Browsing by Subject "Cancer cells"
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Item Correlation of growth and CEA production by a human colon carcinoma cell line(Texas Tech University, 1979-08) Snodgrass, Marcia DonaldNot availableItem Cytotoxicity of antibody-selenium immunoconjugates against erythrocytes and cancer cells(Texas Tech University, 1997-05) Chen, LugenNOT AVAILABLEItem Investigation of the effect of a novel vitamin E derivative (alpha-TEA) alone and in combination with a known chemotherapuetic agent in human breast cancer using cell culture and animal models(2003) Lawson, Karla Ann; Kline, Kimberly; Sanders, Bob G.Several studies have described the potent anti-tumor activity of RRR-α- tocopheryl succinate (vitamin E succinate; VES), a hydrolyzable ester derivative of RRR- α-tocopherol (natural vitamin E), demonstrating that VES is a potent growth inhibitor of a wide variety of epithelial cancer cell types, including breast, prostate, lung, and colon; as well as, hematopoietic-lymphoid leukemia and lymphoma cells, in vitro, and exert these effects via induction of apoptosis, inhibition of DNA synthesis, and induction of cellular differentiation. Recent studies have demonstrated VES to have anti-tumor and anti-metastatic activity in animal xenograft and allograft models when administered intraperitoneally (i.p.), but not when delivered orally, suggesting a possible route specific therapeutic potential. In an effort to develop a clinically useful vitamin E-based chemotherapeutic agent and to administer it in a clinically-relevant manner, a nonhydrolyzable ether analog of RRR-α-tocopherol; namely, 2,5,7,8-tetramethyl-2R-(4R, 8R,12-trimethyltridecyl)chroman-6-yloxyacetic acid (called RRR-α-tocopheryloxyacetic acid or RRR-α-tocopherol ether-linked acetic acid analog; and abbreviated α-TEA) has been produced. Data reported here are promising in that they show that a novel vitamin E analog exhibits the ability to decrease primary tumor burden and reduce lung and lymph node metastasis in a rather rapid and aggressive syngeneic tumor model without any overt toxic effects when administered by clinically relevant routes; namely, aerosol and oral delivery. Increased rates of tumor cell apoptosis and inhibition of cell proliferation in tumors of animals treated with α-TEA, imply that the anti-tumor effect is due, at least in part, to analog triggering of tumor cell death and inhibition of cell proliferation. The mechanism of how α-TEA reduces lung metastasis in this model system is unknown and warrants further investigation, but is unlikely due to a decrease in angiogenesis. In addition, combinations of this vitamin E derivative with 9-nitrocamptothecin (9-NC), a camptothecin derivative used in the treatment of ovarian and pancreatic cancers, show an enhanced effect on the decrease in tumor burden in this model.Item The mechanism by which retinol decreases β-catenin protein in retinoic acid-resistant colon cancer cells(2007-05) Dillard, Alice Clare; Lane, MichelleCancer is the second leading cause of death in the United States, following cardiovascular disease. Colorectal cancer is the third leading cause of cancer death in the United States in both men and women (1). The American Cancer Society predicts over 153,000 new colorectal cancer cases and over 52,000 deaths due to colorectal cancer in 2007 (1). Even though the mortality rate has continued to decrease for colorectal cancer in both men and women, there is only a 64% five-year survival rate, unless a distant metastasis is diagnosed, in which case the five-year survival rate drops to only 10%. All-trans retinoic acid (ATRA) is currently used as a chemotherapy for acute promyelocytic leukemia and some forms of skin cancer. Unfortunately, chemotherapy with ATRA often results in unpleasant side effects and ATRA-resistant tumors are common due to defects in ATRA signaling. The focus of this study is retinol’s effects on β- catenin, a protein essential for colon carcinogenesis. Our goal is to understand the mechanism by which retinol decreases the growth of ATRA-resistant human colon cancer cells. We first determined that retinol, not ATRA, decreases the growth of ATRA-resistant colon cancer cell lines by slowing cell cycle progression. Next, we examined the effects of retinol treatment on β- catenin, a protein which regulates the transcription of cyclin D1 and c-myc, a protein essential for progress through the cell cycle. We found that retinol significantly decreased β-catenin protein by inducing retinoid X receptor (RXR)α-mediated proteasomal degradation. Lastly, we showed that RXRα directs the degradation of β-catenin by binding β-catenin and transporting it to the proteasome for degradation. Based on these results, we propose a mechanism where retinol increases RXRα protein levels and RXRα-β-catenin binding as well as the movement of β-catenin to the cytosol where it is proteosomally degraded, ultimately leading to slowed cell cycle progression.Item The mechanism by which retinol decreases β-catenin protein in retinoic acid-resistant colon cancer cells(2007) Dillard, Alice Clare; Lane, MichelleItem Membrane progestin receptor expression, signaling and function in reproductive somatic cells of female vertebrates(2008-05) Dressing, Gwen Ellen, 1980-; Thomas, P. (Peter)The goal of the current research was to examine the expression, signaling and function of the membrane progestin receptors (mPRs) in the