Search PubMed⌕ Search

Biomedical subjects

H Takita

Publications and source records attributed to H Takita.

At least 19 recordsLinked to original sources
PubMed2005

Growth factor-loaded scaffolds for bone engineering.

The objective of the study presented here was to investigate the bone inductive properties as well as release kinetics of rhTGF-beta1- and rhBMP-2-loaded Ti-fiber mesh and CaP cement scaffolds. Therefore, Ti-fiber mesh and porous CaP cement scaffolds were provided with these growth factors and inserted in subcutaneous and cranial implant locations in rats and rabbits. In vitro, a rapid release of rhTGF-beta1 was observed during the first 2 h of the Ti-fiber mesh scaffolds. During this time, more than 50% of the total dose of rhTGF-beta1 was released. Following this initial peak, a decline in the level of rhTGF-beta1 occurred. After 1 week, the entire theoretical initial dose was observed to have been released. This in contrast to the rhTGF-beta1 and rhBMP-2 release of the porous CaP cement scaffolds. Here, no substantial initial burst release was observed. The scaffolds showed an initial release of about 1% after 1 day, followed by an additional marginal release after 1 week. Histological analysis revealed excellent osteoconductive properties of non-loaded Ca-P material. Inside non-loaded Ti-mesh fiber scaffolds, also bone ingrowth occurred. Quantification of the bone ingrowth showed that bone formation was increased significantly in all scaffold materials by administration of rhTGF-beta1 and rhBMP-2. Consequently, we conclude that the release kinetics of growth factors from porous CaP cement differs from other scaffold materials, like metals and polymers. Nevertheless, orthotopic bone formation in a rabbit cranial defect model was stimulated in rhTGF-beta1- and rhBMP-2-loaded CaP cement and Ti-fiber mesh scaffolds compared with non-loaded implants.

Animals↗
PubMed2004

Carrier dependent cell differentiation of bone morphogenetic protein-2 induced osteogenesis and chondrogenesis during the early implantation stage in rats.

To evaluate the osteoinductive effects of recombinant human bone morphogenetic protein (rhBMP)-2 during the early stages of rat ectopic bone formation, we prepared two distinct carriers. Two carriers, insoluble bone matrix (IBM) and fibrous glass membrane (FGM) were combined with rhBMP-2 and implanted into the backs of rats to evaluate the osteoinductive effects of the two rhBMP-2 carrier systems. Insoluble bone matrix particle size was 320 to 620 microm. Fibrous glass membrane was constructed from unwoven glass fibers 1 microm in diameter. Alkaline phosphatase (ALP) activity and type II collagen were detected in IBM/rhBMP-2 at 5 days postimplantation. Calcium (Ca) was also detected in IBM/rhBMP-2 at 7 and 9 days postimplantation. In contrast, ALP and type II collagen were detected in FGM/rhBMP-2 at 7 days. Calcium was undetected, indicating that the bone formation in IBM/rhBMP-2 proceeded faster than in FGM/rhBMP-2 during the early stage of BMP-induced osteogenesis. In addition, mRNA expression level of KDR, a receptor for vascular endothelial growth factor, was also increased in IBM/rhBMP-2. To investigate the in vivo release profile of rhBMP-2, iodine 125 ((125)I)-labeled BMP-2-incorporating IBM and FGM implants were inserted into the back subcutis of mice. More than 60% of the rhBMP-2 was released from the IBM/rhBMP-2 carrier within 1 day after implantation, whereas 50% of the rhBMP-2 was released from the FGM/rhBMP-2 10 days postimplantation. These results indicated that osteo- and chondrogenesis depends highly upon the geometry of the carrier and the in situ retention of rhBMP-2 during the early stage of rhBMP-2 induced bone formation.

Alkaline Phosphatase↗
PubMed2003

Laser-perforated membranous biomaterials induced pore size-dependent bone induction when used as a new BMP carrier.

