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Biomedical subjects

A Hizuta

Publications and source records attributed to A Hizuta.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effect of low dose cyclophosphamide on the synthesis of acute phase protein and its significance for cancer chemotherapy.

Patients with far advanced colorectal cancers received chemotherapy consisting of low-dose cyclophosphamide (LDCY) 333 mg/m2 every four weeks intravenously and by oral administration of 5'-DFUR (a masked compound of 5-Fluorouracil). Serum levels of immunosuppressive acidic protein (IAP), an acute phase protein, were measured every four weeks for a total of thirty-one LDCY trials of ten patients. LDCY chemotherapy significantly decreased the IAP levels in cancer patients with high IAP levels. These results suggested that LDCY chemotherapy could counteract host responses against tumors and could have decreased immunosuppressive responses in cancer patients.

Acute-Phase Proteins↗
PubMed1996

Enhancement of experimental metastasis by gamma-interferon in a murine adenocarcinoma.

This study was conducted to examine the effect of gamma-interferon (IFN-gamma) on experimental metastasis formation by murine colon 26 adenocarcinoma in BALB/c mice. We found that the number of experimental lung metastases was increased after colon 26 cells were pretreated for 1 h with as little as 1 OIU/ml of IFN-gamma. 5-[125I] iodo-2'-deoxyuridine-radiolabeled colon 26 cells pretreated with IFN-gamma remained at higher level in the lung at 24h after intravenous injection than when the cells were not pretreated. In vivo elimination of asialo GM1-positive cells increased the number of lung metastases and, in such mice, there was no longer a difference in metastatic ability between control and IFN-gamma-treated cells. Colon 26 cells were completely resistant to lysis by isolated splenocytes. Splenocytes incubated in vitro with interleukin 2 exhibited moderate cytotoxicity against colon 26 cells, but there were no significant differences between control and IFN-gamma-treated cells. Colon 26 cells pretreated with IFN-gamma demonstrated resistance to tumor necrosis factor alpha-mediated growth inhibition. The enhancement of metastases by IFN-gamma was dependent on de novo protein synthesis since the enhancement was abolished by cycloheximide. Taken together, the data suggest that the metastatic ability of colon 26 cells pretreated with IFN-gamma is significantly higher due to the resistance to asialo GM1-positive cells accompanied with de novo protein synthesis.

Adenocarcinoma↗
PubMed1996

Cytokine production-suppressive effect by macrophage colony-stimulating factor (M-CSF).

Macrophage colony-stimulating factor (M-CSF) is a protein which is necessary for proliferation and differentiation of monocyte-macrophage precursor cells. We examined the effect of M-CSF on the cytokine production using BCG sensitized mice in vivo. On Day 0, BCG 1 mg/mouse was injected via the tail vein. Starting from Day 2, M-CSF 30 mu g/mouse (1 X 10(8) U/mg) was injected every 2 days for a total of six times (Day 2, 4, 6, 8, 10 and 12). On Day 14. LPS 25 mu g/mouse was injected via the tail vein, and Interferon (IFN)/Tumor necrosis factor-alpha (TNF-alpha) in serum were determined. The productions of IFN and TNF-alpha were suppressed significantly. These cytokine production-suppressive effects of M-CSF were found also in the in vitro experimental system using spleen cells collected. On Day 14, spleen cells were collected and adjusted to 5 X 10(6) cells/ml. 20 micro-grams of LPS was added to 2ml of spleen cells and they were incubated in a C02 incubator for 24 hours. IFN and TNF-alpha in the supernatant were determined. In the experiment using nude mice, the cytokine suppressive effect of M-CSF was not observed. MLR test was performed with spleen cells of C57BL/6 treated with M-CSF as the responder cells, and spleen cells of C3H were treated with mitomycin C as the stimulator cells. MLR was suppressed significantly by administration of M-CSF. These results might possibly reflect the actual effect of M-CSF in the living body, and the T-cell and cellular immunity might be concerned with the mechanism of the cytokine production-suppressive effect of M-CSF.

Animals↗
PubMed1995

Localization of T cell receptor (TCR)-gamma delta + T cells into human colorectal cancer: flow cytometric analysis of TCR-gamma delta expression in tumour-infiltrating lymphocytes.

