Nueva mutación en el gen TSC2 protege contra el cáncer colorrectal en población mexicana / A novel mutation in the TSC2 gene protects against colorectal cancer in the Mexican population

Resumen Introducción: El cáncer colorrectal (CCR) es una enfermedad compleja debido al gran número de factores que influyen en su desarrollo, incluyendo variantes en genes supresores de tumores. Objetivo: Estimar las frecuencias alélicas y genotípicas de las variantes c.3915G>A y c.5371G>A del gen TSC2 en una población mexicana con CCR, así como analizar la asociación con el desarrollo de CCR. Métodos: Se incluyeron 126 muestras de sangre periférica de pacientes con diagnóstico de CCR esporádico y 134 de individuos sanos, considerados como grupo de control. La identificación de los genotipos se llevó a cabo mediante PCR tradicional y digestión enzimática. Todos los individuos firmaron una carta de consentimiento informado. Resultados: El alelo A de la variante c.3915G>A (RM = 0.31, IC 95 % = 0.15-0.69, p = 0.004), así como el haplotipo A/G de las variantes c.3915G>A y c.5371G>A (RM = 0.28, IC 95 % = 0.12-0.68, p = 0.005) mostraron un posible efecto protector contra CCR esporádico. El análisis in silico indicó que ambas variantes generan modificaciones en el proceso de corte y empalme. Conclusión: La presencia de la variante c.3915G>A del gen TSC2 sugiere un posible efecto protector contra CCR esporádico en población mexicana; sin embargo, no se observó esta asociación con la variante c.5371G>A.

Abstract Introduction: Colorectal cancer (CRC) is a complex disease due to the large number of factors that influence its development, including variants in tumor suppressor genes. Objective: To estimate allelic and genotypic frequencies of c.3915G>A and c.5371G>A variants of the TSC2 gene in a Mexican population with CRC, as well as to analyze their association with the development of CRC. Methods: 126 peripheral blood samples from patients diagnosed with sporadic CRC and 134 from healthy individuals, regarded as the control group, were included. Identification of genotypes was carried out using traditional PCR and enzymatic digestion. All individuals signed an informed consent letter. Results: The A allele of the c.3915G>A variant (OR = 0.31, 95% CI = 0.15-0.69, p = 0.004), as well as A/G haplotype of the c.3915G>A and c.5371G>A variants (OR = 0.28, 95% CI = 0.12-0.68, p = 0.005) showed a possible protective effect against sporadic CRC. In silico analysis indicated that both variants generate modifications in the splicing process. Conclusion: The presence of TSC2 gene c.3915G>A variant suggests a possible protective effect against sporadic CRC in the Mexican population; however, no association was observed with the c.5371G>A variant.

Genes involucrados en el cáncer pulmonar / Genes involved in lung cancer

Introducción: El cáncer pulmonar constituye un serio problema de salud mundial por su elevada prevalencia y mortalidad. En la carcinogénesis pulmonar están implicados oncogenes y genes supresores tumorales, que en una compleja interacción con factores ambientales favorecen la transformación cancerosa. Objetivo: Describir los principales genes implicados en el cáncer pulmonar. Métodos: Se buscaron referencias en las bases de datos PubMed Central, Annual Reviews y SciELO. Se revisaron preferentemente los artículos originales, las revisiones bibliográficas, las revisiones sistemáticas y los metaanálisis de los últimos cinco años. Análisis e integración de la información: En la carcinogénesis pulmonar se involucran los oncogenes JUN, FOS, ABL1, BRAF, RAF1, GNAS, KRAS, NRAS, HRAS, CSF 1R, MYC, EGFR, MET, ALK, CCNE1, DDR2, ERBB3, FGFR1, MDM2, ROS1, SOX2 y TP63 y los genes supresores tumorales TP53, CDKN2A, CDKN1A, RB1, CDK2AP1, ATM, ERCC2, BRCA1, CCND1, STK11, PDLIM2, PTEN, ARID1A, ASCL4, CUL3, EP300, KEAP1, KMT2D, NF1, NOTCH1, RASA1, ETD2 y SMARCA4. El conocimiento de la genética molecular del cáncer pulmonar es importante para la identificación de biomarcadores diagnósticos y pronósticos más eficaces y para el diseño de fármacos diana sobre genes específicos(AU)

