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J Shibata

Publications and source records attributed to J Shibata.

At least 19 recordsLinked to original sources
PubMed2003

Phase I clinical study of a novel lipophilic platinum complex (SM-11355) in patients with hepatocellular carcinoma refractory to cisplatin/lipiodol.

SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC). It is administered via the hepatic artery, using a carrier, lipiodol, that consists of ethyl esters of iodized poppy seed oil. We have performed a phase I clinical trial of an SM-11355-lipiodol formulation in 11 HCC patients, in order to investigate the maximum allowable dose and to maximize the efficacy and safety of the drug in the treatment of HCC. The SM-11355 arterial infusion suspension was administered at doses of 6, 12 and 20 mg ml(-1) in a maximum lipiodol volume of 6 ml. An antitumour efficacy rating of complete response was achieved for one patient and a partial response rating was achieved for a second patient, giving an overall response rate of 18.2%. Anorexia, nausea and vomiting, pyrexia, thrombocytopenia and increases in AST, ALT and total bilirubin were observed as adverse effects, but each was transient and each patient had recovered completely by 4 weeks after drug administration. Hence, we concluded that the maximum allowable dose was not reached in this study. Overall, our results suggest that SM-11355 is effective in treating HCC and we suggest that the dose for early phase II trials should be 20 mg ml(-1).

Adult↗
PubMed2001

A potential use of a synthetic retinoid TAC-101 as an orally active agent that blocks angiogenesis in liver metastases of human stomach cancer cells.

TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid) is a novel, synthetic retinoid that is effective against liver metastases of human gastrointestinal cancer cells such as the human stomach carcinoma line AZ-521 in animal models, and is currently in use in phase I cancer trials. However, the mechanism of its antimetastatic action is still poorly understood. Tumor metastasis depends on angiogenesis, and various retinoids have been found to exhibit antiangiogenic activity. Based on these findings we here examined the antiangiogenic effects of TAC-101. Oral administration of TAC-101 (2-8 mg/kg/day) resulted in a drastic suppression of the AZ-521 cell-induced angiogenesis in a mouse dorsal air sac assay system, compared to the vehicle alone. Immunohistochemical analysis with antibody against the endothelial marker CD31 revealed a significant reduction in microvessel density in liver metastases from animals treated with TAC-101 (8 mg/kg p.o.), compared to liver metastases from the untreated control animals. The ability of TAC-101 (8 mg/kg p.o.) to prevent experimental liver metastasis of AZ-521 cells in athymic nude mice was comparable with that of the known angiogenesis inhibitor TNP-470 (30 mg/kg s.c.). TAC-101 also affected angiogenesis in chorioallantoic membranes and some functions of endothelial cells associated with angiogenesis, whereas the retinoid failed to suppress AZ-521 cell proliferation directly. These data suggest that the TAC-101 is an orally active antiangiogenic agent and that this antiangiogenic property may contribute to its efficacy against liver metastasis of human stomach cancer cells.

Administration, Oral↗
PubMed2000

Estrogen agonistic/antagonistic effects of miproxifene phosphate (TAT-59)

PURPOSE: We evaluated miproxifene phosphate (TAT-59) to elucidate its efficacy in antiestrogen therapy for breast cancer patients and to assess its tissue-selective estrogenic/antiestrogenic activity. METHODS: Using DP-TAT-59, a major and active metabolite of TAT-59, an in vitro cell growth inhibition test was performed. Antitumor activity was determined using TAT-59 against human tumor xenografts of the MCF-7 and the Br-10 cell lines and MCF-7-derived tamoxifen-resistant cell lines, R-27 and FST-1. The antitumor activity of DP-TAT-59 and DM-DP-TAT-59, major metabolites of TAT-59 found in human blood following a TAT-59 dose, was also examined after intravenous administration to experimental animals. The residual estrogenic activity of TAT-59, evaluated in terms of bone and lipid metabolism in ovariectomized rats, was then compared with that of tamoxifen. RESULTS: DP-TAT-59 significantly inhibited the proliferation of estrogen receptor-positive MCF-7 and T-47D tumor cells in the presence of 1 nM estradiol. TAT-59, given to mice bearing MCF-7 or Br-10 xenografts, at the dose level of 5 mg/kg, exerted a significant growth inhibitory effect that was stronger than that of tamoxifen. Moreover, R-27 and FST-1 tumors, which show a resistance to tamoxifen, responded strongly to TAT-59, suggesting that TAT-59 might be effective against tumors resistant to tamoxifen. The metabolites of TAT-59, DP-TAT-59 and DM-DP-TAT-59, showed similar antitumor activity. Both TAT-59 and tamoxifen suppressed the decrease in bone density and reduced the blood cholesterol levels in ovariectomized rats, suggesting that the estrogenic activity of TAT-59 is comparable to that of tamoxifen. CONCLUSIONS: On the basis of the above results, one may expect TAT-59 to become an effective drug in patients with tumors less sensitive to tamoxifen, while its estrogenic activity as determined by bone and lipid metabolism is similar to that of tamoxifen.

