Simultaneous identification of two different neuropeptides using a combined PAP and protein A-gold technique in the rat neurohypophysis.
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Animals↗
Biomedical subjects
H Nakada
Publications and source records attributed to H Nakada.
A randomized trial of adriamycin, cyclophosphamide, ftorafur (ACF) and adriamycin, cyclophosphamide, ftorafur, methotrexate (ACFM) in patients with advanced breast cancer.
A prospective randomized trial was conducted comparing the clinical response of 60 patients with advanced breast cancer to a combination of adriamycin, cyclophosphamide, and oral ftorafur (ACF), or to a combination of ACF plus methotrexate (ACFM). The response rate was 12 of 28 (43%) in ACF and 18 of 30 (60%) in ACFM. Responses were seen more frequently in patients in whom fewer than two organs were involved, and responses at dominant metastatic sites were equal for the two arms. The response duration was 21 + (3.5-49.5+) months with ACF, as against 6.9 (1.9-30.8+) months with ACFM (P less than 0.05). The median survival time from start of therapy was 20.8+ months for ACF, while that for ACFM was 13+ months (statistically not significant). The major toxicities were hair loss, GI toxicity, and leukopenia. The response rate with ACFM was higher than that with ACF, but the addition of methotrexate to ACF did not increase the complete response rate or prolong response duration.
Adult↗
[A randomized trial of adriamycin, cyclophosphamide, ftorafur (ACF) and adriamycin, cyclophosphamide, ftorafur, methotrexate (ACFM) in patients with advanced breast cancer].
A prospective randomized trial was conducted to compare the clinical responses of sixty patients with advanced breast cancer to a combination of adriamycin, cyclophosphamide and oral ftorafur (ACF), or to a combination of ACF plus methotrexate (ACFM). The response rate was 12/28 (43%) for ACF compared with 18/30 (60%) for ACFM. Responses were seen more frequently in the cases which had less than 2 organs involved and responses of dominant metastatic sites were equal for the two arms. The duration of response for ACF was 21+ (3.5-49.5+) months as compared to 6.9 (1.9-30.8) months for ACFM (p less than 0.05). The median survival time from the start of chemotherapy for ACF was 20.8+ months, while that for ACFM was 13+ months. The major non-hematological toxicities were hair loss and GI symptoms. Hematological toxicity was similar in the two arms and manageable. No serious cardiac, renal and liver damage was seen in either arm. The response rate for ACFM was higher than that in ACF, but the addition of methotrexate to the ACF regimen did not increase complete response and prolong response duration.
Adult↗
[A phase II clinical trial of oral VP 16-213 in advanced non-Hodgkin's lymphoma].
A phase II clinical trial of oral VP 16-213, a semisynthetic podophyllotoxin, was undertaken in twenty nine patients with advanced non-Hodgkin's lymphoma. All patients had received extensive prior chemotherapies including adriamycin, cyclophosphamide, vinka alkaloids and/or bleomycin and has become refractory to these drugs. The dosage of VP 16-213 was 200 mg/day p.o. bid for 5 days at 3 to 4-week intervals. There were 3 CRs (10.3%) and 6 PRs (20.7%) with a median duration of remission of 16 weeks ranging from 7 to 185+ weeks. Leukopenia less than 4 X 10(3)/cm3 and thrombocytopenia less than 100 X 10(3)/cm3 were seen in 80% and 26.7% of cases, respectively. Alopecia (100%), anorexia (44%) and nausea (26%) were observed but these were well tolerated. We conclude that the oral administration of VP 16-213 has considerable antitumor activity with no cross-resistance to vinka alkaloids, anthracyclines and alkylating agents.
Administration, Oral↗
[Phase II study of mitoxantrone].
A phase II clinical trial of an anthraquinone, mitoxantrone was performed in a total of 31 patients with various advanced solid tumors and 2 patients with malignant lymphomas refractory to extensive prior chemotherapies. Mitoxantrone was administered at dosages of 2 to 4 mg/m2 with a 5-day schedule or 6 to 12 mg/m2 with a one day schedule, repeating at 4-week intervals. Of 18 evaluable patients with breast cancer, one out of 2 patients who had not been exposed to regimens containing adriamycin achieved partial response lasting 3.6 months, while the remaining 16 patients exposed to adriamycin did not respond. Leukopenia less than 4 X 10(3)/cm3 and thrombocytopenia less than 100 X 10(3)/cm3 were observed in 100% and 55% of cases, respectively. Nausea and vomiting were observed in 36% of cases. Diarrhea, pyrexia, liver damage, mucositis and palpitation were observed in one case each. No ECG abnormality was recorded.
