Controlled release of 5-fluorouracil from hydrophilic ethylene-vinyl alcohol copolymer matrices.
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Biomedical subjects
Publications and source records attributed to M Takada.
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A total of 54 cases of carcinoma of the uterine cervix were treated with bleomycin adjuvant to surgery and radiation. Bleomycin was injected intravenously or continuously intraarterially or, using oleaginous bleomycin, locally into the infravaginal portion of the cervix, and its significance in administration routes was evaluated in terms of a five-year survival rate. Furthermore, how bleomycin concentrates in the blood, cancerous lesions and regional lymphnodes was examined after administration using following various methods: an aqueous bleomycin, intravenously, continuously intraarterially, and through dispersion to intrapelvic dead space or injected as an oleaginous bleomycin locally to infravaginal portion or applied as vaginal suppository and cervical pellet. Most appropriate routes with increased focal concentrations and reduced blood concentrations proved to enhance anti-neoplastic effects and alleviate side effects. Among them, results with local injection of oleaginous bleomycin to infravaginal portion and continuous intraarterial injection of aqueous bleomycin were most satisfactory. Complete relief from cervical carcinoma by single administration of bleomycin alone is hardly attainable; however, the efficacy of bleomycin as an adjuvant therapy, using a several types of the bleomycins, is highly appreciated in combination with pre- and post-operative treatment and radiotherapy.
The influence of several factors for response to Chemotherapy and survival was analysed in 310 patients with inoperable lung cancer who were treated by single or combination chemotherapy. In small cell lung cancer, survival was strongly affected by the results of induction chemotherapy, and combination chemotherapy with three or four drugs was most effective. In non-small cell lung cancer, performance status and body weight loss on admission were important factors for response to chemotherapy and survival. Combinations did not improve the response rate in non-small cell lung cancer.
We investigated alteration in nonspecific cell-mediated immunity with the progress in the stages of gynecologic cancer, effects of carcinostatics on this alteration, and the significance of immunotherapy given for recovery of the affected cell-mediated immunities for cancers of the uterine neck, uterine body, and ovaries using the count of leukocytes, lymphocytes, T-cells, B-cells, IgGFcR+ T-cells, SI, and ADCC as indicators. The number of T-cells and SI began to decrease from stage I, showing their importance as parameters most accurately reflecting progress of the stage of the cancers. The number of IgGFcR+ T-cells showed no increasing tendency until stage III. ADCC decreased in stage IV, reflecting the pathosis of cancer in the end stage. Alteration in the number of T-cells and SI with time due to administration of carcinostatics has clearly showed that degree of impairment of nonspecific cell-mediated immunity is more dependent upon the kind of carcinostatics that the performance status of subject patients, and administration of ADR, MMC or CQ resulted in decreases not only in the number of T-cells and SI but also in ADCC and number of IgGFcR+ T-cells. Decreases in nonspecific cell-mediated immunity during treatment with such potent carcinostatics could not be prevented with OK-432 and PSK--even an improving tendency was not obtained. These immunotherapeutic agents exerted their effects to activate nonspecific cell-mediated immunity when they were given during the time when carcinostatics were stopped. But it cannot be readily judged whether these activating effects produce improvements in convalescence from gynecologic cancers as a nonspecific active immunotherapy. Follow-up study on effects of the multiple combination therapy should be carefully performed.
