Nishio S

Correlation of tumor necrosis factor and prostaglandin E2 production of monocytes in bladder cancer patients

Patients with advanced malignant neoplasms have a variety of abnormal monocyte and lymphocyte functions. The authors examined tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) production of monocytes in 48 patients with bladder cancer and 16 control subjects. Monocytes were isolated from peripheral blood mononuclear cells by adherence to plastic tissue. They were cultured with lipopolysac‐charide for 24 hours, and the culture supernatant was obtained. The TNF was measured by enzyme immunoassay using anti‐recombinant human TNF antibody, and PGE2 was measured by radioimmunoassay. As a result, in high‐stage bladder cancer patients, there was a significant inverse correlation between TNF and PGE2 production of monocytes. However, there was no significant correlation in control subjects and low stage patients. Accordingly, some patients with high‐stage bladder cancer had higher TNF production but lower PGE2 production of monocytes, and vice versa.

Combined Effect of Interleukin 2 and Bacillus Calmette-Guérin in the Therapy of Mice with Transitional Cell Carcinoma

We investigated the effect of combination therapy with interleukin 2 (IL-2) and Bacillus Calmette-Guérin (BCG) on C3H/HeN mice implanted with mouse bladder tumor cells (MBT2). MBT2-bearing mice were treated with a local injection of BCG into the tumor at a dose of 1 mg/day for a total of 3 times and/or a 10-day continuous subcutaneous infusion of 5 x 10(4) units IL-2/day from day 11 to day 20. As a result, the growth of the tumor in mice treated with IL-2 alone was slightly suppressed, while tumor growth was hardly suppressed in mice treated with BCG alone. However, when IL-2 was administered with BCG, tumor growth was strongly suppressed and mean survival time was prolonged. Natural killer cell activity in the spleen cells was most elevated in mice treated with IL-2 and BCG, while lymphokine-activated killer cell activity was not observed in all groups. Lymphocyte subset analysis showed that there was little change in the ratio of Lyt2-positive lymphocytes or that of L3T4-positive lymphocytes. These findings suggested that clinical evaluation of combination therapy with IL-2 and BCG may be worthwhile.

Clinical studies on cell-mediated immunity in patients with urinary bladder carcinoma. Depression of cell-mediated immunity by adherent cells.

Lymphocyte blastogenesis by stimulation with phytohemagglutinin was compared in 10 control subjects and 20 patients with bladder cancer. Blastogenesis was measured by the incorporation of 3H-thymidine into lymphocytes using microplate assay. As a result, blastogenesis was significantly decreased in high stage patients compared to control subjects and low stage patients. When the nylon wool adherent cells were removed, lymphocyte blastogenesis was increased in high stage patients, while it was decreased in control subjects and low stage patients. This study provides evidence that in most bladder cancer patients with in vitro immunodepression, adherent suppressor cells are detectable, and that these cells may mediate the noted immunodepression.

Combined effect of tumor necrosis factor α and anticancer chemotherapeutic agents against human renal carcinoma cell lines

Antitumor effect of recombinant human tumor necrosis factor alpha (TNF) alone or in combination with various anticancer chemotherapeutic agents was tested using an in vitro antiproliferative assay on four human renal carcinoma cell lines (VMRC-RCW, VMRC-RCZ, Caki-1 and A-498). When the dose-dependent effect of TNF was studied, none of the four cell lines showed a 50% or more inhibition even at a concentration of 10,000 U/ml of TNF, so that the susceptibility to TNF was low. An enhancing effect of TNF on the cytotoxic effect of almost all the chemotherapeutic agents tested was observed against VMRC-RCZ and A-498. Against VMRC-RCW and Caki-1, the combination of TNF with the chemotherapeutic agents did not result in an enhancing effect. Mitomycin C showed an enhancing effect of TNF against all four cell lines. These results suggested that the combined treatment of TNF with chemotherapeutic agents may have favorable results in clinical trials.

Correlation between Blood Prostaglandins, Plasma Lipids and Atherosclerosis in Dialyzed Patients

The correlations between the degree of atherosclerosis, plasma prostaglandins (PGs) and plasma lipids were examined in maintenance hemodialyzed patients with and without diabetes mellitus. The degree of atherosclerosis was evaluated by pulse wave velocity (PWV) of the aorta. Plasma PGs were radioimmunoassayed. PWV was significantly higher in hemodialyzed patients compared to sex- and age-matched healthy controls. PWV correlated with the plasma thromboxane A2 (TXB2) level and TXB2/6-keto-PGF1 alpha ratio in hemodialyzed patients, without a significant difference between the diabetic and nondiabetic groups. The plasma lipid profile was type IV of the WHO classification in both the diabetic and nondiabetic groups, and PWV did not correlate with these lipid abnormalities. Though not significantly, the decreases in plasma PGE2 and 6-keto-PGF1 alpha and the increase in TXB2 correlated with the degree of type IV hyperlipidemia. The results suggest that plasma PG abnormalities might correlate with the degree of atherosclerosis in hemodialyzed patients.

