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1.
J Pharmacol Sci ; 149(2): 60-65, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35512856

RESUMEN

Infantile hemangioma (IH) is a common tumor in infants that gradually resolves and is often untreated. However, for cosmetic reasons, parents often opt for treatment. Oral propranolol, the first-line therapy for IH, is sometimes associated with several side effects, including hypotension, bradycardia, and hypoglycemia. No clinical studies on topical propranolol have been conducted using standardized procedures. We evaluated the efficacy and safety of topical propranolol in patients with IH. This multicenter, prospective pilot study was conducted from June 2019 to October 2020 and involved eight Japanese infants aged 35-150 days with proliferating IH. Patients were treated with 5% propranolol cream twice daily. We examined the efficacy rate based on central evaluation (complete or near-complete healing of the target hemangioma) at weeks 24 and 12, respectively, compared to baseline values. The efficacy rate at week 24 was 68.8% (95% confidence interval: 44.1-85.9%). The surface area, maximum diameter, and color intensity of the target IH decreased over time. Adverse event and drug-related adverse event rates were 87.5% and 0%, respectively. Propranolol cream may be effective and safe in Japanese patients with IH and may be considered a first-choice treatment for small and superficial IHs in cosmetically problematic areas.


Asunto(s)
Hemangioma Capilar , Hemangioma , Neoplasias Cutáneas , Administración Oral , Antagonistas Adrenérgicos beta/efectos adversos , Hemangioma/inducido químicamente , Hemangioma/tratamiento farmacológico , Hemangioma/patología , Hemangioma Capilar/inducido químicamente , Hemangioma Capilar/tratamiento farmacológico , Humanos , Lactante , Proyectos Piloto , Propranolol/efectos adversos , Estudios Prospectivos , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Resultado del Tratamiento
2.
Chem Pharm Bull (Tokyo) ; 70(4): 277-282, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35370204

RESUMEN

Propranolol is used as the first-line treatment for infantile hemangiomas (IHs). As oral formulations can cause systemic adverse drug reactions (ADRs), we prepared topical propranolol formulations and evaluated their pharmaceutical profiles. We also present three cases of pediatric patients with IHs who were treated with the propranolol formulations. Propranolol cream (hydrophilic cream, 1, 3, and 5%) and gels (carboxyvinyl polymer, hydroxypropyl methylcellulose, gellan gum, 1%) were prepared. The in vitro skin permeability of these formulations was assessed using Franz-type diffusion cells. The pharmaceutical profiles, including propranolol content, pH, and ductility, of the propranolol creams were evaluated. For the stability test, similar pharmaceutical evaluations were performed after the creams were stored at 25 °C and 56% relative humidity for 3 months. We examined three patients treated with propranolol cream to investigate the clinical course of IH and adverse events after the propranolol cream was applied for 5-12 months. In the in vitro skin permeability assay, topical propranolol formulations made of hydrophilic cream and gellan gum permeated the most. The amount of propranolol that permeated increased with propranolol concentration. After storage for 3 months, no substantial changes were observed in any pharmaceutical profile. The IHs were discolored in all patients. Tumor size also decreased in some patients. Furthermore, no adverse events caused by propranolol cream were observed during application. In conclusion, propranolol cream can be prepared as a hospital formulation with adequate quality. Topical propranolol therapy is effective in reducing the incidence of systemic ADRs.


Asunto(s)
Hemangioma , Neoplasias Cutáneas , Niño , Hemangioma/inducido químicamente , Hemangioma/tratamiento farmacológico , Hemangioma/patología , Humanos , Derivados de la Hipromelosa , Lactante , Propranolol/efectos adversos , Propranolol/uso terapéutico , Piel , Neoplasias Cutáneas/tratamiento farmacológico
3.
Pediatr Dermatol ; 32(4): 539-43, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25690955

RESUMEN

Infantile hemangiomas (IHs) are the most common benign tumor of infancy, characterized by a natural history of early proliferation in the first months of life to eventual involution during childhood, often with residual fibrofatty tissue. Once involution has been achieved, IHs do not typically recur. We present two cases of exogenous growth hormone therapy resulting in the recurrence of IHs in late childhood, supported by radiological, immunohistochemical, in vitro, and in vivo evidence.


