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  • 1
    Electronic Resource
    Electronic Resource
    Boston, MA, USA : Blackwell Science Inc
    The @breast journal 7 (2001), S. 0 
    ISSN: 1524-4741
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The developmental pattern of the breast can be assessed by determining the composition of the breast in specific lobular structures, which are designated as lobules type 1 (Lob 1), lobules type 2 (Lob 2), and lobules type 3 (Lob 3), with Lob 1 being the less developed and Lob 3 being the most differentiated or with the highest number of ductules per lobular unit. In the present work, the patient population consisted of three groups of women who underwent surgical procedures: The first group included women who underwent reduction mammoplasty (RM) for cosmetic reasons. The second group included women who underwent prophylactic subcutaneous mastectomy after genetic counseling for either carrying the BRCA-1 gene or belonging to a pedigree with familial breast cancer (FAM), and the third group included women who underwent modified radical mastectomy (MRM) for the diagnosis of invasive carcinoma. The RM group consisted of 33 women, of whom 9 were nulliparous and 24 were parous. The FAM group consisted of 17 women, of whom 8 were nulliparous and 9 were parous. The MRM group consisted of 43 women, of whom 7 were nulliparous and 36 were parous. The analysis of the lobular composition of all of the samples from the RM group, which is considered the control group, revealed that Lob 1 represented 22%, Lob 2 represented 37%, and Lob 3 represented 38%, whereas the tissue examined from the FAM and MRM groups contained a preponderance of Lob 1 at 48% and 74%, respectively, over Lob 3, which was 10% and 3%, respectively. When the results of the analysis of breast tissue were separated according to the pregnancy history of the donor, it was found that in the control group or RM, there was a significant difference in lobular composition. Nulliparous women of the RM group showed a preponderance of Lob 1 (46%) over parous women, which contained only 17%, whereas the percentage of Lob 3 in the nulliparous group was significantly lower (7%) than the parous group (48%). In the breast tissues obtained from FAM and MRM, no significant differences in lobular composition were observed, as all of the samples contained a higher concentration of Lob 1, independent of the pregnancy history. The breast tissue of FAM and MRM of parous women had a developmental pattern that was similar to that of nulliparous women of the same group and that was less developed than the breast of parous women of the control group. An important difference between the Lob 1 of the FAM group versus the control (RM) and the MRM group was that most of these lobules had thin ductules with an increase in hyalinization of the intralobular stroma manifested in the whole-mount preparation as an alteration in the branching pattern. The data suggest that the breast tissue of women with invasive cancer, as well as those from a background of familial breast cancer, have an architectural pattern different from the control or normal tissues and that the BRCA-1 or related genes may have a functional role in the branching pattern of the breast during lobular development, mainly in the epithelial stroma interaction.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 134 (1971), S. 235-242 
    ISSN: 1432-0568
    Keywords: Leydig cells ; Differentiation ; Ultrastructure ; Hamster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This paper describes the morphological events which take place in the hamster Leydig cell during its process of prenatal and postnatal differentiation. The most strinking feature of the prenatal differentiation is the high development of the vesicular form of the smooth endoplasmic reticulum (S.E.R.). At around the end of the first month of postnatal life the vesicular form of the S.E.R. is replaced by a truly reticular S.E.R. formed by numerous interconnected cisternae. From fetal to adult life the amount of ribosomes decreases whereas the number of mitochondria and Golgi cisternae increases. It is concluded that the differentiation mechanism of the hamster Leydig cell differs from that observed in the Leydig cell of other species, even of those closely related to the hamster, such as the mouse.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 146 (1974), S. 219-224 
    ISSN: 1432-0568
    Keywords: Leydig cells ; Differentiation ; Explants ; Ultrastructure ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Testes of newborn mice not older than one day were transplanted into the anterior chamber of one eye of an adult male white Holtzman rat. The events observed in the Leydig cells of the grafted testes can be divided into two periods. Period one is marked by differentiation; period two, by dedifferentiation. In period one, the lipid and glycogen inclusions disappear, possibly owing to the gonadotropins of the host. In period two, which starts after day 15 post-grafting, the lipids and glycogen reappear; the Leydig cells now contain residual bodies, whereas the S.E.R. disappears. Immunological mechanisms can be implicated; it is suggested that the Leydig cells dedifferentiate because the host's gonadotropins may be incapable of evoking and/or activating the genetic memory of the grafted Leydig cells.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of mammary gland biology and neoplasia 3 (1998), S. 49-61 
    ISSN: 1573-7039
    Keywords: RAT MAMMARY CARCINOMAS ; STEROID HORMONES ; GROWTH FACTORS ; ANTIESTROGENS ; ANTIPROGESTINS ; PREGNANCY ; DIFFERENTIATION
