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1.
Nature ; 574(7780): 707-711, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31664194

RESUMO

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5' splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5' cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer.

2.
Nature ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597162

RESUMO

Recurrent somatic single nucleotide variants (SNVs) in cancer are largely confined to protein-coding genes, and are rare in most paediatric cancers1-3. Here we report highly recurrent hotspot mutations of U1 spliceosomal small nuclear RNAs (snRNAs) in ~50% of Sonic hedgehog medulloblastomas (Shh-MB), which were not present across other medulloblastoma subgroups. This U1-snRNA hotspot mutation (r.3a>g), was identified in <0.1% of 2,442 cancers across 36 other tumour types. Largely absent from infant Shh-MB, the mutation occurs in 97% of adults (Shhδ), and 25% of adolescents (Shhα). The U1-snRNA mutation occurs in the 5' splice site binding region, and snRNA mutant tumours have significantly disrupted RNA splicing with an excess of 5' cryptic splicing events. Mutant U1-snRNA-mediated alternative splicing inactivates tumour suppressor genes (PTCH1), and activates oncogenes (GLI2, CCND2), represents a novel target for therapy, and constitutes a highly recurrent and tissue-specific mutation of a non-protein coding gene in cancer.

3.
J Neurooncol ; 145(1): 177-184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31522324

RESUMO

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. METHODS: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. RESULTS: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. CONCLUSION: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.

4.
Nutrition ; 57: 46-51, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30149240

RESUMO

OBJECTIVE: The aim of this study was to assess whether the nutritional status of children with cancer is influenced by variations in cytokine concentrations observed during chemotherapy. We also evaluated whether this relationship could be modified by nutritional status at diagnosis and type of cancer. METHODS: Mexican children with lymphoma or solid tumors were evaluated at diagnosis and at 2- and 6-mo follow-up visits. Blood samples were obtained to determine serum prealbumin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, leptin concentrations, and hemoglobin. Children were classified as undernourished (UN) or well nourished (WN), according to prealbumin concentration. The influence of each cytokine on prealbumin concentration was analyzed by time-series regression model. RESULTS: Fifty patients (ages 2-17 y) were enrolled. There were 17 children with lymphomas and 33 with solid tumors. At baseline, 56% were UN and 26% presented anemia; the frequencies of UN children were higher for those with lymphoma than for those with a solid tumor (P = 0.003). By nutritional status, UN children presented lower leptin (P = 0.002) but higher IL-6 concentrations (P = 0.009) than the WN group. Children with lymphoma presented lower prealbumin (P = 0.003), but higher TNF-α (P = 0.001) and IL-6 (P = 0.011) concentrations than those with solid tumors. At follow-up, the concentration of prealbumin increased and IL-6 decreased in children with lymphoma. Multivariate analysis demonstrated that decreases in prealbumin concentration at the end of follow-up were associated with increases in IL-6 and TNF-α concentration during chemotherapy. CONCLUSIONS: These results suggest that the cytokine responses during chemotherapy are related to nutritional status at the end of 6 mo of treatment regardless of the initial nutritional status and the type of cancer.


Assuntos
Transtornos da Nutrição Infantil/sangue , Transtornos da Nutrição Infantil/complicações , Citocinas/sangue , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Estado Nutricional , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , México , Neoplasias/complicações
5.
Cancer Cell ; 31(6): 737-754.e6, 2017 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-28609654

RESUMO

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.


Assuntos
Meduloblastoma/classificação , Medicina de Precisão , Análise por Conglomerados , Estudos de Coortes , Variações do Número de Cópias de DNA , Metilação de DNA , Perfilação da Expressão Gênica , Genômica , Humanos , Meduloblastoma/genética , Meduloblastoma/terapia
6.
Rev Invest Clin ; 69(1): 28-32, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28239179

