Experimental carcinogenesis with 7, 12-dimethylbenz(a)anthrazene (DMBA) and its inhibition with isothi-ocyanates / Carcinogénesis experimental con 7, 12-dimetilbenzantraceno (DMBA) y su inhibición con isitiocianatos

Introduction: DMBA is a chemical carcinogen that induces carcinomas within a few weeks of its application. We developed an experimental model of carcinogenesis induced by DMBA dissolved in 0,5% paraffin oil (DMBA-PO), verifying the inhibitory effect of the carcinogenicity of phenyl isothiocyanate (PhITC), phenethyl (PhnITC) and benzyl isothiocyanate (BITC). Material and Methods: For this, 88 hamsters were distributed into three groups: one exposed to DMBA-PO (Group 1, n=12), three subgroups (n=12) exposed to PhITC, PhnITC, BITC and DMBA-PO (Group 2, n=36) and four control subgroups (n=10) that were not exposed to the carcinogen in which PO (paraffin oil) and isothiocyanates were applied (Group 3, n=40). Results: The experiment had a duration of 20 weeks, at the end of which the inhibitory effect was established by comparing the lesions developed in the groups that received isothiocyanates with the group that was only treated with DMBA-PO. The carcinogenic effect of DMBA-PO is 100% (35 carcinomas) and the inhibitory effect was 0, whereas in the presence of isothiocyanates the carcinogenic effect decreases, with an inhibitory effect of 86% for BITC (5 carcinomas) and 74% for PhITC (9 carcinomas). Conclusion: The inhibitory effect for PhnITC is 80% in relation to invasive OSCC (1 carcinoma).

Introducción: El DMBA es un carcinógeno químico que induce carcinomas a las pocas semanas de su aplicación. Desarrollamos un modelo experimental de carcinogénesis inducida por DMBA disuelto en aceite de parafina al 0,5% (DMBA-Ap) comprobando el efecto inhibidor de la carcinogénesis de los isotiocianatos fenil (PhITC), fenetil (PhnITC) y bencil isotiocianato (BITC). Material y Métodos: Para ello, se distribuyeron 88 hámsteres en 3 grupos: uno expuesto al DMBA-Ap (Grupo 1, n=12), tres subgrupos (n=12) expuestos a PhITC, PhnITC, BITC y DMBA-Ap (Grupo 2, n=36) y cuatro subgrupos controles (n=10), no expuestos al carcinógeno en el que se aplicaron Ap e isotiocianatos (Grupo 3, n=40). Resultados:El experimento tuvo una duración de 20 semanas, al final de la cual se establece de forma comparativa el efecto inhibidor comparando las lesiones desarrolladas en los grupos que recibieron isotiocianatos con respecto al grupo tratado sólo con DMBA-Ap. El efecto carcinógeno del DMBA-Ap es del 100% (35 carcinomas) y el efecto inhibidor 0, mientras que en presencia de isotiocianatos el efecto carcinógeno disminuye, con un efecto inhibidor del 86% para BITC (5 carcinomas) y del 74% para el PhITC (9 carcinomas). Conclusión:El efecto inhibidor del PhnITC es del 80% en relación con el COCE invasivo (1 carcinoma).

Plantas utilizadas para el tratamiento del cáncer expendidas en los principales mercados de la provincia de Trujillo, Perú, 2016 ­ 2017 / Plants used for the treatment of cancer expanded in the main markets of the province of Trujillo, Peru, 2016 - 2017

Between 2016 and 2017, we conducted structured interviews with herbalists in market stands in the providence of Trujillo, La Libertad, Peru in order to create a catalog of plants with anticarcinogenic properties. Herbalists shared information about species they use in cancer treatment, including common names, part of the plant used, methods of preparation, plant state, and frequency and method of administration as medicine. We combined this information with the Shannon-Wiener diversity and evenness index to complete a quantitative analysis of the anticarcinogenic species. Our results demonstrate that 46 different species representing 24 genera and 19 families are locally used in cancer treatment, with a Shannon-Wiener index of 3.6 and 0.9 respectively. Our catalog thus represents a great variety of species and source of potentially useful knowledge for fighting cancer.

