Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Call number: 03-H:144
    Keywords: Tumor / Entstehung ; Cancer / Prevention ; Cancer / Chemoprevention ; Cancer / Molecular aspects ; Cancer / Genetic aspects
    Notes: This volume is the result of a conference held on September 22-24, 1994, in New York City.
    Pages: xii, 342 p. : ill.
    ISBN: 0897669479
    Signatur Availability
    03-H:144 departmental collection or stack – please contact the library
    BibTip Others were also interested in ...
  • 2
    ISSN: 1573-7217
    Keywords: breast cancer ; cell cycle ; ductal ; histologic subtypes ; lobular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are similar in many respects and their histologic features occasionally overlap. Despite the many similarities, some clinical follow-up data and the patterns of metastasis suggest that ILC and IDC are biologically distinct. Unfortunately, most breast cancer research has focused almost exclusively on the ductal subtype or has not stressed the biologic or molecular genetic distinctions between breast carcinoma subtypes. Several reports have suggested the possibility that ILCs and IDCs differ with respect to expression of antigens involved in proliferation and cell cycle regulation. Therefore, we undertook an immunohistochemical evaluation of cell cycle related antigens in ILCs, including histologic variants thought to represent aggressive neoplasms, and IDCs matched for histologic grade (Modified Bloom–Richardson Grade I). We believe that different antigent expression profiles could elucidate the biological distinctiveness of breast carcinoma subtypes and possibly provide diagnostically relevant information. We studied the expression of the following antigents in 28 archived, formalin-fixed ILCs and 34 well-differentiated IDCs: estrogen receptor (ER), progesterone receptor (PR), Her 2-neu, mib-1, cyclin D1, p27, p53, mdm-2 and bcl-2. 94% of ILCs and 100% of IDCs expressed ER; 75% of ILCs and 76% of IDCs expressed PR; 4% of ILCs and 13% of IDCs expressed c cerb B-2; ILCs and IDCs both expressed mib-1 in approximately 10% of lesional cells; 82% of ILCs and 54% of IDCs expressed cyclin D1; 90% of ILCs and 83% IDCs expressed p27 strongly; 4% of ILCs and 4% of IDCs expressed p53, 25% of ILCs and 33% of IDCs expressed mdm-2; 96% of ILCs and 100% of IDCs expressed bcl-2. None of the apparent differences were statistically significant. The ILC variants demonstrated immunophenotypes that were essentially similar to ILCs of the usual type. We conclude that ILCs and well-differentiated IDCs show similar proliferation and cell cycle control antigen profiles. Despite their unusual histologic features, most ILC variants appear to maintain a characteristic ILC immunophenotype.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1534-4681
    Keywords: Breast cancer ; Bone marrow micrometastasis ; Menstrual cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The timing of breast cancer excision relative to the menstrual cycle has been debated to be of significant prognostic value. The differences in survival relative to the timing in the menstrual cycle have been attributed to the incidence of micrometastasis. Methods: All patients underwent bone marrow aspiration after the diagnostic surgical biopsy, immediately before definitive surgery. The timing of the diagnostic surgical biopsy in the menstrual cycle was calculated according to Senie. Monoclonal antibodies to epithelium-specific antigens were used to detect bone marrow micrometastasis (BMM). Results: This study reports on the effect of the phase of the menstrual cycle on incidence of BMM after surgical biopsy. Ninety-two patients with regular cycles underwent bone marrow aspiration an average of 12 days (range 0–32 days) after biopsy. Thirty-nine patients had undergone biopsy during the follicular phase and 53 patients during the luteal phase. BMM were detected in 31% of patients (29 of 92). We observed BMM in 33% of patients (13 of 39) in the follicular phase and in 30% of patients (16 of 53) in the luteal phase. This difference is not significant (p〉0.70). The mean number of cells detected and the presence of clumps of cells is similar in the two groups. Conclusions: The incidence and characteristics of bone marrow micrometastases are independent of the timing of diagnostic excision biopsy in the menstrual cycle.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1573-7217
    Keywords: erbB-2 protein ; serum ; tumor ; age ; nulliparity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We compared levels of erbB-2 oncoprotein among three groups: Group I included 60 asymptomatic women; Group II had 51 women with benign breast biopsies; and Group III had 67 women with node-negative breast cancer. Serological levels of erbB-2 protein were measured in all participants; tumor levels were measured for Groups II and III. Forty-three percent of usable tumors (25/58), including three of seven lobular tumors, were erbB-2 positive. Tumor and blood oncoprotein levels were unrelated. Blood levels, however, were positively related to tumor volume, but only when the tumor had both a ductal carcinoma in situ (DCIS) component and an invasive component, suggesting a role for erbB-2 protein in progression of DCIS to invasive carcinoma. In Groups I and II serological levels of erbB-2 protein were directly related to age, and inversely related to having had a live birth. Therefore, a model that determined the threshold levels of serological erbB-2 positivity in Group III included age and nulliparity as independent variables. Only three of the 67 women (4.5%) in Group III were positive for serological erbB-2. In a multivariate model, with serological erbB-2 as the dependent variable, and in which the independent variables included Study Group, there was a statistical trend for younger women, in which Group III had the highest serological levels of erbB-2, followed by Group II, and then Group I. In women who were over the age of 50 years the trend was reversed; i.e., levels of erbB-2 tended to be lowest in Group III, followed by Group II, and finally Group I.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1573-7217
