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1.
J Coll Physicians Surg Pak ; 33(2): 170-175, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36797626

RESUMEN

CONCLUSION: For children with recurrent nephroblastoma, intraoperative HIPEC has little impact on the body, can significantly improve the effectiveness and reduce the recurrence rate, and does not increase the adverse reactions. KEY WORDS: Children, Recurrence, Nephroblastoma, Hyperthermic perfusion. METHODOLOGY: Sixty children with recurrent nephroblastoma treated by HIPEC in the Department of Surgical Oncology were analysed and divided into group A and group B, according to different perfused drugs. Additionally, 30 children without a history of HIPEC were selected as the control group (group C). The changes in routine blood indices, albumin, and hepatic and renal function of the three groups were observed before and after treatment. The clinical efficacy, frequency of adverse reactions, as well as 6-month and 1-year tumour recurrence in the three groups were compared. OBJECTIVE: To investigate the clinical efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of recurrent nephroblastoma in children. PLACE AND DURATION OF STUDY: Department of Oncology, Baoding Children's Hospital, from August 2018 to November 2021. RESULTS: The efficacy in groups A and B was significantly higher than that in group C (p<0.05). Changes in routine blood indices, albumin, and hepatic and renal function showed no statistically significant differences among the three groups during each observation period after treatment (all p>0.05). No significant differences were found in the incidence of adverse reactions among the three groups during treatment (all p>0.05). Six months after treatment, the tumour recurrence rate presented no significant differences among the three groups. However, at 12-months after treatment, the recurrence rate in groups A and B was lower than that in group C (p<0.05). STUDY DESIGN: Randomised controlled trial.


Asunto(s)
Hipertermia Inducida , Tumor de Wilms , Niño , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Quimioterapia Intraperitoneal Hipertérmica , Recurrencia Local de Neoplasia/terapia , Estudios Retrospectivos , Tumor de Wilms/tratamiento farmacológico
2.
Altern Ther Health Med ; 29(2): 140-147, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36455140

RESUMEN

Background: A previous study found that microRNA-143-3p (miR-143-3p) is a tumor suppressor in various types of human cancer. However, the roles and molecular mechanisms of miR-143-3p in the progression of Wilms' tumor (WT) remain to be clarified. The aim of the present study was to determine the expression and biological functions of miR-143-3p in WT. Material and Methods: The expression levels of miR-143-3p in primary WT tissues and adjacent tissues were determined using quantitative-reverse transcription polymerase chain reaction (qRT-PCR), and the association of the miR-143-3p expression level with various clinicopathological features of WT was investigated. Western blotting was used to evaluate the protein expression of the related signaling pathway. Results: The expression of miR-143-3p was significantly downregulated in WT tissues and its expression levels were closely associated with tumor stage and lymph node metastasis. Overexpression of miR-143-3p in SK-NEP-1 and G401 cell lines inhibited cell proliferation by G0/G1 cell cycle phase arrest and induction of apoptosis. Moreover, k-Ras, a unique oncogene, was confirmed as a direct target of miR-143-3p, and k-Ras messenger RNA (mRNA) expression was increased in WT tissues and inversely correlated with miR-143-3p. Knockdown of k-Ras by si-k-Ras could inhibit, whereas overexpression of k-Ras could promote. cell proliferation in WT cells. Meanwhile, overexpression of k-Ras reversed the inhibitory effects on WT cells induced by miR-143-3p mimics. Conclusion: Our findings indicate that miR-143-3p may be a potential novel prognostic biomarker and therapeutic target for WT.


Asunto(s)
Neoplasias Renales , MicroARNs , Tumor de Wilms , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Sistema de Señalización de MAP Quinasas , Tumor de Wilms/genética , Tumor de Wilms/metabolismo , Tumor de Wilms/patología , Proliferación Celular , Ciclo Celular , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Línea Celular Tumoral
4.
Urology ; 165: e25-e28, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35500700

RESUMEN

Wilms tumor is a frequent malignant neoplasia in pediatric population. Extension to the inferior vena cava is a complication that occurs in approximately 4%-15% of cases. Surgical techniques derived from the field of adult transplant surgery allow the resection of the tumor with its thrombus extension. In the case of a 6-year-old male patient with a stage III Wilms tumor that originated from the left renal vein, thrombectomy and left radical nephroureterectomy were accomplished without extracorporeal circulation. Surgical technique applied in adult transplant surgery for removal of advanced renal tumors, could be a safe and feasible technique in pediatric population.