Con el objetivo de registrar las plantas con propiedades anticancerígenas distribuidas en la provincia de Trujillo, La Libertad, durante el 2016 y 2017, realizamos entrevistas estructuradas a hierbateros con puesto de venta en los mercados de abastos, quienes brindaron información sobre las especies usadas para el tratamiento del cáncer, detallando nombres vulgares, parte del vegetal utilizado, formas de preparación, estado de la plantas, frecuencia y forma de administración; así mismo aplicando los índices de diversidad Shannon- Wiener y Equidad se hizo el análisis cuantitativo de los datos encontrados. Se evidenció que para el tratamiento del cáncer se usan 46 especies, representadas 24 géneros y 19 familias; valor que refleja un Índice de Diversidad y de Equidad de 3.6 y 0.9 respectivamente, indicando que existe una gran variedad de especies y un conocimiento potencialmente valioso para combatir esta enfermedad.

Cardiovascular adverse events associated with oral antineoplastic therapy / Eventos adversos cardiovasculares asociados a la terapia antineoplásica oral / Eventos adversos cardiovasculares associados à terapia antineoplásica oral

ABSTRACT Objective: To identify in the literature the cardiovascular adverse events resulting from oral antineoplastic therapy. Method: Integrative review of the literature through the SCOPUS, Scientific Electronic Library Online (SciELO), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medical Literature Analysis and Retrieval System Online (MEDLINE) databases. The antineoplastic, cardiotoxicity, cardiovascular system and adverse reaction descriptors were used in Portuguese, English and Spanish. We selected 23 articles published between 1985 and 2015. Results: Twenty studies were related to cardiac events and eleven to peripheral vascular events. The most frequent adverse cardiac events were reduced left ventricular ejection fraction, myocardial infarction, changes in the electrocardiogram, heart failure and angina, whereas peripheral vascular events were hypertension and thromboembolism. Conclusion: Oral antineoplastic therapy is associated with different adverse events, including cardiac and peripheral vascular events.

RESUMEN Objetivo: Identificar en la literatura los eventos adversos cardiovasculares derivados de la terapia antineoplásica oral. Método: Revisión integrativa de literatura en las bases de datos SCOPUS, Scientific Electronic Library Online (SciELO), Cumulative Index to Nursing and Allied Health Literature (CINAHL) y Medical Literature Analysis and Retrieval System Online (MEDLINE). Se utilizaron descriptores antineoplásicos, cardiotoxicidad, el sistema cardiovascular y reacción adversa en Portugués, Inglés y Español. Se seleccionaron 23 artículos publicados entre 1985 y 2015. Resultados: Veinte estudios estaban relacionados con los eventos cardiacos y once con los eventos vasculares periféricos. Los eventos adversos cardiacos más frecuentes fueron la disminución de la fracción de eyección del ventrículo izquierdo, infarto de miocardio, cambios en el electrocardiograma, insuficiencia cardíaca y angina, mientras que los vasculares periféricos fueron hipertensión arterial y tromboembolismo. Conclusión: La terapia antineoplásica oral está asociada a diferentes eventos adversos, entre ellos los cardíacos y los vasculares periféricos.

RESUMO Objetivo: Identificar na literatura os eventos adversos cardiovasculares decorrentes da terapia antineoplásica oral. Método: Revisão integrativa de literatura nas bases de dados SCOPUS, Scientific Electronic Library Online (SciELO), Cumulative Index to Nursing and Allied Health Literature (CINAHL) e Medical Literature Analysis and Retrieval System Online (MEDLINE). Utilizaram-se os descritores antineoplásicos, cardiotoxicidade, sistema cardiovascular e reação adversa, em português, inglês e espanhol. Foram selecionados 23 artigos publicados entre 1985 e 2015. Resultados: Vinte estudos estavam relacionados aos eventos cardíacos e onze aos eventos vasculares periféricos. Os eventos adversos cardíacos mais frequentes foram diminuição da fração de ejeção do ventrículo esquerdo, infarto do miocárdio, alterações no eletrocardiograma, insuficiência cardíaca e angina, enquanto que os vasculares periféricos foram hipertensão arterial e tromboembolismo. Conclusão: A terapia antineoplásica oral está associada a diferentes eventos adversos, dentre eles os cardíacos e os vasculares periféricos.

Prevenção do câncer do colo uterino de quilombolas à luz da teoria de Leininger / Prevención del cáncer de cuello uterino de quilombolas a la luz de la teoría de Leininger / Cervical cancer prevention among quilombola women in the light of Leininger's theory

Resumo OBJETIVO Discutir as práticas de prevenção do câncer do colo do útero de mulheres quilombolas. MÉTODO Estudo qualitativo, realizado em 2014 com vinte mulheres de uma comunidade quilombola, localizada na Bahia. Os dados foram coletados por meio de entrevista semiestruturada e analisados através da etnoenfermagem. RESULTADOS As quilombolas apontaram como práticas preventivas para o câncer do colo uterino o cuidado cultural, através do uso de plantas medicinais, e o cuidado profissional, caracterizado pela realização do Papanicolau. Contudo, uma maioria de mulheres não realizavam prevenção. CONCLUSÃO Questões de ordem social, cultural e de acesso relacionam-se com as práticas preventivas para o câncer do colo uterino de quilombolas. Assim, torna-se imprescindível um planejamento de cuidados congruentes com a realidade dessas mulheres.

