Clinical significance of assay of squamous cell carcinoma related antigen in tumors of the reproductive organs.
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Biomedical subjects
Publications and source records attributed to M Moriyama.
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Further recurrence of superficial bladder cancer after transurethral resection is frequent in patients who have already experienced recurrence. In an attempt to prevent or delay further recurrences in such patients, the effect of preoperative doxorubicin instillation was investigated. A total of 51 patients with recurrent superficial bladder cancer were randomized to receive either TUR alone or TUR with preoperative doxorubicin instillation. Doxorubicin was administered twice a week for 3 weeks before TUR surgery. An objective response (CR + PR) of the tumors was observed at operation in 12 of 25 (48%) evaluable doxorubicin-treated patients. Chemical cystitis was seen in 32% of the patients. Further recurrence after TUR was observed in 13 of 25 (52%) patients in the doxorubicin group, as against 15 of 23 (65%) evaluable patients in the control group. The mean disease-free interval was significantly longer (11.8 as against 7.1 months) in the doxorubicin group. These preliminary results suggest that preoperative doxorubicin instillation might be effective for prolongation of the disease-free interval in patients with recurrent bladder cancer.
A study was made on the antitumor effect of recombinant murine interferon-beta (rMuIFN-beta) against virus-induced mouse malignant glioma. In in vitro experiments, a dose-dependent and a time-dependent manner were observed for 24 h in the antiproliferative activity of rMuIFN-beta. In in vitro experiments, the growth of subcutaneously transplanted gliomas in mice treated with intraperitoneal administration of rMuIFN-beta was inhibited slightly, whereas, with intratumoral administration, it was inhibited more effectively. In immunological studies, natural killer (NK) cell and cytotoxic T-lymphocyte activities of spleen cells were enhanced with intraperitoneal administration of rMuIFN-beta. The analysis of IFN-induced change in a subpopulation of peripheral blood lymphocytes revealed a decrease of Thy.1,2-positive cells and an increase in the ratio of Lyt.1/Lyt.2-positive cells. But these immunological effects of rMuIFN-beta declined on the 7th day with daily administration. Such hyporeactivity may be noteworthy for the clinical application of IFN.
Numerous lymphoblastoid cell lines (LCLs) which secreted antibodies against Pseudomonas aeruginosa (all Fisher's immunotypes and Homma's immunotype 1) were established by Epstein-Barr virus (EBV)-transformation of lymphocytes. Five LCLs were established as long-term culture lines and their properties were determined. These LCLs produced monoclonal antibodies to Fisher's immunotype 1 and 4 and Homma's immunotype 1, and their immunoglobulin classes were IgM, IgG, and IgA. We found that three monoclonal antibodies (G3-1, H7-2, and E10-1) among them successfully protected mice from the corresponding immunotype of P. aeruginosa infection. Their protective dose (PD50) values were 0.5, 2.6, and 3.1 micrograms immunoglobulin/mouse. These human monoclonal antibodies against P. aeruginosa prepared by EBV-transformation method will be a valuable aid for the treatment for severe P. aeruginosa infections.
Early-phase pyrogen tolerance was induced in rabbits by two consecutive daily injections of 125 ng of endotoxin per kg of body weight. The second injection of the same dose of endotoxin evoked only a monophasic fever with a peak response 1.5 h after the injection; no second peak was observed. The rabbits were released from the tolerance to develop a typical biphasic fever by an injection of 125 ng of endotoxin along with human beta interferon (HuIFN-beta), although the tolerance-inducing amount of endotoxin alone could not. The profile of the febrile response of tolerant rabbits injected with both endotoxin and HuIFN-beta could not be distinguished from that of normal rabbits. There was no essential difference between natural and recombinant HuIFN-beta in breaking tolerance. Heat-stable (70 degrees C, 30 min) endogenous pyrogen or tumor necrosis factor was increased significantly in concentration in the serum of tolerance-broken rabbits. These results suggest that HuIFN-beta stimulates the production of tumor necrosis factor in tolerant rabbits to elicit the second peak of febrile response.
Nonpyrogenic amounts of endotoxin (0.1 to 1 ng/kg), hardly detectable by conventional Limulus amoebocyte lysate tests, could produce a fever of around 1 degree C when injected with a nonpyrogenic dose (6 X 10(5) U/kg) of recombinant human beta interferon (IFN-beta) in rabbits. Release of endogenous IFN and tumor necrosis factor by endotoxin was also dramatically increased by recombinant human IFN-beta, and their levels in the blood were closely correlated with the increase of body temperature. These data suggest, if the synergism between IFN and endotoxin also operates in the homologous system (human IFN-human cells), that contaminating endotoxin in IFNs, even if not detectable by Limulus amoebocyte lysate test, can contribute to IFN fever to a considerable extent in humans.
