DNA aneuploidy and cell proliferation in breast tumors

Christov, Konstantin; Milev, A.; Todorov, V.

doi:10.1002/1097-0142(19890801)64:3<673::aid-cncr2820640318>3.0.co;2-d

Cited by 26 publications

(9 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When examining alterations in small palpable mammary cancers, one should note that these tumors are diploid (as evaluated by flow cytometry) and not as genetically advanced as most human malignant tumors. Most human breast cancers (>75%) include DNA-aneuploid cell clones, which differ in their proliferative activity and probably in their sensitivity to preventive/ antitumor agents (33).…”

Section: Discussionmentioning

confidence: 99%

Short-term Modulation of Cell Proliferation and Apoptosis and Preventive/Therapeutic Efficacy of Various Agents in a Mammary Cancer Model

Christov

Grubbs

Shilkaitis

et al. 2007

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: The methylnitrosourea (MNU)-induced mammary cancer model in rats is similar to estrogen receptor^positive breast cancer in women. In prevention studies using this model, tumor incidence and multiplicity were typically primary end points. The ability of various agents administered for a short period to modulate cell proliferation [proliferation index (PI)] and apoptosis [apoptotic index (AI)] in mammary cancers was compared with their efficacy in long-term prevention and therapy studies. Experimental Design: Rats were injected with MNU to induce mammary cancers. For the prevention studies, agents were administered by gavage or in the diet beginning 5 days after MNU. For proliferation (PI) and apoptosis (AI) experiments, animals with a palpable mammary cancer were treated with the agents for only 4 to 7 days. PI was determined following 5-bromodeoxyuridine labeling whereas AI was determined using the terminal deoxyribonucleotidyl transferase^mediated dUTP nick end labeling assay. Therapeutic efficacy was evaluated by measuring cancer size over a 6-week period. Results: Treatments with differing chemopreventive efficacy and mechanism(s) of action were examined: (a) hormonal treatments [tamoxifen, vorozole (an aromatase inhibitor), and ovariectomy]; (b) retinoid X receptor agonists (targretin, 9-cis retinoic acid, and UAB30); (c) inducers of drug-metabolizing enzymes (indole-3-carbinol, 5,6 benzoflavone, and diindoylmethane); (d) agents that alter signal transduction (R115777, a farnesyltransferase inhibitor); Iressa (an epidermal growth factor receptor inhibitor); sulindac and celecoxib (cyclooxygenase 1/2 and cyclooxygenase 2 inhibitors); and (e) diverse agents including meclizine, vitamin C, and sodium phenylbutyrate. Correlations between inhibition of PI, increase of AI, and chemopreventive efficacy were observed. Although most agents with moderate or low preventive efficacy suppressed PI, they minimally affected AI. Conclusions: The data confirmed that the short-term effects of various agents on cell proliferation and apoptosis in small mammary cancers can predict their preventive/therapeutic efficacy. Thus, these biomarkers can be used to help determine the efficacy of compounds in phase II clinical prevention trials.The methylnitrosourea (MNU) model of mammary carcinogenesis in rats was developed f30 years ago by Gulliano et al.(1). The resulting mammary tumors are primarily carcinomas (1, 2) and show many of the histopathologic and biological characteristics of estrogen receptor -positive breast cancer in women (3). In this model, almost all animals develop multiple mammary tumors after a relatively short latency (3-4 months). In addition, the morphology, origin (terminal end buds or terminal ductal lobular units), and preinvasive stages (hyperplasia, ductal carcinoma in situ) of these tumors seem to be similar to human breast cancer (2, 3). More recently, studies on gene expression have shown that MNU-induced mammary cancers are similar in gene expression to that of welldifferentiated duct...

show abstract

Section: Discussionmentioning

confidence: 99%

Short-term Modulation of Cell Proliferation and Apoptosis and Preventive/Therapeutic Efficacy of Various Agents in a Mammary Cancer Model

Christov

Grubbs

Shilkaitis

et al. 2007

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…6 These results are similar to those from the literature in 12 of 15 studies concerning tumor size [13][14][15][16][17][18][19][20][21][22][23][24] and in 8 of 9 studies concerning patient age. 15,16,20 -22,24 -26 A consensus concerning tumor grade and hormone receptor status was reached in 8 studies concerning tumor grade 14,17,[24][25][26][27][28][29] and in 16 studies concerning hormone receptor status. 13,15-20,22-24,26,27,29 -32 SPF was an important prognostic factor in the whole population for both OS and MFS (stratified or not according to treatment).…”