Resumen OBJETIVO Discutir las prácticas de prevención del cáncer de cuello de útero de mujeres quilombolas. MÉTODO Estudio cualitativo, realizado en 2014 con veinte mujeres de una comunidad quilombola, localizada en Bahía. Los datos fueron recolectados por medio de entrevista semiestructurada y analizados a través de la etnoenfermería. RESULTADOS Las quilombolas apuntaron como prácticas preventivas para el cáncer de cuello uterino el cuidado cultural a través del uso de plantas medicinales y el cuidado profesional, caracterizado por la realización del Papanicolau. Sin embargo, la mayoría de las mujeres no realizaron prevención. CONCLUSIÓN Cuestiones de orden social, cultural y de acceso se relaciona con las prácticas preventivas para el cáncer de cuello uterino de quilombolas. Así que se torna imprescindible un planeamiento de cuidados congruentes con la realidad de esas mujeres.

Abstract OBJECTIVE Our purpose was to discuss practices of cervical cancer prevention among Quilombola Women. METHOD This study used, in 2014, a qualitative research approach aiming twenty women from a quilombola community (people who live in quilombos, descendants of Afro-Brazilian slaves), which is located in Bahia. A semi-structured interview was developed by researchers in order to collect data. The Ethno-nursing Research method was used to analyze the data. RESULTS The use of cultural care through medicinal plants, and the nursing professional care (Pap Smear exam procedure) were stated by Quilombola women as serving as prevention practices against cervical cancer. However, most women stated that they did not use any prevention practices. CONCLUSION Social, cultural and health access issues are practices that are linked to the cervical cancer prevention among Quilombola Women. Therefore, it is indispensable to create an appropriate care plan for Quilombola women's reality.

Citotoxicidad in vitro y potencialidades de los compuestos quinoides como agentes antitumorales / Cytotoxicity in vitro and potential of quinoid compounds as antitumor agents

La búsqueda e identificación de nuevos compuestos activos para la terapéutica del cáncer se ha centrado esencialmente en la investigación de productos naturales y de sus análogos sintéticos. El presente trabajo pretende sistematizar los conocimientos sobre las bases moleculares de la actividad citotóxica de los compuestos quinoides y su uso como agente antitumoral. Se realizó una revisión de artículos originales, de corte experimental, publicados en la década 2004-2014 en algunas bases de datos de la Biblioteca Virtual de Salud (BVS). Se constató que numerosos estudios han avalado la capacidad de los productos quinoides de inhibir el crecimiento celular, sustentado en sus posibilidades de dañar al ADN por estrés oxidativo y de interactuar de modo biorreductivo con otras biomoléculas. Además, que la potencia de la citotoxicidad de los compuestos quinoides se incrementa ante cadenas laterales alquiladas y anillos aromatizados unidos al motivo quinona. Las evidencias experimentales sugieren un promisorio futuro de estas moléculas como agentes antitumorales, en base a su citotoxicidad y elevada selectividad ante líneas celulares neoplásicas(AU)

The search and identification of new active compounds for cancer therapy has focused mainly on research of natural products and their synthetic analogs. This paper aims to systematize the knowledge of the molecular basis of the cytotoxic activity of the quinoid compounds and their use as an antitumor agent. A review was performed on original articles, experimental section, published in the 2004-2014 decade in some databases of the Virtual Health Library (VHL). Numerous studies have supported the ability of quinoid products inhibiting cell growth, based on their ability to damage DNA by oxidative stress and thus have a biorreductive interaction with other biomolecules. Furthermore, the power of cytotoxicity increases quinoid compounds alkylated with side chains attached to rings and quinone flavored motif. Experimental evidence suggests a promising future of these molecules as antitumor agents, based on their high selectivity and cytotoxicity against neoplastic cell lines(AU)

Xylooligosaccharides: an economical prebiotic from agroresidues and their health benefits.