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In order to evaluate the clinical benefit of Nocardia rubra cell wall skeleton (N-CWS), a randomized controlled study was performed with inoperable lung cancer patients entered in 5 institutions from October 1978 to June 1981. Patients without pleural effusions were treated initially with conventional therapies such as chemotherapy and/or radiotherapy, according to common protocol, and then patients in performance statuses 0 to 3 were randomized into control and N-CWS groups with stratification into 16 categories according to 4 histological types and 4 clinical stages In the N-CWS group, 400 micrograms N-CWS were initially injected once or twice into the bronchial tumor using a fiberoptic bronchoscope, and subsequently 200 micrograms of N-CWS were injected at monthly intervals into the skin from the shoulders to upper arms. Of 309 patients, 118 patients in the N-CWS group and 108 patients in the control group were eligible for statistical analysis. There was statistically no significant difference in survival rate between the control and the N-CWS groups. According to histological type, significant prolongation of the survival period was observed in patients with small-cell carcinoma. The 97 patients with pleural effusions were initially randomized into control and N-CWS groups. In the control group, local chemotherapy with Adriamycin was performed and, in the N-CWS group, local administrations and monthly intracutaneous injections of N-CWS were given. Tube thoracostomy was performed in both groups. The local response rate was statistically greater in the N-CWS group than in the control group, and survival period was also prolonged significantly in the N-CWS group. The main adverse reactions to N-CWS were skin lesions in the injected sites and fever, but these were temporary and not serious.
A phase I study of VP-16-213 oral capsule was performed in 25 patients with various malignant tumors refractory to standard treatments. Doses were escalated from 50 mg/d to 300 mg/d by a 5-day administration. Leukopenia was dose-related and nadirs at 200 mg/d, 250 mg/d and 300 mg/d were 2,000, 1,600 and 700/cmm respectively, reaching in about 2 weeks and approximately one week was required for recovery. Thrombocytopenia was also dose-related but generally less frequent and milder than leukopenia. Gastrointestinal toxicities such as anorexia, nausea and vomiting occurred in about 20% of patients but well tolerated; alopecia was observed in 40%. The result indicated that an optimal dose of oral VP-16-213 for phase II study was daily 200 mg/d (approximately 130 mg/m2) for 5 consecutive administration in 3-week intervals.
We investigated the relationship between immunosuppressive acidic protein (IAP), an immunosuppressive substance determined in the body fluid from patients with cancer and the stages of cancer, and also its relationship with the progress of cancer during treatment and convalescence in 42 cases of ovary cancer, 47 cases of cancer of the uterine neck, 19 cases of cancer of the uterine body, and 5 cases of other of cancers. In addition, the relationship of IAP with other immunosuppressive substances and cell-mediated immunities was also investigated. The IAP level in the serum was not useful for early diagnosis of gynecologic malignant tumors, but it reflected on stages of cancer more accurately compared to levels of other immunosuppressive substances in the serum: alpha-antitripsine (alpha AT), alpha-glyco-protein (alpha AG), carcinoembrionic antigen (CEA), c-reactive protein (CRP), and serum ferritin (s-Fer), were useful as parameters showing progress of cancer during treatment and convalescence. The IAP level in the peritoneal fluid showed the same tendency. For the relationship with cell-mediated immunity, a stimulate index (SI) showed an inverse correlation from stage I; a T-cell count exhibited the same tendency; IgGFcR+ T-cell count showed a positive correlation in stage III; and ADCC exhibited an inverse correlation in stage III. However, immunosuppressive substances including IAP show high levels also in inflammatory diseases. Therefore, an appreciative value of IAP in the clinical area increases by being used for monitoring gynecologic cancer patients in combination with indicators of cell-mediated immunity, particularly, with SI.
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Identification of motoneurons supplying the tensor veli palatini muscle was attempted by the horseradish peroxidase (HRP) method in the guinea pig and cat. After HRP injection into the tensor veli palatini muscle, HRP-labeled neurons were seen in the regions closely medial to the cluster of the lateral pterygoid motoneurons in the dorsolateral division of the trigeminal motor nucleus. In the guinea pig the tensor veli palatini motoneurons were observed at the level of the whole rostrocaudal extent of the trigeminal motor nucleus, while in the cat they were seen at the level of the rostral two-thirds of the nucleus.
