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

Osteoblast differentiation, defined as the process whereby a relatively unspecialized cell acquires the specialized features of an osteoblast, is directly linked to multiple myeloma (MM) bone disease. Wnt and bone morphogenetic protein (BMP) are proved to be implicated in the pathological or defective osteoblast differentiation process. This study aims to test the involvement of Wnt, bone morphogenetic proteins (BMP) pathways, and empty spiracles homeobox 2 (EMX2) in osteoblast differentiation and MM development. Initially, differentially expressed genes in bone marrow mesenchymal stem cells (MSCs) from MM patients and healthy donors were identified using microarray-based gene expression profiling. The functional role of Wnt and BMP in MM was determined. Next, we focused on the co-operative effects of Wnt and BMP on calcium deposition, alkaline phosphatase (ALP) activity, the number of mineralized nodules, and osteocalcin (OCN) content in MSCs. The expression patterns of Wnt and BMP pathway-related genes, EMX2 and osteoblast differentiation-related factors were determined to assess their effects on osteoblast differentiation. Furthermore, regulation of Wnt and BMP in ectopic osteogenesis was also investigated in vivo. An integrated genomic screen suggested that Wnt and BMP regularly co-operate to regulate EMX2 and affect MM. EMX2 was downregulated in MSCs. The activated Wnt and BMP resulted in more calcium salt deposits, mineralized nodules, and a noted increased in ALP activity and OCN content by upregulating EMX2, leading to induced differentiation of MSCs into osteoblasts. Collectively, this study demonstrated that Wnt and BMP pathways could co-operatively stimulate differentiation of MSCs into osteoblasts and inhibit MM progression, representing potential targets for MM treatment.
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PMID:Wnt and BMP signaling pathways co-operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2. 3045 Jul 75

The proteasome inhibitor bortezomib (BZM) is one of the most potent anti-cancer drugs in the therapy of multiple myeloma. In this study, an adhesive drug delivery system (DDS) for BZM was developed. Therefore, we extended the present DDS concept of polyelectrolyte complex (PEC) nanoparticle (NP) based on electrostatic interactions between charged drug and polyelectrolyte (PEL) to a DDS concept involving covalent bonding between PEL and uncharged drugs. For this purpose, 3,4-dihydroxyphenyl acetic acid (DOPAC) was polymerized via an oxidatively induced coupling reaction. This novel chemo-reactive polyanion PDOPAC is able to temporarily bind boronic acid groups of BZM via its catechol groups, through esterification. PDOPAC was admixed to poly(l-glutamic acid) (PLG) and poly(l-lysine) (PLL) forming a redispersible PEC NP system after centrifugation, which is advantageous for further colloid and BZM loading processing. It was found that the loading capacity (LC) strongly depends on the PDOPAC and catechol content in the PEC NP. Furthermore, the type of loading and the net charge of the PEC NP affect LC and the residual content (RC) after release. Release experiments of PDOPAC/PEC coatings were performed at medically relevant bone substitute materials (calcium phosphate cement and titanium niobium alloy) whereby the DDS worked independently of the surface properties. Additionally, in contrast to electrostatically based drug loading the release behavior of covalently bound, uncharged BZM is independent of the ionic strength (salt content) in the release medium.
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PMID:Catechol Containing Polyelectrolyte Complex Nanoparticles as Local Drug Delivery System for Bortezomib at Bone Substitute Materials. 3284 50

A 63-year-old male with a past medical history of stage 3 chronic kidney disease, type 2 diabetes mellitus, hypertension, and coronary artery disease presented with recurrent symptomatic pleural effusions, low back pain and unintentional weight loss. Labs revealed elevated serum calcium and parathyroid hormone-related peptide, but normal parathyroid hormone, vitamin D, and angiotensin-converting enzyme levels. Malignancy workup was revealing for salt-and-pepper appearance of the bone marrow on MRI of the lumbar spine consistent with multiple myeloma. CT of chest, abdomen, and pelvis was negative for neoplastic process but showed a pleural effusion and calcified granulomas in hilar lymph nodes. Bone marrow biopsy of the lumbar region was subsequently conducted and revealed granulomas confirming the diagnosis of sarcoidosis. Treatment of sarcoidosis resulted in complete resolution of his symptoms and pleural effusion. This case highlights the variable presentation of sarcoidosis and its ability to mimic malignancy. Prompt recognition and treatment is essential in avoiding unnecessary costs and harm to the patient.
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PMID:Recurrent Pleural Effusions and Elevated PTHrP: An Unusual Case of Sarcoidosis. 3319 37


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