Search results for "cancer research"
showing 10 items of 5684 documents
Loss of a novel tumor suppressor gene locus at chromosome 8p is associated with leukemic mantle cell lymphoma
2001
Abstract Patients with mantle cell lymphoma (MCL) may present with either nodal or leukemic disease. The molecular determinants underlying this different biologic behavior are not known. This study compared the pattern of genetic abnormalities in patients with nodal and leukemic phases of MCL using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) for specific gene loci. Although both leukemic and nodal MCL showed similar genomic patterns of losses (involving 6q, 11q22-q23, 13q14, and 17p13) and gains (affecting 3q and 8q), genomic loss of chromosome 8p occurred more frequently in patients with leukemic disease (79% versus 11%,P < .001). Subsequent…
Pure anti-oestrogens
2000
Pure anti-oestrogens are a group of at least five new compounds which are able to antagonize the effects of oestrogen in all tissues and species studied. The mechanism by which the pure anti-oestrogens produce their effects remains in question, but all of them are competitive antagonists of the oestrogen receptors and, moreover, have been proposed to block the shuttling of oestrogen receptors into the cell nucleus. When studied in vitro, these compounds are able to block the oestrogen-stimulated growth of breast cancer cells. In animals, their ability to block the effects of oestrogen on breast, uterus, bone, cardiovascular system and other reproductive-associated tissues has been demonstra…
Involvement of Different networks in mammary gland involution after the pregnancy/lactation cycle: Implications in breast cancer
2015
Early pregnancy is associated with a reduction in a woman's lifetime risk for breast cancer. However, different studies have demonstrated an increase in breast cancer risk in the years immediately following pregnancy. Early and long-term risk is even higher if the mother age is above 35 years at the time of first parity. The proinflammatory microenvironment within the mammary gland after pregnancy renders an "ideal niche" for oncogenic events. Signaling pathways involved in programmed cell death and tissue remodeling during involution are also activated in breast cancer. Herein, the major signaling pathways involved in mammary gland involution, signal transducer and activator of transcripti…
Glutathione, GlutathioneS-Transferase α and π, and Aldehyde Dehydrogenase Content in Relationship to Drug Resistance in Ovarian Cancer
1997
Glutathione, glutathione S-transferases alpha and pi, and aldehyde dehydrogenase are associated with resistance to carboplatin and/or cyclophosphamide in cell lines. Therefore, we examined whether the expression of these factors in ovarian cancer tissue specimens is associated with resistance of the patients to combination chemotherapy with cyclophosphamide/carboplatin. Ovarian cancer tissue specimens were taken intraoperatively from 139 patients and frozen in liquid nitrogen, and the contents of glutathione S-transferases alpha and pi, total glutathione, and aldehyde dehydrogenase activity were determined. No association between the levels of glutathione S-transferases alpha and pi or alde…
Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC.
1994
We have analysed 118 families with inherited medullary thyroid carcinoma (MTC) for mutations of the RET proto-oncogene. These included cases of multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B) and familial MTC (FMTC). Mutations at one of 5 cysteines in the extracellular domain were found in 97% of patients with MEN 2A and 86% with FMTC but not in MEN 2B patients or normal controls. 84% of the MEN2A mutations affected codon 634. MEN 2A patients with a Cys634 to Arg substitution had a greater risk of developing parathyroid disease than those with other codon 634 mutations. Our data show a strong correlation between disease phenotype and the nature and position of the RET mutatio…
Mutations in the NKX2.5 Gene and the PAX8 Promoter in a Girl with Thyroid Dysgenesis
2011
Screening of the known candidate genes involved in thyroid organogenesis has revealed mutations in a small subset of patients with congenital hypothyroidism due to thyroid dysgenesis (TD).We studied a girl with TD who had mutations in two transcription factors involved in thyroid development.Sequencing analysis of candidate genes involved in thyroid gland development revealed a new paternally inherited heterozygous mutation in the NKX2.5 gene (S265R) and a new maternally inherited heterozygous mutation in the PAX8 promoter region (-456CT). Both parents and a brother, who was also heterozygous for both mutations, were phenotypically normal. Immunofluorescence microscopy showed a correct nucl…
Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy and remodeling
2015
Cardiac hypertrophy accompanies many forms of heart disease, including ischemic disease, hypertension, heart failure, and valvular disease, and it is a strong predictor of increased cardiovascular morbidity and mortality. Deletion of bone marrow kinase in chromosome X (Bmx), an arterial nonreceptor tyrosine kinase, has been shown to inhibit cardiac hypertrophy in mice. This finding raised the possibility of therapeutic use of Bmx tyrosine kinase inhibitors, which we have addressed here by analyzing cardiac hypertrophy in gene-targeted mice deficient in Bmx tyrosine kinase activity. We found that angiotensin II (Ang II)-induced cardiac hypertrophy is significantly reduced in mice deficient i…
FLT3 as a therapeutic target in AML: still challenging after all these years
2010
Abstract Mutations within the FMS-like tyrosine kinase 3 (FLT3) gene on chromosome 13q12 have been detected in up to 35% of acute myeloid leukemia (AML) patients and represent one of the most frequently identified genetic alterations in AML. Over the last years, FLT3 has emerged as a promising molecular target in therapy of AML. Here, we review results of clinical trials and of correlative laboratory studies using small molecule FLT3 tyrosine kinase inhibitors (TKIs) in AML patients. We also review mechanisms of primary and secondary drug resistance to FLT3-TKI, and from the data currently available we summarize lessons learned from FLT3-TKI monotherapy. Finally, for using FLT3 as a molecul…
Heat shock protein expression and anti-heat shock protein reactivity in renal cell carcinoma.
2002
Heat shock proteins (HSP) are families of highly conserved proteins which are induced in cells and tissues upon exposure to extreme conditions causing acute or chronic stress. They exhibit distinct functions and have been implicated in the pathogenesis of a number of diseases, including cancer. A causal relationship between HSP expression and immunogenicity has been demonstrated in murine and human tumors and is also associated with the immune response. In order to investigate the correlation of HSP expression and their immunogenic potential in renal cell carcinoma (RCC), we here analyzed (i) the protein expression profile of various members of the HSP family in untreated and interferon (IF…
Lovastatin stimulates p75 TNF receptor (TNFR2) expression in primary human endothelial cells
2005
HMG-CoA reductase inhibitors (statins) exert pleiotropic physiological effects. Among others they attenuate cellular responses to genotoxic and inflammatory stress. We investigated the effect of lovastatin on the expression level of TNF receptors (TNFR) in primary human endothelial cells (HUVEC). ELISA, FACS and immunocytochemical analyses show that lovastatin selectively increases the cell surface expression of TNFR2 without affecting the expression level of TNFR1. This effect of lovastatin is independent from inhibition of cell-cycle progression since cells both in G1- and G2-phase showed elevated levels of TNFR2 after lovastatin treatment. To analyze the physiological relevance of lovast…