RESUMO
In the spinal cord, attenuation of the inhibitory action of glycine is related to an increase in both inflammatory and diabetic neuropathic pain; however, the glycine receptor involvement in diabetic neuropathy has not been reported. We determined the expression of the glycine receptor subunits (α1-α3 and ß) in streptozotocin-induced diabetic Long-Evans rats by qPCR and Western blot. The total mRNA and protein expression (whole spinal cord homogenate) of the α1, α3, and ß subunits did not change during diabetes; however, the α2 subunit mRNA, but not the protein, was overexpressed 45 days after diabetes induction. By contrast, the synaptic expression of the α1 and α2 subunits decreased in all the studied stages of diabetes, but that of the α3 subunit increased on day 45 after diabetes induction. Intradermal capsaicin produced higher paw-licking behavior in the streptozotocin-induced diabetic rats than in the control animals. In addition, the nocifensive response was higher at 45 days than at 20 days. During diabetes, the expression of the glycine receptor was altered in the spinal cord, which strongly suggests its involvement in diabetic neuropathy.
Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas , Ratos , Animais , Glicina/metabolismo , Receptores de Glicina/genética , Receptores de Glicina/metabolismo , Estreptozocina/toxicidade , Neuropatias Diabéticas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Ratos Long-Evans , Medula Espinal/metabolismo , RNA Mensageiro/metabolismoRESUMO
Cervical cancer (CC) is a public health problem worldwide, including Mexico. This type of cancer is the fourth most frequent in women worldwide; in Mexico it is the second most common type in women after breast cancer. The diagnosis of CC is based mainly on Pap smears and colposcopy and the identification of molecular tools that serve as a support for these methods is urgent. Regarding this, differential expressions of specific circulating biomolecules has been detected and, based on this, they have been postulated as potential biomarkers for CC diagnosis, prognosis, and/or to identify the response to treatments. Importantly, the combined analysis of these molecules considerably improves their efficacy as biomarkers and their potential use in the medical attention is promising.
RESUMO
Background: Mature teratomas belong to the group of germ line ovarian tumors; they generally have benign behavior. Malignant transformation occurs in 0.2% to 1% of tumors. The objective is to show the results of peritonectomy with HIPEC in the treatment of a mature teratoma with malignant differentiation with signet ring cells. Clinical case: 43-year-old woman diagnosed with mature malignant teratoma with signet ring cells. It was performed optimal primary cytoreduction surgery, total hysterectomy, bilateral salpingo-oophorectomy, peritonectomy, appendectomy, cholecystectomy and splenectomy adding intraoperative hyperthermic chemotherapy (HIPEC). Conclusions: Malignant transformation of a mature teratoma of the ovary is a rare event, but not exceptional. HIPEC was used after optimal cytoreduction, with good results, since the patient is in a disease-free period of 36 months. It is necessary to report cases in order to compare different types of treatment to improve oncological results.
Introducción: los teratomas maduros pertenecen al grupo de los tumores de ovario de estirpe germinal; por lo general, tienen un comportamiento benigno. La transformación maligna ocurre en un rango de 0.2 a 1% de los tumores. El objetivo es mostrar los resultados de peritonectomía con HIPEC en el tratamiento de un teratoma maduro con diferenciación maligna con células en anillo de sello. Caso clínico: mujer de 43 años de edad, con diagnóstico de teratoma maduro maligno con células en anillo de sello. Se realizó cirugía de citorreducción primaria optima; histerectomía total, salpingooforectomía bilateral, peritonectomía, apendicectomía, colecistectomía y esplenectomía, además de quimioterapia hipertérmica intraoperatoria (HIPEC). Conclusiones: la transformación maligna de un teratoma maduro del ovario es un evento raro, pero no excepcional. Se utilizó HIPEC posterior a la citorredución óptima y hubo buenos resultados, ya que la paciente lleva un periodo libre de enfermedad de 36 meses. Es necesario el reporte de casos a fin de comparar diversos tipos de tratamiento para mejorar resultados oncológicos.
