PubMed Health⌕ Search

Biomedical subjects

N Kan

Publications and source records attributed to N Kan.

At least 55 records · Page 3Linked to original sources
PubMed1990

Comparison between crude interleukin-2 and recombinant interleukin-2 in maintaining killing activity of cultured lymphocytes.

Peripheral blood lymphocytes, regional lymph node lymphocytes or malignant effusion lymphocytes from cancer patients were incubated with crude IL-2 (cIL-2) for 13 days. These effectors, which frequently expressed IL-2 receptor (IL-2R), proliferated well and possessed augmented killing activity against fresh autologous tumor cells and K562. However, when recombinant IL-2 (rIL-2) was added for the last 4 days of culture instead of cIL-2, IL-2R expression and killing activity against fresh autologous tumor cells decreased significantly (P less than 0.05). Phenotypic analysis indicated that cIL-2 significantly promoted the expansion of the cytotoxic population (CD8+.11b-)(P less than 0.05). The decreases in killing activity and IL-2R expression were restored by 0.004% PHA plus rIL-2, but not in the presence of rIFN-gamma, rIL-1 alpha, rIL-1 beta, rIL-4 or rIL-6. PHA-free cIL-2 maintained killing activity, but not IL-2R expression. We conclude that some factors in cIL-2 and a low dose of PHA-P are necessary for the maintenance of killing activity and IL-2R expression of cultured lymphocytes in the late phase of culture.

Cell Division↗
PubMed1990

[Experimental study on the optimal treatment schedule for combination of BRM (immunostimulators, cultured killer cells or interleukin-2) and chemotherapy].

In the present study we tried to reevaluate the optimal combination timing in the experimental treatment with BRM and chemotherapeutic agents. BALB/c mice with advanced malignant ascites tumor (MOPC 104 E) were treated with cyclophosphamide (CPA, 2 mg/kg) and BRM such as immunostimulator (OK-432, Lentinan or Bestatin), interleukin-2 (IL 2) or cultured killer cells. The survival of mice was prolonged when immunostimulators were given before CPA. However, no combined effect was seen when immunostimulators were administered after CPA. Treatment with cultured killer cells and in vivo IL 2 after immunochemotherapy (immunostimulator followed by CPA) was the most effective protocol in which immunostimulator, chemotherapy, killer cells and IL 2 respectively seemed to induce, regulate, supplement and amplify anti-tumor effector cells.

Adjuvants, Immunologic↗
PubMed1989

In vivo and in vitro synergistic antitumor effect of interleukin-2-cultured tumor-bearer spleen cells and immune fresh spleen cells.

The synergistic antitumor effect of interleukin-2(IL-2)-cultured tumor-bearer spleen cells (cultured lymphocytes) and immune fresh spleen cells was examined. Tumor-bearer cultured lymphocytes were obtained by culturing BALB/c spleen cells from syngeneic MOPC104E-tumor-bearing mice for 11 days with crude IL-2 and a soluble tumor extract. These cultured lymphocytes had weak antitumor activity when transferred i.p. into tumor-bearing mice that had been inoculated i.p. with 10(5) tumor cells 5 days previously. Immune fresh spleen cells, obtained from mice in complete remission after the treatment with cyclophosphamide, also had weak antitumor activity when transferred at the same schedule. The cultured cells and the fresh cells, mixed together before transfer, significantly augmented the therapeutic effect. At least 1 x 10(7) tumor-bearer cultured lymphocytes and 4 x 10(7) immune cells were needed for the synergistic effect. A tumor-specific combination was needed for both cultured and fresh cells. The effective subpopulation of tumor-bearer cultured lymphocytes was a cytotoxic one from an Lyt2+ precursor, and that of the immune fresh spleen cells was noncytotoxic, Lyt1+ and Lyt2+ T-cells. A similar synergistic effect was also observed during in vitro coculture of tumor-bearer and immune cells. Cytotoxicity, as assessed by the 51Cr-release test, of tumor-bearer IL-2-cultured lymphocytes was maintained most effectively after 3 or 4 days of culture without IL-2 when the lymphocytes were cocultured with immune fresh spleen cells and tumor cells.

Animals↗
PubMed1989

Preventive and curative effects of prostaglandins on stress ulcer in rats. Application of endoscopic observation.

