Biomedical subjects

Y Sugioka

Publications and source records attributed to Y Sugioka.

At least 19 recordsLinked to original sources

PubMed1998

Serum 1alpha,25-dihydroxyvitamin D3 accumulates into the fracture callus during rat femoral fracture healing.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is thought to be an important systemic factor in the fracture repair process, but the mechanism of action of 1,25(OH)2D3 has not been clearly defined. In this study, the role of 1,25(OH)2D3 in the fracture repair process was analyzed in a rat closed femoral fracture model. The plasma concentration of 1,25(OH)2D3 rapidly decreased on day 3 and continued to decrease to 10 days after fracture. We assessed whether this decrease was based on the accelerated degradation or retardation of the synthesis rate of 1,25(OH)2D3, from 25(OH)D3. After radiolabeled 3H-1,25(OH)2D3 or 3H-25(OH)D3 was injected i.v. into fractured or control (unfractured) rats, the concentrations of 25(OH)D3 and 1,25(OH)2D3 metabolites were measured by HPLC. The plasma concentrations of these radiolabeled metabolites in fractured group were similar to those in control rats early after operation. However, radioactivity in the femurs of fractured rats was higher than that of the control group. Furthermore, the radioactivity was concentrated in the callus of the fractured group analyzed by autoradiography. 1,25(OH)2D3 receptor gene expression was detected early after fracture and, additionally, both in the soft and hard callus on days 7 and 13 after fracture. These results showed that the rapid disappearance of 1,25(OH)2D3 in the early stages after fracture was not due to either increased degradation or decreased synthesis of 1,25(OH)2D3, but rather to increased consumption. Further, these results suggest the possibility that plasma 1,25(OH)2D3 becomes localized in the callus and may regulate cellular events in the process of fracture healing.

Animals↗

PubMed1997

Hydroxyapatite-coating on titanium arc sprayed titanium implants.

We developed a new titanium spray technique using an inert gas shielded arc spray (titanium arc spray). Hydroxyapatite (HA)-coating can be applied to the implant without any surface pore obstruction after the rough surface is made by this technique. Scanning electron microscopy (SEM) of various porous implant surfaces after HA-coating revealed that the bead and fiber metal-coated implants had either a pore obstruction or an uneven HA-coating. On the other hand, the titanium arc sprayed implant demonstrated an even HA-coating all the way to the bottom of the surface pore. In the first set of animal experiments (Exp. 1), the interfacial shear strength to bone of four kinds of cylindrical Ti-6A1-4V (Ti) implants were compared using a canine transcortical push-out model 4 and 12 weeks after implantation. The implant surfaces were roughened by titanium arc spray (group A-C) and sand blasting (group D) to four different degrees (roughness average, Ra = group A: 56.1, B: 44.9, C: 28.3, D: 3.7 microns). The interfacial shear strength increased in a surface roughness-dependent manner at both time periods. However, the roughest implants (group A) showed some failed regions in the sprayed layers after pushout test. In the second set of animal experiments (Exp. 2), four kinds of Ti implants; HA-coated smooth Ti (sHA) with Ra of 3.4 microns, bead-coated Ti (Beads), titanium arc sprayed Ti (Ti-spray) with Ra of 38.1 microns and HA-coated Ti-spray (HA + Ti-spray) with Ra of 28.3 microns were compared using the same model as that in Exp. 1. The interfacial shear strength of HA + Ti-spray was significantly greater than that of sHA and Beads at both time periods, and that of Ti-spray at 4 weeks. Although a histological examination revealed that HA-coating enhanced bone ingrowth, sHA showed the lowest shear strength at both time periods. SEM after pushout test showed that sHA consistently demonstrated some regional failure at the HA-implant substrate interface. HA + Ti-spray had many failed regions either at the HA-bone interface or within the bone tissue rather than at the HA-implant substrate interface. These results suggested that the HA-coated smooth surfaced implants had a mechanical weakness at the HA-substrate interface. Therefore, HA should be coated on the rough surfaced implants to avoid a detachment of the HA-coating layer from the substrate and thus obtain a mechanical anchoring strength to bone. HA-coating on this new type of surface morphology may thus lead to a solution to the problems of conventional HA-coated and porous-coated implants.

