Expresión de E-cadherina y factor de crecimiento epidérmico en leucoplasias orales / Expression of E-cadherin and epidermal growth factor in oral leukoplakia

Introducción: se define a las leucoplasias orales como una placa blancaque no puede desprenderse por raspado y que no puede clasifi carse comoninguna otra lesión. Son lesiones con potencial maligno, relacionadascon la presencia de displasia epitelial. Estos cambios preneoplásicospueden ser evidenciados histológicamente como también a travésde técnicas que pongan en evidencia los diferentes cambios a nivelmolecular. La E-cadherina es una glicoproteína membranosa quedesempeña papeles importantes en el mantenimiento de la adhesióncélula-célula, la preservación de la polaridad del tejido epitelial y laintegridad estructural. Los factores de crecimiento epidérmico son unconjunto de moléculas de naturaleza proteica, biorreguladores, cuyafuncionalidad fundamental radica en el control del ciclo celular. Elobjetivo del presente trabajo es identifi car y comparar parámetros histológicosy moleculares predictores de riesgo de transformación malignaen leucoplasias orales. Material y métodos: El estudio correspondea un diseño observacional descriptivo. Se seleccionaron muestras de26 biopsias de leucoplasias orales, las cuales fueron evaluadas contécnica histológica de rutina y tinción con hematoxilina y eosina, luegosometidas a inmunomarcación con factor de crecimiento epidérmico yE-cadherina, donde se evaluó la intensidad de tinción y cambios en laexpresión de cada marcador, así como la localización en los diferentessubtipos celulares. Resultados: De las 26 leucoplasias observadas,16 mostraron histología con cambios hiperplásicos y 10 con cambiosdisplásicos leves a moderados. La expresión de E-cadherina no mostróalteraciones signifi cativas en leucoplasias sin displasia, sólo hubopérdida de expresión en aquellas leucoplasias con cambios displásicosde alto grado, en concordancia a los hallazgos histológicos...

Introduction: oral leukoplakia is defined as a white plaque thatcannot be removed by scraping and cannot be classifi ed as any otherdisease entity. They are potentially malignant lesions related to thepresence of epithelial dysplasia. These preneoplastic changes can bedetected histologically, as well as through techniques that demonstratediff erent changes at the molecular level. E-cadherin is a membraneglycoprotein that plays a major role in maintaining cell-cell adhesion,preserving structural integrity and the polarity of epithelial tissue.Epidermal growth factors are a group of bio-regulatory proteins,whose primary function is to control the cell cycle. The aim of thisstudy is to identify and compare the parameters for histological andmolecular markers for malignant transformation in oral leukoplakia.Material and methods: The study was observational and descriptive indesign. Samples were selected from 26 oral leukoplakia biopsies, whichwere routinely evaluated for histology and stained with hematoxylinand eosin, then subjected to immunostaining with epidermal growthfactor and E-cadherin, with the intensity of staining and changes inthe expression of each marker being evaluated. Results: Of the 26leukoplakia examined, 16 showed hyperplastic changes and 10 mildto moderate dysplastic changes. The expression of E-cadherin showedno signifi cant changes in non-dysplastic leukoplakia, while a lossof expression was found in only those leukoplakias with high-gradedysplastic changes, which was consistent with the histological fi ndings...

Cancer stem cell: A rogue responsible for tumor development and metastasis.

Cancer stem cells are a small population of cells in a tumor. They have the ability to self-renew and maintain the tumor. The most apt and accepted hypothesis for tumor development is Cancer Stem Cells. This review focuses on this concept of cancer stem cells, serving their purpose and leading to the development of tumor. There are many cell biomarkers which have been described for the identification and characterization of cancer stem cells. The most prominent of the cellular markers for the detection of cancer stem cells; CD133, CD44, ALDH-1 along with some others have been discussed in detail in this review.

A review of Indian literature for association of smokeless tobacco with malignant and premalignant diseases of head and neck region.

