Shinya Arinaga

Minimal increase in serum interleukin-6 levels during laparoscopic cholecystectomy.

The chronologic changes in the serum levels of interleukin-6 (IL-6), a mediator for acute-phase inflammation, were compared between laparoscopic cholecystectomy (LC) and open cholecystectomy (OC), since these two types of operations were considered to be a unique model for examining the role of local tissue injury in postoperative inflammatory reactions. The increase in the serum IL-6 level during LC was found to be significantly smaller than that during OC and resulted in a smaller extent of postoperative elevations for C-reactive protein. These results suggest that laparoscopic surgery associated with minimal tissue injury can help limit an increase in the serum IL-6 level during surgery, thus contributing to a reduction in surgical stress.

Enhanced production of interleukin 1 and tumor necrosis factor by peripheral monocytes after lentinan administration in patients with gastric carcinoma

The effect of intravenous administration of lentinan, an immunopotentiating polysaccharide, on the production of interleukin 1-alpha (IL 1-alpha), interleukin 1-beta (IL 1-beta) and tumor necrosis factor-alpha (TNF-alpha) by monocytes in peripheral blood mononuclear cells (PBM) was studied in patients with gastric carcinoma. Peripheral blood samples were obtained from 10 patients before and 3, 5 and 7 days after a single dose of 2 mg lentinan injection. The ability of monocytes in PBM to produce IL 1-alpha was significantly augmented 3 and 5 days after lentinan administration, as compared with that before treatment. IL 1-beta production was also significantly increased 3, 5 and 7 days after the drug injection. Further, the capacity to produce TNF-alpha was significantly enhanced 3, 5 and 7 days after the drug administration. Thus, it is likely that the augmentation of these cytokines production may contribute to the antitumor action of lentinan in patients with gastric carcinoma.

Enhanced induction of lymphokine-activated killer activity after lentinan administration in patients with gastric carcinoma

In 15 patients with gastric carcinoma, peripheral blood mononuclear cells (PBM) were obtained serially before and 3, 5 and 7 days after lentinan administration. The generation of lymphokine-activated killer (LAK) activity, induced by in vitro activation of PBM with interleukin 2 (IL 2), was significantly augmented 5 days after a single intravenous dose of 2 mg lentinan, when compared with that before lentinan injection. Natural killer (NK) activity of PBM was also significantly enhanced 7 days after the drug injection. However, the distribution of lymphocyte subsets exhibited no significant change following lentinan administration.

Correlation of eosinophilia with clinical response in patients with advanced carcinoma treated with low-dose recombinant interleukin-2 and mitomycin C

SummaryOn the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 700 U/m2 (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentages of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy.

A reliable operative procedure for preparing a sufficiently nourished gastric tube for esophageal reconstruction

We developed a reliable procedure for obtaining sufficient blood flow at the anastomotic site of the gastric tube for esophageal reconstruction. By utilizing the junction between the left gastroepiploic and short gastric vessels via the splenic hilar vascular arcade, the distal portion of the gastric tube could be sufficiently nourished. The application of this technique resulted in a complete prevention of postoperative anastomotic leakage after antesternal esophageal reconstruction.

Apoptosis in antibody-dependent monocyte-mediated cytotoxicity with monoclonal antibody 17-1a against human colorectal carcinoma cells : enhancement with interferon γ

Abstract Antibody-dependent cell-mediated cytotoxicity (ADCC) has been considered to be one of the main effector mechanisms by which unconjugated monoclonal antibody (mAb) 17-1A can exert an antitumor effect in vivo. Since the apoptotic pathway as well as the necrotic pathway have been shown to be utilized in various cytotoxic effector mechanisms, we investigated the role of apoptosis in ADCC mediated by monocytes (ADMC) using mAb 17-1A as an antibody and the human colorectal carcinoma cell line, COLO205, as target cells in vitro. The implications of the apoptosis during ADMC was demonstrated by means of both a DNA fragmentation assay and a TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. Furthermore, interferon γ (IFNγ) was also found to enhance the induction of apoptosis significantly. The addition of superoxide dismutase did not reduce the level of the apoptosis, although superoxide anion (O2–) was observed to be produced. However, the release of tumor necrosis factor α (TNFα) was significantly enhanced during ADMC, while, in addition, apoptosis was significantly inhibited by the addition of anti-TNFα antibody. These findings indicated that apoptosis might be implicated in ADMC with mAb 17-1A, which was augmented by IFNγ, while, in addition, TNFα may also be one of the major mediators of apoptosis.

