Radiotherapy combined with pepleomycin administration for the treatment of esophageal cancer

A combined therapy of pepleomycin (NK-613) and radiation was performed in 15 cases of esophageal and cancer. Twelve cases out of 15 were inoperable, and 3 cases were operable. NK-631 was administered by drip intravenous injection at a dose of 5 mg per day for 3 consecutive days weekly, aiming at total dose of 60-120 mg. Tumor regression rates, which were measured by planimeter on esophagogram, were 42-92% (mean 72%): two cases were more than 90%, and more than 50% in 12 cases. An average of the survival period of 15 cases was 57 weeks with 7 cases (46.7%) of 1 year survival, 2 cases (13.3%) of 2 year survival. The side effects of NK-631 observed in the present study consisted of fever 6, stomatitis 2, skin rash 2, and reversible pneumonitis 2. This study suggests that NK-631 exhibit remarkable anti-tumor effects on esophageal carcinoma, and seem to be less toxic.     

Electrophysiological studies on the neural networks among estrogen and progesterone effective brain areas on lordosis behavior of the rat

The present study was performed in an attempt to elucidate the possible neural networks and their functional modification by progesterone among estrogen and progesterone effective brain areas for lordosis behavior of the rat. Single and multiple unit activities were recorded in the medial preoptic area (MPO), dorsomedial thalamic nucleus (MD), interpeduncular nucleus (IP) and ventral part of midbrain reticular formation (MRF), and single or train pulse stimulation was applied to the MPI, MD, IP, MRF, caudate-putamen (CP), habenular nucleus (HB), dorsal hippocampus (HPC), medial and lateral septum (m- and 1-SEPT) and lateral amygdala (1-AMYG). Unit activity was recorded under urethane anesthesia in ovariectomized rats pretreated with estrogen or with estrogen and progesterone. MPO units showed facilitatory responses to stimulation in the MRF, HB and 1-SEPT, and inhibitory responses to stimulation in the MD, HPC, m-SEPT and 1-AMYG in ovariectomized estrogen-primed rats. CP stimulation inhibited the MD unit activity. Stimulation in the IP had no effect on the MPO or MD units, while the IP units were affected by stimulation in the MPO, MD, CP and HB. MRF unit was accelerated by the MD and CP and inhibited by the MPO stimulation. In the ovariectomized, estrogen and progesterone-treated rat, the MPO unit responses to the MRF and MD stimulation, and the MD unit responses to the MRF and CP stimulation were different from those in the rat with only estrogen treatment. In addition, in the ovariectomized estrogen-primed rat, local application of progesterone to the MD prevented the inhibitory effect of the MD on the MPO unit. Progesterone, when given to the stimulated brain area, accelerated the MPO unit which was activated by the MRF stimulation, and inhibited the MD neuron which was inhibited by the CP stimulation. Multiple unit recordings showed similar results. Moreover, multi-unit activity in the HB and IP was elevated following a systemic progesterone application. On the basis of these results, the possible neural networks in the brain which participate in the lordosis control mechanisms are discussed.     

Studies on enzymatic dealkylation of D-lysergic acid diethylamide (LSD)

New dealkylated metabolites, D-lysergic acid monoethylamide (LAE) and D-N^?6-demethyl-lysergic acid diethylamide (norLSD), were formed by incubation of D-lysergic acid diethylamide (LSD) with rat liver 9000 g supernatant fractions. It was elucidated that these dealkylations were mediated by an NADPH and oxygen dependent enzyme in liver microsomes and were inhibited by SKF 525-A. Tranquillizing agents such as chlorpromazine, nitrazepam and meprobamatc, and certain brain monoamines inhibited these enzymatic dealkylations of LSD. Species differences were investigated.