In India, about 60% of tobacco users use smokeless tobacco (ST) alone. Head and neck squamous cell carcinoma is one of the most common cancers in India. International Agency for Research on Cancer (IARC) monograph (Vol 89) found a significant association between ST use and oral cancer. However, only a few articles from India were included in this monograph. To overcome this lacuna, we have reviewed the articles published from India investigating the association between ST use and malignant and premalignant diseases of head and neck region. Data collection has been performed by computer-aided search of the MedLine and PubMed databases using different combinations of the key words. For malignant lesions, only cohort and case control studies were considered for review. For premalignant lesions and dental diseases other than case control studies, some cross-sectional studies have also been reviewed. Studies found a significant association between ST use and cancer of the oral cavity. The association was stronger for the buccal mucosa compared to tongue and for females compared to males. Significant association noted between cancer of the hypopharynx and oropharynx with ST use but no definitive association noted for cancer of the larynx and nasopharynx. Some dental disease and oral premalignant conditions were also associated with ST use. Indian studies suggest ST use is strongly associated with cancer of the oral cavity, oropharynx and hypopharynx.

Repercussão hepática da carcinogênese colorretal induzida pelo azoximetano / Hepatic repercussions of azoxymethane-induced colorectal carcinogenesis

OBJETIVO: Avaliar as repercussões hepáticas da carcinogênese colônica induzida por diferentes doses e tempos de exposição ao azoximetano em ratos Wistar. MÉTODOS: Quarenta e quatro ratos foram distribuídos em quatro grupos. Os animais tinham oito semanas no início do experimento. No grupo 1, receberam 1.0mL de solução salina intraperitonealmente uma vez por semana por duas semanas. No grupo 2, receberam 15 mg/kg de azoximetano intraperitonealmente uma vez por semana por duas semanas. Esses animais foram mortos na 15ª semana do experimento. Os animais do grupo 3 receberam solução salina intraperitonealmente uma vez por semana por duas semanas. Os animais do grupo 4 receberam 20mg/kg de azoximetano intraperitonealmente uma vez por semana por duas semanas. Esses animais foram mortos na 26ª semana do experimento. Os fragmentos de tecido hepático foram corados pela hematoxilina e eosina e avaliadas microscopicamente. RESULTADOS: Grupo 1 e grupo 2 diferiram significantemente em relação a esteatose, mas não houve diferença entre o grupo 3 e o grupo 4. No entanto, no grupo 4 foram observadas lesões pré-neoplásicas (focos de células alteradas, claras, vacuoladas, basofílicas, anfofílicas, tigróides, oncocíticas, pequenas ou acidófilas, espongioses e pelioses) e lesões neoplásicas (colangiomas e adenomas) contendo hepatócitos atípicos de permeio, não identificados no grupo 3. CONCLUSÃO: No modelo de carcinogênese colorretal, lesões hepáticas pré-neoplásicas e neoplásicas aparecem e evoluem na proporção do tempo e dose de exposição ao azoximetano.

OBJECTIVE: To evaluate the hepatic effects of colonic carcinogenesis induced by azoxymethane at different doses and times of exposure in rats. METHODS: Forty-four Wistar rats were divided into four groups. The animals were eight weeks at the beginning of the experiment. group 1 received 1.0ml of saline intraperitoneally once a week for two weeks. Group 2 received 15 mg/kg of azoxymethane intraperitoneally once a week for two weeks. These animals were killed at the 15th week of the experiment. The animals of group 3 received saline intraperitoneally once a week for two weeks. Group 4 animals received 20mg/kg of azoxymethane intraperitoneally once a week for two weeks. These animals were killed at the 26th week of the experiment. The fragments of liver tissue were stained with hematoxylin and eosin and evaluated microscopically. RESULTS: Groups 1 and 2 differed significantly in relation to steatosis, no difference having been found between group 3 and group 4. However, in group 4 we observed pre-neoplastic lesions (foci of altered, clear, vacuolated, basophilic, amphophilic tigroid, oncocytic, small or acidophilus cells, spongiosis and peliosis) and neoplastic lesions (adenomas and colangiomas) containing atypical hepatocytes in between, not identified in group 3. CONCLUSION: In the model of colorectal carcinogenesis, preneoplastic and neoplastic hepatic lesions appear and evolve in proportion to the time of exposure and dose of azoxymethane.