Previously we found that laser perforation of a collagen membrane (35 microm thickness, Koken Co., Tokyo) produced an effective bone morphogenetic protein (BMP) carrier, if the created pore sizes were larger than 0.5 mm. In this study we applied the same technique to create pores of 0.2 and 1.0 mm in a thicker (1.2 mm thickness) porous biodegradable membrane made of polylactic acid and an epsilon-caprolactone copolymer (PLA-CL) to obtain an effective membranous BMP carrier with higher mechanical strength. Pieces of PLA-CL (0.5 x 1.0 x 0.12 cm) combined with rhBMP-2 (5 microg) were implanted subcutaneously into rats and processed for analyses at 1-3 weeks. The laser-perforated PLA-CL membranes equipped with 1.0 mm pores induced mineralization beginning from the margins of the pores judging from the X-ray patterns, but bone formation seemed to proceed irregularly inside the pores. In the perforated PLA-CL membrane with 1.0-mm pores bone formation did not significantly increase compared with the nonperforated one. This was due to the fact that the PLA-CL membrane was already a porous structure (85% porosity). In contrast with laser-perforated PLA-CL 0.2 mm pores, bone was induced on the collagen fibers and fiber bundles inside the pores. The different patterns of bone formation between the PLA-CL membranes with 1.0 and 0.2 mm pores seemed to be related to the active formation of perpendicular collagen fibers through the 0.2 mm pores.

Animals↗
PubMed2002

Histological characterization of the early stages of bone morphogenetic protein-induced osteogenesis.

On the basis of currently available knowledge, we hypothesize that the initial bone formation, as induced by bone morphogenetic protein (BMP), is influenced by the chemical composition and three-dimensional spatial configuration of the used carrier material. Therefore, in the current study, the osteoinductive properties of porous titanium (Ti) fiber mesh with a calcium phosphate (Ca-P) coating (Ti-CaP), insoluble bone matrix (IBM), fibrous glass membrane (FGM), and porous particles of hydroxy apatite (PPHAP) loaded with rhBMP-2 were compared in a rat ectopic assay model at short implantation periods. Twelve Ti-CaP, 12 IBM, 12 FGM, and 12 PPHAP implants, loaded with rhBMP-2, were subcutaneously placed in 16 Wistar King rats. The rats were sacrificed at 3, 5, 7, and 9 days post-operative, and the implants were retrieved. Histological analysis demonstrated that IBM and Ti-CaP had induced ectopic cartilage and bone formation by 5 and 7 days, respectively. However, in PPHAP, bone formation and cartilage formation were seen together at 7 days. At 9 days, in Ti-CaP, IBM, and PPHAP, cartilage was seen together with trabecular bone. At 9 days, in FGM, only cartilage was observed. Quantitative rating of the tissue response, using a scoring system, demonstrated that the observed differences were statistically significant (Wilcoxon rank sum test, p < 0.05). We conclude that IBM, CaP-coated Ti mesh, FGM, and PPHAP provided with rhBMP-2 can indeed induce ectopic bone formation with a cartilaginous phase in a rat model at short implantation periods. Considering the different chemical composition and three-dimensional spatial configuration of the carrier materials used, these findings even suggest that endochondral ossification is present in rhBMP-2-induced osteogenesis, even though the amount of cartilage may differ.

Animals↗
PubMed2001

Geometric effect of matrix upon cell differentiation: BMP-induced osteogenesis using a new bioglass with a feasible structure.

A new biocompatible glass, which is composed of CaO, P2O5, SiO2, and Al2O3 (abbreviated CPSA) and is characterized by higher elasticity than previous bioglass products, was molded into fibers with a diameter of 9 microm. With CPSA fibers, two geometrically different structures, balls and bundles (each 20 mg in weight), were prepared, combined with 2.2 microg of rhBMP-2 (a gift from Yamanouchi Co., Japan) and implanted subcutaneously into rats. The histology showed remarkably higher bone formation in the ball-CPSA/BMP at 2 and 4 weeks than in the bundle-CPSA/BMP. The ball-CPSA/BMP showed 10 times higher alkaline phosphatase (ALP) activity at the second week and 5 times higher osteocalcin content at the fourth week than the bundle-CSPA/BMP. Vascular development in the implants was evaluated by mRNA expression of Flt-1 and KDR, two receptors for vascular endothelial growth factor (VEGF). Both receptors showed higher expression in the case of the ball, while they were not detected in the bundle. It is concluded that the BMP-induced bone formation depends highly upon the porous vasculature-inducing geometry of the matrix, which can be constructed with the new CPSA fibers.