Alloys↗

PubMed1997

Effects of pulse methylprednisolone on bone and marrow tissues: corticosteroid-induced osteonecrosis in rabbits.

OBJECTIVE: To investigate the effects of pulse methylprednisolone acetate on bone and bone marrow tissues and to clarify the causal factors of corticosteroid-induced osteonecrosis (ON) by using an experimental animal model. METHODS: Male adult Japanese white rabbits were injected once with 20 mg/kg of methylprednisolone into the right gluteus medius muscle. Seven rabbits were killed at 4 weeks, 4 at 6 weeks, 4 at 8 weeks, and 6 at 10 weeks. Both histopathologic and hematologic studies were performed every week. RESULTS: By 4 weeks after the steroid injection, 43% of the rabbits studied had developed multifocal ON lesions in the femur and/or humerus. In 1 rabbit, a thrombus was detected in an arteriole adjacent to the necrotic area at 4 weeks. After 6 weeks, there was also progressive histologic evidence of revascularization, with granulation tissue, and osteoblastic repair, with appositional bone formation. Hyperlipemia, fatty liver, and intraosseous fat embolism were observed in conjunction with thrombocytopenia and hypofibrinogenemia. CONCLUSION: A single injection of high-dose corticosteroids was found to be capable of inducing thrombocytopenia, hypofibrinogenemia, and hyperlipemia with multifocal ON in several bones.

Animals↗

PubMed1997

Localization and quantification of proliferating cells during rat fracture repair: detection of proliferating cell nuclear antigen by immunohistochemistry.

Bilateral femurs of 12-week-old female Sprague-Dawley rats were fractured, and the fractured femurs were harvested 36 h, 3, 7, 10, and 14 days after the fracture. Localization of cell proliferation in the fracture calluses was investigated using immunohistochemistry with antiproliferating cell nuclear antigen (PCNA) monoclonal antibodies. Thirty-six hours after the fracture, many PCNA-positive cells were observed in the whole callus. The change was not limited to mesenchymal cells at the fracture site where the inflammatory reaction had occurred, but extended in the periosteum along almost the entire femoral diaphysis where intramembranous ossification was initiated. On day 3, periosteal cells or premature osteoblasts in the newly formed trabecular bone during intramembranous ossification still displayed intense staining. On day 7, many premature chondrocytes and proliferating chondrocytes were PCNA positive. Endochondral ossification appeared on days 10 and 14, and the premature osteoblasts and endothelial cells in the endochondral ossification front were stained with anti-PCNA antibodies. Quantification of PCNA-positive cells was carried out using an image analysis computer system, obtaining a PCNA score for each cellular event. The highest score was observed in the periosteum early after the fracture near the fracture site. Immunohistochemistry using anti-PCNA antibodies showed that the distribution of proliferating cells and the degree of cell proliferation varied according to the time lag after the fracture, suggesting the existence of local regulatory factors such as growth factors, and that significant cell proliferation was observed at the beginning of each cellular event.

Animals↗

PubMed1997

Nationwide survey of bone grafting performed from 1980 through 1989 in Japan.

Nationwide surveys were conducted in 1985 and 1989 on the status of bone grafting performed in Japan. At the first survey, questionnaires were sent to 527 hospitals, with 218 responding. Of 26,800 bone grafts performed, 96.4% were autografts, and the remaining 3.6% were allografts and xenografts. Most allografts were bone chip grafts (85%), followed by massive bone grafts excluding osteoarticular grafts (14%). Osteoarticular allografts and whole bone allografts composed only 0.4% and 0.5% of the total, respectively. At the second survey, questionnaires were sent to 2053 hospitals, with 967 responding. The use of synthetic bone substitutes and bone grafts was investigated in the second survey. Of 87,994 bone grafts performed, 94.3% were autografts, 3.2% were synthetic bone substitutes, 1.9% were banked bone allografts, 0.4% were fresh allografts, and 0.2% were xenografts. Most of all grafts were bone chip grafts (57.1%), followed by massive bone grafts excluding osteoarticular grafts (40.3%). Osteoarticular grafts and whole bone grafts accounted for only 0.3% and 2.3% of the totals, respectively. Although the number of patients requiring bone grafts increased yearly, bone allografts were not widely used in Japan.

