Former TRIP Scholars
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This community contains collections of works by authors formerly affiliated with IUPUI and the Center for Translating Research into Practice (TRIP)
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Item 'Translating scholarship into practice': An alternative metaphor(http://trip.iupui.edu, 1999-05) Petronio, SandraExcerpt: Effectively translating scholarship can help people solve social problems. We may contribute to alleviating obstacles and dilemmas that people face. We may enhance the lives of others if communication scholars become translators of their own work or encourage others to function as transporters. Although we may initially concern ourselves with contributions that the communication discipline brings to the everyday world, this is a two-wy street. Not only might others benefit, but the discipline also stands to gain heartily from this investment. Showing how communication contributes to improve our understanding of the mundane and traumatic gives the discipline credibility in a wider arena. ... Through translation, we are able to preserve the integrity of the research and theory because it bridges knowledge production with knowledge utilization. Translating means that we take the knowledge discovered through research or theory and interpret it for everyday use.Item Elevated protein kinase C alpha expression may be predictive of tamoxifen treatment failure(Cancer Research UK, 2003-04-29) Tonetti, D.A.; Morrow, M.; Kidwai, N.; Gupta, A.; Badve, Sunil; Pathology and Laboratory Medicine, School of MedicineWe previously reported that stable transfection of protein kinase C alpha (PKCα) into T47D human breast cancer cells results in tamoxifen (TAM)-resistant tumour growth. Relevance of PKCα expression in clinical specimens was determined by comparing PKCα expression in tumours from patients exhibiting disease recurrence with patients remaining disease-free following TAM treatment. Our results suggest that PKCα expression may predict TAM treatment failure.Item Interleukin-1α Promotes Tumor Growth and Cachexia in MCF-7 Xenograft Model of Breast Cancer(Elsevier, 2003-12) Kumar, Suresh; Kishimoto, Hiromitsu; Chua, Hui Lin; Badve, Sunil; Miller, Kathy D.; Bigsby, Robert M.; Nakshatri, HarikrishnaProgression of breast cancer involves cross-talk between epithelial and stromal cells. This cross-talk is mediated by growth factors and cytokines secreted by both cancer and stromal cells. We previously reported expression of interleukin (IL)-1α in a subset of breast cancers and demonstrated that IL-1α is an autocrine and paracrine inducer of prometastatic genes in in vitro systems. To understand the role of IL-1α in breast cancer progression in vivo, we studied the growth of MCF-7 breast cancer cells overexpressing a secreted form of IL-1α (MCF-7IL-1α) in nude mice. MCF-7IL-1α cells formed rapidly growing estrogen-dependent tumors compared to parental cells. Interestingly, IL-1α expression alone was not sufficient for metastasis in vivo although in vitro studies showed induction of several prometastatic genes and matrix metalloproteinase activity in response to cross-talk between IL-1α-expressing cancer cells and fibroblasts. Animals implanted with MCF-7IL-1α cells were cachetic, which correlated with increased leptin serum levels but not other known cachexia-inducing cytokines such as IL-6, tumor necrosis factor, or interferon gamma. Serum triglycerides, but not blood glucose were lower in animals with MCF-7IL-1α cell-derived tumors compared to animals with control cell-derived tumors. Cachexia was associated with atrophy of epidermal and adnexal structures of skin; a similar phenotype is reported in triglyceride-deficient mice and in ob/ob mice injected with leptin. Mouse leptin-specific transcripts could be detected only in MCF-7IL-1α cell-derived tumors, which suggests that IL-1α increases leptin expression in stromal cells recruited into the tumor microenvironment. Despite increased serum leptin