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RFO UPF ; 28(1): 115-131, 20230808.
Article in Portuguese | LILACS, BBO | ID: biblio-1509418


Objetivos: Instruir e orientar ao cirurgião dentista e demais profissionais de saúde a importância da detecção e rastreio precoce de lesões pré-malignas. Revisão de Literatura: O Líquen Plano Oral é uma condição dermatológica crônica, de origem auto-imune, relativamente comum na população, que atinge o epitélio de mucosa e pele, sendo considerada, pela Organização Mundial de Saúde (OMS), uma desordem potencialmente maligna quando associado a áreas de ulceração. A revisão de literatura foi realizada nas bases de dados PubMed e Lilacs. Buscamos investigar o potencial de malignização do Líquen Plano Oral associado a condições erosivas, analisando o processo de carcinogênese no processo inflamatório. Conclusão: Conclui-se que o objeto de estudo ainda é um assunto pouco explorado pela literatura, porém há indícios etiopatológicos que enfatizam o processo de malignização oriundo de uma lesão pré-maligna como o Líquen Plano Oral. Além disso, enfatizamos a importância do diagnóstico precoce das lesões estomatognáticas, para que assim possamos aumentar as chances de cura do paciente.(AU)

Objectives: To instruct and guide dentists and other health professionals on the importance of early detection and screening of pre-malignant lesions. Literature Review: Oral Lichen Planus is a chronic dermatological condition, of autoimmune origin, relatively common in the population, which affects the epithelium of the mucosa and skin, being considered, by the World Health Organization (WHO), a potentially fatal disorder. malignant when associated with areas of ulceration. A literature review was performed on the PubMed and Lilacs databases. We sought to investigate the potential for malignancy of Oral Lichen Planus associated with erosive conditions, analyzing the process of carcinogenesis in the inflammatory process. Conclusion: It is concluded that the object of study is still a subject little explored in the literature, but there are etiopathological accusations that emphasize the process of malignancy arising from a pre-malignant lesion such as Oral Lichen Planus. In addition, we emphasize the importance of early diagnosis of stomatognathic lesions, so that we can increase the patient's chances of cure.(AU)

Humans , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Cell Transformation, Neoplastic/pathology , Lichen Planus, Oral/pathology , Mouth Neoplasms/diagnosis , Carcinoma, Squamous Cell/diagnosis , Lichen Planus, Oral/diagnosis , Early Detection of Cancer
Braz. oral res. (Online) ; 34: e052, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1132707


Abstract The purpose of this study was to analyze the differential expression of DEC1 in oral normal mucosa (NM), oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Surgically excised specimens from patients with OLK (n = 47), OSCC (n = 30) and oral normal mucosa (n=11) were immunostained for DEC1. The expression of DEC1 protein was evaluated, and its association with the clinicopathological features was analyzed. The expression of DEC1 in NM, OLK and OSCC tissues increased in turn, and significant differences were observed among the groups (P < 0.0001). In terms of the association between DEC1 expression and epithelial dysplasia, DEC1 expression was lower in hyperkeratosis without dysplasia (H-OLK) than in OLK with moderate to severe dysplasia (S-OLK), and these differences were significant (p < 0.05). The expression of DEC1 in OSCC with OLK was significantly higher than that in OSCC without OLK (p < 0.01). Therefore, DEC1 could be a potential biomarker of malignant transformation in the carcinogenesis of OSCC, which may provide a new research direction for the transformation of oral potentially malignant disorders (OPMDs) into OSCC.

