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Biomedical subjects

M Ohgaki

Publications and source records attributed to M Ohgaki.

At least 19 recordsLinked to original sources
PubMed2001

Manipulation of selective cell adhesion and growth by surface charges of electrically polarized hydroxyapatite.

Adherence of cells to a surface, such as a biomaterial surface, can be significantly influenced by the surface charge on that material. The applicability of electrically charged hydroxyapatite ceramics to selective cell adhesion was examined, and we show that polarized hydroxyapatite has significant effects on cell growth and adhesion. The surface charge applied to polarized hydroxyapatite promotes (i) enhanced colony formation of osteoblast-like cells, (ii) activation of gap junctions, and (iii) specific orienting of neuroblastoma cells. These findings will be of great utility and have significance in applications of tissue engineering, for example, in potential treatments for osteoporosis.

Cell Adhesion↗
PubMed2001

A new approach to enhancement of bone formation by electrically polarized hydroxyapatite.

An electrical field may affect osteogenesis. Since we found that hydroxyapatite (HA) ceramics may be polarizable, we hypothesized that electrically polarized HA may foster production of new bone in vivo. Both polarized and non-polarized HA ceramics were inserted into the subperiosteum spaces at the parietal bone area of rats. After 2, 4, and 8 weeks, the implant sites were examined histologically. Morphometric analysis revealed that new bone formation was accelerated on the negatively charged surface of the polarized HA (N-surface) at 2 weeks. The newly formed bone approached maturation at 4 weeks and was thicker on the N-surface than in the controls. By 8 weeks, newly formed bone in the controls was almost the same as that on the N-surface. These findings suggest that polarized HA is biocompatible and that bone formation on the N-surface is enhanced in the early stage of bone healing.

Animals↗
PubMed1997

Overexpression of bax enhances the radiation sensitivity in human breast cancer cells.

Bax-alpha, a splice variant of bax which promotes apoptosis, is expressed in many kinds of untransformed cell lines and breast tissue, whereas only weak or no expression could be detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weak bax gene expression, were stably transfected with pCX2neo bax, encoding human bax and neomycin-resistant genes, and two unique clones (MCF-7/bax-1 and MCF-7/bax-2) were thus generated which expressed different levels of bax-alpha. Sensitivity to ionizing radiation (IR) was examined and each was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax, and IR was found to induce intranucleosomal DNA fragmentation in stable transfectant but not in parent cells, thus suggesting that this sensitization is due to apoptosis. We suggest that exogenous bax-alpha expression might therefore be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may potentially have a therapeutic application by enhancing radiation sensitivity in breast cancer cells.

Apoptosis↗
PubMed1997

Endoscopic local injection of a new drug delivery formulation, anticancer drug bound to carbon particles, for digestive cancers: pilot study.

A new dosage formulation consisting of an anticancer drug bound to activated carbon particles was developed for the treatment of digestive cancer in patients in whom operation is contraindicated. The new formulation is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site compared to distribution of the drug in aqueous solution. In 12 patients with histologically proven carcinoma (7 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), an anticancer drug bound to carbon particles (total dose, 40-100 mg peplomycin or 250-500 mg methotrexate per person) was injected endoscopically into the primary lesions. Eleven of the 12 patients are currently alive, 12-64 months after therapy, or they died without evidence of cancer 12-98 months after the treatment. One patient has remained cancer-free for 32 months after a second course of the new formulation therapy given to treat a recurrence detected 26 months after the first treatment. Endoscopic injection of this new dosage formulation seems to control these digestive cancers in patients in whom operation is contraindicated.

Adenocarcinoma↗
PubMed1997

Selective delivery of 5-fluorouracil (5-FU) to i.p. tissues using 5-FU microspheres in rats.

A new formulation has been developed for the delivery of 5-fluorouracil (5-FU) in treating peritoneal carcinomatosis. The new formulation (5-FU-MS) involves the incorporation of 5-FU into microspheres composed of a poly(glycolide-co-lactide) matrix. The incorporated 5-FU is released slowly over a 3 week period. We investigated the drug distribution and pharmacokinetics of 5-FU in rats receiving an i.p. injection of 5-FU-MS or aqueous 5-FU solution. The concentration of 5-FU was higher in the i.p. tissues (omentum and mesentery) and lower in the extraperitoneal tissues (blood plasma, lung and heart) in rats given 5-FU-MS than in rats given the aqueous 5-FU solution. Pharmacokinetic analysis showed that the area under the curve (AUC) was significantly greater in the omentum and the mesentery than in other tissues of rats given 5-FU-MS. There was no significant difference in the AUC in the tissues of rats given the aqueous 5-FU solution.

