We examined morphological changes using phase-contrast microscopy and immuohistochemistry. In accordance, TNK2 overexpression was shown to promote invasion of cancer cells but the mechanism by which TNK2 mediates these effects is unresolved.
Conclusions:
Our documents propose that TNK2 can enhance migration and invasion of breast cancer cells via preservation of EGFR expression, notwithstanding its previously reported signalling via BCAR1, explaining its oncogenic behaviour in vitro and correlation with metastatic human breast cancer in vivo. We could demonstrate that the main functional effect of activating these surface EGFRs in breast cancer cells is stimulation of migration. In that study, we sought to investigate whether negative targeting of TNK2 by siRNA could be used to inhibit cancer cell invasion, set up the contribution of its effect on the EGFR and consequently attempt to resolve the issue of TNK2’s mechanism of action. We thus hypothesised that a component of the […]
Original post by Jillian Howlin, Jeanette Rosenkvist and Tommy Andersson
Samples were assayed by Luminex for 55 serum biomarkers including: cancer antigens, growth/angiogenic factors, apoptosis-related molecules, metastasis-related molecules, adhesion molecules, adipokines, cytokines, chemokines, hormones, and other proteins. Serum biomarker levels are increasingly being investigated for their ability to predict therapy response and aid in the development of individualized treatment regimens. Samples were collected prior to each of four rounds of treatment and prior to definitive surgery.
Materials and Methods: Serum samples were collected from 44 patients enrolled in a phase I-II, open-label study of liposomal doxorubicin and paclitaxel in combination with whole breast hyperthermia for the neoadjuvant treatment of locally advanced breast cancer (stage IIB or III).
Conclusions:
We demonstrate here that serum biomarker profiles may offer predictive capability concerning treatment response and outcome in the neoadjuvant setting. Multianalyte profiles may offer greater predictive ability for neoadjuvant treatment response than the individual […]
Original post by Brian M Nolen, Jeffrey R Marks, Shlomo Ta’san, Alex Rand, The Minh Luong, Yun Wang, Kimberly Blackwell and Anna Lokshin
The expression of matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs (TIMPs) were determined using an MMP array kit and enzyme-linked immunosorbent assays. Upregulation of TIMP-2 production is one mechanism by which JS-K mediates its anti-invasive effects. IntroductionTumor invasion and metastasis remain a major cause of mortality in breast cancer patients. JS-K and other NO prodrugs may represent an innovative biological approach in the prevention and treatment of metastatic breast cancer. JS-43-126, a non-NO-releasing analog of JS-K, had no effect on NO levels or invasion. Conclusions:
We report the novel findings that JS-K inhibits breast cancer invasion across the Matrigel basement membrane, and NO production is vital for that activity. Methods:
that study was designed to determine the effects of the NO-releasing prodrug JS-K on breast cancer invasion and the mechanisms involved. High concentrations of nitric oxide (NO) suppress tumor invasion and metastasis in […]
Original post by Ann-Marie Simeone, Vanity McMurtry, Rene Nieves-Alicea, Joseph Saavedra, Larry Keefer, Marcella Johnson and Ana M Tari
However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues. that effect is sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones.
Methods:
Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with estrogen and progesterone (E+P) for 14 days, thereupon were tested for p53-dependent responses to ionizing radiation.
Conclusions:
Therefore, E+P and parity confer a sustained increase in p53-mediated apoptosis within the mammary epithelium and suppresses mammary tumorigenesis, but that effect was not retained in epithelial outgrowths. IntroductionTreatment with estrogen and progesterone mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether […]
Original post by Karen A Dunphy, Anneke C Blackburn, Haoheng Yan, Lauren R O’Connell and D JOSEPH Jerry
In contrast, total IGFBP-3 levels were positively correlated with WHR (r = 0.115; P = 0.002), parity (rs = 0.089; P = 0.02), BMI (r = 0.115; P = 0.002), physical activity (r = 0.118; P = 0.002), IGF-I levels (r = 0.588; P < 0.0001), and negatively correlated with percent or absolute breast density (r = -0.095; P = 0.01 and r = -0.075; P = 0.04, respectively). However, associations of IGFBP-3 levels with breast cancer risk have been inconsistent, possibly due to the different predominant forms of circulating IGFBP-3 (intact versus fragmented) that were measured in these studies. Intact and total IGFBP-3 levels were correlated with age and smoking. The associations were evaluated using generalized linear models and Pearson’s (r) or Spearman’s (rs) partial correlation coefficients. These findings propose that different molecular forms of IGFBP-3 may bear different relations to premenopausal breast cancer risk. […]
Original post by Caroline Diorio, Jacques Brisson, Sylvie Berube and Michael Pollak
Results:
Tumor growth varied considerably amoung subjects, with 5 % of tumors using less than 1.2 months to grow from 10 to 20 mm in diameter, and another 5 % using more than 6.3 years. IntroductionKnowledge of tumor growth is critical in the planning and evaluation of screening programs, clinical trials, and epidemiological studies. Compared to previously used Markov models for tumor progression, the applied model gave considerably higher model fit (85 % increased predictive power) and provided estimates directly linked to tumor size.