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast cancer, the most frequent spontaneousmalignancy diagnosed in women in the Western world, isa classical model of hormone dependent malignancy. Thereis substantial evidence that breast cancer risk is associated with prolonged exposure to femalehormones, since early onset of menarche, late menopause,hormone replacement therapy and postmenopausal obesityare associated with greater cancer incidence. Among these hormonal influences a leading roleis attributed to estrogens, either of ovarian orextra-ovarian origin, as supported by the observationsthat breast cancer does not develop in the absence of ovaries, ovariectomy causes regression ofestablished malignancies, and in experimental animalmodels estrogens can induce mammary cancer. Estrogensinduce in rodents a low incidence of mammary tumors after a long latency period, and only in thepresence of an intact pituitary axis, with induction ofpituitary hyperplasia or adenomas andhyperprolactinemia. Chemicals, radiation, viruses andgenomic alterations have all been demonstrated to have a greatertumorigenic potential in rodents. Chemical carcinogensare used to generate the most widely studied rat models;in these models hormones act as promoters or inhibitors of the neoplastic process. Theincidence and type of tumors elicited, however, arestrongly influenced by host factors. The tumorigenicresponse is maximal when the carcinogen is administered to young and virgin intact animals in which themammary gland is undifferentiated and highlyproliferating. The atrophic mammary gland ofhormonally-deprived ovariectomized or hypophysectomizedanimals does not respond to the carcinogenic stimulus.Administration of carcinogen to pregnant, parous orhormonally treated virgin rats, on the other hand, failsto elicit a tumorigenic response, a phenomenon attributed to the higher degree ofdifferentiation of the mammary gland induced by thehormonal stimulation of pregnancy. In women a majorityof breast cancers that are initially hormone dependentare manifested during the postmenopausal period. Estradiolplays a crucial role in their development and evolution.However, it is still unclear whether estrogens arecarcinogenic to the human breast. The apparentcarcinogenicity of estrogens is attributed to receptor-mediatedstimulation of cellular proliferation. Increasedproliferation could result in turn in accumulation ofgenetic damage and stimulation of the synthesis of growth factors that act on the mammaryepithelial cells via an autocrine or paracrine loop.Alternatively estrogens may induce cell proliferationthrough negative feedback by removing the effect of one or several inhibitory factors present in theserum. Multidisciplinary studies are required for theelucidation of the mechanisms responsible for theinitiation of breast cancer. Understanding of suchmechanisms is indispensable for developing a rationalbasis for its prevention and control.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 187-200 
    ISSN: 1573-7039
    Keywords: rat ; mammary cancer ; carcinogenesis ; classification ; mammary cancer ; diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies performed in experimental animal models have demonstrated that mammary cancer is a complex multistep process that can be induced either by chemicals, radiation, viruses, or genetic factors. Rodent models have been useful for dissecting the initiation, promotion, and progression steps of mammary carcinogenesis. Chemically induced mammary tumors, such as those induced by 7,12-dimethylbenz(a)anthracene and N-methyl-N-nitrosourea, are, in general, hormone-dependent adenocarcinomas whose incidence, number of tumors per animal, tumor latency, and tumor type are influenced by the age, reproductive history, and endocrinologic milieu of the host at the time of carcinogen exposure as well as by diet and the dose of carcinogen administered. There is a need to classify tumors according to their histopathological type because those characteristics have implications in the interpretation of experimental data. In the classification presented here we attempt to provide a working framework for diagnosis of the type of lesions found in the mammary glands of rats treated with chemical carcinogens or radiation and to clarify criteria for establishing the basic biological characteristics of tumors.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7217
    Keywords: breast cancer ; clinical correlates ; prostaglandins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Determination of the levels of prostaglandin E2 (PGE2) and PGF2α were carried out using homogenized primary human breast tumors. Measurable levels of both prostaglandins were found in all but one tumor examined. In most samples, the absolute PGF2α level was higher than that of PGE2. Higher PGE2 levels are more often seen in postmenopausal women than in pre- or perimenopausal patients, though among postmenopausal women, PGE2 levels do not correlate with age. Thus, the ratio of PGF:PGE is higher in pre/perimenopausal women than in postmenopausal women. Differences in PGF2α do not appear to be associated with age or menopausal status. Tumors that are estrogen receptor positive (ER +) tend to have higher PGE2 levels than ER negative tumors. PGF2α is not associated with the presence of ER and neither prostaglandin is associated with the presence of progesterone receptor. Higher levels of both PGE2 and PGF2α are associated with less differentiated tumors, while tumor maximum diameter is negatively associated with PGE2 levels.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-7217