The present study investigated the preventive and curative effects of prostaglandins (PGs) on gastric ulcer in rats induced by physical or psychological stresses; some rats were electrically shocked, while others were exposed to affective stimuli arising from the shocked animals. The synthetic PGs dimethyl-PGE2 and rioprostil were administered orally, and their preventive effect on gastric ulceration was evaluated by determining the incidence and the ulcer index of lesions. The curative effect of drugs on ulcer healing was evaluated by determining a time-dependent change in the mucosal surface of the stomach with an endoscopic technique. Oral administration of dimethyl-PGE2 or rioprostil (25 and 50 micrograms/kg) prevented gastric ulceration significantly. Oral administration of these drugs (50 micrograms/kg, twice per day) significantly promoted the healing process of lesions 24 and 36 hr after termination of stress loading. The present results give direct evidence of the curative effect of PGs on stress ulcers and suggest that application of the endoscopic technique to the pathology of the rat's stomach may be a substantial aid in the preclinical evaluation of antiulcer drugs.

16,16-Dimethylprostaglandin E2↗
PubMed1989

Therapeutic efficacy of sequential therapy with OK-432, cyclophosphamide, IL2-cultured lymphocytes and in vivo IL2 against advanced murine plasmacytoma.

BALB/c mice inoculated IP with a syngeneic plasmacytoma MOPC104E were treated with a combination of a streptococcal preparation, OK-432 (1 KE, 0.1 mg/mouse), low-dose of cyclophosphamide (CPA, 1 mg/kg) and adoptive transfer of tumor-bearer-spleen cells (2 x 10(7) cells) cultured with IL2 and sonicated tumor extract (adoptive immunotherapy; AIT). The consecutive protocol of OK-432 (day 8, 9 post inoculation) - CPA (day 10) - AIT (day 11) was the most effective. Rate of complete remission was highest when recombinant (r-) IL2 was injected to the mice after AIT. Moreover, another bacterial preparation, Nocardia rubra cell wall skeleton and another low-dose chemotherapy, Mitomycin C could be used successfully instead of OK-432 or CPA. Transfer test of intraperitoneal cells (tumor cells plus host cells) of mice on day 11 post inoculation (on the day of AIT) revealed that OK-432 augmented the susceptibility of peritoneal cells to cultured lymphocytes in inhibition of transplantability, and that CPA after OK-432 augmented the anti-tumor effect of tumor-bearer-spleen cells which act synergistically with cultured lymphocytes. This therapy schedule seems to be the best model to augment the effect of AIT with minimal side effect.

Animals↗
PubMed1989

Properties of a murine retroviral recombinant of avian acute leukemia virus E26: a murine fibroblast assay for v-ets function.

A replication-defective murine retroviral construct, termed pME26, was generated by inserting avian gag-myb-ets sequences derived from the cloned avian acute leukemia virus E26 into an Abelson murine leukemia virus-derived retroviral vector. ME26 virus can be rescued efficiently from transfected NIH 3T3 cells by replicating murine leukemia viruses. Either pME26-transfected nonproducers or ME26 virus-infected NIH 3T3 cells expressed a 135-kilodalton fusion protein (p135) which was detectable by immunoprecipitation with antiserum directed against avian leukemia virus p27gag, myb or ets oncogene protein, or murine leukemia virus p15gag and was principally localized in the nucleus. NIH 3T3 cells infected with ME26 exhibited morphological alterations and increased proliferation in reduced serum and formed small colonies in agar suspension. Discrete foci could be readily recognized in cells maintained in a defined medium containing 0.03 to 0.1% calf serum. In newborn NFS/N mice, ME26 induced a significantly higher mortality and incidence of erythroid and myeloid leukemias. Analysis of a series of mutants affecting the expression of various portions of p135 indicated that the v-ets gene acts to mitogenically stimulate the proliferation of NIH 3T3 fibroblasts and reduces or abolishes their serum dependence. These properties provide an assay system to study functions of the ets gene family.

Animals↗
PubMed1989

[The therapeutic effects of OK-432 combined adoptive immunotherapy (AIT) against liver metastases of breast cancer].