Asunto(s)
Hemangioma/inducido químicamente , Hormona de Crecimiento Humana/efectos adversos , Recurrencia Local de Neoplasia/inducido químicamente , Neoplasias Cutáneas/inducido químicamente , Biopsia , Niño , Femenino , Hemangioma/patología , Hemangioma/cirugía , Hormona de Crecimiento Humana/deficiencia , Humanos , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía
4.
Pediatr Int ; 57(2): e34-6, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25868957

RESUMEN

Diffuse neonatal hemangiomatosis (DNH) is a rare condition characterized by the concomitant development of multiple cutaneous infantile hemangiomas (IH) and visceral hemangiomas. Recently, an association between erythropoietin treatment and an increased incidence of infantile hemangioma was noted. A Japanese male infant was born via cesarean section at 27 weeks of gestation. Following the commencement of erythropoietin treatment for anemia of prematurity, he developed multiple cutaneous hemangiomas, high cardiac output heart failure and hepatomegaly. Abdominal imaging indicated comorbidity of diffuse infantile hepatic hemannigomas, resulting in the final diagnosis of DNH. The discontinuation of erythropoietin treatment and long-term therapy with propranolol improved the hepatic lesions and cutaneous hemangiomas. The possibility of multiple organ involvement and the exacerbating effects of erythropoietin treatment should be considered in cases in which multiple cutaneous hemangiomas develop in preterm infants receiving erythropoietin treatment.


Asunto(s)
Eritropoyetina/efectos adversos , Hemangioma/inducido químicamente , Recién Nacido de muy Bajo Peso , Inestabilidad de la Articulación/inducido químicamente , Fimosis/inducido químicamente , Anomalías Cutáneas/inducido químicamente , Antagonistas Adrenérgicos beta/uso terapéutico , Anemia Neonatal/tratamiento farmacológico , Edad Gestacional , Hemangioma/diagnóstico , Hemangioma/tratamiento farmacológico , Humanos , Recién Nacido , Recien Nacido Prematuro , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Fimosis/diagnóstico , Fimosis/tratamiento farmacológico , Propranolol/uso terapéutico , Anomalías Cutáneas/diagnóstico , Anomalías Cutáneas/tratamiento farmacológico
6.
Toxicol Pathol ; 41(5): 709-21, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23125116

RESUMEN

It is unclear whether the process of spontaneous and chemically induced hemangiosarcoma and hemangioma formation in mice involves the transformation of differentiated endothelial cells (ECs) or recruitment of multipotential bone marrow-derived hematopoietic stem cells or endothelial progenitor cells (EPCs), which show some degree of endothelial differentiation. In the present study, immunohistochemical staining for hematopoietic stem cell markers (CD45 and CD34), EC markers (vascular endothelial growth factor receptor 2 [VEGFR2], CD31, and factor VIII-related antigen), and a myeloid lineage marker (CD14) was employed to better define the origin of hemangiosarcomas and hemangiomas in mice. Staining was negative for CD45, factor VIII-related antigen, and CD14 and positive for CD34, VEGFR2, and CD31, indicating that mouse hemangiosarcomas and hemangiomas are composed of cells derived from EPCs expressing CD34, VEGFR2, and CD31 but not factor VIII-related antigen. The lack of CD45 expression suggests that mouse vascular tumors may arise from EPCs that are at a stage later than hematopoietic stem cells. Since factor VIII-related antigen expression is known to occur later than CD31 expression in EPCs, our observations may indicate that these tumor cells are arrested at a stage prior to complete differentiation.  In addition, myeloid lineage cells do not appear to contribute to hemangiosarcoma and hemangioma formation in mice.


