Isolation of a protease from the cell-free medium of in vitro cultured mammary carcinoma.

Trypsin-like protease with wide spectrum of enzymatic activities have been isolated from cell-free medium from in vivo cultured human mammary carcinoma cells, and from peripheral blood lymphocytes of patients with mammary carcinoma cultured in presence of cell-membrane carcinoma-associated glycoprotein.     

Inhibition de la cancérogenèse spontanée chez les souris R III et AkR par des implants de tissus cancéreux modifiés

Summary (1) After a 24-h passage in a rabbit, fragments of spontaneous isologous mammary carcinoma were implanted under the skin of young R III females. This procedure was found to prevent the appearance of spontaneous mammary tumours in a high percentage of these animals. The subsequent appearance of carcinoma was to be observed in only 23% of treated animals as compared with 51% in controls.(2) After a 24-h passage in a rabbit, fragments of leukotic isologous tissue, implanted subcutaneously in young AkR females, reduced subsequent spontaneous leukomogenesis from 85 to 38%.     

Tumor incidence in Visna virus inoculated mice.

Mice (female Swiss albino) inoculated when newborn with Visna virus had tumors in 77% of cases when examined 8-12 months later. The tumors were mainly of the mammary carcinoma type. The tumor incidence in non-infected control animals was only 20%. In contrast, no increased incidence of tumors was observed among Visna virus-inoculated inbred mice (BALB/c, CBA and DBA) with low incidence of spontaneous mammary carcinoma.     

Newly synthesized elastin is associated with neoplastic epithelial cells in human mammary carcinoma

Summary Indirect immunofluorescence with a purified antiserum to human foetal elastin has identified newly synthesized elastin on the membranes of neoplastic epithelial cells in human mammary carcinoma.This research was supported by a project grant from the Medical Research Council, London.     

Tumor incidence in Visna virus inoculated mice

Summary Mice (female Swiss albino) inoculated when newborn with Visna virus had tumors in 77% of cases when examined 8–12 months later. The tumors were mainly of the mammary carcinoma type. The tumor incidence in noninfected control animals was only 20%. In contrast, no increased incidence of tumors was observed among Visna virus-inoculated inbred mice (BALB/c, CBA and DBA) with low incidence of spontaneous mammary carcinoma.This study was supported by grant No. B75-16X-4511-01 of the Swedish Medical Research Council.     

Persistent and atypical lobules in the human breast may be precancerous

Summary Persistent human mammary lobules (PL) remaining after the menopause, and certain atypical lobules (ALA) are morphologically similar to the common preneoplastic hyperplastic alveolar nodule (HAN) of mice of strains having a high incidence of mammary carcinoma. This and other evidence suggest that like the HAN of mice human PL and ALA are precancerous.This work was supported by a contract from the National Institutes of Health. PHS NOI-CB-43908, and funds from the Cancer Research Coordinating Committee, University of California.     

Isolation of a growth-stimulating agent from human skin fibroblast cultures

Summary Cell-free supernatants were harvested from cultures of human skin fibroblasts, were applied on to DEAE-cellulose columns, and the first fraction eluted with phosphate-buffered saline contained the growth-stimulating agent. The eluted fraction was then passed through a series of amicon membranes. After passing through PM-10, the filtrate stimulated growth of bovine vascular endothelial, canine myocardial, and human mammary carcinoma cells.     

Changes in lactic dehydrogenase isoenzyme pattern in muscle of tumor-bearing mice

Summary The lactic dehydrogenase isoenzyme distribution shifts gradually toward the isoenzyme pattern of the tumor in mouse muscles located distally from a transplanted mammary carcinoma.This study was supported by a grant from the Minnesota Masonic Memorial Cancer Research Fund and, in part, by Grant No. 16-P-5681015-17 from the Rehabilitation Services Administration, U.S. Dept. of Health, Education and Welfare.     