Animals↗
PubMed2000

Papillary serous carcinoma of the peritoneum: analysis of clonality of peritoneal tumors.

Papillary serous carcinoma of the peritoneum (PSCP) is a primary neoplasm of peritoneal origin, and is histologically difficult to differentiate from papillary serous carcinoma of the ovary (PSCO). PSCP is frequently accompanied by many peritoneal tumors, and has been managed as a disseminated disease. In previous reports, however, the clonality of the tumors has not been fully discussed. Recently, the significant roles of the p53 and BRCA1 genes in PSCP have been reported. In this study, we investigated immunohistochemical staining for p53 proteins, and investigated p53 gene mutations, using DNA sequencing analysis, to clarify the clonality of PSCP tumors. Immunohistochemically, all the tumor samples demonstrated nuclear overexpression of p53 proteins, and the DNA sequencing analysis of the p53 gene showed diverse point mutations at codons 167 and 192 in two of four anatomically different tumors. In conclusion, the possibility of polyclonality of PSCP tumors is suggested.

Aged↗
PubMed2000

UFT and its metabolites inhibit cancer-induced angiogenesis. Via a VEGF-related pathway.

Treatment with UFT for spontaneous lung metastasis of murine renal carcinoma (RENCA) after resection of the primary tumor has resulted in significant prolongation of the life span of tumor-bearing animals. UFT inhibited the growth of metastatic nodules in the lung, apparently via decreased density of microvessels in the metastatic foci. Subsequent experiments used dorsal air sac assay to directly trace newly forming microvessels. UFT abrogated the process of angiogenesis, induced by the RENCA cells, in a dose-dependent manner. The inhibitory effect appeared to originate from tegafur, a component of UFT, and from its known metabolites: fluorouracil (5-FU), gamma-hydroxybutyric acid (GHB), and gamma-butyrolactone (GBL). The inhibition of angiogenesis by UFT appeared to be a common phenomenon, also observed in other human cancer cell lines characterized by an excessive production of vascular endothelial growth factor (VEGF)--such as gastric, lung, and colon cancers. In vitro analysis revealed that 5-FU and gamma-hydroxybutyric acid regulated VEGF-dependent responses of human umbilical vein endothelial cells. Dorsal air sac assay revealed that UFT, 5-FU, and gamma-hydroxybutyric acid strongly inhibited the angiogenesis induced by recombinant human VEGF. These data suggest that the antiangiogenic activity of UFT is at least partially associated with an ability of the metabolites of UFT to interfere with VEGF-dependent responses of vascular endothelial cells.

Air Sacs↗
PubMed1999

Characterization of the YbBa2Cu3O7-y and YBa2Cu3O7-y thin superconducting films prepared by chemical solution deposition on MgO(001) substrate.