Animals↗
PubMed1997

Selective drug delivery to peri-tumoral region and regional lymphatics by local injection of aclarubicin adsorbed on activated carbon particles in patients with breast cancer--a pilot study.

ACR-CH, which consists of aclarubicin (ACR) adsorbed onto activated carbon particles, was developed for locoregional chemotherapy for breast cancer. Thirty patients with breast cancer received an ACR (10 mg) injection intra- and peri-tumorally, either as ACR-CH or as ACR aqueous solution (ACR-AQ) 5 min before the operation for breast cancer. The ACR concentrations were significantly higher in the peritumoral regions and regional lymph nodes, and were also significantly lower in the blood plasma in patients given ACR-CH versus patients given ACR-AQ.

Aclarubicin↗
PubMed1997

Prevention of peritoneal metastasis of cancer with dextran sulfate--an experimental study in mice.

Peritoneal metastases occur most often in the greater omentum, where tumor implantation sites are densely distributed. We used dextran sulfate (S-Dex) as an anti-cell-adherence agent to prevent i.p. seeded malignant cells from causing peritoneal metastases. S-Dex was tested for its anti-adherent activity against B-16 melanoma cells on plastic, and was examined for its ability to prevent implantation in the omentum and to improve survival in mice after B-16 melanoma was inoculated i.p. S-Dex prevented B-16 melanoma cells from adhering to the plastic wall. S-Dex reduced the number of B-16 melanoma cells implanted into the greater omentum and improved the survival of mice inoculated with B-16 melanoma cells. We conclude that S-Dex attenuated peritoneal metastases when B-16 melanoma cells were seeded i.p.

Animals↗
PubMed1997

[Endoscopic local injection of anticancer drugs bound to carbon particles for treatment of upper digestive tract cancers--clinical trials].

A new dosage formulation consisting of anticancer drugs bound to carbon particles was developed for treating cancers of the upper digestive tract, and is designed to distribute higher levels of anticancer drug to the regional lymph nodes and at the injection site, as compared to a drug in aqueous solution form. Thirteen patients with histologically proven carcinoma (8 with superficial esophageal cancer and 5 with early or proper muscle layer-infiltrating gastric cancer), in whom surgical treatment was contraindicated, received intra- and peritumoral injection of the new dosage formulation (total dose of 35-100 mg of peplomycin or 250-500 mg of methotrexate) guided by esophago- or gastro-fiberscope. Eleven of these 13 patients are currently alive, 12-64 months after therapy, or they died without evidence of recurrence 12-98 months after the treatment. One patient has remained cancer-free for 37 months after a second course of the therapy given to treat a recurrence found 26 months after the first treatment. Another patient has a recurrent tumor 9 months after the therapy and is now going to undergo a second course of treatment. Side effects were not severe and well-tolerable.

Adenocarcinoma↗
PubMed1997

[Visualising lymph nodes by aclarubicin bound to activated carbon particles in breast cancer surgery].

A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine activated carbon particles, has been developed for the treatment of lymph node metastases in breast cancer. ACR-CH is designed to (a) adsorb a great amount of aclarubicin and desorb in a free state; (b) distribute a greater amount of ACR for a longer period of time selectively to the regional lymph nodes; (c) be decreased in the systemic toxicity; and (d) enhance its therapeutic effect on lymph node metastases. In this clinical trial in 20 patients with breast cancer, ACR-CH was injected intra- and peritumorally just before operation for breast cancer, and we examined the extent of blackened nodes produced by ACR-CH. ACR-CH blackened about 70% of the axillary lymph nodes with cancer metastasis as well as the nodes without metastasis. In conclusion, ACR-CH will be useful for dissection of lymph nodes by visualizing the nodes during operation for breast cancer.