Bone Diseases↗

PubMed1997

Macrophage inflammatory protein-1 alpha (LD78) expressed in human bone marrow: its role in regulation of hematopoiesis and osteoclast recruitment.

Human macrophage inflammatory protein-1 alpha (hMIP-1 alpha), also known as LD78, is a member of the chemokine/ intercrine family and an inhibitor of the proliferation of the hematopoietic stem cells in vitro. Using a specific monoclonal antibody, we observed significant localization of hMIP-1 alpha in eosinophilic myelocytes in human bone marrow. We further examined the expression of hMIP-1 alpha mRNA in human bone tissue by in situ hybridization. A high level of hMIP-1 alpha mRNA expression was detected in eosinophilic myelocytes in bone marrow, confirming these cells as the site of hMIP-1 alpha synthesis. hMIP-1 alpha mRNA expression was also detected in osteoblasts in the bone-remodeling sites, and osteoclasts were frequently observed in the vicinity of these osteoblasts. hMIP-1 alpha was also able to induce osteoclastogenesis on calcified matrices in the absence of any other osteotropic hormones. These results strongly suggest that hMIP-1 alpha is involved not only in the regulation of hematopoiesis but also in the modulation of bone remodeling.

Animals↗

PubMed1997

Histopathologic alterations of retinacular vessels and osteonecrosis.

To probe into the pathogenesis of osteonecrosis of the femoral head, the authors obtained 37 asymptomatic human femoral heads at autopsy; of these, 13 were cases of high dosage corticosteroid therapy (steroid group) and 24 were cases without steroid therapy (nonsteroid group). The steroid group included two asymptomatic cases of osteonecrosis incidentally recognized. These femoral heads then were studied histologically and morphometrically using 2-mm stepwise tissue sections of the whole femoral head and serial sections to examine the histopathologic alterations of superior retinacular arteries and veins in detail. There was no significant difference in the luminal stenotic rate of the superior retinacular arteries between the steroid and nonsteroid groups. However, the draining veins morphometrically were more stenotic or obliterated in the steroid group than were those in the nonsteroid group. In fact, the number of stenotic veins was significantly greater in the steroid group. These findings indicate that the stenotic changes of the draining veins may participate in the development and progression of steroid induced osteonecrosis of the femoral head.

Adult↗

PubMed1996

A quantitative assay using basement membrane extracts to study tumor angiogenesis in vivo.

We describe a quantitative assay for assessing tumor angiogenesis in vivo using basement membrane extracts (Matrigel). Nude mice were injected s.c. with liquid Matrigel mixed with HT1080 human fibrosarcoma cells. Since Matrigel rapidly forms a solid gel at body temperature, the gel containing tumor cells can be removed immediately and then processed for histological studies. Tumor angiogenesis was monitored quantitatively by measuring both the number and the total area of neovessels present in the gels using an image analyzer, which could be achieved approximately 72 hr later. Furthermore, HT1080 cell-conditioned medium, which may contain various tumor-derived factors, promoted the basement membrane degradation, migration, proliferation and tube formation of endothelial cells in vitro, as did Matrigel, although to a lesser extent. In addition, Northern blot analysis demonstrated that the amount of vascular endothelial growth factor (VEGF) mRNA in HT1080 cells was much higher than that in human fibroblasts or NIH3T3 cells. Our results suggest that angiogenesis observed in our assay may be due to the synergic effects of tumor angiogenic factors such as VEGF, and Matrigel. The advantages of our assay are: 1) it is possible to assess early angiogenesis quantitatively; and 2) this assay may be applicable for screening anti-angiogenic therapeutic agents to be used against human neoplasms.

