Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case of a male patient is reported, who presented with renal carcinoma and tumor thrombus in the inferior vena cava (IVC) extending from the right atrium (RA) to the bifurcation of IVC, common and external right iliac vein thrombosis, common and deep right femoral vein thrombosis, right popliteal vein thrombosis, with pulmonary and hepatic metastasis, treated with sorafenib. Renal cell carcinoma (RCC), the most common form of kidney cancer, occurs in 90% of cases and is nearly twice as common in men as in women. The diagnosis of RCC is accompanied by intravascular tumor thrombus in 10% of cases, and further extension of the tumor reaching RA is detected in approximately 1% of all patients. Therapy for advanced renal cell cancer has evolved considerably in the past decade, with new agents greeted like "buried treasure." Before 2005, the widely used systemic agents were cytokine interferon alfa and interleukin-2, which yielded modest efficacy and substantial toxicity. Tyrosine kinase inhibitors (TKIs) increase progression-free survival and/or overall survival as both first-line and second-line treatments for metastatic RCC. Sorafenib is an oral multikinase inhibitor with activity against Raf-1 serine/threonine kinase, B-Raf, vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor (PDGFR), FMS-like tyrosine kinase 3 (FLT-3), and c-KIT.
 ...
PMID:Renal Cell Carcinoma With Extensive Tumor Thrombus Into the Inferior Vena Cava and Right Atrium in a 70-Year-Old Man. 3104 82

Antitumor drug resistance remains a major challenge in cancer chemotherapy. Here we investigated the mechanism of acquired resistance to a novel anticancer agent RH1 designed to be activated in cancer cells by the NQO1 enzyme. Data show that in some cancer cells RH1 may act in an NQO1-independent way. Differential proteomic analysis of breast cancer cells with acquired resistance to RH1 revealed changes in cell energy, amino acid metabolism and G2/M cell cycle transition regulation. Analysis of phosphoproteomics and protein kinase activity by multiplexed kinase inhibitor beads showed an increase in the activity of protein kinases involved in the cell cycle and stemness regulation and downregulation of proapoptotic kinases such as JNK in RH1-resistant cells. Suppression of JNK leads to the increase of cancer cell resistance to RH1. Moreover, resistant cells have enhanced expression of stem cell factor (SCF) and stem cell markers. Inhibition of SCF receptor c-KIT resulted in the attenuation of cancer stem cell enrichment and decreased amounts of tumor-initiating cells. RH1-resistant cells also acquire resistance to conventional therapeutics while remaining susceptible to c-KIT-targeted therapy. Data show that RH1 can be useful to treat cancers in the NQO1-independent way, and targeting of the cancer stem cells might be an effective approach for combating resistance to RH1 therapy.
 ...
PMID:Proteomic Analysis of Breast Cancer Resistance to the Anticancer Drug RH1 Reveals the Importance of Cancer Stem Cells. 3133 14


<< Previous 1 2 3 4 5