Oligosaccharides and dietary fibres are non-digestible food ingredients that preferentially stimulate the growth of prebiotic Bifidobacterium and other lactic acid bacteria in the gastro-intestinal tract. Xylooligosaccharides (XOS) provide a plethora of health benefits and can be incorporated into several functional foods. In the recent times, there has been an over emphasis on the microbial conversion of agroresidues into various value added products. Xylan, the major hemicellulosic component of lignocellulosic materials (LCMs), represents an important structural component of plant biomass in agricultural residues and could be a potent bioresource for XOS. On an industrial scale, XOS can be produced by chemical, enzymatic or chemo-enzymatic hydrolysis of LCMs. Chemical methods generate XOS with a broad degree of polymerization (DP), while enzymatic processes will be beneficial for the manufacture of food grade and pharmaceutically important XOS. Xylooligomers exert several health benefits, and therefore, have been considered to provide relief from several ailments. This review provides a brief on production, purification and structural characterization of XOS and their health benefits.

Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice

OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM). Cell proliferation was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of α-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc ...

Sulfane sulfur deficiency in malignant cells, increasing the inhibiting action of acetone cyanohydrin in tumor growth

PURPOSE: To demonstrate the irreversible poisoning action of the acetone cyanohydrin (AC) in malignant cells. METHODS: Thirty male Swiss mice were inoculated with 1x10³ Ehrlich tumor (ET) cells. The mice were divided into three groups (n=10): CG (saline); ACG1 (1.864 mg/Kg of AC) and ACG2 (2.796 mg/Kg of AC), treated every 48 hours from day 3 until day 13. On day 15 the mice were euthanized and the number of viable cells in ascites was determined. In the meantime, ET cells were incubated with AC (0.5, 1.0, 2.0 μg/mL). Cell viability and percentage of growth inhibition (PGI) were checked after one, two, three, four, 18 and 24 hours. RESULTS: There was reduction in volume and number of viable cells in ACG1 and ACG2 compared to CG. In ACG1 one of the animals did not present ascites. In ACG2 two mice did not present ascites and in CG none of the mice present ascites. The action of AC was dose and time dependent and there was no significant difference among the three doses. CONCLUSION: The acetone cyanohydrin promoted reduction of the tumor and also prevented tumor development in 20% of the treated animals.

Consumo de licopeno como reductor de incidencia en sujetos con elevado riesgo de padecer cáncer de próstata / Lycopene consumption and reduction of incidence in subjects at high risk of prostate cancer

Este CAT (Critically Appraised Topics) respondió a la interrogante “en sujetos con alto riesgo de padecer cáncer de próstata ¿puede el licopeno reducir la incidencia y mortalidad?” Se analizó la pregunta clínica en tres partes: paciente, intervención y outcome. El objetivo fue comprobar la validez de los resultados y aplicabilidad respecto de la efectividad del consumo de licopeno en la reducción de la incidencia del cáncer de próstata a partir del articulo Lycopene for the prevention of prostate cáncer de Ilic, et al. (2011).

This CAT (Critically Appraised Topic) answered the question: in subjects at high risk for prostate cancer, can lycopene reduce incidence and mortality of this cancer? The clinical question was analyzed in three parts: patient, intervention and outcome. The purpose was to verify the validity and applicability of the results regarding lycopene consumption on effectiveness in reducing the incidence of prostate cancer.

Evaluation of the effect of newer antioxidant lycopene in the treatment of oral submucous fibrosis.

Background and Objective: Oral submucous fibrosis (OSMF) is a well-known premalignant condition encountered in Indian population. Although the disease is advancing rapidly, its reliable treatment modality for its various stages has not yet evolved. The aim of the present study is to compare the effect of newer antioxidant lycopene with a placebo in conjunction with the cessation of causative habit in the treatment of OSMF. Materials and Methods: The study group included 92 patients with OSMF. The OSMF diagnosis was established through a composite of accepted clinical and histopathological characteristics. Out of 92, 46 patients were given lycopene and remaining 46 were on placebo drug. Lycopene group patients received 8 mg Lycored TM per day in two divided doses of 4 mg each, while placebo group patients received placebo tablet twice a day. Patients were examined for changes in mouth opening and other clinical symptoms of OSMF during three months and were followed up for next two months. Results: Lycopene was found to be significantly efficacious in the amelioration of signs and symptoms of OSMF. It was effective in reducing the objective signs of OSMF as demonstrated by the improved maximal mouth opening, percentage of which was 69.56%(P<0.05). Interpretation and Conclusion: Reactive oxygen compounds or free radicals have been implicated as one of the major harmful factors for premalignant and malignant conditions. Present study concludes that lycopene, a newer antioxidant, appears to be a very promising drug in the management of OSMF.