Thin superconducting films of the YbBa2Cu3O7-y (Yb123) and YBa2Cu3O7-y (Y123), prepared by post-deposition annealing of the metal naphthenates gels spin-coated on MgO(001) substrate, have been characterized by cross-sectional high-resolution electron microscopy and X-ray diffraction. It was found that the c-axis Yb123 films were epitaxially grown on the MgO(001) substrate at the temperature range from 700 degrees C to 775 degrees C in a gas mixture containing Ar and O2 with the oxygen partial pressure of p(O2) = 10(-4) atm. In contrast to the Yb123 films, it was found that Y123 films could be derived at a wider temperature range from 750 degrees C to 950 degrees C. Randomly oriented Y123 films were also grown on the MgO(001) substrate besides the majority of in-plane c-axis oriented growth.

Barium↗
PubMed1999

TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid) inhibits spontaneous mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma.

The anti-tumor and anti-metastatic effects of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid (TAC-101) were investigated using our established lung cancer model. Orthotopic implantation of Lewis lung carcinoma (LLC) cells into the lung parenchyma produced a solitary tumor nodule in the lung followed by mediastinal lymph node metastasis. Daily oral administration of TAC-101 at doses ranging from 4 to 16 mg/kg resulted in a significant inhibition of lymphatic metastasis (inhibition rate=57 to 76%), while only the dose of 16 mg/kg significantly inhibited tumor growth at the implanted sites (inhibition rate=46%). Combined treatment with cis-diamminedichloroplatinum (CDDP) and TAC-101 (8 mg/kg, p.o., daily) enhanced the anti-tumor effect of CDDP (7 mg/kg, i.v., bolus) against both the growth of implanted tumor and lymphatic metastasis. In addition, this combined treatment significantly prolonged the survival time of LLC tumor-bearing mice as compared to treatment with each agent alone. The anti-activating protein-1 (AP-1) activity of TAC-101 caused inhibition of LLC cell invasion through the repression of expression of urokinase-type plasminogen activator and its receptor. The anti-invasive activity of TAC-101 may be involved in its in vivo anti-metastatic activity. These findings suggest that TAC-101 is a novel anti-cancer agent that may improve the therapeutic modalities for lung cancer patients with metastatic disease.

Angiogenesis Inhibitors↗
PubMed1999

Regulation of tumour necrosis factor (TNF) induced apoptosis by soluble TNF receptors in Helicobacter pylori infection.

BACKGROUND: Tumour necrosis factor (TNF) is a predominant cytokine produced in the gastric mucosa of patients with Helicobacter pylori infection. TNF induces apoptosis in a variety of cells. The soluble TNF receptors (sTNF-Rs) can be divided into sTNF-RI and sTNF-RII, both of which inhibit TNF activity. However, their precise mechanisms remain unclear. AIM: To investigate the role of sTNF-Rs in H pylori infection. METHODS: In 40 patients, production of TNF and sTNF-Rs in gastric mucosa was measured using biopsy specimens. In addition, in gastric epithelial cells, sTNF-R release in response to TNF and the protective effect of sTNF-Rs against the cytotoxic and apoptotic activities of TNF were examined. RESULTS: TNF and sTNF-R expression was significantly higher in H pylori positive than H pylori negative patients. TNF dose-dependently induced sTNF-RI release from gastric epithelial cells. sTNF-RII was also released from the cells. TNF decreased cell viability, but the effect was very small. A combination of anti-sTNF-RI and anti-sTNF-RII monoclonal antibodies significantly increased TNF induced cytotoxicity and apoptosis of gastric epithelial cells. CONCLUSIONS: These results show that sTNF-Rs are actively produced in H pylori infected gastric mucosa. sTNF-Rs appear to protect gastric epithelial cells from TNF induced apoptosis in H pylori infection.

Adult↗
PubMed1999

A case of intraabdominal bleeding following pancreatoduodenectomy successfully treated by transcatheter arterial embolization.