Alkaline Phosphatase↗
PubMed2001

Ectopic bone formation in titanium mesh loaded with bone morphogenetic protein and coated with calcium phosphate.

The osteoinductive properties of porous titanium fiber mesh, with or without a calcium phosphate coating and loaded with recombinant human bone morphogenic protein-2 (rhBMP-2) or rhBMP-2 and native bovine BMP (S-300) were investigated in a rat ectopic assay model. A total of 112 calcium phosphate-coated and 112 noncoated porous titanium implants, either loaded with rhBMP-2 and S-300 or loaded with rhBMP-2 alone, were subcutaneously placed in 56 Wistar-King rats. The rats were killed 5, 10, 20, and 40 days postoperatively, and the implants were retrieved. Histologic analysis demonstrated that all growth factor and carrier combinations induced ectopic cartilage and bone formation at 5 and 10 days, respectively. At 20 days, bone formation increased and was characterized by trabecular bone and bone marrow-like tissue. At 40 days, more lamellar bone and hemopoietic bone marrow-like tissue were present. At both times, more bone had been formed in calcium phosphate-coated implants than in noncoated samples. Further, in rhBMP-2 and S-300-loaded specimens, bone formation was higher than in rhBMP-2 only-loaded specimens. In rhBMP-2 only-loaded specimens, bone formation was mainly localized inside the mesh material, whereas in specimens loaded with both rhBMP-2 and S-300, the bone was localized inside and surrounding the titanium mesh. The histological findings were confirmed by calcium content and alkaline phosphatase activity measurements. In addition, all specimens showed osteocalcin expression as early as 5 days postoperatively. Our results show that the combination of titanium mesh with BMPs can induce ectopic bone formation and that this bone formation seems to be similar to "enchondral" ossification. In addition, a thin calcium phosphate coating can have a beneficial effect on the bone-inducing properties of a scaffold material. Finally, rhBMP-2 and native BMP act synergistically in ectopic bone induction.

Alkaline Phosphatase↗
PubMed2001

Geometry of carriers controlling phenotypic expression in BMP-induced osteogenesis and chondrogenesis.

BACKGROUND: The effect of the geometry of extracellular matrices on bone morphogenetic protein (BMP)-induced osteogenesis has not been systematically studied. Geometry is crucially important for the scaffold in bone and joint tissue engineering. The purpose of this study was to elucidate principles of geometry of matrices in designing new scaffolds and matrices for use in reconstruction of bone and joints. METHODS: More than ten biomaterials with different geometries, including a unique device of honeycomb-shaped hydroxyapatite, were combined with BMPs of recombinant (rhBMP-2) or natural bovine origin (S300 BMP cocktail) and implanted subcutaneously into 4-week-old Wistar-King rats. The implanted pellets were removed at 1-4 weeks and analyzed for bone and cartilage formation by histological and biochemical methods. RESULTS: BMP-induced bone and cartilage induction was highly dependent on the geometric properties of the carrier. Some carriers such as porous particles or blocks of hydroxyapatite induced osteogenesis directly, without detectable chondrogenesis, whereas other carriers such as fibrous glass membrane induced cartilage exclusively. Still other carriers induced mostly cartilage followed by bone formation. Solid particles of hydroxyapatite and fibrous glass membrane with too tight a meshwork did not induce bone or cartilage. The optimal pore size for bone-forming efficacy in porous blocks of hydroxyapatite was a diameter of 300-400 microm. In straight tunnel structures with various diameters in honeycomb-shaped hydroxyapatite, tunnels with smaller diameters (90-120 microm) induced cartilage followed by bone formation, whereas those with larger diameters (350 microm) induced bone formation directly within the tunnels. CONCLUSIONS: BMP carriers were classified into three types: bone-inducing, cartilage-inducing, and cartilage-bone-inducing. From the analysis of causative factors inducing osteogenesis and chondrogenesis in the BMP system, we concluded that the geometry of the carrier is crucially important and vasculature-inducing geometry should be considered in designing effective scaffolds for bone formation. We propose a classification of geometry of the artificial extracellular matrices that is useful for designing a scaffold for tissue engineering of bone and related tissues. CLINICAL RELEVANCE: Conventional requisites of the BMP carriers for clinical use have mainly concerned the affinities of carriers with cells and biomolecules and their mechanical strength. The vasculature-inducing geometry of carriers adds a new criterion in designing systems for effective bone and joint reconstruction. The geometries of porous structures-their sizes, continuity, and straightness as verified by hydroxyapatite in this study-will be applicable for other biomaterials for clinical reconstruction therapy.

