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National Cancer Institute®
Ultima Vez Modificado: 1 de junio del 2002
UI - 11990703
AU - Reichardt P; Apel TW; Domula M; Trobs RB; Krause I; Bierbach U; Neumann
TI - HP; Kiess W Recurrent polytopic chromaffin paragangliomas in a 9-year-old boy resulting from a novel germline mutation in the von Hippel-Lindau gene.
SO - J Pediatr Hematol Oncol 2002 Feb;24(2):145-8
AD - Intensive Care Unit, Children's Hospital of the University of Leipzig, Germany. email@example.com
Pheochromocytomas are frequently associated with inherited cancer syndromes such as von Hippel-Lindau disease (VHL). Retinal angioma and hemangioblastomas of the central nervous system are hallmarks of VHL, but its clinical variety is remarkably broad. Pheochromocytomas as the sole or first manifestation of VHL are rare but have been observed. In this case report, the authors describe an unusual case of initial collapse, seizures, and hypertensive crisis in a child who later was found to have multiple extraadrenal pheochromocytomas. Molecular diagnostics revealed a novel point mutation in the VHL gene (VHL nt. 406 T-->G). Only 7 months after the first lesions had been removed, a new paraganglioma developed in the contralateral periadrenal region. When encountering pheochromocytomas in children, the clinician should be aware that an associated tumor syndrome might be present, and appropriate molecular screening should be initiated. Molecular genetics aid in the clinical decision-making and clinical management of individual patients with pheochromocytoma.
UI - 11904337
AU - Duffy K; Al-Saleem T; Karbowniczek M; Ewalt D; Prowse AH; Henske EP
TI - Mutational analysis of the von hippel lindau gene in clear cell renal carcinomas from tuberous sclerosis complex patients.
SO - Mod Pathol 2002 Mar;15(3):205-10
AD - Medical Oncology Division, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by seizures, mental retardation, autism, and tumors of multiple organs. Renal disease in TSC includes angiomyolipomas, cysts, and renal cell carcinomas. It is known that somatic mutations in the von Hippel Lindau (VHL) tumor suppressor gene occur in most clear cell renal carcinomas. To determine whether TSC-associated clear cell carcinomas also contain VHL mutations, we analyzed six tumors for loss of heterozygosity in the VHL gene region of chromosome 3p and for mutations in the VHL gene. Four of the patients were women between the ages of 34 and 68 years, and two were males under the age of 21 years. The loss of heterozygosity analysis was performed using polymorphic microsatellite markers, and the mutational analysis was performed using direct sequencing. Chromosome 3p loss of heterozygosity was not detected, and no VHL mutations were identified. These findings suggest that mutations in the TSC1 and TSC2 genes lead to clear cell renal carcinogenesis via an alternate pathway not involving VHL mutations.
UI - 12000816
AU - Neumann HP; Bausch B; McWhinney SR; Bender BU; Gimm O; Franke G;
TI - Schipper J; Klisch J; Altehoefer C; Zerres K; Januszewicz A; Eng C; Smith WM; Munk R; Manz T; Glaesker S; Apel TW; Treier M; Reineke M; Walz MK; Hoang-Vu C; Brauckhoff M; Klein-Franke A; Klose P; Schmidt H; Maier-Woelfle M; Peczkowska M; Szmigielski C; Eng C; The Freiburg-Warsaw-Columbus Pheochromocytoma Study Group Germ-line mutations in nonsyndromic pheochromocytoma.
SO - N Engl J Med 2002 May 9;346(19):1459-66
AD - Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany. firstname.lastname@example.org
BACKGROUND: The group of susceptibility genes for pheochromocytoma that included the proto-oncogene RET (associated with multiple endocrine neoplasia type 2 [MEN-2]) and the tumor-suppressor gene VHL (associated with von Hippel-Lindau disease) now also encompasses the newly identified genes for succinate dehydrogenase subunit D (SDHD) and succinate dehydrogenase subunit B (SDHB), which predispose carriers to pheochromocytomas and glomus tumors. We used molecular tools to classify a large cohort of patients with pheochromocytoma with respect to the presence or absence of mutations of one of these four genes and to investigate the relevance of genetic analyses to clinical practice. METHODS: Peripheral blood from unrelated, consenting registry patients with pheochromocytoma was tested for mutations of RET, VHL, SDHD, and SDHB. Clinical data at first presentation and follow-up were evaluated. RESULTS: Among 271 patients who presented with nonsyndromic pheochromocytoma and without a family history of the disease, 66 (24 percent) were found to have mutations (mean age, 25 years; 32 men and 34 women). Of these 66, 30 had mutations of VHL, 13 of RET, 11 of SDHD, and 12 of SDHB. Younger age, multifocal tumors, and extraadrenal tumors were significantly associated with the presence of a mutation. However, among the 66 patients who were positive for mutations, only 21 had multifocal pheochromocytoma. Twenty-three (35 percent) presented after the age of 30 years, and 17 (8 percent) after the age of 40. Sixty-one (92 percent) of the patients with mutations were identified solely by molecular testing of VHL, RET, SDHD, and SDHB; these patients had no associated signs and symptoms at presentation. CONCLUSIONS: Almost one fourth of patients with apparently sporadic pheochromocytoma may be carriers of mutations; routine analysis for mutations of RET, VHL, SDHD, and SDHB is indicated to identify pheochromocytoma-associated syndromes that would otherwise be missed.
UI - 12016154
AU - Hemminki K; Jiang Y; Ma X; Yang K; Egevad L; Lindblad P
TI - Molecular epidemiology of VHL gene mutations in renal cell carcinoma patients: relation to dietary and other factors.
SO - Carcinogenesis 2002 May;23(5):809-15
AD - Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden. email@example.com
Carcinogenic chemicals act through DNA damage and mitogenic effects. No established mechanism explains the cancer preventive effects, if any, of food items, such as vegetables and fruit. If such data were available, preferably on tumor-initiating genes, the evidence for the protective effects would become stronger. The von Hipple-Lindau (VHL) gene is the tumor suppressor gene predisposing to both sporadic renal cell carcinoma (RCC) and von Hippel-Lindau disease. We have earlier analyzed VHL mutations in RCCs from 102 Swedish patients identified in a case-control study and here examine associations between patient characteristics, including dietary habits and mutations, considering the type of mutation. The results are given as odds ratios (OR), separately for smokers and all patients. In univariate analysis, consumption of vegetables and citrus fruit decreased the frequency of VHL mutations among smokers and citrus fruit among all patients. In multivariate analysis of smokers' characteristics, welding fumes showed a risk of 5.63 for multiple VHL mutations. In smokers, citrus fruit decreased the OR of GC to AT mutations to 0.13 and that of multiple mutations to 0.17; vegetables decreased the OR for single mutations to 0.22. Among all subjects, welding fumes were a risk factor and citrus fruit a protective factor. Additionally, an intake of selenium protected against multiple mutations. The present results provide evidence that the intake of vegetables, selenium and particularly of citrus fruit protects the renal VHL gene from mutational insults that may be endogenous or common in a population. Even though most of the associations are biologically plausible, and vegetables and fruit were an a priori hypothesis, fortuitous results cannot be ruled out in this relatively small study.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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