To understand the mechanisms leading to trastuzumab resistance in HER2-overexpressing breast tumors, we created trastuzumab-insensitive cell lines (SKBR3/100-8 and BT474/100-2). The maintain HER2 receptor overexpression show increase EGF (EGFR). Upon treatment, SKBR3/100-8 BT474/100-2 displayed increased growth rate invasiveness. was accompanied with activation of Wnt/β-catenin signaling pathway. Further investigation found that Wnt3 played a key role toward development resistance....

Clinically, HER2 proto-oncogene amplification is found in about 25-30% of human breast cancers, where it correlated to a poor prognosis. Constitutive STAT3 activation 50-60% the tumors and associated with tumorigenesis drug resistance. In this study, we showed that was phosphorylated HER2-overexpressing, ER-positive and, furthermore, promoted stem-like cell phenotype. We examined dysregulation stem markers (Oct-4, Sox-2 CD44) tumorsphere formation HER2-overexpressing cancer lines....

Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven to be beneficial patients with metastatic breast cancer BRCA1/2 (BReast CAncer type 1 and 2 genes) mutations. However, certain PARPi in pre-clinical studies been shown inhibit cell growth promote the death of cells lacking mutations BRCA1/2. Here, we examined inhibitory potency 13 different 12 lines without BRCA-mutations using viability assays. The results showed that 5 8 triple-negative (TNBC) were susceptible regardless...

Triple-negative breast cancer (TNBC) is the most aggressive type of that lacks ER/PR and HER2 receptors. Hence, there urgency in developing new or novel therapeutic strategies for treatment TNBC. Our study shows Monocyte Chemoattractant Protein-1 (MCP-1) a marker associated with TNBC may play key role disease progression. ELISA method was used to measure secreted MCP-1, mRNA levels were determined by Real-time PCR numerous cell lines, representing various subtypes. Cellular invasiveness...

Background Vitamin D plays a role in cancer development and acts through the vitamin receptor (VDR). Although African-Americans have lowest levels of serum D, there is dearth information on VDR gene polymorphisms breast among Hispanics. This study examines whether are associated with these cohorts. Methods Blood was collected from 232 patients (Cases) 349 non-cancer subjects (Controls). Genotyping for four polymorphic variants (FokI, BsmI, TaqI ApaI) performed using PCR-RFLP method. Results...

Combining curcumin (A), green tea polyphenol (B) with arctigenin (C) synergistically enhanced the anti-proliferative effect in prostate and breast cancer cells.

In vitro studies have shown that insulin-like growth factor (IGF) is a mitogen for breast cancer cells. However, the associations of plasma IGF-I with tumor histopathology in high-risk groups need further investigation. We hypothesize and serum IGFBP3 concentrations patients may provide useful information on progression their disease, determine probability recurrence survival. carried out retrospective study 130 minority patients. Plasma were correlated histopathology, menopausal status,...

Abstract Promoter DNA methylation of CpG islands is an important epigenetic mechanism in cancer development. We have characterized the promoter profile 82 genes three prostate cell lines (LNCaP, PC3, and DU145) two normal (RWPE1 RWPE2). The pattern was analyzed using a Panomics gene array system that consists immobilized probes known promoters on nitrocellulose membrane. Methylation binding protein–purified methylated hybridized membrane detected by chemiluminescence method. (RWPE1) versus...

Abstract Background Epigenetic changes associated with promoter DNA methylation results in silencing of several tumor suppressor genes that lead to increased risk for formation and progression the cancer. Methods Methylation specific PCR (MSP) bisulfite sequencing were used determination proapoptotic gene Caspase 8 (CASP8) maspin four breast cancer two non-tumorigenic cell lines. Involvement histone H3 those lines examined by CHIP assay. Results The CpG sites region CASP8 methylated all but...

BackgroundAfrican-American women have higher mortality from breast cancer than other ethnic groups. The association between poor survival and differences with tumor phenotypes is not well understood. purpose of this study to assess the clinical significance (1) Stem cell-like markers CD44 CD24; (2) PI3K/Akt pathway associated targets PTEN, activation Akt, FOXO1; (3) Insulin-like growth factor-1 (IGF-I) IGF binding protein-3 (IGFBP3) in different subtypes, compare African-American...

Background Studies from our laboratory and others have shown that cysteine-rich 61 (Cyr61) may be involved in tumor proliferation invasion. In earlier studies, we demonstrated increased insulin-like growth factor-I (IGF-1) is associated with breast formation poor clinical outcomes. current study investigated IGF-1 regulation of Cyr61 whether targeting could inhibit induced proliferation. Methods Several ATCC derived normal cancer cell lines were used this study: MDA-MB231, BT474, MCF-7,...

// David Austin 1 , Nalo Hamilton 2 Yahya Elshimali Richard Pietras 3, 4 Yanyuan Wu and Jaydutt Vadgama 1, Department of Medicine, Division Cancer Research Training, Charles Drew University School Medicine Science, Los Angeles, CA 90059, USA UCLA Nursing, California at 90095, 3 Johnson Comprehensive Center, Geffen Hematology-Oncology, Correspondence to: Vadgama, email: jayvadgama@cdrewu.edu Keywords: estrogen receptor-beta; triple negative breast cancer; insulin-like growth factor 2; DPN;...

BACKGROUND Vitamin D plays a role in cancer tumorogenesis and acts through the vitamin receptor (VDR). Although African Americans have lowest serum levels, supplementation has not yielded significant improvement cancer. Gene polymorphisms VDR may play role. There is dearth of information on gene colorectal (CRC) among under‐represented ethnic groups. In this study, authors examined whether single nucleotide (SNPs) were associated with CRC predominately American Hispanic study participants....

Abstract Purpose The aim of this study is to investigate the mechanisms interactions between TGF-β and Wnt/β-catenin pathways that induce regulate EMT promote breast cancer cells become resistant treatment. Methods effect on signaling pathway was examined by using a human Wnt/β-catenin-regulated cDNA plate array western blot analysis. interaction Twist at promoter Wnt3 chromatin immunoprecipitation (ChIP) assay. Secreted level determined ELISA Results HER2-overexpressing treated with have...

Hormone therapy targeting estrogen receptor α (ERα) is the most effective treatment for breast cancer. However, this eventually fails as tumor develops resistance. Although reduced expression of ER-α a known contributing factor to endocrine resistance, mechanism downregulation in resistance still not fully understood. The present study shows that Slug has an inverse relationship with ERα and prostate cancer patient samples. Also inhibition blocks mammary stem cell activity primary epithelial...

Abstract Introduction Breast cancer patients with HER2/neu overexpression have poor outcomes a decrease in disease-free survival (DFS) and overall survival. The biology of breast tumors African-American Latina women is poorly understood. purpose this study to understand the clinical significance activated Akt (phospho-Akt or pAkt) expression from corresponding tissue overexpression. Cellular molecular studies shown that activation cell signaling phosphatidylinositol-3-kinase/Akt cascade via...

Abstract Trastuzumab treatment has improved the overall survival of HER2-overexpressing breast cancer patients. However, many these patients will eventually become resistant to treatment. The mechanisms that contribute resistance trastuzumab are unknown. In this study, we tested hypothesis targeting FKHR transcription factor FOXO1A in tumor cells can overcome vitro. We have shown overexpression HER2 leads activation phosphatidylinositol 3-kinase (PI3K)/Akt pathway and subsequent inactivation...