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Biomedical subjects

A Hizuta

Publications and source records attributed to A Hizuta.

At least 55 records · Page 3Linked to original sources
PubMed1994

Synergistic effect of tumor necrosis factor-alpha and interferon-alpha on the induction of apoptosis detected by BM-1/JIMRO: a new marker of apoptosis.

The effects of the combination of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha) on the induction of apoptosis were investigated by immunohistochemical analysis with BM-1/JIMRO monoclonal antibody in RPMI 4788 tumor cells. Few tumor cells in the control culture could spontaneously undergo apoptosis. The number of positive cells increased at 2 and 4 h after treatment with nHuTNF-alpha (1 x 10(5) U/ml) and nHulFN-alpha (1 x 10(5) IU/ml). This effect was clearly maintained from 8 h up to 72 h of culture. The number of apoptotic cells also greatly increased with doses, suggesting that the apoptosis induced by nHuTNF-alpha and nHuIFN-alpha in combination was dose-dependent. nHuTNF-alpha or nHuIFN-alpha alone could induce apoptosis, but the induction increased significantly when the two cytokines were combined. These findings indicate that by combining nHuTNF-alpha and nHuIFN-alpha apoptosis can be synergistically induced in RPMI 4788 tumor cells, and may have specific therapeutic implications for clinical treatments using these two cytokines.

Antibodies, Monoclonal↗
PubMed1994

Ovarian metastasis in patients with colorectal carcinoma.

The records of 159 patients who underwent surgical resection of colorectal cancer were reviewed to assess the incidence of ovarian metastasis and to define the role of oophorectomy. Four of these patients presented with metachronous metastases, and one patient had synchronous ovarian involvement. The incidence of ovarian involvement was higher in younger patients. While most patients with ovarian involvement had the primary tumor located at the rectosigmoid region, a similar distribution of the primary tumor was observed in patients without ovarian metastasis. The histological type and degree of differentiation was similar regardless of whether or not ovarian metastasis was present. Of the patient without ovarian metastasis, 57% presented with nodal metastases and 3.2% with peritoneal dissemination, while all patients with ovarian metastasis had nodal and peritoneal involvement. Our results suggest that histological type and degree of differentiation of the primary tumor do not influence likelihood of ovarian metastasis. However, the exposure of the tumor to the serosal surface and the subsequent peritoneal dissemination may be an important route by which malignant tumor cells reach the ovaries. However, due to the wide lymphatic involvement in patients with ovarian metastasis, the lymphatic route may be important as well. Thus, we consider that oophorectomy should be performed in all postmenopausal women, when the ovaries are macroscopically affected, and in premenopausal patients with Astler-Coller B2 tumors or over.

Adult↗
PubMed1994

Synchronous colorectal carcinomas.

Eighteen (5.0%) out of 358 patients who underwent resection of a colorectal carcinoma during the period 1978 through 1990 had synchronous colorectal carcinomas, and were 5.6 years younger on average than those with a single carcinoma. The distance between synchronous lesions was less than 10 cm in 69.6% of all the patients in the study. Among the synchronous carcinomas there was a higher incidence of ascending colon involvement, mucinous carcinoma, family history of malignant diseases, multiple malignant neoplasms associated with other organs and benign neoplastic polyps of the colorectum, and it is suggested that hereditary oncogenic factors influence these carcinomas. The synchronous lesions were detected pre-operatively in 14 of 18 patients with synchronous carcinomas, and the most common reason why synchronous lesions were missed was that the lesions on the anal side prevented the lesions on the proximal side from being examined. The prognosis in the synchronous lesion group was worse than in the solitary lesion group. Since it is difficult to predict synchronous colorectal carcinomas, careful pre-operative examination, including that of other organs, is necessary, and intra-operative colonoscopy should be carried out when pre-operative examination was insufficient.

Adenocarcinoma↗
PubMed1993

Hyperthermotherapy for postoperative local recurrences of rectal cancer.

Between November 1984 and August 1992 we used hyperthermotherapy in six cases of local recurrence of rectal cancer. Hyperthermotherapy was performed on the average 8.7 times (range: 3-18) for each patient for 60 min each. All patients underwent combined radiotherapy and received a mean radiation dose of 42.5 Gy (range: 9-60 Gy). Five patients underwent heating within 1 h after irradiation and one patient simultaneously with the irradiation. Four patients underwent combined chemotherapy and two patients immunotherapy. Before the treatment all patients had painful lesions, but pain decreased posttherapeutically in five patients. Performance status improved in two patients. High carcinoembryonic antigen levels prior to the therapy in four patients decreased in all cases after treatment. Posttherapeutical computed tomograms revealed only minor response or no changes. After the treatment, four patients died of exacerbations of recurrent tumors and one patient of distant metastases. The patient who underwent simultaneous radiohyperthermotherapy is presently alive, in August 1992, 38 months after initiation of the treatment. The 50% survival time after initiation of the treatment was 25 months (range: 10-38 months). Hyperthermotherapy combined with radiotherapy, chemotherapy and/or immunotherapy was useful for the alleviation of pain in patients who developed local recurrence after surgery, and improved survival after recurrences can be expected.

