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Twenty-eight patients with small cell lung cancer were treated with high dose 4'-epidoxorubicin (EDX). Fifteen patients underwent EDX monotherapy (cumulative dose: 800 mg/m2) while 13 were treated with EDX (cumulative dose: 660 mg/m2) associated with cyclophosphamide, etoposide and cisplatin. A 2D-echo was performed in basal condition, after the third and sixth dose and 2 months after the end of the therapy. In the patients without cardiovascular disease (n = 19) left ventricular end-diastolic volume (EDV), end systolic volume (ESV) and ejection fraction (EF) were unchanged. The patients with coronary artery disease (n = 5) showed a statistically significant decrease in EF with an increase of ESV. All patients with systemic hypertension (n = 4) showed a significant reduction of EF and a significant increase of ESV and EDV.

The sperm collected from mammary tumor virus (MTV)-carrying mice (C3H, BALB/cfC3H, BALB/cfRIII and RIII) was separately tested for mammary tumor-inducing activity in (BALB/c × C3Hf)F1, (BALB/c × RIIIf)F1, and BALB/c female recipients by i.p. injection of 0.1 ml of the sperm at 1–2 weeks or at 3 months of age. A total of 551 recipients was observed, including control mice. The results may be summarized as follows: 1) mammary tumor incidence in experiments with or without histocompatibility between sperm donor and recipient is the same; 2) bioactivity is related to the type of MTV (C3H, RIII) and to the type of recipient, not to the sperm donor; 3) the activity of RIII MTV released in the sperm appears to be less influenced by the age of recipients than is that of C3H MTV; 4) BALB/c recipients are more susceptible to C3H than to RIII sperm-released MTV; 5) (BALB/c × RIIIf)F1 hybrids are resistant to sperm-released MTV, especially to C3H MTV infection, and show a 34% incidence of late spontaneous lymphomas inherited by the RIIIf male parent; 6) (BALB/c × C3Hf)F1 hybrids are susceptible to both C3H and RIII sperm-released MTV and show a 30% incidence of late spontaneous mammary tumors due to genetic transmission of MTV by the C3Hf male parent.

Monoclonal antibodies B 6.2, B 72.3 and B 1.1, reactive against tumor-associated antigens of human breast cancer, have been tested on histologic sections of paraffin blocks from 49 cases of breast cancer and from 13 cases of mammary dysplasia. The results have shown that: (a) the three monoclonal antibodies recognize different antigenic determinants of the cancer cells; (b) monoclonal antibodies B 6.2 and B 1.1 recognize antigens which are frequently expressed in cancer cells; (c) the antigen recognized by monoclonal antibody B 72.3, at the concentrations used, is less frequently expressed in tumors, while it seems to be selective for the apical cell border and luminal secretions of apocrine metaplastic lobules or cysts occurring in mammary dysplasia; (d) intracytoplasmic expression of the antigens is observed only in cancer cells, with rare exceptions; (e) tumor cell populations are heterogeneous in respect to the expression of the antigens detected by the monoclonal antibodies tested; (f) the antigens detected are unrelated to the tumor histotype; (g) the frequency of axillary lymph nodal metastases is not influenced by the presence or intensity of antigenic expression in the primary tumors; but (h) in metastatic tumor cell populations the antigenic expression is higher than in primary tumors. This fact suggests some relationship between tumor metastatization and the expression of antigens recognized by the monoclonal antibodies tested.

In order to more clearly define the factors influencing prognosis, 113 cases of T1-T2N0 breast cancers, all operated on by means of radical mastectomy, were reviewed. The following pathologic parameters were analyzed in relation to 5 years survival: histological type, nuclear grading, vascular embolization, size and border of the tumour, and sinus histiocytosis, diffuse cortical hyperplasia and germinal center hyperplasia of axillary nodes. We observed a close correlation between the presence of sinus histiocytosis and prognosis, as many authors have reported. Diffuse cortical hyperplasia stands out from our data as the most unfavourable prognostic factor.