Humans , Male , Female , Adult , Aged , Aged, 80 and over , Leukoplakia, Oral/pathology , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Tumor Suppressor Proteins/analysis , Reference Values , Immunohistochemistry , Biomarkers, Tumor/analysis , Cell Transformation, Neoplastic/pathology , Reproducibility of Results , Risk Factors , Analysis of Variance , Age Factors , Statistics, Nonparametric , Middle Aged
Medicina (B.Aires) ; 79(1): 67-70, feb. 2019. ilus
Article in Spanish | LILACS | ID: biblio-1002590


Los teratomas son tumores germinales malignos compuestos por dos o más capas de tejido, que ocasionalmente se transforman en estirpes con crecimiento agresivo. Se presenta el caso de un paciente de 29 años con un tumor germinal gonadal localizado en testículo, cuya evolución fue desfavorable por presentar transformación en un fenotipo correspondiente a un rabdomiosarcoma. La patología aquí descripta deviene del crecimiento diferencial de un componente ya existente en el tumor original o la transformación en un linaje somático que se hace dominante. Los tumores transformados como el del caso descripto son raros y presentan características diferentes de la mayoría de las neoplasias germinales respecto del comportamiento, el pronóstico y la sensibilidad a los tratamientos establecidos.

Teratomas are malign germ cell tumors composed of two or more tissue layers. When there is specific organ differentiation they are called mature teratoma. They rarely grow aggressively. We report the case of a 29 year-old man with a diagnosis of gonadal germ cell tumor whose evolution was unfavorable owing to transformation into a different phenotype corresponding to a rhabdomyosarcoma. This phenomenon occurs through differential growth of a single histological component of the original tumor or transformation of a somatic lineage that becomes dominant. Transformed tumors such as the one herein described differ from most germ cell neoplasms regarding behavior, prognosis, and susceptibility to established treatments.

Humans , Male , Adult , Rhabdomyosarcoma/pathology , Teratoma/pathology , Testicular Neoplasms/pathology , Cell Transformation, Neoplastic/pathology , Neoplasms, Gonadal Tissue/pathology , Teratoma/drug therapy , Testicular Neoplasms/drug therapy , Fatal Outcome
Journal of Zhejiang University. Science. B ; (12): 39-48, 2019.
Article in English | WPRIM | ID: wpr-1010442


Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.

Animals , Cattle , Female , Carcinogenesis/pathology , Cell Cycle Proteins/metabolism , Cell Proliferation/drug effects , Cell Transformation, Neoplastic/pathology , Cells, Cultured , Epithelial Cells/pathology , Histone Deacetylase 2/metabolism , Imatinib Mesylate/pharmacology , Interferon-gamma/pharmacology , Mammary Glands, Animal/pathology , Mammary Neoplasms, Experimental/pathology , Proto-Oncogene Proteins c-abl/metabolism , Signal Transduction , Valproic Acid/pharmacology
São Paulo med. j ; 136(6): 586-590, Nov.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-991690


ABSTRACT BACKGROUND: Malignant transformation of endometriosis in the abdominal wall is a rare and still poorly understood event. Less than 30 cases have been reported in the worldwide literature. Most cases of solid tumors are report in a previous abdominal scar with malignant transformation of a focus of endometriosis. Presence of lymph node metastases in nearby chains is frequent and is associated with poor prognosis. CASE REPORT: We report a case of a 42-year-old woman with a history of abdominal surgery (Pfannenstiel) to resect abdominal wall endometriosis. Physical examination revealed a solid mass of approximately 10 cm x 6 cm in the anterior wall of the abdomen. Computed tomography (CT) of the abdomen and pelvis showed a heterogeneous, predominantly hypoattenuating expansive formation measuring 10.6 cm x 4.7 cm x 8.3 cm. The patient underwent exploratory incisional laparotomy, block resection of the abdominal mass and lymphadenectomy of the external and inguinal iliac chains. The abdominal wall was reconstructed using a semi-absorbable tissue-separating screen to reconstitute the defect caused by resection of the tumor. Histological evaluation revealed infiltration by malignant epithelioid neoplasia, thus confirming the immunohistochemical profile of adenocarcinoma with clear cell components. Lymphadenectomy showed metastatic involvement of an external iliac chain lymph node. CONCLUSION: Resection of the mass along with the abdominal wall, with wall margins, is the most effective treatment. Reconstruction is a challenge for surgeons. The patient has been followed up postoperatively for eight months, without any evidence of disease to date.

