Ichiro Yonome

Brachytherapy for penile cancer using silicon mold

We analyzed the treatment results of 15 patients with penile cancer treated by afterloading brachytherapy with a silicon-made mold we devised. The group included 8 patients with T1, 5 with T2 and 2 with T3 tumors, and inguinal lymph node metastases were noted in 4 patients. The total dose of brachytherapy ranged from 32 to 74 Gy with or without an electron beam boost. The median dose rate was 200 cGy/h ranging from 100 to 350 cGy/h. Local control was achieved in 12 of the 15 patients (80%), and was related to the T category, with 100% of T1 and 80% of T2, in contrast to 0% of T3 tumor. Three patients with partial response or residual tumor underwent amputation. Local recurrence was recognized in 1 patient with a T2 tumor, but salvaged by surgery. Penis conservation was achieved in 11 of 15 patients (73%). Of the 4 patients with inguinal lymph node metastases, 3 were controlled by surgery and radiation therapy. The other with a T3 tumor died from the disease. Brachytherapy with a mold for penile cancer was considered to be the first choice for penis-conserving therapy, and the patients with T1 and T2 tumors have good indications for this method of treatment.

Plasmodium falciparum: attenuation by irradiation

The effect of irradiation on the in vitro growth of Plasmodium falciparum was investigated. The cultured malarial parasites at selected stages of development were exposed to gamma rays and the sensitivity of each stage was determined. The stages most sensitive to irradiation were the ring forms and the early trophozoites; late trophozoites were relatively insensitive. The greatest resistance was shown when parasites were irradiated at a time of transition from the late trophozoite and schizont stages to young ring forms. The characteristics of radiosensitive variation in the parasite cycle resembled that of mammalian cells. Growth curves of parasites exposed to doses of irradiation upto 150 gray had the same slope as nonirradiated controls but parasites which were exposed to 200 gray exhibited a growth curve which was less steep than that for parasites in other groups. Less than 10 organisms survived from the 10(6) parasites exposed to this high dose of irradiation; the possibility exists of obtaining radiation-attenuated P. falciparum.

Plasmodium yoelii: Induction of attenuated mutants by irradiation

When erythrocytic forms of Plasmodium yoelii nigeriensis, which is invariably fatal in mice, were exposed to X rays, the dose to reduce surviving parasites to one millionth was 100 gray (10 Krad). A suspension of 5 X 10(6) per ml of parasitized erythrocyte was irradiated at 100 gray, and 0.2 ml aliquots were inoculated into 22 mice. Eleven mice showed patent parasitemia, and in these the growth curves were less steep than that found in nonirradiated parasites. The infections of 8 mice of the 11 were self-resolving, and the attenuated feature of the parasites maintained following a limited number of blood passages. The parasites were slowly growing even in nude mice and cause self-resolving infections in intact mice. BALB/c mice immunized with the attenuated parasites were protected against subsequent challenge infections with the original virulent erythrocytic and sporogonic forms. These findings indicate that attenuated mutants of malaria parasites can be readily induced by this method.

X-ray sensitivity and DNA synthesis in synchronous culture ofPlasmodium falciparum

The relationship between parasite development and sensitivity to irradiation with X-rays was investigated during a single synchronous cycle ofPlasmodium falciparum in culture. The sensitivity of the parasites to irradiation was closely correlated with the phases of DNA synthesis. Their sensitivity was greatest at the ring stage in development, but decreased at the trophozoite stage when DNA synthesis begins. Lowest sensitivity was found when DNA synthesis was most rapid as the parasites were transforming from late trophozoite to schizont forms. These findings suggest that DNA is the target of the lethal radiation damage in the parasites.

Radioimmunodetection of lung cancer with IMACIS-1, I-131 labeled monoclonal antibodies to CEA and CA19-9

IMACIS-1 is a radiopharmaceutical containing a mixture of Iodine-131 labeled monoclonal antibodies to CEA and CA19-9. IMACIS-1 immunoscintigraphy was evaluated for tumor detection in 7 primary lung cancer and 2 metastatic lung cancer patients who received radiotherapy. No adverse side effects due to IMACIS-1 were observed in this study. Positive detection was achieved in 5 of 9 patients (55.6%). It was less, but nearly the same as the detection rate obtained with Gallium-67 citrate (67Ga-citrate) in these patients. There was no clear correlation between IMACIS-1 accumulation and the CEA or CA19-9 serum levels. The IMACIS-1 positive detection rate decreased in many of the irradiated lesions. We considered that the decreased number of tumor cells and changes in blood perfusion are some of the factors controlling accumulation in tumors.