Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Valproic acid (VPA) is an effective antiepileptic drug and mood stabilizer. It has recently been demonstrated that VPA could promote neurite outgrowth, activate the extracellular signal-regulated kinase pathway, and increase B-cell lymphoma/leukemia-2 (bcl-2)and growth cone-associated protein 43 (GAP-43) levels in spinal cord. We hypothesized that VPA could enhance axonal regeneration in the rat. In the present research, we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function through a silicon tube implanted with VPA. The left sciatic nerves were exposed through dorsal-splitting incisions, and 8-mm nerve sections were excised at the middle of the thigh. Then, a 1.0-cm-long silicone tube (internal diameter,1.0 mm; exterior diameter, 2.0 mm) was used to bridge the nerve deficit, anchored to the proximal and distal terminals of the excised deficit of sciatic nerves with 9-0 nylon epineural suture. Sterile petroleum jelly was used to seal the ends of the tubes to avoid leakage. The rats in the VPA group and control group were locally delivered 10 muL VPA injection (400 mg/5 mL) and normal saline, respectively, after the operation. The sciatic nerve index (SFI) was observed in each animal at 2-week intervals and electrophysiology was studied at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed at the end of the experiment (12 weeks after the operation). Using the digital image-analysis system, the thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity, amplitude of activity potential), and morphometrical results (regenerated axon number and thickness of myelin sheath) in nerve regeneration between the VPA group and controls ( P < 0.05). The results demonstrated that VPA is able to enhance sciatic nerve regeneration in rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans.
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PMID:Enhanced rat sciatic nerve regeneration through silicon tubes implanted with valproic acid. 1849 77

The role of Notch signaling in cervical cancer is seemingly controversial. To confirm the function of Notch signaling in this type of cancer, we established a stable Notch1-activated cervical cancer HeLa cell line. We found that Notch1 activation resulted in apoptosis, cell cycle arrest, and tumor suppression. At the molecular level, we found that a variety of genes associated with cyclic AMP, G protein-coupled receptor, and cancer signaling pathways contributed to Notch1-mediated tumor suppression. We observed that the expression of somatostatin (SST) was dramatically induced by Notch1 signaling activation, which was accompanied by enhanced expression of the cognate SST receptor subtype 1 (SSTR1) and SSTR2. Certain genes, such as tumor protein 63 (TP63, p63), were upregulated, whereas others, such as B-cell lymphoma 2 (BCL-2), Myc, Akt, and STAT3, were downregulated. Subsequently, knockdown of Notch1-induced SST reversed Notch1-induced decrease of BCL-2 and increase of p63, indicating that Notch1-induced tumor suppression may be partly through upregulating SST signaling. Our findings support a possible crosstalk between Notch signaling and SST signaling. Moreover, Notch-induced SSTR activation could enhance SSTR-targeted cancer chemotherapy. Valproic acid (VPA), a histone deacetylase inhibitor, suppressed cell growth and upregulated the expression of Notch1 and SSTR2. A combination therapy with VPA and the SSTR2-targeting cytotoxic conjugate CPT-SST strongly led to greater suppression, as compared to each alone. Our findings thus provide us with a promising clinical opportunity for enhanced cancer therapy using combinations of Notch1-activating agents and SSTR2-targeting agents.
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PMID:Notch1-mediated tumor suppression in cervical cancer with the involvement of SST signaling and its application in enhanced SSTR-targeted therapeutics. 2229 Oct 92