Combined effect of interleukin 2 and cyclophosphamide in therapy of mice with transitional cell carcinoma

We investigated the effect of combination therapy with interleukin 2 (IL-2) and cyclophosphamide (CPM) in C3H/HeN mice implanted with mouse bladder tumor cells (MBT2). MBT2-bearing mice were treated with a single intraperitoneal injection of 120 mg/kg CPM on day 10 and/or subcutaneous administration of 5 x 10(4) units IL-2/day from day 11 to day 20. As a result, the growth of tumor in mice treated with IL-2 alone was slightly suppressed. On the other hand, regression was observed in all mice treated with CPM alone, although regrowth of tumor was seen in all of them. However, when IL-2 was administered with CPM, regrowth of tumor was completely suppressed. An immunologic study was done that showed cytotoxicity against YAC-1 and P815 in the spleen cells was suppressed in mice treated with CPM alone, but that both recovered to control levels when IL-2 was administered with CPM. Cytotoxicity against MBT2 in the spleen cells was most elevated in mice treated with both IL-2 and CPM. These findings suggested that clinical evaluation of combination therapy with IL-2 and CPM may be worthwhile.

Ethylchlorformate polymerized tumor protein immunotherapy of the murine bladder tumor

Using murine transplantable transitional cell carcinoma (MBT2), the effect of ethylchlorformate (ECF) polymerized tumor protein was compared with that of bacillus Calmette‐Guerin (BCG). Seventy‐five C3H/He mice were challenged with an intradermal inoculation of 5 × 105 viable MBT2 tumor cells and divided into five groups. Each group was intradermally administered with 0.01 mg of ECF (low ECF), 0.25 mg of ECF (high ECF), 0.1 mg of ECF and 106 CFU BCG (ECF/BCG), 106 CFU of BCG alone or normal saline (control) weekly for 10 weeks. The mean survival rate for the treatment groups was 64 to 73 days and significantly longer than that for the control group (P < 0.001, Savage). The incidence of biologically active tumor progression was significantly less for the treatment groups (low ECF, 53%; high ECF, 33%; ECF/BCG, 7%rpar; BCG, 27%) compared with the control group (87%; P < 0.5, chi‐square. The mean rate of tumor growth was significantly lower for all treatment groups than for the control group (P < 0.001, ANOVA and SNK), and the ECF/BCG group had the lowest growth rate despite a higher incidence of local granulomatous reaction. In this study, immunotherapy significantly prolonged the survival rate, decreased the incidence of biologically active tumor progression, and slowed the rate of tumor growth. The combination of ECF polymerized tumor protein and BCG had the greatest effect, suggesting that the effect of the vaccine was increased with BCG.

A case of idiopathic thrombocytopenic purpura treated by plasmapheresis and splenectomy.

今回我々は種々の治療を試みたが, 治療に抵抗性で全身の著明な出血傾向を呈したITPの患者にtherapeutic plasmapheresis (TPP) による治療を行い, 血小板を増加させた上で摘脾を施行し, 持続的な血小板数の増加を認めたので報告する.症例は23歳, 男性, 特別な誘因なく歯肉出血, 全身紫斑が認められ, 血小板数0.1×104/mm3と著明に減少していたため, 濃厚血小板液20パックずつ3日間輸血, ハイドロコルチゾン500mg, プレドニゾロン60mg, メチルプレドニゾロン1gの投与をうけたが血小板数は0.1×104/mm3と効果なく, 入院となった.入院時, 鼻出血少量, 歯肉出血, 血尿, 黒褐色便, 全身に散在性の点状出血, 紫斑が多数認められるなど, 出血傾向が著明であり, 抗血小板抗体は陰性であったが, PA-lgG 390.1ng/107 cellsと明らかに上昇していた. また, 骨髄穿刺所見から, megakaryocyteの増加が認められたため, ITPと診断した. メチルプレドニゾロン大量療法として, メチルプレドニゾロン1,000mg/dayから漸次減量して投与を行い, γ-グロブリン大量療法として乾燥pH4処理ヒト免疫グロブリン2.5g×20V静注するも血小板数は最高1.2×104/mm3までしか改善せず, 出血傾向が持続したため, エンドキサン1,000mg/day投与を行ったが, 症状改善が得られないため, TPP施行に踏切った. その後血小板の上昇傾向が認められ, 計6回施行した. その間血小板数のピーク値は10.4×104/mm3であったが, 再び血小板数減少傾向となったため, 血小板数6.1×104/mm3の状態で脾臓摘出術を施行したところ, 血小板は著明に増加し血小板67.2×104/mm3となったため, 退院となった.