3T3 Cells↗

PubMed1996

Tortuosity of the vertebral artery in patients with cervical spondylotic myelopathy. Risk factor for the vertebral artery injury during anterior cervical decompression.

STUDY DESIGN: The case report presented herein shows tortuosity of the vertebral artery in a patient with cervical myelopathy. This case led the authors to evaluate 22 other patients who also had undergone anterior cervical fusion. They were studied before operation by either magnetic resonance imaging angiography or selective vertebral angiography. OBJECTIVES: To analyze the radiographs, computed tomography, magnetic resonance imaging, and angiography findings to detect any tortuosity of the vertebral artery in patients with cervical myelopathy to show the risk factors of vertebral artery injury during anterior decompression. SUMMARY OF BACKGROUND DATA: Complications of vertebral artery laceration during cervical anterior decompression are rare, so this injury and abnormality in the course of vertebral artery in patients with cervical myelopathy receive little attention. METHODS: The tortuosity of the vertebral artery was assessed by angiography, magnetic resonance imaging, and computed tomography. RESULTS: Mild vertebral artery tortuosity was observed in 10 patients and loop formation in three associated with cervical spondylotic changes. CONCLUSIONS: This study suggests that vertebral artery loop formation is developed associated with cervical spondylotic changes. During the anterior decompression of cervical spondylotic myelopathy or radiculopathy, the looped vertebral artery could be injured by an excessive wide rejection of the bone or disc material. In the case of vertebral artery migration, the looped vertebral artery can even be injured by routine procedures.

Adolescent↗

PubMed1996

A new method using top views of the spine to predict the progression of curves in idiopathic scoliosis during growth.

STUDY DESIGN: A prospective longitudinal study of 51 patients with idiopathic scoliosis using spinal stereoradiographs was performed. The top view, which was obtained from stereoscopic anteroposterior and lateral radiographs, was analyzed for predicting the progression of spinal deformity. OBJECTIVES: To show that the top view facilitates prediction of curve progression in idiopathic scoliosis at the initial examination. SUMMARY OF BACKGROUND DATA: Four progression factors were set up using the top view and were analyzed statistically for predicting progression. No previous study has assessed this concept. METHODS: Fifty-one patients with idiopathic thoracic scoliosis or combined thoracic and lumbar scoliosis were studied longitudinally. There were 24 untreated patients and 27 patients treated with braces. Four potential progression factors were evaluated using the top view: 1) the ratio of the frontal size and the sagittal size in the top view, 2) the magnitude and direction of the vector describing the plane of maximum curvature in the thoracic spine, 3) the magnitude and direction of the vector describing the plane of maximum curvature in the lumbar spine, and 4) the balance of these vectors between the thoracic and lumbar curve. All cases were classified into five groups according to these four factors. RESULTS: The probability of the progression was evaluated statistically, and the prevalence of curve progression was found in each group. The probability of progression of a scoliosis curve increased according to the increase of these four factors. No significant difference was found between Cobb angle at the initial examination and that at skeletal maturity in untreated patients with a small risk of progression. The patients with a large risk of progression and who were treated with braces showed progression of curvature despite brace treatment. CONCLUSION: The present study has evaluated factors relating to progression in scoliosis using the top view. These results may help predict the risk of progression in idiopathic scoliosis.

Adolescent↗

PubMed1996

Basic fibroblast growth factor stimulates articular cartilage enlargement in young rats in vivo.