We analysed TCR-gamma delta expression in tumour-infiltrating lymphocytes (TIL) obtained from 13 patients with colorectal cancer and simultaneously isolated the T lymphocytes from normal intestinal tissue (IL) to compare the frequencies of TCR-gamma delta expression in TIL, IL, and peripheral blood lymphocytes (PBL) in the same patient. Flow cytometric analysis showed that the frequency of TCR-gamma delta expression in TIL (2.75 +/- 1.84%) was significantly lower than that in IL (15.28 +/- 9.45%, P < 0.01). However, a larger quantity of TIL was separated than IL per unit weight of specimen, so the total number of gamma delta T cells obtained per unit weight was not different between tumour tissue and normal intestine. In addition, phenotypic analysis revealed that about half of the TCR-gamma delta + TIL were CD8+ (CD4+, 3.0 +/- 3.1%; CD8+, 54.7 +/- 19.9%, mean +/- s.d. of five patients), and a very similar result was obtained in TCR-gamma delta + IL (CD4+, 2.7 +/- 2.4%; CD8+, 53.1 +/- 17.4%). In contrast, most TCR-gamma delta + PBL were double-negative (CD4+, 3.2 +/- 3.0%; CD8+, 20.6 +/- 7.4%). These results indicated that TCR-gamma delta + CD8+ T cells selectively and consistently localized in colorectal tumour tissue, similarly to normal intestinal epithelium.

Aged↗
PubMed1995

Surgical treatment for Crohn's disease.

The medical records of 16 consecutive patients with Crohn's disease surgically treated in our department from 1978 to 1993 were retrospectively reviewed. The indication for surgery was obstructive symptoms due to Crohn's strictures that were unresponsive to conservative therapy. The types of operations performed were classified into five categories. Nine patients (56.3%) had small bowel resection only, 4 (25.0%) underwent an ileocolonic resection, 1 (6.3%) had a total colectomy, 1 (6.3%) had Mile's operation and 1 (6.3%) had subtotal gastrectomy with gastrojejunostomy and antral mucosectomy. Of these 16 patients, 13 (81.3%) had resection with a single anastomosis and strictureplasty was concomitantly performed in only 2 cases (12.5%). Crohn's disease recurred in 3 patients (18.8%), 1 of whom required a second operation.

Adult↗
PubMed1995

Combined therapy with interleukin 2 and indomethacin in mice inoculated with MH134 hepatoma.

The antitumor effects of indomethacin and interleukin 2 (IL-2) were studied in C3H/HeJ mice inoculated with MH134 hepatoma cells. Combined treatment with indomethacin and IL-2 augmented natural killer (NK) cells in mice with MH134-induced peritoneal carcinomatosis, and the survival of the treated mice was significantly longer than the non-treated mice. In animals with subcutaneous MH134 tumors, the combined therapy with indomethacin and IL-2 significantly suppressed tumor growth and induced complete regression of the tumor in three out of five mice. These results suggest that indomethacin and IL-2 therapy could be effective on human gastrointestinal cancer cells as well.

Animals↗
PubMed1995

Decreased serum tryptophan in patients with cancer cachexia correlates with increased serum neopterin.

We investigated serum tryptophan (Trp), neopterin (NPT) and immunosuppressive acidic protein (IAP), one of tumor-associated tumor marker, concentrations in 28 patients with gastrointestinal tumors representing cancer cachexia and 10 healthy controls. NPT comes from activated macrophages presumably activated by tumor-sensitized T cells via gamma-interferon (IFN-gamma) excitation of the macrophages. We found that the NPT level was significantly higher than the control value. The negative correlation of NPT and Trp concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO), a Trp degradating enzyme, in cancer-burden patients. The activity of IDO can be induced by cytokines such as IFN-gamma, and therefore low Trp levels may result from endogenous IFN-gamma production due to immune activation against tumors. We also found a positive correlation between NPT and IAP levels, suggesting that host immune activation against tumors played a role in the immunosuppression of cancer-burden states, followed by cancer-cachexia.

Adult↗
PubMed1995

Plasma neopterin/C-reactive protein ratio as an adjunct to the assessment of infection and cancer cachexia.

Neopterin (NPT), a pteridine intermediate metabolite in the biopterine synthetic pathway, is synthesized and secreted by monocytes/macrophages upon stimulation, mainly by gamma-interferon produced by activated T cells. C-reactive protein (CRP) is one of the major acute-phase reactants and its release is thought to be mediated by interleukin-6. Plasma concentrations of NPT and CRP were synchronously analyzed in 25 determinations of 5 patients with severe infectious complications and 50 determinations of 10 cancer-burden patients representing cachexia. The mean value of NPT (pmol/ml) was 201.6 in the infection group and 16.5 in the cancer cachexia group. The mean value of CRP (mg/dl) was 12.5 in the infection group and 3.4 in the cancer cachexia group. The number of samples in which NPT alone exceeded the cut-off level were 0/25 (0%) in the infection group and 38/50 (76.0%) in the cancer cachexia group. The number of samples in which both NPT and CRP exceeded the cut-off level was 25/25 (100%) in the infection group and 12/50 (24.0%) in the cancer cachexia group. The mean ratio of NPT to CRP was 11.3 in the infection group and 30.7 in the cancer cachexia group, respectively. These results suggest that gamma-interferon could play the principal role in the pathogenesis of cancer cachexia and that interleukin-6 modified the disease status. Interleukin-6 would be the critical mediator of host responses in infectious complications.

