European Journal of Cancer (1965)最新文献

Six laboratories performing estrogen receptor analysis in breast cancer for patients included in clinical protocols of the Eastern Cooperative Oncology Group participated in a quality control study for estrogen receptor assay. Three tissue powders containing 10–50 femtomoles of estrogen receptors/mg cytosol protein were distributed and the results analyzed for interlaboratory and intralaboratory variations. Frequency of misclassification of the receptor-positive powders as receptor-negative was related to the quantity of receptors. All labs except one were able to distinguish “low content” from “medium content” and the “medium” from the “high content” powders despite the variability in the numerical values reported for the powders. Two of the six labs reported consistently low values for all samples and the results of one lab were consistently higher than the average of the values obtained for the powders. These results could not be explained by the variations in protein content reported by these laboratories for different powders. Implications of the degree of inter-lab and intra-lab variations in the assay results are discussed with reference to their effect on selecting patients for hormonal vs chemotherapy. Based on the results of this study, tentative suggestions for quality control for the receptor assay are also made.

The reactivity of mouse anti-F9 serum on rat embryonal carcinoma cells (F3/1) and xenogeneic as well as syngeneic host immune responses against F3/1 cells were studied. Mouse anti-F9 serum was reactive on the cell surface of F3/1 cells by immunofluorescence. The same antiserum, however, was not cytotoxic against F3/1 cells. The F3/1 cells were not immunogenic in syngeneic hosts as tested by in vivo and in vitro assays. Thus, in the present study, F3/1 antigen(s) could not be defined with syngeneic antiserum but only defined with non-cytotoxic, surface-binding antibodies (IgG) of xenogeneic anti-F3/1 serum.

The synergistic anti-tumor interaction between heat and cyclophosphamide (CP) was investigated. Synergism between local hyperthermia (42.5°C, 30 min) and CP was observed in mice bearing the Lewis lung carcinoma tumor in their hind leg. Local hyperthermia reduced the CP dose needed for cure or a specific tumor growth delay. CP was less effective when given in fractions. A fractionated dose regimen was more effective than CP alone when combined with heat. The thermal enhancement ratio was larger when CP was administered in more than three fractions. It is concluded that combined heat and CP chemotherapy of cancer may be clinically feasible.

The search for derivatives of 9-anilinoacridine by Cain and co-workers [1] using murine L1210 leukemia as a test system, culminated in the synthesis of 4′-(9-acridinylamino)methanesulphon-m-anisidide (m-AMSA, NSC 249,992), which is now undergoing clinical trial. The steps on the development of this and related compounds have been retraced using L1210 cells in culture. The results obtained with the in vitro system have indicated m-AMSA to have an appropriate choice of substituents for optimal activity, in agreement with results of the corresponding in vivo test system. m-AMSA causes a 50% inhibition of L1210 cell growth in culture under standard conditions (3 day cultures) at 3.5 × 10⁻⁸ M. Three compounds in which the substituent on the anilino ring contains a second benzene ring are highly active in culture, one being 100-fold more active than m-AMSA.

The antitumor activity of two representatives of the metallocene dihalides, titanocene dichloride (TDC) and vanadocene dichloride (VDC), is investigated by the use of various experimental tumor systems. Against the lymphoid leukemia L1210 and the lymphocytic leukemia P388, TDC and VDC induce significant increases of life span corresponding to T/C values which exceed 125%. On treating advanced stages of fluid EAT with single doses, TDC causes, when applied within 5 days after transplantation, the survival of 80–100% of the treated animals, whereas VDC cures progressed stages of fluid EAT to a much minor extent. Investigations using a solid EAT subcutaneously growing in the nuchal region show that the intraperitoneally applied metallocene dihalides are able to inhibit tumor growth in a highly significant manner so that the minimum tumor sizes attain 14% (TDC) or 31% (VDC) of the control values. This result indicates that the antiproliferative activity of the metallocene dihalides is based on a systemic effect.

Microbiological and immunological studies were carried out on 73 acute leukemia patients in order to establish the relationship between the host immune defense and the frequency and severity of infections. Pronounced disturbances in the functional activity of granulocytes, the total complement hemolytic activity and C₃ component of the complement are found during induction chemotherapy; in this period the infectious complications are more frequent and severe than at the onset of the disease. No relationship is established between serum lysozyme levels and resistance to infections. The elevated immunoglobulins G and M as a possible response to the infectious agents are considered. It is emphasized that a pronounced immunosuppression as well as the most frequent infectious complications are found in patients in relapse.

A transplanted murine ovarian tumor (M5076/73A, M5, of $\text{C57B1}\text{6}$ origin) with unique metastatic potential is described. After i.m. or s.c. inoculation of the M5 ovarian tumor, spontaneous metastases were consistently observed in liver, spleen, kidney, ovary and uterus, but lung lesions were not usually found. Even after i.v. inoculation the tumor showed a selective tropism for the abdominal organs mentioned. When M5 ovarian carcinoma cells were injected i.p., the tumor grew as scattered lesions in the abdomen and resulted in carcinomatous ascites. Surgical excision of i.m. tumors as early as 5days after implantation failed to protect mice against metastases, suggesting early widespread dissemination from the primary lesion. The tumor was poorly immunogenic as assessed by in vivo immunization with irradiated cells and by concomitant immunity experiments.

Bone marrow cells from 25 AML patients were exposed to cytosine arabinoside and the effects of the drug on the incorporation of ³H-TdR by the cells were measured and compared to the response of the patients to antileukemia chemotherapy with ara C and an anthracycline. The majority of the leukemic cells of the patients in whom bone marrow hypoplasia was not achieved as a result of treatment were classified as resistant to the drugs administered. Incubation with 0.3 μg/ml ara C inhibited DNA synthesis in 11 of 12 resistant patients by 20–95%. Exposure to 3.0 μg/ml drug inhibited the incorporation of ³H-TdR in 10 of 11 resistant patients by 38–98%. The in vivo resistance of the leukemic cells to ara C was not reflected by the in vitro response of the synthesis of DNA by these cells to ara C. The effects of ara C on DNA synthesis were also not correlated to the drug's effects on the clonogenic cells in 21 bone marrow specimens. We conclude that the effects of ara C on DNA synthesis are not predictive to a patient's response to therapy, nor do they reflect the cytocidal effects of the drug on the clonogenic cells.

Cellular proliferation was obtained from 30 out of 58 labial tumours examined. None of the cellular cultures obtained presented Herpes Simplex Virus type 1 (HSV-1) specific antigens. Tumour cell cultures demonstrated the same susceptibility to HSV-1 as cells from normal lip tissue, HEp-2 and BHK cells. The presence of HSV-1 DNA was investigated in 12 labial tumours by the blotting technique. The sensitivity of the technique made it possible to reveal 0.5 viral genome equivalent per cell. Viral DNA was not detected in any of the tumours tested.