Asunto(s)
Carcinoma de Células Renales , Kava , Neoplasias Renales , Trombosis , Tumor de Wilms , Adulto , Carcinoma de Células Renales/cirugía , Puente Cardiopulmonar , Niño , Humanos , Neoplasias Renales/patología , Masculino , Nefrectomía/efectos adversos , Nefrectomía/métodos , Trombectomía , Trombosis/complicaciones , Trombosis/cirugía , Vena Cava Inferior/cirugía , Tumor de Wilms/complicaciones , Tumor de Wilms/patología , Tumor de Wilms/cirugía
5.
Cancer Epidemiol ; 67: 101769, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32659726

RESUMEN

BACKGROUND: Little is known about the etiology of childhood Wilms tumor (WT) and potentially modifiable maternal risk factors, in particular. METHODS: Unpublished data derived from the hospital-based, case-control study of the Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) were included in an ad hoc conducted systematic literature review and meta-analyses examining the association between modifiable maternal lifestyle risk factors and WT. Eligible data were meta-analysed in separate strands regarding the associations of WT with (a) maternal folic acid and/or vitamins supplementation, (b) alcohol consumption and (c) smoking during pregnancy. The quality of eligible studies was evaluated using the Newcastle-Ottawa Scale. RESULTS: Effect estimates from 72 cases and 72 age- and sex-matched controls contributed by NARECHEM-ST were meta-analysed together with those of another 17, mainly medium size, studies of ecological, case-control and cohort design. Maternal intake of folic acid and/or other vitamins supplements during pregnancy was inversely associated with WT risk (6 studies, OR: 0.78; 95 %CI: 0.69-0.89, I2 = 5.4 %); of similar size was the association for folic acid intake alone (4 studies, OR: 0.79; 95 %CI: 0.69-0.91, I2 = 0.0 %), derived mainly from ecological studies. In the Greek study a positive association (OR: 5.31; 95 %CI: 2.00-14.10) was found for mothers who consumed alcohol only before pregnancy vs. never drinkers whereas in the meta-analysis of the four homogeneous studies examining the effect of alcohol consumption during pregnancy the respective overall result showed an OR: 1.60 (4 studies, 95 %CI: 1.28-2.01, I2 = 0.0 %). Lastly, no association was seen with maternal smoking during pregnancy (14 studies, OR: 0.93; 95 %CI: 0.80-1.09, I2 = 0.0 %). CONCLUSIONS: In the largest to-date meta-analysis, there was an inverse association of maternal folic acid or vitamins supplementation with WT risk in the offspring, derived mainly from ecological studies. The association with maternal alcohol consumption found in our study needs to be further explored whereas no association with maternal smoking was detected. Given the proven benefits for other health conditions, recommendations regarding folic acid supplementation as well as smoking and alcohol cessation should apply. The maternal alcohol consumption associations, however, should be further explored given the inherent limitations in the assessment of exposures of the published studies.


Asunto(s)
Tumor de Wilms/etiología , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Estilo de Vida , Masculino , Madres , Tumor de Wilms/patología
6.
Med Sci Monit ; 26: e920725, 2020 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-32214060

RESUMEN

BACKGROUND Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. MATERIAL AND METHODS Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. RESULTS From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. CONCLUSIONS RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.


