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Drug
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Target Concepts:
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Query: UMLS:C0026764 (
multiple myeloma
)
36,148
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (
18
F-FDG) is a promising technique in
multiple myeloma
(MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of
myeloma
cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with
copper
-64 (
64
Cu) or zirconium-89 (
89
Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for
64
Cu and
89
Zr labeling, respectively.
64
Cu-TE2A-9E7.4 and
89
Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to
18
F-FDG-PET imaging. In biodistribution and PET studies,
64
Cu-TE2A-9E7.4 and
89
Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with
64
Cu-TE2A-9E7.4 and
89
Zr-DFO-9E7.4 showed higher uptake than with
18
F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of
89
Zr-DFO-9E7.4 than
64
Cu-TE2A-9E7.4. Because of free
89
Zr's tropism for bone when using
89
Zr-anti-CD138,
64
Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.
...
PMID:What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between
89
Zr- and
64
Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model. 3113 58
A 46-year-old woman who presented for progressive glare was found to have dense deposition of
copper
within Descemet's membrane and lens capsule in both eyes (OU). Systemic workup revealed elevated serum
copper
secondary to
multiple myeloma
. Following bilateral Descemet stripping automated endothelial keratoplasty and cataract extraction, a green discoloration of the vitreous was noted. The patient was followed for 3 years with serial exams and electroretinograms. Electroretinograms showed declining photopic response amplitude OU, indicative of progressive retinal toxicity from
copper
. Although retinal toxicity and vitreous
copper
deposition are common in chalcosis, this appears to be the first case of hypercupremia associated with these findings. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e324-e326.].
...
PMID:Intraocular Deposition of Copper and ERG Findings in a Patient With Progressive Vision Loss From Hypercupremia. 3175 85
Disulfiram (DSF) is an FDA approved anti-alcoholism drug in use for more than 60 years. Recently, antitumor activity of the DSF/
copper
(DSF/Cu) complex has been identified. Its anti-
multiple myeloma
activity, however, has barely been investigated. In the present study, our results demonstrated that the DSF/Cu complex induced apoptosis of MM cells and MM primary cells. The results indicated that DSF/Cu significantly induced cell cycle arrest at the G2/M phase in MM.1S and RPMI8226 cells. Moreover, JC-1 and Western blot results showed that DSF/Cu disrupted mitochondrial membrane integrity and cleaved caspase-8 in MM cells, respectively, suggesting that it induced activation of extrinsic and intrinsic apoptosis pathways. Interestingly, DSF/Cu induced caspase-3 activation was partly blocked by Z-VAD-FMK (zVAD), a pan-caspase inhibitor, indicating at caspase-dependent and -independent paths involved in DSF/Cu induced
myeloma
cell apoptosis machinery. Additionally, activation of the c-Jun N-terminal kinase (JNK) signaling pathway was observed in DSF/Cu treated MM cells. More importantly, our results demonstrated that DSF/Cu significantly reduced tumor volumes and prolonged overall survival of MM bearing mice when compared with the controls. Taken together, our novel findings showed that DSF/Cu has potent anti-
myeloma
activity in vitro and in vivo highlighting valuable clinical potential of DSF/Cu in MM treatment.
...
PMID:Disulfiram/copper markedly induced myeloma cell apoptosis through activation of JNK and intrinsic and extrinsic apoptosis pathways. 3214 87
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