Adult↗
[Phase II study of 4'-O-tetrahydropyranyladriamycin(THP-ADM)].
A phase II clinical trial of a new anthracycline, 4'-O-tetrahydropyranyladriamycin (THP-ADM), was performed in thirty-one patients with advanced malignant tumors refractory to standard chemotherapies. The dosage of THP-ADM was 40 mg/m2 by iv bolus injection repeated every 3 weeks. Of 3 evaluable patients with non-Hodgkin's lymphoma, one achieved partial remission. A minor response was noted in one out of 7 patients with gastric cancer and one out of 5 patients with ovarian cancer. Leukopenia less than 4 X 10(3)/cmm and thrombocytopenia less than 100 X 10(3)/cmm were seen in 81% and 19% of cases, respectively. Mild gastrointestinal toxicities including nausea and vomiting and anorexia were observed in about one third of the patients. Mild hair loss occurred in 2 patients (6%). No ECG abnormalities on clinical sign of cardiotoxicity were seen.
Aged↗
[A combination chemotherapy with adriamycin, cyclophosphamide and DTIC (ACD) for advanced adult soft part sarcoma].
Eighteen patients with advanced adult soft part sarcoma were treated with a combination chemotherapy (ACD) consisting of adriamycin 40 mg/m2 iv day 1, cyclophosphamide 500 mg/m2 iv day 1, and DTIC 200 mg/m2 iv days 1 to 5. The regimen was repeated in 3-weeks intervals. Of 16 patients with measurable metastatic diseases, there were one complete response, 4 partial responses, 7 no changes and 4 progressive diseases. The response rate (CR + PR) was 31% (5/16). A median duration of responses was 7 weeks ranging 6 to 106 + weeks. A median survival time from initiation of the chemotherapy was 42 weeks in responders, and 36 weeks in non-responders, respectively. Patients with no prior chemotherapy had a 71% (5/7) response rate while none responded in 9 patients who had prior chemotherapy; furthermore, metastatic lesions in soft tissue were well responded. Leukopenia less than 4,000/cmm occurred in 16/18 (89%) and the median nadir was 2,500/cmm (800-3900). Thrombocytopenia less than 10 X 10(4)/cmm occurred in 2/18 (11%) and the median nadir was 13.4 X 10(4)/cmm (7.5-20.1 X 10(4). Alopecia and gastrointestinal toxicity were moderate to severe but clinically manageable. The result indicated that ACD combination is a useful regimen in remission induction for advanced adult soft part sarcoma.
Adolescent↗
[Hypercalcemia in breast cancer].
In a total of 277 patients with advanced breast cancer treated between July 1977 and November 1983 at Cancer Institute Hospital, there were 26 cases (9.4%) showing hypercalcemia (Ca greater than or equal to 11.0 mg/dl). All these patients had bone metastasis examined by either X-ray films or bone scintigram during clinical course of the disease and confirmed at the time of autopsy, thus an overall incidence of hypercalcemia in 149 patients with bone metastasis was 17.4%. Major clinical signs due to hypercalcemia were gastrointestinal symptoms such as anorexia, nausea and vomiting, renal dysfunction and neurological symptoms but there was no definitive correlation in between clinical signs and values of serum calcium. Among various treatments performed, a combination of hydration, steroids and calcitonin was the most effective. Mean survival time from the diagnosis of hypercalcemia was 288 + days for responders, and 28.8 days for non-responders (p less than 0.001). Seven patients expired due to hypercalcemia and were died suddenly, while others died of renal failures.
Adult↗
Intracellular forms of transferrin oligosaccharide chains in rat liver.
Glycosylation of transferrin was investigated in vivo by using antibody monospecific for rat serum transferrin. Pulse-chase experiments indicated that, after intravenous injection of [35S]methionine, labeled transferrin appeared in the rough and smooth microsomes and Golgi subfractions in rapid succession in 10 min and that an additional 10 min was required for it to be secreted. Most of the intracellular transferrin (95%) immunoprecipitated from the total microsome fraction was sensitive to endo-beta-N-acetylglucosaminidase H (endo H), whereas serum transferrin was completely resistant to it. Further fractionation of the total microsomes has revealed that the intracellular transferrin immunoprecipitated from the rough and smooth microsomes and GF3 are all endo-H-sensitive and most of the endo-H-sensitive oligosaccharides were eluted at the position corresponding to Man8GlcNAc on high-resolution Bio-Gel chromatography. This finding suggests that the major form of intracellular transferrin oligosaccharide in the course of intracellular transport from the endoplasmic reticulum to the Golgi apparatus is Man8GlcNAc2. Endo-H-resistant forms were first detected in the GF2 but more in GF1, most of which were sensitive to neuraminidase. Since the heavy Golgi subfraction contains mainly cis-Golgi elements, such as cisternae, and the light subfraction mainly trans-Golgi elements, such as secretory granules, it is strongly suggested that the processing of these large mannosyloligosaccharide chains and the subsequent addition of terminal sugars to them are performed successively in the trans-Golgi region just before secretion.