A 58-year-old male underwent pancreatoduodenectomy based on a diagnosis of middle bile duct cancer. Because abdominal drainage revealed bile leakage 5 days postoperatively, leakage at the site of cholangiojejunostomy was diagnosed, and continuous aspiration was performed. Seventeen days postoperatively, pus was discharged through the abdominal drain. Because bleeding was detected by abdominal drainage, and shock ensued 20 days postoperatively, emergency abdominal angiography was carried out to identify the bleeding site. A false aneurysm in the proper hepatic artery and extravasation from the gastroduodenal artery stump were recognized, and therefore, the proper hepatic artery and common hepatic artery were embolized at a site distal to the false aneurysm using microcoils. Celiac arteriography after transcatheter arterial embolization (TAE) did not show extravasation, and revealed blood flow from the right inferior phrenic artery to the liver. Liver function was normal after TAE, and the patient recovered and was discharged from the hospital 54 days postoperatively. This paper presents a patient in whom intraabdominal bleeding due to leakage at the site of cholangiojejunostomy complicated by infection was successfully treated by hemostasis with TAE.

Abdomen↗
PubMed1999

Inhibition of angiogenesis and intrahepatic growth of colon cancer by TAC-101.

We demonstrated in this study that inhibition of intra-hepatic growth of colon cancer by TAC-101 is mediated by inhibition of angiogenesis. In vitro experiments showed that TAC-101 inhibited the proliferation of murine hepatic sinusoidal endothelial (HSE) cells induced by coculture with murine colon 26-L5 (L5) cells. HSE cell proliferation was also enhanced by conditioned medium of L5 cells (CM-L5), and this enhancement of proliferation was abrogated by anti-vascular endothelial growth factor antibody. CM-L5 also induced in vitro tube formation of HSE cells on Matri-gel, and this activity of CM-L5 was abrogated by TAC-101 in a concentration-dependent manner. On the other hand, p.o. administration of TAC-101 inhibited tumor-induced angiogenesis in vivo and decreased the weights of L5 tumors in the mouse liver. Reverse transcriptase-PCR analysis using in vivo tumor tissue suggested that repression of vascular endothelial growth factor expression by TAC-101 was associated with the antiangiogenic activity. TAC-101 alone and 5-fluorouracil (5-FU)/D,L-leucovorin (LV) significantly inhibited the intrahepatic growth of L5 tumors (P = 0.002 and 0.001, respectively), whereas 5-FU alone did not (P = 0.088). When TAC-101 was administered with 5-FU/LV, marked enhancement of antitumor activity was observed (95% inhibition; P<0.001). This enhanced antitumor effect was also observed in experiments using Co-3 human colon adenocarcinoma. Concurrent treatment with TAC-101 and 5-FU/LV and sequential treatment with 5-FU/LV followed by TAC-101 resulted in significant augmentation of antitumor activity against Co-3 (overall P = 0.007 and 0.015, respectively). These findings indicate that TAC-101 inhibits tumor angiogenesis and suggest that it may be effective against hepatic metastasis of colon cancer.

Adenocarcinoma↗
PubMed1999

[Anti-metastatic and anti-angiogenic activity of UFT in a lung spontaneous metastasis model in mice].

We investigated the effect of UFT on a pulmonary metastasis after excision of the primary lesion, which was induced by implantation of murine renal carcinoma cells, RENCA. The cells were implanted into the left kidney of Balb/cA mice, and nephrectomy of the left kidney with a primary tumor was performed on day 10 after implantation. Administration of antitumor drugs, was started on day 13 [UFT (20 mg/kg, p.o., 5'-DFUR (24.6 mg/kg, p.o.), 5-FU (19 mg/kg, i.v.), TNP-470 (30 mg/kg, s.c.)]. In this metastasis model, the estimated mean survival time of the control group was 41.3 +/- 2.9 days. A significant life-prolonging effect was observed for UFT and 5-FU (T/C: 160.8%, 125.7%, respectively). An inhibitory effect on the growth of metastatic tumors in the lung was detected for both UFT and TNP-470 (TWI: 55.5%, 48.7%, respectively), but not 5'-DFUR. In a dorsal air sac (DAS) model, UFT abrogated angiogenesis induced by RENCA in a dose-dependent manner. These data suggest that the life-prolonging effect of UFT results from the continuous exposure of a tumor to its cytotoxic effects and anti-angiogenic activity.

Animals↗
PubMed1998

A case of atypical aortic coarctation with refractory congestive heart failure--treatment with axillo-iliac artery bypass.