Introduction: Lung cancer is a serious global health problem due to its high prevalence and mortality. Lung carcinogenesis involves oncogenes and tumor suppressor genes which interact in complex manners with environmental factors, paving the way for the cancerous transformation. Objective: Describe the main genes involved in lung cancer. Methods: References were searched for in the databases PubMed Central, Annual Reviews and SciELO. Particular attention was paid to original papers, bibliographic reviews, systematic reviews and meta-analyses published in the last five years. Data analysis and integration: Lung carcinogenesis involves the oncogenes JUN, FOS, ABL1, BRAF, RAF1, GNAS, KRAS, NRAS, HRAS, CSF 1R, MYC, EGFR, MET, ALK, CCNE1, DDR2, ERBB3, FGFR1, MDM2, ROS1, SOX2 and TP63, and the tumor suppressor genes TP53, CDKN2A, CDKN1A, RB1, CDK2AP1, ATM, ERCC2, BRCA1, CCND1, STK11, PDLIM2, PTEN, ARID1A, ASCL4, CUL3, EP300, KEAP1, KMT2D, NF1, NOTCH1, RASA1, ETD2 and SMARCA4. Knowledge about the molecular genetics of lung cancer is important to identify more efficient diagnostic and prognostic biomarkers and to design targeted drugs for specific genes(AU)

Estudo da correlação das proteínas INGs com a P53 em lesões odontogênicas epiteliais benignas / Study of the correlation of INGs proteins with P53 in benign epithelial odontogenic lesions

As proteínas INGs (inhibitor of growth gene) desempenham papel de supressoras tumorais e podem agir por vias dependentes, ou independentes, da p53 na sinalização do ciclo celular e da apoptose. Este trabalho investigou, por meio de imuno-histoquímica, a correlação entre a expressão das proteínas INGs e a expressão da proteína p53 em ceratocistos odontogênicos (20), TOAs (20) e ameloblastomas sólidos (20). Os espécimes foram submetidos à marcação utilizando os anticorpos anti-Ing3, anti-Ing4, anti-Ing5 e anti-p53. Foi realizada análise quantitativa levando-se em consideração a localização citoplasmática e/ou nuclear para as proteínas INGs e a localização nuclear para a proteína p53. A análise da imunoexpressão das proteínas ING1 e ING2 foi realizada em um estudo prévio e os resultados foram considerados apenas para a análise de correlação com as proteínas estudadas neste estudo. Os dados foram analisados pelo Statistical Package for Social Sciences para Windows (SPSS versão 22.0; IBM, USA). Para a comparação da imunoexpressão entre os grupos de lesões foi utilizado o teste de Kruskal Wallis, e para a investigação das correlações foi utilizado o teste de Spearman. Foram considerados significativos os valores de p ≤ 0.05. O presente estudo evidenciou redução da expressão nuclear e citoplasmática das proteínas ING3, ING4 e ING5 em ceratocistos odontogênicos (COs) e ameloblastomas (AMBs). Além disso, em alguns casos, a perda da expressão nuclear das INGs esteve negativamente correlacionada à expressão da proteína p53. As análises de correlação entre as proteínas INGs indicam a existência de mecanismos compensatórios entre as proteínas INGs em folículos dentários (FDs) e tumores odontogênicos adenomatoides (TOAs), estes mecanismos parecem ser menos evidentes em COs e AMBs. Observou-se redução na expressão da proteína ING3 em AMBs (p=0,003); redução na expressão da proteína ING4, tanto em AMBs (p=0,02) quanto em COs (p=0,001); e uma redução da expressão nuclear da proteína ING5 nos COs (p=0,09) e nos AMBs (p=0,012). Foram evidenciadas correlações positivas entre a expressão nuclear da p53 com a expressão citoplasma/núcleo da proteína ING1 (r=0,603; p=0,05) em COs, e com a expressão citoplasma/ núcleo das proteínas ING3 (r=0,475; p=0,034) e ING4 (r=0,448; p=0,047) em AMBs. Por fim, os resultados deste estudo sugerem que a redução na expressão nuclear das proteínas INGs pode ser um evento envolvido na etiopatogênese de lesões odontogênicas mais agressivas, e que a redução da expressão nuclear/citoplasmática das proteínas INGs não está relacionada ao aumento expressão da p53 em COs e AMBs, o que sugere que a expressão destas proteínas deve resultar em alterações funcionais de maneira independente da p53 em lesões odontogênicas (AU).