levels, animals with MCF-7IL-1α cell-derived tumors were not anorexic suggesting only peripheral action of tumor-derived leptin, which principally targets lipid metabolism. Taken together, these results suggest that cancer cell-derived cytokines, such as IL-1α, induce cachexia by affecting leptin-dependent metabolic pathways.Item Foreign aid: A doctored image of impact on social welfare development in developing countries(2005) Gentle-Genitty, CarolynForeign aid is primarily intended as a wealth transfer mechanism from rich, to poor, countries. Billions of dollars have been distributed in aid largely to assist in social welfare development. Still many are in poverty and tools to evaluate real impact are not in use.Item The macrophage inhibitory cytokine integrates AKT/PKB and MAP kinase signaling pathways in breast cancer cells(Oxford University Press, 2005-05-01) Wollmann, Wyatt; Goodman, Mike L.; Bhat-Nakshatri, Poornima; Kishimoto, Hiromitsu; Goulet, Robert J.; Mehrotra, Sanjana; Morimiya, Akira; Badve, Sunil; Nakshatri, HarikrishnaMacrophage inhibitory cytokine 1 (MIC-1), a divergent member of the transforming growth factor beta superfamily, plays a role in the progression of a number of cancers, including breast, gastric, prostate and colorectal carcinomas. Serum MIC-1 levels are elevated in patients with metastatic prostate, breast and colorectal carcinomas. In vitro studies have revealed a cell type-specific role for MIC-1 in senescence and apoptosis. MIC-1 activates the survival kinase AKT/PKB in neuronal cells. Depending on the cell type, it activates or represses the MAP kinases ERK1/2. Mechanisms responsible for an increased MIC-1 expression in cancers and the consequences of MIC-1 overexpression, however, are not known. In this study, we show that AKT/PKB directly regulates the expression of MIC-1 in breast cancer cells. Sequences within −88 to +30 of the MIC-1 promoter are required for the AKT-mediated induction of MIC-1. This region of the promoter contains two SP-1 binding sites (SP-1B and SP-1C), which bind to the SP-1 and SP-3 proteins. Mutation of SP-1C but not SP-1B reduced the AKT-mediated activation of MIC-1. MIC-1 increased the basal ERK1 phosphorylation and prolonged the estrogen-stimulated ERK1 phosphorylation in MCF-7 breast cancer cells without altering the phosphorylation status of AKT/PKB. Immunohistochemistry with MIC-1 antibody revealed an MIC-1 expression within the cancer cells of primary breast cancer and in the MCF-7 xenografts. Furthermore, a limited analysis of RNA from primary breast cancers revealed an overexpression of MIC-1 in tumors, compared with normal tissues. These results suggest that AKT/PKB through MIC-1 could regulate the ERK1 activity and the MIC-1 expression levels may serve as a surrogate marker for the AKT activation in tumors.Item Unmasking the Doctored Image of Foreign Aid: A Mirror Model(2006) Gentle-Genitty, CarolynForeign aid is primarily a wealth transfer mechanism from rich, developed countries to poor, developing countries. Throughout the world, developing countries have received billions in aid to assist in their social welfare development and rise from poverty. Yet, there are still many in poverty. This paper examines the impact, if any, on social welfare development in the recipient countries because of foreign aid from donor countries.Item CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis(BMC, 2006) Sheridan, Carol; Kishimoto, Hiromitsu; Fuchs, Robyn K; Mehrotra, Sanjana; Bhat-Nakshatri, Poornima; Turner, Charles H; Goulet, Robert; Badve, Sunil; Nakshatri, HarikrishnaIntroduction A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells has the unique ability to invade, home, and proliferate at sites of metastasis. Methods CD44 and CD24 expression was determined by flow cytometry. Northern blotting was used to determine the expression of proinvasive and 'bone and lung metastasis signature' genes. A matrigel invasion assay and intracardiac inoculation into nude mice were used to evaluate invasion, and