Chemoprevention with green propolis green propolis extracted in L-lysine versus carcinogenesis promotion with L-lysine in N-Butyl-N-[4-hydroxybutyl] nitrosamine (BBN) induced rat bladder cancer / Quimioprevenção com própolis verde extraído em L-Lisina versus promoção da carcinogênese como L-Lisina em ratos induzidos ao câncer de bexiga pelo N-Butyl-N-[4-hydroxybutyl] nitrosamine (BBN)

PURPOSE: To determine the effects of green propolis extracted in L-lysine (WSDP) and of L- lysine for 40 weeks on induced rat bladder carcinogenesis. METHODS: The animals (groups I, II, III, IV, V and VI) received BBN during 14 weeks. Group I was treated with propolis 30 days prior received BBN, and then these animals were treated daily with propolis; Groups II and III was treated with subcutaneous and oral propolis (respectively) concurrently with BBN. The animals of Group IV were treated L-lysine; Group V received water subcutaneous; and Group VI received only to BBN. Among the animals not submitted to carcinogenesis induction, Group VII received propolis, Group VIII received L-lysine and Group IX received water. RESULTS: The carcinoma incidence in Group I was lower than that of control (Group VI). The carcinoma multiplicity in Group IV was greater than in Group VI. All animals treated with L-lysine developed carcinomas, and they were also more invasive in Group IV than in controls. On the other hand, Group VIII showed no bladder lesions. CONCLUSION: The WSDP is chemopreventive against rat bladder carcinogenesis, if administered 30 days prior to BBN , and that L-lysine causes promotion of bladder carcinogenesis.

OBJETIVO: Determinar os efeitos da própolis verde extraída em L - Lisina (WSDP) e da L-Lisina por 40 semanas em ratos induzidos a carcinogênese de bexiga. MÉTODOS: Os animais (grupos I, II, III, IV, V e VI) receberam BBN por 14 semanas. O grupo I foi tratado com própolis 30 dias antes de receber BBN e em seguida estes animais foram tratados diariamente com própolis; Os grupos II e III foram tratados com própolis subcutânea e oral (respectivamente) e concorretemente com BBN. Os animais do grupo IV foram tratados com L- Lisina; o grupo V recebeu água subcutânea; o grupo VI recebeu apenas BBN. Entre os animais não submetidos a indução de carcinogênese, Grupo VII, receberam própolis, Grupo VIII, receberam L-Lisina e Grupo IX receberam água. RESULTADOS: A incidência de carcinoma no grupo I foi menor que no grupo controle (grupo IV) A multiplicidade de carcinoma no grupo IV foi maior que no grupo VI. Todos os animais tratados com L - Lisina desenvolveram carcinomas e estes foram mais invasivos no grupo IV que no grupo controle. Por outro lado o grupo VIII não apresentou lesões. CONCLUSÃO: WSDP é quimiopreventiva contra a carcinogese de bexiga se administrada 30 dias antes do início do BBN, e a L - Lisina causa promoção da carcinogênese de bexiga.

Autophagy and cancer

Basal autophagy plays a critical role in maintaining cellular homeostasis and genomic integrity by degrading aged or malfunctioning organelles and damaged or misfolded proteins. However, autophagy also plays a complicated role in tumorigenesis and treatment responsiveness. It can be tumor-suppressing during the early stages of tumorigenesis (i.e., it is an anti-tumor mechanism), as reduced autophagy is found in tumor cells and may be associated with malignant transformation. In this case, induction of autophagy would seem to be beneficial for cancer prevention. In established tumors, however, autophagy can be tumor-promoting (i.e., it is a pro-tumor mechanism), and cancer cells can use enhanced autophagy to survive under metabolic and therapeutic stress. The pharmacological and/or genetic inhibition of autophagy was recently shown to sensitize cancer cells to the lethal effects of various cancer therapies, including chemotherapy, radiotherapy and targeted therapies, suggesting that suppression of the autophagic pathway may represent a valuable sensitizing strategy for cancer treatments. In contrast, excessive stimulation of autophagy may also provide a therapeutic strategy for treating resistant cancer cells having high apoptotic thresholds. In order for us to develop successful autophagy-modulating strategies against cancer, we need to better understand how the roles of autophagy differ depending on the tumor stage, cell type and/or genetic factors, and we need to determine how specific pathways of autophagy are activated or inhibited by the various anti-cancer therapies.

Endpoints in advanced breast cancer: methodological aspects & clinical implications.