Assuntos
Neoplasias Ovarianas , Teratoma , Feminino , Humanos , Adulto , Quimioterapia Intraperitoneal Hipertérmica , Teratoma/cirurgia , Teratoma/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , HisterectomiaRESUMO
OBJECTIVE: The objective of the study was to determine the expression levels of BIK in breast cancer (BC) tissues of different histological subtype and to delve into the participation of BIK in this type of cancer. MATERIALS AND METHODS: BIK and p-BIK (the phosphorylated form) protein expressions were tested by immunohistochemistry in BC tissue microarrays (Tumoral [n = 90] and adjacent [n = 40] tissues). RESULTS: The data revealed an overexpression of BIK in invasive ductal (Grades I, IIA, and IIB) and in lobular (Grades IIA and IIB) carcinomas compared to their respective adjacent tissues. By contrast, canalicular carcinoma (Grades I and IIB) and phyllodes tumors had very low expression levels of BIK. Only levels of p-BIK were shown to be increased in invasive ductal carcinoma (Grades I, IIA, and IIB). Meanwhile, quantitative polymerase chain reaction analysis showed lower BIK levels in MCF-10A and MCF-7 cells than in MDA-MB-231 and human mammary epithelial cells. In agreement with this, BIK protein was shown to be overexpressed in MDA-MB 231 relative to MCF-7 cells. CONCLUSIONS: Our results showed an association between BIK expression and the BC tumor subtype under study, which could be related to different BIK functions in the BC subtypes.
OBJETIVO: Determinar el grado de expresión de BIK en tejidos de cáncer de mama de diferente subtipo histológico para ahondar en la participación de BIK en este tipo de cancer. MÉTODO: Por medio de inmunohistoquímica se determinó la expresión de BIK y de su forma fosforilada (p-BIK) en microarreglos de tejidos (tumores [n = 90] y tejidos adyacentes [n = 40]) y líneas celulares. RESULTADOS: Los datos mostraron una sobreexpresión de BIK en los carcinomas de tipo ductal invasivo (grados I, IIA y IIB) y lobular (grados IIA y IIB) con respecto a sus tejidos adyacentes respectivos. En contraste, el carcinoma canalicular (grados I y IIB) y los tumores filoides mostraron una baja expresión de BIK en relación con sus tejidos adyacentes respectivos. El análisis de la qPCR mostró una menor expresión de BIK en las células MCF-10A y MCF-7 en comparación con las células MDA-MB-231 y HMEC. En concordancia con esto, la expresión proteica de BIK fue mayor en las células MDA-MB 231 que en las células MCF-7. CONCLUSIÓN: Nuestros resultados mostraron una asociación entre la expresión de BIK y el subtipo tumoral en estudio, lo cual sugiere una función diferencial de BIK en el cáncer de mama.
Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Proteínas Mitocondriais/biossíntese , Neoplasias da Mama/classificação , Carcinoma Ductal de Mama/classificação , Carcinoma Lobular/classificação , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de TumoresRESUMO
Diabetes mellitus is a metabolic disease that leads to several complications which include retinopathy. Neuronal abnormalities have been reported to appear before microvasculature alterations. We analyzed the expression levels of GlyR subunits in the retina at 7, 20, and 45 days after streptozotocin-induced diabetes to gain insight into the pathogenesis of diabetic retinopathy. We determined the mRNA and protein expression by qPCR and western blot, respectively. The mRNA and protein expression of the α1 subunit was not altered over the study period; however, they were slightly reduced in α2 yet statistically significant. While protein expression of α3 subunit was only reduced at 45 days diabetes. The mRNA and protein expression of the α4 subunit was remarkably decreased since day 7 of diabetes, remaining only â¼20% on day 45 of diabetes. Surprisingly, the mRNA of the ß subunit was highly increased, while its protein levels were not changed. The decrease in GlyR α subunits expression in the retina from diabetic animals suggest a perturbation in the inhibitory glycine signaling pathway, which might be related to the visual alterations observed in diabetes.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Receptores de Glicina/metabolismo , Retina/metabolismo , Animais , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Neurônios/metabolismo , Ratos , Ratos Long-Evans , Receptores de Glicina/genética , Transmissão Sináptica/fisiologiaRESUMO
Expression changes for long non-coding RNAs (lncRNAs) have been identified in adult glioblastoma multiforme (GBM) and in a mixture of adult and pediatric astrocytoma. Since adult and pediatric astrocytomas are molecularly different, the mixture of both could mask specific features in each. We determined the global expression patterns of lncRNAs and messenger RNA (mRNAs) in pediatric astrocytoma of different histological grades. Transcript expression changes were determined with an HTA 2.0 array. lncRNA interactions with microRNAs and mRNAs were predicted by using an algorithm and the LncTar tool, respectively. Interactomes were constructed with the HIPPIE database and visualized with the Cytoscape platform. The array showed expression changes in 156 and 207 lncRNAs in tumors (versus the control) and in pediatric GBM (versus low-grade astrocytoma), respectively. Predictions identified lncRNAs that have putative microRNA binding sites, which might suggest that they function as sponges in these tumors. Also, lncRNAs were shown to interact with many mRNAs, such as Pleckstrin homology-like domain, family A, member 1 (PHLDA1) and sulfatase 2 (SULF2). For example, qPCR found long intergenic non-coding RNA regulator of reprogramming (linc-RoR) expression levels upregulated in pediatric GBM when they were compared with control tissues or with low-grade tumors. Meanwhile, PHLDA1 and ELAV-like RNA binding protein 1 (ELAV1) showed expression changes in tumors relative to the control. Our data showed many lncRNAs with expression changes in pediatric astrocytoma, which might be involved in the regulation of different signaling pathways.