INGs (inhibitor of growth gene) proteins play a role of tumor suppressors and can act via p53-dependent or independent pathways in signaling cell cycle and apoptosis. The aim of this study is to evaluate correlation between expression of proteins of ING proteins and expression of protein p53 in dental follicles (DF), odontogenic keratocysts (OK), adenomatoid odontogenic tumors (AOT) and solid ameloblastomas (AMBs). The sample was intentional and non-probabilistic, consisting of 20 cases of solid AMBs, 20 cases of AOT, 20 cases of OKs and 10 samples of DFs. The specimens were subjected to immunohistochemical method, using antibodies anti-Ing3, anti-Ing4, anti-Ing5 and antip53. Quantitative analysis was performed taking into account cytoplasmic and / or nuclear location for ING proteins and nuclear location for the p53 protein. The analysis of ING1 and ING2 immunoexpressions was performed in a previous study and the results were considered only for the correlation analysis. Data were analyzed by Statistical Package for Social Sciences for Windows (SPSS version 22.0; IBM, USA). Kruskal Wallis test was used to compare the immunoexpression between the groups of lesions, and Spearman test was used to investigate correlations. Values of p ≤ 0.05 were considered significant. This study showed a reduction in nuclear and cytoplasmic expression of ING3, ING4 and ING5 in odontogenic keratocysts (OKs) and ameloblastomas (AMBs). In addition, in some cases, loss of INGs nuclear expression was negatively correlated with p53 expression. Correlation analyzes may indicate existence of compensatory mechanisms between all the ING proteins in dental follicles (FDs) and adenomatoid odontogenic tumors (TOAs). These mechanisms seem to be less evident in COs and AMBs. The results of this study showed a reduction in ING3 expression in AMBs (p = 0.003); a reduction in ING4 expression, in OKs (p = 0.02) and in AMBs (p = 0.001); and a reduction in ING5 nuclear expression, also in OK (p = 0.09) and in AMBs (p = 0.012). Positive correlations were found between p53 nuclear expression with ING1 cytoplasm / nucleus expression (r = 0.603; p = 0.05) in OKs, and with ING3 cytoplasm / nucleus expression (r = 0.475; p = 0.034) and also ING4 cytoplasm / nucleus expression (r = 0.448; p = 0.047) in AMBs. Finally, this study suggests that reduction in the expression of INGs proteins seems to be an event that occurred in etiopathogenesis of more aggressive odontogenic lesions. Futhermore, nuclear / cytoplasmic expression of INGs proteins is not related to increase in p53 expression in OKs and AMBs, which indicates that loss of expression of these proteins may results in functional changes independently of p53 (AU).

Reversal of Hypermethylation in Tumor Suppressor Genes Using Phytochemicals in Cervical Cancer

Cervical cancer is most familiar neoplasm among women worldwide. Surgery, radiotherapy, and chemotherapy are common treatments, however high stage tumors have frequently poor prognosis. HPV 16 and 18 are major etiological factors for cervical cancer. Likewise, epigenetics is the study of inherited changes and modulated gene expression without alteration in DNA sequences. In mammals epigenetic modifications include DNA methylation, histone modifications and miRNA. Phytochemicals are mainly contained in fruits, seeds, and vegetables as well as in foods supplements. Numerous dietary compounds exhibit potent anti-tumor activities through the reversion of epigenetic alterations associated to oncogenes activation and inactivation of tumor suppressor genes in cervical cancer cell lines SiHa and HeLa, demethylation of the tumour suppressor genes such as RARβ2, MGMT, RASSF1A, DAPK etc. Reversal of hypermethylated genes as a tumor-suppressor gene, is related to inhibition of cell proliferation, development and differentiation. The impact of phytochemicals lead to the reversal of hypermethylation which may help to cure cervical cancer. This study concludes the effect of phytochemicals on genetic and epigenetic modifications and reveals how these modifications help to prevent various types of cancers and improve health outcomes.

The Roles of miRNAs in Medulloblastoma: A Systematic Review

Medulloblastoma is considered one of the most threatening malignant brain tumors with an extremely high mortality rate in children. In the medulloblastoma, there are several genes and mutations found to work in an unregulated manner that works together to push the cells into a cancerous state. With the discovery of non-coding RNAs such as microRNAs (miRNAs), it has been shown that a different layer of gene regulations may be disrupted which would cause cancer. This fact led scientists to put their focus on the role of miRNAs in cancer. A mature miRNA contains a seed sequence which gives the miRNA to identify and attach to the interest mRNA; this attachment may lead degradation of mRNA or suppress of translation of the mRNA. The expression of miRNAs in medulloblastoma shows that some of these non-coding RNAs are overexpressed (OncomiRs) which help cells to proliferate and keep their stemness features. On the other hand, there are other forms of these miRNAs which normally inhibit cell proliferation and promote cell differentiation (tumor suppressor). These are down-regulated during cancer progression. In this systematic review, we attempted to gather several important studies on miRNAs’ role in medulloblastoma tumors and the importance of these non-coding RNAs in the future study of cancer.