Animals↗
PubMed2000

Effects of geometry of hydroxyapatite as a cell substratum in BMP-induced ectopic bone formation.

Three different types of porous hydroxyapatite with pore sizes of 100-200 micrometer in diameter-porous particles of hydroxyapatite (PPHAP), porous blocks of hydroxyapatite (PBHAP), and honeycomb-shaped hydroxyapatite (HCHAP)-were compared in terms of their abilities to induce osteogenesis when implanted subcutaneously with recombinant human BMP-2 into rats and extracted at 1, 2, 3, and 4 weeks. Histologically, direct bone formation occurred in PPHAP and PBHAP while only endochondral ossification took place in HCHAP. Interestingly, cartilage in the central zones and bone in the orifice zones of the tunnels of the HCHAP were observed at 2 weeks. After 3 weeks, the cartilage disappeared and bone formation occurred throughout the inner surface of the tunnels of the HCHAP, always leaving space for capillaries within the tunnels. Alkaline phosphatase activity and osteocalcin content were the highest in HCHAP among the three hydroxyapatite implants. These results clearly indicate that BMP-induced bone formation is highly dependent on the geometry of the carrier, which provides feasible structural factors for vascularization.

Alkaline Phosphatase↗
PubMed2000

Identification of genes differentially over-expressed in lung squamous cell carcinoma using combination of cDNA subtraction and microarray analysis.

In order to develop effective vaccine products against human cancer, we are interested in identifying genes over-expressed in tumor cells. Through a combination of cDNA library subtraction and microarray technology, we identified seventeen genes preferentially expressed in lung squamous cell carcinoma, including four novel genes. To date, expression profiles of these genes were confirmed by Northern and/or real-time analysis, and several genes were also found to be expressed in head and neck squamous tumors. Thus, these combined methods represent a high throughput approach for identifying tumor specific genes. Furthermore, the report of characterization on these genes will allow them to be exploited for their diagnostic, prognostic, and therapeutic potentials including immunotherapy and antibody based anticancer therapy.

Antigens, Neoplasm↗
PubMed2000

CD40 expression on human lung cancer correlates with metastatic spread.

PURPOSE: The poor prognosis associated with lung cancer is related to the high incidence of regional and distant metastasis. There is a crucial need to identify parameters that can predict a tendancy to metastatic spread to allow better prognostic evaluation and therapeutic approach. METHODS: Using flow cytometry we evaluated 18 human lung cancer cell lines for the expression of different surface markers on lung cancers suggested to be possible prognostic parameters, including epidermal growth factor receptor (EGFR), intercellular adhesion molecule 1 (ICAM-1), Fas and CD40. RESULTS: No correlation was found between tumor prognosis and EGFR, ICAM-1 or Fas. However, a statistically significant correlation was found between the surface expression of CD40 and the metastatic spread of the tumor. In this study, 14 of 18 lung cancer cell lines (78%) expressed CD40 on their surface. All of the 4 tumors that were CD40-negative, were stage I tumors, without any evidence of regional or distant metastasis. Of the 14 tumors that expressed CD40, all but 1 (93%) had either nodal or systemic metastasis at the time of diagnosis. Patients whose tumors were CD40-negative showed a significantly better N stage, overall stage at presentation and survival than those patients with CD40-positive patients. No significant differences between the two groups were observed in tumor size, gender, age, histology, differentiation or preoperative therapy. CONCLUSIONS: These results suggest that CD40 expression on lung cancer may play a role in metastatic spread, and also may serve as a prognostic marker and an indicator of advanced disease.

