Tumor accumulation mechanism of 99mTc-DL-homocysteine, a model compound for the development of tumor-imaging radiopharmaceuticals.

To elucidate the tumor accumulation mechanism of 99mTc-DL-homocysteine (99mTc-Hcy), the role of mercaptalbumin, a carrier protein of 99mTc-Hcy in blood, was studied. 99mTc-Hcy bound to serum mercaptalbumin was carried to tumor tissue, efficiently adsorbed onto the cell surface, released from albumin, and taken up by the cells. An enlarged capillary permeability observed in tumor tissue played an important role in the transport process.

[Prevention of hepatitis B--HLA DR/DQ in HBs Ag nonresponder].

To evaluate the immunological background in HBs Ag nonresponders against hepatitis B vaccine, the lymphocyte surface marker and HLA-DR/DQ antigen were determined on hospital personnel, 70 males and 256 females, injected hepatitis B vaccine for three times. The vaccine made from the plasma of HBs Ag carriers was injected at the first and second vaccination and recombinant hepatitis B vaccine was injected at the third vaccination. A month after the third vaccination, blood was withdrawn for HBs antigen test by RIA.

[A case of RAEB in transformation successfully treated by low-dose Ara-C treatment].

A 65-year-old male admitted to the Anjo Kosei Hospital due to pancytopenia. The findings at the time of admission were; leukocyte count 2,000/microliters, erythrocyte count 1,580,000/microliters, and platelet count 88,000/microliters. Bone marrow specimen revealed mild hypocellularity with 26% of the blast cells.

[Impact absorbing properties of the human knee joint].

A biomechanical study has been carried out on 20 cadaveric knee joints to investigate the load absorbing mechanism of the knee. The impact load was applied using a falling weight onto the transected proximal femur and the force transmitted through the knee joint was measured at the transected distal tibia using a load transducer. The transmitted peak force applied through the joint was first measured through the intact knee (100%).

Impact-absorbing properties of the human knee.

A biomechanical study has been carried out on 20 cadaveric knees to investigate their load-absorbing mechanism. The impact load was applied using a weight falling onto the transected proximal femur and the force transmitted through the knee was measured at the transected distal tibia using a load transducer. The peak force transmitted increased as, sequentially, meniscus, articular cartilage and subchondral bone were damaged or removed.

Inhibition by epidermal growth factor of glucocorticoid-induced epidermal alpha-type keratinization of chick embryonic skin cultured in the presence of delipidized fetal calf serum.

When a 13-day-old chick embryonic tarsometatarsal skin was cultured for 4 days in medium containing hydrocortisone (20 nM) and 5% delipidized fetal calf serum (FCS), epidermal growth factor (EGF, 100 ng/ml) decreased epidermal DNA content 42% and inhibited epidermal DNA synthesis 87%. Tonofilament bundles within the basal and intermediate cells of the EGF-treated epidermis were not as conspicuous as those in the glucocorticoid-induced keratinized epidermis, and the upper region of the EGF-treated epidermis did not form either the filament bundles or the electron-dense amorphous masses seen in the cytoplasm of the glucocorticoid-induced keratinized layer. EGF stimulated degradation of glucocorticoid-induced alpha-keratin.

Phase I clinical and pharmacokinetic study of orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine.

A phase I study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was conducted in 88 patients; 36 with solid tumors and 52 with hematological malignancies, using 2 different schedules. Schedule 1 employed a single oral administration and Schedule 2, 5-day consecutive daily oral administration. In Schedule 1, the daily dose was initiated with 1 mg kg-1 which was escalated up to 24 mg kg-1 according to the modified Fibonacci's method.

Treatment of acute leukemia and malignant lymphoma with (2"R)-4'-O-tetrahydropyranyladriamycin.

Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2"R)-4'-O-tetrahydropyranyladriamycin (THP). THP (10-55 mg/m2) was administered by i.v.

[Combination chemotherapy with cyclophosphamide, adriamycin, cisplatin, nimustine, and methotrexate (EACAM) in advanced adenocarcinoma of the lung].

Twenty-eight patients with advanced adenocarcinoma of the lung were treated with the combination chemotherapy "EACAM" consisting of cyclophosphamide (333 mg/m2 X 1), adriamycin (27 mg/m2 X 1), cisplatin (25 mg X 5), nimustine (33 mg/m2 X 1), and methotrexate (27 mg/m2 X 3). This regimen was repeated once every 4 or 5 weeks. One complete response (CR) and 10 partial responses (PR) were obtained in 27 evaluable patients and the response rate was 40.

