Potentiation of the chemotherapeutic action of tegafur against solid adenocarcinoma 755 by combination with L-cystine.

The chemotherapeutic action of tegafur (FT) against adenocarcinoma 755 in mice was markedly potentiated by oral administration of L-cysteine and L-cystine without increasing its toxicity. In particular, the combination of FT at 200 mg/kg per day (maximum dose) and 1000 mg/kg per day of L-cystine markedly inhibited tumor growth. The dose ratio of L-cysteine or L-cystine to FT needs 5 by weight to potentiate the antitumor activity of FT.

Clonogenic patterns of human pulmonary adenocarcinoma cell lines (PC-9, PC-13 and PC-14) and how they influence the results of test for chemosensitivity to cisplatin in the human tumor clonogenic assay.

The clonogenic patterns of three human pulmonary adenocarcinoma cell lines (PC-9, PC-13 and PC-14) were studied by human tumor clonogenic assay (HTCA), and factors which could influence the results of tests for the chemosensitivity of these tumor cells to cisplatin in HTCA were determined. The results showed that each tumor cell line had a characteristic clonogenic pattern. The time intervals for the cells to grow to the plateau phase varied from 9 to 16 days, depending on the cell line and number of cells plated.

Natural killer (NK) and lymphokine-activated killer (LAK) cell activity in healthy volunteers with special emphasis on the familial incidence of cancer.

Natural killer (NK) and lymphokine activated killer (LAK) cell activities in 133 healthy volunteers were analyzed with regard to the volunteer's sex, age, smoking history and the familial incidence of cancer. None of these factors had any influence on NK and LAK cell activities. It was concluded that identifying individuals with increased risk of cancer development by examining NK and LAK activities would be difficult.

Amino acid sequence of an amyloidogenic Bence Jones protein in myeloma-associated systemic amyloidosis.

The complete amino acid sequence of an amyloidogenic Bence Jones protein (NIG-84) from an individual with myeloma-associated systemic amyloidosis has been determined. The protein, with a blocked N-terminus, represents a complete light chain consisting of 217 residues and it has a structural feature characteristic of the V lambda II subgroup. In addition to a two-residue insertion at positions 28 and 29, it has an additional rare insertion of alanine at position 100.

Phase II study of cis-diamminedichloroplatinum in patients with non-small cell lung cancer.

A phase II study of cis-diamminedichloroplatinum (CDDP, 80 mg/m2, every 3 weeks) was performed in patients with non-small cell lung cancer (NSCLC). The overall response rate to CDDP was 14% (6/42). In patients without prior chemotherapy, the response rate was 20% (2/10), and in patients with prior chemotherapy, the response rate was 13% (4/31).

Detection of NK activity and antibody-dependent cellular cytotoxicity of lymphocytes by human tumor clonogenic assay--its correlation with the 51Cr-release assay.

NK activity of human peripheral blood lymphocytes (PBL) for cells of the human myeloid line K562, and antibody-dependent cellular cytotoxicity (ADCC) of PBL for cells of human lung adenocarcinoma line PC-9 were determined by the human tumor clonogenic assay (HTCA). Incubation of K562 cells or anti-PC-9 serum treated PC-9 cells with PBL before plating inhibited the formation of colonies of these tumor cells. The percent inhibition of tumor cell colony formation was dependent on the effector/target ratio, the incubation time before plating and, in the case of PC-9 cells, on the dilution of anti-PC-9 serum.

Phase II study of 7-N-(p-hydroxyphenyl)-mitomycin C (KW2083) in patients with advanced non-small cell carcinoma of the lung and metastatic pulmonary tumors.

Twenty-six patients with non-small cell carcinoma of the lung and 25 with metastatic pulmonary tumors were treated by intravenous injection of 7-N-(p-hydroxyphenyl)-mitomycin C (KW2083), a derivative of mitomycin C, either at a single 70-mg/m2 dose or at a dose of 20-30 mg/m2 once a week for 3 weeks. Two patients with adenocarcinoma among 21 evaluable patients with non-small cell carcinoma of the lung, and one with embryonal cell carcinoma among 21 patients with metastatic pulmonary tumors achieved partial response lasting 5 to 7 weeks. In these three patients, KW2083 was administered by a single 70-mg/m2 dose, and no patients who received a dose of 20-30 mg/m2 weekly achieved objective response.

