Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human intervertebral disc undergoes multifactorial biochemical and morphologic degenerative changes during the process of aging. The frequency of degeneration, especially lumbar degeneration increases sharply with age and is regarded as a major cause of discogenic low back pain. Since degenerative discs are often asymptomatic, the pathobiology of discogenic back pain remains unclear. Degenerated discs spontaneously produce increased amounts of inflammatory mediators suggesting their role in the degenerative process of the intervertebral disc. However, the relationship between aging, degenerative processes, and actual illness is far from clear. Basic science research has demonstrated that the intervertebral disc is an avascular tissue element occupied by inadequately characterized cells in an extensive extracellular matrix. While the annulus fibrosus is predominantly collagenous, the matrix of the central nucleus pulposus is rich in proteoglycans. With aging, the substance of proteoglycans significantly decreases which is believed to be a critical factor in intervertebral disc degeneration. A variety of inflammatory mediators have been implicated in the degeneration of the intervertebral disc including nitric oxide (NO), interleukins, matrix metalloproteinases (MMP), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-alpha) and a group of cytokines. MMPs, PGE2, and a variety of cytokines have been already been shown to play a role in the degradation of articular cartilage. Nitric oxide is a novel mediator that is drawn into much attention recently for its role in disc abnormalities. Elevated nitric oxide production derived from NO synthase activity has been manifested in cerebrospinal fluid in patients with degenerative lumbar disease. However, the regulatory mechanism of NO and its relationship to the clinical manifestations are unclear. The biochemical events that occur with the 'aging spine' and in particular, the role of inflammatory mediators in intervertebral disc degeneration have not been studied assertively. Correspondingly, the association between degeneration of the intervertebral disc and the nociceptive mechanism of back pain is also not fully elucidated. However, there is high incidence of degenerated disc disorders manifested as back and neck pain and are among the most commonly encountered complaints in elderly population. It is hypothesized that the degenerative cascade ultimately leads to extensive structural defects and loss of normal motion segment function and configuration.
Cell Mol Biol (Noisy-le-grand) 2007 May 30
PMID:The aging spine: the role of inflammatory mediators in intervertebral disc degeneration. 1754 40

Disc degeneration is strongly associated with back or neck pain, sciatica, and disc herniation or prolapse. It places an enormous economic burden on society and can greatly affect quality of life. Alternative treatment approaches, such as genetic therapies, are urgently needed to slow or reverse the disc degeneration process. We downloaded gene expression data from Gene Expression Omnibus during various stages of disc degeneration and identified differentially expressed genes (DEGs) as well as dysfunctional pathways through comparisons with controls. We identified 2 significant DEGs between grade II and III discs and 8 significant DEGs between grade II and IV discs. By constructing an interactive network of the DEGs, we found that mitogen-activated protein family genes and Ras homologous (Rho) family genes - in particular, MAP2K6 and RHOBTB2 - may play important roles in the progression of degeneration of grade III and IV discs, respectively. MAP2K6 and RHOBTB2 may be specific therapeutic molecular targets in the treatment of disc degeneration. However, further experiments are needed to confirm this result.
Genet Mol Res 2013 Apr 26
PMID:Genes associated with disc degeneration identified using microarray gene expression profiling and bioinformatics analysis. 2366 66

Intra-arterial infusion chemotherapy for locally advanced breast cancer (LABC) has been previously performed. However, the main complications of this type of chemotherapy remain to be clarified. In the present study, catheterization chemotherapy was carried out for 53 LABC cases (stage IIIa-IIIc) between May, 2006 and March, 2007. For IIIB and IIIC patients, the catheters were guided to the opening of the subclavian artery. For stage IIIa patients, the catheters were placed into the thoracic artery through a subcutaneous femoral artery puncture. One to four cycles of chemotherapy (mean, 1.6 cycles) were administered for the patients using taxotere, epidoxorubicin, 5-fluorouracil and/or cyclophosphamide. The interval time between the two cycles was 21 days. Seven cases were identified as complete response (CR, 13.2%), 41 cases were partial response (PR, 77.4%) with a rate of effectiveness of (CR + PR, 90.6%), 5 cases were stable disease (SD, 9.40%) and no case was progressive. Pain of the ipsilateral upper extremity was present in 7 cases. Two cases exhibited ipsilateral upper extremity atrophy following drug administration from the opening of the subclavian artery. One case experienced neck pain and headache, while in one case necrosis of local skin was evident. Hematological toxicity over grade 3 was observed in 6 cases (11.30%). Systemic toxicity was mild and did not affect the quality of life of the patients. Overall survival was identified as 18/51 (35.3%), and free-disease survival as 10/51 (19.6%). In conclusion, intra-arterial infusion chemotherapy is an effective local control treatment for LABC. The main complications are pain of the ipsilateral upper extremity and neck as well as headache. Severe complications are ipsilateral upper extremity atrophy and necrosis of local skin. During the treatment, controlling the pressure of the tourniquet and velocity of drug administration are crucial for reducing local complications.
Mol Clin Oncol 2013 Jul
PMID:Main complications and results of treatment with intra-arterial infusion chemotherapy through the subclavian and thoracic arteries for locally advanced breast cancer. 2464 39