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1.
Braz. arch. biol. technol ; 64: e21200093, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153294

ABSTRACT

HIGHLIGHTS Sodium arsenite can cause neoplastic transformation in cells. Curcumin reduced cell viability and increased LDH activity in transformed Balb/c 3T3 cells. Curcumin caused DNA damage in transformed Balb/c 3T3 cells. Curcumin may play a protective role in sodium arsenite-induced toxicity.


Abstract Arsenic is a toxic substance that spreads widely around the environment and accumulates as metalloid in the earth's crust. Arsenic and its derivatives are found in drinking water, nutrients, soil, and air. Exposure to arsenic is associated with lung, blood, skin cancer and various lesions. Curcumin is a polyphenolic compound derived from Curcuma longa (turmeric) rhizome and is one of the main curcuminoids. Curcumin is known to be antioxidant, antibacterial, anti-inflammatory, analgesic effects. This study aimed to investigate the potential of sodium arsenite to transform embryonic fibroblast cells and to evaluate the cytotoxic and genotoxic effects of curcumin in neoplastic transformed cells. Neoplastic cells transformation was induced by sodium arsenite in Balb/c 3T3 cells at the end of 32 days. After transformation assay, the transformed cells were treated with various concentration of curcumin to evaluate cell viability, lactate dehydrogenase activity and DNA damage for 24h. The results revealed that curcumin decreased cell viability and increased the activity of lactate dehydrogenase enzyme in neoplastic transformed Balb/c 3T3 cells. In conclusion, the results demonstrated that curcumin has an anticancer effect on neoplastic transformed Balb/c 3T3 cells by causing DNA damage.


Subject(s)
Animals , Mice , Arsenic/toxicity , DNA Damage , Cell Transformation, Neoplastic , Curcumin/pharmacology , Fibroblasts/drug effects , BALB 3T3 Cells , Fibroblasts/pathology
2.
Frontiers of Medicine ; (4): 178-207, 2021.
Article in English | WPRIM | ID: wpr-880961

ABSTRACT

Breast cancer is one of the most common malignancies that seriously threaten women's health. In the process of the malignant transformation of breast cancer, metabolic reprogramming and immune evasion represent the two main fascinating characteristics of cancer and facilitate cancer cell proliferation. Breast cancer cells generate energy through increased glucose metabolism. Lipid metabolism contributes to biological signal pathways and forms cell membranes except energy generation. Amino acids act as basic protein units and metabolic regulators in supporting cell growth. For tumor-associated immunity, poor immunogenicity and heightened immunosuppression cause breast cancer cells to evade the host's immune system. For the past few years, the complex mechanisms of metabolic reprogramming and immune evasion are deeply investigated, and the genes involved in these processes are used as clinical therapeutic targets for breast cancer. Here, we review the recent findings related to abnormal metabolism and immune characteristics, regulatory mechanisms, their links, and relevant therapeutic strategies.


Subject(s)
Breast Neoplasms , Cell Proliferation , Cell Transformation, Neoplastic , Energy Metabolism , Female , Humans , Lipid Metabolism , Signal Transduction
3.
Braz. j. med. biol. res ; 54(5): e10637, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153548

ABSTRACT

Transcription factors control, coordinate, and separate the functions of distinct network modules spatially and temporally. In this review, we focus on the transcription factor 21 (TCF21) network, a highly conserved basic-helix-loop-helix (bHLH) protein that functions to integrate signals and modulate gene expression. We summarize the molecular and biological properties of TCF21 control with an emphasis on molecular and functional TCF21 interactions. We suggest that these interactions serve to modulate the development of different organs at the transcriptional level to maintain growth homeostasis and to influence cell fate. Importantly, TCF21 expression is epigenetically inactivated in different types of human cancers. The epigenetic modification or activation and/or loss of TCF21 expression results in an imbalance in TCF21 signaling, which may lead to tumor initiation and, most likely, to progression and tumor metastasis. This review focuses on research on the roles of TCF21 in development and tumorigenesis systematically considering the physiological and pathological function of TCF21. In addition, we focus on the main molecular bases of its different roles whose importance should be clarified in future research. For this review, PubMed databases and keywords such as TCF21, POD-1, capsulin, tumors, carcinomas, tumorigenesis, development, and mechanism of action were utilized. Articles were selected within a historical context as were a number of citations from journals with relevant impact.