Asunto(s)
Antígenos CD/análisis , Células Endoteliales/metabolismo , Hemangioma/metabolismo , Hemangiosarcoma/metabolismo , Células Madre Hematopoyéticas/metabolismo , Células Mieloides/metabolismo , Animales , Antígenos CD/química , Biomarcadores/análisis , Biomarcadores/química , Células Endoteliales/química , Células Endoteliales/inmunología , Femenino , Hemangioma/inducido químicamente , Hemangioma/inmunología , Hemangiosarcoma/inducido químicamente , Hemangiosarcoma/inmunología , Células Madre Hematopoyéticas/química , Células Madre Hematopoyéticas/inmunología , Inmunohistoquímica , Masculino , Ratones , Mutágenos/toxicidad , Células Mieloides/química , Células Mieloides/inmunología
7.
Medwave ; 23(11): e2753, 2023 Dec 07.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38061014

RESUMEN

Introduction: Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a non-selective lipophilic beta-blocker, is usually considered the therapy of choice. However, its use has been associated with several adverse events related to its ß-2 action and its ability to cross the blood-brain barrier. Because of this, oral atenolol, a hydrophilic ß-1 receptor-selective beta-blocker, may represent a valid treatment alternative. Nonetheless, there is still controversy regarding the efficacy and safety of atenolol when compared with propranolol as monotherapy for this condition. Methods: We searched Epistemonikos, the largest database of systematic reviews in health science, which is maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane, among others. Data were extracted from the identified reviews, data from the primary studies were analyzed, a meta-analysis was performed, and a summary table of the results was prepared using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Results: Nine systematic reviews were identified, including 10 primary studies and three randomized trials. The three randomized trials were included in the analysis of this investigation. Conclusion: The use of oral atenolol compared with oral propranolol as monotherapies may result in little or no difference in terms of likelihood of complete remission, decrease in Hemangioma Activity Score, likelihood of post-treatment relapse, and risk of adverse events and severe adverse events, in infantile hemangioma (low certainty of evidence).


Introducción: El hemangioma infantil corresponde al tumor vascular benigno más frecuente de la infancia, con una incidencia de 3 a 10%. Entre los pacientes que requieren tratamiento el uso oral de propranolol, un betabloqueador no selectivo de tipo lipofílico, es usualmente considerado como la terapia de elección. Sin embargo, su uso se ha asociado a diversos efectos adversos, relacionados con su acción ß-2, y a su capacidad de cruzar la barrera hematoencefálica. Debido a esto, el uso oral de atenolol, un betabloqueador selectivo de receptores ß-1, de tipo hidrofílico, podría representar una alternativa válida de tratamiento. Sin embargo, aún existe controversia en relación con la eficacia y seguridad del tratamiento con atenolol como monoterapia, en comparación con el uso de propranolol como monoterapia para esta condición. Métodos: Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Se extrajeron los datos desde las revisiones identificadas, se analizaron los datos de los estudios primarios, se realizó un metanálisis y se preparó una tabla de resumen de los resultados utilizando el método GRADE. Resultados: Se identificaron nueve revisiones sistemáticas, que en conjunto incluyeron 10 estudios primarios y tres ensayos aleatorizados. Se incluyeron los tres ensayos aleatorizados en el análisis del presente trabajo. Conclusiones: El uso de atenolol oral como monoterapia, comparado con el uso de propranolol oral como monoterapia, podría resultar en poca o nula diferencia en cuanto a la probabilidad de remisión completa, la disminución del , la probabilidad de recaída posterior al tratamiento y el riesgo de presentar efectos adversos y efectos adversos severos, en el hemangioma infantil (certeza de la evidencia baja).


Asunto(s)
Hemangioma Capilar , Hemangioma , Humanos , Propranolol/efectos adversos , Atenolol/efectos adversos , Resultado del Tratamiento , Recurrencia Local de Neoplasia/inducido químicamente , Revisiones Sistemáticas como Asunto , Antagonistas Adrenérgicos beta/efectos adversos , Hemangioma Capilar/inducido químicamente , Hemangioma/tratamiento farmacológico , Hemangioma/inducido químicamente
8.
Toxicol Pathol ; 40(1): 18-32, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22131108

