Synonyms for gpnmb or Related words with gpnmb
Examples of "gpnmb"
; ; PKD1; PKD1L1; SILV; SORCS1; SORCS2; SORCS3;
In preclinical studies glembatumumab vedotin was capable of killing
expressing melanoma and breast cancer cells "in vitro" and inducing partial or complete regression of
-expressing tumors in mouse models.
Based on Immunohistochemical analysis, two studies have shown that
is commonly expressed in breast tumors. In the first study,
was detected in 71% (10/14) of breast tumors. In the second study, 64% of human breast tumors express
in the tumor stroma and an additional 10% of tumors express
in the tumor epithelium. In this study it was reported that
expression in the tumor epithelium was an independent prognostic indicator of breast cancer recurrence. Moreover, epithelial
expression was most abundant in triple negative breast cancers and it was found to be a prognostic marker for shorter metastasis-free survival times within this breast cancer subtype. Finally,
expression in breast cancer cells is capable of promoting cell migration, invasion, and metastasis both "in vitro" and "in vivo".
Some TNBC overexpresses epidermal growth factor receptor (EGFR). Some TNBC over expresses transmembrane glycoprotein NMB (
is a type I transmembrane glycoprotein which shows homology to the pmel17 precursor, a melanocyte-specific protein.
C7ORF30 is neighbored by
upstream and IGF2BP3 downstream, however the latter gene is transcribed on the opposite strand running from the 3' to the 5' end. There is some slight overlap of the untranslated regions of C7ORF30 and IGF2BP3 whereas the distance between C7ORF30 and
is 24,211 base pairs.
A novel antibody-drug conjugate known as Glembatumumab vedotin (CDX-011), which targets the protein
, has also shown encouraging clinical trial results in 2009.
Nov 2013: An accelerated approval Phase II clinical trial (METRIC) investigating glembatumumab vedotin versus capecitabine has begun, expected to enroll 300 patients with
-expressing metastatic TNBC.
In May 2010, the U.S FDA granted Fast Track designation to CDX-011 for the treatment of advanced, refractory, or resistant
-expressing breast cancer.
Transmembrane glycoprotein NMB is a protein that in humans is encoded by the "
" gene. Two transcript variants encoding 560 and 572 amino acid isoforms have been characterized for this gene in humans. The mouse and rat orthologues of
are known as DC-HIL and Osteoactivin (OA), respectively.
has been reported to be expressed in various cell types, including: melanocytes, osteoclasts, osteoblasts, dendritic cells, and it is overexpressed in various cancer types. In melanocytic cells and osteoclasts the
gene is transcriptionally regulated by Microphthalmia-associated transcription factor.
was originally identified as a gene that was expressed in poorly metastatic human melanoma cell lines and xenografts and not expressed in highly metastatic cell lines. However, several recent studies have identified high
expression in aggressive melanoma, glioma, and breast cancer specimens.
Glembatumumab vedotin (also known as CDX-011 and CR011-vcMMAE) is an antibody-drug conjugate (ADC) that targets cancer cells expressing transmembrane glycoprotein NMB (
In September 2010 a Phase 2b clinical study started of glembatumumab vedotin in 120 patients with
-expressing breast cancer including those with triple negative breast cancer.
, Phase I/II clinical trials of glembatumumab vedotin for the treatment of advanced melanoma and breast cancer have been completed but no official study result was posted. Preliminary results from these trials have shown that glembatumumab vedotin has some clinical activity (promotes tumor shrinkage) in both cancer types. Patients whose tumors express
respond better to glembatumumab and have longer progression-free survival than those whose tumors do not express
; in melanoma, and breast cancer.
is the target of the antibody glembatumumab (CR011) which is used in the antibody-drug conjugate glembatumumab vedotin (CDX-011, CR011-vcMMAE) which is in clinical trials for melanoma and breast cancer. (See glembatumumab vedotin)
It uses a valine-citrulline enzyme-cleavable linker. The linkage is stable in the bloodstream. The antibody binds to
on the cancer cells, the ADC is internalised, the linkage is broken and MMAE is released to kill the cell.
An accelerated approval Phase II clinical trial (METRIC) investigating glembatumumab vedotin versus capecitabine (2:1 with crossover allowed) has begun in November 2013, expected to enroll 300 patients with
-expressing metastatic triple negative breast cancer. Patients who have progressed after receiving anthracyclines and taxanes are eligible.
ARSB has been studied in a variety of cancers. Cultured normal mammary epithelial and myoepithelial cells had significantly higher ARSB activity than cultured malignant mammary cells. Immunohistochemistry in the colon showed decreased membrane ARSB staining in colon cancer compared to normal colon, as well as in higher grade malignancies. ARSB activity was lower in malignant than normal prostate tissue, and immunostaining of prostate tissue microarrays showed not only decreasing ARSB staining in prostate cancer tissue of a higher Gleason score, but also lower staining in patients with recurrent compared to non-recurrent cancer. ARSB staining was a greater predictor of recurrence than Prostate-specific antigen (PSA) test, indicating possible future role of ARSB as a prognostic biomarker of prostate cancer. Further evidence of ARSB as a tumor suppressor was determined by molecular studies in cell cultures where ARSB was silenced by siRNA. The studies showed that decrease of ARSB leads to increase in free galectin-3, which attaches more strongly to less sulfated chondroitin 4-sulfate. Galectin-3 then acts on transcription factors AP-1 to increase expression of chondroitin sulfate proteoglycan versican and SP-1 to increase expression of WNT9A. Another mechanism by which reduced ARSB is associated with carcinogenesis is through increased binding of SHP2 to more sulfated chondroitin 4-sulfate, which leads to increased phosphorylation of p38 and MITF with subsequently increased expression of
. In melanoma cells and normal melanocytes, ARSB silencing increased invasiveness and expression of CSPG4 and MMP2, known markers of melanoma progression. CSPG4 expression was mediated by reduced binding of galectin-3 to C4S, while MMP2 expression was mediated by increased binding of SHP2 to C4S.
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