1,751 research outputs found
P53 mutations in human adrenocortical neoplasms
The mechanisms of tumorigenesis of adrenocortical neoplasms have not been elucidated as yet. However, loss of heterozygosity at chromosomal locus 17p has been consistently observed in adrenocortical cancer. p53 is a recessive tumor suppressor gene located on chromosome 17p. Mutations in the p53 gene play an important role in the tumorigenesis of diverse types of human neoplasms including breast and colon cancers. More than 90% of all mutations discovered in such tumors have been detected in 4 hot spot areas that lie between exons 5 and 8. In contrast to wild-type p53, mutant p53 accumulates intracellularly and can be easily detected by immunohistochemistry. We therefore investigated the frequency of p53 mutations in human adrenocortical neoplasms using molecular biology and immunohistochemistry techniques. Five patients with adrenocortical adenomas (5 female; ages 39-72 yr), 11 patients with adrenocortical carcinomas (8 female, 3 male; ages 15- 50 yr), and two adrenocortical tumor cell lines were studied. After DNA extraction from frozen tumor tissue or paraffin-embedded material, exons 5 through 8 were amplified using the polymerase chain reaction and directly sequenced by the dideoxy termination method. Immunohistochemistry was performed on paraffin-embedded tumor specimens obtained during adrenalectomy using a monoclonal antibody reacting with both wild-type and mutant p53. Prevalence of mutations was adenomas, 0/5, carcinomas, 3/11, and adrenocortical cell lines, 2/2. Single point mutations were detected in 3 cases (exons 5, 6, and 7, respectively), and rearrangements of exon 7/8 and 8 were found in 2 cases. Immunohistochemistry detected strong nuclear and/or cytoplasmic p53 immunoreactivity in all adrenocortical carcinomas with point mutations of the p53 gene but not in adenomas and carcinomas with the wild-type sequence or with deletion/rearrangement of the p53 gene. We conclude that p53 plays a role in the tumorigenesis of adrenocortical carcinomas but is of less importance to benign adenomas
Report of Laboratory Tests and Analytical Sudies of Structural Characteristics of Cold-formed Steel-joist Floor Systems
Kidney cancer
Over 65,000 Americans are diagnosed with kidney cancer each year and nearly 13,000 die of this disease. Kidney cancer is not a single disease, it is made up of a number of different types of cancer, each with a different histology, a different clinical course, responding differently to therapy and caused by a different gene. Study of the thirteen genes that are known to cause kidney cancer has led to the understanding that kidney cancer is a metabolic disease. Recent discoveries of chromatin remodeling/histone modifying genes, such as PBRM1 and SETD2, has opened up new areas of intense interest in the study of the fundamental genetic basis of kidney cancer. New approaches to immunotherapy with agents such as the CTLA4 inhibitor, ipilumumab, have opened up promising new directions for clinical trials. A number of new agents targeting of VEGF receptor signaling and the mTOR pathways as well as novel approaches targeting HIF2 will hopefully provide the foundation for the development of effective forms of therapy for this disease
Familial Renal Cancer: Molecular Genetics and Surgical Management
Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis renal cell carcinoma (HLRCC), and Birt-Hogg-Dubé (BHD) are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer
Back to the Future: The American Society of Tropical Medicine and Hygiene, Its Journal and the Continuing Commitment to Global Health
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