Adult↗
PubMed1993

Therapeutic effect of neuraminidase-treated LAK cells on liver metastasis of Colon 26.

To improve the lymphokine-activated killer (LAK) cell therapy for liver metastasis, two methods which enhance accumulation of LAK cells in the liver were examined for their effects on the liver metastasis of Colon 26 cancer cells in BALB/c mice. Distribution of LAK cells in the mice was examined by the 51Cr labeling method. Portal vein infusion of LAK cells or tail vein infusion of neuraminidase treated-LAK (N-LAK) cells showed an augmented accumulation of infused cells in the liver. In the first experiment, LAK cells (5 x 10(7) cells) were infused in the portal vein or tail vein at days 3 and 7 after the inoculation of 5 x 10(4) tumor cells and 1 x 10(4) units of IL-2 were given three times a day from day 3 to day 7. The portal infusion of LAK cells produced a greater reduction of liver metastases compared with the peripheral infusion. In the second experiment, 5 x 10(7) LAK cells or N-LAK cells were infused via the tail vein on days 1 and 3, and 1 x 10(4) units of IL-2 were given once a day from day 1 to day 5 after the inoculation of 1 x 10(4) tumor cells. The therapeutic effect of N-LAK cells was greater than non-treated LAK cells on the number of metastatic lesions and the survival time of mice. Since access to the human portal vein is difficult and risky in clinical situation, peripheral infusion of N-LAK cells is preferable.

Adenocarcinoma↗
PubMed1993

Inhibition of liver regeneration in mice following extended hepatectomy by transfusion of lymphokine activated killer cells.

Lymphokine activated killer (LAK) cells can destroy not only tumor cells but also syngeneic liver cells. In this study, the effects of passive transfer of LAK cells on liver regeneration were examined by the 3H-thymidine uptake and bromodeoxyuridine (BrdU) labeling methods after resection of 70% of the volume of the liver. LAK cells were infused 12h after hepatectomy and the effects on regeneration of liver cells were examined 36 h later. The transfusion of LAK cells induced significant inhibition of liver regeneration at a dose of 5-10 x 10(7) cells. Neuraminidase treatment of lymphocytes is desirable to enhance the selective entrapment of LAK cells into the liver. When LAK cells were treated with neuraminidase (0.5 units/ml), and transfused into hepatectomized mice, more potent suppression of liver regeneration was induced in comparison with the same dose of LAK cells. The intraperitoneal injection of recombinant interleukin 2 (rIL-2) after partial hepatectomy also inhibited the regeneration of remnant liver. From these results, lymphocytes such as LAK cells appear to regulate liver regeneration.

Animals↗
PubMed1993

[In vivo comparative study of the pharmacokinetics of chemotherapeutic agents infused via hepatic artery or portal vein against hepatic metastases. DRC Group].

Recently, the treatment for hepatic metastasis has been performed by injection of chemotherapeutic agents via hepatic artery. Although this therapeutic procedure has been contributing to a relatively higher response rate, the resulting increased response has not significantly improved prognosis. So, we assessed the infusion of chemotherapeutic agents via portal vein in rabbits and compared the results with those from arterial infusion. Two weeks after inoculation of VX-2 tumor cells into the liver, subcapsularly, injection of chemotherapeutic agents as well as sampling of the livers was started. The rabbits were allocated into two groups, an arterial infusion group and a portal vein infusion group. They received a single shot of mitomycin C (MMC, 1.7 mg/kg), or 5-fluorouracil (5-FU, 9.5 mg/kg) or cisplatin (CDDP, 1.6 mg/kg) injected by infusion pump for 1 h. The drug concentration into the normal liver and intratumorally was measured by HPLC method for 5-FU and MMC, and by flameless atomic absorption spectrometry for CDDP. Either drug concentration in the liver or tumor did not substantially differ between the two groups. This experiment revealed that portal vein infusion can contribute as much drug concentration intratumorally as by arterial infusion.

Animals↗
PubMed1992

Outcome in patients with early colorectal carcinoma.