Assuntos
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/metabolismo , Transdução de Sinais/fisiologia , Adolescente , Astrocitoma/genética , Neoplasias Encefálicas/genética , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Masculino , RNA Longo não Codificante/genéticaRESUMO
The development of new fields of study in genetics, as the -omic sciences (transcriptomics, proteomics, metabolomics), has allowed the study of the regulation and expression of genomes. Therefore, nowadays it is possible to study global alterations--in the whole genome--and their effect at the protein and metabolic levels. Importantly, this new way of studying genetics has opened new areas of knowledge, and new cellular mechanisms that regulate the functioning of biological systems have been elucidated. In the clinical field, in the last years new molecular tools have been implemented. These tools are favorable to a better classification, diagnosis and prognosis of several human diseases. Additionally, in some cases best treatments, which improve the quality of life of patients, have been established. Due to the previous assertion, it is important to review and divulge changes in the study of genetics as a result of the development of the -omic sciences, which is the aim of this review.
El desarrollo de nuevas áreas de estudio dentro de la genética, como las ciencias ómicas (transcriptómica, proteómica, metabolómica), ha permitido estudiar al genoma a diferentes niveles de regulación y expresión. Gracias a esto, actualmente se pueden estudiar las alteraciones génicas de un organismo de forma global ("genoma") y se puede identificar el efecto que tienen estas alteraciones a nivel de proteína y de la producción de metabolitos. De manera importante, esta nueva forma de estudiar la genética ha abierto nuevos campos de conocimiento y ha dilucidado nuevos mecanismos celulares que rigen el funcionamiento de los sistemas biológicos. A nivel clínico, en los últimos años se han implementado nuevas herramientas moleculares que permiten hacer una mejor clasificación, un mejor diagnóstico, así como un pronóstico más acertado de diversas enfermedades. Asimismo, en algunos casos se han establecido mejores tratamientos que favorecen la calidad de vida de los pacientes. Debido a todo lo anterior, es importante revisar y divulgar el cambio que ha tenido el estudio de la genética gracias al desarrollo de las ciencias ómicas, el cual es el objetivo de esta revisión.
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Genômica , Medicina/métodos , HumanosRESUMO
BACKGROUND: In Mexico, breast cancer represents the first cause of cancer death in females. At the molecular level, non-coding RNAs and especially microRNAs have played an important role in the origin and development of this neoplasm In the Anglo-Saxon population, diverse genetic variants in microRNA genes and in their targets are associated with the development of this disease. In the Mexican population it is not known if these or other variants exist. Identification of these or new variants in our population is fundamental in order to have a better understanding of cancer development and to help establish a better diagnostic strategy. METHODS: DNA was isolated from mammary tumors, adjacent tissue and peripheral blood of Mexican females with or without cancer. From DNA, five microRNA genes and three of their targets were amplified and sequenced. Genetic variants associated with breast cancer in an Anglo- Saxon population have been previously identified in these sequences. RESULTS: In the samples studied we identified seven single nucleotide polymorphisms (SNPs). Two had not been previously described and were identified only in women with cancer. CONCLUSION: The new variants may be genetic predisposition factors for the development of breast cancer in our population. Further experiments are needed to determine the involvement of these variants in the development, establishment and progression of breast cancer.
Antecedentes: en México, el cáncer de mama es la primera causa de muerte por cáncer en la mujer. A nivel molecular, los RNAs no codificantes y, en particular, los microRNAs, han tomado un papel importante en el origen y crecimiento de esta neoplasia. En población anglosajona se han reportado diversas variantes genéticas en los genes que codifican los microRNAs y en sus blancos, que se asocian con esta enfermedad. En la población mexicana se desconoce la existencia de estas u otras variantes; por eso su identificación en nuestra población es decisiva para comprender mejor la patogénesis del cáncer y contribuir a establecer una mejor estrategia diagnóstica. Objetivo: buscar y analizar variantes genéticas de tipo SNPs en cinco genes que codifican microRNAs y en tres sitios blancos de estos relacionados con predisposición al cáncer de mama, de mujeres mexicanas con o sin esta neoplasia. Material y métodos: estudio retrospectivo y longitudinal en el que se aisló ADN de tumores mamarios, tejido adyacente al tumor y sangre periférica de mujeres mexicanas con o sin cáncer. A partir del ADN se amplificaron y secuenciaron cinco genes de microRNAs y tres sitios blanco de estos en los que se han reportado variantes genéticas asociadas con el cáncer de mama en población anglosajona. Resultados: en las muestras estudiadas se identificaron siete polimorfismos de un solo nucleótido (SNPs). Dos son variantes no descritas que se encontraron sólo en mujeres con cáncer. Conclusión: las nuevas variantes identificadas pueden ser factores de predisposición genética para cáncer de mama en nuestra población. Para conocer cuál es la participación de estas variantes en el desarrollo, establecimiento y progresión del cáncer de mama se necesita experimentar más.
Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , RNA Neoplásico/genética , Idoso , Neoplasias da Mama/epidemiologia , DNA Complementar/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , México/epidemiologia , MicroRNAs/ultraestrutura , Pessoa de Meia-Idade , Conformação de Ácido Nucleico , Estudos Retrospectivos , Análise de Sequência de DNARESUMO
Anti-estrogens such as tamoxifen are widely used in the clinic to treat estrogen receptor-positive breast tumors. Patients with estrogen receptor-positive breast cancer initially respond to treatment with anti-hormonal agents such as tamoxifen, but remissions are often followed by the acquisition of resistance and, ultimately, disease relapse. The development of a rationale for the effective treatment of tamoxifen-resistant breast cancer requires an understanding of the complex signal transduction mechanisms. In the present study, we explored some mechanisms associated with resistance to tamoxifen, such as pharmacologic mechanisms, loss or modification in estrogen receptor expression, alterations in co-regulatory proteins and the regulation of the different signaling pathways that participate in different cellular processes such as survival, proliferation, stress, cell cycle, inhibition of apoptosis regulated by the Bcl-2 family, autophagy, altered expression of microRNA, and signaling pathways that regulate the epithelial-mesenchymal transition in the tumor microenvironment. Delineation of the molecular mechanisms underlying the development of resistance may aid in the development of treatment strategies to enhance response and compromise resistance.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Antagonistas de Estrogênios/uso terapêutico , Tamoxifeno/uso terapêutico , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Antagonistas de Estrogênios/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologiaRESUMO
We report on a 16-year-old girl with a complex phenotype, including intellectual disability, facial dysmorphisms, and obesity. During her infancy, she presented with weak sucking, global developmental delay, and later with excessive eating with central obesity. The girl was clinically diagnosed with probable Prader-Willi syndrome. Chromosomal analysis showed a de novo deletion 46,XX,del(15)(q21q22). However, the use of the Affymetrix CytoScan HD Array defined the exact breakpoints of the deleted 15q21q22 region. The imbalance, about 10.5 Mb in size, is to date the second largest deletion ever described in this chromosomal region. In addition, our patient carries a microdeletion in the 1q44 region and a gain in 9p24. The array result was arr[hg19] 9p24.1(6,619,823-6,749,335)×3, 1q44(248,688,586-248,795,277)×1, 15q21.2 q22.2(50,848,301-61,298,006)×1. Although our patient presents additional chromosomal alterations, we provide a correlation between the clinical findings and the phenotype of the 15q21 deletion syndrome.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/genética , Anormalidades Múltiplas/patologia , Adolescente , Cromossomos Humanos Par 15/genética , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Hibridização in Situ Fluorescente , FenótipoRESUMO
Pediatric astrocytomas, a leading cause of death associated with cancer, are the most common primary central nervous system tumors found in children. Most studies of these tumors focus on adults, not on children. We examined the global protein and microRNA expression pattern by 2D SDS-PAGE, mass spectrometry (MALDI-TOF), and RT(2) miRNA PCR Array System. Proteomic studies revealed 49 proteins with changes on the expression. Interactome showed that vimentin, calreticulin, and 14-3-3 epsilon protein are hub proteins in these neoplasms. MicroRNA analyses demonstrated for the first time novel microRNAs involved in the astrocytoma biology. In conclusion, our results show that novel proteins and microRNAs with expression changes on pediatric astrocytoma could serve as biomarkers of tumor progression. BIOLOGICAL SIGNIFICANCE: Astrocytomas are tumors that progress rapidly and that invade surrounding tissues. Although some drugs have been developed to treat these neoplasms, the mortality of patients is still very high. In this study, we describe for the first time, to our knowledge, some proteins and miRNAs associated with the biology of astrocytic tumors that could be postulated as possible diagnostic or prognostic biomarkers. Altogether, our results indicate that large-scale analyses allow making a fairly accurate prediction of different cellular processes altered in astrocytic tumors.