Coarctation of the aorta is rare. We present a case of atypical coarctation due to aortitis syndrome with congestive heart failure refractory to conventional medical treatment. Although indications for surgical treatment are not well established and, in general, treatment of choice is an aorto-aortic bypass, we selected axillo-iliac bypass with subcutaneous tunnel because of severe heart failure. Postoperatively, the pressure gradient disappeared and heart failure was improved.

Aged↗
PubMed1998

TAC-101, a benzoic acid derivative, inhibits liver metastasis of human gastrointestinal cancer and prolongs the life-span.

We examined the anti-tumor effect of a novel benzoic acid derivative, TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid) on models with liver metastasis. Oral administration of TAC-101 significantly inhibited spontaneous liver metastasis of AZ-521 (human gastric cancer ) by orthotopic implantation to athymic nude mice. It also inhibited both the liver metastasis of AZ-521 induced by intrasplenic injection and the secondary lung metastasis from the liver. In addition, TAC-101 inhibited the proliferation of Co-3 (human colon adenocarcinoma) that formed a single nodule in the liver of athymic nude mice by intrahepatic implantation. The growth inhibitory effect of TAC-101 on AZ-521 experimental liver metastasis was observed when treatment was started on day 7, 14, or 21 which may correspond to the progressive stage of liver metastasis in clinical settings. Multiple administration of TAC-101 (8 mg/kg/day) significantly prolonged survival time of the animals with liver metastasis by intrasplenic injection of AZ-521 (T/C = 230%) and A549 (human lung adenocarcinoma; T/C = 186%). These effects of TAC-101 were stronger than those of 5-FU, CDDP or ATRA. Furthermore, TAC-101 inhibited the binding of AP-1 to DNA on electrophoretic mobility shift assay using nuclear extract of AZ-521 cells, although ATRA did not inhibit. These findings suggested that TAC-101 may be a candidate for a new class of anti-cancer agents for liver metastasis.

Adenocarcinoma↗
PubMed1998

[Antitumor activity of miproxifene phosphate (TAT-59) against human mammary carcinoma].

DP-TAT-59, an active metabolite of miproxifene phosphate (TAT-59), showed a strong anti-proliferating activity against ER-positive human mammary carcinoma cell lines, MCF-7 and T-47D, in the presence of 1 nM of estradiol. The ED50 value of DP-TAT-59 for each cell line was 30-fold lower than that of tamoxifen. TAT-59 suppressed the growth of mammary carcinoma, MCF-7 and Br-10, xenografted into nude mouse at a dose of 5 mg/kg/day, which is equivalent to 20 mg/body of daily dose to the patients. TAT-59 inhibited the growth of tamoxifen-resistant breast cancer cell lines, R-27 and FST-1, but not tamoxifen, suggesting the possible efficacy of TAT-59 for tamoxifen-refractory patients. DP-TAT-59 and DM-DP-TAT-59, major metabolites of TAT-59 detected in blood after oral administration in the patients, exhibited equal growth-inhibitory activity against human mammary tumor xenograft, meaning the antitumor activity of TAT-59 may equally depend on these two metabolites. In uterotrophic testing using both immature mice and ovariectomized rats, while the effective dose of TAT-59 was lower than that of tamoxifen, TAT-59 showed dose-dependent estrogenic activity against their uteri, similar to tamoxifen. These results suggested that TAT-59 had a stronger antagonistic activity against estrogen-dependent mammary tumor than tamoxifen. We expect that TAT-59 will become an effective therapeutic agent for patients with high estrogen levels in their blood, such as premenopausal women, and the patients with whom the tamoxifen modality failed.

Animals↗
PubMed1997

Antiestrogenic activity of DP-TAT-59, an active metabolite of TAT-59 against human breast cancer.

