Taisuke Ohnoshi

Immunochemotherapy in human lung cancer using the streptococcal agent OK-432.

Streptococcal agent OK‐432 was administered at maintenance levels with conventional inductive chemotherapeutic agents to stage III and IV lung cancer patients. Survival rates were longer in patients treated with OK‐432 than in patients treated without OK‐432. An enhancement of lymphocyte blastogenic activity and a delayed PPD skin reaction were found in patients treated by OK‐432. A low grade fever was present as a side effect of this agent in some patients. The results suggest that OK‐432 may be a useful immunotherapeutic agent in combination with induction chemotherapy in reducing host damage in advanced stages of lung cancer.

Placebo-controlled double-blind comparative study on the preventive efficacy of mesna against ifosfamide-induced urinary disorders

SummaryIn order to evaluate the preventive efficacy, safety and usefulness of mesna (Sodium 2-mercaptoethane sulfonate) against ifosfamide-induced urinary disorders, a placebo-controlled double-blind comparative study was performed. Ifosfamide was administered by intravenous drip infusion at a daily dose of 2 g/m2 for 5 consecutive days, and mesna was intravenously administered at 20% of the ifosfamide dose, three times daily for 5 consecutive days. The results obtained are as follows. (a) Of 101 accrued patients, 91 patients were evaluated consisting of 45 for the mesna group and 46 for the placebo group. There was no intergroup difference in the number of the evaluated cases and patient characteristics. (b) Micturition pain and feeling of residual urine graded as moderate or severe were not observed for the mesna group, but were observed for the placebo group with incidences of 19.6% (9/46) for micturition pain and 15.2% (7/46) for feeling of residual urine; the intergroup differences in the appearance of these urinary symptoms were statistically significant (P=0.0003 for micturition pain;P=0.0009 for feeling of residual urine). The incidence of hematuria graded as moderate or severe was 6.7% (3/45) in the mesna group, which was significantly lower than the 32.6% (15/46) in the placebo group (P=0.0008). (c) No side-effect attributable to mesna was observed. (d) A judgment of “useful” was obtained in 80.0% (36/45) of the patients treated with mesna, which was significantly higher than the 34.8% (16/46) of the patients treated with placebo (P= near 0). On the basis of the above results, we conclude that the preventive efficacy, safety and usefulness of mesna against ifosfamide-induced urinary disorders have been well demonstrated in this study.

Production of tumor antibody-neocarzinostatin(NCS) conjugate and its biological activities

SummaryRabbit xenoantiserum was produced against a human leukemia cell line (NALL-1) derived from a patient with acute lymphoblastic leukemia, and IgG was purified. Anti-NALL-1 rabbit IgG was reacted with NCS, an unique membrane-reactive anticancer antibiotic, in the presence of water-soluble carbodiimide. The resulting mixture was concentrated and chromatographed on a Sephadex G-200 column. The first and second fractions were shown by immunoelectrophoresis and the Ouchterlony double-diffusion method to contain NCS-IgG but not free NCS. The conjugates inhibited the growth of Sarcina lutea, and the growth and 3H-TdR incorporation of NALL-1 cells. A membrane immunofluorescent test with FITC-labeled rabbit anti-NCS and goat anti-rabbit IgG antibodies demonstrated specific localization of NCS-IgG on NALL-1 cell surfaces. These results indicate that IgG-bound NCS retained both NCS and antibody activities, and thus should be useful for cancer therapy.