Twenty-four patients seen between 1978 and 1990 with early colorectal carcinoma were reviewed to determine the outcome of surgical treatment. The mean age was 62 (range 35-79) years; there were 16 men and eight women. The site of the tumour was the ascending colon in two patients, sigmoid colon in ten and rectum in 12. The polypoid and flat-elevated ulcerated (IIa+IIc) subtypes were detected in 14 and nine lesions respectively. Restorative colectomy was carried out in 19 patients, and five required Mile's operation. There were no postoperative complications or deaths at a mean follow-up of 71 (range 12-151) months. Neither recurrence nor distant metastasis was found during follow-up. There was a close relationship between the depth of submucosal invasion and presence of flat-elevated ulcerated subtype lesions with lymphatic infiltration. This association may play an important role in the mechanism of metastasis. Major surgical resection is probably required if longer disease-free intervals and better cure rates are desired.

Adult↗
PubMed1992

Flow cytometric analysis on perforin induction in peripheral blood mononuclear cells with interleukin-2 or OK-432.

Perforin is a protein present in the cytoplasmic granules of killer cells and is considered to be an important effector molecule. We assessed the perforin appearance via flow cytometry in human peripheral blood mononuclear cells stimulated in vitro for 3 days by recombinant interleukin-2 (rIL-2) or OK-432, a biological response modifier. The relationship between the lymphocyte subsets and perforin was investigated via two-color assay. CD4-positive cells had almost no perforin, and most of the CD16-positive cells did. Regarding the relationship with CD8, some of the bright positive cells (which were likely T cells) and most of the dull positive cells (likely NK cells) had perforin. Mean fluorescence was greatest in perforin-positive cells incubated with rIL-2, less in cells incubated with OK-432, and minimal in cells incubated in a medium without additives. Immunohistochemical staining with antiperforin antibody revealed that blast-transformed and enlarge cells were stained positively and that the intensity of staining of each cell alone was enhanced in cells incubated with OK-432 or rIL-2. If the fluorescence intensity of perforin-positive cells correlates with the amount of perforin in those cells, then the appearance of perforin was enhanced with OK-432, more enhanced with rIL-2, and consistent for cytotoxicity against K562 and Daudi cells. IL-2 was induced by OK-432, suggesting that the indirect effect of this IL-2 may play a role in OK-432-perforin induction. The results suggest that perforin may be an effector molecule in killer cells induced by rIL-2 or OK-432.

Cytotoxicity, Immunologic↗
PubMed1992

Inhibitory effect of nafamostat mesilate on metastasis into the livers of mice and on invasion of the extracellular matrix by cancer cells.

Although many agents that interfere with clotting mechanisms have been investigated for their potential to inhibit metastasis, their toxicity has prevented administration of sufficiently high doses to achieve inhibition of metastasis in clinical trials. Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, inhibited liver metastasis in a CDF1 mice model with colon 26 adenocarcinoma cells. The apparently dose-dependent inhibitory effect was seen 21 days after all of the doses tested (0.3, 1.0, 3.0 and 10.0 mg/kg for 7 days) but the effect was only statistically significant (P less than 0.01) at the highest dose. The blood concentrations 3 min after dosing were less than 10(-6) M for all of the doses tested. At a concentration of 10(-5) M or less nafamostat mesilate was not cytotoxic towards colon 26 cells in vitro. The results indicate that it may not be difficult to achieve blood nafamostat mesilate concentrations that inhibit metastasis in mouse liver. Possible mechanisms of nafamostat mesilate are inhibition of extravasation and invasion of cancer cells, inactivation of collagenase due to inhibition of plasmin activity and inhibition of the formation of the cancer cell thrombus, and arrest in the capillaries through inhibition of thrombin activity. These preliminary results suggest that peri-operative administration of nafamostat mesilate may prevent metastasis into the liver after surgery for gastrointestinal malignancies.

Adenocarcinoma↗
PubMed1992

Assessment of lymph node metastasis and vessel invasion in early rectal cancer.

Thirteen patients with rectal carcinoma seen between December 1980 and December 1990 have been reviewed to determine the risk of lymph node metastasis and its implication for subsequent treatment. The mean age was 64 years (from 38 to 79; 9 males, 4 females). The site of the tumor was predominantly in the lower rectum (53.8 percent). The polypoid (I) and flat-elevated ulcerated (IIa + IIc) subtypes were detected in seven and six lesions, respectively. Sphincter-saving techniques were carried out in eight cases, and five cases required Miles' operation. Neither postoperative complications nor deaths were noted. The mean follow-up period was 57 months (6 to 133 months). No recurrence or distant metastasis was found during this follow-up. IIa + IIc subtype lesions with deep submucosal invasion at or beyond Smlc level were closely related with lymphatic and vascular invasion. Although this association was not necessarily accompanied by an increased number of involved lymph nodes, major surgical resection is suggested in such IIa + IIc cases due to an increased possibility for lymph node metastasis.