PURPOSE: The purpose of this study was to clarify the mechanism(s) of antiestrogenic action of DP-TAT-59 ((Z)-2-(4-(1-(4-hydroxyphenyl)-2-(4-isopropyl-phenyl)- 1-butenyl)phenoxy)-N,N-dimethylethylamine), the main active metabolite of TAT-59. METHODS: Using 4-OH-tamoxifen (a hydroxylated metabolite of tamoxifen) as a reference compound, we examined the relationship between hormone-dependent tumor cells and DP-TAT-59 and characterized estrogen receptor (ER) complexes with DP-TAT-59 using ion-exchange chromatography. RESULTS: DP-TAT-59 inhibited the in vitro proliferation of MCF-7 cells under serum-free conditions at a lower concentration than did 4-OH-tamoxifen. The conditioned medium (CM) obtained from the culture supernatant of MCF-7 cells in the presence of these antiestrogens suppressed the growth of ER-negative cell lines, but that from ER-negative human mammary carcinoma MX-1 cells did not. The CM from DP-TAT-59-treated cells showed a higher growth-inhibitory potency against human mammary carcinoma ZR-75-1 cells than did that from 4-OH-tamoxifen-treated cells. The growth-inhibitory potency of the CM was neutralized by the addition of the anti-TGF-beta antibody. The CM obtained from cells treated with DP-TAT-59 contained more TGF-beta and less TGF-alpha than that treated with 4-OH-tamoxifen. As the antiestrogenic activity of TAT-59 might be mediated through ER, the interaction of these antiestrogens with a cytoplasmic receptor of MCF-7 cells was examined. While the competitive binding of [3H]-estradiol with these antiestrogens to ER was similar, ER complexes with DP-TAT-59 showed a different elution profile by ion-exchange chromatography, indicating that DP-TAT-59 formed a different complex with ER from either 4-OH-tamoxifen or estradiol. CONCLUSION: These findings suggest that at least a part of the growth suppressive ability of DP-TAT-59 against human mammary carcinoma might depend on the production of growth inhibitory factors and/or the suppression of production of growth factors from ER-positive cells, and that the production of growth inhibitory factors might be stimulated by ER complexes with antiestrogens rather than with estrogen.

Binding, Competitive↗
PubMed1997

Three-dimensional helical computed tomography with intravenous cholangiography for sclerosing cholangitis manifested as postcholecystectomy symptom.

A 46-year-old woman who had upper abdominal pain 10 years after cholecystectomy, and who had incidental sclerosing cholangitis (SC), was investigated by three-dimensional helical computed tomographic (3-DHCT) cholangiography with contrast medium, because endoscopic retrograde cholangiography (ERC) was unsuccessful and a second ERC was not permitted by the patient. The cholangiogram demonstrated annular strictures of the bilateral hepatic duct at the confluence of the common hepatic duct, and dilatation of the left intrahepatic biliary duct. Although we could not clarify the cause of the biliary tract deformity at the time of the 3-DHCT, the tentative diagnosis of postcholecystectomy deformity of the biliary tree led to successful treatment by right liver lobectomy and hepaticojejunostomy. Histologic findings were compatible with SC. From this experience and the literature, we suggest that 3-DHCT cholangiography with contrast medium can contribute to the preoperative diagnosis of morphological changes in the biliary tree in patients with postcholecystectomy symptoms.

Cholangiography↗
PubMed1997

[Evaluation of ileocolon interposition after total gastrectomy].

The most serious complaints after total gastrectomy are alkaline esophagitis and postalimentary syndrome. We have performed ileocolon interposition as a gastric substitution which uses the ileocecal valve to prevent bile reflux. The ileocolon segment consists of 7 cm of terminal ileum and 10 cm of coecum and ascending colon on a vascular pedicle. This isolated segment is rotated upwards between the esophagus and the duodenum. To evaluate the function of the ileocolon as a gastric substitute, Barium X rays, O-GTT and gastric emptying time (99Tc EDTA) were examined. Barium X-rays showed that the air at the coecal portion looks like a gastric fornix and there is no barium reflux into the esophagus even in the supine position. Likewise, there were no complaints from patients of symptoms of reflux esophagitis. In case of Rouxen-Y reconstructions, blood sugar level after O-GTT show oxyhyperglycemia. Those in ileocolon interposition rose rapidly, but almost to the same degree as in normal subjects. The appearance of the gastric emptying curve using Tc-DTPA in case of ileocolon interposition shows that there is good reservoir function.

Colon↗