CD40 Antigens↗
PubMed2000

A 25-year thymoma treatment review.

Most thymomas are stage I or II at presentation, and they have a good prognosis with surgical treatment. Higher stage thymomas are less common and their treatment is more problematic. Our center tends to attract patients with higher stage thymomas for treatment. We reviewed our experience and contrasted it with other published series. A 25-year retrospective record review of thymomas was done. 38 patients were treated. Median age was 49 years. Four had myasthenia gravis. Masaoka staging was: stage I--9; stage II--6; stage III--15; stage IVa--4; stage IVb--4. Resection was done in 25 patients (21 had R0 resection), chemotherapy was given to 15 patients, and 27 patients received radiotherapy. Overall median survival was 55 months. Overall 5 and 10-year survivals were 30% and 18%. 5-year survival by stage was: stage I--75%; stage II--50%; stage III/IV--23%. Negative prognostic factors on univariate analysis included presence of symptoms at presentation (p = 0.02), unresectable tumor (p = 0.06), stage III/IV (p = 0.04), and disease recurrence after resection (p = 0.0001). On multivariate analysis, only stage (p = 0.04) and recurrence (p = 0.0001) were independent predictors of survival. All patients who recurred after resection eventually died of disease. Our overall treatment results are disappointing, but we had higher stage patients than reported by most other centers. Early stage thymomas are suitable for complete surgical resection, and the prognosis is favorable. However, higher stage thymomas (stage III and higher) pose problems for complete surgical resection and their prognosis is poor. Newer multimodality treatment approaches are indicated for higher stage thymomas.

Adolescent↗
PubMed2000

Bronchogenic carcinoma in patients age 30 and younger.

BACKGROUND: Lung cancer is rare in patients 30 years of age or younger. There is very little published data on lung cancer in this group of patients. METHODS: A retrospective review of patients 30 years of age and younger with bronchogenic carcinoma treated at Roswell Park Cancer Institute between 1973 and 1994 was done. RESULTS: There were 20 patients (11 female and 9 male). Mean age was 27 years (range, 19-30). The predominant histologic types were adenocarcinoma in 11 patients (55%), and undifferentiated large-cell carcinoma in 5 patients (25%). All patients presented with either stage III (8 patients) or IV disease (12 patients). Eight patients (40%) underwent surgical resection (2 lobectomies, 6 pneumonectomies). Other treatments included chemotherapy in 15 patients (75%) and radiation therapy in 7 (35%). Median survival was only 5.5 months, and there were no 5-year survivors. Univariate analysis identified stage (p = 0.05), resection (p = 0.0005), and treatment with chemotherapy (p = 0.001) as predictors of survival. On multivariate analysis, resection (p = 0.0001) and chemotherapy (p = 0.001) remained as independent predictors of survival. CONCLUSIONS: Young patients with lung cancer present with advanced-stage disease and their cancers appear to be biologically aggressive. Although curative treatment is rarely possible, aggressive multimodality therapy is warranted.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2000

Induction chemotherapy for locoregional lung cancer using paclitaxel combination. A preliminary report.

Induction chemotherapy has been reported to be effective in treatment of locally advanced, borderline resectable, (Stage III), non small cell lung carcinoma (NSCLC). A logical extension of the indication for the induction chemotherapy may be to treat earlier stage resectable lung cancers (stages I and II) because the cure rate of the resectable lung cancers still remains poor and is below 60% except for stage IA. Thirty eight patients with a diagnosis of loco-regional NSCLC were treated with paclitaxel combination chemotherapy. Following two courses of induction chemotherapy, patients underwent surgical therapy whenever possible. There were ten patients with stage I disease, four patients with stage II, 13 with stage IIIA, nine had stage IIIB, and two with stage IV. An overall response rate of 74% was observed. The response rate for 14 resectable patients (stage I and II) was 86%. The chemotherapy regimen was well tolerated and apart from one instance of anaphylaxis, no serious side effects were observed.

Adult↗
PubMed2000

Radiation induced chemotherapy sensitization in trimodality therapy of stage III non small cell lung cancer. A preliminary report.