RESUMO

BACKGROUND: Although pulmonary involvement is common in patients with cancer, its frequency and nature is seldom reported in the medical literature. OBJECTIVE: To determine the frequency and type of lung pathological conditions revealed by autopsy in children with cancer. METHODS: All reports from autopsies performed in children with cancer from 1989 to 2012 in a pediatric hospital were reviewed. RESULTS: In the analyzed period, 118 autopsies (10.2% of all autopsies) corresponded to children who died with cancer; 76 had complete information and were included in the analysis. Children were seen in the Hematology (41 cases) or the Oncology (35 cases) services. Their median age at decease was 7 years (range, 15 days to 16.1 years) and 46.1% were females. Main diagnoses were acute lymphoblastic (31 patients) or myeloblastic (10 patients) leukemias and tumors of the central nervous system (12 patients). A pathological respiratory condition was diagnosed antemortem in 31 (40.8%) patients, and at autopsy in 62 (81.6%) cases. Omitted diagnoses occurred in 58 (76.3%) children, being pneumonia (24 cases) and pulmonary hemorrhage (23 cases) the most frequent omissions. Nine patients had clinically unsuspected tumor infiltration or metastases. CONCLUSIONS: In these children with cancer, more than 80% of autopsies revealed some lung pathology, mainly of infectious or hemorrhagic nature. Thus, pulmonary involvement should be investigated in all children with cancer in a timely and intentional manner.


Assuntos
Hemorragia/epidemiologia , Pneumopatias/epidemiologia , Neoplasias/complicações , Adolescente , Autopsia , Criança , Pré-Escolar , Feminino , Hemorragia/diagnóstico , Humanos , Lactente , Recém-Nascido , Pneumopatias/diagnóstico , Pneumopatias/patologia , Masculino , Neoplasias/patologia
7.
BMC Cancer ; 17(1): 125, 2017 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-28193268

RESUMO

BACKGROUND: There is a growing body of evidence indicating that pediatric survivors of cancer are at a greater risk of developing metabolic syndrome. This study evaluated some probable predictors of metabolic syndrome (MS), such as leptin and adiponectin concentrations, the leptin/adiponectin ratio, insulin resistance, and adiposity, in a sample of child survivors of lymphoma and leukemia in Mexico City. METHODS: Fifty two children (leukemia n = 26, lymphoma n = 26), who were within the first 5 years after cessation of therapy, were considered as eligible to participate in the study. Testing included fasting insulin, glucose, adipokines and lipids; body fat mass was measured by DXA. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. Comparisons between continuous variables were performed according to the data distribution. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. With the purpose of assessing the risk of a present MS diagnosis, odds ratios (OR) with a 95% confidence interval (95% IC) were obtained using logistic regression analysis according to the various metabolic markers. RESULTS: The median children age was 12.1 years, and the interval time from the completion of therapy to study enrollment was 4 years. Among the MS components, the prevalence of HDL-C low was most common (42%), followed by central obesity (29%). The HOMA-IR (OR 9.0, 95% CI 2.0; 41.1), body fat (OR 5.5, 95% CI 1.6; 19.3), leptin level (OR 5.7, 95% CI 1.6; 20.2) and leptin/adiponectin ratio (OR 9.4, 95% CI 2.0; 49.8) in the highest tertile, were predictive factors of developing MS; whereas the lowest tertile of adiponectin was associated with a protective effect but not significant. CONCLUSIONS: Biomarkers such as HOMA-IR, leptin and leptin/adiponectin are associated with each of the components of the MS and with a heightened risk of suffering MS among children survivors of cancer. Given the close relationship between MS with risk of developing type 2 diabetes and cardiovascular disease, it is imperative to implement prevention measures in this population and especially in developing countries where these pathologies have become the leading cause of death.