Primary structure of the variable region of an amyloidogenic Bence Jones protein NIG-77.

The complete amino acid sequence of the variable region of a Bence Jones protein NIG-77 from an individual with myeloma-associated systemic amyloidosis has been determined. This protein represents a complete light chain consisting of 216 residues and it has a sequence characteristic of V lambda I subgroup, which is closely homologous to that of another amyloidogenic V lambda I Bence Jones protein NIG-51, differing by 20 of 111 residues (82% homology). In contrast, it differs by 29 residues (74% homology) to that of non-amyloidogenic V lambda I light chain NIG-64.

Complete amino acid sequence of a unique protein related to the variable domain of lambda light chain from a case with Fanconi syndrome.

The complete amino acid sequence has been determined of a unique protein from a 55-years-old female with multiple myeloma associated with Fanconi syndrome. It existed in a monomer form with an apparent molecular weight of 10K daltons, and was consisted of 106 amino acid residues. The sequence was characteristic of the V-region of lambda light chains and was highly homologous with that of the first 106 residues of V lambda III subgroup.

Time-schedule dependency of the inhibiting activity of various anticancer drugs in the clonogenic assay.

To analyze the discrepancy between the in vitro response in the clonogenic assay and the clinical response, the time-schedule dependencies of various anticancer drugs were determined by comparing the inhibiting effect against colony formation by PC-7 cells treated with the drugs for 1 h with that of those treated for 24 h. According to their schedule dependency the drugs can be divided into a schedule-dependent drug group (5-fluorouracil, methotrexate, bleomycin, pepleomycin, etoposide, cisplatin, teniposide, vindesine, and vinblastine) and a non-schedule-dependent drug group (adriamycin, actinomycin D, ranomustine, mitomycin C, aclacinomycin, daunomycin, nimustine, melphalan, and KW 2083). In the clonogenic assay, the 1-h exposure schedule is appropriate for predicting clinical response for the non-schedule-dependent drugs.

Evaluation of a new drug 7-N-(p-hydroxyphenyl)-mitomycin C [KW 2083] against carcinoma of the lung by the human tumor clonogenic assay.

KW 2083, which is a new mitomycin C derivative currently under clinical investigation, was tested for its antitumor effect on the growth of human carcinoma of the lung by using an in vitro clonogenic assay system. The in vitro results in this study were as follows: We succeeded in producing clonal growth at a high rate in all histologic types of carcinoma of the lung in the assay system. That is, 61 of 81 specimens (75%) of either primary or metastatic tumors gave adequate growth for chemosensitivity testing.

A variant prealbumin-related low molecular weight amyloid fibril protein in familial amyloid polyneuropathy of Japanese origin.

Amyloid fibril protein with a molecular weight of 8K daltons, in addition to one of 16K daltons, has been isolated and characterized from an autopsy sample of a patient with familial amyloid polyneuropathy in a Japanese family from Ogawa Village, Nagano Prefecture. The component was shown to react with an antiserum to normal plasma prealbumin, as did the other. Following the purification by reverse phase liquid chromatography, it was digested with trypsin and the peptides, after the purification by HPLC were sequenced.

Phase II study of oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR) for solid tumors.

A phase II trial of 5'-deoxy-5-fluorouridine (5'-DFUR), a new fluorinated pyrimidine analog which has been demonstrated to have potential superiority over 5-FU and tegafur for chemotherapy of murine tumors, was performed in patients with advanced non-small cell carcinoma of the lung and metastatic pulmonary tumors. 5'-DFUR at a dose of 800 mg/m2 was given per os every day for more than four weeks. None of 15 evaluable patients with non-small cell carcinoma of the lung and 15 evaluable patients with metastatic pulmonary tumors showed a complete or partial response.

Biological activity of vitamin D3 derivatives in inducing differentiation of HL-60 human promyelocytic leukemia cells.

Induction of cell differentiation by twenty-one derivatives of vitamin D3 and their binding affinity for the receptor of 1 alpha,25-dihydroxyvitamin D3, an active vitamin D3 metabolite, were examined using HL-60 human promyelocytic leukemia cells and chick intestinal cytosol, respectively. 1 alpha,24(R)-dihydroxy-26-chlorovitamin D3 is found to be more active than 1 alpha,24(R)-dihydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3 in the two abilities to induce the differentiation and to bind to the receptor. The results suggest that a hydroxy group at C-1 position of vitamin D3 and a hydroxy or oxo group at C-25 or C-24 position are essential for both abilities.