Epidemiologia da infecção pelo HPV em mulheres infectadas pelo HIV / Epidemiology of HPV infection in women infected by HIV

A infecção pelo papilomavírus humano (HPV) é um importante fator de risco para o desenvolvimento de lesões pré-neoplásicas e neoplásicas do colo uterino, com maior chance de desenvolvimento em portadoras do HIV (vírus da imunodeficiência humana), em decorrência da imunossupressão. A alta prevalência de lesões intraepiteliais escamosas (SIL - squamous intraepithelial lesion) associadas ao HPV, em mulheres infectadas pelo HIV, sugere que a resposta imune do hospedeiro desempenha um papel importante no desenvolvimento do câncer cervical associado ao HPV. Mulheres HIV positivas apresentam alta prevalência de DNA do HPV, de câncer cervical e de SIL. A infecção pelo HIV resulta em uma progressiva perda de células TCD4+, a qual, por sua vez, está associada a um aumento na prevalência das infecções pelo HPV, levando a uma maior persistência da infecção e do risco aumentado para o desenvolvimento de câncer cervical. Nas mulheres infectadas pelo vírus HIV, as infecções são mais persistentes e geralmente apresentam múltiplos genótipos do HPV, sendo os tipos oncogênicos os mais prevalentes. O objetivo deste estudo foi revisar o corrente conhecimento sobre a associação existente entre a infecção pelo HPV nas mulheres infectadas pelo HIV, analisando os aspectos epidemiológicos da coinfecção HPV e HIV.

The human papillomavirus (HPV) infection is an important risk factor for the development of pre-neoplasics and neoplasics cervix lesions, with higher possibility of development in HIV (human immunodeficiency virus) carriers, as a result of the immunossupression. The high prevalence of squamous intraepithelial lesions (SIL) associated with HPV, in women infected by HIV, suggests that the immune response of the host plays an important role in the development of the cervical cancer associated with HPV. Women with HIV presents high DNA of the HPV, cervical cancer, and SIL. The HIV infection result in a gradual loss of TCD4+ cells, which, in turn, is associated with an increase in the prevalence of HPV infections, leading to a higher persistence of the infection and increased risk for the development of cervical cancer. In women infected by HIV, the infections are more persistent and generally presents multiple genotypes of the HPV, being most prevalent the oncogenics types. The aim of this study was to revise the current knowledge on the existing association between HPV infection in women infected by HIV, analyzing the epidemiologic aspects of the HPV and HIV coinfection.

Indicadores de riesgo en pacientes etilistas - fumadores: estudio preliminar / Risk indicators in drinker - smoker patients: preliminary study

Lesiones precancerosas y cáncer bucal están frecuentemente asociados en su etiología al tabaco y al alcohol. En este trabajo evalúanse las alteraciones citológicas en 19 pacientes con adicción tabaco alcohol que no presentan lesiones orales clínicas manifiestas en relación con la intensidad de dichos factores de riesgo, incluyéndose un grupo de control que no desarrollaba ninguno de los hábitos mencionados precedentemente. Se realizaron exámenes estomatológicos que incluían un interrogatorio sobre hábitos. En todos los pacientes se tomaron muestras por técnica de raspado de mucosa yugal, dorso de lengua y piso de boca. Los extendidos se fijaron en alcohol 95º y coloreados mediante técnica estándar de Papanicolaou, fueron evaluados según presentasen alteraciones o modificaciones -citoplasmáticas y nucleares - en escamas, hipercromasia y cariomegalia, que la relacionaron con indicadores de riesgo paquete/año; alcohol/año y un índice combinado tabaco-alcohol/año. Los resultados obtenidos revelaron que del grupo etilista fumadores 7 (37 por ciento) pacientes presentaban alteraciones citoplasmáticas y nucleares, de ellos 3 (16 por ciento) con cariomegalia, presentaban indicadores tabaco-alcohol/año superiores al valor promedio para dicho grupo, no observándose modificaciones de ningún tipo en el grupo testigo. En un significativo porcentaje de pacientes alcoholistas-fumadores, se observaron alteraciones nucleares mínimas que podrían considerarse como estadíos previos a lesiones precancerosas, que en relación a los indicadores propuestos servirían para prevenir y detectar precozmente la aparición de dichas lesiones, si bien un número mayor de casos deberían ser estudiados para confirmar esta observación incial.