Methods:
A likelihood based estimating procedure was used, where both tumor growth and screen pop quiz sensitivity [STS] were modeled as continuously increasing functions of tumor size. STS was estimated to increase sharply with tumor size, going from 26 % at 5 mm to 91 % at 10 mm. The mean instance a tumor needed to grow from 10 to 20 mm in […]
Original post by Harald HWF Weedon-Fekjaer, Bo Henry BHL Lindqvist, Odd Olai OOA Aalen, Lars Johan LJV Vatten and Steinar ST Tretli
Sequencing analysis revealed that six phage proteins were in-frame and rare. The putative tumor-associated phage clones were collected for PCR and sequencing analysis. IntroductionCurrently only a limited number of tumor markers for breast cancer are available. different and ORF phage-expressed proteins were soon after used to develop phage protein enzyme-linked immunosorbent assays (ELISAs) to measure corresponding autoantibodies using 87 breast cancer patients and 87 normal serum samples. Antibodies to these six phage-expressed proteins were measured by ELISAs and results showed that three of the phage clones had statistical significance in discriminating patients from normals. Antibodies to tumor-associated proteins may expand the number of available tumor markers for breast cancer and be used together in a serum profile to enhance sensitivity and specificity. The enrichment of tumor-associated proteins after biopanning was tested using plaque-lift assay and immunochemical detection.
Results:
We harvested 100 putative tumor-associated phage […]
Original post by Li Zhong, Kun Ge, Jin-chi Zu, Long-hua Zhao, Wei-ke Shen, Jian-fei Wang, Xiao-gang Zhang, Xu Gao, Wanping Hu, Yun Yen and Kemp H Kernstine
In that study we aimed to identify a possible mechanism of action for the antiproliferative effect of eupatorin, which can be attributed to CYP1 family mediated metabolism. Results:
Eupatorin showed a dose dependent inhibitory effect of cell growth on MDA-MB-468 cells with a sub-micromolar IC50 whereas the IC50 of that compound in MCF-10A cells was considerably higher.
Methods:
The study focuses on the antiproliferative action of eupatorin on the human breast carcinoma cell line MDA-MB-468, and on a cell line derived from normal mammary tissue, MCF-10A. CYP1B1 and CYP1A1 have plus been proposed as targets for cancer chemotherapy for their differential and selective overexpression in tumor cells. Eupatorin was further shown to arrest the cell cycle of the CYP1-expressing cell line MDA-MB-468 in G2/M phase, whereas no effect was noticed in MCF-10A cells which do not express CYP1 enzymes. The effect of eupatorin on the MDA-MB-468 […]
Original post by Vasilis P Androutsopoulos, Randolph RJ Arroo, John F Hall, Somchaiya Surichan and Gerry A Potter
Epidemiologic evidence for a protective role of NSAIDs in breast cancer, however, is equivocal. Neither aspirin nor nonaspirin NSAIDs were associated with risk of ER-negative breast cancer. As cyclooxygenase inhibition by aspirin (but not other NSAIDs) is irreversible, we tested associations by NSAID type.
Methods:
We tested NSAID use for its organization with breast cancer incidence in the National Institutes of Health-AARP Diet and Health Study, where 127,383 female AARP (formerly known as the American organization of Retired Persons) members with no history of cancer, aged 51 to 72 years, completed a mailed questionnaire (1996 to 1997). Although we observed no significant differences in risk for daily use (versus nonuse) of aspirin (relative risk = 0.93, 95% confidence interval = 0.85 to 1.01) or nonaspirin NSAIDS (relative risk = 0.96, 95% confidence interval = 0.87 to 1.05), risk of ER-positive breast cancer was significantly reduced with daily […]
Original post by Gretchen L Gierach, James V Lacey, Arthur Schatzkin, Michael F Leitzmann, Douglas Richesson, Albert R Hollenbeck and Louise A Brinton
Among the ER-positive cancers, the proliferation signature (FDR q =0.001) and the Genomic Grade Index (FDR q =0.015) were additionally significantly enriched in cases with pCR. IntroductionOur goal was to examine the organization within biological pathways and response to chemotherapy in estrogen receptor (ER)-positive and ER-negative breast cancers separately.
Ki67 expression, as one gene marker of proliferation, did not supply the same knowledge as the entire proliferation signature. Among the ER-negative cancers, a proliferation gene signature (FDR q=0.1), the Genomic Grade Index (FDR q =0.044) and the E2F3 pathway (FDR q =0.22, p=0.07) signature were enriched in the pCR group.
Conclusion:
Proliferation- and genomic grade-related gene signatures are associated with chemotherapy sensitivity in both ER-negative and -positive breast cancers. An ER-associated gene set (FDR q = 0.03) and a mutant p53-gene signature (FDR q = 0.0019) were enriched in ER-positive cancers with residual cancer. Genes […]
Original post by Attila Tordai, Jing Wang, Fabrice Andre, Cornelia Liedtke, Kai Yan, Christos Sotiriou, Gabriel N Hortobagyi, Fraser W Symmans and Lajos Pusztai