Correlation between drug sensitivity determined by clonogenic cell assay and clinical effect of chemotherapy in patients with primary lung cancer.

Correlation studies between the sensitivity of tumor cells determined by clonogenic cell assay and the clinical effect of chemotherapy were performed in patients with primary lung cancer. Thirty-four of 48 patients showed adequate colony formation (greater than or equal to 30 colonies) to test in vitro chemosensitivity. Colony formation of tumor specimens did not differ with regards to prognostic factors such as sex, age, stage, performance status, and prior chemotherapy.

Mechanism of inhibition of phosphoribosylation of 5-fluorouracil by purines.

The mechanism of the abolishment of the cytotoxicity of 5-flurouracil by purines in L5178Y cells was determined by using phosphoribosylation enzymes for both 5-fluorouracil and hypoxanthine. Hypoxanthine inhibited the phosphoribosylation of 5-fluorouracil in the presence of both enzymes, but no inhibition by hypoxanthine was found without hypoxanthine phosphoribosyltransferase or at a high concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP). Hypoxanthine, adenine and inosine decreased the intracellular concentration of PRPP to less than one-tenth of that of the control.

[Effect of 7-N-(P-hydroxyphenyl)-mitomycin C (KW-2083) against pleuritis carcinomatosa].

Fourteen cases of adenocarcinoma with pleuritis carcinomatosa (lung cancer 10 cases, ovarian cancer 2 cases, colon cancer 2 cases) were treated with intra-pleural instillation of 7-N-(p-hydroxyphenyl)-mitomycin C (KW-2083), a derivative of mitomycin C. KW-2083 was administered at a dose of 40 mg once or twice weekly. In 14 evaluable patients, the rate of decrease of pleural fluid was 79%, and that of disappearance of tumor cells in pleural fluid was 64%.

[Effect of peripheral blood lymphocytes on in vitro colony formation of human lung cancer cell line (PC-7)].

The influence of peripheral blood lymphocytes (PBL) on colony formation of cultured tumor cells was examined in tumor colony-forming assay. PBL could suppress colony formation of PC-7 cells effectively in dose-dependent manner. Maximal suppression of colony formation of PC-7 cells was achieved at the PBL-to-tumor-cell ratio of 25 : 1-50 : 1.

[Effect of CDDP administration on NK activity of human peripheral lymphocytes and its modification by corticosteroid as anti-emetic agent].

The effect of cDDP (cis-diamminedichloroplatinum) on NK (natural killer) activity of peripheral blood lymphocytes in 12 patients (7 primary lung cancer, 3 metastatic pulmonary tumor and 2 malignant mediastinal tumor) was examined with emphasis on the combination of corticosteroid. To all patients, 80 mg/m2 of CDDP was administered intravenously every 3 weeks. Four patients were treated with CDDP alone, and 8 patients received 375 mg of methylprednisolone on the same day of CDDP administration and 125 mg on each of following consecutive 5 days respectively.

Influence of molar ratio on the combination effect of 5-fluorouracil with guanosine 5'-monophosphate on P388 and L1210 leukemias.

To obtain more effective treatment with the combination of 5-fluorouracil (FUra) and guanosine 5'-monophosphate (GMP), the influence of the time interval between FUra and GMP administration and of the molar ratio of GMP to FUra on the effect on P388 murine leukemia were investigated. The antitumor activity of FUra was significantly potentiated when GMP was administered either 0-60 min before or 5 min after FUra. The potentiated increase in lifespan (ILS) was almost the same as after simultaneous injection of the two agents.

[Analysis of the mechanism of cancer metastasis by using anticancer agents].

For the analysis of the mechanism of cancer metastasis, effects of anticancer agents on the NK activity of spleen cells and on the artificial metastasis of B-16 melanoma cells were comparatively studied. The inhibitory effect of these anticancer agents on the growth of B-16 melanoma inoculated to foot pad of C57/BL6 mice was also examined. The growth of B-16 melanoma was inhibited by intravenous administration of 6 mg/kg of MMC, 18 mg/kg of KW-2083 and 5 mg/kg of CDDP, but not of 6 mg/kg of KW-2083.