Asunto(s)
Antineoplásicos/uso terapéutico , Evaluación Preclínica de Medicamentos , Simulación del Acoplamiento Molecular , Análisis de Secuencia de ARN , Tumor de Wilms/tratamiento farmacológico , Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica , Ontología de Genes , Humanos , Estimación de Kaplan-Meier , Ligandos , Pronóstico , Unión Proteica , Curva ROC , Tumor de Wilms/genética
7.
Cancer Causes Control ; 31(5): 491-501, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32144681

RESUMEN

PURPOSE: Wilms tumor (WT), or nephroblastoma, is an embryonic tumor that constitutes the most common renal tumor in children. Little is known about the etiology of WT. The aim of this study was to investigate whether maternal or perinatal characteristics were associated with the risk of WT. METHODS: The ESTELLE study is a national-based case-control study that included 117 cases of WT and 1,100 controls younger than 11 years old. The cases were children diagnosed in France in 2010-2011 and the controls were frequency matched with cases by age and gender. The mothers of case and control children responded to a telephone questionnaire addressing sociodemographic and perinatal characteristics, childhood environment, and lifestyle. Unconditional logistic regression models adjusted on potential cofounders were used to estimate the odds ratios (OR) and their confidence intervals (95% CI). RESULTS: High birth weight and the presence of congenital malformation were associated with WT (OR 1.9 [95% CI 1.0-3.7] and OR 2.5 [95% CI 1.1-5.8], respectively). No association with breastfeeding or folic acid supplementation was observed. CONCLUSIONS: Although potential recall bias cannot be excluded, our findings reinforce the hypothesis that high birth weight and the presence of congenital malformation may be associated with an increased risk of WT. Further investigations are needed to further elucidate the possible role of maternal characteristics in the etiology of WT.


Asunto(s)
Neoplasias Renales/patología , Tumor de Wilms/patología , Adulto , Peso al Nacer , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Francia , Humanos , Lactante , Recién Nacido , Masculino , Madres , Embarazo , Factores de Riesgo , Encuestas y Cuestionarios , Adulto Joven
8.
Future Oncol ; 15(11): 1231-1241, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30810052

RESUMEN

AIM: To investigate the role of the transcription factor YY1 in Wilms tumor (WT). PATIENTS & METHODS: We measured YY1 expression using tissue microarray from patients with pediatric renal tumors, mainly WT and evaluated correlations with the predicted clinical evolution. YY1 expression was measured using immunohistochemical and protein expression was determined by digital pathology. RESULTS & CONCLUSION: YY1 significantly increased in WT patients. In addition, an increase in YY1 expression had a greater risk of adverse outcomes in WT patients with favorable histology. YY1 expression was higher in the blastemal component of tumors, and high nuclear expression positively correlated with metastasis. YY1 may be considered as a metastasis risk factor in WT.


Asunto(s)
Expresión Génica , Neoplasias Renales/genética , Neoplasias Renales/patología , Factor de Transcripción YY1/genética , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Lactante , Neoplasias Renales/mortalidad , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Tumor de Wilms
9.
Bioelectromagnetics ; 39(5): 375-385, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29719057

RESUMEN

Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of this MF. Exposure to the field decreased cell proliferation and induced apoptosis. Combinational use of MF together with chemotherapeutics cisplatin (DDP) was performed in both in vitro and in vivo experiments. In cell lines, combinational treatment further increased the inhibition rate compared with single use of either DDP or MF. In G401 nephroblastoma tumor model in nude mice, combination of MF and DDP resulted in significant decrease of tumor mass, and the side effect was limited in mild liver injury. MF exposure by itself did not hamper liver or kidney functions. In summary, the antitumor effect of an established MF against neuroblastoma and nephroblastoma is reported, and this field has the potential to be used in combination with DDP to achieve increased efficacy and reduce side effects in these two childhood malignancies. Bioelectromagnetics. 39:375-385, 2018. © 2018 Wiley Periodicals, Inc.