RESUMEN

Tesaglitazar was developed as a dual peroxisome proliferator-activated receptor (PPARα/γ). To support the clinical program, a hamster carcinogenicity study was performed. The only neoplastic findings possibly related to treatment with tesaglitazar were low incidences of hemangioma and hemangiosarcoma in the liver of male animals. A high-power, two-year investigative study with interim necropsies was performed to further elucidate these findings. Treatment with tesaglitazar resulted in changes typical for exaggerated PPARα pharmacology in rodents, such as hepatocellular hypertrophy and hepatocellular carcinoma, but not an increased frequency of hemangiosarcomas. At the highest dose level, there was an increased incidence of sinusoidal dilatation and hemangiomas. No increased endothelial cell (EC) proliferation was detected in vivo, which was confirmed by in vitro administration to ECs. Immunohistochemistry and gene expression analyses indicated increased cellular stress and vascular endothelial growth factor (VEGF) expression in the liver, which may have contributed to the sinusoidal dilatation. A two-fold increase in the level of circulating VEGF was detected in the hamster at all dose levels, whereas no effect on VEGF was observed in patients treated with tesaglitazar. In conclusion, investigations have demonstrated that tesaglitazar does not produce hemangiosarcomas in hamster despite a slight effect on vascular morphology in the liver.


Asunto(s)
Alcanosulfonatos/toxicidad , Neoplasias Hepáticas Experimentales/inducido químicamente , PPAR alfa/agonistas , PPAR gamma/agonistas , Fenilpropionatos/toxicidad , Animales , Área Bajo la Curva , Pruebas de Carcinogenicidad , Proliferación Celular/efectos de los fármacos , Cricetinae , Femenino , Perfilación de la Expresión Génica , Hemangioma/inducido químicamente , Hemangiosarcoma/inducido químicamente , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Inmunohistoquímica , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Estadísticas no Paramétricas , Factor A de Crecimiento Endotelial Vascular/metabolismo
9.
Folia Med (Plovdiv) ; 64(1): 67-74, 2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35851882

RESUMEN

AIM: Infantile hemangiomas are the most common benign vascular tumours in infants. In this study, we aimed to evaluate the effectiveness of propranolol therapy in patients with infantile hemangioma.


Asunto(s)
Hemangioma Capilar , Hemangioma , Neoplasias Cutáneas , Administración Oral , Hemangioma/inducido químicamente , Hemangioma/tratamiento farmacológico , Hemangioma Capilar/tratamiento farmacológico , Humanos , Lactante , Propranolol/efectos adversos , Propranolol/uso terapéutico , Resultado del Tratamiento
11.
J Eur Acad Dermatol Venereol ; 23(8): 940-4, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19453792

RESUMEN

BACKGROUND: Skin lesions are among the most common complications of contact with sulfur mustard. OBJECTIVE: This study was aimed to measure skin water content and transepidermal water loss (TEWL) in patients with a history of sulfur mustard contact. METHODS: Three hundred ten male participants were included in this study: 87 (28.1%) sulfur mustard-exposed patients with current skin lesions (group 1), 71 (22.9%) sulfur mustard-exposed patients without skin lesions (group 2), 78 (25.2%) patients with dermatitis (group 3) and 74 (23.8%) normal controls (group 4) The water content and TEWL of skin was measured at four different locations of the body: forehead, suprasternal, palm and dorsum of hand. Nonparametric statistical tests (Kruskal-Wallis) were used to compare the four groups, and P < 0.05 was considered statistically significant. RESULTS: The mean age of participants were 44.0 +/- 6.7, 41.9 +/- 5.9, 43.8 +/- 9.3 and 44.8 +/- 8.9 years in groups 1 to 4, respectively (P = 0.146). Xerosis, post-lesional hyperpigmentation and lichenification were significantly more common in either sulfur mustard-exposed participants or non-exposed participants with dermatitis (P < 0.05). Skin hydration was higher in subjects with sulfur mustard contact than in non-injured participants (P < 0.05) in the dorsum and palm of hands and forehead. TEWL was significantly higher in participants only in suprasternal area and dorsum of hand. CONCLUSION: Contact with sulfur mustard agent can alter biophysical properties of the skin--especially the function of stratum corneum as a barrier to water loss-several years after exposure.