Assuntos
Adiponectina/metabolismo , Adiposidade , Biomarcadores/análise , Resistência à Insulina , Linfoma/complicações , Síndrome Metabólica/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Criança , Pré-Escolar , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Obesidade/fisiopatologia , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Sobreviventes
8.
J Pediatr Hematol Oncol ; 38(3): 191-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26907640

RESUMO

Febrile neutropenia (FN) is a common and potentially fatal adverse drug reaction of cisplatin-based chemotherapy (CDDPBC) in pediatric patients. Hence, the aim of this study was to determine the incidence and independent risk factors for FN in pediatric patients with solid tumors treated with CDPPBC. Cohort integration was performed in the first cycle of chemotherapy with CDDPBC and patients were followed up to 6 months after the last cycle. FN was defined according to the Common Terminology Criteria for Adverse Events. Relative risks were calculated with confidence intervals at 95% (95% CI) to determine FN risk factors. Multiple logistic regression was performed to identify independent risk factors. One hundred and thirty-nine pediatric patients (median age 7.4 y, range 0.08 to 17 y) were included in the study. FN incidence was 62.5%. Independent risk factors for FN were chemotherapy regimens including anthracyclines (odds ratio [OR]=19.44 [95% CI, 5.40-70.02), hypomagnesaemia (OR=8.20 [95% CI, 1.81-37.14]), and radiotherapy (OR=6.67 [95% CI, 1.24-35.94]). It is therefore concluded that anthracyclines-containing regimens, hypomagnesaemia, and radiotherapy are independent risk factors for FN in patients receiving CDDPBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Neutropenia Febril/induzido quimicamente , Neoplasias/tratamento farmacológico , Adolescente , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Estudos de Coortes , Neutropenia Febril/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Magnésio/sangue , Masculino , Neoplasias/radioterapia , Estudos Retrospectivos , Fatores de Risco
9.
Rev Med Inst Mex Seguro Soc ; 53 Suppl 3: S240-5, 2015.
Artigo em Espanhol | MEDLINE | ID: mdl-26509299

RESUMO

BACKGROUND: Survival of children with pineal region tumors has increased significantly in the last decade; these tumors have an insidious outcome associated with endocrine disorders with high morbidity and mortality, especially after gross resection. The objective was to report the survival, outcome, morbidity and mortality according to type of surgery, histology and treatment in children with pineal region tumors. METHODS: This retrospective study included all patients of 17 years or less with diagnosis of pineal region tumor, who went over a period of 10 years to a children's hospital. A histopathological review was made, and the extent of resection was determined. The survival was also estimated. RESULTS: Forty-six patients were included, out of which 36 had complete medical records and adequate pathologic material. Gross resection was performed in 24 (66.6 %), and biopsy in 12 (33.3 %); 23 (88 %) patients died; hydroelectrolytic imbalance was the cause of 14 deaths (60 %) and the other nine (39.1 %) were secondary to tumor progression. Ten-years survivals among patients treated with gross resection and biopsy were 52 and 75 %, respectively (p = 0.7). Endocrine alterations were observed in 13 patients (36.1 %); in 10 of these (76.9 %) the total resection was performed. CONCLUSIONS: Pineal region tumors in children can be treated with diagnostic biopsy, followed by adjuvant treatment consisting of chemotherapy and radiotherapy.


Assuntos
Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Germinoma/cirurgia , Tumores Neuroendócrinos/cirurgia , Glândula Pineal/cirurgia , Adolescente , Astrocitoma/mortalidade , Astrocitoma/patologia , Astrocitoma/terapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Quimiorradioterapia Adjuvante , Criança , Pré-Escolar , Feminino , Seguimentos , Germinoma/mortalidade , Germinoma/patologia , Germinoma/terapia , Humanos , Lactente , Masculino , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Glândula Pineal/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
10.
Rev Med Inst Mex Seguro Soc ; 52 Suppl 2: S98-103, 2014.
Artigo em Espanhol | MEDLINE | ID: mdl-24983567

RESUMO

BACKGROUND: Cytogenetics has revealed that the development of brain tumors might be induced by molecular alterations. The association of chromosomal imbalances with survival will allow for the prognosis and treatment of these tumors to be assessed. The objective of this study was to determine chromosomal imbalances and overall and disease-free survival in pediatric patients with astrocytoma and the association between chromosomal imbalances and survival. METHODS: Medical charts of patients diagnosed with astrocytoma according to records from 1995 to 2005 were reviewed. Paraffin blocks were retrieved in order to extract tumor material and a comparative genomic hybridization technique was used to search for chromosomal gains and losses. RESULTS: Out of 35 patients, 31 had at least some alteration in chromosomes 1, 5, 9 or 18, the latter with gains or losses in 65.7 % of the patients. By histology, 7/9 pilocytic astrocytomas had alteration of chromosome 9, and in 5/6 anaplastic astrocytomas, of chromosome 18. Patients with alterations in these chromosomes had a worse survival. CONCLUSIONS: The results of this study suggest that there is an association between the anaplastic histology and chromosome 18 alterations, as well as between diffuse astrocytoma and alterations in chromosome 5, which could be relevant in the Latin American population.