    Keywords: mammary epithelial cells ; RAS-transfection ; biomarkers ; tumorigenicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Deregulated expression of the RAS oncogene is associated with tumorigenic transformation of mammary cells. Because of the complex, multiphasic nature of cancer progression, it is important to systematically identify the biomarkers specific for initiation, promotion, and progression of breast cancer. Mouse mammary epithelial cells (MMEC) were transfected with normal c-Ha-RAS proto oncogene (pH06N) and with mutant c-Ha-RAS oncogene (pH06T). The parental MMEC and the cloned transfectants pH06N1, pH06N2, pH06T1, and pH06T12 were evaluated for the acquisition of transformed characteristics by determining altered cellular metabolism of estradiol, increased ability for anchorage-independent growth, and ability to form tumors at the transplant site in athymic ‘nude’ mice. Persistent, functional integration of c-Ha-RAS was evidenced by the presence of a 1.2 kb c-Ha-RAS transcript in the four transfectants but not in MMEC. All the transfectants also exhibited a substantial increase in the binding of c-Ha-RAS p21 to [α-32P] GTP relative to MMEC (P〈0.003). The relative extent of estradiol metabolism leading to the formation of 16α-hydroxyestrone was increased (P〈0.004) in all the four transfectants. These four transfectants also showed a 100–400 fold increase in colony forming efficiency in 0.33% agar, relative to MMEC (P〈0.0009), and formed rapidly growing tumors within 3–5 weeks of transplantation. Our results demonstrate that i) persistent expression of normal and mutant c-Ha-RAS can bring about tumorigenic transformation of mouse mammary epithelial cells; and ii) alteration in estradiol metabolism and acquisition of anchorage-independent growth precede the emergence of a tumorigenic phenotype. These endpoints therefore may constitute useful intermediate biomarkers to examine oncogene-induced tumorigenic transformation of mammary epithelial cells.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1573-7217
    Keywords: anticarcinogenesis ; intermediate biomarkers ; mammary epithelial cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA) is a metabolism-dependent procarcinogen whose tumorigenicity is modified by dietary and endocrine manipulationsin vivo. DMBA initiates molecular and cellular alterations in the mammary tissue, while dietary components and estrogens affect the post-initiational phase of tumorigenic transformation. The mechanism(s) responsible for modulation of tumorigenic transformation remain unclear. This study examines the effects of selected tumor suppressing agents and estradiol (E2) metabolites onin vitro DMBA carcinogenesis utilizing a newly established mouse mammary epithelial cell line C57/MG. Alteration in DNA repair synthesis, metabolism of E2 via the C2- and C16α-hydroxylation pathways, and acquisition of anchorage-independent growth were utilized as molecular, endocrine, and cellular biomarkers to quantitate the cellular transformation by DMBA and its modulation by tumor suppressing agents and E2 metabolites. A single 24 hr exposure of 0.78 µM DMBA to C57/MG cells resulted in a 193.9% increase in DNA repair synthesis and a 73.1% decrease in C2/C16α hydroxylation of E2. The DMBA treated C57/MG cells also exhibited increased anchorage-independencein vitro prior to tumorigenesisin vivo. A simultaneous treatment of cells with DMBA and with the highest non-cytotoxic doses of the tumor suppressing agents 5 µM N-(4-hydroxyphenyl) retinamide (HPR), 50 µM indole-3-carbinol (I3C), or 1 µM tamoxifen (TAM) resulted in a 35.6% to 63.9% decrease in DNA repair synthesis, a 23.8% to 1347.6% increase in C2/C16α hydroxylation of E2, and a 53.8% to 72.4% decrease in anchorage-independent growth. The E2 metabolites at the highest non-cytotoxic doses of 0.76 µM estrone (E1), 0.69 µM 2-hydroxyestrone (2-OHE1), and 0.66 µM 2-methoxyestrone (2-MeOHE1) suppressed DMBA-induced DNA repair synthesis by 56.0% to 68.8%. These tumor suppressing agents and E2 metabolites also effectively suppressed post-initiational, anchorage-independent growth by 24.9% to 72.4%. These results indicate that DMBA induces cellular transformation in part by causing DNA damage, altering C2/C16α hydroxylation in favor of C16α-hydroxylation, and inducing anchorage-independent growth prior to tumor development. Effective downregulation of these genotoxic, endocrine and proliferative end points by prototypic tumor suppressing agents and by E2 metabolites generated via the C2-hydroxylation pathway suggest that these agents may influence mammary tumorigenesis by inhibiting early occurring initiational and/or post initiational events.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1573-7217