Subject(s)
Humans , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Carcinogenesis/genetics , Signal Transduction , Cell Differentiation , Cell Transformation, Neoplastic/genetics
4.
Rev. ADM ; 77(2): 70-79, mar.-abr. 2020. ilus, graf
Article in Spanish | LILACS | ID: biblio-1100338

ABSTRACT

Las enfermedades autoinmunes tienen múltiples manifestaciones en estomatología, entre las más frecuentes se encuentra el liquen plano oral (LPO), se trata de una enfermedad crónica con manifestaciones clínicas en piel y mucosas. Se agrupa en dos formas anatomoclínicas, la de curso evolutivo benigno identificado como típico y la susceptible de transformación maligna, identificada como atípico. Histológicamente, la degeneración vacuolar del estrato basal del epitelio es el signo histomorfológico patognomónico seguido de apoptosis celular. La apoptosis es un evento esencial entre los fenómenos del ciclo celular, sucede con la finalidad de eliminar células dañadas o inútiles. De todas las proteínas implicadas las caspasas son los responsables de la ejecución de este mecanismo, especialmente la caspasa 3 por fragmentar y activar otras caspasas responsables de la proteólisis. El potencial de transformación maligna del LPO podría estar en relación con el fallo de este mecanismo de regulación del ciclo de las células epiteliales agredidas y la persistencia de células dañadas. El presente trabajo de investigación tuvo como objetivo analizar la presencia y proporción de apoptosis en las distintas variantes de LPO con técnicas histológicas de rutina y posterior aplicación de inmunohistoquímica, utilizando como marcador la caspasa 3. Se obtuvieron 20 biopsias de LPO de cinco variedades clínicas nueve variantes típicas (VT): cinco placa, cuatro reticulares y 11 variantes atípicas (VA): dos atróficos, seis erosivos, tres ampollares. El método de evaluación fue semicuantitativo, se consideró en función del porcentaje, se realizó un recuento celular de un total de 100 células en cinco campos de gran aumento considerando las siguientes categorías según ausencia, presencia leve (< 10%), moderada (10 ≤ 25%), intensa (25 ≤ 50%), no valorables. Se encontró una buena correlación de los cambios histológicos y el grado de expresión del marcador utilizado para poner en evidencia la apoptosis, sobre todo con las muestras de LPO de variante atípica. En los casos de las variantes atípicas de liquen observados en comparación con la tinción de rutina (H/E) se observó igualdad o una disminución en algunos casos del número de queratinocitos apoptóticos. En cuanto a las variantes clínicas consideradas «típicas¼ se observó que el recuento de células en apoptosis estaba significativamente elevado. Obtuvimos excelentes resultados con el inmunomarcador caspasa 3, el cual coincide con la literatura en su alta sensibilidad como recurso para cuantificar el número de apoptosis en estas lesiones orales (AU)


Autoimmune diseases have multiple manifestations in stomatology, among the most frequent is oral lichen planus (LPO), it is a chronic disease with clinical manifestations in skin and mucous membranes. It is grouped into two anatomoclinic forms, the benign evolutionary course identified as typical and susceptible to malignant transformation, identified as atypical. Histologically, vacuolar degeneration of the basal stratum of the epithelium is the pathognomonic histomorphological sign followed by cellular apoptosis. Apoptosis is an essential event among cell cycle phenomena, it happens in order to eliminate damaged or useless cells. Of all the proteins involved, caspases are responsible for the execution of this mechanism, especially caspase-3 for fragmenting and activating other caspases responsible for proteolysis. The potential for malignant transformation of the LPO could be related to the failure of this mechanism to regulate the cycle of attacked epithelial cells and the persistence of damaged cells. This research work aimed to analyze the presence and proportion of apoptosis in the different variants of LPO with routine histological techniques and subsequent application of immunohistochemistry, using caspase as a marker 3. 20 LPO biopsies from 5 clinical varieties were obtained 9 typical variants (VT): 5 plate, 4 reticular and 11 atypical variants (VA): 2 atrophic, 6 erosive, 3 ampoules. The evaluation method was semi-quantitative considering the percentage, making a cell count of a total of 100 cells, in five large-scale fields considering the following categories according to absence, mild presence (< 10%), moderate (10 ≤ 25%), intense (25 ≤ 50%), not valuable. We found a good correlation of histological changes and the degree of expression of the marker used to highlight apoptosis, especially with the atypical variant LPO samples. In the cases of atypical variants of lichen observed, compared with routine staining (H/E) we find equality or a decrease in some cases of the number of apoptotic keratinocytes. For clinical variants considered «typical¼ it was observed that the cell count in apoptosis was significantly increased. We obtained excellent results with the caspase 3 immunomarker coinciding with the literature of its high sensitivity as a resource to quantify the number of apoptosis in these oral lesions (AU)