Animals↗
Phase I clinical trial of a new anthracycline: 4'-o-tetrahydropyranyl adriamycin.
The phase I study of a new anthracycline, 4'-o-tetrahydropyranyl adriamycin, was performed. A dose-limiting factor was leukopenia while thrombocytopenia was less frequent and a maximum tolerated dose was determined as 54 mg/m2. Mild gastrointestinal toxicities including anorexia, nausea and vomiting occurred in about half of the patients, while very minimal alopecia was seen in only one patient. A recommended dose for phase II study was established: 40 mg/m2 at 3-week intervals.
Adult↗
[Antibiotic therapy of infections in cancer patients with leukopenia].
Cancer patients with leukopenia developing infections were treated with a combination antibiotic therapy consisting of sulbenicillin and amikacin with (B) or without (A) S-sulfonated gamma-globulin. Fifty patients were randomized to either A or B, respectively. Fourty-two patients in group A and 43 in group B were evaluable for responses. Twenty-eight of 42 patients (67%) in group A and 30 of 43 (70%) in group B showed a response. These results did not demonstrate that S-sulfonated gamma-globulin enhanced the effects of the combination with sulbenicillin and amikacin, although the background factors in both groups were not completely identical. Further efforts for detecting infection were required because causes of fever were thought to be fevers of unknown origin in more than three-fourths of the patients. Few patients died of infection within 2 weeks after initiation of these therapies in both groups, indicating that these therapies presumably contributed to prolongation of life span even in patients with no response.
Amikacin↗
Isolation and some properties of a new binding protein for asialoorosomucoid from rat liver.
Binding proteins for asialoorosomucoid were prepared from rat liver previously labeled in vivo with [3H]leucine by affinity chromatography on asialoorosomucoid-Sepharose 4B. They were subjected again to the same affinity chromatography and eluted into two fractions successively with 10 mM Tris-HCl buffer, pH 7.8, containing 1.25 M NaCl, 1% Triton X-100 and 50 mM lactose and 20 mM ammonium acetate buffer, pH 6.0, containing 1.25 M NaCl and 1% Triton X-100, and designated as ABP-I and ABP-II (asialoorosomucoid binding proteins), respectively. ABP-I corresponds to the receptor protein specific for asialoglycoproteins which has been extensively investigated by Ashwell and collaborators (J. Biol. Chem. 254, 1038-1043, 1979). ABP-II is different from ABP-I in several properties such as molecular weight, antigenicity and solubility. The molecular weight of ABP-II was estimated to be 29,000 by SDS-PAGE. On gel filtration it behaved as a pentamer with an apparent molecular weight of 150,000. Unlike ABP-I, ABP-II showed no detectable binding activity when assayed according to the procedures of Hudgin et al. (J. Biol. Chem. 249, 5536-5543, 1974). The calcium ion was, however, essential for the binding of ABP-II to asialoorosomucoid-Sepharose 4B similar to ABP-I. ABP-II can be extracted from the total microsomes of rat liver in 1.0 M NaCl by sonication after freezing and thawing. This suggests that ABP-II is either a soluble protein or a peripheral membrane protein loosely attached to the intracisternal cavities of the microsomal membranes.
Animals↗
[Clinical trial of human lymphoblastoid interferon on advanced malignancy].
A clinical study on human lymphoblastoid interferon (HLBI) in various advanced malignant diseases was performed. HLBI was administered to a total of 25 patients with various advanced malignant diseases in order ot investigate antitumor effect and toxicity. The diseases evaluated were as follows: 8 multiple myeloma (MM), 2 chronic lymphocytic leukemia (CLL), 2 adult T cell leukemia (ATL), 1 acute lymphocytic leukemia (ALL), 8 breast cancer, 3 gastric cancer and 1 ovarian cancer. Twenty-three patients received either 3 million or 6 million units of HLBI by daily intramuscular injection or every other day. One patient with ATL received 18 million units of HLBI by i. v. daily and 1 patient with ALL received 30.32 million units of HLBI i. v. daily. Tumor regression (PR) was observed in 2 patients with MM, each one patient with ATL and ALL, respectively. Major toxicities were pyrexia, myelosuppression, general malaise and G.I. toxicity. Several patients showed abnormality of hepatic or renal function. Two patients who received HLBI for more than a year developed cardiac toxicity.