Precancerous and cancerous lesions of oral mucosa are frequently by associated in their etiology to tobacco and alcohol intake, In this presentation the cytological alterations of 19 patients addicted to tobacco and alcohol without clinical evidence of disease related to the intensity of these habits were evaluated. A control group without any of these habits was included. The clinical examinations included all pertinent clinical data and samples from yugal mucosa, dorsal aspect of tongue and floor of the mouth were taken in each patients. The smears were fixed in 95 per cent alcohol, stained according the Papanicolaou technique and evaluated according the presence of squames, hiperchromasia and cariomegaly and their relationship to risk indicators such as tobacco pack / year; alcohol /year and combined index of tobacco-alcohol /year. The obtained results revealed that 7 (37 per cent) patients of the alcohol tobacco group presented cytoplasmic and nuclear changes and 3 (16 per cent) of them with cariomegaly presented indicators of tobacco-alcohol / year higher to the average for that group while no changes of any type were observed in the control group. In a significant percentage of alcoholic-smoker patients minimal nuclear changes that could be considered as previous stages to precancerous lesions were observed. These observations related to the proposed indicators could be useful to prevent and detect increment changes, although a larger number of cases should be evaluated to confirm this initial observation.

Actinic lesions in fishermen's lower lip: clinical, cytopathological and histopathologic analysis

INTRODUCTION: Actinic cheilitis (AC) is considered to be a pre-malignant lesion or an incipient and superficial form of lip squamous cell carcinoma. It is commonly found in individuals whose occupational activities are related to chronic sun exposure and the definitive diagnosis is performed with biopsy. Althoug Exfoliative cytology has been used as a screening procedure to evaluate cancer of the oral cavity no studies have proposed the use of exfoliative cytologic analysis to evaluate and diagnose AC. OBJECTIVE: The purpose of this study was to evaluate lower lip lesions on fishermen related to chronic solar exposure using clinical, cytologic and histopathologic analyses. PATIENTS AND METHODS: Smears taken from the vermilion of the lower lips of 125 fishermen and 30 control individuals were subjected to cytologic analysis. RESULTS: The harvested cells were sufficient for cytologic analysis in 83.2 percent of the samples. Sixteen fishermen exhibited prominent lower lip lesions that justified biopsy and histological studies. In total, 4 specimens were malignant (3.2 percent), and 12 displayed epithelial dysplasia, demonstrating that the prevalence of epithelial dysplasia and malignant lesions was high among the fishermen population. These conditions were strongly associated with infiltration and blurring of the vermilion margin of the lower lip. CONCLUSION: The cytologic analysis was not useful for detecting epithelial dysplasia or malignant alterations.

Pituitary toxicity but lack of rat colon carcinogenicity of a DC-magnetic field in a medium-term bioassay.