Subject(s)
Humans , Male , Female , Biomarkers , Cell Transformation, Neoplastic , Apoptosis , Lichen Planus, Oral/immunology , Caspase 3 , Biopsy , Immunohistochemistry , Statistical Analysis
5.
Article in English | WPRIM | ID: wpr-828955

ABSTRACT

The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.


Subject(s)
Animals , Carcinoma, Squamous Cell , Pathology , Cell Transformation, Neoplastic , Pathology , Mice , Mouth Mucosa , Mouth Neoplasms , Pathology , Oral Submucous Fibrosis , Pathology , Stem Cells
6.
Braz. oral res. (Online) ; 34: e052, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1132707

ABSTRACT

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.


Subject(s)
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
7.
Arch. endocrinol. metab. (Online) ; 63(5): 536-544, Sept.-Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1038502

ABSTRACT

ABSTRACT Thyroid cancer has been rapidly increasing in prevalence among humans in last 2 decades and is the most prevalent endocrine malignancy. Overall, thyroid-cancer patients have good rates of long-term survival, but a small percentage present poor outcome. Thyroid cancer aggressiveness is essentially related with thyroid follicular cell loss of differentiation and metastasis. The discovery of oncogenes that drive thyroid cancer (such as RET, RAS, and BRAF), and are aligned in the MAPK/ERK pathway has led to a new perspective of thyroid oncogenesis. The uncovering of additional oncogene-modulated signaling pathways revealed an intricate and active signaling cross-talk. Among these, microRNAs, which are a class of small, noncoding RNAs, expanded this cross-talk by modulating several components of the oncogenic network - thus establishing a new layer of regulation. In this context, TGFβ signaling plays an important role in cancer as a dual factor: it can exert an antimitogenic effect in normal thyroid follicular cells, and promote epithelial-to-mesenchymal transition, cell migration, and invasion in cancer cells. In this review, we explore how microRNAs influence the loss of thyroid differentiation and the increase in aggressiveness of thyroid cancers by regulating the dual function of TGFβ. This review provides directions for future research to encourage the development of new strategies and molecular approaches that can improve the treatment of aggressive thyroid cancer.


Subject(s)
Humans , Thyroid Gland/pathology , Thyroid Neoplasms/pathology , Transforming Growth Factor beta/metabolism , MicroRNAs/metabolism , Thyroid Neoplasms/metabolism , Signal Transduction , Cell Transformation, Neoplastic , Disease Progression , Neoplasm Invasiveness , Neoplasm Metastasis
8.
Rev. medica electron ; 41(3): 756-764, mayo.-jun. 2019. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1094083

ABSTRACT

RESUMEN Los melanomas mucosos son tumores poco frecuentes y de mal pronóstico. Presentan un comportamiento agresivo, y pueden tener varias localizaciones en el aparato digestivo. Este tipo de tumores es más frecuente en la región anorectal. Se presentó un caso de una paciente femenina de 59 años, con un cuadro de varios meses de evolución; caracterizado por ardor, prurito anal y sensación de masa que prolapsaba a través del ano. Se constató al examen físico masa tumoral aspecto polipoideo. Se realizó polipectomía donde la biopsia arrojó como resultados el aspecto histológico de un melanoma mucoso de canal anal.


ABSTRACT Mucous melanomas are few frequent and have a bad prognosis. They present an aggressive behavior and might have several locations in the digestive system. This kind of tumors is more frequent at the anus-rectal region. The authors presented the case of a female patient, aged 59 years, with clinical conditions of several months of evolution, characterized by burning, anal pruritus and the sensation of a mass prolapsing through the anus. A tumor mass of polypoid aspect was found at physical examination. Polypectomy was carried out and the biopsy showed the histologic aspect of a mucous melanoma of the anal canal.