[Phase II study of mitoxantrone in advanced breast cancer].

A phase II study of mitoxantrone in cases of advanced breast cancer was conducted by a cooperative study group involving 7 institutions. Mitoxantrone was administered at doses of 10-12 mg/m2 at 3-4-week intervals. A total of 36 patients were entered and 31 were evaluable.

Phase I clinical and pharmacokinetic study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine.

A phase I study of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC) was conducted in 66 patients, 41 with solid tumors and 25 with hematological malignancies. The patients received either a 2-h single intravenous (i.v.

Treatment of acute myelogenous leukemia in adults with N4-behenoyl-1-beta-D-arabinofuranosylcytosine.

Forty-five previously-untreated adult patients with acute myelogenous leukemia (AML) were treated with N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine (BHAC) in a multi-institutional cooperative study. Among 41 evaluable patients, 15 (36.6%) achieved complete remission (CR) and 10 (24.

[Effects of combination chemotherapy M-VEMFH including mitoxantrone in advanced breast cancer].

The effects of combination chemotherapy including mitoxantrone (MXN) "M-VEMFH" for advanced breast cancer were studied. The M-VEMFH regimen consisted of MXN 7 mg/m2, VCR 0.7 mg/m2, EX 333 mg/m2, MTX 13.

[Combination chemotherapy with cyclophosphamide, adriamycin, cisplatin, nimustine(ACNU), and methotrexate (EACAM) in advanced adenocarcinoma of the lung].

Twenty-two patients with advanced adenocarcinoma of the lung were treated with the combination chemotherapy "EACAM" consisting of cyclophosphamide (333mg/m2 X 1), adriamycin (27mg/m2 X 1), cisplatin (25mg X 5), nimustine (33mg/m2 X 1), and methotrexate (27mg/m2 X 3). This regimen was repeated once every 4 or 5 weeks. One complete response (CR) and 8 partial responses (PR) were obtained in 21 evaluable patients and the response rate was 42.

[Phase II study of VP-16 (capsule) in malignant lymphomas. A cooperative study].

A new semisynthetic podophyllotoxin derivative VP-16 has been evaluated in a phase II study on malignant lymphomas. The drug was administered orally by capsule at a dose of 100mg twice a day for 5 consecutive days at 3-4-week intervals to a total of 53 patients. Objective responses were noted in 9 patients (25%), 4 with CR and 5 with PR, out of 36 patients with non-Hodgkin's lymphoma, while none of 5 patients with Hodgkin's disease responded.

[Effects of combination chemotherapy of MCNU with various anti-cancer agents].

Combination chemotherapy using the water-soluble nitrosourea MCNU with various anti-cancer agents was studied using L1210 leukemia and P388 leukemia. In titration experiments MCNU showed remarkable antitumor effects at doses from 5 mg/kg to 80 mg/kg, producing numbers of 60-day survivors with L1210 leukemia. In L1210 leukemia, respective combinations of MCNU with the antimetabolites, MTX, 6-MP, 6-TG, MCNU, 5-FU and Cyclo-C showed enhanced antitumor effects.

[Phase II study of VP-16 (capsule) in solid tumors. A cooperative study].

A phase II study of VP-16, a semisynthetic Podophyllotoxin, was performed in patients with solid tumors. VP-16 was administered orally at a dose of 200mg/day for 5 consecutive days at 3 to 4-week intervals. Out of 41 patients who were entered into the study, 35 patients comprising 17 lung cancer, 10 hepatoma and 8 other tumors were evaluable.

The effects of multiple combination chemotherapy with vincristine, cyclophosphamide (Endoxan), methotrexate, 5-fluorouracil, adriamycin and prednisolone (VEMFAH) for advanced breast cancer.

Thirty-eight patients with advanced breast cancer were treated with the 'VEMFAH' multiple-drug combination chemotherapy, consisting of vincristine (V), cyclophosphamide (Endoxan; E), methotrexate (M), 5-fluorouracil (F), adriamycin (A), and prednisolone (H). Disease response was evaluated by the UICC criteria. Among the 35 evaluable cases, 4 complete responses (CR), 23 partial responses (PR), 2 cases of no change (NC), and 6 of progressive disease (PD) were observed.