Assuntos
Astrocitoma/genética , Astrocitoma/mortalidade , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Aberrações Cromossômicas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Cariótipo , Masculino , Taxa de Sobrevida
11.
Pediatr Dermatol ; 31(5): 618-20, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23106131

RESUMO

Onychomycosis in children has a low incidence worldwide; certain conditions such as immunosuppression have been described as risk factors for it. We studied 72 children receiving chemotherapy for different neoplasms to determine the frequency of onychomycosis. Only one patient had white superficial onychomycosis from Trichophyton rubrum, a frequency of 1.3%, not different from that reported in healthy patients.


Assuntos
Antineoplásicos/efeitos adversos , Hospedeiro Imunocomprometido , Neoplasias/tratamento farmacológico , Onicomicose/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
12.
J Proteomics ; 94: 162-75, 2013 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-24060999

RESUMO

UNLABELLED: 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.


Assuntos
Astrocitoma/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , Proteínas do Tecido Nervoso/biossíntese , Proteoma/biossíntese , RNA Neoplásico/biossíntese , Adulto , Astrocitoma/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Proteômica
13.
Bol. méd. Hosp. Infant. Méx ; 69(5): 376-383, sep.-oct. 2012. tab
Artigo em Espanhol | LILACS-Express | ID: lil-701209

RESUMO

Introducción. El diagnóstico de infección bacteriana en el paciente con cáncer, fiebre y neutropenia se dificulta debido a una pobre respuesta inflamatoria. Se han realizado evaluaciones con reactantes de fase aguda, como la proteína C reactiva, con resultados variables. El objetivo de este trabajo fue calcular la sensibilidad, especificidad, valores predictivos positivos y negativos y razones de verosimilitud de la proteína C reactiva para el diagnóstico de infección bacteriana en pacientes con cáncer y neutropenia febril. Métodos. Se realizó el estudio de la prueba diagnóstica. Se incluyeron pacientes pediátricos con cáncer, y neutropenia (<500 NA/mm³). La proteína C reactiva se cuantificó por nefelometría. Los episodios se clasificaron en cuatro grupos: grupo I, infección microbiológicamente documentada; grupo II, infección clínicamente documentada; grupo III, fiebre por otras causas; y grupo IV, pacientes con neutropenia sin fiebre. Se realizó el cálculo de sensibilidad, especificidad, valores predictivos positivos y negativos, curvas operantes del receptor y razones de verosimilitud. Para la comparación de variables cuantitativas se emplearon la U de Mann-Whitney y Kruskal-Wallis y para variables cualitativas, χ². Resultados. Se incluyeron 127 episodios que se distribuyeron en: 29, 47, 20 y 31 episodios para los grupos I, II, III y IV, respectivamente. Las medianas de la proteína C reactiva fueron 282 mg/L para el grupo I, 205 mg/L grupo II, 27.3 mg/L grupo III y 5.1 mg/L para el grupo IV (p < 0.001). Con la proteína C reactiva de 60 mg/L se obtuvo una sensibilidad de 94%, especificidad de 94%, valor predictivo positivo 96% y valor predictivo negativo 92%; razón de verosimilitud para un resultado positivo 15.6 y de 0.06 para resultado negativo. Conclusiones. La proteína C reactiva es una prueba útil y económica para el diagnóstico de infección bacteriana en el paciente con cáncer, fiebre y neutropenia.