Basic fibroblast growth factor is a potent mitogen for chondrocytes and influences the protein synthesis of their extracellular matrix in vitro. To investigate its effect on normal developing articular cartilage in vivo, we injected basic fibroblast growth factor once into the knee joints of 4-week-old rats. Phosphate buffered saline was similarly injected into the contralateral knee joints as controls. A histological analysis showed that an injection of basic fibroblast growth factor induced enlargement of the articular cartilage area, especially in the condylar ridge region on day 7 after the injection. The extent of the enlargement was dose-dependent. The localization and amount of proliferating cells in the articular cartilage were analyzed immunohistochemically by the detection of proliferating cell nuclear antigen. On day 1 after the injection, the number of cells positive for proliferating cell nuclear antigen increased significantly in the joints that were injected compared with the controls, and Northern blot analysis showed that the level of messenger RNA for alpha 1(II) procollagen was lower in these joints than in the controls. The message in the joints that had been injected increased on day 7, and it was greater than that in the controls. This suggests that proliferating chondrocytes in developing articular cartilage respond to basic fibroblast growth factor with a resulting proliferation of chondrocytes followed by enlargement of cartilage.

Animals↗

PubMed1996

Proliferative activities in conventional chordoma: a clinicopathologic, DNA flow cytometric, and immunohistochemical analysis of 17 specimens with special reference to anaplastic chordoma showing a diffuse proliferation and nuclear atypia.

Chordoma shows various degrees of atypia histologically, however, the relationship between the histological features and the biological behavior still remains controversial. The authors subclassified 17 specimens with chordoma into two groups (ie, trabecular type showing a trabecular patterns and solid type mainly consisting of a diffuse proliferation of tumor cells). The histological grading was performed according to the degree of nuclear atypia on a scale of 1 to 3. Using DNA flow cytometric and immunohistochemical techniques, both the proliferative index (% S + G2 + M phase) and the MIB-1 labeling index (LI) of the tumor cells were estimated regarding their proliferative activities. In addition, p53 overexpression was also investigated using immunohistochemical techniques. There were eight (47.1%) specimens of trabecular type and nine (52.9%) of solid type. In nine specimens of solid type, those with higher nuclear atypia (grade 2 or 3) were significantly more frequent (five specimens, 55.6%) than in trabecular type in which all of the eight specimens were grade 1 (P = 0.44). The proliferative index was significantly higher in grade 2 or 3 lesions than in grade 1 lesions (P = .014), and the MIB-1 LI tended to be higher in solid type than in trabecular (P = .088). p53 overexpression was detected in two specimens of solid type, and the MIB-1 LI in these two specimens was significantly higher (P = .037) than that in the specimens without p53 overexpression. It was considered that the preceding anaplastic histological features, including either diffuse proliferation or high grade nuclear atypia, together with p53 overexpression, were thus closely related to the proliferative activities in chordomas.

Adolescent↗

PubMed1996

Radial closing wedge osteotomy for Kienböck's disease.

Twenty-six patients with Kienböck's disease who were treated with a radial closing wedge osteotomy and then followed for a total of 4 years and 5 months were studied. Their mean age at surgery was 31.7 years. Clinical results were excellent in 8, good in 11, fair in 6, and poor in 1 patient using the Nakamura scoring system. Nineteen (73%) patients had excellent or good results, and 25 (96%) were content with their results. Factors affecting the clinical results included the postoperative Ståhl index and the preoperative radiolunate angle. It was concluded that radial closing wedge osteotomy is an effective procedure for patients with Kienböck's disease but that a flexion deformity of the lunate limits clinical success.

Adolescent↗

PubMed1996

Inhibition of angiogenesis, tumour growth and experimental metastasis of human fibrosarcoma cells HT1080 by a multimeric form of the laminin sequence Tyr-Ile-Gly-Ser-Arg (YIGSR).

