European Journal of Cancer (1965)最新文献

With age, oestradiol receptor concentrations increased in primary breast carcinoma while age did not seem to affect the progesterone receptor levels. Above the age of 70, all tumours examined proved to be hormone-dependent. Analysis by light microscope did not allow correlation of the receptor-positive tumours to any specific or predominant cellular structure. Presurgical radiotherapy of 20 gray significantly reduced the oestradiol and to an even greater extent the progesterone receptor concentrations in the tumours. Prebioptic irradiation with 8 gray accentuated the inhibition of steroid receptor proteins. This reduction in receptor concentration after radiotherapy should be taken into account when interpreting steroid receptor values.

Two transplantable rat central nervous system (CNS) tumors induced by N-ethyl-N-nitrosourea (ENU) were employed to study the mechanisms controlling extracranial metastasis from intracranial tumors. Cells derived from a serially passaged anaplastic astrocytoma and a malignant glioma were injected intracerebrally at doses of 10⁴, 10⁵ and 10⁶ cells per rat (Sprague-Dawley and WAG/Rij rats). As soon as neurological dysfunction appeared, animals were sacrificed and examined histologically for (1) extracerebral outgrowth of the intracerebral tumor, (2) the presence of distant metastases within the CNS and (3) remote metastases outside the CNS. In addition to histology, a bioassay procedure was performed. Metastases were found in cervical lymph nodes (74%), lung (21%) and liver (5%). For both tumor groups, rats with both distant CNS metastases and local extracerebral outgrowth developed remote metastases more frequently (P < 0.05) than animals with intracerebral growth only. The data indicate that both local extracranial spread due to surgical intervention as well as local and distant invasion of leptomeninges promote extracranial metastatic spread.

The presence of HSV-2 DNA was investigated in ten dysplasias and five genital tumours by the blotting technique. The sensitivity of the technique employed could reveal 0.5 viral genome equivalents per diploid cell genome. Viral DNA was not detected in any of the tested tumours.

The cytotoxic effect of the combination of cyclophosphamide and 5-fluorouracil against AKR and L1210 leukemias was quantitated by a spleen colony assay. We used different sequences, a number of doses of each agent, and different intervals between the agents and noted different degrees of synergistic cell-kill. By proper scheduling of these agents, greater than 100-fold increase in cell killing was noted, an effect not demonstrable for normal hematopoietic stem cells. However, the pattern of response for AKR was opposite to that for L1210 leukemia; we suggest that this reflects a difference in the metabolism of 5-FU.

Spayed GR mice treated with progesterone and estrone develop mammary lumors within 3 weeks. The present paper demonstrates that uterine sarcomas develop in a high percentage of those animals that survive 17 weeks of hormone treatment. The growth of the tumors is hormone dependent, and estrogen as well as progesterone receptors were demonstrated in the tumor tissue. Tumor cells were cultivated in monolayer culture. After subcultivation the cells retained their hormone dependence as tested by retransplantation in vivo. The uterine tumors in the GR mouse are suggested as a supplementary model to the widely used mammary tumors to investigate steroid hormone action on tumor growth.

Estrogens, cytoplasmic estradiol receptors, nuclear estradiol receptors and peroxidase activity were measured in human breast carcinomas. No correlation was found between either estrogens, cytoplasmic estradiol receptor or nuclear estradiol receptors and peroxidase activity. The lack of correlation between cytoplasmic estradiol receptors and peroxidase activity is not likely to be due to inhibition of estrogen-inducible peroxidase by endogenous progesterone or the presence of nuclear estradiol receptors in the absence of cytoplasmic receptors. It is concluded that peroxidase activity is not a specific marker for a functional cytoplasmic estradiol receptor in human mammary carcinomas.

The urotoxic potency of various (mainly alkylating) drugs was studied in an extensive series of experiments. It was found that damage to the kidneys and to the efferent urinary tract (haemorrhagic cystitis) is a specific side effect of compounds possessing the oxazaphosphorine ring. This effect is due to the renal excretion of toxic metabolites. The only carriers of urotoxicity are the renally eliminated fractions of the 4-hydroxy-oxazaphosphorines and acrolein which is formed spontaneously therefrom. Other oxazaphosphorine metabolites and breakdown products such as the directly alkylating phosphoric acid diamides, 4-keto-derivatives and carboxyderivatives, have at most only a very slight urotoxic potency. The relationships between the chemical structure and the urotoxicity have been clarified in the group of oxazaphosphorines. Using a standardised test model (rat) the urotoxic side effects of cytostatics were studied experimentally and were measured quantitatively. The urotoxic effects were found to be dose- and concentration-dependent and also showed a marked dependence on the pH. The manifestations of inflammation were more pronounced in an alkaline than in an acidic milieu.

We determined for 14 patients with acute myeloblastic leukemia, prior to therapy with an anthracycline-ara-C combination, the relationship of clinical response to dose-dependent DNA synthesis inhibition produced by each agent on each patient's cultured leukemic cells. Using a microculture system ara-C and adriamycin sensitivity (D²) was determined for each patient based upon each individual's dose response curve. The 9 patients achieving complete remission and one patient who died during induction had D² values to both agents less than 7, while 4 non-responding patients had D² values in excess of 9. Correlation of D² levels with in vivo chemotherapy-induced bone marrow cytoreduction was noted for adriamycin (P < 0.005) and for ara-C (P = 0.1). A relationship between in vitro ara-C and adriamycin sensitivity (P < 0.05) suggests that they act upon similar leukemic cell populations. Inhibition of thymidine synthesis over a range of concentrations deserves further study as a rapid in vitro test for drug sensitivity in acute myeloblastic leukemia.

Using methylcellulose based semi-solid medium enriched with complete alpha medium and undialysed fetal calf serum, we compared the cytotoxic effects between the clonogenic cell (CFU) of a lymphoblastic leukemia cell line (MOLT-4) and normal bone marrow granulocytic progenitor cells (CFU-C) of methotrexate (MTX), vincristine (VCR), hydrocortisone (HC) and daunorubicin (DNR), as well as the reversibility by leukovorin (LV) of MTX cytotoxicity. The neoplastic cells were more markedly inhibited by MTX, VCR and HC following either brief or continuous exposure of the cell to the drugs. Inhibition by DNR was identical for both cell types. In order to reverse the inhibitory effects of MTX in MOLT-4 CFU, LV concentrations needed were at least one log order higher than MTX concentrations. At higher concentrations of MTX, LV reversal was less effective. Only one of four different human bone marrows studied were significantly inhibited by MTX under the experimental conditions. It is suggested that the high concentrations of nucleosides and deoxynucleosides present in the medium aborted the MTX cytotoxicity on CFU-C of normal human marrow but not on MOLT-4 CFU, while the differential inhibition observed with VCR and HC was due to greater sensitivity of the leukemic cells.