Background. Diagnosis of bacterial infection in the patient with cancer, fever and neutropenia is difficult due to the poor inflammatory response. Several evaluations of acute phase reactants such as C-reactive protein (C-RP) have been performed with diverse results. The aim of this study was to calculate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and likelihood ratios (LR) for C-RP in the diagnosis of bacterial infection of patients with cancer, neutropenia and fever. Methods. We carried out a diagnostic test study. Pediatric patients with cancer and neutropenia (<500 NA/mm³) were selected. C-RP was determined by nephelometry. Episodes were classified into the following groups: group I: microbiologically documented infection; group II: clinically documented infection; group III: fever of unknown origin; group IV: patients with neutropenia without fever. Sensitivity, specificity, PPV, NPV, receiving operating curves (ROC) and LR were calculated. Mann-Whitney U test and Kruskal-Wallis test were used for comparison of quantitative variables. For qualitative variables, χ2 test was used. Results. There were 127 episodes distributed as follows: 29, 47, 20 and 31 for groups I, II, III and IV, respectively. Median of C-RP values were 282 mg/L for group I, 205 mg/L group II, 27.3 mg/L group III and 5.1 mg/L group IV (p <0.001). With a C-RP value of 60 mg/L, we obtained a sensitivity of 94%, specificity 94%, PPV 6% and NPV 92%. LR for a positive test was 15.6 and LR for a negative test was 0.06. Conclusions. C-RP is a useful and economically feasible test for diagnosis of bacterial infection in patients with cancer, neutropenia and fever.

14.
Gac Med Mex ; 146(2): 118-23, 2010.
Artigo em Espanhol | MEDLINE | ID: mdl-20626127

RESUMO

BACKGROUND: Pediatric patients with malignant gliomas and same histological diagnosis respond distinctly to treatment. It is thus necessary to determine other factors that may influence the response to treatment and survival. Over expression of the Ki67 protein has been associated with poor treatment response. The aim of this study was to determine if the expression of this antigen influences survival of patients treated for malignant gliomas in the CMN SXXI Pediatrics Hospital. METHODS: We included patients with anaplasic astrocitoma or glioblastoma multiforme seen at our hospital between 1995 and 2005. We determined the expression of Ki67 by immunohistochemistry and correlated the findings with tumor histology and patient survival. RESULTS: Of the 21 patients studied, 12 overexpressed antigen Ki67. There was no significant association between over expression of Ki67 and survival, although we observed a clinical association. Over expression of Ki67 correlated with more aggressive histology. Being under the age of 11 was a poor prognostic factor. Overall survival was 49% at 120 months. CONCLUSIONS: Being young (under 11 years) is a marker of poor prognosis among pediatric patients with anaplasic astrocytoma or glioblastoma multiforme. Overexpression expression of antigen Ki67 is associated with histology and may be associated with poor survival among patients treated in our hospital.


Assuntos
Astrocitoma/metabolismo , Astrocitoma/mortalidade , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Antígeno Ki-67/biossíntese , Adolescente , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos , Humanos , Masculino , Prognóstico , Taxa de Sobrevida
15.
Gac. méd. Méx ; 146(2): 118-123, mar.-abr. 2010. tab, ilus
Artigo em Espanhol | LILACS | ID: lil-566764

RESUMO

Antecedentes: Los pacientes pediátricos con astrocitomas de alto grado con mismas histologías presentan respuestas diferentes a idéntico tratamiento. Es necesario identificar los factores que influyen en el pronóstico y respuesta al mismo. La sobreexpresión de la proteína Ki67 se ha asociado con respuestas poco favorables. El objetivo fue determinar si la expresión de este antígeno influye en la sobrevida de los pacientes con astrocitoma de alto grado del Hospital de Pediatría del Centro Médico Nacional Siglo XXI. Métodos: Se incluyeron pacientes con astrocitoma anaplásico o glioblastoma multiforme atendidos entre 1995 y 2005. Por inmunohistoquímica se determinó la expresión del antígeno Ki67 en las muestras de tejido tumoral y se correlacionó con la histología tumoral y la sobrevida de los pacientes. Resultados: De 21 pacientes, 12 sobreexpresaron el antígeno Ki67. No se encontró asociación estadísticamente significativa entre la sobreexpresión del antígeno Ki67 y la sobrevida, aunque sí clínica. Se encontró asociación estadísticamente significativa entre la sobreexpresión del Ag Ki67 y el grado de malignidad del tumor. La edad menor de 11 años resultó un factor de mal pronóstico. La sobrevida global fue de 49 % a 120 meses. Conclusiones: La edad menor de 11 años fue un factor de mal pronóstico en los pacientes estudiados con astrocitoma o glioblastoma multiforme. La sobreexpresión del antígeno Ki67 está asociada con la histología y pareciera tener relación con la sobrevida de los pacientes pediátricos con astrocitoma.