Mechanism of tumor suppressor gene DKK2 inhibiting proliferation of nephroblastoma cells in children / 实用肿瘤学杂志

Objective The aims of this study were to investigate the expression of DKK2,a WNT signaling pathway regula-tor,in nephroblastoma cells and tissues of children,the effect on the proliferation of nephroblastoma SK-NEP-1 cells,and to explore its mechanism. Methods The relative expression of DKK2 in nephroblastoma cells and tissues was analyzed by qRT-PCR and im-munoblotting assays. Overexpressing DKK2 SK-NEP-1 cells were set as the experimental group( DKK2 group);the blank control plasmid group was set as a control group( Vector group),transfected with pcDNA3. 1 ( +) -Flag-DKK2 plasmid( Experimental group)and pcDNA3. 1( +) -Flag-Vector plasmid(Control group). The over-expression of DKK2 was confirmed in SK-NEP-1 cells by RT-PCR and immunoblotting. CCK-8 and cell cloning assays were used to determine the effect of DKK2 on cell prolifera-tion;flow cell cycle and apoptosis assays were used to confirm the effect on cell proliferation in overexpressed DKK2 cells. The xen-graft formation assay in nude mice was to verify the effect of DKK2 on proliferation in overexpressed DKK2 cells;the mechanism of DKK2 in inhibitory proliferation was analyzed by qRT-PCR,Western blotting and immunohistochemistry. Results Compared with normal renal epithelial tissues,DKK2 mRNA was down-regulated in children with nephroblastoma,and the difference was statistically significant(P<0. 001). Compared with the control group,transfected DKK2 cell viability was significantly inhibited after treatment for 24,48 and 72 h( P<0. 05),cell clone formation in the experimental group was significantly inhibited(31. 11% ± 2. 14% ) ( P<0. 05),the cell cycle in the experimental group was significantly arrested at the G1 phase(P<0. 001),and the apoptosis rate in the experimental group was significantly increased(P<0. 001). Compared with the control group,the tumor weight and volume in nude mice were significantly low in the experimental mice which were injected DKK2 overexpression cells(P<0. 001). Active-β-cate-nin and downstream genes were significantly inhibited in over-expressed DKK2 SK-NEP-1 cells. Conclusion DKK2 is down-regulated in human cutaneous nephroblastoma and participates in the mechanism of nephroblastoma by antagonizing Wnt/β-catenin signaling pathway.

Epigenética del cáncer colorrectal / Epigenetics of Colorectal Cancer

Resumen El cáncer colorrectal (CCR) es una enfermedad con una amplia distribución geográfica, que afecta a millones de personas en el mundo. Esta neoplasia se presenta de manera esporádica en el 80% de los casos, el porcentaje restante tiene una historia familiar. Las alteraciones epigenéticas, como la metilación del ADN, modificación de las histonas y los ácidos ribonucleicos (ARN) no codificantes, están involucradas en el desarrollo de esta enfermedad. En la actualidad, estas alteraciones tienen un potencial valioso como biomarcadores para la detección temprana del CCR y se considera que podrían ser útiles para el diagnóstico y pronóstico de los individuos con CCR. El propósito de esta revisión es describir los principales mecanismos epigenéticos involucrados en el cáncer colorrectal, que tienen una función importante en el desarrollo y progresión de la enfermedad.

Abstract Colorectal cancer (CRC) has broad geographic distribution and affects millions of people throughout the world. It occurs sporadically in 80% of cases, but the rest have family histories. Epigenetic alterations such as DNA methylation and modification of histones and non-coding RNA are involved in the development of this disease. At present, these alterations have valuable potential as biomarkers for early detection of CRC and could be useful for diagnosis and determination of prognosis for individuals with CRC. The purpose of this review is to describe the main epigenetic mechanisms involved in colorectal cancer and the important roles they have in the development and progression of the disease.

Deficiency of Follistatin-Like Protein 1 Accelerates the Growth of Breast Cancer Cells at Lung Metastatic Sites / 한국유방암학회지

