Although mechanical stress as a result of spinal instability is known to cause hypertrophy of the ligameiitum flavum resulting in degenerative spinal canal stenosis, the mechanism of the ligament hypertrophy is not well understood. In the present study, we investigated the effect of mechanical stretching force on collagen synthesis and transforming growth factor-/3 1 (TGF-PI) production using ligament cells isolated from human ligamentum flavum in vitro. Ligamenturn flavum cells (LFCs) were isolated from human ligamenturn flavum obtained from patients who underwent lumbar spine surgery. The LFCs were subjected to a mechanical stretching force using a cominercially available stretching device that physically deformed the cells. Collagen synthesis and TGF-PI production levels in the LFCs were then examined. Notable increases were observed in the gene expressions of collagen types I, 111, and V in LFCs subjected to mechanical stretching force. The increase in collagen gene expression of LFCs was inhibited in the presence of anti-TGF-pl antibodies. Production of TGF-PI by the LFCs also increased significantly by the mechanical stretching force. Exogenous application of TGF-PI was confirmed to increase collagen synthesis of the LFCs. This data indicated that mechanical stretching force can promote TGF-Dl production by LFCs, resulting in hypertrophy of the ligament.
We retrospectively reviewed fine-needle aspiration biopsy (FNAB) specimens of 301 soft tissue lesions of the extremities and trunk. Final diagnoses were 137 benign and 86 malignant neoplasms and 78 nonneoplastic lesions. Of the 301 FNAB samples, 279 (93%) were adequate for cytologic diagnosis. The adequate FNAB specimens were initially grouped into three broad categories: benign (197 cases), malignant (57 cases), and suspicious for malignancy (25 cases). Sensitivity and specificity for diagnosis of a malignant lesion were 92% and 97%, respectively. The specimens were cytomorphologically classified into nine categories: small round (14 cases), spindle cell (77 cases), epithelioid/polygonal (16 cases), pleomorphic (29 cases), myxoid (19 cases), lipomatous (37 cases), epithelial (23 cases), inflammatory lesions (28 cases), and others (36 cases). Specific FNAB diagnoses were correct in 151 of 279 cases (54%) in combination with clinical and radiologic findings. FNAB is a valuable technique for the primary diagnosis of soft-tissue lesions.
Heat shock protein 90 (Hsp90) is constitutively expressed at 2-10-fold higher levels in tumor cells compared to normal cells, suggesting that it may be critically important for tumor cell growth and survival. These features make Hsp90 a potential target for anticancer drug development. Inhibition of Hsp90 activity not only results in rapid degradation of Hsp90 client proteins but also induces apoptosis of various tumor cells. Hsp90 also plays an important role in autophagy. An Hsp90 inhibitor induces autophagy through inhibition of mTOR. It is still under debate whether chemotherapy-induced autophagy in tumor cells is a protective response or is invoked to promote cell death. The aim of this study was to examine the effects of the Hsp90 inhibitor, geldanamycin (GA), on KTHOS osteosarcoma cells. We further examined whether a combination of GA and the autophagy inhibitor 3-methyl-adenine (3-MA) enhanced GA-induced apoptosis in KTHOS cells. GA had an inhibitory effect on cell proliferation and inhibited the Akt/mTOR signaling pathway in KTHOS cells. GA alone induced autophagy and apoptosis in KTHOS cells, but treatment with a combination of GA and 3-MA suppressed autophagy and induced apoptosis to a much greater extent than GA alone in these cells. It was considered that the autophagy inhibitor 3-MA suppressed a protective mechanism induced by Hsp90 inhibitor in tumor cells and induced apoptosis. Therefore, the combination of an Hsp90 inhibitor and an autophagy inhibitor may be an effective treatment for osteosarcoma because this combination effectively induces apoptotic pathways.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.