Aclarubicin↗
PubMed1996

Methotrexate bound to carbon particles used for treating cancers with lymph node metastases in animal experiments and a clinical pilot study.

BACKGROUND: A new dosage formulation, methotrexate adsorbed onto activated carbon particles (MTX-CH), was developed for treating cancer patients with lymph node metastases. METHODS: MTX-CH injected subcutaneously into the left hind foot pad of rats delivered greater amounts of methotrexate selectively to the regional lymph nodes and to the injection site for longer periods than did the same dose of methotrexate in aqueous solution. Seven days after mice received a subcutaneous inoculation with 5 x 10(5) P388 leukemia cells in the left hind foot pad, when metastasis had occurred in the left popliteal lymph node, methotrexate was injected subcutaneously into the left hind foot pad in the form of either MTX-CH or methotrexate aqueous solution. In clinical trials, patients with cancers in relatively early stages (5 patients with gastric cancer and 1 with esophageal cancer) each received local injections of MTX-CH doses of 250 to 500 mg under fiberscope. RESULTS: MTX-CH extended the survival time better than did methotrexate aqueous solution. In mice who received an inoculation of P388 leukemia cells and drug treatment using the same procedures, the treatment effects on metastases to the regional lymph nodes were significantly greater in mice treated with the MTX-CH than in those given methotrexate aqueous solution. MTX-CH controlled the disease well for 25 to 35 months. CONCLUSIONS: Local injection of MTX-CH is apparently useful for treating digestive cancers with lymph node metastases in patients who have difficulty tolerating surgery.

Aged↗
PubMed1996

Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis.

Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy and ionizing radiation (IR). bax, which forms a heterodimer with bcl-2 and accelerates apoptosis, is not, or only weakly, expressed in most human breast cancer cells, and weak bax expression is considered to be related to the resistance of breast cancer cells to apoptosis. bax expression vector was introduced to human breast cancer MCF-7 cells, which exhibit weak expression of bax, to demonstrate its role of modulating radiation-induced apoptosis. bax overexpression in MCF-7 cells by stable transfection does not affect viability by itself, but each stable transfectant was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax. IR upregulated p53 and p21WAF1 about 5- to 10-fold and downregulated bcl-2 and bcl-XL by 80-90% at 6 hr in both parent and bax stably transfected MCF-7 cells to the same degree. FACS analysis and DNA electrophoresis revealed that this sensitization was due to apoptosis. We suggest that exogenous bax expression might be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may have therapeutic applications for enhancing radiation sensitivity in breast cancer cells.

Apoptosis↗
PubMed1996

Role of milky spots as selective implantation sites for malignant cells in peritoneal dissemination in mice.

We investigated the significance of milky spots for malignant cells in peritoneal dissemination using three mouse carcinomatous peritonitis models. P388 leukemia and Colon 26 cancer cells were labeled with bromodeoxyuridine (BrdU) and mice were inoculated intraperitoneally. After 24 h the greater omentum and the mesenterium were removed and stained immunohistochemically with anti-BrdU antibody. The labeled cells were found to have preferentially infiltrated into the milky spots in these specimens. Next, using B16 PC melanoma cells, which can be easily distinguished from the other cells by the intrinsic black melanin, the distribution of the melanoma cells was observed macro- and microscopically following intraperitoneal inoculation. The melanoma cells were similarly found to have selectively infiltrated into the milky spots in the omentum and mesenterium after 1 day. Moreover, the melanoma cells were growing and forming distinct metastic lesions within the milky spots 1 week later.

Animals↗
PubMed1996

Pharmacological effects of 5-fluorouracil microspheres on peritoneal carcinomatosis in animals.

A new delivery formulation (5FU-MS) of 5-fluorouracil (5FU), 5FU incorporated in microspheres composed of poly(glycolide-co-lactide) matrix, has been developed for the treatment of peritoneal carcinomatosis, and is designed to slowly release the incorporated 5FU for 3 weeks. Intraperitoneal 5FU-MS distributed higher concentrations of 5FU to the intraperitoneal tissues, such as the omentum and the mesentery, for a longer period with lower blood plasma concentrations than did the aqueous 5FU solution in rats. In experiments using mice, the lethal toxicity, determined by the probit method, in 5FU-MS was reduced to less than half that in aqueous 5FU solution. We evaluated the therapeutic effects on peritoneal carcinomatosis induced by the intraperitoneal inoculation of B-16 PC melanoma cells. The therapeutic effects of 5FU-MS were enhanced when compared with both the equivalent doses and same toxicity doses of the aqueous 5FU solution.

