Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desmoplastic melanoma (DM) and malignant peripheral nerve sheath tumor (MPNST) can appear morphologically and immunophenotypically similar. We attempted to determine whether microarray comparative genomic hybridization could detect copy number differences between them to aid in the diagnosis. S-100 immunohistochemistry was performed on 5 cases of DM and 9 cases of MPNST using formalin-fixed paraffin-embedded specimens. Genomic DNA was extracted from microdissected cells. Whole genome amplification was performed on 5 of 5 DMs and 6 of 9 MPNST cases. A multiplex polymerase chain reaction assay was used to determine the quality of the DNA samples, which were run on the Spectral Chip 2600 bacterial artificial chromosome array platform. DM showed gains involving chromosomes 1p, 2p, 9q, 13q, 14q, and 20q and losses involving chromosomes 5p, 11p, 12q, 15q, and 18q. Several cancer-associated genes were involved, including gain of BCL2L1, ARTN, AMPK, NRAS, and CCNA1 and loss of IGF2, CDKN1C, PAX6, WT1, TRAF6, MAPK8IP1, and IMP3. MPNST had gains involving chromosomes 1p, 2q, and 19p and loss of chromosome 21q. Gains of MUM1, APC2, MAP2K2, JMJD2B, SP110, PTMA, GPI, and CDKN2D were detected. DM and MPNST have chromosomal alterations detected by array comparative genomic hybridization that might be useful in distinguishing these 2 tumors, although further studies with a larger sample size will be needed to test this.
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PMID:Microarray comparative genomic hybridization detection of copy number changes in desmoplastic melanoma and malignant peripheral nerve sheath tumor. 2178 29

Desmoplastic malignancies such as cholangiocarcinoma (CCA) are characterized by a dense stroma containing an abundance of myofibroblasts termed cancer-associated fibroblasts (CAF). The CAF phenotype represents an "activated state" in which cells are primed for cell death triggered by BH3 mimetics. Accordingly, this primed state may be therapeutically exploited. To elucidate the mechanisms underlying this poorly understood apoptotic priming, we examined the role of platelet-derived growth factor (PDGF) in CAF priming for cell death given its prominent role in CAF activation. PDGF isomers PDGF-B and PDGF-D are abundantly expressed in CCA cells derived from human specimens. Either isomer sensitizes myofibroblasts to cell death triggered by BH3 mimetics. Similar apoptotic sensitization was observed with co-culture of myofibroblasts and CCA cells. Profiling of Bcl-2 proteins expressed by PDGF-primed myofibroblasts demonstrated an increase in cellular levels of Puma. PDGF-mediated increases in cellular Puma levels induced proapoptotic changes in Bak, which resulted in its binding to Bcl-2. Short hairpin RNA-mediated down-regulation of Puma conferred resistance to PDGF-mediated apoptotic priming. Conversely, the BH3 mimetic navitoclax disrupted Bcl-2/Bak heterodimers, allowing Bak to execute the cell death program. Treatment with a Bcl-2-specific BH3 mimetic, ABT-199, reduced tumor formation and tumor burden in a murine model of cholangiocarcinoma. Collectively, these findings indicate that apoptotic priming of CAF by PDGF occurs via Puma-mediated Bak activation, which can be converted to active full-blown apoptosis by navitoclax or ABT-199 for therapeutic benefit.
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PMID:Platelet-derived growth factor primes cancer-associated fibroblasts for apoptosis. 2497 8

Pancreatic cancer is the 4th leading cause of cancer deaths in the United States. The pancreatic cancer phenotype is primarily a consequence of oncogenes disturbing the resident pancreas parenchymal cell repair program. Many solid tumor types including pancreatic cancer have severe tumor fibrosis called desmoplasia. Desmoplastic stroma is coopted by the tumor as a support structure and CAFs aid in tumor growth, invasion, and metastases. This stroma is caused by cancer associated fibroblasts (CAFs), which lay down extensive connective tissue in and around the tumor cells. CAFs represent a heterogeneous population of cells that produce various paracrine molecules such as transforming growth factor-beta (TGF-beta) and platelet derived growth factors (PDGFs) that aid tumor growth, local invasion, and development of metastases. The hard, fibrotic shell of desmoplasia serves as a barrier to the infiltration of both chemo- and immunotherapy drugs and host immune cells to the tumor. Although there have been recent improvements in chemotherapy and surgical techniques for management of pancreatic cancer, the majority of patients will die from this disease. Therefore, new treatment strategies are clearly needed. CAFs represent an under-explored potential therapeutic target. This paper discusses what we know about the role of CAFs in pancreatic cancer cell growth, invasion, and metastases. Additionally, we present different strategies that are being and could be explored as anti-CAF treatments for pancreatic cancer.
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PMID:Pancreatic Cancer Associated Fibroblasts (CAF): Under-Explored Target for Pancreatic Cancer Treatment. 3246 66

Desmoplastic tumors have an abundance of stromal cells and the extracellular matrix which usually result in therapeutic resistance. Current treatment prescriptions for desmoplastic tumors are usually not sufficient to eliminate the malignancy. Recently, through modulating cancer-associated fibroblasts (CAFs) which are the most abundant cell type among all stromal cells, natural products have improved chemotherapies and the delivery of nanomedicines to the tumor cells, showing promising ability to improve treatment effects on desmoplastic tumors. In this review, we discussed the latest advances in inhibiting desmoplastic tumors by modeling CAFs using natural products, highlighting the potential therapeutic abilities of natural products in targeting CAFs for cancer treatment.
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PMID:Natural products remodel cancer-associated fibroblasts in desmoplastic tumors. 3330 82