PURPOSE: Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has been shown to play a role in various types of cancer. However, the clinical significance and function of FSTL1 in breast cancer have not been reported. We investigated the role of FSTL1 in breast cancer in this study. METHODS: Enzyme-linked immunosorbent assays, western blot analysis, and reverse transcription polymerase chain reaction were used to monitor the expression of FSTL1 in breast cancer tissue and in serum samples from breast cancer patients. We employed a 4T1 breast cancer model and Fstl1(+/−) mice for in vivo studies. Hematoxylin and eosin staining, western blot analysis, and RNA sequencing were used to analyze the effect of FSTL1 on primary tumor growth and lung metastasis. RESULTS: We demonstrated that the expression of FSTL1 is reduced in both the breast cancer tissue and the serum of breast cancer patients. We showed that reduced levels of FSTL1 in serum correlate with elevated expression of Ki-67 and epidermal growth factor receptor (EGFR) in cancer tissues. Moreover, lowered expression of FSTL1 was associated with decreased survival in breast cancer patients. Experiments on the Fstl1(+/−) mouse model established that FSTL1 deficiency had no effect on primary tumor growth, but increased the lung metastases of breast cancer cells, resulting in reduced survival of tumor-bearing mice. RNA sequencing found significantly reduced expression of Egln3 and increased expression of EGFR in Fstl1(+/−) mice. Thus, our results suggest that FSTL1 may affect the expression of EGFR through Egln3, inhibiting the proliferation of breast cancer cells at lung metastatic sites. CONCLUSION: In conclusion, we suggest a suppressor role of FSTL1 in breast cancer lung metastasis. Furthermore, FSTL1 may represent a potential prognostic biomarker and a candidate therapeutic target in breast cancer patients.

Research progress of relevance between miRNAs and hepatocellular carcinoma / 中国药理学通报

Hepatocellular carcinoma(HCC)is one of the most common malignancies worldwide.Due to the difficulty of diagnosis in the early stage of HCC, most HCCs are diagnosed in intermediate-advanced stage.Moreover, the high invasion, metastasis and recurrence rate of HCC result in the high mortality of HCC.MicroRNAs(miRNAs) are a class of highly conserved, endogenous, small, non-coding ,single stranded RNA with the length of 22 nucleotides.There are plentiful of miRNAs in liver.MiRNAs not only can regulate the growth and development of liver, but also are closely related to the formation of HCC.In the process of HCC formation, miRNAs could function as oncogenes or tumor suppressor genes to regulate multiple biological processes related to HCC, including cell differentiation,proliferation,tumorigenesis,angiogenesis,invasion,and metastasis.With the intensive study of molecular mechanisms of miRNAs in the process of HCC formation, increasingly studies have revealed that miRNAs could become sensitive biomarkers and effective therapeutic targets for HCC.

Effects of tumor suppressor gene Dickkopf-3 on proliferation and apoptosis of cutaneous malignant melanoma cells / 中华皮肤科杂志

Objective To investigate the expression of Dickkopf-3 (DKK3) in human malignant melanoma cell lines and tissues,and to evaluate effects of DKK3 on the proliferation and apoptosis of malignant melanoma cell line A375.Methods Reverse transcription PCR (RT-PCR) and real-time fluorescence-based quantitative PCR (qRT-PCR) were performed to measure the mRNA expression of DKK3 in human malignant melanoma cell lines HM,A375,WM451,WM35,SK-MEL-1,Hs-695T and MDA-MB-435s,as well as in 38 primary melanoma tissues,4 metastatic melanoma tissues and 20 pigmented nevus tissues.Cultured malignant melanoma A375 cells were divided into 2 groups to be transfected with pcDNA3.1 (+)-Flag-DKK3 (experiment group) and pcDNA3.1 (+)-Flag-Vector (control group) respectively.The overexpression of DKK3 was verified by RT-PCR.Cell counting kit-8 (CCK8) assay and plate colony formation assay were performed to evaluate the proliferative activity of A375 cells,flow cytometry was conducted to detect apoptosis of A375 cells,and Western blot analysis was performed to determine the expression of cell cycle-and cell apoptosis-related proteins.Results The mRNA expression of DKK3 was downregulated in WM35 cells,absent in HM cells,A375 cells,WM451 cells,SK-MEL-1 cells and Hs-695T cells,but upregulated in MDA-MB-435s cells.Compared with pigmented nevus tissues,the mRNA expression of DKK3 was significantly decreased in malignant melanoma tissues (P ＜ 0.001).Compared with the control group (100％),cell colony formation was markedly suppressed in the experiment group (23.22％ ± 3.55％),and the proliferative activity of A375 cells was also significantly inhibited in the experiment group 24,48,72 hours after the transfection (all P ＜ 0.05).Flow cytometry showed that compared with the control group,A375 cells were significantly arrested in G1 phase (48.68％ ± 3.92％ vs.25.38％ + 2.92％,P ＜ 0.001),and the apoptosis rate of A375 cells was significantly increased in the experiment group (P ＜ 0.001).Compared with the control group,the experiment group showed significantly higher expression of p21,Bax,cleaved-parp and cleaved-casp3,but significantly lower expression of cyclin D1 and Bcl2 (all P ＜ 0.001).Conclusion DKK3 expression is downregulated in human malignant melanoma tissues,so it may serve as a potential tumor suppressor gene involved in the development of cutaneous malignant melanoma.