Humans , Female , Adult , Cell Transformation, Neoplastic/pathology , Adenocarcinoma, Clear Cell/etiology , Endometriosis/complications , Lymphatic Metastasis/pathology , Abdominal Neoplasms/etiology , Tomography, X-Ray Computed , Adenocarcinoma, Clear Cell/surgery , Adenocarcinoma, Clear Cell/pathology , Neoadjuvant Therapy , Abdominal Wall/surgery , Lymph Node Excision , Abdominal Neoplasms/surgery , Abdominal Neoplasms/pathology
Int. j. odontostomatol. (Print) ; 12(3): 237-245, Sept. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-975740


RESUMEN: Este estudio pretendió describir las características sociodemográficas y clínicas de los pacientes tratados por primera vez por cáncer escamocelular oral (CEB) en Medellín (Colombia). Para ello se realizó un estudio descriptivo anidado en una cohorte dinámica retrospectiva de casos de CEB, procedente de 9 centros oncológicos especializados de la ciudad entre 2000 y 2011, según la información de las historias clínicas y clasificadas según la CIE-10. Se recolectaron variables sociodemográficas y clínicas como: tratamiento recibido, localización del tumor, estadio del tumor, atención recibida (profesional), reporte de consumo de alcohol o cigarrillo, complicaciones asociadas al tratamiento de CEB. Se describieron las variables del estudio y pruebas Chi cuadrado para observar diferencias entre algunas características clínicas y el sexo. Se encontraron 778 casos de CEB en el periodo estudiado, con una edad promedio de diagnóstico de 63,5 (±13,6) años. Más de la mitad tenían estratos socioeconómicos y niveles educativos bajos. Un 56 % de las mujeres y un 63 % de los hombres fueron diagnosticados en un estadio IV del tumor. Los tratamientos más realizados fueron de tipo combinado o cirugía. Un 35% presentaron problemas cardiovasculares, aunque no se reportaron diferencias estadísticamente significativas entre la presencia de determinadas comorbilidades y el sexo. Se reportó el consumo de alcohol en un 19 % y de cigarrillo en un 51 % con mayor consumo en hombres en ambos casos y diferencias estadísticamente significativas (p<0,0001) con respecto a las mujeres. En cuanto a complicaciones asociadas al tratamiento para CEB, se reportaron con mayor frecuencia disfagia (47 %) y mucositis (24 %). Más de la mitad de los tumores de presentaron en la lengua. Se requieren estrategias que permitan sistemas de vigilancia epidemiológica para el CEB, así como mejorar los programas de prevención y tratamiento precoz para esta enfermedad en consonancia con las políticas y los planes nacionales y globales.

ABSTRACT: This study aimed to describe the sociodemographic and clinical characteristics of patients treated for first-time oral squamous cell carcinoma (OSCC), in Medellín (Colombia). For this purpose, a descriptive study was carried out within a retrospective dynamic cohort of OSCC cases from 9 specialized oncology centers in the city between 2000 and 2011, according to the information of the clinical records and classified according to the ICD-10. Sociodemographic characteristics were recorded and clinical variables were collected such as: Treatment received, tumor location, tumor stage, care received (professional), report of alcohol or cigarette consumption, complications associated with OSCC treatment. The study variables were described, and Chi square test was calculated in order to observe differences between some clinical characteristics and sex. In the study period 778 cases of OSCC were found, with an average age of diagnosis of 63.5 (± 13.6) years. More than half had low socioeconomic and educational levels. Fifty six percent of women and 63 % of men were diagnosed in stage IV of the tumor. Treatments performed most, were either combined or for surgery. Thirty five percent of the cases had cardiovascular problems, although no statistically significant differences were reported between the presence of certain comorbidities and sex. Alcohol consumption was reported in 19 % and smoking in 51 %, with higher consumption in men in both cases and statistically significant differences (p <0.0001) with respect to women. Regarding complications associated with treatment for OSCC, dysphagia (47 %) and mucositis (24 %) were reported more frequently. More than half of the tumors were presented in the tongue. Strategies are required that allow epidemiological surveillance systems for the OSCC, as well as to improve prevention and early treatment programs for this disease in line with national and global policies and plans.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Precancerous Conditions/diagnosis , Mouth Neoplasms/diagnosis , Carcinoma, Squamous Cell/diagnosis , Socioeconomic Factors , Cell Transformation, Neoplastic/pathology , Epidemiology, Descriptive , Colombia , Carcinogenesis
Braz. j. otorhinolaryngol. (Impr.) ; 82(6): 687-694, Oct.-Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-828255