Augmentation of the generation of cell-mediated cytotoxicity in culture by mitomycin C

SummaryThe effects of mitomycin C (MMC) on the generation of cell-mediated cytotoxicity in primary stimulation culture of human peripheral blood mononuclear cells (PBM) with the B lymphoblastoid Raji cell line were assessed. The cell-mediated cytotoxicity induced in culture was significantly augmented when MMC was added to cultures on day −1 to day 3 for 24 h at concentrations of 2.5×10−2 μg/ml and 2.5×10−3 μg/ml. To identify the cell populations affected by MMC, PBM were separated by adherence to plastic after treatment with MMC for 24 h (day −1). The two populations were recombined with untreated separated cells and stimulated with antigen. The ability to develop an augmented cell-mediated cytotoxicity was associated with the adherent cell fraction of MMC-treated PBM. Therefore, the ability of MMC-treated adherent cells to produce interleukin 1 (IL 1) was examined. Significantly higher levels of IL 1 were produced by treated cells as compared to untreated adherent cells. The results appear to indicate that the selective effects of MMC on the adherent cell fraction, especially the modification of IL 1 production, may be involved in the mechanisms of MMC-induced augmented cell-mediated cytotoxicity.

Enhanced chemosensitivity of cells from malignant effusions under condition of exposure to high temperature

Utilizing a clonogenic assay, the effects of hyperthermia and selected chemotherapeutic drugs on growth of cells from malignant effusions were studied. Fourteen of 25 samples obtained from 25 patients with various carcinomas formed at least 30 colonies per plate. Exposure of the cells to heat at 42°C for 1 hr before the plating slightly inhibited the colony growth. The drugs, adriamycin (AM) and mitomycin C (MMC), were tested at 3 different concentrations. When the cells were treated with these two drugs for 1 hr at 42°C, the percent of surviving colonies was significantly decreased, as compared to findings at 37°C, in both groups, at 3 different concentrations. The combination of drugs and hyperthermia appeared to function synergistically in one-third of such cases. These results suggest that cells from malignant effusions in patients with various carcinomas were more sensitive to AM or MMC, under condition of a higher temperature (42°C).

Lymphokine-activated killer cell function of peripheral blood mononuclear cells, spleen cells and regional lymph node cells in gastric cancer patients.

Lymphokine‐activated killer (LAK) cells generated by culture of peripheral blood mononuclear cells (PBMC). spleen cells (SPC) and regional lymph node cells (LNC) with IL‐2 for 4 days were examined for their functional capabilities m 29 patients with gastric carcinoma. The cytotoxic activity of LAK cells induced from LNC was significantly lower than that from either PBMC or SPC. although there was no difference between PBMC or SPC. The induction of mRNA of interferon‐gamma (IFN‐γ) or tumour necrosis factor‐alpha (TNF‐α) and the production of these cytokines in the non‐adherent LAK cells from LNC were also significantly reduced compared with those from PBMC or SPC. Further, the LAK cells from LNC secreted significantly lower levels of these cytokines when stimulated with tumour target, Raji cells, although the production of these cytokines was markedly increased by stimulation with the targets in all three cell populations. Phenotypic analysis of each cell population revealed a decreased proportion of the cells mediating natural killer (NK) activity, including CD16+. CD56+, and CD57+ cells in LNC either before or after culture, although OKIal+ and CD25+ cells were uniformly increased in all ceil populations after culture. Changes in subpopulations of CD4+ and CD8+ cells in LNC were not apparently different from PBMC or SPC. These results indicated the differential reactivity of each lymphocyte population to IL‐2 and the reduced LAK cell function of LNC compared with PBMC or SPC in patients with gastric carcinoma.

Heterotopic ossification of rectal adenocarcinoma: Report of a case

Heterotopic ossification of gastrointestinal tract tumors is rare. We report the case of a 67-year-old man with heterotopic ossification of a rectal adenocarcinoma. The patient presented with intermittent abdominal pain and frequent diarrhea, and colonoscopic examination showed a large polypoid tumor partially obstructing the rectal lumen. Abdominal computed tomography (CT) revealed a large tumor in the rectal lumen with calcified spots. We performed low anterior resection of the rectum, and histologic examination showed a well-differentiated adenocarcinoma with heterotopic ossification infiltrating the full thickness of the rectum. Local recurrence and liver metastases were found 2 months after surgery, and the patient died 3 months later. Such a rapidly progressive course of rectal adenocarcinoma with heterotopic ossification is very unusual.