Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rearrangements of chromosome 11q13 are frequently observed in human cancer. The 11q13 region harbors several chromosomal breakpoint clusters found in hematologic malignancies and exhibits frequent DNA amplification in carcinomas. DNA amplification patterns in breast tumors are consistent with the existence of at least 4 individual amplification units, suggesting the activation of more than 1 gene in this region. Two candidate oncogenes have been identified, CCND1 and EMS1/CORTACTIN, representing centrally localized amplification units. Genes involved in the proximal and distal amplicons remain to be identified. Recently we reported on a putative transforming gene, MYEOV, mapping 360 kb centromeric to CCND1. This gene was found to be rearranged and activated concomitantly with CCND1 in a subset of t(11;14)(q13;q32)-positive multiple myeloma (MM) cell lines. To evaluate the role of the MYEOV gene in the proximal amplification core, we tested 946 breast tumors for copy number increase of MYEOV relative to neighboring genes or markers. RNA expression levels were studied in a subset of 72 tumors for which both RNA and DNA were available. Data presented here show that the MYEOV gene is amplified in 9.5% (90/946) and abnormally expressed in 16.6% (12/72) of breast tumors. Amplification patterns showed that MYEOV was most frequently coamplified with CCND1 (74/90), although independent amplification of MYEOV could also be detected (16/90). Abnormal expression levels correlated only partially with DNA amplification. MYEOV DNA amplification correlated with estrogen and progesterone receptor-positive cancer, invasive lobular carcinoma type and axillary nodal involvement. In contrast to CCND1 amplification, no association with disease outcome could be found. Our data suggest that MYEOV is a candidate oncogene activated in the amplification core located proximal to CCND1.
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PMID:MYEOV: a candidate gene for DNA amplification events occurring centromeric to CCND1 in breast cancer. 1244 2

During the past decade, progress in endocrine therapy and the use of trastuzumab has significantly contributed to the decline in breast cancer mortality for hormone receptor-positive and ERBB2 (HER2)-positive cases, respectively. As a result of these advances, a breast cancer cluster with poor prognosis that is negative for the estrogen receptor (ESR1), the progesterone receptor (PRGR) and ERBB2 (triple negative) has come to the forefront of medical therapeutic attention. DNA microarray analyses have revealed that this cluster is phenotypically most like the basal-like breast cancer that is caused by deficiencies in the BRCA1 pathways. To gain further improvements in breast cancer survival, new types of drugs might be required, and small molecules targeting the ubiquitin proteasome system have moved into the spotlight. The success of bortezomib in the treatment of multiple myeloma has sent encouraging signals that proteasome inhibitors could be used to treat other types of cancers. In addition, ubiquitin E3s involved in ESR1, ERBB2 or BRCA1 pathways could be ideal targets for therapeutic intervention. This review summarizes the ubiquitin proteasome pathways related to these proteins and discusses the possibility of new drugs for the treatment of breast cancers. PUBLICATION HISTORY : Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
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PMID:The UPS: a promising target for breast cancer treatment. 1900 32

Lactoferrin (Lf) expression was investigated by using a Lf monoclonal antibody in 50 formalin-fixed and paraffin-embedded human bone tumours [10 giant cell tumours (GCTs), 7 osteoid osteomas, 6 ossifying fibromas, 19 enchondromas, 2 chondroblastomas, 2 chondrosarcomas, 2 chondroblastic osteosarcomas, 1 myeloma and 1 adamantinoma] as well as in 8 samples of adult and foetal human normal bone specimens. In addition, the immunohistochemical expression of the estrogen receptor (ER), progesterone receptor (PR) and Ki-67 antigen was analysed on parallel sections from the same specimens. Quantification of Lf immunoreactivity was performed by using an Intensity Distribution (ID) score. Lf immuno-expression with a variable ID score was encountered in 19/50 tumours and specifically in 10/10 GCTs, in 5/7 osteoid osteomas, in 2/2 chondroblastomas as well as in the adamantinoma and in the myeloma. With reference to normal bone samples, Lf was expressed by the osteoblasts only in the foetal bone. No immunoreactivity for ER and PR was encountered in all neoplastic samples, and no correlation was found between Lf and sex steroid hormone receptor (ER and PR) immuno-expression. Even more, no association was evidenced between Lf immuno-reactivity and the growth fraction of the tumours, reflected by the Ki-67 labelling index. Lf expression in the osteoblastic lineage of bone-forming tumours, together with its presence in the osteoblasts of foetal bone, requires further investigations, although it cannot be ruled out that Lf might be involved in the bone formation in humans, similarly to what has been demonstrated in other species.
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PMID:Lactoferrin immuno-expression in human normal and neoplastic bone tissue. 1924 Sep 70


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