Asunto(s)
Magnetoterapia , Neuroblastoma/terapia , Tumor de Wilms/terapia , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Cisplatino/efectos adversos , Cisplatino/farmacología , Terapia Combinada/efectos adversos , Diseño de Equipo , Humanos , Riñón/efectos de los fármacos , Riñón/fisiopatología , Hígado/efectos de los fármacos , Hígado/fisiopatología , Magnetoterapia/efectos adversos , Imanes , Masculino , Ratones Desnudos , Trasplante de Neoplasias , Neuroblastoma/patología , Factores de Tiempo , Carga Tumoral , Tumor de Wilms/patología
10.
S. Afr. j. clin. nutr. (Online) ; 31(4): 74-77, 2018.
Artículo en Inglés | AIM | ID: biblio-1270565

RESUMEN

Background: Assessment of nutritional status of paediatric oncology patients is crucial, as it may influence treatment and clinical outcomes. Concurrent malnutrition and cancer in children may lead to reduced chemotherapy delivery due to impaired tolerance and increased toxicity.Aim: This study aimed to determine the relationship between nutritional status and the prevalence, frequency and duration of treatment-related neutropenia in a cohort of South African children with nephroblastoma.Methods: Seventy-seven children between the ages of 1 and 12 years diagnosed with nephroblastoma at Inkosi Albert Luthuli Central Hospital (IALCH), Durban, between 2004 and 2012, were studied prospectively. Nutritional status was assessed using weight, height, mid-upper arm circumference (MUAC), triceps skinfold thickness (TSFT) and serum albumin. The administration of filgastrim (Neupogen®) was used as a surrogate for neutropenia and the frequency and duration of its use was recorded.Results: There was a significant relationship between the prevalence of treatment-induced neutropenia and malnutrition defined by MUAC. The mean frequency and duration of neutropenia was significantly higher in those classified as malnourished using MUAC. There was a positive correlation between frequency and duration of neutropenia.Conclusions: Malnutrition was prevalent among children with nephroblastoma. The prevalence of treatment-induced neutropenia was higher in those with poor nutritional status, identified by MUAC. Poor nutritional status according to MUAC was also linked to an increased frequency and duration of neutropenia. It is important to include MUAC in the nutritional assessment of children with nephroblastoma


Asunto(s)
Neoplasias , Neutropenia , Sudáfrica , Terapéutica , Tumor de Wilms
12.
Paediatr Anaesth ; 27(4): 338-345, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28211128

RESUMEN

Newer techniques that have found a place in cancer management in adults are offered far less commonly in pediatric patients. We present a case of a patient with recurrent Wilms' tumor managed with a novel combination of cytoreductive surgery, intraperitoneal brachytherapy, and subsequent hyperthermic intraperitoneal chemotherapy. Each stage presents challenges that the pediatric anesthetist is unlikely to have faced before. Such cases require flexibility and thorough planning to manage the combination of major surgery, remote anesthesia with brachytherapy and hyperthermic chemotherapy with its potential for metabolic derangement, significant fluid shifts, analgesic care, and potential exposure of staff to cytotoxic agents. Comprehensive care can be offered in pediatric centers.


Asunto(s)
Anestesia General/métodos , Braquiterapia/métodos , Hipertermia Inducida , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/radioterapia , Tumor de Wilms/tratamiento farmacológico , Tumor de Wilms/radioterapia , Adolescente , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Fentanilo , Humanos , Inyecciones Epidurales , Riñón , Masculino , Éteres Metílicos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Peritoneo , Propofol , Sevoflurano , Resultado del Tratamiento
13.
J Pediatr Hematol Oncol ; 38(5): 372-7, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27164527

RESUMEN

OBJECTIVE: The aim of this study was to analyze the survival of children with Wilms tumor and other malignant renal tumors treated with the TWPINDA-99 protocol. MATERIALS AND METHODS: Between January 1999 and December 2013, 226 patients were registered on this trial, based on National Wilms Tumor Study-5. Patient characteristics and survival were evaluated. RESULTS: Two hundred seven patients were diagnosed with Wilms tumor, which represented 91.6% of renal tumors. The male to female ratio was 0.7:1. The median age at diagnosis was 3.3 years. Stage III was the most frequent (39.2%). Metastatic disease was present in 16.7% of the cases. Synchronous bilateral disease was observed in 9.3% of the cases. Favorable histology was diagnosed in 93.6% and anaplastic histology in 6.4% of the patients. Median follow-up was 7.5 years. Ten-year event-free survival and overall survival (OS) for assessable patients with Wilms tumor (n=192) were 82.0% and 89.9%, respectively. OS for patients with stage I was 100% (n=36), stage II: 97.1% (n=35), stage III: 88.6% (n=71), stage IV: 77.9% (n=32), and stage V: 80.8% (n=18). OS for favorable histology (n=180) and anaplastic histology tumors (n=12) were 91.0% and 72.9%, respectively. Other malignant renal tumors had a poorer survival. CONCLUSION: Prognosis for patients with Wilms tumor treated on TWPINDA-99 seems to be better than previous national trials and is similar to developed countries.