The overall cure rate of locally advanced non-small cell lung carcinoma (NSCLC) remains poor. Although there have been encouraging reports of preoperative use of chemotherapy, more recent trend is the trimodal approach of radiation, chemo, and surgical-therapies. With the trimodal therapy, increased tumor response and resectability are reported, however, there are increased treatment related side effects. We observed that a relatively small dose of radiation given prior to induction chemotherapy greatly enhanced the tumor response to the chemotherapy without increased toxicity. A total of 18 patients (8 IIIA and 10 IIIB) were initially given 20 Gy of radiation therapy in 10 fractions and then received 2 courses of Taxol combination chemotherapy. The overall response rate was 83% (15/18) and 13 out of 18 patients underwent surgery. There was one postoperative death (not therapy related). It is speculated that the small dose of radiation therapy may have sensitized the tumor to subsequent chemotherapy, and we suggest a new hypothesis of "Radiation therapy induced chemotherapy sensitization".

Aged↗
PubMed1999

Primary tumors of the mediastinum.

BACKGROUND AND OBJECTIVES: Diagnostic and therapeutic approaches to mediastinal tumors have changed over the past three decades. We reviewed our recent experience with these tumors and assessed the role of a multidisciplinary treatment approach. METHODS: A retrospective review of 124 patients with primary mediastinal tumors over a 25-year period. RESULTS: Median age was 35 years. Symptoms were present in 86 of 124 (69%) patients. One hundred and eleven of 124 (90%) tumors were malignant. Distant metastases were present at diagnosis in 14 of 124 (11%) patients. The most common tumor was thymoma (38/124, 31%), followed by germ-cell tumor (29/124, 23%), lymphoma (24/124, 19%), and neurogenic tumors (15/124, 12%). Seventy-four of 124 (60%) patients underwent resection, 88 (71%) received chemotherapy, and 97 (78%) received radiation therapy. Tumor recurrence occurred in 52% (47/91) of patients who initially had a complete resection or response to treatment. Median time to recurrence was 10 months. Overall median survival was 44 months. Metastatic disease at presentation (P = 0.02) and tumor recurrence (P = 0.00001) were the only significant independent predictors of survival on multivariate analysis. CONCLUSIONS: Malignant primary mediastinal tumors often require multimodality treatment. Despite improvements in survival with multimodality treatment, death from recurrent disease remains a problem.

Adolescent↗
PubMed1999

Bronchogenic carcinoma in young patients.

BACKGROUND AND OBJECTIVES: Some investigators have suggested that lung cancer in young patients has a more aggressive course and poorer prognosis than lung cancer in older patients. METHODS: A retrospective review is presented of patients less than 40 years of age with bronchogenic carcinoma treated at Roswell Park Cancer Institute between 1984 and 1994, with comparison to a cohort of patients treated in the previous decade. RESULTS: There were 76 patients (41 male and 35 female). Mean age was 35 years (range, 26-39). Adenocarcinoma in 33 patients (43%) and undifferentiated large-cell carcinoma in 22 patients (29%) were the predominant histologic types. Stage IIIa or greater disease was present in 63 (83%) patients. Treatment consisted of chemotherapy (55 patients), radiation therapy (54 patients), and surgery (33 patients). Surgical procedures included pneumonectomy (14 patients), lobectomy (11 patients), wedge resection (1 patient), and thoracotomy only for unresectable disease (7 patients). Operative mortality was 6% (two patients who had radical pneumonectomy for T4 cancer). Median survival for the entire group of patients was 10.4 months, and 5-year survival was 8%. Univariate analysis identified acute presentation (P = 0.02), no resection (P = 0.0001), and higher stage (P = 0.0001) as negative prognostic factors. On multivariate analysis, stage of disease was the only independent predictor of survival (P = 0.005). Resectability was slightly higher (34%, 26/76, vs. 21%, 19/89; P = 0.06) and survival was marginally better (median 10.4 vs. 7.5 months; P = 0.05) than that seen at our institution in the previous decade. CONCLUSIONS: Young patients with lung cancer often have advanced disease at the time of presentation. Nevertheless, they should be treated in accordance with standard stage-specific treatment guidelines.

Adenocarcinoma↗