The present study was designated to evaluate the effect of direct current induced permanent magnetic field (DC-MF) on chemically induced rat colon carcinogenesis. Five experimental groups of male S.D. rats were injected with 1,2-dimethylhydrazine (DMH) subcutaneously, 20 mg/kg b.wt., once a week for four weeks, with exposure to 1 mT DC-MF (12 hours/day) as follows: Before (pre) the carcinogen administration (group 1), simultaneously (group 2), after (post) the carcinogen administration (group 3) and daily from the beginning to the end of the experiment after 12 weeks (group 4). Rats of group 5 served as carcinogen-only treated controls while those of group 6 were non-treated controls. There were no differences in the incidences and multiplicities of colonic aberrant crypt foci (ACF), putative preneoplastic lesions, among all groups except that large foci in group 1 were significantly fewer in numbers than those found in group 5. Proliferating cell nuclear antigen labeling indexes (PCNA-LI) in the colon epithelium were essentially the same in MF-treated and control rats. Histopathological examination showed evident hemorrhage in the pituitary glands of some rats of groups 1-3, and in most rats of group 4. Transmission electron microscopy also revealed ultrastructural changes, but DNA ploidy analysis revealed no carcinogenicity to MF-exposed pituitary glands. Serum levels of AST, ALT, total protein, creatinine, albumin, albumin/globulin ratio and growth hormone levels did not change among the groups. The present study revealed that the action of an artificial MF on rats is not carcinogenic/or cancer-promoting, at least in the present protocol for colon carcinogenesis.

Recurrent endocervical-like mucinous borderline tumor (ELMBT) arising in a case of long-standing endometriosis--a case report.

Endometriosis is a well-known precursor lesion of ovarian malignancies, particularly those of endometrioid and clear-cell types and rarely of serous or mucinous types. The association of endometriosis with mucinous borderline tumors also varies. This case is of a 60 year old female, who had a long history of more than thirty years of endometriosis and developed recurrent endocervical-like mucinous borderline tumor (ELMBT) in endometriotic foci. This case highlights challenges in the management of such complications associated with endometriosis and emphasizes the importance of long-term follow-up in cases of endometriosis.

Lesiones intraepiteliales de cuello uterino: marcadores bioquímicos y virus de papiloma humano / Intraepithelial lesions of the uterine cervix: biochemical markers and human papillomavirus

Con el fin de establecer el valor de ciertos marcadores indicadores del grado de evolución de las neoplasias intraepiteliales cervicales (CIN), se realizó la determinación de glucosa-6-fosfato deshidrogenasa (G6PDH) por enzimoquímica y de antígeno carcinoembrionario (CEA) por inmunomarcación en biopsias y extendidos citológicos, procedentes de cervix uterinos en casos de infección por virus de papiloma humano (HPV) y de CIN de diferentes grados (CIN 1 a CIN 3). La actividad de G6PDH, ensayada en células exfoliadas, fue en aumento desde CIN 1 a CIN 3, donde alcanzó el nivel 3+ en una escala fijada con un máximo de 4+ para el carcinoma pavimentoso. El CEA, demostrado en cortes histológicos y en células exfoliadas de diversas patología de cérvix uterino, varió desde 1+ en las lesiones de bajo grado hasta 3+ en las de alto grado. De los datos obtenidos en G6PDH y CEA, podría inferirse que las lesiones intraepiteliales de cérvix uterino se suceden en forma continua desde la lesión viral hasta CIN 3. Se realizó la tipificación de HPV mediante hibridación in situ. En los condilomas y CIN 1 fue detectado HPV 6/11 episomal y en los CIN 2 se encontraron tipos virales de moderado y alto riesgo predominantemente libres. Todos los CIN 3 fueron positivos para HPV 16/18 en estado integrado. Sin embargo, la presencia de HPV 16/18 no sería un factor por sí mismo suficiente para la completa transformación celular, aunque su presencia sea necesaria para la promoción de la neoplasia cervical

Pesquisaje de lesiones precancerosas y cancerosas del colon en los trabajadores del asbesto / Screening of precancerous and cancerous lesions of the colon in asbestos-cement exposed workers