Aged↗
PubMed1995

Endogenous gamma-interferon activates thymidine phosphorylase in colorectal cancer tissue.

We measured neopterin (NPT), an indirect marker of gamma (gamma)-interferon, and the activity of thymidine phosphorylase (dThdPase) in the advancing front of colorectal carcinoma and in normal mucosa. Cancer showed a higher concentration of NPT than normal mucosa and also showed significantly higher (p < 0.0001) dThdPase activity than normal mucosa. There was a strong correlation between NPT concentration and dThdPase activity in cancerous and normal mucosa. These results suggest that endogenous gamma-interferon could activate dThdPase activity, which is essential to nucleic acid metabolism because it regulates the availability of thymidine.

Adenocarcinoma↗
PubMed1995

Role of endotoxin in wound healing impairment.

We studied the effect of endotoxin on cutaneous wound healing and the mechanism involved. Rats underwent dorsal skin incision and subcutaneous placement of plastic nylon wound chambers. Immediately after this procedure, lipopolysaccharide (LPS) was administered intraperitoneally at doses of 1 to 10 mg/kg. In the rats given LPS at doses of 3 mg/kg or higher, the wound breaking strength and the production of hydroxyproline in the wound chambers were significantly reduced in a dose-dependent manner. The wound fluid serially collected from the wound chambers after surgery was examined for the effect on the growth of fibroblast. While the wound fluid from control rats showed a marked fibroblast growth-accelerating activity on postoperative day 7, this activity in the wound fluid from LPS-treated rats was significantly decreased. In the wound fluid from LPS-treated rats, the fibroblast growth-accelerating activity recovered to the control level by the addition of anti-TNF-alpha neutralizing antibody. These results suggested the following: wound healing is accelerated as a result of the production of fibroblast growth factor(s) in the site of the wound. The production of tumor necrosis factor-alpha (TNF-alpha) induced by endotoxin inhibits the effect of the growth factor(s) in the wound area, which results in decreased collagen production. Subsequently the wound healing process is impaired.

Animals↗
PubMed1994

Lateral lymph node dissection for rectal carcinoma below the peritoneal reflection.

Lateral lymph node dissection has been advocated for advanced low rectal tumours. However, its benefit is debatable because of the possibility of postoperative bladder and sexual impairment. To assess the role of lateral lymph node dissection 95 patients who underwent the procedure between 1981 and 1991 were reviewed and compared with 83 who had resection of rectal cancer without lateral node dissection. Only ten (11 per cent) of the 95 patients had lateral lymph node involvement; all had Dukes' C tumours. Lymphovascular invasion was present in 50.6 per cent of all patients and neural invasion in 27 per cent of 65 examined specimens. Local recurrence, distant metastasis and overall 5-year survival rates were 7, 9 and 76 per cent respectively in patients undergoing extended lymphadenectomy and 16, 7 and 72 per cent respectively in those who had resection alone. There were no statistically significant differences in survival between the two groups for any Dukes' stage. Recurrence, metastasis and survival were related more to venous or neural invasion and tumour spread than to node dissection. These results demonstrate that patients with Dukes' A tumours do not benefit from lateral lymph node dissection, and that local recurrence rates in those with Dukes' B and C lesions are not significantly decreased. It is concluded that extended lymphadenectomy is unlikely to provide significant benefit to patients with low rectal cancer.

Adenocarcinoma↗
PubMed1994

Enhancement of antitumor cytotoxicity of hepatic lymphocytes by oral administration of PSK.

We have studied the effects of oral administration of a biological response modifier (BRM), PSK, on hepatic lymphocytes. Many PSK positive cells were observed in the liver by anti-PSK antibody staining. Flow cytometric analysis revealed an increase in the number of OX8 (CD8) positive cells in the non-parenchymal nonadherent liver cells (NPNALCs) which were isolated from the liver enzymatically digested by perfusion with collagenase. NPNALCs were fractionated by discontinuous density gradient centrifugation, and the number and cytotoxic activity of these cells were examined in each fraction. Although the yield of lymphocytes in each fraction was not significantly increased by the oral administration of PSK, the natural killer (NK) activity was markedly enhanced in low density fractions. The present findings suggest that oral administration of PSK is effective for prevention of liver metastasis through the augmentation of organ-associated NK activity.