Adult↗
[Combination chemotherapy of advanced gastric cancer with adriamycin, mitomycin C, and ftorafur].
Thirty patients with advanced gastric cancer were treated with a combination chemotherapy consisting of adriamycin 20-30 mg/m2 iv day 1 q3wks, mitomycin C 2.7-4 mg/m2 iv day 1 weekly, and ftorafur 267 mg/m2 po b.i.d. daily. Five (28%) of 18 patients with measurable lesions achieved partial responses with a median duration of 2 months ranging 1.5 to 8 months. The median survival time from initiation of the chemotherapy was 4 months in responders, and 5 months in non-responders, respectively. The response rate did not correlate with the various baseline parameters including initial performance status, resectability of the primary tumor, histologic differentiation of the tumor, and prior chemotherapy. Gastrointestinal and hematologic toxicities were mild and well manageable. Cumulative thrombocytopenia and renal damage probably due to mitomycin C, were seen in 5(17%) and 2(7%) patients, respectively. Clinical cardiotoxicity induced by adriamycin was observed in one patient. The result indicated that the enhancement of antitumor effect with a combination of adriamycin, mitomycin C, and ftorafur for advanced gastric cancer was not significantly remarkable as expected. Thus, further study will be required for obtaining more favorable result.
Adenocarcinoma↗
[Microwave coagulation under ultrasound guidance in liver hemangioma].
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Diathermy↗
[Co-administration of adriamycin and 5-fluorouracil for the treatment of advanced stomach cancer].
Twenty-one patients with advanced gastric cancer were treated with a combination chemotherapy of adriamycin and 5-fluorouracil (AF). The AF regimen consisting of adriamycin 35-50 mg/m2 intravenously on day 1, 5-fluorouracil 350-500 mg/m2 intravenously on days 1-3 was repeated in every three weeks intervals. Partial response was obtained in four patients (25%) in 16 evaluable patients and responded lesions were abdominal mass and skin metastasis. Two patients had minor responses, seven had stable diseases, and three had progressive diseases. The median duration of response for responders was three months ranging one to five months and the median survival time of responders was twelve months ranging two to fourteen months, whereas that of non-responders was eight months. Moderate bone marrow suppression was seen; that is, seven (33%) out of twenty-one patients had leukopenia less than 2,000/mm3 and two (10%) out of twenty-one patients had thrombocytopenia less than 10 X 10(4)/mm3. Moderate nausea occurred in thirteen patients (62%), whereas vomiting did in nine patients (43%). Nearly total alopecia was observed in sixteen patients (76%). Based on these results, we conclude that AF regimen can be administered without severe toxicities and it is one of the useful regimens for advanced gastric cancer.
Adenocarcinoma↗
Distribution of an asialoglycoprotein receptor on rat hepatocyte cell surface.
Direct ferritin immunoelectron microscopy was applied to visualize the distribution of the hepatocyte cell surface of the asialoglycoprotein receptor which is responsible for the rapid clearance of serum glycoproteins and lysosomal catabolism. For this purpose, rabbit antibody against the purified hepatic binding protein specific for asialoglycoproteins was prepared and coupled to ferritin by glutaraldehyde. The specific antibody conjugates were incubated with the hepatocytes, which were isolated from rat liver homogenate after fixation by glutaraldehyde perfusion. These cells preserved well the original polygonal shape and polarity, and it was easy to identify the sinusoidal, lateral, and bile canalicular faces. The surface density of the ferritin particles bound to the sinusoidal face was about four times higher than that of particles bound to the lateral face, while the bile canalicular face was hardly labeled and almost at the control level. Using the surface area of hepatocyte measured by morphometrical analyses, it was estimated that approximately 90% of bound ferritin particles were at the sinusoidal face, approximately 10% at the lateral face, and approximately 1% at the bile canalicular face. Nonhepatic cells such as endothelial and Kupffer cells had no receptor specific for asialoglycoproteins.
Animals↗
[Muscle irritation study on T-1982].
The local irritation effect of T-1982 after the intramuscular injection into the musculus vastus lateralis was examined in rabbits. T-1982 was dissolved by the way of clinical use and was injected singly into the musculus vastus lateralis. Then the degree of muscular injury at the time of 2 days and 7 days after the injection was judged from muscle weight ratio, gross local observation and histological observation. The degree of muscular injury caused by T-1982 was compared with that of saline, 0.75% acetic acid and 6% acetic acid. On the degree of muscular injury of T-1982 was almost equal to that of 0.75% acetic acid, but milder than 6% acetic acid. From these, it was concluded that the local irritation effect of T-1982 was grade 3.
Animals↗