Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several new cytotoxic agents with activity in relapsed ovarian cancer are being combined with paclitaxel plus platinum as the first step to assess their impact in randomized trials against the standard treatment. These include topotecan, gemcitabine, epirubicin, and liposomal doxorubicin. Because of overlapping toxicities, there have been challenges in combining some of these agents in full dose with combination paclitaxel plus platinum. These have been overcome by use of sequenced administration. In addition to these new agents, novel non-cytotoxic drugs targeting specific signaling molecules or the tumor microenvironment provide additional avenues for clinical investigation. Many of these agents are rational to assess in ovarian cancer where laboratory research has pinpointed a number of alterations in molecules involved in cell signaling and cell cycle control. Examples include the antibody to HER 2/neu, agents targeting protein kinase C alpha, the p53 gene, and matrix metalloproteinase inhibitors. The challenges facing their assessment include how to determine adequate dosing when toxic effects are minimal and how to assess evidence of antitumor activity, short of conducting randomized studies. Finally, how best to use such agents together with conventional chemotherapy, in combination or in sequence, is unknown. Large clinical studies with some of these agents will provide some answers to their impact and how best to use them in the first-line management of advanced epithelial ovarian cancer.
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PMID:New cytotoxics and non-cytotoxics in epithelial ovarian cancer. 1124 Jul 31

This study characterizes 3 cases of mesenchymal chondrosarcoma (MC) utilizing a proteomic approach that allows for the detection, visual quantification, cellular compartmentalization, and assessment of the functional state of certain proteins that may promote tumor growth and/or oppose apoptosis. Immunohistochemical procedures were performed to detect the following protein antigens: CD99, interleukin (IL)-1alpha, IL-6, transforming growth factor (TGF)-alpha, conventional (c) protein kinase C (cPKC)-alpha, cPKC-betaII, phosphorylated (p)-PKC-alpha/betaII, c-kit (CD117), platelet-derived growth factor receptor (PDGFR)-alpha, PDGFR-beta, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)-2/neu, cathepsin D, angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor, p21ras, the alpha subunit of farnesyl and geranylgeranyl transferase (FTalpha/GGTalpha), phospho (p)-c-Jun N-terminal kinase (p-JNK), p-p38 mitogen-activated protein kinase (MAPK), cyclin D1, c-Jun, Ki-67, bcl-2, TGF-beta1 latency-associated peptide (LAP), TGF-betaRII, and cyclooxygenase (COX)-2. Immunoreactivities were scored from 0 to 3+ positivity using bright-field microscopy. The results showed that malignant mesenchymal chondroblasts exhibit stronger expressions of CD99, IL-1alpha, cPKC-alpha, p-PKC-alpha/betaII, PDGFR-alpha, p-JNK, Ki-67, and bcl-2 antigens than their more mature-appearing chondrocytic counterparts in MC. In conclusion, molecular profiling of mesenchymal chondrosarcoma using a proteomic approach characterized the mesenchymal chondroblasts as possessing pathways that incorporate PKC-alpha and PDGFR-alpha signaling and anti-apoptotic bcl-2 expression. Specific therapies to target the mesenchymal chondroblasts in mesenchymal chondrosarcoma might include interferon-alpha, rapamycin, ciprofloxacin, and STI571.
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PMID:Mesenchymal chondrosarcoma: molecular characterization by a proteomic approach, with morphogenic and therapeutic implications. 1281 16