Asunto(s)
Sustancias para la Guerra Química/efectos adversos , Gas Mostaza/efectos adversos , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/fisiopatología , Fenómenos Fisiológicos de la Piel , Pérdida Insensible de Agua/fisiología , Equilibrio Hidroelectrolítico/fisiología , Adulto , Estudios de Casos y Controles , Hemangioma/inducido químicamente , Hemangioma/epidemiología , Hemangioma/fisiopatología , Humanos , Hiperpigmentación/inducido químicamente , Hiperpigmentación/epidemiología , Hiperpigmentación/fisiopatología , Incidencia , Irán , Masculino , Persona de Mediana Edad , Prurito/inducido químicamente , Prurito/epidemiología , Prurito/fisiopatología , Enfermedades de la Piel/epidemiología , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/fisiopatología
12.
Medwave ; 23(11): e2753, 31-12-2023. tab, ilus
Artículo en Inglés, Español | LILACS | ID: biblio-1524728

RESUMEN

INTRODUCCIÓN: El hemangioma infantil corresponde al tumor vascular benigno más frecuente de la infancia, con una incidencia de 3 a 10%. Entre los pacientes que requieren tratamiento el uso oral de propranolol, un betabloqueador no selectivo de tipo lipofílico, es usualmente considerado como la terapia de elección. Sin embargo, su uso se ha asociado a diversos efectos adversos, relacionados con su acción ß-2, y a su capacidad de cruzar la barrera hematoencefálica. Debido a esto, el uso oral de atenolol, un betabloqueador selectivo de receptores ß-1, de tipo hidrofílico, podría representar una alternativa válida de tratamiento. Sin embargo, aún existe controversia en relación con la eficacia y seguridad del tratamiento con atenolol como monoterapia, en comparación con el uso de propranolol como monoterapia para esta condición. MÉTODOS: Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Se extrajeron los datos desde las revisiones identificadas, se analizaron los datos de los estudios primarios, se realizó un metanálisis y se preparó una tabla de resumen de los resultados utilizando el método , GRADE. RESULTADOS: Se identificaron nueve revisiones sistemáticas, que en conjunto incluyeron 10 estudios primarios y tres ensayos aleatorizados. Se incluyeron los tres ensayos aleatorizados en el análisis del presente trabajo. CONCLUSIONES: El uso de atenolol oral como monoterapia, comparado con el uso de propranolol oral como monoterapia, podría resultar en poca o nula diferencia en cuanto a la probabilidad de remisión completa, la disminución del , la probabilidad de recaída posterior al tratamiento y el riesgo de presentar efectos adversos y efectos adversos severos, en el hemangioma infantil (certeza de la evidencia baja).


INTRODUCTION: Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a non-selective lipophilic beta-blocker, is usually considered the therapy of choice. However, its use has been associated with several adverse events related to its ß-2 action and its ability to cross the blood-brain barrier. Because of this, oral atenolol, a hydrophilic ß-1 receptor-selective beta-blocker, may represent a valid treatment alternative. Nonetheless, there is still controversy regarding the efficacy and safety of atenolol when compared with propranolol as monotherapy for this condition. METHODS: We searched Epistemonikos, the largest database of systematic reviews in health science, which is maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane, among others. Data were extracted from the identified reviews, data from the primary studies were analyzed, a meta-analysis was performed, and a summary table of the results was prepared using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. RESULTS: Nine systematic reviews were identified, including 10 primary studies and three randomized trials. The three randomized trials were included in the analysis of this investigation. CONCLUSION: The use of oral atenolol compared with oral propranolol as monotherapies may result in little or no difference in terms of likelihood of complete remission, decrease in Hemangioma Activity Score, likelihood of post-treatment relapse, and risk of adverse events and severe adverse events, in infantile hemangioma (low certainty of evidence).