Adult↗
PubMed1992

Can cytokines prolong survival in ampullary neuroendocrine carcinomas?

Herein we report the case of an ampullary tumor in a 53-yr-old Japanese woman who presented in March 1988 with abdominal pain, weight loss, and jaundice. A pancreatoduodenectomy was carried out, and 3 months later, she presented with a Virchow's node. She was initially treated with cytokines plus 5-fluorouracil derivative, resulting in a complete remission lasting over a year. However, in July 1990, the Virchow's node reappeared and was surgically excised. Histology revealed a small-cell neuroendocrine carcinoma (SCNC) similar to the prior ampullary tumor, which was confirmed by immunohistochemical studies and electron microscopic examination. The patient was discharged within 1 month, remaining disease-free over a 18-month period following excision. We suggest that the use of cytokines can be effective, and can increase survival in gastrointestinal neuroendocrine tumors.

Ampulla of Vater↗
PubMed1992

[Antitumor effect of pirarubicin (THP) against human colon cancer transplanted into nude mice and the mechanism of cell cycle progression].

Pirarubicin (THP) is a derivative of adriamycin (ADM) which has been reported to have a lower cardiotoxicity than ADM. The authors investigated the in vivo antitumor effect of THP against human colon cancer cells (RPMI 4788) xenografted into nude mice. In the model of intra-abdominal carcinomatosis, intraperitoneal administration of THP (6 mg/kg) resulted in a significant prolongation of the survival compared with the saline control group (p less than 0.01). Intravenous administration of THP (8 mg/kg) significantly inhibited tumor growth compared with the saline control group. Labeling index with bromodeoxyuridine (BrdU) of RPMI 4788 tumors treated with THP was smaller than that in the control group. Mitotic index was also smaller in the group treated with THP. Labeling index with BrdU indicates the proportion of cells in the S phase. Thus, the tumor cells in both S and M phases have decreased after treatment with THP. This change in the cell cycle progression may be due to the accumulation of G2 phase similar to in vitro study. From these results, it was suggested that the change in cell cycle progression revealed in vitro might be caused by THP in vivo.

Animals↗
PubMed1991

[Effect of UFT by oral administration using a murine hepatic metastasis model].

We examined the antitumor effect of UFT, a 5-FU derivative using a hepatic metastasis model in mice. BALB/c and CDF1 mice were given orally UFT (30 mg/kg, 50 mg/kg daily or 120 mg/kg every other day) for 20 days after inoculation of colon-26 tumor cells into the portal vein. The number of metastatic nodules and the weight of the liver decreased significantly in all groups of UFT treatment. The therapeutic effect with 50 mg/kg UFT was better than those with the other doses. NK and LAK activities of spleen cells obtained from UFT-treated tumor bearing mice were not significantly different from the untreated control. IL-1 and IL-2 production of the spleen cells were also not significantly changed by the treatment with UFT. These results suggested that the oral administration of UFT represents an antitumor effect against hepatic metastasis in mice without sever suppression of the host immune system.

Administration, Oral↗
PubMed1988

[Augmentation of murine organ-associated natural immune responses by cepharanthin].

Oral administration of cepharanthin (bisbenzylisoquinoline alkaloid) to mice was effective in the organ-associated immune responses. Cepharanthin, as a biological response modifier (BRM), augmented natural killer (NK) activity of leukocytes isolated from the spleen, lymph node, lung, and liver. The degree of NK augmentation was almost the same in these organs without lymph node, and reached to the maximum levels 3 days after cepharanthin administration. In addition, adherent leukocytes (greater than 95% macrophages) isolated from the lung or liver following cepharanthin administration also exhibited an augmented macrophage-mediated cytotoxicity. These results suggest that such organ-associated immune responses may play an important role in the antitumor and/or antimetastatic effects mediated by cepharanthin.

Administration, Oral↗
PubMed1988

[Local administration of recombinant interferon-beta to patients with cancer-associated body cavity fluids].

The effects of local administration of interferon-beta produced by recombinant DNA technology (GKT-beta, Kyowa Hakko) on malignant effusion were studied in cancer patients and evaluated on the basis of the Criteria for the Evaluation of the Clinical Effects of Solid Cancer Chemotherapy (effects on malignant effusion). Out of 13 cases of peritoneal effusion, the effects were evaluated in 9 cases. Four of these cases remained free from ascites for 4 weeks and were evaluated as complete response (CR). Administration of GKT-beta alone was performed in 4 of 7 cases of pleural effusion, and CR was obtained in 1 case each of breast cancer, gastric cancer and malignant mesothelioma. In cases of gastric cancer, CR was obtained in 5 of 10 cases. The above results suggest that GKT-beta is a very effective drug against malignant effusion.

Aged↗