Abstract Introduction: A key step of cancer development is the progressive accumulation of genomic changes resulting in disruption of several biological mechanisms. Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive neoplasm that arises from a pleomorphic adenoma. CXPA derived from a recurrent PA (RPA) has been rarely reported, and the genomic changes associated with these tumors have not yet been studied. Objective: We analyzed CXPA from RPAs and RPAs without malignant transformation using array-comparative genomic hybridization (array-CGH) to identify somatic copy number alterations and affected genes. Methods: DNA samples extracted from FFPE tumors were submitted to array-CGH investigation, and data was analyzed by Nexus Copy Number Discovery Edition v.7. Results: No somatic copy number alterations were found in RPAs without malignant transformation. As for CXPA from RPA, although genomic profiles were unique for each case, we detected some chromosomal regions that appear to be preferentially affected by copy number alterations. The first case of CXPA-RPA (frankly invasive myoepithelial carcinoma) showed copy number alterations affecting 1p36.33p13, 5p and chromosomes 3 and 8. The second case of CXPA-RPA (frankly invasive epithelial-myoepithelial carcinoma) showed several alterations at chromosomes 3, 8, and 16, with two amplifications at 8p12p11.21 and 12q14.3q21.2. The third case of CXPA-RPA (minimally invasive epithelial-myoepithelial carcinoma) exhibited amplifications at 12q13.3q14.1, 12q14.3, and 12q15. Conclusion: The occurrence of gains at chromosomes 3 and 8 and genomic amplifications at 8p and 12q, mainly those encompassing the HMGA2, MDM2, WIF1, WHSC1L1, LIRG3, CDK4 in CXAP from RPA can be a significant promotional factor in malignant transformation.

Resumo Introdução: Uma etapa fundamental do desenvolvimento do câncer é o acúmulo progressivo de alterações genômicas, resultando na ruptura de vários mecanismos biológicos. Carcinoma ex-adenoma pleomórfico (CXAP) é uma neoplasia agressiva que surge a partir de um adenoma pleomórfico. O CXAP derivado de um AP recorrente (APR) foi raramente relatado e, até o momento, as alterações genômicas associadas a esses tumores não foram estudados. Objetivo: Avaliar as diferenças entre os CXAPs decorrentes de APRs e os APRs sem transformações malignas usando hibridização genômica comparativa em microarrays (array Comparative Genomic Hibridization - aCGH) a fim de identificar alterações no número de cópias somáticas e os genes afetados. Método: Amostras de DNA extraídas de tumores provenientes de tecido emblocado em parafina foram submetidos à investigação com a técnica aCGH, e os dados foram analisados com o Nexus Copy Number Discovery Edition v.7. Resultados: Não observamos alterações no numero de cópias somáticas nos APRs sem transformação maligna. Quanto ao CXAP de APR, embora os perfis genômicos sejam exclusivos para cada caso, detectamos algumas regiões cromossômicas que pareciam ser preferencialmente afetadas por alterações no número de cópias. O primeiro caso de CXAP-APR (carcinoma mioepitelial francamente invasivo) apresentou alterações no numero de cópias afetando 1p36.33p13, 5p e cromossomos 3 e 8. O segundo caso de CXAP-APR (carcinoma epitelialmioepitelial francamente invasivo) apresentou várias alterações nos cromossomos 3, 8 e 16, com duas amplificações em 8p12p11.21 e 12q14.3q21.2. O terceiro caso de CXAP-APR (carcinoma epitelial-mioepitelial minimamente invasivo) apresentou amplificações em 12q13.3q14.1, 12q14.3, e 12q15. Conclusão: A ocorrência de ganhos de cromossomos 3 e 8, e as amplificações genômicas em 8p e 12q, principalmente aquelas que englobam os HMGA2, MDM2, WIF1, WHSC1L1, RG3, CDK4 no CXAP decorrente de APR podem ser fatores promocionais significativos para a transformação maligna.