Subject(s)
Humans , Female , Adult , Anus Neoplasms/diagnosis , Anus Neoplasms/pathology , Anus Neoplasms/blood , Cell Transformation, Neoplastic , Sarcoma, Clear Cell/diagnosis , Melanocytes/metabolism , Melanoma/diagnosis , Melanoma/pathology , Melanoma/blood , Anal Canal/physiopathology , Pruritus Ani/diagnosis , Neoplasm Metastasis
9.
Medicina (B.Aires) ; 79(1): 67-70, feb. 2019. ilus
Article in Spanish | LILACS | ID: biblio-1002590

ABSTRACT

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.


Subject(s)
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
10.
Article in English | WPRIM | ID: wpr-719675

ABSTRACT

OBJECTIVE: This study aimed to analyze the clinical features of clear cell carcinoma in relation to endometriosis and to determine an appropriate surveillance strategy for the early detection of malignant transformation of endometrioma in asymptomatic patients. METHODS: We retrospectively reviewed the clinicopathologic data of 50 patients with ovarian clear cell carcinoma. Clinicopathologic characteristics, treatment outcomes, and the association between endometriosis and the risk of malignant transformation were analyzed. RESULTS: Ten (20%) patients had been diagnosed with endometrioma before the diagnosis of clear cell carcinoma. The median period from the diagnosis of endometrioma to clear cell carcinoma diagnosis was 50 months (range, 12–213 months). After complete staging surgery, histological confirmation of endometriosis was possible in 35 (70%) patients. Of the 50 patients, 39 (78%) had not undergone any gynecologic surveillance until the onset of symptoms, at which time many of them presented with a rapidly growing pelvic mass (median 10 cm, range 4.6–25 cm). With the exception of 2 patients, all cancer diagnoses were made when the patients were in their late thirties, and median tumor size was found to increase along with age. Asymptomatic patients (n=11) who had regular gynecologic examinations were found to have a relatively smaller tumor size, lesser extent of tumor spread, and lower recurrence rate (P=0.011, 0.283, and 0.064, respectively). The presence of endometriosis was not related to the prognosis. CONCLUSION: Considering the duration of malignant transformation and the timing of cancer diagnosis, active surveillance might be considered from the age of the mid-thirties, with at least a 1-year interval, in patients with asymptomatic endometrioma.


Subject(s)
Cell Transformation, Neoplastic , Diagnosis , Endometriosis , Female , Humans , Prognosis , Recurrence , Retrospective Studies
11.
Article in Chinese | WPRIM | ID: wpr-774296

ABSTRACT

OBJECTIVE@#To explore whether tumor suppressor gene Foxo1 and PTEN play a critical role in the tumorigenesis of mouse natural killer-cell lymphoma.@*METHODS@#NKp46-iCre mice were crossed with mice carrying floxed Foxo1 alleles (Foxo1) as well as floxed PTEN alleles (PTEN) to generate mice in which Foxo1 and PTEN in NK cells were knock-out, referred as Foxo1PTEN. The growth and development of the mice and tumor formation were observed. The flow cytometry was used to detect the percentages of NK cells in main lymphatic organs. B16F10 metanoma model of tumor metastasis was utilized to investigate NK cell-mediated tumor surveillance in vivo after NK cells special deletion of Foxol and PTEN.@*RESULTS@#The mouse model with NK cell-special Foxo1 and PTEN double knockout was established. Compared with control group (Foxo1PTEN mice), Foxo1PTEN mice were born alive and appeared to be healthy over a period of 46 weeks. No spontaneous tumor formation was observed at this stage. There were no significant differences in NK cell percentages of gated lymphocytes from various organs including blood, bone marrow, peripheral lymph node and spleen between Foxo1PTEN mice and Foxo1PTEN mice [PB: 4.76%±0.46% vs 4.17%±0.64% (P>0.05, n=8); BM: 1.13%±0.23% vs 1.31%±0.10% (P>0.05, n=8) ; LN: 0.50%±0.10% vs 0.85%±0.20% (P>0.05, n=8); SP: 4.41%±0.65% vs 3.50%±0.24% (P>0.05, n=8)]. B16F10 melanoma metastasis model of tumor was established, No differences in median survival time were observed in the 2 types of mice (P>0.05, n=13).@*CONCLUSION@#The simultaneous deletion of the Foxo1 and PTEN genes may not plays significant role in the tumorigenesis of mouse natural killer-cell lymphoma and NK cell-mediated tumor surveillance in vivo.