Asunto(s)
Neoplasias Renales/terapia , Tumor de Wilms/terapia , Adolescente , Niño , Preescolar , Chile , Países Desarrollados , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Recién Nacido , Neoplasias Renales/mortalidad , Masculino , Programas Nacionales de Salud/normas , Estadificación de Neoplasias , Pediatría , Tasa de Supervivencia , Resultado del Tratamiento , Tumor de Wilms/mortalidad
14.
Pediatr Blood Cancer ; 62(9): 1562-6, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26207356

RESUMEN

BACKGROUND: Sorafenib is an oral small molecule inhibitor of multiple kinases controlling tumor growth and angiogenesis. The purpose of the phase 2 study was to determine the response rate of sorafenib and gain further information on the associated toxicities, pharmacokinetics, and pharmacodynamics of sorafenib in children and young adults with relapsed or refractory tumors including rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), and papillary thyroid carcinoma (PTC). PROCEDURE: Sorafenib, 200 mg/m(2) /dose, was administered every 12 hr continuously for 28 day cycles using a two-stage design in two primary strata (rhabdomyosarcoma and Wilms tumor) and two secondary strata (HCC and PTC). Correlative studies in consenting patients included determination of sorafenib steady state trough concentrations and assessments of VEGF and sVEGFR2. RESULTS: Twenty patients (median age of 11 years; range, 5-21) enrolled. No objective responses (RECIST) were observed in the 10 evaluable patients enrolled in each of the two primary disease strata of rhabdomyosarcoma and Wilms tumor. No patients with HCC or PTC were enrolled. Sorafenib was not associated with an excessive rate of dose-limiting toxicity (DLT). The mean ± SD steady state concentration during cycle 1 day 15 was 6.5 ± 3.9 µg/ml (n = 10). CONCLUSIONS: Sorafenib was well tolerated in children at 200 mg/m(2) /dose twice daily on a continuous regimen with toxicity profile and steady state drug concentrations similar to those previously reported. Single agent sorafenib was inactive in children with recurrent or refractory rhabdomyosarcoma or Wilms tumor.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Rabdomiosarcoma/tratamiento farmacológico , Terapia Recuperativa , Tumor de Wilms/tratamiento farmacológico , Adolescente , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/farmacocinética , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Niño , Preescolar , Femenino , Humanos , Neoplasias Renales/sangre , Neoplasias Renales/enzimología , Masculino , Proteínas de Neoplasias/sangre , Niacinamida/efectos adversos , Niacinamida/farmacocinética , Niacinamida/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/farmacocinética , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacocinética , Rabdomiosarcoma/sangre , Rabdomiosarcoma/enzimología , Sorafenib , Insuficiencia del Tratamiento , Factor A de Crecimiento Endotelial Vascular/sangre , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangre , Tumor de Wilms/sangre , Tumor de Wilms/enzimología , Adulto Joven
15.
J Pediatr Surg ; 50(9): 1484-9, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25783402