Humans , Male , Female , Adult , Aged , Salivary Gland Neoplasms/genetics , Cell Transformation, Neoplastic/genetics , Adenoma, Pleomorphic/genetics , Salivary Gland Neoplasms/pathology , Cell Transformation, Neoplastic/pathology , Adenoma, Pleomorphic/pathology , Neoplasm Recurrence, Local
Rev. med. Rosario ; 80(1): 21-32, ene.-abr. 2014. ilus
Article in Spanish | LILACS | ID: lil-716648


Las lesiones precursoras y formas tempranas del cáncer de ano y de la zona perianal ha sido en los últimos años mejor reconocidas y definidas; ello ha ido en paralelo a un interés cada vez mayor en esta patología debido a su incidencia creciente. En esta revisión se analiza el tema, actualizando los aspectos patogénicos que vinculan las neoplasias anales con subtipos oncogénicos del Papilomavirus Humano, y correlacionándolo con la existencia de poblaciones en riesgo y de alteraciones inmunitarias predisponentes o asociadas. Se describe la expresión morfológica de las lesiones precursoras y tempranas, en el contexto mas amplio de las neoplasias intraepiteliales similares de la zona genital baja. Tambien se realiza una puesta al día de las diversas técnicas de diagnóstico disponibles en este momento desde el punto de vista proctológico y antomopatologico y finalmente, una actualización de las diversas opciones terapéuticas y los cambios de enfoque y conducta que se plantean en lesiones anales y perianales diagnosticadas en etapas relativamente tempranas de su evolución.

The precursor precancerous lesions and early invasive cancer of the anus and the perianal area have been better recognized and defined in the last decade; it has been also a greater interest in this kind of precancers and cancers because of their increasing incidence. We analyzed in this paper this subject, updating the knowledge about the pathogenic link between anal neoplasias and oncogenics subtypes of Human Paplilomavirus, and correlating this neoplasias with the populations at risk and associated/predisposing immune alterations. The morphologic expression of the precursor and early invasive lesions is described, in the full context of similar intraepithelial neoplasias of the low genital area. Also we made an update of the proctologic and cytopathologic diagnostic techniques available at this moment and, finally, the therapeutic options and the changes of approach in anal and perianal preneoplastic and neoplastic lesions diagnosed in early stages of their evolution were revised.

Humans , Carcinoma, Squamous Cell/classification , Early Diagnosis , Papillomavirus Infections/pathology , Precancerous Conditions , Anus Neoplasms/pathology , Therapeutics/methods , Terminology as Topic , Cell Transformation, Neoplastic/pathology , Condylomata Acuminata/pathology , Diagnostic Techniques and Procedures
Braz. j. otorhinolaryngol. (Impr.) ; 79(1): 112-118, jan.-fev. 2013.
Article in Portuguese | LILACS | ID: lil-667985