ovarian follicular cells of the Atlantic croaker (Micropogonias undulatus) and in human breast cancer cells. Multiple studies have examined the role of mPRs in the germ cells of several vertebrate classes, yet few studies have examined the role of the mPRs in the somatic cells of reproductive tissues. Therefore this research examines the mechanism of mPR action and its function in somatic cells of female reproductive tissues. Results from studies on the expression, localization and signaling of the mPR[alpha] in co-cultures of granulosa and theca cells from the croaker suggest that the mPR[alpha] is localized to the plasma membrane of both cell types and that the mPR[alpha] is associated with and signals via pertussis toxin-sensitive inhibitory G proteins to decrease intracellular cAMP and activate ERK. In addition, exposure of follicular co-cultures to progestins that activate the mPR[alpha] results in a decrease in serum starvation-induced cell death which is not replicated by progestins which activate the nuclear progestin receptor (nPR), indicating mPR mediation. Similar studies in two immortalized human breast cancer cell lines, MDA-MB-468 and SKBR3, suggest that the mPR[alpha] is also present in the membranes of these cells and signals in human breast cancer cell lines via activation of a pertussis toxin-sensitive G protein to significantly decrease in intracellular cAMP and activate ERK. Progesterone exposure also decreased serum starvation-induced cell death in SKBR3 cells which are nPR positive and in MDA-MB-468 cells which are nPR negative. Synthetic progestins which activate the nPR but not the mPR were ineffective in inhibiting death in either cell type suggesting that the mPR is the mediator of this progestin action. mPR[alpha], mPR[beta] and mPR[gamma] expression analysis of paired normal and malignant breast tissue biopsies from thirteen women revealed that at least one mPR isoform was upregulated in the malignant tissue of 70% of the women. In addition the expression of mPR[gamma] was positively correlated with the expression of the nPR and CK19, a breast epithelial cell marker.Item Molecular specific photoacoustic imaging using plasmonic gold nanoparticles(2009-12) Mallidi, Srivalleesha; Emelianov, Stanislav Y.Cancer has become one of the leading causes of death today. The early detection of cancer may lead to desired therapeutic management of cancer and to decrease the mortality rate through effective therapeutic strategies. Advances in materials science have enabled the use of nanoparticles for added contrast in various imaging techniques. More recently there has been much interest in the use of gold nanoparticles as optical contrast agents because of their strong absorption and scattering properties at visible and near-infrared wavelengths. Highly proliferative cancer cells overexpress molecular markers such as epidermal growth factor receptor (EGFR). When specifically targeted gold nanoparticles bind to EGFR they tend to cluster thus leading to an optical red-shift of the plasmon resonances and an increase in absorption in the red region. These changes in optical properties provide the foundation for photoacoustic imaging technique to differentiate cancer cells from surrounding benign cells. In photoacoustic imaging, contrast mechanism is based on the optical absorption properties of the tissue constituents. Studies were performed on tissue phantoms, ex-vivo and in-vivo tumor models to evaluate molecular specific photoacoustic imaging technique. The results indicate that highly sensitive and selective detection of cancer cells can be achieved by utilizing the plasmon resonance coupling effect of EGFR targeted gold nanoparticles and photoacoustic imaging. In conclusion, the combined ultrasound and photoacoustic imaging technique has the ability to image molecular signature of cancer using bioconjugated gold nanoparticles.Item Nano-mechanical studies of prostate cancer cells using atomic force microscopy(2012-05) Bastatas, Lyndon D; Park, Soyeun; Myles, Charles W.Nano-mechanical properties of prostate cancer cells with different metastatic potentials were investigated, in vitro, to shed light on the issue whether those properties could be utilized as indicators of their aggressiveness. Experimentations involved atomic force microscopy-based indenting and force mapping experiments acquired at LNCaP (lowly metastatic) and CL-1 (highly metastatic) prostate cancer cells that were cultured on plain glass and nano-scaffolds. Various models were applied to extract the mechanical information pertaining to the elasticity, adhesion and topography of the cells. Deviating from the general perspective for metastasis, the elasticity measurements reveal that the elastic modulus of highly metastatic cancer cells, CL-1, is about twice as high (i.e., stiffer) as the elastic modulus of lowly metastatic cancer cells, LNCaP, both at the center of cells’ body and lamellipodia. The two-dimensional maps of adhesion property, in conjunction with the results from the experiments conducted on the nano-scaffolds, reveal that the stiffer cells, CL-1, are more adherent than softer cells, LNCaP. These findings are consistent to the reports observed at in vitro nano-mechanical studies that cultured adherent cells are less deformable than the non-adherent ones. We postulate that the enhanced adhesion generates larger cortical tension that leads to higher elastic modulus observed in CL-1.