A multimeric peptide, Ac-Y16, consisting of 16 YIGSR sequences from laminin was evaluated for its effect on experimental metastasis, angiogenesis and tumour growth of HT1080 human fibrosarcoma cells. Co-injection of 0.5 mg per mouse of Ac-Y16 i.v. with HT 1080 cells inhibited lung colonisation by 100%, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(AcY1) inhibited by 94%. Ac-Y16 did not show any direct cytotoxicity in tumour cells in vivo. The effect of the peptides on angiogenesis and tumour growth respectively were evaluated by counting areas of neovessels and weighing tumours after the s.c. implantation of HT1080 cells with basement membrane extracts and the peptide into nude mice. Co-injection of 0.5 mg per mouse of AC-Y16 s.c. with HT1080 cells inhibited angiogenesis and tumour growth by 92% (P<0.05) and 76% (P<0.05) respectively, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(Ac-Y1) inhibited angiogenesis and tumour growth by 40% (P<0.05) and 9% (P>0.05) respectively. It can be inferred from these data that anti-tumour effects of Ac-Y16 are likely to result from anti-angiogenesis. Intraperitoneal administration of Ac-Y16 was also effective in inhibiting angiogenesis, tumour growth and lung colonisation of HT1080 cells. It was concluded that the multimeric YIGSR-containing peptide, Ac-Y16, inhibits angiogenesis, tumour growth and experimental metastasis more than the monomeric form and that it is active when administered i.p., iv. and s.c.

Amino Acid Sequence↗

PubMed1996

1,25-Dihydroxyvitamin D3 enhances the enzymatic activity and expression of the messenger ribonucleic acid for aromatase cytochrome P450 synergistically with dexamethasone depending on the vitamin D receptor level in cultured human osteoblasts.

Not every postmenopausal woman with a low level of estrogen suffers from osteoporosis, and no correlation of bone density with serum estrogen level, but a significant correlation with adrenal androgens is often noted. Vitamin D3 has been reported to be osteoclastic in vitro, whereas the effectiveness of vitamin D3 for the treatment of osteoporosis is clinically relevant. To study the roles of these factors in the development of osteoporosis, we characterized aromatase activity converting androgens to estrogens in human osteoblasts, because postmenopausal women maintain considerable levels of adrenal androgens. Glucocorticoids at 10(-9)-10(-7) M transiently induced the expression and enzymatic activity of aromatase cytochrome P450 (P450AROM) in primary cultured osteoblasts, and the Km value for androstenedione (4.7 +/- 2.9 nM) was lower than that in adipose tissue and skin. Human osteoblasts showed a promoter specificity different from that found in other tissues. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] alone did not induce aromatase activity, but enhanced and maintained glucocorticoid-induced P450AROM gene expression. This synergistic effect was not observed by other sex steroids or retinoic acids. The enhancement of P450AROM activity by 1,25-(OH)2D3 varied from 0.94-fold (no enhancement) to 2.40-fold (maximal enhancement) among the individual human osteoblasts examined, but the magnitude of the enhancement was significantly correlated with the level of vitamin D receptor messenger RNA (P < 0.05). Cycloheximide did not abolish the synergistic effect of 1,25-(OH)2D3, suggesting that de novo protein synthesis is not required for the synergism with 1,25-(OH)2D3. These results suggest that bone tissue can synthesize estrogen from adrenal androgens by a unique aromatase activity depending on the level of vitamin D receptor expressed.

Adolescent↗

PubMed1996

Experimental osteochondritis dissecans--the role of cartilage canals in chondral fractures of young rabbits.

Skeletal immature rabbits were used to study the pathogenesis of Osteochondritis Dissecans (OCD). Both histological studies and a radiographical examination were utilized after sagittal and coronal surgical chondral fractures were made in the femoral condyles cartilage. Serial microangiographies were performed in rabbits between 0 and 84 days after the chondral fractures were made. Analyses of the histology and microradiography findings suggest in either a coronal or sagittal direction, that avascular lesions like an experimental OCD occur as a sequence of chondral injury. A fracture in a wide pedicle of a stable cartilaginous flap with abundant cartilage canals heals in the usual way. However, a fracture in an unstable fragment with a small isthmus devoid of cartilage canals and of nutritious vessels, probably doesn't heal completely and a fragment closely resembling OCD is instead formed. An experimental OCD depends on the slender hinge of the flap and on the lack of stability in a rabbit's non-ossified epiphyseal cartilage. The damage to the cartilage canals and the rupture of vessels in the canals by a chondral fracture and the disturbance in the revascularization in the healing process by abnormal mechanical forces are thus most likely considered to be the main factor for OCD production.