We studied the effect of OK-432 combined AIT in 24 cases of liver metastases of breast cancer. Eleven of the 16 patients (69%) who received intraarterial transfer responded to this therapy. On the other hand, no patients responded to intravenous or intraportal transfer. The minimum cell number for a therapeutic response was 10(9) cells. Four patients had abscopal effects after therapy. The serum CEA level paralleled the therapeutic effects. There were no severe side effects accompanying this therapy. These results indicate that intra-arterial OK-432 combined AIT should be the first choice therapy against liver metastases of breast cancer.

Biological Products↗
PubMed1989

[Experimental and clinical study of adoptive immunotherapy combined with preadministration of OK-432: a method to augment the therapeutic effect].

Our previous method of adoptive immunotherapy using IL2-cultured autologous lymphocytes consists of (1) in vitro sensitization by sonicated autologous tumor extract, (2) the induction and proliferation of active CTL by crude IL2, and (3) the preadministration of OK-432 for the augmentation of the therapeutic effect. Here we describe a new method to augment the therapeutic effect of OK432-combined AIT. In BALB/c mice with advanced malignant ascites (MOPC 104E), serial therapy with OK-432, cyclophosphamide and AIT significantly prolonged the survival compared with other therapeutic schedules through synergism between host's effector cells induced by immuno-chemotherapy and transferred killer cells. Many patients with advanced malignancies, for example, unresectable gastrointestinal cancer, locally advanced breast cancer or lung metastases of breast cancer, respond to such immuno-chemo-lymphocytotherapy, while previous OK432-combined AIT was effective only in malignant pleural effusion or metastatic liver tumor from breast cancer or peritoneal dissemination of gastric cancer.

Adult↗
PubMed1988

[Clinical therapeutic effect of adoptive immunotherapy using IL-2-cultured autologous lymphocytes].

Our method of adoptive immunotherapy (AIT) using autologous IL-2-cultured lymphocytes differs from so-called LAK therapy in several points. We (1) obtain cultured lymphocytes from effusion lymphocytes (EL) or regional lymph-node lymphocytes (RLNL), when possible, rather than peripheral blood lymphocytes (PBL), (2) use crude IL-2 to induce T cell proliferation and to maintain killer activity, (3) use sonicated autologous tumor extract as antigen (Ag) to stimulate proliferation of cytotoxic T cells, and (4) pretreat the patients with local administration of OK-432 before AIT to induce effector cells that act synergistically with transferred killer cells. Surface marker analysis showed that OKT3, IL-2 receptor, Leu 2+15- cells were elevated while Leu 11a and Leu 3+8+ cells were decreased. Culture of RLNL augmented the expression of Leu 3+8- marker. Both of PBL and RLNL responded to Ag, and their auto-tumor killing activities were augmented in about half of the patients while rarely decrease by the addition of Ag. Response rates of patients with pleural effusion due to breast cancer and those with liver metastasis of breast cancer were 94% and 60%, respectively. Moreover, the survival was prolonged in the treated patients with pleural effusion or gastric cancer patients with peritoneal dissemination.

Cells, Cultured↗
PubMed1988

[Immunotherapy of gastric cancer].

Two immunotherapeutic methods were developed as adjuvant therapy for gastrointestinal malignancies, one using oral administration of a streptococcal preparation, OK-432, and the other with adoptive immunotherapy (AIT), local transfer of IL2-cultured and autologous lymphocytes, combined with local preadministration of OK-432. Tsuchitani and Nio in our laboratory have revealed experimentally that oral OK-432 stimulates tumor-specific and non-specific immune mechanisms of gut-associated lymphoid tissues and inhibits the growth of some murine syngeneic tumors that were transplanted into cecal patches. The clinical efficacy of oral OK-432 on gastric cancer patients has been examined by a controlled randomized trial involving a total of about 1000 cases. Oral OK-432 (5KE, once a week) was revealed to be significantly effective in curatively resected group but not effective in non-curatively resected group. Ten consecutive patients with peritoneal dissemination of gastric cancer were treated with intraperitoneal OK-432 and AIT. AIT was performed by transferring autologous lymph node-lymphocytes cultured for 13 days with crude IL2 and tumor-extract. The survival of the treated patients was significantly longer (50% survival period exceeded 1 year) than that of historical control (95 cases, 50% survival period was 5 months). These immunotherapeutic methods are expected to be useful for multidisciplinary therapy of gastric cancer by a combination of each method with other therapeutic methods.

