【摘 要】
:
Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer (BC) that lacks the expression of estrogen receptor, pro.gesterone receptor and human epidermal growth factor receptor-2.
【机 构】
:
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University
【出 处】
:
BITs 3rd Annual World Cancer Congress-2012(2012第五届世界癌症大会)
论文部分内容阅读
Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer (BC) that lacks the expression of estrogen receptor, pro.gesterone receptor and human epidermal growth factor receptor-2.Despite TNBC represents only 15 % of all types of BC, it accounts a disproportionate number of metastatic cases and deaths.Because of the poor prognosis and the high rate of metastasis, local and systemic recurrence associated with TNBC, researchers have been actively looking for target therapies and innovative therapeutic strategies to effectively treat this aggressive disease.Unfortunately, molecular targets and predictors for the treatment of TNBC do no currently exist.Accordingly,this study has been initiated to investigate the differential expression of biological markers in TNBC and Non-TNBC Saudi females that might be utilized as potential targeted-therapy and/or predict sensitivity to currently available therapeutic regimens.To achieve the ultimate goal of this study, a total of 200 formalin-fixed and paraffin-embeded (FFPE) breast cancer samples were selected and divided into 3 groups;control benign and normal breast tissues (20),TNBC (80) and Non-TNBC (100).Expression ofmRNA in FFPE tissues was performed using RT-PCR for the following genes;poly(ADP-ribose)polymerase (PARP-1), topoisomerase-2A (TOP-2A), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP-2 and MMP-9), human epidermal growth factor-1 (HER-1) and multidrug resistance genes.In TNBC group, mRNA expression ofPARP-1, TOP-2A,HER-1, VEGF, bFGF and MMP-2 genes showed a highly significant and differential increase as compared to NonTNBC group.Data from this study suggest that inhibition of these target genes is emerging as one of the most exciting and promising targeted therapeutic strategies to treat TNBC in which the intended targets are DNA repair, tumour angiogenesis and metastasis.Accordingly, TNBC patients will be more benefited from PARP-1, TOP-2A and HER-1 inhibitors as well as antiangiogenic and antimetastatic therapies.
其他文献
Macrophages are major inflammatory cells in the tumor microenvironment that can contribute to tumor progression.Tumor-associated macrophages (TAMs) in established tumors generally have an M2 phenotype
Death receptors (DRs), including TNFR1, Fas/CD95, DR4 and DR5, are attractive targets for cancer treatment.When expressed on cell surface, they can transduce death signals from their cognate ligands s
The process of tumor progression was described by Rous in 1939 as that by which "tumors go from bad to worse".In recent years, this has been attributed to the sequential acquisition of successive gene
The HER family of receptor tyrosine kinase has been extensively studied in breast cancer, however systematic studies of EGFR gene amplification and protein overexpression in breast carcinoma are lacki
Longitudinal cancer biomarker studies are frequently regarded as difficult, probably because there is no consensus on how to design and conduct these types of investigations.To aid in the appropriate
We have used proteomic methodology to identify putative biomarkers for chemo and radioresistance in human tumours.Proteomics has the advantage that results may not be confounded by alternative splicin
We discovered an immunogenic 90kD glycoprotein tumor-associated antigen (TAA), and developed a murine monoclonal antibody based ELISA to detect TAA specific immune complexes (IC) in sera of breast can
The urokinase plasminogen activator (uPA) system comprises the serine protease uPA, its receptor uPAR and two inhibitors PAI-1 and PAI-2.Components of the uPA system have an important role in tumorige
The majority of smooth muscle tumors found in the uterus are benign, but uterine leiomyosarcoma (LMS) are extremely malignant, with high rates of recurrence and metastasis.The development of gynecolog
Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed.We investigated the pretr