Adjuvants, Immunologic↗
PubMed1994

Lectin-activated killer cells rapidly induced by pokeweed mitogen conjugated beads and their in vivo antitumor effects.

Pokeweed mitogen (PWM) was found to induce rapidly killer cells in human peripheral blood mononuclear cells (PBMC). To avoid PWM contamination in infused lymphocytes, PBMC were stimulated with PWM-coated beads, CMC-1. One hour of stimulation with CMC-1 led to distinct cytotoxic activity in PBMC at 7 h, this reaching a peak at 23 h in the following in vitro culture. The cytotoxic activity and target cell spectrum of CMC-1-activated killer (PWM-AK) cells were similar to those of lymphokine-activated killer (LAK) cells, the precursor cells of PWM-AK cells, as are those of LAK cells which are also low-density lymphocytes. The in vivo antitumor effects of PWM-AK cells were examined in nude mice with peritoneal carcinomatosis generated by the human colon cancer cell line, RPMI 4788. The intraperitoneal (i.p.) injection of PWM-AK cells immediately after stimulation with CMC-1 significantly prolonged the survival of tumor-bearing mice, suggesting that these cells could be of value for clinical cancer therapy.

Animals↗
PubMed1994

The importance of family study in the patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is a well-known autosomal dominant disorder characterized by the formation of multiple adenomatous polyps of the colon. Gardner's syndrome is a variant of familial polyposis coli, and both can be associated with colonic or extracolonic benign and/or malignant tumors. It has been widely recognized that an adenocarcinoma of the colon develops in virtually all cases, usually at an earlier age, if polyps are left untreated. Families of four individuals diagnosed of FAP were surveyed and 56 relatives of the families were examined. Of these 56, 21 had multiple colon polyps, 3 of whom had early-stage adenocarcinomas. We consider that familial survey of FAP individuals can be of considerable benefit for this high-risk population due to the autosomal nature of the disease, allowing diagnosis of an associated cancer at an earlier stage.

Adenomatous Polyposis Coli↗
PubMed1994

Clinical value of soluble interleukin-2 receptor in infectious complications.

In this study, we investigated serum-soluble interleukin-2 receptor (sIL-2r) and neopterin (NPT) levels in five patients with severe postoperative infections. A total of 25 synchronous determinations of sIL-2r and NPT were performed. A marked increase in sIL-2r and NPT levels was observed, and the increase in sIL-2r was significantly correlated to that of NPT which is a marker of macrophage activity. These results suggest that macrophages are involved in the stimulation of sIL-2r release, representing a potentially negative biological effect. The results indicate that sIL-2r may be a useful indicator of the efficacy of antibiotics and of prognosis.

Aged↗
PubMed1994

Suppression of hepatic natural killer activity by liver metastasis of cancer and restoration of killer activity by oral administration of a Basidomycetes-derived polysaccharide, PSK.

PSK (Krestin) is a protein-bound polysaccharide with antitumor and immunomodulatory activity. In this study, the effects of the oral administration of PSK were investigated on the natural killer (NK) activity of liver-associated lymphocytes and their subfractions separated by density gradient centrifugation, in WKAH rats with liver metastasis of KDA hepatoma. PSK was administered orally, at a dose of 500 mg/kg once a day for 3 weeks. The NK activity of nonparenchymal liver cells (NPLC) and their subfractions, including large granular lymphocytes (LGL), was markedly augmented by this treatment. The effects of oral PSK were also examined in CDF1 mice with liver metastases of Colon 26 adenocarcinoma; the survival of tumor-bearing mice was prolonged and both metastatic foci and liver weight were decreased. These results suggest that PSK may be effective for the suppression of liver metastasis through activation of liver-associated NK cells.

Adjuvants, Immunologic↗
PubMed1994

Endoscopical segmental piecemeal tumorectomy for nodular elevation of colorectal tumor: applicability and patient's quality of life.

Endoscopical segmental piecemeal tumorectomy (ESPT) for nodular elevation of colorectal tumor is advantageous in terms of minimizing both surgical invasion and postoperative burden to the patients. Nodular elevation of colorectal tumors is said to occur when the body of the tumor is adenomatous and the surface of the focal cancer grows more horizontally into the lumen than vertically. We report here four cases of nodular elevation of colorectal tumors which were each treated by different surgical procedures.

Aged↗