Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026764 (
multiple myeloma
)
36,148
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Major histocompatibility complex class I
-related chain A (MICA) molecules are frequently expressed in lymphoproliferative malignancies including
multiple myeloma
(MM). MICA activates NK cells and co-stimulates T cells by interaction with its immunoreceptor NKG2D. In contrast, soluble MICA (sMICA) molecules impair the functions of NKG2D(+) T and NK cells, which may facilitate tumor cell escape from immunosurveillance. Here, we analyzed the clinical relevance of sMICA in 97 MM patients. sMICA (mean+/-SEM pg/ml) was significantly increased (p<0.0001) in patients (429+/-20) compared to controls (230+/-20; N=43). Serial determination showed a strong correlation between increments of sMICA and paraprotein levels (r=0.543, p<0.0001, N=49). sMICA levels >305 pg/ml are associated with a poor overall (p=0.004) and progression-free survival (p=0.002). Multivariate analysis revealed sMICA as an independent predictive factor for overall (p=0.007) and progression-free survival (p=0.002). Thus, our results suggest sMICA as a potent prognostic marker in MM, which may be useful to identify risk patients.
...
PMID:Soluble MICA as an independent prognostic factor for the overall survival and progression-free survival of multiple myeloma patients. 1721 52
Serum protein fingerprints associated with MGUS and MM and their changes in MM after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored. Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM,
P
corr
= .0004), Growth differentiation factor 15 (GDF15,
P
corr
= .003), and soluble
Major histocompatibility complex class I
-related chain A (sMICA,
P
corr
= .023), all prosurvival and chemoprotective factors for
myeloma
cells, were detected in MM comparing to MGUS. Comparison of MGUS and healthy subjects revealed elevation of angiogenic and antia-poptotic midkine (
P
corr
= .0007) and downregulation of Transforming growth factor beta 1 (TGFB1,
P
corr
= .005) in MGUS. Importantly, altered serum pattern was associated with MM-ASCT compared to paired MM at the diagnosis as well as to healthy controls, namely by upregulated B-Cell Activating Factor (sBAFF) (
P
corr
< .006) and sustained elevation of other pro-tumorigenic factors. In conclusion, the serum fingerprints of MM and MM-ASCT were characteristic by elevated levels of prosurvival and chemoprotective factors for
myeloma
cells.
...
PMID:Serum protein fingerprinting by PEA immunoassay coupled with a pattern-recognition algorithms distinguishes MGUS and multiple myeloma. 2905 Feb 13
B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein expressed on malignant plasma cells of patients with
multiple myeloma
(MM), and it is a defined therapeutic target.
Major histocompatibility complex class I
-related chain A (MICA) is frequently expressed in lymphoproliferative malignancies including MM. MICA activates natural killer (NK) cells and costimulates T cells by interaction with its immunoreceptor NK cell receptor G2D (NKG2D). Nonetheless, during full-blown MM, tumor cells promote efficient MICA shedding, which evokes NKG2D internalization and immune suppression. To enhance the directional killing efficacy of immune cells against
myeloma
cells, we constructed a novel bispecific antibody 2A9-MICA and explored its potential antimyeloma activity against MM. 2A9-MICA consists of human MICA extracellular region and a single-chain antibody fragment (scFv) that targets BCMA generated by phage display technology. In vitro, 2A9-MICA activated NK cell-mediated cytotoxicity and induced NK cells to kill BCMA-positive human
myeloma
cells. Moreover, in BCMA-positive, MM-bearing nude mice, 2A9-MICA specifically targeted tumor tissue, where it effectively recruited immune cells and inhibited tumor tissue growth showed superior antitumor activity. Taken together, bispecific antibody 2A9-MICA provides a new approach for MM-targeting immunotherapy and has attractive potential for clinical applications.
...
PMID:BCMA-targeting Bispecific Antibody That Simultaneously Stimulates NKG2D-enhanced Efficacy Against Multiple Myeloma. 3234 46