Asunto(s)
Humanos , Hemangioma Capilar/inducido químicamente , Hemangioma/inducido químicamente , Hemangioma/tratamiento farmacológico , Propranolol/efectos adversos , Atenolol/efectos adversos , Resultado del Tratamiento , Antagonistas Adrenérgicos beta/efectos adversos , Revisiones Sistemáticas como Asunto , Recurrencia Local de Neoplasia/inducido químicamente
13.
Cancer Lett ; 238(2): 271-83, 2006 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-16150539

RESUMEN

To elucidate which is the major determinant of susceptibility of p53 deficient mice, the carcinogen or the target organ, N-bis(2-hydroxypropyl)nitrosamine was administered to induce tumors in multi-organs. In a 15-week experiment, the incidences of both lung and hepatic vascular tumors were found to be significantly higher in p53 nullizygous (-/-) than in heterozygous (+/-) and wild-type (+/+) mice, indicating universal susceptibility of p53 (-/-) mice. In a 40-week experiment, p53 (+/-) mice showed increased susceptibility only with regard to vascular tumors, coinciding with significantly more frequent (60%) p53 gene mutations, in comparison with lung tumors with their low mutation rate (10.8%) (P<0.005). These results indicate that the target organ may be a more important factor than the carcinogen in determining susceptibility of p53 (+/-) mice.


Asunto(s)
Nitrosaminas/toxicidad , Proteína p53 Supresora de Tumor/fisiología , Animales , Femenino , Genes p53 , Hemangioma/inducido químicamente , Hemangiosarcoma/inducido químicamente , Neoplasias Hepáticas/inducido químicamente , Neoplasias Pulmonares/inducido químicamente , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación , Especificidad de Órganos
14.
J Dermatol ; 33(12): 877-9, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17169094

RESUMEN

We report a 27-year-old man who had suffered with vitiligo for 7 years and with eruptive cherry angiomas within or around the repigmented vitiliginous skin for 2 years. After continual therapy for vitiligo with topical nitrogen mustard in a concentration of 0.001% for 5 years, multiple cherry angiomas erupted within or around the repigmented vitiliginous plaques. The discontinue therapy with nitrogen mustard stopped the appearance of new cherry angiomas. The presence of eruptive cherry angiomas was evident and was confirmed by histopathology. We suggest that the chronic chemical stimuli caused by topical nitrogen mustard might result in the formation of eruptive cherry angiomas.


Asunto(s)
Alquilantes/efectos adversos , Fármacos Dermatológicos/efectos adversos , Hemangioma/inducido químicamente , Mecloretamina/efectos adversos , Neoplasias Cutáneas/inducido químicamente , Vitíligo/tratamiento farmacológico , Adulto , Capilares/patología , Hemangioma/patología , Humanos , Masculino , Neoplasias Cutáneas/patología , Pigmentación de la Piel/efectos de los fármacos , Telangiectasia/patología
15.
J Natl Cancer Inst ; 77(2): 573-82, 1986 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3461216

RESUMEN

Propylene oxide (CAS: 75-56-9) was studied for potential carcinogenicity and chronic toxicity by inhalation in F344/N rats and (C57BL/6 x C3H)F1 mice. Groups of 50 animals of each sex were exposed to 0, 200, or 400 ppm propylene oxide for 6 hours/day, 5 days/week, for up to 103 weeks. Survival decreased in mice exposed to propylene oxide; the decrease was significant (P less than .005) in mice exposed to 400 ppm. Survival of exposed rats was comparable to that of controls. Mean body weight of rats and mice exposed to 400 ppm propylene oxide decreased, when compared to that of controls, during the 2d year of exposure. Exposure to propylene oxide for up to 2 years induced inflammatory and proliferative responses in nasal cavity of both species. There was clear evidence of carcinogenicity in mice exposed to 400 ppm propylene oxide; 10 of 50 males and 5 of 50 females had hemangiomas or hemangiosarcomas of the nasal submucosa. Papillary adenomas involving the nasal respiratory epithelium and underlying submucosal glands were observed in 3 female rats and 2 male rats exposed to 400 ppm propylene oxide.