Persistent and atypical lobules in the human breast may be precancerous.

Persistent human mammary lobules (PL) remaining after the menopause, and certain atypical lobules (ALA) are morphologically similar to the common preneoplastic hyperplastic alveolar nodule (HAN) of mice of strains having a high incidence of mammary carcinoma. This and other evidence suggest that like the HAN of mice human PL and ALA are precancerous.     

Effects of prolactin and growth hormone on DNA synthesis of rat mammary carcinomas in vitro

Summary Explants derived from mammary carcinomas of DMBA-treated female Sprague-Dawley rats were cultured for 5 days in Medium 199 containing insulin and corticosterone. The addition of ovine prolactin to the culture media resulted in a consistent significant increase in H³-thymidine incorporation into DNA. DNA synthesis of explants treated with either ovine or human growth hormone was intermediary to prolactin-treated cultures and control cultures. A combination of prolactin and human growth hormone often increased DNA synthesis above either hormone alone, suggesting a possible growth synergism between these peptides.Supported by NIH research grant No. CA-13777 and American Cancer Society research grant No. ET-59.NIH Research Career Development Awardee No. CA-35027.     

The effect of dietary amino acids on the growth of tumors

Summary In C3H mice, a direct dose response relationship between tumor growth and dietary amino acid is seen for fibrosarcoma and mammary carcinoma, extending over a range the lower limit of which is defined by the minimum amino acid requirements, and the upper limit by the amino acid level found in most stock diets.Supported by Medical Research Council of Canada.     

Demonstration of antigen associated with human breast cancers]

The insoluble pellet of human mammary carcinomas was solubilized by an acid buffer. Antiserum prepared with this acidosoluble fraction, after suitable absorption gave one precipitin line with the immunizing extracts: this line is different from those given by the tumor associated antigens actually known. The same antiserum reacted only with sections of human mammary carcinomas by immunofluorescence . It did not stain sections of normal mammary glands or benign mammary diseases. Reactivity with cancers of other organs was absent or doubtful. Hence it is likely that an antigen associated to human mammary carcinomas was characterized.     

姜黄素逆转人结肠癌细胞HCT-8／VCR的双向凝胶电泳技术的建立及优化

目的建立并优化姜黄素逆转人结肠癌细胞HCT-8／VCR蛋白质纽的双向电泳技术。方法姜黄素作用于人结肠癌细胞HCT-8／VCR,提取蛋白质。对双向凝胶电泳中蛋白质样品的处理,蛋白上样量,IPG胶条的选择,以及聚焦条件等进行调整和每化。结果采用瓶内刮取的方法裂解细胞,pH3-10NL的胶条,上样量200ug,延长除盐时间,聚焦60000伏小时,可以得到分辨率较高、重复性较好的双向电泳图谱。结论初步建立了分辨率较高且重复性较好的姜黄素逆转人结肠癌细胞HCT-8／VCR蛋白质双向凝胶电泳图谱。     

Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer

The mammary gland undergoes major developmental changes during puberty and pregnancy. It is thought that stem cells drive mammary gland development during puberty and are responsible for tissue maintenance as well as the major growth and remodelling that occurs with every pregnancy. The use of sophisticated cell separation procedures has facilitated the prospective isolation of mammary epithelial stem and differentiated cell subpopulations from the mouse mammary gland, while studies of primary human breast cancers have described sub-populations of tumourigenic cells capable of initiating tumour growth in immuno-compromised mice. These potential tumour 'stem cells' constitute an important therapeutic target population with respect to cancer therapy, as these are likely to be the cells which maintain tumour growth. Understanding the origin of these cells, their relationship to breast cancer subtypes, and how and why they differ from normal breast stem cells will lead to a revolution in tumour understanding, treatment and prevention. (Part of a Multi-author Review).     