Subject(s)
Animals , Cell Transformation, Neoplastic , Forkhead Box Protein O1 , Genes, Tumor Suppressor , Killer Cells, Natural , Lymphoma , Mice , Mice, Knockout
12.
Article in Korean | WPRIM | ID: wpr-760147

ABSTRACT

Inverted papilloma is a benign epithelial tumor that arises from the sinonasal epithelium and occurs in 0.5–4% of all sinonasal tumors. Although benign, it is associated with malignant transformation in 2–27% of the cases, with the most commonly accompanying malignant tumor being squamous cell carcinoma. The malignant transformation of inverted papilloma into adenocarcinoma is extremely rare, with two cases reported worldwide to date. Here, along with a literature review, we report a recent case of a 53-year-old man with non-intestinal type adenocarcinoma associated with a sinonasal inverted papilloma. This case shows the possibility of a malignant transformation of inverted papilloma into non-intestinal type adenocarcinoma, which may be associated with human papilloma virus and thus requires further investigation.


Subject(s)
Adenocarcinoma , Carcinoma, Squamous Cell , Cell Transformation, Neoplastic , Epithelium , Humans , Maxillary Sinus , Middle Aged , Papilloma, Inverted , Papillomaviridae , Paranasal Sinuses
13.
Säo Paulo med. j ; 136(6): 586-590, Nov.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-991690

ABSTRACT

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.


Subject(s)
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
14.
Int. j. odontostomatol. (Print) ; 12(3): 237-245, Sept. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-975740

ABSTRACT

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.


Subject(s)
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
15.
Braz. j. otorhinolaryngol. (Impr.) ; 84(3): 338-343, May-June 2018. tab
Article in English | LILACS | ID: biblio-951840

ABSTRACT

Abstract Introduction: Sinonasal inverted papilloma constitute relevant therapeutic problem due to destructive character of growth, tendency to recur and the possibility of malignant transformation. Therefore, many attempts to identify risk factors for inverted papilloma occurrence have been undertaken, as well as research to find markers that would allow for the earlier detection of tumors and the application of adequate therapy. A widely known risk factor of inverted papilloma is HPV infection. One of the markers of HPV infection and the ongoing effect of this change (although arousing some controversy) is the expression of the p16 protein. Objective: The aim of the study was to analyze the correlation between the expression of p16 as a surrogate of HPV infection in analyzed histopathological material and epidemiological variables, recurrences or malignant transformation. Methods: The retrospective study includes a group of 53 patients (18 women and 35 men) undergoing treatment for sinonasal inverted papilloma in the period of 2002-2012. The intensity of the p16 protein in histopathological material was scored as: 0 - no expression, 1 - diffuse expression (borderline) and 2 - positive expression; or 0 - no expression/diffuse expression (borderline); 1 - positive expression. The Ethics Committee agreement was obtained (1089/12; 245/13). Results and conclusion: There was no statistically significant relationship between the expression of p16 and the age of patients, cigarette smoking, tumor location, tumor staging according to the Krouse and Cannady classification, the presence of dysplasia or the occurrence of relapse.


Resumo Introdução: Papiloma invertido nasossinusal constitui um problema terapêutico relevante devido ao caráter destrutivo do crescimento, a tendência à recorrência e a possibilidade de transformação maligna. Assim, muitas tentativas têm sido realizadas para identificar fatores de risco para ocorrência de papiloma invertido, bem como pesquisas para encontrar marcadores que permitam a detecção precoce de tumores e a utilização de terapia adequada. Um fator de risco amplamente conhecido de papiloma invertido é a infecção pelo HPV. Um dos marcadores da infecção por HPV e do efeito contínuo dessa alteração (embora suscite alguma controvérsia) é a expressão da proteína p16. Objetivo: Analisar a correlação entre a expressão de p16 como um substituto da infecção pelo HPV no material histopatológico analisado e as variáveis epidemiológicas, recorrências ou transformação maligna. Método: O estudo retrospectivo inclui um grupo de 53 pacientes (18 mulheres e 35 homens) submetidos a tratamento para papiloma invertido nasossinusal de 2002 a 2012. A intensidade da expressão da proteína p16 no material histopatológico foi pontuada como: 0 - sem expressão, 1 - expressão difusa (limite) e 2 - expressão positiva; ou 0 - sem expressão/expressão difusa (limite); 1 - expressão positiva. O Comitê de Ética aprovou o estudo (1.089/12; 245/13). Resultados e conclusão: Não houve relação estatisticamente significante entre a expressão de p16 e a idade dos pacientes, o tabagismo, a localização tumoral e o estadiamento tumoral de acordo com a classificação de Krouse e Cannady, presença de displasia ou ocorrência de recidiva.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Paranasal Sinus Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Papilloma, Inverted/metabolism , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Immunohistochemistry , Gene Expression Regulation, Neoplastic , Cell Transformation, Neoplastic , Retrospective Studies , Neoplasm Recurrence, Local
16.
Biol. Res ; 51: 23, 2018. tab, graf
Article in English | LILACS | ID: biblio-950911