Animals↗

PubMed1995

Osteosarcoma versus malignant fibrous histiocytoma of bone in patients older than 40 years. A clinicopathologic and immunohistochemical analysis with special reference to malignant fibrous histiocytoma-like osteosarcoma.

BACKGROUND: It is often difficult to discriminate between osteosarcoma and malignant fibrous histiocytoma (MFH) of bone, especially in older patients because of the clinical similarities, including the lytic radiologic appearance. A histologic analysis of MFH-like osteosarcoma, which closely resembles MFH of bone both clinically and radiologically, has not yet been conducted thoroughly, and therefore this issue remains controversial. METHODS: Using clinicopathologic and immunohistochemical techniques, the authors studied 24 cases of osteosarcoma arising in patients older than 40 years of age and compared them with 20 cases of MFH of bone from similarly aged patients. RESULTS: Radiography revealed that 68.2% of the osteosarcoma cases were predominantly lytic, whereas all cases of MFH of bone showed either a predominantly or purely lytic pattern. Histologically, osteosarcoma was subclassified as conventional osteoblastic (54.2%), MFH-like (29.2%) containing various amounts of tumor osteoid and/or bone in each of the cases, and conventional fibroblastic (4.2%), whereas all the cases of MFH of bone had a storiform-pleomorphic pattern. Immunohistochemically, no overexpression of p53 protein was found in MFH-like osteosarcoma, whereas it tended to occur more frequently in osteoblastic osteosarcoma (66.7%) and MFH of bone (50.0%). The Ki-67 labeling index was significantly lower in MFH-like osteosarcoma than in MFH of bone. The 5-year survival rate was 18.2% in patients with osteoblastic osteosarcoma, 66.7% in patients with MFH-like osteosarcoma, and 21.5% in patients with MFH of bone. A significant difference in the survival curve was observed between osteoblastic and MFH-like osteosarcoma. CONCLUSIONS: It is proposed that MFH-like osteosarcoma, which shows characteristically different clinical and histologic features from that of conventional osteosarcoma, thus may be considered a variant of osteosarcoma.

Adult↗

PubMed1995

Cyclic AMP-regulated synthesis of the tissue inhibitors of metalloproteinases suppresses the invasive potential of the human fibrosarcoma cell line HT1080.

Tissue inhibitors of metalloproteinases (TIMPs) play an important role in regulating the activity of matrix metalloproteinases (MMPs). Tumor cell invasion and metastasis closely correlate with the activities of two members of MMPs, MMP2 and MMP9, both of which degrade type IV collagen in basement membranes. We herein report that the treatment of HT1080 cells with 8-bromo-cAMP and other chemicals that activate cyclic adenylase activity induces the expression of TIMP1 and TIMP2 both at the mRNA and the protein levels and that this induction of TIMPs correlates with suppression of invasive phenotypes of HT1080 cells. Treatment with various cAMP-elevating reagents induced the expression of TIMPs and MMP2 in HT1080 cells, whereas the expression of MMP9 was not significantly affected. The protein amounts of TIMP1, TIMP2, and MMP2 secreted into the medium from HT1080 cells treated with 1 mM 8-bromo-cAMP were 7.9-, 9.3-, and 8.5-fold higher than those secreted from untreated cells, respectively. Induction of these mRNAs by 8-bromo-cAMP was blocked by HA1004, a protein kinase A inhibitor, but not by calphostin C, a protein kinase C inhibitor. Cycloheximide abolished the induction of TIMPs and MMP2 mRNAs by 8-bromo-cAMP, indicating that the induction depends on a newly synthesized protein(s) whose expression may be regulated by cAMP. Type IV collagenolytic activity and the invasiveness of HT1080 cells, both of which were suppressed by 8-bromo-cAMP, were efficiently restored when the cells were exposed to anti-TIMP antibodies, demonstrating the importance of the increased levels of TIMP1 and TIMP2 proteins for the cAMP-mediated suppression of both type IV collagenolytic activity and the invasiveness of HT1080 cells.

8-Bromo Cyclic Adenosine Monophosphate↗