Animals↗
PubMed1996

Cisplatin microcrystals suspended in oil: pathological study of acute toxicity in mice.

The pathological changes brought about by the i.p. administration of a new dosage format, cisplatin microcrystals suspended in oil (CDDP-Oil), was examined in mice. CDDP-Oil decreased the absolute weight and the relative weight (organ weight/body weight) of the kidney, liver and spleen in the mice receiving the dosage form. However, the severity of the reduction of the organ weight in the CDDP-Oil administration groups was not different from that in the cisplatin aqueous solution (CDDP-Sol) administration groups. Histologically, severe degeneration and atrophy were recognized in the kidney, large intestine, small intestine, thymus, spleen, bone marrow and lymph nodes in the CDDP-Oil administration groups as well as CDDP-Sol administration groups. However, there were no additional changes in the macroscopic and microscopic findings in the CDDP-Oil groups. From these results, we concluded that this dosage form did not change the toxicity of cisplatin in terms of pathological effects.

Animals↗
PubMed1996

New formulation of 5-fluorouracil in microspheres reduces toxicity in mice.

A new dosage formulation of 5-fluorouracil incorporated in microspheres (5-FU-MS) was developed for the treatment of peritoneal carcinomatosis. We studied the acute toxicity and side effects of i.p. 5-FU-MS in mice. The 50% lethal dose value for 5-FU-MS was 535.4 mg/kg of 5-FU, which was 2.22 times that of the aqueous 5-FU solution. Deaths occurred 12-17 days after the administration of 5-FU-MS, but within 11 days after the administration of aqueous 5-FU. Thus, lethal toxicity appeared later with 5-FU-MS than with aqueous 5-FU. There were no differences in pathologic findings on autopsy between mice given the two dosage formulations.

Animals↗
PubMed1996

[Prophylaxis of peritoneal carcinomatosis with intraperitoneal administration of cell-adhesion inhibitor, in mice].

DSD was studied for its prophylactic effect against peritoneal carcinomatosis using B-16 melanoma cell line. In in vitro examinations, incubation in medium containing 0.2% DSD significantly inhibited B-16 melanoma cells from adhering both to the plastic wall and the injured peritoneum, as compared to incubation in normal medium. Upon in vivo examination, intraperitoneal administration of 0.2% of DSD (1 ml/mouse) diminished the cancer cell number implanted into the injured peritoneum more than intraperitoneal administration of DSD-free medium.

Animals↗
PubMed1995

Therapeutic effects of the angiogenesis inhibitor TNP-470 against carcinomatous peritonitis in mice.

The therapeutic effects of the new anti-angiogenesis factor TNP-470 were examined against carcinomatous peritonitis in mice. In the first experiment using carcinomatous peritonitis caused by i.p. inoculation of 10(6) M5076 tumor cells, TNP-470 solution was injected i.p. in a bolus of 50 mg/kg body weight into two groups of 10 mice either 1 or 8 days after the i.p. inoculation. The administration of TNP-470 on day 1 extended the survival time of the mice compared with 10 control mice receiving no treatment, whereas TNP-470 given on day 8 did not affect the survival time. In the next experiment on the M5076 tumor, TNP-470 solutions at 100 or 300 mg/kg were injected i.p. in a bolus into two groups of 20 mice 1 day after the inoculation 10(6) tumor cells, respectively. The administration of TNP-470 at 100 mg/kg also had an inhibitory effect. However, TNP-470 at 300 mg/kg caused toxic death in half of the mice. Next, we examined the effects of TNP-470 on another type of carcinomatous peritonitis model, which was caused by i.p. inoculation of 10(6) B16 melanoma cells. In this experiment, TNP-470 solutions in a bolus of 150 mg/kg were injected i.p. into six groups of 10 mice each on day 1 only (group 1), on days 1 and 4 (group 2), on days 1, 4 and 7 (group 3), on day 8 only (group 4), on days 8 and 11 (group 5), or on days 8, 11 and 14 (group 6), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