Decreased monocyte-mediated cytostasis of human cancer cell in patients with lung cancer

SummaryIn vivo animal studies support the concept that monocytes and macrophages are important in the immune surveillance of oncogenesis and that in vitro activated murine macrophages are cytocidal for tumour cells. In this study, the tumour cell cytotoxic activity of human peripheral blood monocytes was examined by measuring the inhibition of 3H-thymidine uptake in the human cancer cell line, established in our laboratory from human squamous cell lung cancer. The monocytes from 8 of the 31 lung cancer patients (26%) showed a percentage growth inhibition of less than 69.8%, which exceeded the 95% confidence limits of the percentage growth inhibition observed with healthy control monocytes. On the other hand, among the 16 sarcoidosis and the 8 tuberculosis cases no value was below 69.8%. However, there was no significant difference between the growth inhibition and the clinical stages or histological type. When OK-432, a Streptococal agent, was administered in vivo to patients with lung cancer, an elevation of the growth inhibition was observed in 7 out of 8 patients. It was confirmed that the tumour cell cytostatic activity of the monocyte is suppressed in patients with lung cancer, and these monocyte deficits hinder the inhibition of tumour growth and metastasis.

Pilot study of cyclophosphamide-doxorubicin-vincristine-cisplatin-etoposide hybrid chemotherapy in small cell lung cancer.

Background. Small cell lung cancer (SCLC) is highly sensitive to chemotherapy. Despite the introduction of intensive combination chemotherapy, long‐term disease‐free survivors are still rare. The emergence of drug‐resistant tumor cells during chemotherapy is presumed to be the major cause of poor outcome.

A NOTE ON THE SO-CALLED LENNERT'S LYMPHOMA (LYMPH0 EPITHELIOID CELLULAR LYMPHOMA) CONCERNING ITS DISEASE ENTITY

Two cases of so‐called Lennerts lymphoma, which is characterized by massive infiltraions of focally aggregated epithelioid cells, are presented. Since this lesion was particularly emphasized by Lennert and Mestdagh in 1968, the major conflicting issue has been focussed on its precise disease entity whether this is an independent or already‐established lymphoproliferative disorder. Based on our experiences, we are rather inclined to regard this lesion to be “a curious histologic variant of an already‐established disease entity”. In order to investigate its precise disease entity and also in view of a possible significance of the presence of epithelioid histiocytes in the lymph nodes and of tonsillar involvement in relation to imunocompetence of the patients, further accumulation of similar cases is required.

Spontaneous regression of malignant pleural mesothelioma

We describe the spontaneous regression of a malignant pleural mesothelioma with left pleural effusion, chest pain, and a high fever (38° to 39°C) in a 37-year-old man. The patient was referred to us because multiple nodules were seen on his chest radiograph after he was successfully treated with thoracocentesis and conventional antibiotic therapy for pleural effusion. Our diagnosis was malignant pleural mesothelioma, based on histologic findings in a biopsy specimen obtained during thoracoscopy. Interestingly, the tumors markedly regressed without treatment, and the patient was doing well more than 5 months after the cancer was diagnosed. The spontaneous regression of malignant pleural mesothelioma is rare, and this may represent the first case report.

A case of acute myelogenous leukemia developing during complete remission of small cell lung cancer.

肺小細胞癌の完全寛解中に急性骨髄性白血病 (AML) を発症した興味ある1症例を経験した.症例は, 肺小細胞癌の確定診断のもとに, 多剤併用交替療法と胸部放射線療法により完全寛解となった.治療開始後22ヵ月頃より血小板減少が出現し, 骨髄塗抹標本で, アウエル小体を伴う骨髄芽球が少数認められ, さらに7ヵ月後, AMLに移行し死亡した.病理解剖の結果, 肺小細胞癌の残存は全く認められず, 肺小細胞癌は完全寛解の状態であった.

Two cases of small cell carcinoma of the lung associated with carcinomatous leptomeningitis.

肺小細胞癌69例の治療経過中に2例の癌性髄膜症を経験した.症例1は, 化学療法により完全寛解を得た後, 癌性髄膜症で再発し, 発症後7週間で死亡した.剖検時, 腫瘍細胞は髄膜のみに認められ, 癌性髄膜症の発症がなければさらに長期の生存が可能と思われた.症例2は, 化学療法による部分寛解中に癌性髄膜症を発症し, 脳脊髄への放射線照射と抗癌剤髄腔内投与が著効を示し, 発症後9ヶ月間の長期にわたり癌性髄膜症を管理し得た.