Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, the expression of cyclin E and kinase p34 cdc2 was investigated in preinvasive bladder tumors. The study material consisted of bladder sections (grades: GI--16 cases, GII--10, and GIII--12) collected from 38 patients in the course of the tumor electroresection. Immunohistochemical examinations were carried out with immunoperoxidase method. Antigens were labeled with NCL-CYCLIN E or NCL-p34 cdc2 monoclonal antibodies (Novocastra, UK). Positive reaction was demonstrated using ABC-universal Kit (Novocastra, UK). Differences in the protein expression in relation to the tumor grade were determined with a non-parametric Mann-Whitney's test. Increasing grade of tumors was associated with down regulation of cyclin E visible as lower percentage of cyclin E-positive cells. These changes were statistically significant for GI group as compared to groups GII and GIII (p<0.001). There were no differences between the study groups in the p34 protein expression. Cyclin E expression was inversely correlated with tumor grade therefore may be helpful in establishing therapeutic procedure.
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PMID:Quantitative analysis of cyclin E and protein p34 cdc2 expression in superficial bladder cancer. 1673 82

Metastatic or advanced breast cancer (mBC/ABC) remains incurable despite many different systemic treatment options. Hormone receptor positive (HR+) disease represents the most common subtype in both early and advanced disease. A better understanding of the biology of this BC subtype, in particular regarding potential mechanisms of endocrine resistance, has led to the development of CDK4/6 inhibitors. All three selective CDK4/6 inhibitors, palbociclib, ribociclib and abemaciclib have shown to significantly improve progression-free survival (PFS) when combined to endocrine therapy as first-line treatment for patients with HR+/HER-2 negative ABC, who have progressed on or after adjuvant endocrine therapy. All three of them have also shown an improved PFS as 2nd line therapy for HR+/Her2 negative ABC. Their toxicity profile is favorable, with hematological toxicity (mainly neutropenia) being predominant, followed by diarrhea and fatigue. Quality of life has been maintained in the 1st line setting or improved in the 2nd line setting. Overall survival (OS) has been reported so far only in 2 out of 7 trials as first line therapy and the difference did not reach statistical significance. In this article we review the biology of CDK signaling pathway and its inhibitors, preclinical and clinical data of all three investigated selective CDK4/6 inhibitors and their toxicity. We also discuss how these agents are being included in current international guidelines and future directions for these agents in other subtypes of breast cancer, in both advanced disease and early-stage disease.
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PMID:Targeting CDK4/6 pathways and beyond in breast cancer. 3035 83