Autophagy, an evolutionarily conserved lysosomal degradation process, has drawn an increasing amount of attention in recent years for its role in a variety of human diseases, such as cancer. Notably, autophagy plays an important role in regulating several survival and death signaling pathways that determine cell fate in cancer. To date, substantial evidence has demonstrated that some key autophagic mediators, such as autophagy-related genes (ATGs), PI3K, mTOR, p53, and Beclin-1, may play crucial roles in modulating autophagic activity in cancer initiation and progression. Because autophagy-modulating agents such as rapamycin and chloroquine have already been used clinically to treat cancer, it is conceivable that targeting autophagic pathways may provide a new opportunity for discovery and development of more novel cancer therapeutics. With a deeper understanding of the regulatory mechanisms governing autophagy, we will have a better opportunity to facilitate the exploitation of autophagy as a target for therapeutic intervention in cancer. This review discusses the current status of targeting autophagic pathways as a potential cancer therapy.
Antibiotics, Antineoplastic ; therapeutic use ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; drug effects ; genetics ; Beclin-1 ; Chloroquine ; therapeutic use ; Drug Discovery ; Humans ; Membrane Proteins ; metabolism ; Molecular Targeted Therapy ; Neoplasms ; metabolism ; pathology ; therapy ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Signal Transduction ; Sirolimus ; therapeutic use ; TOR Serine-Threonine Kinases ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVESTo analyze the correlation between intervertebral disc-endplate degeneration and bony construction parameter and to explore its roles in adult degenerative scoliosis.

METHODSThe imaging data of 79 patients with adult degenerative scoliosis from March 2005 to March 2010 were retrospectively reviewed as the study group. The imaging data of 41 patients with adolescent idiopathic scoliosis were selected as the control group. The vertebral body and intervertebral height in both sides on frontal X-ray, and the facet joint orientation in both sides on CT scan were measured respectively. The average vertebral body height, average intervertebral disc height and average facet orientation were regarded as bony structural parameters. The quantitative grading methods were used in the intervertebral disc and endplate degeneration. The relationship of bony construction parameter and intervertebral disc-endplate degeneration, and the relationship of bony construction parameter and Cobb's angle of scoliosis were analyzed by comparing all bony construction parameters in both groups.

RESULTSAnalyzed by paired-t test, the intervertebral height, vertebral body height and facet joint orientation between convex and concave sides of the study group were of significant difference (t = 3.411, 2.623 and 2.085, P < 0.05). The intervertebral height between convex and concave sides of the control group were of significant difference (t = 3.276, P < 0.01), while the vertebral body height and the facet joint orientation were of no statistical significance (t = 1.572 and 1.493, P > 0.05). By linear correlation and regression analysis, the asymmetric degree of bony construction parameter showed good correlation with the score of intervertebral disc-endplate degeneration (-1 < r < 1, P < 0.05), which was positively correlated with Cobb's angle of scoliosis (0 < r < 1, P < 0.05). Linear regression existed between asymmetric degree of bony construction parameter and Cobb's angle (F = 427.342, P < 0.01). The regression function was obtained: Cobb's angle = -8.904+8.136 × IAD + 3.274 × VAD-0.713 × FAD (IAD: intervertebral asymmetry degree, VAD: vertebral asymmetry degree, FAD: facet joint asymmetry degree).

CONCLUSIONSThe asymmetric change of bony construction exists in adult degenerative scoliosis, which significantly correlated with intervertebral disc-endplate degeneration and Cobb's angle of scoliosis. The asymmetric bony construction parameter probably plays a biomechanical role in the progression of scoliosis, which maybe the reason for the asymmetric degeneration of intervertebral disc-endplate.

Aged ; Female ; Humans ; Intervertebral Disc ; pathology ; Intervertebral Disc Displacement ; pathology ; Male ; Middle Aged ; Scoliosis ; pathology

OBJECTIVESTo investigate the correlation between scoliosis angle and the asymmetric index of degenerative lumbar scoliosis, the degree of intervertebral disc degeneration, decreased bone density.

METHODSAs a retrospectively study, a total of 96 patients with degenerative lumbar scoliosis were retrospectively enrolled from January 2002 to August 2010 as scoliosis group, meanwhile 96 patients with lumbar spinal stenosis matched in gender, age and body mass index (BMI) were selected as control group. All patients were studied with plain radiographs, MRI and dual energy X-ray absorptiometry at presentation. Radiographic measurements include Cobb angle, the height of the convex and concave side of the apical disc and the contiguous disc superiorly and inferiorly, the height of the convex and concave side of the apical and the contiguous vertebral body superiorly and inferiorly in scoliosis group, the height of L(2-3), L(3-4), L(4-5) discs and the height of L(2-4) vertebral body in control group. The average relative signal intensity of lumbar intervertebral disc and cerebrospinal fluid in T2WI sagittal image was measured in apex intervertebral disc and adjacent discs by Adobe Photoshop 6.0 in scoliosis group, which was measured in L(2-3), L(3-4), L(4-5) disc in control group. The bone density of lumbar, femoral neck, trochanter, and Ward's triangle regions were measured with dual-energy X-ray absorptiometry.

RESULTSThe intervertebral disc height in convex side was greater than the height in the concave side [(40 ± 7) mm vs. (28 ± 7) mm, P < 0.01], the vertebral body height in convex side was greater than the height in the concave side [(76 ± 12) mm vs. (72 ± 10) mm, P = 0.016] in scoliosis group. There was significant statistically difference in the degenerative degree of intervertebral discs between two groups (P = 0.003). There was significant statistically difference of the average T-value and the rate of osteoporosis between two groups (P < 0.01). Multiple linear regression analysis showed that the asymmetric disc index, the degenerative degree of intervertebral disc and osteoporosis were the predominant correlative factors, which affected the development of degenerative lumbar scoliosis.

CONCLUSIONSDegenerative lumbar scoliosis is always accompanied by the height asymmetry of intervertebral discs and vertebral body from convex and concavity sides. There is positive correlation between the angle of scoliosis and the asymmetric disc index, the degeneration of intervertebral disc, and negative correlation between the angle of scoliosis and the bone density (T-value).

Aged ; Bone Density ; Female ; Humans ; Intervertebral Disc ; pathology ; Linear Models ; Lumbar Vertebrae ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Spinal Stenosis ; pathology