Motoneurons innervating the tensor tympani muscle were identified in the adult guinea pig and cat by the horseradish peroxidase (HRP) method. After HRP injection into the tensor tympani muscle, HRP-labeled neurons were seen in the regions outside the cytoarchitectonically-defined confines of the trigeminal motor nucleus; in the regions rostral to the rostral pole of the nucleus, as well as in the regions ventral and ventrolateral to the nucleus at the levels of the rostral half (guinea pig) or the rostral two-thirds (cat) of the nucleus. The tensor tympani motoneurons were generally smaller than the masticatory motoneurons.
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Reduced and oxidized coenzyme Q10 (Q10H2 and Q10) in guinea-pig liver mitochondria were rapidly extracted and determined by high-performance liquid chromatography (HPLC). The percentages of Q10H2 as compared to the total (sum of Q10 and Q10H2) were increased by the addition of respiratory substrates such as succinate, malate and beta-hydroxybutyrate (State 4). The levels of Q10H2 in State 4 were increased more extensively with electron-transport inhibitors such as KCN, NaN3 and antimycin A. These results indicate that the method for determining Q10H2 and Q10 by HPLC is quite useful for investigation of the physiological function of coenzyme Q in mitochondria and other organelles. The reduced and oxidized coenzyme Q levels of rat liver mitochondria, which contain both coenzyme Q9 and coenzyme Q10, were measured simultaneously. The results suggest that coenzymes Q9 and Q10 play a similar role as an electron carriers. The liver microsomes of guinea-pig contained approx. 133 nmol total coenzyme Q10 per g protein. The Q10H2 levels of microsomes were increased from 46.5 to 67.5 and 64.8% with NADH and NADPH, respectively. The plasma levels of total coenzyme Q were 0.92 microgram/ml for man, 0.35 microgram/ml for guinea-pig and 0.27 microgram/ml for rat. The reduced coenzyme Q were also present in those plasma samples. The levels of reduced coenzyme Q were 51.1, 48.9 and 65.3%, respectively.
B lymphocytes separated from anti-HBe-positive donors were established as lymphoblastoid cell lines by infection with EBV, but anti-HBe in the culture supernatant from such lymphoblastoid cell lines could not be detected. The lymphoblastoid cell lines were rosetted with HBe antigen-coupled SRBC to prepare cells for the production of specific anti-HBe. Antibody activity in the culture supernatant against rosette forming cells was detected by RIA, ID, and R-PHI tests during the first 1 to 4 wk, but not after 5 wk. The activity in the supernatant was not destroyed by treatment with 2-mercaptoethanol, indicating that the antibody might be IgG.
More than 95% of the apparent cathepsin D activity in the lysosomes of porcine adrenal cortex was due to a genuine cathepsin D that has a molecular weight of 42,800 +/- 800 (mean +/- standard deviation of the mean in 5 runs) as determined by Sephadex G-100 column chromatography. On CM-Sephadex C-50 column chromatography at pH 6.9, the enzyme was resolved into five peaks which were termed Fractions D1 through D5 in order of their elution from the column. Fraction D4 and Fraction D5 together constituted more than 70% of the total cathepsin D, and were purified through chromatographic procedures to constant specific activities. The content of lysosomal cathepsin D was estimated to be about 1% of the total cellular protein. On isoelectric focusing, Fraction D4 was resolved into one major band with pI of 7.34 (termed Form D4-1) and one minor band of 7.20 (Form D4-2), while Fraction D5 gave one major band with pI of 7.50 (Form D5-1) and two minor ones of 7.37 (Form D5-2) and of 7.20 (Form D5-3). All of these 5 bands were enzymatically active. On SDS-polyacrylamide gel electrophoresis, both Form D4-1 and Form D5-1 dissociated into three subunits with molecular weights of 27,400 +/- 500 (termed Subunit A), 24,600 +/- 400 (Subunit B) and 13,800 +/- 600 (Subunit C) (mean +/- standard deviation of the mean in 16 determinations). The three subunits all contained carbohydrates.
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