ABSTRACT

The exact cause of cancer is one of the most immutable medical questions of the century. Cancer as an evolutionary disease must have a purpose and understanding the purpose is more important than decoding the cause. The model of cancer proposed herein, provides a link between the cellular biochemistry and cellular genetics of cancer evolution. We thus call this model as the "Nexus model" of cancer. The Nexus model is an effort to identify the most apparent route to the disease. We have tried to utilize existing cancer literature to identify the most plausible causes of cellular transition in cancer, where the primary cancer-causing agents (physical, chemical or biological) act as inducing factors to produce cellular impeders. These cellular impeders are further linked to the Nexus. The Nexus then generates codes for epigenetics and genetics in cancer development.


Subject(s)
Humans , Cell Transformation, Neoplastic , Epigenesis, Genetic/physiology , Carcinogenesis , Models, Biological , Neoplasms/etiology , Neoplasms/physiopathology , Neoplasms/genetics
17.
Clinics ; 73(supl.1): e549s, 2018. tab, graf
Article in English | LILACS | ID: biblio-974946

ABSTRACT

Most human papillomavirus infections are readily cleared by the host immune response. However, in some individuals, human papillomavirus can establish a persistent infection. The persistence of high-risk human papillomavirus infection is the major risk factor for cervical cancer development. These viruses have developed mechanisms to evade the host immune system, which is an important step in persistence and, ultimately, in tumor development. Several cell types, receptors, transcription factors and inflammatory mediators involved in the antiviral immune response are viral targets and contribute to tumorigenesis. These targets include antigen-presenting cells, macrophages, natural killer cells, Toll-like receptors, nuclear factor kappa B and several cytokines and chemokines, such as interleukins, interferon and tumor necrosis factor. In the present review, we address both the main innate immune response mechanisms involved in HPV infection clearance and the viral strategies that promote viral persistence and may contribute to cancer development. Finally, we discuss the possibility of exploiting this knowledge to develop effective therapeutic strategies.


Subject(s)
Humans , Female , Papillomaviridae/immunology , Uterine Cervical Neoplasms/virology , Papillomavirus Infections/virology , Immunity, Innate/immunology , Cell Transformation, Neoplastic , Disease Progression , Immune Evasion
18.
Clinics ; 73(supl.1): e551s, 2018. graf
Article in English | LILACS | ID: biblio-952836

ABSTRACT

Infection with human papillomaviruses is associated with a series of benign and malignant hyperproliferative diseases that impose a heavy burden on human populations. A subgroup of mucosal human papillomavirus types are associated with the majority of cervical cancers and a relevant fraction of vulvar, vaginal, anal, penile and head and neck carcinomas. Human papillomaviruses mediate cell transformation by the expression of two pleiotropic oncoproteins that alter major cellular regulatory pathways. However, these viruses are not complete carcinogens, and further alterations within the infected cells and in their microenvironment are necessary for tumor establishment and progression. Alterations in components of the extracellular matrix for instance, matrix metalloproteinases and some of their regulators such as tissue inhibitors of metalloproteinases, have been consistently reported in human papillomaviruses-associated diseases. Matrix metalloproteinases function by remodeling the extracellular matrix and alterations in their expression levels and/or activity are associated with pathological processes and clinical variables including local tumor invasion, metastasis, tumor relapse and overall patient prognosis and survival. In this review we present a summarized discussion on the current data concerning the impact of human papillomavirus infection on the activity and expression of extracellular matrix components. We further comment on the possibility of targeting extracellular matrix molecules in experimental treatment protocols.