RESUMEN

PURPOSE: Antiangiogenic agents show significant antitumor activity against various tumor types. In a study evaluating the combination of sorafenib, bevacizumab, and low-dose cyclophosphamide in children with solid tumors, an unexpectedly high incidence of pneumothorax was observed. We evaluated patient characteristics and risk factors for the development of pneumothorax in patients receiving this therapy. PATIENTS AND METHODS: Demographics, clinical course, and radiographic data of 44 patients treated with sorafenib, bevacizumab and cyclophosphamide were reviewed. Risk factors associated with the development of pneumothorax were analyzed. RESULTS: Pneumothorax likely related to study therapy developed in 11 of 44 (25%) patients of whom 33 had pulmonary abnormalities. Median age of patients was 14.7 years (range, 1.08-24.5). Histologies associated with pneumothorax included rhabdoid tumor, synovial sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and renal cell carcinoma. Cavitation of pulmonary nodules in response to therapy was associated with pneumothorax development (P<0.001). Median time from start of therapy to development of pneumothorax was 5.7 weeks (range, 2.4-31). CONCLUSION: The development of cavitary pulmonary nodules in response to therapy is a risk factor for pneumothorax. As pneumothorax is a potentially life-threatening complication of antiangiogenic therapy in children with solid tumors, its risk needs to be evaluated when considering this therapy.


Asunto(s)
Inhibidores de la Angiogénesis/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Neumotórax/inducido químicamente , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma Sinovial/tratamiento farmacológico , Tumor de Wilms/tratamiento farmacológico , Adolescente , Adulto , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/efectos adversos , Bevacizumab/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Niacinamida/efectos adversos , Niacinamida/análogos & derivados , Niacinamida/uso terapéutico , Osteosarcoma/tratamiento farmacológico , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Neumotórax/diagnóstico , Sorafenib , Adulto Joven
16.
Genes Dev ; 29(5): 467-82, 2015 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-25737276

RESUMEN

Wilms' tumor, or nephroblastoma, is the most common pediatric renal cancer. The tumors morphologically resemble embryonic kidneys with a disrupted architecture and are associated with undifferentiated metanephric precursors. Here, we discuss genetic and epigenetic findings in Wilms' tumor in the context of renal development. Many of the genes implicated in Wilms' tumorigenesis are involved in the control of nephron progenitors or the microRNA (miRNA) processing pathway. Whereas the first group of genes has been extensively studied in normal development, the second finding suggests important roles for miRNAs in general-and specific miRNAs in particular-in normal kidney development that still await further analysis. The recent identification of Wilms' tumor cancer stem cells could provide a framework to integrate these pathways and translate them into new or improved therapeutic interventions.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Neoplasias Renales/genética , Riñón/embriología , Organogénesis/genética , Tumor de Wilms/genética , Animales , Epigénesis Genética/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Riñón/patología , MicroARNs/genética
17.
Genet Test Mol Biomarkers ; 19(2): 75-81, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25536437

RESUMEN

AIM: Embryonic tumors are associated with an interruption during normal organ development; they may be related to disturbances in the folate pathway involved in DNA synthesis, methylation, and repair. Prenatal supplementation with folic acid is associated with a decreased risk of neuroblastoma, brain tumors, retinoblastoma, and nephroblastoma. The aim of this study was to investigate the association between MTHFR rs1801133 (C677T) and RFC-1 rs1051266 (G80A) genotypes with the risk of developing nephroblastoma and neuroblastoma. MATERIALS AND METHODS: Case-mother/control-mother dyad study. Samples from Brazilian children with nephroblastoma (n=80), neuroblastoma (n=66), healthy controls (n=453), and their mothers (case n=93; control n=75) were analyzed. Genomic DNA was isolated from peripheral blood cells and/or buccal cells and genotyped to identify MTHFR C677T and RFC-1 G80A polymorphisms. Differences in genotype distribution between patients and controls were tested by multiple logistic regression analysis. RESULTS: Risk for nephroblastoma and neuroblastoma was two- to fourfold increased among children with RFC-1 polymorphisms. An increased four- to eightfold risk for neuroblastoma and nephroblastoma was seen when the child and maternal genotypes were combined. CONCLUSION: Our results suggest that mother and child RFC-1 G80A genotypes play a role on the risk of neuroblastoma and nephroblastoma since this polymorphism may impair the intracellular levels of folate, through carrying fewer folate molecules to the cell interior, and thus, the intracellular concentration is not enough to maintain regular DNA synthesis and methylation pathways.