Section: Discussionmentioning

confidence: 99%

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Michels

Duigou

Marescaux

et al. 2003

Cancer

View full text Add to dashboard Cite

BACKGROUNDBetween January 11, 1991 and January 8, 1992, 104 patients with previously untreated, invasive, primitive breast carcinoma were admitted to the authors' hospital.METHODSFor each patient, flow cytometry DNA analyses on frozen samples and on immunohistochemical staining were performed, including Ki‐67, cyclin A, p53, and p21waf1 (p21), with assessment of the percentages of positive nuclei were assessed. Correlations with classic clinicopathologic data and survival (overall, metastasis free, or recurrence free) and a multivariate analysis were performed.RESULTSAfter a multivariate analysis according to a Cox model that was stratified by age, tumor size, tumor grade, lymph node status, and receptor status, among the factors studied, the presence of p21 was the unique remaining prognostic factor for patients with invasive breast carcinoma. Because of the lack of a correlation between p21 and proliferative factors (Ki‐67, S‐phase, and cyclin A), the authors combined p21 with those markers and found that, for the different combinations, after statistical analysis, only p21 combined with S‐phase or with cyclin A and lymph node status were salient survival prognostic factors.CONCLUSIONSImmunohistochemical study of proteins involved in the cell cycle and assessment of proliferative activity using flow cytometric DNA analysis aided the authors in singling out correlations of cyclin A and S‐phase, along with p21, with metastasis free survival and overall survival in patients with invasive breast carcinoma. These promising results will require confirmation in a larger series of patients. Cancer 2003;97:1376–86. © 2003 American Cancer Society.DOI 10.1002/cncr.11209

show abstract

“…The state of proliferation and lack thereof have hecome prime concerns for oncologists in their evaluation of prognosis and predictive response to therapeutic modalities. The evaluative and prognostic implications have been amplified by investigations that correlate increased proliferative activity with increased metastatic propensity (29,341 and decreased patient survival (3,11,24,35,37,44,45).…”

mentioning

confidence: 99%

Expression of proliferation‐associated antigens (PCNA, p120, p145) during the reentry of G₀ cells into the cell cycle

Bolton¹,

Freeman

Mikulka³

et al. 1994

Cytometry

View full text Add to dashboard Cite

Flow cytometric bivariate analysis was used to evaluate the expression of PCNA, p120, and p145 during the Go reentry of CHO-K1 cells into the cell cycle. CHO-K1 cells were placed in a G,-like state using serum depletion and stimulated to reenter the cell cycle by replating into fresh, serum-containing medium. At discrete intervals after stimulation, replicate samples were stained for either PCNA, p120, or 145; stained for DNA (Coulter DNAPrep); evaluated on the EPICS Profile I; and analyzed on the EPICS ELITE workstation. PCNA stained less than 10% of the Go cells; in contrast, however, 3035% of the Go cells were positive for p120 and p145. Eight hours after stimulating Go cells to reenter the cell cycle (during Go/ GI), p120 reached 88% positivity, while p145 and PCNA were 63% and 30% positive, respectively. Cells in S phase (12 and 16 h following Go stimulation) were greater than 90% positive for all three antigens. PCNA had the greatest change throughout the Go reentry process, both in percentage positive and quantitatively (mean channel fluorescence).This report indicates that all three proliferation-associated antigens studied are differentially expressed during the reentry of Go cells into the cell cycle. Furthermore, these antigens may be useful in the early detection of Go recruitment.

show abstract

DNA aneuploidy and cell proliferation in breast tumors

Cited by 26 publications

References 22 publications

Short-term Modulation of Cell Proliferation and Apoptosis and Preventive/Therapeutic Efficacy of Various Agents in a Mammary Cancer Model

Short-term Modulation of Cell Proliferation and Apoptosis and Preventive/Therapeutic Efficacy of Various Agents in a Mammary Cancer Model

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Expression of proliferation‐associated antigens (PCNA, p120, p145) during the reentry of G₀ cells into the cell cycle

Contact Info

Product

Resources

About

DNA aneuploidy and cell proliferation in breast tumors

Cited by 26 publications

References 22 publications

Short-term Modulation of Cell Proliferation and Apoptosis and Preventive/Therapeutic Efficacy of Various Agents in a Mammary Cancer Model

Short-term Modulation of Cell Proliferation and Apoptosis and Preventive/Therapeutic Efficacy of Various Agents in a Mammary Cancer Model

Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma

Expression of proliferation‐associated antigens (PCNA, p120, p145) during the reentry of G0 cells into the cell cycle

Contact Info

Product

Resources

About

Expression of proliferation‐associated antigens (PCNA, p120, p145) during the reentry of G₀ cells into the cell cycle