    Keywords: estradiol metabolism ; mammary tissue ; explant culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vivo experiments have demonstrated a correlation between the extent of 16α-hydroxylation of estradiol and incidence of mammary cancer. The ability of mammary ductal epithelium (MDE), the site for neoplastic transformation, to metabolize estradiol or to accumulate estradiol metabolites has not been unequivocally established. Using a newly developed mammary explant culture system and a radiometric assay, we have compared the site-specific metabolism of estradiol (E2) by the C-17-oxidation and C-16α-hydroxylation pathways in mouse tissues that differ in relative risk for mammary cancer. A comparison between MDE (target tissue) and liver (nontarget tissue) from NFS (low risk) and C3H/ouj (high risk) mice revealed that: a) increase in C-17-oxidation was similar in MDE and liver from the two strains, and b) while C-16α-hydroxylation was similar in liver from the two strains (p = 0.5, n.s.), it was increased 4-fold in the MDE from the high risk C3H/ouj strain relative to that from the low risk NFS strain (p = 0.001). Furthermore,in vivo administration of progesterone resulted in modulation of cell proliferation as well as of E2 metabolism in mammary explant cultures. The effect of progesterone depended upon the presence of the MtV-2 proviral gene. This study demonstrates that mammary explants can extrahepatically metabolize estradiol. The specific risk-related increase in C-16α-hydroxylation suggests that intrinsic metabolic ability of the target tissue leading to the formation of 16α-hydroxyestrone from estradiol may be a determinant in the relative risk for developing mammary cancer.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 0741-0581
    Keywords: Stereocilia ; Postmortem cochlea ; Scanning electron microscopy ; Human ; Guinea pig ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: The morphology of hair bundles has been studied by high resolution scanning electron microscopy using a variety of fixatives, including glutaraldehyde, glutaraldehyde-picrate, glutaraldehyde-tannic acid, glutaraldehyde followed by post-fixation in osmium tetroxide, and the osmium thiocarbohydrazide technique. Critical evaluation of several metal coatings, gold, gold-palladium, and platinum has been carried out.Both the surface texture of stereocilia and their cross-links are sensitive to fixation and metal coating. We are of the opinion that glutaraldehyde gives the best general quality of fixation and preservation for all types of cross-links. We have described three major sets of cross-links: first, lateral links connecting stereocilia within the same row; second, lateral links connecting stereocilia of adjacent rows; and third, upward-pointing links, one per stereocilium, connecting the tip of each shorter stereocilium to the lateral surface of the adjacent taller stereocilium. Current physiological and anatomical evidence suggests that the lateral links couple the individual stereocilia within the hair bundle so that they function as a single mechanical unit. The upward-pointing tip links are ideally placed to respond to mechanical deformation of the hair bundle, being stretched when the stereocilia are deflected in the excitatory direction towards the tallest row and relaxed when deflected in the opposite, inhibitory direction.Postmortem morphological changes are detected within 15 minutes of cardiac arrest and become progressively more pronounced in time. These results enabled us to distinguish specific druginduced changes which could not be attributed simply to cell death. Effects of cisplatin and kanamycin upon hair bundles are described. The work reported here is based on studies using the guinea pig cochlea. Some of the postmortem changes described have also been confirmed in human cochleas.It is stressed that many of the postmortem and drug-induced effects can only reliably be studied by high resolution scanning electron microscopy coupled with appropriate prearation procedures.
    Additional Material: 34 Ill.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1534-4681
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Studies from this laboratory have demonstrated that negative modulation of the C-2/C-16α ratio of estradiol metabolites serves as a marker of the action of oncogenes and carcinogens which increase tumorigenicity, while positive modulation of this ratio measures the preventive effects of chemotherapeutic and chemopreventive agents on tumors and tumor cells. In order to facilitate human studies on chemopreventive agents and facilitate the measurement of this ratio, we have validated an ELISA assay using monoclonal antibodies developed by Immunocare, Inc., coated to 96-well plates.Urine samples (10λ) were diluted in buffer and hydrolyzed with mixed glucuronidase and sulfatase to cleave the conjugates. Aliquots of the hydrolysate were added to ELISA plates coated with the C-2 and C-16α antibodies respectively and the appropriate labeled antigens were added. After incubation the plates were washed, the color reagent added, and the plates read kinetically to determine the amount of compound present. A standard curve is run on each plate along with high and low standards. All samples were run in triplicate and the mean values determined. The ratios were computed automatically by the reader.Blind comparisons of duplicate urine samples showed a mean r value of 97%. Mean intra-assay variability was under 8% and inter-assay variability was under 10%.Studies involving diet modification and the differences between breast cancer patients and controls are underway.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...