Asunto(s)
Neoplasias Renales/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Madres , Proteínas de Neoplasias/genética , Neuroblastoma/genética , Polimorfismo de Nucleótido Simple , Proteína de Replicación C/genética , Tumor de Wilms/genética , Brasil/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Ácido Fólico/metabolismo , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Neuroblastoma/epidemiología , Riesgo , Tumor de Wilms/epidemiología
18.
Pediatr Blood Cancer ; 61(5): 922-4, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24166988

RESUMEN

Pixantrone, a novel aza-anthracenedione with cytotoxic activity, was tested against the PPTP in vitro panel (3.0 nM to 30.0 µM) and against a limited panel of PPTP Wilms tumors and sarcomas (7.5 mg/kg) administered intravenously using an every 4 day × 3 schedule. In vitro pixantrone showed a median relative IC50 value of 54 nM (range <3 nM to 1.03 µM). In vivo pixantrone induced significant differences in EFS distribution compared to controls in two of eight solid tumor xenografts at dose levels relevant to human drug exposure. A complete response was observed for one Wilms tumor xenograft.


Asunto(s)
ADN-Topoisomerasas de Tipo II/química , Isoquinolinas/farmacología , Rabdomiosarcoma/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Inhibidores de Topoisomerasa II/farmacología , Tumor de Wilms/tratamiento farmacológico , Animales , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Proliferación Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Isoquinolinas/farmacocinética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Ratones , Ratones SCID , Rabdomiosarcoma/patología , Sarcoma de Ewing/patología , Distribución Tisular , Inhibidores de Topoisomerasa II/farmacocinética , Células Tumorales Cultivadas , Tumor de Wilms/patología , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Mol Med Rep ; 8(5): 1537-41, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24002362

RESUMEN

Wilms' tumor is a type of kidney cancer that affects young children. Although a number of Wilms' tumor samples have been collected through international trials, the mechanisms underlying its progression remain challenging to determine. Extensive studies have identified somatic mutations at several loci in Wilms' tumorigenesis, including WT1, catenin, Wilms' tumor gene on the X chromosome (WTX) and TP53. Berberine is a benzylisoquinoline alkaloid extracted from numerous types of medicinal plants and has been extensively used as a Chinese traditional medicine. Recently, berberine has been demonstrated to possess antitumoral activities. AMP-activated protein kinase (AMPK) is suggested to be one of the various cellular targets of berberine, which regulates tumor progression and metastasis. However, the specific involvement of berberine­induced AMPK activation and its effects on the proliferation potential of Wilms' tumor cells remains unknown. The present study investigated the berberine­induced activation of AMPK and its effects on G401 Wilms' tumor cell proliferation. The results demonstrated that berberine inhibited growth and decreased the expression of cell­cycle regulators in these cells. At the molecular level, berberine treatment led to a significant increase of WTX expression and G401 cells were protected against berberine­induced growth inhibition by small interfering RNA against WTX. In conclusion, these results suggest a novel mechanism that may contribute to the antineoplastic effects of berberine which was also demonstrated by recent population studies; however, further studies are required to investigate the potential therapeutic use of berberine in patients with Wilms' tumor.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Berberina/farmacología , Proliferación Celular/efectos de los fármacos , Cromosomas Humanos X/genética , Neoplasias Renales/tratamiento farmacológico , Proteínas Supresoras de Tumor/metabolismo , Tumor de Wilms/tratamiento farmacológico , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/genética , Apoptosis/efectos de los fármacos , Western Blotting , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor/antagonistas & inhibidores , Proteínas Supresoras de Tumor/genética , Tumor de Wilms/genética , Tumor de Wilms/patología
20.
Lima; s.n; 2013. 46 p. ilus, tab, graf.
Tesis en Español | LILACS, LIPECS | ID: biblio-1113351