Breast cancer is an increasingly important public health problem in developing countries, with disproportionately high mortality. The increasing availability of active agents against advanced breast cancer makes the development of novel treatments and their choice in clinical practice progressively more complex. Furthermore, there is often a tension between the adequacy of endpoints used in clinical trials and the clinician's aim of improving survival and quality of life, the two most important therapeutic goals in advanced breast cancer. However, overall survival (OS) is no longer a suitable indicator of treatment efficacy within clinical trials in settings for which effective subsequent-line therapy exists. Conversely, progression-free survival (PFS) currently represents the most sensitive parameter to assess the efficacy of a new drug or combination in such settings. When coupled with a favourable toxicity profile and cost, the demonstration of an improved PFS may be enough evidence for the superiority of a treatment. Despite arguments favouring the use of PFS as a primary endpoint in clinical trials, clinicians who need to make sense of the available literature may be reluctant to use PFS as an indicator of clinical benefit when deciding among different therapeutic strategies for their patients. This choice is further complicated if one fails to distinguish between the use of an efficacy parameter as an indicator of therapeutic objective for individual patients and as a clinical trial endpoint. This brief review aims at helping clinicians in their daily need to interpret the literature and make informed treatment choices for patients with advanced breast cancer.

Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

β-ionone (βI), a cyclic isoprenoid, and geraniol (GO), an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group) weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight), GO (25 mg/100 g body weight), βI combined with GO or corn oil (control). Number of total aberrant crypt foci (ACF) and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively) compared to control (102 ± 9 and 17 ± 3) and without differences in the βI (91 ± 11 and 14 ± 3) and βI+GO groups (96 ± 5 and 19 ± 2). Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm²) compared to control (0.91 ± 0.07 apoptotic cells/mm²). The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry) were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcrvpdate=20110329inogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

Effect of sustained virologic response on the incidence of hepatocellular carcinoma in patients with HCV cirrhosis

BACKGROUND AND OBJECTIVES: Evidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma. METHODS: A cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy. RESULTS: The mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55 percent) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3 percent) vs. 8 (17 percent) responders and non responders respectively (p = 0.02). CONCLUSION: Patients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.

Probióticos e prebióticos na atenção primária ao câncer de cólon / Probiotics and prebiotics in primary care for colon cancer

CONTEXTO: As neoplasias de cólon são a terceira forma mais comum de câncer atualmente. Seus tratamentos ainda estão associados a elevado risco de complicações, ressaltando, assim, a necessidade de elaborar novas estratégias de tratamento. A ingestão de probióticos, prebióticos ou a combinação de ambos (simbióticos), representa nova opção terapêutica. Diante da importância do equilíbrio quantitativo e qualitativo da microbiota intestinal para saúde humana e com objetivo de melhor elucidar o papel dos probióticos e prebióticos, o tema citado procura abordar a importância destes como coadjuvantes na prevenção e tratamento de câncer de cólon. METODOLOGIA: Foi realizada pesquisa em bancos de dados científicos (Medline, Lilacs, PubMed, Ovid, Scielo) através de levantamento de artigos científicos, além da busca direta aos periódicos, priorizando-se os mesmos do período de 2003 a 2008. Foram, também, coletadas informações através de sites da internet, como forma de melhor compreender a epidemiologia, conceitos e tratamentos dessa patologia. RESULTADOS: Estudos apontam relação inversa entre o consumo de probióticos e prebióticos e o diagnóstico de câncer de cólon, sendo que alguns dos possíveis mecanismos englobam: aumento da resposta imune, redução da resposta inflamatória, inibição de formação de células tumorais e da conversão de substâncias pré-carcinogênicas em carcinogênicas. CONCLUSÃO: Através da realização desta revisão literária foi possível obter respostas positivas quanto ao uso de probióticos e prebióticos na carcinogênese, colocando seu uso como recomendado de forma adequada.

CONTEXT: Colon neoplasias are presently the third most common cancer type. Its treatment is still associated with high risk of complications, thus emphasizing the need to design new treatment strategies. The ingestion of probiotics and prebiotics, or the combination of both (symbiotics), represents a new therapeutic choice. In front of the importance among qualitative and quantitative balance in intestinal microbiota for human's health and with the purpose to evaluate the application of probiotics and prebiotics, this study tries to approach the importance of these in both the prevention and treatment of colon cancer. EVIDENCE ACQUISITION: A study was conducted on scientific databases (Medline, Lilacs, PubMed, Ovid, SciELO), and a review was made of recent scientific articles in the literature, from 2003 to 2008. Additional informations were taken from sites in the internet. RESULTS: Studies point out the inverse relation between the consumption of probiotics and prebiotics in colon cancer diagnosis through various action mechanisms, including: immune response stimulation, reduction in inflammation, for directly inhibiting the formation of tumor cells and for converting pre-carcinogenic substances into carcinogenic ones. CONCLUSION: Through this literature review, it was possible to achieve positive answers as regards the use of probiotics and prebiotics in carcinogenesis, which can be adequately recommended.