Clinicopathological Significance of Large Tumor Suppressor (LATS) Expression in Gastric Cancer

PURPOSE: The aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS). MATERIALS AND METHODS: LATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009. RESULTS: Low expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (≥65, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low LATS1 (P=0.037) and LATS2 (P=0.037) expression. CONCLUSIONS: Expression of LATS1 or LATS2 is a significant marker for a good prognosis in patients with gastric cancer.

Factores de riesgo de cáncer bucal / Risk factors for oral cancer

Introducción: el cáncer bucal, una enfermedad con elevada morbilidad y mortalidad, se asocia a factores de riesgo, cuya compleja interrelación está sometida a debate científico. Objetivo: actualizar a los profesionales acerca de los factores de riesgo de cáncer bucal. Métodos: la revisión bibliográfica se realizó en SciELO Regional con los descriptores factores de riesgo y cáncer bucal; se encontraron 31 referencias a texto completo. En Clinical Key con cáncer de labio y cavidad bucal se hallaron 1 746; con los descriptores en inglés genes y oral cancer se obtuvieron 9 822 resultados. En PubMed con el descriptor oral cancer se encontraron 1 207 artículos. En EBSCO con el descriptor oral cancer se encontraron a texto completo de los últimos 5 años, 839 artículos. Se recuperaron 200 artículos en inglés y español, principalmente desde 2010 hasta 2015 y se acotaron 62 artículos. Resultados: en la carcinogénesis bucal se afectan los oncogenes y los genes supresores tumorales. Los factores de riesgo no genéticos son el hábito de fumar, consumo de bebidas alcohólicas, estados carenciales de nutrientes, factores ambientales como las radiaciones y los metales pesados y diferentes infecciones bacterianas, micóticas y virales. Estos factores se relacionan también con inmunodepresión, fricción mecánica por prótesis desajustadas y mala higiene bucal. Conclusiones: se describen los principales factores de riesgo de cáncer bucal. Los genes de susceptibilidad al cáncer interaccionan con factores de riesgo relacionados principalmente con estilos de vida y factores ambientales en una compleja red, cuya identificación y control en la atención primaria de salud es importante en la prevención del cáncer bucal por parte de los estomatólogos(AU)

Introduction: oral cancer is a disease with high morbidity and mortality, associated with risk factors whose complex interplay is subject to scientific debate. Objective: to upgrade to the professionals about the risk factors for oral cancer. Methods: the literature review was conducted in SciELO Regional with the descriptors risk factors and oral cancer, for which 31 full-text references were found. In Clinical Key, with the descriptor cancer of the lip and oral cavity, we found 1746; English descriptors with genes and oral cancer retrieved 9822 results. PubMed, with the descriptor "oral cancer", retrieved 1207 items. EBSCO, with the descriptor "oral cancer", offered full texts of 5 recent years (839 articles). 200 articles in English and Spanish were retrieved, mainly from 2010-2015, and 62 papers were used. Data analisys and integration: in the oral carcinogenesis, tumor suppressor genes and oncogenes are affected. The non-genetic risk factors are smoking, alcohol consumption, and nutrient deficiency states, environmental factors such as radiation and heavy metals and different bacterial, fungal and viral infections. These factors are also related to immunosuppression, mechanical friction by maladjusted dentures and poor oral hygiene. Conclusions: the main risk factors for oral cancer are described. Susceptibility genes to cancer interact with risk factors mainly related to lifestyle and environmental factors in a complex network, whose identification and control in primary health care is important in the prevention of oral cancer by dentists(AU)

Papel de la reprogramación metabólica en la carcinogénesis / Role of Metabolic Reprogramming in Carcinogenesis

El papel de los oncogenes y genes supresores de tumor en el control del ciclo celular es conocido, pero, su efecto directo en el metabolismo de la célula tumoral resulta un tema novedoso en la Oncología actual. El concepto de reprogramación metabólica es retomado como un concepto interesante. Por ello, se realizó la presente búsqueda bibliográfica en la base de datos PubMed usando los descriptores: genes, suppressor and metabolism; oncogenes and metabolism; neoplasms and metabolism. Las mutaciones en oncogenes que codifican para PI3K, AKT, mTORC y Myc inducen un aumento de la expresión de isoenzimas de la vía glucolítica y reprimen la fosforilación oxidativa, lo que garantiza un metabolismo anabólico, además, se relacionan con el aumento del consumo de glucosa y liberación de lactato. En células transformadas se demuestra la importancia del metabolismo anabólico para la progresión del tumor, esta es una alternativa para su tratamiento.