We have previously shown that mice simultaneously infected with the murine mammary tumor virus (MuMTV) and with certain slow murine leukemia viruses (MLV) have an increased resistance to the pathological effects of both agents. Here we report that milk-transmitted MuMTV also delays the development of the acute erythroleukemia induced by Friend leukemia virus (FLV), and retards, or prevents in some cases, the development of long-term lymphomas caused by its helper component. This is confirmed by the observation that the average life span of MuMTV-carrying mice infected with FLV or its helper component is prolonged by over 30% as compared to that of MuMTV-free animals infected with the same agents and by the finding that the replication of Friend viruses is reduced in mice neonatally exposed to MuMTV. Since the antibody responses of mice to MuMTV and to FLV were not cross-reactive, we searched for antiviral activity in the tissues of mice exposed to MuMTV, FLV, or the helper component of FLV. Low levels of interferon-alpha/beta were consistently detected in spleen extracts from mice infected with all these agents but could not be demonstrated in the spleens of uninfected BALB/c mice; thus, the chronic production of endogenous interferon is likely to play a major role in the reciprocal interference in vivo between retroviruses belonging to different genera.

In BALB/cfC3H and BALB/cfRIII virgin female mice, i.e., BALB/c mice carrying milk-transmitted C3H and those carrying RIII murine mammary tumor virus infection, respectively, mammary noduligenesis and tumorigenesis are remarkably different. Focal hyperplastic alveolar changes or hyperplastic alveolar nodules were removed from BALB/cfRIII or BALB/cfC3H breeding female donors and transplanted into the gland-free mammary fat pads of syngeneic BALB/c virgin female recipients with or without hormonal supplementation. The results obtained have shown significant differences in: (a) the morphological type of outgrowths; (b) the incidence of malignant transformations; and (c) the hormonal responsiveness of the tumors arisen after pituitary transplants.

The ability to metastasize via the bloodstream of mammary tumors occurring in Balb/cfC3H and Balb/cfRIII mice (two substrains of identical Balb/c genotype carrying milk-transmitted C3H or RIII murine mammary tumor virus (MuMTV) infection, respectively) has been compared in MuMTV-free Balb/c virgin female recipients given intravenous tumor cell suspensions or subcutaneous solid tumor transplants from mammary tumor-bearing Balb/cfC3H and Balb/cfRIII breeding female donors. Tumor cell suspensions different for MuMTV inducing variant, growth rate, tumor size, and clinical duration, injected intravenously to Balb/c virgin female recipients, have been compared with respect to the foci of lung colonization induced in recipient hosts. The results obtained indicate that MuMTV variant, growth rate and clinical duration of the primary mammary tumor, but not the size of the primary tumor, significantly influence the lung colonization. Similar results were obtained with solid subcutaneous transplants of the same mammary tumors. The significance of these results for the understanding of the general mechanisms of tumor metastases is discussed.

The morphological growth of the mammary glandular tree from 3 to 18 months of age has been quantified in three groups of genetically identical virgin female mice: BALB/c mice free of milk-transmitted mouse mammary tumor virus (MMTV) infection and BALB/cfC3H and BALB/cfRIII mice carrying milk-transmitted MMTV infection of C3H or RIII origin, respectively. Mice were killed at 3-month intervals, and their mammary glands were prepared for stereoscopic examination as whole mounts. Any cluster of alveoli from 0.1 mm in diameter was counted and measured at 0.1-mm intervals. The small clusters of alveoli (less than or equal to 0.3 mm) were used to measure the amount of lobuloalveolar differentiation. The larger clusters of alveoli, the hyperplastic alveolar nodules, and the mammary tumors were used to measure the frequency of tumor cell transformations. Lobuloalveolar differentiation in BALB/c mice was increased significantly by both C3H (p less than 0.001) and RIII (p less than 0.001) MMTV infections. RIII MMTV induced a significantly higher lobuloalveolar differentiation as compared to that induced by C3H MMTV (p less than 0.001). C3H MMTV showed a significantly higher capability in inducing hyperplastic alveolar nodules and mammary tumors as compared to that of RIII MMTV (p less than 0.001). The conclusions were that two different activities are carried out by MMTV, namely, lobuloalveolar differentiation and noduligenesis, and that these two MMTV activities are distinct from each other.