Role of the vitamin C in diethylnitrosamine-induced esophageal cancer in Wistar rats / O efeito inibidor da vitamina C na carcinogênese esofágica induzida pela dietilnitrosamina em ratos Wistar

PURPOSE: To evaluate the inhibitory effect of vitamin C on the experimental esophageal carcinogenesis induced by diethylnitrosamine (NDEA). METHODS: Sixty Wistar male rats aged three months, with mean weight of 210 g were employed in the study and were divided into four different groups according to the drinking drugs: group I - controls: only water, seven days a week; group II - only vitamin C, seven days a week; group III - NDEA, three days a week and water during the other four days; group IV - NDEA, three days a week and vitamin C during the other four days; group V - NDEA together with vitamin C three days a week, and only water during the other four days and group VI - NDEA together with vitamin C three days a week and vitamin C during the other four days. The dosages of NDEA were: - 10 mg. / Kg / day and vitamin C - 200 mg / animal / day, dissolved in drinking water. The animals were observed during 180 days and after that each one was sacrificed and its esophagus and the stomach were removed together and macro and microscopically analyzed to identify any tumors. RESULTS: The largest number of tumors was observed in the group III: 48 macroscopic lesions (4.8 lesions per animal) and 23 microscopic lesions (2.3 lesions per animal). The groups that received vitamin C (groups IV, V and VI) showed smaller number of tumors: group V - 0.5 macroscopic lesions and 0.3 microscopic lesions per animal and group VI - 0.1 macroscopic lesions and 0.1 microscopic lesions per animal. The incidence of tumors in the groups V and VI showed statistical significance (p<0.05), when compared to the other groups. CONCLUSION: The vitamin C administered together with diethylnitrosamine showed an inhibitory effect on the experimental esophageal carcinogenesis in Wistar rats.

OBJETIVO: Avaliar o efeito inibidor da vitamina C na carcinogênese esofágica experimental induzida pela dietilnitrosamina (DEN). MÉTODOS: Sessenta ratos Wistar, com idade de três meses, machos, com peso médio de 210 g foram utilizados no estudo e divididos em quatro grupos diferentes, conforme ingestão das drogas: grupo I - controles: ingerindo água sete dias por semana; grupo II - só vitamina C, sete dias por semana; grupo III - DEN, três dias por semana e água durante os outros quatro dias; grupo IV - DEN, três dias por semana e vitamina C durante os outros quatro dias; grupo V - DEN junto com vitamina C três dias por semana, e água os outros quatro dias e grupo VI - DEN junto com vitamina C três dias por semana e só vitamina C durante os outros quatro dias. As dosagens de DEN empregadas foram - 10 mg. / Kg / dia e de vitamina C - 200 mg / animal / dia, dissolvidos na água de beber. Os animais foram observados durante 180 dias e depois disso sacrificados, tiveram o seu esôfago e o estômago retirados, e macro e microscòpicamente analisados para identificar qualquer tumor. RESULTADOS: O número maior de tumores foi observado no grupo III: 48 lesões macroscópicas (4.8 lesões por animal) e 23 lesões microscópicas (2.3 lesões por animal). Os grupos que receberam vitamina C (grupos IV, V e VI) evidenciaram número menor de tumores: grupo V - 0.5 lesões macroscópicas e 0.3 lesões microscópicas por animal e grupo VI - 0.1 lesões macroscópicas e 0.1 lesões microscópicas por animal. A incidência de tumores nos grupos V e VI mostraram diferença estatística significa (p <0.05), quando comparados aos outros grupos. CONCLUSÃO: A vitamina C administrada junto com dietilnitrosamina mostrou efeito inibidor no aparecimento de tumores esofágicos.

Rutina: estrutura, metabolismo e potencial farmacológico / Rutin: estructure, metabolism and pharmacological potency

Os Flavonóides são substâncias naturais amplamente distribuídas no Reino Vegetal. Há um interesse crescente na investigação dessas substâncias, devido ao volume de evidência dos benefícios que eles proporcionam para a saúde. A Rutina é um flavonol glicosídico pertencente a uma importante classe de Flavonóides, sendo extensamente encontrados na natureza, em frutas, vegetais e bebidas como chá e vinho. Pouco se sabe sobre a farmacocinética e biodisponibilidade da rutina, e estes mecanismos tem sido foco de muita controvérsia. Apesar disso, a Rutina apresenta grande importância terapêutica por melhorar a resistência e permeabilidade dos vasos capilares, atividades antioxidante, antiinflamatória, anticarcinogênica dentre outras, razão que levou à realização da presente revisão.