RESUMEN

Objetivo: Describir las características clínicas y tomográficas del tumor de Wilms en los pacientes del INSTITUTO NACIONAL DE ENFERMEDADES NEOPLASICAS, Lima-Perú, durante el periodo 2007-2011. Métodos: Se diseñó un estudio descriptivo, observacional, perfil radiológico-epidemiológico, retrospectivo. Resultados: La edad promedio fue 3,04 años y el tiempo de enfermedad fue 68 días. El género se distribuyó mayormente en el sexo femenino con 50,7 por ciento La masa abdominal predominó en los pacientes con tumor de Wilms con 81,3 por ciento; en segundo lugar se evidenció al dolor abdominal con 66,7 por ciento. Con menos frecuencia se presentó la hematuria y fiebre con 21,3 por ciento y 16 por ciento cada uno, respectivamente. La forma del tumor de Wilms predominante fue ovalada en el 54,7 por ciento; seguido de la forma redondeada en 36 por ciento; lobulada con 6,7 por ciento y bilobulada en el 2,6 por ciento. Los bordes regulares se presentaron en el 94,7 por ciento. El tamaño promedio del tumor fue 12,5 cm, predominaron los tumores con tamaño de 11 cm a más con 69,3 por ciento. Existió cruce de la línea media en el 73,3 por ciento de los casos. La estructura interna evidenciada por tomografía fue heterogénea en el 98,7 por ciento de los casos. La estructura interna heterogénea del tumor de Wilms se manifestó con características de necrosis en el 97,2 por ciento y combinada con calcificación y hemorragia en el 1,4 por ciento de los casos cada uno, respectivamente. El tumor de Wilms desplazó a las estructuras vasculares en el 62,7 por ciento; engloba a las mismas en el 24 por ciento e infiltra en el 8 por ciento de los casos. La trombosis de la vena renal y vena cava se presentó en el 13,3 por ciento y 9,3 por ciento cada uno respectivamente. No se encontró ninguna relación del tumor con los vasos en el 22,7 por ciento. Las metástasis a las adenopatías regionales se presentan en el 12 por ciento; las adenopatías a distancia en el 26,7 por ciento. La metástasis a...


Objective: To describe the clinical and tomographic Wilms tumor patients of the NATIONAL INSTITUTE OF NEOPLASTIC DISEASES, Lima, Peru, during the period 2007-2011. Methods: We performed a descriptive, observational, radiological and epidemiological profile, retrospective. Results: The mean age was 3.04 years and the disease duration was 68 days. The genus is distributed mostly in females with 50.7 per cent. The predominant abdominal mass in patients with Wilms tumor with 81.3 per cent, second abdominal pain was evident with 66.7 per cent. Less often presented with hematuria and fever 21.3 per cent and 16 per cent each, respectively. The shape of the predominant Wilms tumor was oval in 54.7 per cent, followed by the rounded shape in 36 per cent; lobed with 6.7 per cent and 2.6 per cent in bilobed. The regular margins occurred in 94.7 per cent. The average tumor size was 12.5 cm predominated tumors with a size of 11 cm with 69.3 per cent more. There was crossing the midline in 73.3 per cent of cases. The internal structure was heterogeneous tomography evidenced in 98.7 per cent of cases. The heterogeneous internal structure of Wilms tumor with features of necrosis expressed in 97.2 per cent and combined with calcification and hemorrhage in 1.4 per cent of cases each, respectively. Wilms tumor vascular structures displaced in 62.7 per cent; encompasses the same in 24 per cent and 8 per cent infiltrates cases. Thrombosis of the renal vein and vena cava was presented in 13.3 per cent and 9.3 per cent each respectively. There was no relationship of tumor vessels in 22.7 per cent. Metastases to regional Iymph nodes occur in 12 per cent, Iymphadenopathy distance in 26.7 per cent. The liver metastases occurred in 16 per cent of cases and 18.7 per cent in the lungs. Other metastases occurred in 13.3 per cent of cases. Conclusion: The most prevalent clinical features was the mass and abdominal pain. The tumor characteristics were tomographic oval regular edge larger...


Asunto(s)
Masculino , Femenino , Humanos , Recién Nacido , Lactante , Preescolar , Diagnóstico Clínico , Tomografía , Tumor de Wilms , Estudio Observacional , Estudios Retrospectivos , Informes de Casos
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