Biological Products↗
PubMed1987

[Breast cancer-specific immunity evaluated by a new in vitro method--IL-2 enhanced MLTR].

Peripheral blood lymphocytes from 81 patients with breast cancer were stimulated in vitro with solubilized sonicated autologous tumor extract as an antigen source . The significance of tumor-stimulation (mixed lymphocyte tumor reaction; MLTR) was evaluated with or without the addition of interleukin-2 (IL-2,90 U/ml). As a result, MLTR with the addition of IL-2 (IL-2 enhanced MLTR) showed a higher significance even at a stimulation index (S.I.) of 1.5 than MLTR without IL-2. The values of S. I. in IL-2 enhanced MLTR in preoperative cancer patients were the highest in the patients without lymph node metastasis (n0). The patients with advanced lymph node metastasis (n2) showed a lower response preoperatively but their response was similar to that of the n0-patients 1 to 2 was after operation. These difference were not observed in the blastogenic response to IL-2. These results suggest that IL-2 enhanced MLTR is a useful method to assess the tumor-specific immunological status of the cancer patients.

Antigen-Antibody Reactions↗
PubMed1986

[Effect of anxiolytic drugs on the development and healing process of stress ulcer: application of endoscopic observation].

The present study was conducted to investigate the effect of anxiolytic drugs on the development and healing process of gastric mucosal lesions (GML). In order to produce the GML in mice and rats, we employed a communication box paradigm which can differentially induce a physical and psychological stress. The following drugs (2.5, 50.0, 7.5 mg/kg for mice and 5.0, 10.0 mg/kg for rats) were administered orally: diazepam, clotiazepam, ethyl loflazepate and vehicle (0.5% CMC solution). To define the drug effects on the healing process of GML in rats, we applied an endoscopic technique using the ultra-thin fiberscope. The endoscopic observation was performed under ether anesthesia at 1, 24, 36 and 60 hr after the termination of stress. Both diazepam and ethyl loflazepate significantly suppressed the development of GML in mice, while the preventive effect of clotiazepam was less potent than those of the other anxiolytics. In rats, only ethyl loflazepate showed a significant preventive effect. The curative effect of clotiazepam on the healing process of GML in rats was clearly demonstrated, whereas diazepam was ineffective on the healing process. Ethyl loflazepate also showed a tendency to facilitate the healing process of GML. The present study suggests that the application of the endoscopic technique to rats may provide a potential tool for evaluating the curative effect of drugs on the GML.

Animals↗
PubMed1986

[An in vitro sensitivity assay for anti-cancer agents by measuring the inhibition rate of DNA synthesis (3H-thymidine uptake of cancer cells). II. Clinical study of 110 cases of breast cancer].

The sensitivity of cancer cells to anti-cancer agents (ACA) was assessed in 110 cases of breast cancer (87 primary cases and 23 recurrent cases). The cancer cells were cultured with ACAs: Mitomycin C (MMC), Adriamycin (ADR), 5-Fluorouracil (5-FU), Cytosine Arabinoside (Ara-C), Carboquone (CQ), Nimustine Hydrochloride (ACNU), Cis-platinum Diammine Dichloride (CPDD) or Vincristine (VCR) for 3 days and their sensitivity was estimated by the inhibition rate (I.R.) of DNA synthesis (3H-thymidine uptake) of cancer cells. The DNA synthesis was higher in recurrent cases than in primary cases. The primary cases showed high sensitivity to ADR or CQ, and the recurrent cases showed high sensitivity to ADR. Histologically, papillotubular or medullary tubular carcinoma showed high sensitivity to CQ, and scirrhous carcinoma showed high sensitivity to ADR, CQ or 5-FU. The sensitivities of medullary tubular or scirrhous carcinoma to ADR, 5-FU and CQ in patients with stage III and IV were lower than those in patients with stages I and II. No difference of ACA sensitivity was observed between estrogen receptor (+) and (-) cases. All recurrent cases were treated with 5-FU or its derivatives. The 50% survival period in the 5-FU high sensitivity (I.R. greater than 80%) group was 7.0 months and that of the low sensitivity (I.R. less than 80%) group 3.0 months, respectively.

Adenocarcinoma↗