Se realizo un pesquisaje mediante la aplicacion de la prueba de sangre oculta en heces fecales y colonoscopia a los trabajadores de la Fabrica de Asbesto-Cemento "Armando Mestre" de Ciudad de la Habana. De los 400 trabajadores con que cuenta la fabrica fueron encuestados 272, de los cuales solo161 (59,1 por ciento), acudieron a entregar las heces fecales para la determinacion de sangre oculta. La prueba fue positiva en el 19,8 por ciento, es decir, 32trabajadores de estos 161. De los casos positivos solo 16 aceptaron hacerse la colonoscopia, y en 6 de ellos (37,5 por ciento) se encontraron polipos. De estosultimos 2 presentaron lesiones multiples y 4, lesiones unicas. El estudio histologico mostro que todos los polipos eran adenomas y 2 de ellos presentaban displasias. Ninguno de los trabajadores con polipos tenia evidencias de sangramiento rectal, ni aun los que presentaban lesiones mayores de 1 cm. No se observo cancer de colon en este pesquizaje. Por los resultados de nuestro trabajo no parece existir relacion entre la presencia o no de polipos y los anos de exposicion al asbesto

Smokeless tobacco and premalignant and malignant lesions of the oral cavity.

The paper compares the prevalence of oral carcinoma and dysplasia in smokeless tobacco users and non users. A total of 3205 subjects were studied. Of the smokeless tobacco users, 1.96 percent had oral carcinoma compared with 0.36 percent of non-users. The prevalence of oral dysplasia in the users' group was 14.4 percent as compared with 6.85 percent in the group of non-users.

Consideraçöes sobre as lesöes precursoras do câncer da vagina / Vaginal precancerous lesions

Säo tecidas consideraçöes sobre as lesöes precursoras dos dois carcinomas mais freqüentes da vagina: o denocarcinoma de células e o carcinoma epidermóide. Ressalta-se a adenose de vagina e sua provável relaçäo, em pequena porcentagem de casos, com o adenocarcinoma de células claras, em mulheres expostas intra-útero ao dietilestilbestrol. A seguir, descarta-se como precursora do carcinoma espinocelular a maioria das condiçöes já estudadas neste sentido. Säo referidas recentes publicaçöes que demonstram o aparecimento de neoplasias intra-epiteliais da vagina do tipo escamoso em focos de adenose vaginal. Por fim, levanta-se a hipótese de que as rara glândulas presentes na vagina de uma minoria de mulheres näo expostas intra-útero poderiám ser, em nosso meio, a lesäo precursora do carcinoma epidermóide de vagina

Aspectos biopsicosociales y epistemológicos en la investigación del cáncer / Biopsychosocial and epistemological aspects in cancer research

El cáncer muestra variabilidad epidemiológica en términos geográficos, étnicos y de clase social. Estas variaciones pudieron ser debidas a una combinación de factores genéticos, étnicos y socioeconómicos. No se ha podido demostrar que los factores psicosociales puedan determinar por sí mismos el origen de la neoplasia, ni tampoco afectar el pronóstico una vez que se establece el diagnóstico de acuerdo con los criterios anatomopatológicos. Una de las áreas que más promete y podría mejorar los aspectos preventivos es la bioquímica de los elementos nutritivos. Desde luego, la abstinencia de alcohol y de tabaco debe incluirse en cualquier programa de prevención a nivel primario. Las hipótesis que postulan conflictos psicológicos en la etiología del cáncer, y las que incluyen grados de sociabilidad como factores involucrados, deben examinarse en su propio contescto y considerarse en conjunto cuando se evalúan programas integrales de manejo del paciente oncológico. En otras palabras, el psiquiatra debe compenetrarse de la problemática psicosocial del paciente para auxiliar mejor al oncólogo durante las consultas psiquiátricas. El banefício que pueden obtener los pacientes de la psicofarmacología y de otras terapia biológicas, está fuera de discusión. Los nuevos descubrimientos en el área de la genética y la virología probablemente aumentarán la participación de los psiquiatras en los programas de atención integral al paciente oncológico