Asunto(s)
Compuestos Epoxi/toxicidad , Éteres Cíclicos/toxicidad , Neoplasias Nasales/inducido químicamente , Animales , Relación Dosis-Respuesta a Droga , Femenino , Hemangioma/inducido químicamente , Hemangiosarcoma/inducido químicamente , Masculino , Ratones , Papiloma/inducido químicamente , Ratas , Ratas Endogámicas F344 , Rinitis/inducido químicamente , Especificidad de la Especie , Factores de Tiempo
16.
J Natl Cancer Inst ; 75(3): 581-7, 1985 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-3861903

RESUMEN

Mongolian gerbils (Meriones unguiculatus) were given an sc injection (40 mg/kg body wt) of N-ethyl-N-nitrosourea [(ENU) CAS: 759-73-9] on postnatal day 1 (group I) or day 29 (group II). Untreated gerbils served as controls (group III). Of 32 gerbils in group I, 10 (31%) developed a total of 14 gliomas after an observation period of 12 months, whereas no gliomas were observed in groups II and III. Seven gliomas were located in the spinal cord, 6 were in the cerebrum, and 1 was in the cerebellum. Histologically, all were oligodendrogliomas. In group II, 1 meningeal tumor (4%) was observed among 27 gerbils. ENU also induced cutaneous melanomas (22% in group I, 15% in group II, and 0% in group III), kidney hemangiomas (6% in group I, 26% in group II, and 0% in group III), and ameloblastomas of the lower jaw (6% in group I and 0% in groups II and III).


Asunto(s)
Etilnitrosourea , Glioma/inducido químicamente , Compuestos de Nitrosourea , Animales , Animales Recién Nacidos , Neoplasias Encefálicas/inducido químicamente , Femenino , Gerbillinae , Hemangioma/inducido químicamente , Neoplasias Renales/inducido químicamente , Masculino , Melanoma/inducido químicamente , Tumores Odontogénicos/inducido químicamente , Neoplasias Cutáneas/inducido químicamente , Neoplasias de la Médula Espinal/inducido químicamente
17.
J Natl Cancer Inst ; 57(5): 1179-83, 1976 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1034021

RESUMEN

Tetramethylhydrazine hydrochloride (TEMH) was administered in drinking water as a 0.125% solution to randomly bred Swiss mice for life beginning at 6 weeks of age. As a result of treatment, the incidence of blood vessel tumors rose from 5 to 96% in females and from 6 to 88% in males, while that of lung tumors increased from 21 to 36% in females and from 23 to 28% in males, as compared with untreated controls. The increased incidence of blood vessel tumors, but not of lung neoplasms, was statistically significant. Histopathologically, the tumors exhibited the characteristics of angiomas and angiosarcomas of blood vessels and adenomas of the lung. The investigation proved for the first time the tumorigenicity of TEMH. The possible role of increased methyl substitution on hydrazine in tumorigenesis was also discussed, as well as hydrazine derivatives as a tumor-producing class.


Asunto(s)
Adenoma/inducido químicamente , Carcinógenos , Hemangiosarcoma/inducido químicamente , Hidrazinas/toxicidad , Neoplasias Pulmonares/inducido químicamente , Animales , Femenino , Hemangioma/inducido químicamente , Neoplasias Renales/inducido químicamente , Masculino , Metilación , Metilhidrazinas , Ratones , Monometilhidrazina/toxicidad , Neoplasias Experimentales/inducido químicamente , Relación Estructura-Actividad
18.
J Natl Cancer Inst ; 55(4): 893-7, 1975 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-171427

RESUMEN

The effects of splenectomy on carcinogenesis by a single 10-mg dose of 7,12-dimethylbenz[alpha]anthracene (DMBA) given in olive oil by gavage was tested on BTOs, C57BL/60s, C3H/HeOs, and BALB/cOs mice. The splenectomy, performed a week before the DMBA was given, did not affect physical status or the incidence of acute toxic death of animals. DMBA-treated animals developed neoplasms at a significantly higher rate than did untreated mice. Splenectomy did not influence the overall incidence of neoplasms. Observed tumors in DMBA-treated groups were those of skin, forestomach, colon, liver, lung, adrenal, ovary, breast, hematopoietic-lymphoreticular system, and vascular system, depending on the strain. Types of DMBA-treated neoplasms were affected by prior splenectomy, depending on the strain: Splenectomy inhibited lung adenomas in BALB/cOs females and hepatomas in C57BL/60s females; splenectomy enhanced skin neoplasms in C57BL/60s and squamous cell carcinoma of the forestomach in BTOs males. The most significant change was in the incidence of the group of lymphomas. Myelogenous leukemia was increased in DMBA-treated groups of all strains, but splenectomy inhibited the development of this type of lymphoma.


