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)

We report a case of von Recklinghausen neurofibromatosis associated with myelomatosis. The association of these two relatively common conditions has not been described previously. We discuss the hypothesis that the NF-1 gene confers a degree of protection from certain common adult malignancies.
 ...
PMID:von Recklinghausen neurofibromatosis and myelomatosis. 212 26

Previous studies have shown that human ornithine decarboxylase (ODC)-encoding sequences map to two chromosome regions: 2pter-p23 and 7cen-qter. In the present work we have cloned the expressed human ODC gene from a genomic library of myeloma cells that overproduce ODC protein due to selective gene amplification and determined its entire nucleotide sequence. The gene comprises 12 exons and 11 introns and spans about 8 kb of chromosome 2 DNA. The organization of the human gene is very similar to that of the mouse and rat, with the major difference being the presence of longer intronic sequences in the human gene. Some of these differences can be accounted for by the insertion of four Alu sequences in the human gene. Several potential regulatory elements are present in the promoter region and in 5'-proximal introns, including a TATA box; GC boses; AP-1-, AP-2- and NF-1-binding sites; and a cAMP-responsive element. The 5'-untranslated sequence of ODC mRNA is extremely GC-rich, and computer predictions suggest a very stable secondary structure for this region, with an overall free energy of formation of -225.4 kcal/mol. In addition to the active ODC gene on chromosome 2, ODC gene-related sequences were isolated from human chromosome 7-specific libraries and shown to represent a processed ODC pseudogene.
 ...
PMID:Human ornithine decarboxylase-encoding loci: nucleotide sequence of the expressed gene and characterization of a pseudogene. 222 39

Brain tissue of a patient with multiple myeloma suffering from neurological disorders similar to those seen in progressive multifocal leukoencephalopathy (PML) patients was evaluated for the presence of the papovavirus, JCV. Results from polymerase chain reaction (PCR) revealed the presence of JCV with structural organization at the control region which is distinct from well-characterized isolates, ie Mad-1 and Mad-4. The control region of the new isolate, named JCVPhila-1' contains a 22 nucleotide insertion which separates the TATA box from the NF-1 regulatory motif. Only 18 nucleotides of the insert are duplicated in the second copy of the enhancer/promoter of the new isolate, which is 84 nucleotides in size. Results from a transcription assay indicate a modest elevated level of JCVPhila-1 early promoter activity compared to that of JCVMad-4 in glial cell lines. The basal and T-antigen-induced transcriptional activities of the JCVPhila-1 late promoter was lower with respect to Mad-4 late gene activity in glial cells. Of particular interest was the observation that in the cells producing the early protein, T-antigen, JCVPhila-1 DNA replicated more efficiently then the Mad-4 DNA. These results suggest that the alterations seen in the JCVPhila-1 control region may differentially influence early and late gene expression and facilitate amplification of the viral genome in cells derived from the CNS.
 ...
PMID:Isolation and characterization of a type II JC virus from a brain biopsy of a patient with PML. 922 69

We present a case of a 64-year-old woman with neurofibromatosis (NF1) and smoldering multiple myeloma (SMM). SMM was diagnosed 9 years ago when the asymptomatic patient was found to have mild anemia, IgA paraproteinemia, hypogammaglobulinemia, osteopenia without any lytic bone lesions and bone marrow plasmacytosis. During follow-up period she remained stable in an excellent clinical condition without requiring any therapy for almost 4 years. Forty-two months after diagnosis she had a femoral fracture and since then biphosphonates have been administered intravenously, once monthly. Subsequent evaluations of the disease showed a dramatic reduction of IgA paraprotein to below half the initial value. We will discuss the probable pathogenesis of plasma cell dyscrasia in NF1 patients, as well as the likely antimyeloma activity of biphoshonates.
 ...
PMID:Neurofibromatosis type I and smoldering multiple myeloma: a case report. 1652 49

So far no effective therapeutic has been developed for the FDA-approved treatment of ovarian cancer patients. Recently we provided the first evidence indicating that an old antibiotic (antiparasitic drug) called Ivermectin suppresses the growth of a variety of human ovarian cancer cell lines in vitro by inactivating the oncogenic kinase PAK1 somehow (Hashimoto H, et al. Drug Discov Ther. 2009;3:243-246). This kinase is now known to be essential for the growth of more than 70% of all human cancers including breast, prostate, pancreatic, colon, gastric, lung, cervical, thyroid cancers as well as hepatoma, glioma, melanoma, MM (multiple myeloma) and NF (neurofibromatosis) tumors. In this study, using the cell-permeable PAK1-inactivating peptide TAT-PAK18 which blocks the essential PAK1-PIX interaction, we examined the relationship between the sensitivity of ovarian cancer cell lines to this anti-PAK1 peptide and the protein expression/autophosphorylation levels of PAK1 in these cell lines, and found that the more PAK1 is abnormally activated (autophosporylated at Thr 423), the more their growth is sensitive to this peptide, regardless of their PAK1 expression levels. This observation provides the first direct evidence that ovarian cancers also belong to the PAK1-dependent cancers which represent more than 70% of all human cancers, suggesting that anti-PAK1 drugs would be effective therapeutics for ovarian cancers.
 ...
PMID:The direct PAK1 inhibitor, TAT-PAK18, blocks preferentially the growth of human ovarian cancer cell lines in which PAK1 is abnormally activated by autophosphorylation at Thr 423. 2249 Nov 45

The past decade has witnessed a growing role and increasing use of whole-body magnetic resonance imaging (WB-MRI). Driving these successes are developments in both hardware and software that have reduced overall examination times and significantly improved MR imaging quality. In addition, radiologists and clinicians have continued to find promising new applications of this innovative imaging technique that brings together morphologic and functional characterization of tissues. In oncology, the role of WB-MRI has expanded to the point of being recommended in international guidelines for the assessment of several cancer histotypes (multiple myeloma, melanoma, prostate cancer) and cancer-prone syndromes (Li-Fraumeni and hereditary paraganglioma-pheochromocytoma syndromes). The literature shows growing use of WB-MRI for the staging and follow-up of other cancer histotypes and cancer-related syndromes (including breast cancer, lymphoma, neurofibromatosis, and von Hippel-Lindau syndromes). The main aim of this review is to examine the current scientific evidence for the use of WB-MRI in oncology.
 ...
PMID:Whole-body magnetic resonance imaging (WB-MRI) in oncology: recommendations and key uses. 3043 Mar 85

Recent advances in imaging technology have enabled the acquisition of anatomical and functional imaging from head to toe in a reasonably short scan time. Accordingly, whole body magnetic resonance imaging (WB-MRI) and diffusion-weighted imaging (WB-DWI) have gained recent attention for the management of musculoskeletal problems such as bone tumors and rheumatologic diseases. WB-MRI is especially useful in diagnosing systemic or widespread disease requiring whole body evaluation, such as bone metastases, multiple myeloma, lymphoma, neurofibromatosis, and spondyloarthropathies. Among WB-MRI sequences, the WB-DWI technique greatly increases the value of WB-MRI in the evaluation of disease extent and characterization as well as treatment monitoring. In support of the utilization of WB-MRI and WB-DWI in orthopedic clinics for various musculoskeletal diseases, we provide an overview of the technical aspects of WB-MRI and WB-DWI and their clinical applications in musculoskeletal tumors and rheumatic diseases.
 ...
PMID:Advances in whole body MRI for musculoskeletal imaging: Diffusion-weighted imaging. 3131 39