The role of the genes that suppress tumors and oncogenes in cellular cycle control is known but its effect in tumoral metabolism is a novel topic in the modern oncology. Nowadays the concept of metabolic reprograming in tumors has been reexamined as an important process related to carcinogenesis. A literature review was done in PubMed database by using descriptors such as genes, suppressor and metabolism; oncogenes and metabolism; neoplasms and metabolism. Oncogenes mutations of code for PI3K, AKT, mTORC and Myc induce an increase of the expression of isoenzimes of the glycolytic path, while they inhibit oxidative phosphorylation. This makes possible anabolic metabolism. They are also related to an increase in glucose consumption rates and the release of lactase to the tumoral microenvironment. The importance of anabolic metabolism in cancer progression has been proved in tumor cells, which is another option in the treatment of the disease.

Research advance of PDSS2 gene on carcinoma / 中国病理生理杂志

[ ABSTRACT] Prenyl diphosphate synthase subunit 2 ( PDSS2), which encodes the second subunit of prenyl diphosphate synthase, an essential enzyme involved in the biosynthesis of coenzyme Q10 (CoQ10), is almost expressed in all tissues and organs at different developmental stages of human beings.The abnormal expression of PDSS2 may result in many diseases through impacting the biosynthesis of CoQ10.Recent studies show that PDSS2 gene has decreased in mela-noma, gastric cancer, lung cancer and hepatocellular carcinoma, and the degree of reduced level is closely related to the clinical features, which enlighten us that PDSS2 maybe a tumor suppressor gene involves in the development and progres-sion of carcinoma.This review aims to introduce the recent research progress about PDSS2 gene on carcinoma, discuss its roles and value on cancer research.

Effects of a small interfering RNA targeting HPV16E7 on proliferation and apoptosis of SiHa cells and expressions of six tumor suppressor genes / 中华皮肤科杂志

Objective To evaluate effects of human papilloma virus(HPV)16E7 on expressions of six tumor suppressor genes(including MT1G, NMES1, RRAD, SFRP1, SPARC and TFPI2)in a cell line SiHa, as well as on its proliferation and apoptosis. Methods SiHa cells were divided into two groups to be transfected with a small interfering RNA targeting HPV16E7(E7SiRNA, experimental group)and an empty vehicle(negative control group) respectively, with SiHa cells receiving no treatment serving as the blank control group. After 48 hours, qPCR was performed to measure the mRNA expressions of E7 and six tumor suppressor genes, CCK?8 assay to evaluate cellular proliferative activity, and flow cytometry to assess apoptosis of SiHa cells. Results At 48 hours after the transfection, the experimental group showed significantly decreased E7 mRNA expression(0.25 ± 0.036, P0.05). Conclusion E7 may participate in HPV16?induced cellular malignant transformation by suppressing the mRNA expressions of 6 tumor suppressor genes, including MT1G, NMES1, RRAD, SFRP1, SPAR and TFPI2.

Applicability of RNA interference in cancer therapy: Current status.

Cancer is a manifestation of dysregulated gene function arising from a complex interplay of oncogenes and tumor suppressor genes present in our body. Cancer has been constantly chased using various therapies but all in vain as most of them are highly effective only in the early stages of cancer. Recently, RNA interference (RNAi) therapy, a comparatively new entrant is evolving as a promising player in the battle against cancer due to its post‑transcriptional gene silencing ability. The most alluring feature of this non‑invasive technology lies in its utility in the cancer detection and the cancer treatment at any stage. Once this technology is fully exploited it can bring a whole new era of therapeutics capable of curing cancer at any stage mainly due to its ability to target the vital processes required for cell proliferation such as response to growth factors, nutrient uptake/synthesis, and energy generation. This therapy can also be used to treat stage IV cancer, the most difficult to treat till date, by virtue of its metastasis inhibiting capability. Recent research has also proved that cancer can even be prevented by proper modulation of physiological RNAi pathways and researchers have found that many nutrients, which are a part of routine diet, can effectively modulate these pathways and prevent cancer. Even after having all these advantages the potential of RNAi therapy could not be fully tapped earlier, due to many limitations associated with the administration of RNAi based therapeutics. However, recent advancements in this direction, such as the development of small interfering RNA (siRNA) tolerant to nucleases and the development of non‑viral vectors such as cationic liposomes and nanoparticles, can overcome this obstacle and facilitate the clinical use of RNAi based therapeutics in the treatment of cancer. The present review focuses on the current status of RNAi therapeutics and explores their potential as future diagnostics and therapeutics against cancer.