BACKGROUND: Pediatric patients with malignant gliomas and same histological diagnosis respond distinctly to treatment. It is thus necessary to determine other factors that may influence the response to treatment and survival. Over expression of the Ki67 protein has been associated with poor treatment response. The aim of this study was to determine if the expression of this antigen influences survival of patients treated for malignant gliomas in the CMN SXXI Pediatrics Hospital. METHODS: We included patients with anaplasic astrocitoma or glioblastoma multiforme seen at our hospital between 1995 and 2005. We determined the expression of Ki67 by immunohistochemistry and correlated the findings with tumor histology and patient survival. RESULTS: Of the 21 patients studied, 12 overexpressed antigen Ki67. There was no significant association between over expression of Ki67 and survival, although we observed a clinical association. Over expression of Ki67 correlated with more aggressive histology. Being under the age of 11 was a poor prognostic factor. Overall survival was 49% at 120 months. CONCLUSIONS: Being young (under 11 years) is a marker of poor prognosis among pediatric patients with anaplasic astrocytoma or glioblastoma multiforme. Overexpression expression of antigen Ki67 is associated with histology and may be associated with poor survival among patients treated in our hospital.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , /biossíntese , Astrocitoma/metabolismo , Astrocitoma/mortalidade , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Hospitais Pediátricos , Prognóstico , Taxa de Sobrevida
16.
BMC Cancer ; 9: 266, 2009 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-19650918

RESUMO

BACKGROUND: Neuroblastoma (NB) is the principal tumor of the sympathetic nervous system in children under one year of age. The incidence in developed countries is greater than that in developing countries. The aim of this article is to present the epidemiological and some clinical characteristics of Mexican children with NB. METHODS: A population-based, prolective study, with data obtained from the Childhood Cancer Registry of the Instituto Mexicano de Seguro Social. STATISTICAL ANALYSIS: The simple frequencies of the variables of the study and the annual average incidence (per 1,000,000 children/years) by age and sex were obtained. The trend was evaluated by calculating the annual percentage of change. The curves of Kaplan-Meyer were employed for the survival rate and the log-rank test was used to compare the curves. RESULTS: Of a total of 2,758 children with cancer registered during the period from 1996-2005, 72 (2.6%) were identified as having Group IV, defined according to the International Classification of Childhood Cancer. The incidence for NB was 3.8 per 1,000,000 children/year; NB was highest in the group of children under one year of age, followed by the group of children between the ages 1-4 years (18.5 and 5.4 per 1,000,000 children/years, respectively). The male/female ratio was 1.1 and there was no trend toward an increase. The time of diagnosis was 26 days (median), but varied according to the stage at diagnosis. Stages III and IV were presented in 88% of the cases. There was no association between the stage, the age at time of diagnosis, or the histological pattern. The overall five-year survival rate was 64%; the patients with stage I, II, III, or IVs did not die; and the five-year survival rate of cases in Stage IV was 40%. CONCLUSION: It is possible that the low incidence of neuroblastoma in Mexican children is due to the difficulty in diagnosing the cases with the best prognosis, some of which could have had spontaneous regression. There was no trend to an increase; the majority of the cases were diagnosed in the advanced stages; and the overall five-years survival rate was similar to that for developed countries.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Neuroblastoma/diagnóstico , Neuroblastoma/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , México , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
17.
Gac Med Mex ; 145(1): 7-13, 2009.
Artigo em Espanhol | MEDLINE | ID: mdl-19256405