Flavonoids are natural products widely distributed in the vegetable kingdom. There has been increasing interest in research of flavonoids, due to growing evidence of the health benefits of them. Rutin is a glycoside flavonol which belongs to an important class of flavonoids, being extensively found in the nature in fruit, vegetable and beverages, such as tea and wine. About the pharmacokinetics and bioavailability of Rutin, little is stil know, and tis mechanisms have been a matter of much controversy. Dispite it, Rutin presents a therapeutical importance due to improve resistance and permeability of capillaries vessels, antioxidante, antiinflamatory, anticarcinogenic and other important activities. Reason that led to the completion of this review.

Effect of black tea in diethylnitrosamine-induced esophageal carcinogenesis in mice / Efeito do chá preto sobre a carcinogênese esofágica induzida por dietilnitrosamina em camundongos

PURPOSE: To evaluate the effect of black tea on esophageal carcinogenesis induced by the oral administration of diethylnitrosamine (DEN). METHODS: A population of 120 female mice (Mus musculus, strain CF1) were studied for 160 days. The animals were assigned to two control groups and three treatment groups. The control groups received water or tea throughout the study period, while the three experimental groups received DEN weekly, for three consecutive days, and water, tea, or both, in the other days of the week. On completion of the 160-day period, the animals were killed and their esophagi promptly examined macroscopically and subsequently submitted to histopathology (using the hematoxylin-eosin technique). RESULTS: In the comparative analysis between the treatment groups, tumor incidence (macroscopy) was significantly lower in those animals that received black tea besides the carcinogen. As regards the histopathologic changes, there was a greater number of low grade epithelial lesions in the same groups (p < 0.001). CONCLUSION: The animals that received black tea had a lower incidence of effects related to the carcinogen's action, thus indicating that, in this model, the infusion had a significant chemoprophylactic effect on experimental diethylnitrosamine-induced carcinogenesis.

OBJETIVO: Avaliar o efeito do chá preto sobre a carcinogênese esofágica experimental induzida pela administração oral de dietilnitrosamina (DEN). MÉTODOS: Durante 160 dias foi estudada uma população de 120 camundongos fêmeas, gênero Mus musculus, da cepa CF1, dividida em dois grupos controles e três grupos de tratamento. Os grupos controles receberam água ou chá durante todo o período do estudo. Os três grupos tratados receberam DEN semanalmente, durante três dias consecutivos, e água, chá ou ambos, nos demais dias da semana. Ao completar o período de 160 dias foram efetuadas as eutanásias dos animais e seus esôfagos foram analisados macroscopicamente (a fresco) e, posteriormente, à histopatologia (empregando a técnica da hematoxilina e eosina - HE). RESULTADOS: Na análise comparativa entre os grupos de tratamento, a incidência tumoral (macroscopia) foi significativamente menor naqueles animais que receberam chá preto, além do carcinógeno. No que se refere às alterações histopatológicas, houve maior número de lesões epiteliais de baixo grau nesses mesmos grupos (p < 0,001). CONCLUSÃO: Os animais que receberam chá preto apresentaram menor incidência dos efeitos relacionados à ação do carcinógeno, indicando que, neste modelo, a infusão apresentou efeito quimioprofilático significativo sobre a carcinogênese experimental induzida pela dietilnitrosamina.

Suppression of prostate cancer growth by resveratrol in the transgenic rat for adenocarcinoma of prostate (TRAP) model.

Research into actions of resveratrol, abundantly present in red grape skin, has been greatly stimulated by its reported beneficial health influence. Since it was recently proposed as a potential prostate cancer chemopreventive agent, we here performed an in vivo experiment to explore its effect in the Transgenic Rat for Adenocarcinoma of Prostate (TRAP) model, featuring the rat probasin promoter/SV 40 T antigen. Resveratrol suppressed prostate cancer growth and induction of apoptosis through androgen receptor (AR) down-regulation, without any sign of toxicity. Resveratrol not only downregulated androgen receptor (AR) expression but also suppressed the androgen responsive glandular kallikrein 11 (Gk11), known to be an ortholog of the human prostate specific antigen (PSA), at the mRNA level. The data provide a mechanistic basis for resveratrol chemopreventive efficacy against prostate cancer.