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.

Alteraciones moleculares implicadas en la fisiopatogenia del cáncer y su utilidad para la investigación en medicina / Molecular changes involved in physiopathogeny of cancer and their utility for research in medicine

La neoplasia es una enfermedad genética que usa mecanismos de progresión e invasión similares a los de los tejidos normales cuando proliferan. Su aparición se debe a la suma de alteraciones genéticas que facilitan la progresión tumoral por fallos en los mecanismos de senescencia celular y apoptosis. Dentro de las principales alteraciones moleculares destacan la expresión aberrante de oncogenes, genes supresores tumorales, enzimas y factores de transcripción que promueven un ciclo celular anómalo. El objetivo de esta revisión es el de conocer algunos de los cambios moleculares implicados en el inicio, promoción y progresión de las neoplasias, con el fin de tener información de los genes útiles para realizar diagnósticos más tempranos del cáncer, que favorezcan el pronóstico de la enfermedad y que sean útiles para la investigación en biotecnología diagnóstica y en terapia génica.

Neoplasia, considered as a genetic disease that uses progression mechanisms similar to the normal tissues' when proliferates. Its presence is due to genetic alterations that facilitate tumor progression by failures in the mechanisms of cellular senescence and apoptosis. Within the main molecular alterations the most important are: aberrant expression of oncogenes, tumor suppressor genes, enzymes and transcription factors that promote abnormal cell cycle. The main objective of this paper is to review some of the molecular changes involved in the initiation, promotion and progression of neoplasms, in order to have genes useful information for earlier diagnosis of cancer, favoring the prognosis of genes disease, for diagnostic research in biotechnology and gene therapy.

Regulation and Function of the Peg3 Imprinted Domain

A subset of mammalian genes differ functionally between two alleles due to genomic imprinting, and seven such genes (Peg3, Usp29, APeg3, Zfp264, Zim1, Zim2, Zim3) are localized within the 500-kb genomic interval of the human and mouse genomes, constituting the Peg3 imprinted domain. This Peg3 domain shares several features with the other imprinted domains, including an evolutionarily conserved domain structure, along with transcriptional co-regulation through shared cis regulatory elements, as well as functional roles in controlling fetal growth rates and maternal-caring behaviors. The Peg3 domain also displays some unique features, including YY1-mediated regulation of transcription and imprinting; conversion and adaptation of several protein-coding members as ncRNA genes during evolution; and its close connection to human cancers through the potential tumor suppressor functions of Peg3 and Usp29. In this review, we summarize and discuss these features of the Peg3 domain.

Loss of Heterozygosities in Five Tumor Suppressor Genes (FHIT Gene, p16, pRb, E-Cadherin and p53) in Thyroid Tumors

OBJECTIVES: To evaluate the loss of heterozygosities (LOH) of chromosomes 3p14 (FHIT gene), 9p21 (p16), 13q21 (pRb), 6q22 (E-cadherin) and 17p13 (p53) in various thyroid tumors. METHODS: Eighty thyroid tumor cases (20 follicular adenomas, 10 follicular carcinomas, and 50 papillary carcinomas) have been analyzed for the presence of LOH in chromosomes 3p14, 9p21, 13q21, 6q22, and 17p13 allelic loss, using microsatellite markers and DNA obtained from formalin-fixed paraffin-embedded archival tissues. RESULTS: LOH on 3p14 was found in 10.5%, 33.3%, and 30.4% of follicular adenomas, follicular carcinomas, and papillary carcinomas, respectively. LOH on 9p21 was detected in 6%, 44.4%, and 47.8%, respectively. LOH on pRb gene was found in 5.3%, 20.0%, and 35.4%, respectively. LOH on E-cadherin gene was found in 5.3%, 22.2%, and 43.8%, respectively. LOH on 17p13 was detected in 0%, 40%, and 45.8%, respectively. LOH in FHIT gene, p16, pRb, E-cadherin, and p53 genes were more frequently identified in follicular carcinoma and papillary carcinoma than in follicular adenoma. CONCLUSION: LOH results of the five tumor suppressor genes (FHIT gene, p16, pRb, E-cadherin, and p53) showed statistical differences between benign tumor and malignant tumor. Among papillary carcinoma, LOH in p16, E-cadherin and p53 genes well correlated with poorly differentiated grade, and LOH of E-cadherin was associated with lymph node metastasis.