RESUMO

BACKGROUND: Ependymomas constitute the third most common intracranial tumors in children. Risk factors include age, location, extent of surgical excision, and radiation therapy. Recently, chromosomal imbalances have been described. OBJECTIVE: Determine global survival of patients with ependymomas according to different prognostic factors. METHODS: We reviewed the medical charts of every pediatric patient with ependymoma from 1996 to 2005. Genomic imbalances were determined using comparative genomic hybridization (CGH). Survival was calculated using the Kaplan and Meier method. We used the Log Rank test for each risk factor. Death risk was calculated by odds ratio (OR). RESULTS: We included 24 patients. Global survival was 58.04%. The presence of chromosomal imbalances, particularly in chromosome 21, significantly affected survival Being under 5 years of age, anaplastic histology, chemotherapy other than ICE (ifosfamida-carboplatin-etoposide) and partial resection increased the risk of death. CONCLUSIONS: Known risk factors were confirmed in our study, including chromosomal imbalances. We describe a new chromosomal imbalance in chromosome 21 among 30% of study participants.


Assuntos
Neoplasias Encefálicas/mortalidade , Ependimoma/mortalidade , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Prognóstico , Taxa de Sobrevida
18.
Gac. méd. Méx ; 145(1): 7-13, ene.-feb. 2009. tab, ilus
Artigo em Espanhol | LILACS | ID: lil-567739

RESUMO

Antecedentes: El ependimoma es el tercer tumor intracraneano más frecuente en pediatría. Los factores que influyen en el pronóstico son la localización, la edad del paciente, la resección quirúrgica y el tratamiento con radioterapia. Recientemente se ha descrito la presencia de alteraciones cromosómicas en el tumor como factor de mal pronóstico. El objetivo de esta investigación fue determinar la sobrevida de pacientes pediátricos con ependimoma de acuerdo con los diferentes factores pronósticos. Métodos: Se revisaron los expedientes de pacientes pediátricos con ependimoma de 1996 a 2005. Se determinaron las alteraciones cromosómicas mediante hibridación genómica comparativa. Se calculó la sobrevida de acuerdo con el método Kaplan-Meier y prueba de log rank de acuerdo a cada factor pronóstico. Se calculó el riesgo de morir para cada factor de acuerdo con la razón de momios. Resultados: Se incluyeron 24 pacientes. La sobrevida global fue de 58.04%. La presencia de alteraciones cromosómicas, particularmente en el cromosoma 21, afectó significativamente la sobrevida. La edad menor a cinco años, la histología anaplásica, la quimioterapia diferente a ifosfamida-carboplatino-etopósido y la resección parcial aumentaron el riesgo de morir. Conclusiones: Se confirman los factores descritos anteriormente en la literatura, incluyendo alteraciones cromosómicas. Se describe un nuevo desbalance en el cromosoma 21 en 30% de los pacientes.


BACKGROUND: Ependymomas constitute the third most common intracranial tumors in children. Risk factors include age, location, extent of surgical excision, and radiation therapy. Recently, chromosomal imbalances have been described. OBJECTIVE: Determine global survival of patients with ependymomas according to different prognostic factors. METHODS: We reviewed the medical charts of every pediatric patient with ependymoma from 1996 to 2005. Genomic imbalances were determined using comparative genomic hybridization (CGH). Survival was calculated using the Kaplan and Meier method. We used the Log Rank test for each risk factor. Death risk was calculated by odds ratio (OR). RESULTS: We included 24 patients. Global survival was 58.04%. The presence of chromosomal imbalances, particularly in chromosome 21, significantly affected survival Being under 5 years of age, anaplastic histology, chemotherapy other than ICE (ifosfamida-carboplatin-etoposide) and partial resection increased the risk of death. CONCLUSIONS: Known risk factors were confirmed in our study, including chromosomal imbalances. We describe a new chromosomal imbalance in chromosome 21 among 30% of study participants.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Lactente , Ependimoma/mortalidade , Neoplasias Encefálicas/mortalidade , Prognóstico , Taxa de Sobrevida
19.
Arch Med Res ; 39(7): 655-62, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18760193