Asunto(s)
9,10-Dimetil-1,2-benzantraceno , Benzo(a)Antracenos , Neoplasias Experimentales/inducido químicamente , Bazo/fisiología , 9,10-Dimetil-1,2-benzantraceno/envenenamiento , Adenoma/inducido químicamente , Neoplasias de las Glándulas Suprarrenales/inducido químicamente , Amiloidosis/inducido químicamente , Animales , Carcinoma Hepatocelular/inducido químicamente , Neoplasias del Colon/inducido químicamente , Femenino , Hemangioma/inducido químicamente , Leucemia Experimental/inducido químicamente , Leucemia Experimental/patología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Pulmonares/inducido químicamente , Linfoma/inducido químicamente , Linfoma de Células B Grandes Difuso/inducido químicamente , Linfoma de Células B Grandes Difuso/patología , Neoplasias Mamarias Experimentales/inducido químicamente , Ratones , Neoplasias Ováricas/inducido químicamente , Neoplasias Cutáneas/inducido químicamente , Esplenectomía , Neoplasias Gástricas/inducido químicamente
19.
J Natl Cancer Inst ; 75(2): 381-4, 1985 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3860690

RESUMEN

Effect on hepatocarcinogenesis of dietary sorbitan fatty acid ester (SorFAE), which had been known to cause decrease in pyruvate kinase (PK) activity, was studied in rats fed a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) for 6 weeks. The incidence of hyperplastic nodules and/or hepatocellular carcinomas in the rats fed the 3'-Me-DAB diet alone was 45.0% at the end of 51 weeks, whereas the incidence in the rats fed 3'-Me-DAB diet followed by 5 or 10% SorFAE or 0.1% phenobarbital (PB) diet were 76.2, 90.5, and 95.0%, respectively. These incidences were significantly higher compared with the group fed 3'-Me-DAB diet alone (P less than .05). No tumors were observed in rats fed 10% SorFAE diet alone. The results show that SorFAE has an enhancing effect on hepatocarcinogenesis, although the effect was weak compared to that of the effective PB dose. The results seem to confirm our assumption that a chemical that causes decrease in PK activity in rat liver might promote hepatocarcinogenesis.


Asunto(s)
Neoplasias Hepáticas/inducido químicamente , Hígado/enzimología , Polisorbatos/farmacología , Piruvato Quinasa/antagonistas & inhibidores , Animales , Conductos Biliares/patología , Peso Corporal/efectos de los fármacos , Hemangioma/inducido químicamente , Hígado/efectos de los fármacos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas Experimentales/inducido químicamente , Masculino , Metildimetilaminoazobenceno/farmacología , Tamaño de los Órganos/efectos de los fármacos , Fenobarbital/farmacología , Ratas , Ratas Endogámicas
20.
Cancer Res ; 36(3): 917-21, 1976 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-943238

RESUMEN

The continuous lifetime administration of 0.015% beta-phenylethylhydrazine sulfate in the drinking water of Swiss mice, beginning at 6 weeks of age, gave rise to tumors of the lungs and blood vessels. As compared to untreated controls, the incidence of lung tumors rose from 21 to 56% in females and from 23 to 36% in males, while the incidence of vascular tumors increased from 5 to 44% in females and from 6 to 8% in males. Statistically, the increased incidence of tumors of lungs and blood vessels in females appears to be significant. The treatment had no statistically significant effect on the development of tumors in males. Histopathological examination revealed the characteristic appearance of adenoma and adenocarcinoma of the lungs, and angioma and angiosarcoma of blood vessels. This study reports for the first time the tumorigenicity of beta-phenylethylhydrazine sulfate, which is currently used to treat mental depression.


Asunto(s)
Neoplasias Experimentales/inducido químicamente , Fenelzina/toxicidad , Adenocarcinoma/inducido químicamente , Adenoma/inducido químicamente , Animales , Hemangioma/inducido químicamente , Hemangiosarcoma/inducido químicamente , Neoplasias Pulmonares/inducido químicamente , Masculino , Ratones , Factores Sexuales
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