
Effect of removing user fees on attendance for curative and preventive primary health care services in rural South Africa  [cached]
Wilkinson David,Gouws Eleanor,Sach Marlene,Karim Salim S. Abdool
Bulletin of the World Health Organization , 2001,
Abstract: User fees are used to recover costs and discourage unnecessary attendance at primary care clinics in many developing countries. In South Africa, user fees for children aged under 6 years and pregnant women were removed in 1994, and in 1997 all user fees at all primary health care clinics were abolished. The intention of these policy changes was to improve access to health services for previously disadvantaged communities. We investigated the impact of these changes on clinic attendance patterns in Hlabisa health district. Average quarterly new registrations and total attendances for preventive services (antenatal care, immunization, growth monitoring) and curative services (treatment of ailments) at a mobile primary health care unit were studied from 1992 to 1998. Regression analysis was undertaken to assess whether trends were statistically significant. There was a sustained increase in new registrations (P = 0.0001) and total attendances (P = 0.0001) for curative services, and a fall in new registrations (P = 0.01) and total attendances for immunization and growth monitoring (P = 0.0002) over the study period. The upturn in demand for curative services started at the time of the first policy change. The decreases in antenatal registrations (P = 0.07) and attendances (P = 0.09) were not statistically significant. The number of new registrations for immunization and growth monitoring increased following the first policy change but declined thereafter. We found no evidence that the second policy change influenced underlying trends. The removal of user fees improved access to curative services but this may have happened at the expense of some preventive services. Governments should remain vigilant about the effects of new health policies in order to ensure that objectives are being met.
Control of potato early blight with triazole fungicide using preventive and curative spraying, or a forecasting system
Mantecón,Jorge D;
Ciencia e investigación agraria , 2009, DOI: 10.4067/S0718-16202009000200013
Abstract: during the 2005 and 2006 growing seasons, two field trials were conducted at the inta balcarce experimental station (argentina) to study the control of potato early blight (alternaria solani). uncut virus-free seed tubers of potato (solanum tuberosum) cv. pampeana pnta that were susceptible to early blight and resistant to late blight were machine planted in 0.20-m intervals in rows spaced 0.8 mapart. each plot consisted of 4 rows that were 5 meters long. difenoconazole (bogard 25ec) was sprayed weekly at a rate of 0.25 l· ha-1 or bi-weekly at a rate of 0.50 l· ha-1 on a preventive program and on a curative program. the same treatments and rates were also applied when the forecast model (specware 6.02) reached 300 p-days after emergence, and applications were then repeated thereafter every 7 east severity values. disease severity was rated using the 0-50 rating scale (0 = no infection; 50 = maximum infection). tubers from the two center rows of each plot were harvested and graded into two categories, either marketable (>60 g) or undersize tubers "seeds" (<60 g), and weighed for total yield. climatic conditions were very favorable for disease development. in both years, untreated plants showed severe early blight symptoms and reached the maximum disease severity. preventive fungicide applications at the high dose and applications following the specware 6.02 disease prediction model showed similar efficacy. curative fungicide applications at the lowest dose and applications on the basis of the specware 6.02 disease prediction model resulted in a poor control of foliar symptoms, and yields were lower than those obtained with a preventive control program.
Coordinated Increased Expression of Cyclooxygenase2 and Nuclear Factor B Is a Steady Feature of Urinary Bladder Carcinogenesis  [PDF]
Stylianos Kontos,Georgia Sotiropoulou-Bonikou,Athina Kominea,Maria Melachrinou,Eleni Balampani,Dionysis Bonikos
Advances in Urology , 2010, DOI: 10.1155/2010/871356
Abstract: Objectives. The inescapable relationship between chronic inflammation and carcinogenesis has long been established. Our objective was to investigate COX-2 and NF- B immunohistochemical expression in a large series of normal epithelium and bladder carcinomas. Methods. Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females with bladder carcinomas). Results. COX-2 expression is increased in the cytoplasm of bladder cells, during loss of cell differentiation ( , ) and in muscle invasive carcinomas ( ). A strong positive association between tumor grade and nuclear expression of NF B has been established. A positive correlation between COX-2 and nuclear NF B immunoreactivity was observed. Conclusions. The possible coordinated upregulation of NF B and COX-2, during bladder carcinogenesis, indicates that agents inhibitors of these two molecules may represent a possible new treatment strategy, by virtue of their role in bladder carcinogenesis. 1. Introduction Urothelial carcinoma (UC) of the urinary bladder is the third most common cancer in men and the 15th most common cancer in women. UC-related deaths are mainly caused by the invasive type of the disease [1]. However, the more frequent form of this carcinoma is either non-invasive or superficially invasive disease, which is usually curable, but demonstrates a challenge to the clinician because of its recurrent nature. Thus, more effective therapies are needed to prevent recurrence of superficial UC and to inhibit progression of noninvasive tumors to invasive carcinomas [2]. The inescapable relationship between chronic inflammation and carcinogenesis has long been established and rests on DNA damage. Chronic inflammation is now recognized as crucial in the pathogenesis of a variety of diseases, such as arthritis, diabetes, atherosclerosis, Alzheimer’s disease, and cancer development, including bladder cancer [3]. To better understand the importance of chronic inflammation in bladder cancer pathogenesis and progression, we investigated COX-2 and NF- B p65 immunohistochemical expression in a large series of normal epithelium and bladder carcinomas, and we correlated those findings with cancer cell differentiation, tumor grade and stage, and clinical-pathologic features of bladder cancer patients. Cyclooxygenase-2 (COX-2) is an enzyme missing from most healthy tissues, while its presence is well detected in neoplastic and inflammatory foci [4]. As a catalyst of prostaglandin synthesis, it promotes the
Enhancement of Urinary Bladder Carcinogenesis by the Role of Chronic Bacterial Infection-induced Inflammation (Imunnohistochemical and Biochemical studies)
Gabri MS*, Ashmawy AM**, Ibrahim MA*, Hosny RM
Egyptian Journal of Hospital Medicine , 2012,
Abstract: Background: Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Escherichia coli infection. E. coli has been epidemiologically linked to urothelial carcinoma of the urinary bladder by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds.Material and methods: After each 3, 6 and 9 months of daily oral administration of dibutyl amine (DBA) plus sodium nitrate (nitrosamine precursors) in drinking water, curcuma in grinding diet and bladder injection with E. coli, rats were sacrificed. The excited bladder were dissected, processed and stained with H&E and anti-Ki67 immunohistochemical stains. This was followed by Elisa for caspse-3 and statistical analysis.Results: The current results indicated that E. coli infection in the bladder tissues increases the carcinogenic ability of nitrosamine precursors through caused marked alteration in the form hyperplastic, dysplastic and metaplastic urothelium. Also, there was a statistically significant increase in ki67 immunoreactivity in urothelium. However, a statistically significant decrease in the concentration of caspase-3 in bladder tissue consequently caused the process of carcinogenesis. All these changes were less marked after curcuma treatment when compared with the group that not treated with curcuma. Conclusion: Bacterial infection of the urinary bladder may play a major additive and possible role in bladder carcinogenesis. Rhizome of curcuma may have a protective action during induction of urinary bladder tumors.
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