Os miofibroblastos são células especializadas que exibem um fenótipo híbrido, com características de fibroblastos e células musculares lisas. Devido sua habilidade contrátil e capacidade de síntese de componentes da matriz extracelular, citocinas, proteases e fatores pró-angiogênicos, os miofibroblastos têm sido implicados na patogênese de doenças fibrocontráteis e na progressão de diversos tumores, incluindo o carcinoma de células escamosas (CCE) oral. OBJETIVO: Fazer uma revisão da literatura sobre a origem dos miofibroblastos, seus principais aspectos morfofisiológicos e imuno-histoquímicos, assim como discutir sua relação com o CCE oral. MÉTODO: Realizou-se uma busca eletrônica na base de dados PubMed, selecionando os principais artigos da literatura em língua inglesa relacionados ao tema, publicados entre janeiro de 1991 e dezembro de 2011. CONCLUSÃO: Os miofibroblastos representam um componente importante do estroma de CCE orais, embora não estejam presentes em todos os casos desta neoplasia. A presença abundante destas células pode estar associada com a recorrência local da doença e diminuição da sobrevida dos pacientes. No entanto, em virtude do número relativamente limitado de estudos sobre o assunto, pesquisas ainda são necessárias para esclarecer os mecanismos moleculares pelos quais os miofibroblastos são capazes de influenciar no comportamento biológico do CCE oral.

Myofibroblasts are hybrid-phenotype differentiated cells in between fibroblasts and smooth muscle cells. Due to their contractile features and ability to synthesize extracellular matrix components, cytokines, proteases, and proangiogenic factors, myofibroblasts have been implicated in the pathogenesis of fibrocontractive diseases and in the progression of many tumors, including oral squamous cell carcinoma (SCC). OBJECTIVE: To perform a literature review on the origin of myofibroblasts, their main morpho-physiological and immunohistochemical aspects, and to discuss the correlations with oral SCC. METHOD: A search was made on the PubMed database to select the main papers in the literature in English related to the subject, published between January 1991 and December 2011. CONCLUSION: Myofibroblasts are an important component of the stroma of oral SCCs, although they are not present in all tumors. Abundant presence of myofibroblasts may be associated with local disease recurrence and decreased patient survival. However, given the relatively limited number of studies on the subject, further research is needed to clarify the molecular mechanisms by which myofibroblasts influence the biological behavior of oral SCC.

Humans , Carcinoma, Squamous Cell/pathology , Cell Transformation, Neoplastic/pathology , Mouth Neoplasms/pathology , Myofibroblasts/pathology , Immunohistochemistry
Article in English | IMSEAR | ID: sea-147336


Mature teratoma is a common anterior mediastinal tumour. However, occurrence of transformed malignant component within it is very rare. We report a case of a 32-year-old female presenting with dry cough and chest pain. Contrast-enhanced computed tomography (CT) showed a large thin-walled cystic lesion measuring 11.4cmx10.6cmx10.0cm in the anterior mediastinum. Right postero-lateral thoracotomy was performed and the tumour was completely excised. Histopathological examination of the excised specimen was suggestive of mature teratoma with transformed malignant component, adenocarcinoma (somatic-type malignancy).

Adenocarcinoma/pathology , Adult , Cell Transformation, Neoplastic/pathology , Female , Humans , Mediastinal Neoplasms/pathology , Teratoma/pathology , Tomography, X-Ray Computed
Braz. j. med. biol. res ; 45(11): 995-1001, Nov. 2012. ilus
Article in English | LILACS | ID: lil-650573


Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy.

Humans , Male , Prostatic Neoplasms/metabolism , RNA Interference , Securin/metabolism , Cell Line, Tumor , Cell Proliferation , Cell Transformation, Neoplastic/pathology , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Securin/genetics , Up-Regulation
West Indian med. j ; 61(1): 10-16, Jan. 2012. ilus, tab
Article in English | LILACS | ID: lil-672843


