The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1...

Dendritic cell (DC)-based vaccines have exhibited minimal effectiveness in treating established tumors, likely because of factors present in the tumor microenvironment. One such factor is transforming growth factor (TGF), a cytokine that is produced by numerous tumor types and has been demonstrated to impair DC functions in vitro. We have evaluated the effect of TGFon the immunostimulatory acti...

Housing temperature has been shown to influence thermoregulation and behavior of preclinical cancer models; and anti-cancer drugs typically reduce peripheral blood flow and body temperature. In the present study, the effects of paclitaxel (PTX)-induced reduction of body temperature and peripheral blood flow on metastatic 4T1 breast cancer was investigated in a mouse model and the modification o...

Activin A is a member of the transforming growth factor beta (TGFb) superfamily and a pleiotropic cytokine that regulates many processes, from reproduction and development to cancer and immunity. Activin A shares the smad2/3 signal transduction pathway with TGFb and displays overlapping biological activities with the latter, including the ability to promote the differentiation of CD4 T cells to...

Purpose Transforming growth factor β (TGFβ) promotes cell survival by endorsing DNA damage repair and mediates an immunosuppressive tumor microenvironment. Thus, TGFβ activation in response to radiation therapy is potentially targetable because it opposes therapeutic control. Strategies assess this potential the clinic are needed. Methods Materials We evaluated positron emission tomography (PET...

Breast cancer cells typically metastasize to the lung, liver, bones, and brain. Metastasis of the cancer cells is the primary cause of death in breast cancer patients. The mechanisms of cancer cell dissemination and proliferation at the secondary organ are not very well understood. Our goal is to identify the differences in the molecular pathway between high and low metastatic murine mammary ca...

We investigated anti-angiogenic/vascular targeting therapy of established tumors in immunocompetent mice using an anti-human endoglin (EDG; CD105) monoclonal antibody (mAb) SN6j. SN6j weakly cross-reacted with murine endothelial cells but reacted neither with colon-26 murine colon carcinoma cells nor with 4T1 murine mammary carcinoma cells. Systemic administration of naked (unconjugated) SN6j s...

Constitutively activated STAT3 is involved in the formation of multiple types of tumors including breast cancer. We examined the effects of Stat3 protein knockdown by RNA interference using a dicistronic lentivirus small hairpin (shRNA) delivery system on the growth of mammary tumors in BALB/c mice induced by the 4T1 cell line. A single exposure of 4T1 cells to shRNA/STAT3 lentivirus transduced...

Through their ability to degrade the extracellular matrix, proteases mediate cancer cell invasion and metastasis. Paradoxically, some serine protease inhibitors (serpins) are often overexpressed in human tumors. Using computational analysis, we found that the RNA level of protease nexin-1 (PN-1), a serpin that blocks numerous proteases activity, is significantly elevated in estrogen receptor-al...

Background The adjuvanticity potential of Lactobacillus casei was first suggested in an old survey. The present study was designed to investigate the efficacy of a new immunotherapy against breast cancer made by mixing an extract of heated 4T1 mammary carcinoma cell line and a heat-killed preparation of Lactobacillus casei. Methods Female BALB/c mice (6-8 weeks old, n=40) were challenged subc...