The effect of clobazam, a 1,5-benzodiazepine, on kindling seizures was compared with the effects of 1,4-benzodiazepines, diazepam and bromazepam, in amygdaloid and hippocampal kindled rats. After kindled seizures were established (stage 5 seizure), the test drugs were administered intraperitoneally. In amygdaloid kindled rats, clobazam significantly suppressed the motor seizures (MS) at doses of 20 and 50 mg/kg and significantly shortened the duration of after-discharge (AD) at doses of 10 to 50 mg/kg. Diazepam at doses of 2 to 10 mg/kg and bromazepam at 1 to 5 mg/kg also significantly suppressed the MS and significantly shortened the duration of AD. Similar suppressive effects by these three benzodiazepines were observed in hippocampal kindled rats. From these results, clobazam was found to have a qualitatively similar but weaker anticonvulsive effect than those of 1,4-benzodiazepines.
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The contractile responses of isolated uterine segments from 17 beta-estradiol-3-benzoate-treated ovariectomized rats to acetylcholine (ACh) and high KCl in Ca-depleted modified Locke-Ringer solution on addition of CaCl2 were used as indicators of Ca2+ influxes through ACh receptor- and voltage-operated Ca2+ channels, respectively. L-Methionine (L-Met) significantly enhanced these responses. The enhancement depended on the time of treatment with L-Met and concentration of L-Met. 3-Deazaadenosine (3-DAA) plus homocysteine thiolactone (HCTL), which inhibit S-adenosylmethionine-dependent methylation, caused dose-dependent inhibition of these contractile responses to ACh and high KCl. These inhibitory effects of 3-DAA plus HCTL were significantly attenuated in the presence of L-Met. Protein carboxylmethyltransferase and phospholipid methyltransferase activities were detected in the isolated uterine segment under conditions similar to those in which the contractile responses were observed. 3-DAA plus HCTL inhibited these enzyme activities. These findings suggest that S-adenosylmethionine-dependent methylations of protein and/or phospholipid in isolated uterine segment are involved in the contractile responses to ACh and high KCl in Ca-depleted modified Locke-Ringer solution on addition of CaCl2.
The anti-ulcer action of clotiazepam (a thienodiazepine derivative) was studied in mice subjected to non-physical and physical stimuli in a communication box. There were two groups of mice: the "sender" mice that received electric shocks on the feet and responded by squealing and jumping, and the "responder" mice that were affected by the senders' responses without receiving shocks on the feet. Gastric ulcers resulted in both groups. The effect of clotiazepam was compared with that of diazepam. The incidence of gastric ulcers was suppressed by clotiazepam at a dose of 3 mg/kg, per os, in "responder" and "sender" mice, and by diazepam at a dose of 1 mg/kg, per os, in "responder" mice. These results suggest that clotiazepam has a suppressive action against gastric ulcers produced by non-physical or physical stimuli, although its potency is slightly weaker than that of diazepam.
Twenty-four hour (24-h) urinary creatinine excretion was measured and correlated with anthropometric measurements (height, weight, skinfold thickness, and arm muscle area (AMA)) in 119 healthy Japanese children, aged 2 to 18 years. The results indicated highly significant correlations between creatinine excretion and age (r = 0.88 for boys, 0.90 for girls), height (r = 0.91, 0.88), weight (r = 0.96, 0.94), and AMA (r = 0.91, 0.70). In the multiple regression estimation, weight alone, or weight and height, accounted for most of the variation in 24-h creatinine excretion (r2 = 0.93 for boys, 0.89 for girls), and the addition of other variables did not further improve the estimation.
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Locally invasive carcinoma of the kidney, prognosis of which still remains unsatisfactory, is a therapeutic challenge in uro-oncology. Our recent experience has indicated that mitomycin C microcapsule therapy which is introduced as a prototype of intravascular targeting chemotherapy is an effective preoperative adjuvant in terms of improving the prognosis of locally invasive kidney carcinoma. Two cases with huge kidney carcinoma directly invading into the caval wall were presented. They were initially considered inoperable, but repeated microcapsule therapy for 5 months provided substantial tumor reduction and facilitated radical operation. The patients are tumor-free at 2 and 8 year after the treatment respectively. The role of targeting chemotherapy in the treatment of locally invasive carcinoma was discussed.
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