OBJECTIVES: Adenocarcinoma of the colon and rectum is the third most common cause of cancer deaths and the sixth most common cancer in the world. Adenomas are benign neoplastic lesions which can be transformed into carcinomas, but this is usually not the case. There should be some risk factors which lead to the development of carcinomas into adenomas. The aim of this study is to find out the early changes and high risk factors related to carcinogenesis in colonic polyps. METHODS: IIn this study, we reviewed nearly 1000 colonoscopic biopsies and chose 72 biopsies. We developed three groups (tubular adenomas group 1, villous adenomas group 2, normal mucosa group 3); each group had 24 different biopsies. P53, Ki-67, bcl-2, cyclin D1, E-cadherin, c-erb B2 immunohistochemistry and human papillomavirus (HPV) in-situ hybridization were used for analysis. RESULTS: Five of the seventy-two cases were positive in HPV in-situ analysis. Four of them were villous adenomas and one was a tubular adenoma. Ki-67 expression was limited only to crypts in group 3 but in groups 1 and 2, Ki-67 expression was seen both in crypt epithelium and surface epithelium. Cyclin D1, c-erb B2, bcl-2 expression was significantly increased in neoplastic polyps. CONCLUSION: Ki-67 expression, both in the crypt and surface epithelium, and cyclin D1, c-erb B2, bcl-2 over-expression may be a clue of dysplastic epithelium and if the role of HPV is elucidated and shown to be important in colonic carcinogenesis, then vaccination might prevent carcinogenesis caused by HPV.

OBJETIVOS: El adenocarcinoma del colon y recto es la tercera causa más común de muertes por cáncer y el sexto tipo de cáncer más común en el mundo. Los adenomas son lesiones neoplásicas benignas que pueden transformarse en carcinomas, pero éste normalmente no es el caso. Debe haber algunos factores de riesgo que conducen al desarrollo de carcinomas en adenomas. El objetivo de este estudio es averiguar los cambios tempranos y los factores de alto riesgo relacionados con la carcinogénesis en los pólipos colónicos. MÉTODOS: En este estudio, revisamos casi 1000 biopsias colonoscópicas y escogimos 72 biopsias. Desarrollamos tres grupos (grupo 1: adenomas tubulares, grupo 2: adenomas vilosos, grupo 3: mucosa normal); cada grupo tuvo 24 biopsias diferentes. Para el anílisis se utilizaron la inmunohistoquímica de P53, Ki-67, bcl-2, ciclina D1, E-cadherina, y c-erb B2, así como la hibridación in situ para la detección del virus del papiloma humano (VPH) RESULTADOS: Cinco de setenta y dos casos resultaron positivos en el análisis del VPH in-situ. Cuatro de ellos fueron adenomas vilosos, de los cuales uno era un adenoma tubular. La expresión Ki-67 está limitada sólo a las criptas en el grupo 3, pero en los grupos 1 y 2, la expresión Ki-67 se observó tanto en el epitelio de la cripta como en el epitelio de la superficie. La expresión de la ciclina D1, c-erb B2, y bcl- 2 se halla significativamente aumentada en los pólipos neoplásicos. CONCLUSIÓN: La expresión de Ki-67 tanto en el epitelio de la cripta como de la superficie, y la sobre-expesión de la ciclina D1, c-erb B2, bcl-2 puede ser una clave para el epitelio displásico, y si se aclara y demuestra que el papel del VPH es importante en la carcinogénesis colónica, entonces la vacunación podría prevenir los carcinogénesis inducidos por el VPH.

Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adenoma/pathology , Cell Transformation, Neoplastic/pathology , Colonic Neoplasms/pathology , Colonic Polyps/pathology , Rectal Neoplasms/pathology , Adenoma/metabolism , Cadherins/metabolism , Cell Transformation, Neoplastic/metabolism , Colonic Neoplasms/metabolism , Colonic Polyps/metabolism , Cyclin D1/metabolism , /metabolism , /metabolism , /metabolism , Rectal Neoplasms/metabolism , /metabolism
Article in English | IMSEAR | ID: sea-140000