Changes in mammary tissue lipid metabolism in the goats during the first 2 months of lactation]

5 French Alpine Goats were studied after normal or premature parturition. Mammary tissue acetyl-C oA carboxylase, glucose-6-phosphate dehydrogenase, malic enzyme and lipoprotein lipase (LPL) activities varied in parallel with milk fat secretion from the 3rd to the 9th week of lactation. Variations of mammary LPL activity and of long chain fatty acid secretion were positively highly correlated during that period. In goats with normal parturition, lipogenic activities seemed to reach a maximum level shortly after parturition. There was a positive correlation between mammary Ll activities and plasma non esterified fatty acid contents, possibly reflecting a relationship between adipose tissue mobilisation and mammary metabolism.     

Lipid peroxidation,low-level chemiluminescence and regulation of secretion in the mammary gland

In mammary explants of lactating mice, changes in the intensity of chemiluminescence (CL) were observed after the addition to the incubation medium of hormones and mediators that are involved in the regulation of secretion: oxytocin, acetylcholine, epinephrine and norepinephrine. A 15-min period of treatment with oxytocin, epinephrine or norepinephrine changed the level of thiobarbituric acid-reactive substances (TBARS). Two mammary explants, one of which was treated with oxytocin, acetylcholine, epinephrine or norepinephrine, were found to interact even when separated by a quartz glass wall. Analysis of the level of TBARS formation in these two explants showed that the observed interactions might be connected with light emission resulting from lipid peroxidation (LP) processes. The possible role of LP and low-level CL in the regulation of mammary gland secretion is discussed.     

The mammary cellular hierarchy and breast cancer

Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.     

The growth of human fibroblasts and A431 epidermoid carcinoma cells on gamma-irradiated human amnion collagen substrata

Summary Human fibroblasts and A431 human epidermoid carcinoma cells were cultured on gamma-irradiated human amnion collagen as well as on plastic dishes and non-irradiated collagen coated dishes. The morphology, attachment, growth and short-term cytotoxicity of these culture conditions have been determined. Both irradiated and non-irradiated amnion collagen enhanced the attachment and proliferation of fibroblasts as compared to the plastic dishes. No differences in these properties were observed for A431 cells cultured on irradiated collagen when compared with culture on non-irradiated collagen substrates. Cytotoxicity assays showed that irradiated and non-irradiated collagens were not cytotoxic for either fibroblasts or A431 cells. The results demonstrated that amnion collagen irradiated at doses of 0.25–2.0 Mrads is optimal for cell growth.     

Properties of gamma-glutamyltranspeptidase, and glutathione levels in rat mammary gland

gamma-Glutamyltranspeptidase activity and glutathione levels were studied in rat mammary gland during the lactogenic cycle; both increased during mid-lactation. The enzyme's specific activity with several amino acids showed that glutamine and methionine were the best substrates. Maleate decreased the transpeptidation reaction and increased the hydrolytic activity. These results suggest that gamma-glutamyltranspeptidase from the mammary gland is similar to the enzyme described in other tissues in relation to these properties and the physiological role proposed in amino acids transport.     

Loss of CD24 expression promotes ductal branching in the murine mammary gland

CD24 is expressed on mammary stem cells and is used as a marker for their isolation, yet its function in the mammary gland still needs to be examined. Here we show that CD24 is expressed throughout the luminal epithelial cell layer, but only weakly in myoepithelial cells. During lactation, CD24 expression was suppressed within alveoli, but upregulated post-lactation, returning to a pre-pregnant spatial distribution. CD24-deficient mice exhibited an accelerated mammary gland ductal extension during puberty and an enhanced branching morphogenesis, resulting in increased furcation in the ductal structure. CD24−/− mammary epithelial cells were able to completely repopulate cleared mammary fat pads and to give rise to fully functional mammary glands. Together, these data suggest that while CD24 is expressed in mammary epithelium compartments thought to contain stem cells, CD24 is not a major regulator of mammary stem/progenitor cell function, but rather plays a role in governing branching morphogenesis.