Markers of progression and invasion in short term follow up of untreated breast cancer patients

Rabi, Zaki Abu; Todorović‐Raković, Nataša; Vujasinović, Tijana; Milovanović, Jelena; Nikolić‐Vukosavljević, Dragica

doi:10.3233/cbm-150516

Cited by 13 publications

(6 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Carlos reported that hyaluronan promotes cancer cell migration and increases the secretion of matrix metalloproteinase, specifically the increased active form of MMP-2 28 . Several studies indicated that a high MMP-2 expression is correlated to poor prognosis in prostate cancer 11 , bladder cancer, and breast cancer 29 . In addition, MMP-2 upregulation is associated with poor prognosis in RCC patients, and thus the inhibition of MMP-2 activity can suppress cancer metastasis 30 .…”

Section: Discussionmentioning

confidence: 99%

Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways

Hung

Chen

et al. 2017

Int. J. Med. Sci.

View full text Add to dashboard Cite

Kaempferol, which is isolated from several natural plants, is a polyphenol belonging to the subgroup of flavonoids. Kaempferol exhibits various pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. In this study, kaempferol can significantly inhibit the invasion and migration of 786-O renal cell carcinoma (RCC) without cytotoxicity. We examined the potential mechanisms underlying its anti-invasive activities on 786-O RCC cells. Western blot was performed, and the results showed that kaempferol attenuates the manifestation of metalloproteinase-2 (MMP-2) protein and activity. The inhibitive effect of kaempferol on MMP-2 may be attributed to the downregulation of phosphorylation of Akt and focal adhesion kinase (FAK). By examining the SCID mice model, we found that kaempferol can safely inhibit the metastasis of the 786-O RCC cells into the lungs by about 87.4% as compared to vehicle treated control animals. In addition, the lung tumor masses of mice pretreated with 2-10 mg/kg kaempferol were reduced about twofold to fourfold. These data suggested that kaempferol can play a promising role in tumor prevention and cancer metastasis inhibition.

show abstract

Section: Discussionmentioning

confidence: 99%

Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways

Hung

Chen

et al. 2017

Int. J. Med. Sci.

View full text Add to dashboard Cite

show abstract

“…The presence of the IL8 (-251) A allele and/or the CXCR2 (+1208) T allele showed a significant association with decreased overall survival and decreased disease-free survival. We have recently shown the prognostic relevance of IL8 in adjuvantly untreated early breast cancer patients in short-term and long-term follow-up (Milovanović et al 2013;Abu Rabi et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Interleukin 8 in progression of hormone-dependent early breast cancer

et al. 2017

Self Cite

View full text Add to dashboard Cite

The only way to perceive the real clinical course of disease and the prognostic significance of potential biomarkers is follow-up of patients who did not receive any kind of adjuvant therapy. Many studies have confirmed high levels of interleukin 8 (IL8) in HER2-enriched and basal-like (ER-) primary breast tumours, but less is known about the significance of IL8 in hormone-dependent breast cancer. The aim of this study was to evaluate the prognostic significance of IL8 and clinicopathological parameters in hormone-dependent breast cancer, and to examine possible associations between them that might imply possible biological dependence. The study included 91 early-stage breast cancer patients with detectable levels of hormone receptors (ER>0, PR>0). None of the patients received adjuvant therapy according to valid protocol at that time. HER2 status was determined on paraffin-embedded tumour tissue sections by CISH. IL8 levels were determined by ELISA in cytosol tumour extracts of 65 patients with long-term follow-up (144 months). Nonparametric statistical tests were used for data analyses. Patients with low IL8 levels (M<88.8 pg/mg) had significantly longer relapse-free survival (RFS) compared to patients with high IL8 levels (M≥88.82 pg/mg) (Log rank test, p=0.002). Patients with ERhighIL8low phenotype had significantly longer RFS compared to those with ERhighIL8high and ERlowIL8high phenotypes (p=0.04 and p=0.02, respectively); patients with PRlowIL8low phenotype had significantly longer RFS compared to those with PRlowIL8high and PRhighIL8high phenotypes (p=0.003 and p=0.02, respectively); patients with HER2-IL8low phenotype had significantly longer RFS compared to those with HER2-IL8high and HER2+IL8high phenotypes (p=0.01 and p=0.02, respectively). Our results indicate significant contribution of IL8 on survival of hormone-dependent early-stage breast cancer patients and association with established parameters such as ER/PR and HER2.

show abstract

“…Our findings confirm those of numerous other studies that have reported uPA and PAI-1 to be statistically independent prognostic factors in lymph node-negative breast cancer patients. 10 - 18 However, these studies did not include HER2 status which is now an important part of the decision about adjuvant systemic therapy. Because of the observed associations between overexpression of the HER2/ neu protein and tumor proteolytic factors in breast and in other cancers 19 - 21 , HER2/neu has been suggested to up-regulate the proteolytic enzymes, including uPA and PAI-1, and thus play a direct role in tumor invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients

Dovnik

Takač

2016

Radiology and Oncology

View full text Add to dashboard Cite

BackgroundThe association of HER2 status with urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) levels raises the question whether uPA/PAI-1 level carries additional clinically relevant prognostic information independently from HER2 status. The aim of our study was to compare the prognostic value of uPA/PAI-1 level, HER2 status, and traditional prognostic factors for survival in node-negative breast cancer patients.Patients and methodsA retrospective analysis of 858 node-negative breast cancer patients treated in Maribor University Clinical Center, Slovenia, in the years 2000–2009 was performed. Data were obtained from patient medical records. The median follow-up time was 100 months. Univariate and multivariate analyses of disease-free (DFS) and overall survival (OS) were performed using the Cox regression and the Cox proportional hazards model.ResultsIn univariate analysis, age, tumor size, grade, lymphovascular invasion, HER2 status and UPA/PAI-1 level were associated with DFS, and age, tumor size, grade, and uPA/PAI-1 level were associated with OS. In the multivariate model, the most important determinants of DFS were age, estrogen receptor status and uPA/PAI-1 level, and the most important factors for OS were patient age and tumor grade. The HR for death from any cause in the multivariate model was 1.98 (95% CI 0.83–4.76) for patients with high uPA and/or PAI-1 compared to patients with both values low.ConclusionsuPA/PAI-1 level clearly carries an independent prognostic value regardless of HER2 status in node-negative breast cancer and could be used in addition to HER2 and other markers to guide clinical decisions in this setting.

show abstract

Markers of progression and invasion in short term follow up of untreated breast cancer patients

Abstract: Higher concentrations of IL-8, uPA, PAI-1 and MMP2, as is MMP9 and VEGF, confirmed aggressive phenotype and poor prognosis in different subgroups.

Cited by 13 publications

References 39 publications

Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways

Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways

Interleukin 8 in progression of hormone-dependent early breast cancer

Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients

Contact Info

Product

Resources

About