Background: Heat shock proteins are a highly conserved group of protective cellular proteins whose synthesis is increased in response to a variety of environmental or pathophysiological stresses. Heat shock proteins are useful biomarkers for carcinogenesis in tissues and signal the degree of differentiation and the aggressiveness of cancers. Regulation of heat shock protein 70 (HSP70) expression in oral submucous fibrosis is not known much, and the aim of this study was to evaluate HSP70 expression in oral submucous fibrosis and oral squamous cell carcinoma by immunohistochemical method and to understand the role of HSP70 in tumorigenesis. Materials and Methods: Immunohistochemical method was used to detect HSP70 expression in normal oral mucosa, oral submucous fibrosis (n=30) and oral squamous cell carcinoma (n=20). HSP70 immunoreactivity was correlated with histological and clinicopathological features. Results: A significant increase in expression of HSP70 was observed (P<0.000) as the tissue progressed from oral submucous fibrosis towards oral squamous cell carcinoma. Conclusion: HSP70 is synthesized upon stress situations arising in cells of all living organisms. Expression of HSP70 indicates that stress plays an important role as a predisposing factor in oral submucous fibrosis and its subsequent progression to oral squamous cell carcinoma.

Adolescent , Adult , Age Factors , Aged , Biomarkers/analysis , Carcinoma, Squamous Cell/pathology , Cell Transformation, Neoplastic/pathology , Child , Child, Preschool , Disease Progression , Gingiva/anatomy & histology , HSP70 Heat-Shock Proteins/analysis , Humans , Immunohistochemistry , Middle Aged , Mouth Mucosa/pathology , Mouth Neoplasms/pathology , Oral Submucous Fibrosis/pathology , Precancerous Conditions/pathology , Young Adult
Clinics ; 66(4): 523-528, 2011. ilus, tab
Article in English | LILACS, SES-SP | ID: lil-588898


OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70 percent actinic keratoses, 76 percent squamous cell carcinoma-I, and 90 percent squamous cell carcinoma-II, to 100 percent squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and squamous cell carcinomas indicate the presence of a spectrum of malignant progression.

Humans , Carcinoma, Squamous Cell/genetics , DNA Primers/genetics , Keratosis, Actinic/genetics , Loss of Heterozygosity/genetics , Microsatellite Instability , Skin Neoplasms/genetics , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , Chromosomes, Human, Pair 9 , DNA Fingerprinting , Disease Progression , Keratosis, Actinic/pathology , Random Amplified Polymorphic DNA Technique/methods
Clinics ; 66(6): 1051-1054, 2011. ilus, graf
Article in English | LILACS | ID: lil-594377


OBJECTIVE: The present study was designed to evaluate the effects of urban, traffic-related, fine particulate matter (PM2.5) on mice lung tumorigenesis under controlled exposure conditions. METHODS: Four groups of female Swiss mice were treated with intraperitonial injections of urethane and saline solution. Urethane was used to start the carcinogenesis process. The animals were housed in two chambers receiving filtered and polluted air. In the polluted air chamber, pollutant levels were low. After two months of exposure, the animals were euthanized and lung tumoral nodules were counted. RESULTS: Saline-treated animals showed no nodules. Urethane-treated animals showed 2.0+2.0 and 4.0+3.0 nodules respectively, in the filtered and non-filtered chambers (p = 0.02), thus showing experimental evidence of increased carcinogenic-induced lung cancer with increasing PM2.5 exposure. CONCLUSION: Our data support the concept that low levels of PM2.5 may increase the risk of developing lung tumors.

Animals , Female , Mice , Air Pollutants/toxicity , Lung Neoplasms/chemically induced , Carcinogens , Cell Transformation, Neoplastic/pathology , Disease Models, Animal , Environmental Exposure/adverse effects , Lung Neoplasms/pathology , Particulate Matter/adverse effects , Particulate Matter/analysis , Particulate Matter/toxicity , Random Allocation , Risk Factors , Time Factors , Urethane