RESUMO

BACKGROUND: Brain stem tumors (BST) constitute 20% of all intracranial tumors. Survival for these patients has been very poor worldwide. Four different treatment schemes have been evaluated at our institution, with only a discrete increment in survival when treated with carboplatin-vincristine and fluvastatin (CVF). Low-dose, continuous antiangiogenic treatment has been recently introduced in the treatment of cancer. Our objective was to determine tumor response to metronomic chemotherapy combined with an antiangiogenic drug and fluvastatin and to calculate the survival of pediatric patients with brain stem tumors. METHODS: This was a phase II study. A magnetic resonance (MRI) study was made at inclusion and after the fourth course. Routine laboratory analyses were performed prior to each treatment scheme. Patients received four courses of chemotherapy every 28 days consisting of thalidomide alternating with fluvastatin every 14 days and combined with carboplatin and vincristine every 14 days followed by radiotherapy (56 cGy) and four more courses of the same chemotherapy. Toxicity was evaluated according to Miller criteria. RESULTS: Nine recently diagnosed BST patients were included. Five patients had low-grade astrocytomas, three patients had glioblastoma multiforme, and one patient presented high-grade astrocytoma. There was a significant reduction in tumor volume and a significant increase in survival at 24 months. Two patients died. Toxicity included carboplatin allergy in one patient, grades 1 and 3 neutropenia in two patients, and grade 4 thrombocytopenia in two patients. CONCLUSIONS: Metronomic treatment with carboplatin and vincristine associated with fluvastatin and thalidomide significantly increased survival of pediatric brain stem tumor patients. Tumor volume showed a significant reduction. Quality of life was also increased. Sample size must be increased in order to make final conclusions.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Talidomida/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Tronco Encefálico/mortalidade , Neoplasias do Tronco Encefálico/radioterapia , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Criança , Pré-Escolar , Ácidos Graxos Monoinsaturados/administração & dosagem , Ácidos Graxos Monoinsaturados/uso terapêutico , Feminino , Fluvastatina , Humanos , Indóis/administração & dosagem , Indóis/uso terapêutico , Lactente , Imagem por Ressonância Magnética , Masculino , Qualidade de Vida , Taxa de Sobrevida , Talidomida/administração & dosagem , Vincristina/administração & dosagem , Vincristina/uso terapêutico
20.
Arch Med Res ; 39(6): 601-6, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18662592

RESUMO

BACKGROUND: Emesis and nausea are common adverse effects of chemotherapy. Consequences include dehydration, acute renal failure, esophageal rupture, electrolyte imbalance and undernutrition, among others. First-generation 5-HT3 antagonists significantly reduce these symptoms but are expensive and require administration every 8-12h. Palonosetron, a second generation 5-HT3 antagonist has proven better results in adult populations. Other benefits include a one-dose administration with effect for up to 7 days and a lower treatment cost. No clinical studies have evaluated the safety and efficacy of palonosetron in children. METHODS: Prior to every course, patients were randomized to receive palonosetron or ondansetron. Patients or guardians recorded the number of emetic events and the intensity of nausea over a 7-day period. They also reported any possible adverse effects. Statistical analysis included chi(2) test, relative risk, and Student's t test. RESULTS: Fifty courses were analyzed for each group. There was a significant reduction in emesis on the first 3 days and in the intensity of nausea in the first four days in the palonosetron group. There was an increased risk of presenting emesis and nausea in the acute phase when treated with ondansetron. No adverse effects were reported. The cost of treatment was also reduced when using palonosetron. CONCLUSIONS: Palonosetron is a safe and effective antiemetic treatment in children, as well as being cost effective.


Assuntos
Antineoplásicos/efeitos adversos , Isoquinolinas/uso terapêutico , Náusea/induzido quimicamente , Quinuclidinas/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Vômito/induzido quimicamente , Criança , Feminino , Humanos , Isoquinolinas/efeitos adversos , Masculino , Palonossetrom , Quinuclidinas/efeitos adversos , Antagonistas da Serotonina/efeitos adversos
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