Subject(s)
Humans , Male , Female , Cell Transformation, Neoplastic/metabolism , Papillomavirus Infections/metabolism , Extracellular Matrix/metabolism , Papillomavirus Infections/virology , Genital Neoplasms, Female/virology , Genital Neoplasms, Male/virology , Head and Neck Neoplasms/virology
19.
Clinics ; 73(supl.1): e429s, 2018. graf
Article in English | LILACS | ID: biblio-952824

ABSTRACT

The immunologic landscape of tumors has been continuously unveiled, providing a new look at the interactions between cancer cells and the immune system. Emerging tumor cells are constantly eliminated by the immune system, but some cells establish a long-term equilibrium phase leading to tumor immunoediting and, eventually, evasion. During this process, tumor cells tend to acquire more mutations. Bearing a high mutation burden leads to a greater number of neoantigens with the potential to initiate an immune response. Although many tumors evoke an immune response, tumor clearance by the immune system does not occur due to a suppressive tumor microenvironment. The mechanisms by which tumors achieve the ability to evade immunologic control vary. Understanding these differences is crucial for the improvement and application of new immune-based therapies. Much effort has been placed in developing in silico algorithms to predict tumor immunogenicity and to characterize the microenvironment via high-throughput sequencing and gene expression techniques. Each sequencing source, transcriptomics, and genomics yields a distinct level of data, helping to elucidate the tumor-based immune responses and guiding the fine-tuning of current and upcoming immune-based therapies. In this review, we explore some of the immunological concepts behind the new immunotherapies and the bioinformatic tools to study the immunological aspects of tumors, focusing on neoantigen determination and microenvironment deconvolution. We further discuss the immune-based therapies already in clinical use, those underway for future clinical application, the next steps in immunotherapy, and how the characterization of the tumor immune contexture can impact therapies aiming to promote or unleash immune-based tumor elimination.


Subject(s)
Humans , Immunotherapy/methods , Neoplasms/immunology , Neoplasms/therapy , Genetic Therapy , Cell Transformation, Neoplastic , Combined Modality Therapy , Tumor Escape/immunology , Cancer Vaccines/therapeutic use , Tumor Microenvironment/immunology , Mutation , Antigens, Neoplasm/analysis , Neoplasms/genetics
20.
Chinese Medical Journal ; (24): 1191-1198, 2018.
Article in English | WPRIM | ID: wpr-688146

ABSTRACT

<p><b>Background</b>The hedgehog signaling system (HHS) plays an important role in the regulation of cell proliferation and differentiation during the embryonic phases. However, little is known about the involvement of HHS in the malignant transformation of cells. This study aimed to detect the role of HHS in the malignant transformation of human bronchial epithelial (16HBE) cells.</p><p><b>Methods</b>In this study, two microfluidic chips were designed to investigate cigarette smoke extract (CSE)-induced malignant transformation of cells. Chip A contained a concentration gradient generator, while chip B had four cell chambers with a central channel. The 16HBE cells cultured in chip A were used to determine the optimal concentration of CSE for inducing malignant transformation. The 16HBE cells in chip B were cultured with 12.25% CSE (Group A), 12.25% CSE + 5 μmol/L cyclopamine (Group B), or normal complete medium as control for 8 months (Group C), to establish the in vitro lung inflammatory-cancer transformation model. The transformed cells were inoculated into 20 nude mice as cells alone (Group 1) or cells with cyclopamine (Group 2) for tumorigenesis testing. Expression of HHS proteins was detected by Western blot. Data were expressed as mean ± standard deviation. The t-test was used for paired samples, and the difference among groups was analyzed using a one-way analysis of variance.</p><p><b>Results</b>The optimal concentration of CSE was 12.25%. Expression of HHS proteins increased during the process of malignant transformation (Group B vs. Group A, F = 7.65, P < 0.05). After CSE exposure for 8 months, there were significant changes in cellular morphology, which allowed the transformed cells to grow into tumors in 40 days after being inoculated into nude mice. Cyclopamine could effectively depress the expression of HHS proteins (Group C vs. Group B, F = 6.47, P < 0.05) and prevent tumor growth in nude mice (Group 2 vs. Group 1, t = 31.59, P < 0.01).</p><p><b>Conclusions</b>The activity of HHS is upregulated during the CSE-induced malignant transformation of 16HBE cells. Cyclopamine can effectively depress expression of HHS proteins in vitro and prevent tumor growth of the transformed cells in vivo.</p>


Subject(s)
Animals , Cell Transformation, Neoplastic , Genetics , Metabolism , Gene Expression Regulation, Neoplastic , Genetics , Physiology , Hedgehog Proteins , Genetics , Metabolism , Lab-On-A-Chip Devices , Mice , Mice, Inbred BALB C , Mice, Nude , Microfluidics , Signal Transduction , Genetics , Physiology , Smoke , Smoking
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