    Keywords: carcinogen-treated human breast epithelial cell lines ; cathepsin D ; estrogen and progesterone receptors ; epidermal growth factor receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The objective of this work was to determine whether transformation of the human breast epithelial cell line MCF-10F by the chemical carcinogens 7, 12-dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene (BP), or c-Ha-ras oncogene transfection, influence the expression of epidermal growth factor receptor (EGFR), estrogen (ER) or progesterone (PR) receptors, and the content of cathepsin-D (Cath.D). MCF-10F control cells did not express any of the phenotypes of neoplastic transformation, whereas carcinogen-treated cells and clones derived from the latter formed colonies in agar-methocel, and exhibited increased chemotaxis and chemoinvasion. Clone BP-1E was also tumorigenic in SCID mice. The BP1 cell line transfected with mutated c-Ha-ras oncogene, named BP1-Tras, became more aggressive after transfection and decreased the latency time to tumorigenesis. Radioligand binding and immunocytochemical reactions were utilized for determining the receptors and Cath.D content of control and carcinogen-treated cells and their derived clones. MCF-10F cells contained 37 fmol/mg of protein of EGFR, ER and PR were undetectable, and Cath.D content was 70 fmol/mg protein. EGFR content was significantly higher in D3-1 and BP1-E cell lines vs the control MCF-10F and the other DMBA and BP clones, correlating positively with the emergence of the transformation phenotype. Whereas EGFR levels were not significantly different in BP1-Tras cells when compared with BP1-E, the former were more tumorigenic in SCID mice, an observation suggesting an alternative pathway in these cells in the formation of tumors. PR, ER, and Cath.D content was not modified by either carcinogen treatment or ras transfection in most of the clones and subclones, except clone BP2 that has a significant increase in ER content, and was not associated with any of the neoplastic phenotypes. These data allowed us to conclude that the level of EGFR is associated with the expression of carcinogen-induced transformation phenotypes whereas ER, PR, and Cath.D did not seem to be modified during the process of chemically induced or c-Ha-ras enhanced transformation of MCF-10F cells.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-7217
    Keywords: breast cancer ; cell lines ; image analysis ; infiltrating ductal carcinoma ; polypeptides ; two-dimensional polyacrylamide gel electrophoresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The protein populations of epithelial cells cultured from two neoplastic and five non-neoplastic human breast tissues were resolved and displayed by two-dimensional polyacrylamide gel electrophoresis and silverstaining. With a computer-based image analysis system, we identified eight polypeptides which are present in both of the neoplastic cell lines, but absent from all five of the cultures of non-neoplastic breast cells. The eight polypeptides are not unique to cells cultured from neoplastic breast, because they are also found in cells cultured from non-breast tissues, both neoplastic and non-neoplastic. Two of the eight polypeptides (∼ Mr 25,000/pI 4.4 and ∼ Mr 31,000/pI 5.5) are present in the patterns of whole tissue samples from infiltrating ductal carcinomas and absent in most normal breast tissue.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 2 (1982), S. 5-73 
    ISSN: 1573-7217
    Keywords: breast cancer ; cell cycle ; DNA-DMBA binding ; DNA repair ; DNA synthesis ; pathogenesis of breast cancer ; susceptibility to carcinogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been demonstrated that in humans certain factors such as early menarche, late pregnancy, and nulliparity are associated with a higher risk of developing breast cancer, while early pregnancy acts as a protective factor. Induction of mammary cancer in rats by administration of the chemical carcinogen 7, 12-dimethylbenz(a)anthracene reveals that the same factors influencing human breast cancer risk also affect the susceptibility of the rat mammary gland to the chemical carcinogen. Nulliparous rats and rats undergoing pregnancy interruption are more susceptible to developing carcinomas. This fact has been attributed to the incomplete differentiation of the gland at the time of carcinogen administration. Parous rats are resistant to the carcinogenic effect of DMBA, which is explained by the complete development of the gland attained during pregnancy and lactation. This development is manifested by the differentiation of terminal end buds into secretory units, which have a smaller proliferative compartment; the epithelial cells of these secretory units have a longer cell cycle, less avidity for binding DMBA, and possess a more efficient DNA excision repair capacity.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 39 (1996), S. 7-20 
    ISSN: 1573-7217
    Keywords: animal models ; carcinogens ; DMBA-induced rat mammary tumors ; terminal end buds ; tumor evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Among the multiple experimental animal models employed for analyzing the various aspects of mammary carcinogenesis, the induction of mammary tumors in rats by chemical carcinogens is one of the models most utilized. Experimentally-induced mammary tumors in rodents have proven to constitute useful tools for the study of the pathogenesis of cancer and of the molecular mechanisms involved in the initiation and progression of the neoplastic process. In vivo experimental animal models provide information not available in human populations; they are adequate for hazard identification, dose-response modeling, exposure assessment, and risk characterization, the four required steps for quantifying the estimated risk of cancer development associated with toxic chemical exposure. Using the DMBA rat mammary model, we have been able to demonstrate that the carcinogen acts on the intermediate cell of the terminal end bud (TEB), and that this structure is the one that evolves to intraductal proliferation, carcinoma in situ, and invasive carcinoma. There are several factors that regulate the susceptibility of the TEB; some of them are: a) topographic location of the mammary gland, b) age of the animal, and c) reproductive history. The understanding of the mechanisms that modulate tumorigenesis will further our knowledge and understanding in the prevention of the disease, as a result of the development of strategies for stopping the progression of the initiated cells.
    Type of Medium: Electronic Resource
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