homing and proliferation at sites of metastasis, respectively. Results Five among 13 breast cancer cell lines examined (MDA-MB-231, MDA-MB-436, Hs578T, SUM1315, and HBL-100) contained a higher percentage (>30%) of CD44+/CD24- cells. Cell lines with high CD44+/CD24- cell numbers express basal/mesenchymal or myoepithelial but not luminal markers. Expression levels of proinvasive genes (IL-1α, IL-6, IL-8, and urokinase plasminogen activator [UPA]) were higher in cell lines with a significant CD44+/CD24- population than in other cell lines. Among the CD44+/CD24--positive cell lines, MDA-MB-231 has the unique property of expressing a broad range of genes that favor bone and lung metastasis. Consistent with previous studies in nude mice, cell lines with CD44+/CD24- subpopulation were more invasive than other cell lines. However, only a subset of CD44+/CD24--positive cell lines was able to home and proliferate in lungs. Conclusion Breast cancer cells with CD44+/CD24- subpopulation express higher levels of proinvasive genes and have highly invasive properties. However, this phenotype is not sufficient to predict capacity for pulmonary metastasis.Item Racializing the Commonplace Landscape: An Archaeology of Urban Renewal Along the Color Line(2006) Mullins, Paul R.In the 1960’s Indianapolis, Indiana’s near-Westside was transformed by urban renewal projects that carved space for the Indiana University-Purdue University Indianapolis (IUPUI) campus out of a predominately African-American neighborhood. Within two decades that longstanding community was totally displaced, and today the former neighborhood covering 300 acres is completely effaced and the community is largely forgotten. This paper examines how archaeology on the University campus provides a mechanism to illuminate the processes that remade the near-Westside. Archaeological research conducted along with the displaced community and its descendants provides a powerful tool to rethink the otherwise prosaic campus landscape as a space shaped by racial and class privilege.Item Effects of HIV Protease Inhibitor Ritonavir on Akt-Regulated Cell Proliferation in Breast Cancer(American Association for Cancer Research, 2006-03-15) Srirangam, Anjaiah; Mitra, Ranjana; Wang, Mu; Gorski, J. Christopher; Badve, Sunil; Baldridge, Lee Ann; Hamilton, Justin; Kishimoto, Hiromitsu; Hawes, John; Li, Lang; Orschell, Christie M.; Srour, Edward F.; Blum, Janice S.; Donner, David; Sledge, George W.; Nakshatri, Harikrishna; Potter, David A.Purpose These studies were designed to determine whether ritonavir inhibits breast cancer in vitro and in vitro and, if so, how. Experimental Design Ritonavir effects on breast cancer cell growth were studied in the estrogen receptor (ER)-positive lines MCF7 and T47D and in the ER-negative lines MDA-MB-436 and MDA-MB-231. Effects of ritonavir on Rb-regulated and Akt-mediated cell proliferation were studied. Ritonavir was tested for inhibition of a mammary carcinoma xenograft. Results ER-positive estradiol-dependent lines (IC50, 12–24 µmol/L) and ER-negative (IC50, 45 µmol/L) lines exhibit ritonavir sensitivity. Ritonavir depletes ER-α levels notably in ER-positive lines. Ritonavir causes G1 arrest, depletes cyclin-dependent kinases 2, 4, and 6 and cyclin D1 but not cyclin E, and depletes phosphorylated Rb and Ser473 Akt. Ritonavir induces apoptosis independent of G1 arrest, inhibiting growth of cells that have passed the G1 checkpoint. Myristoyl-Akt, but not activated K-Ras, rescues ritonavir inhibition. Ritonavir inhibited a MDA-MB-231 xenograft and intratumoral Akt activity at a clinically attainable serum Cmax of 22 ± 8 µmol/L. Because heat shock protein 90 (Hsp90) substrates are depleted by ritonavir, ritonavir effects on Hsp90 were tested. Ritonavir binds Hsp90 (KD, 7.8 µmol/L) and partially inhibits its chaperone function. Ritonavir blocks association of Hsp90 with Akt and, with sustained exposure, notably depletes Hsp90. Stably expressed Hsp90α short hairpin RNA also depletes Hsp90, inhibiting proliferation and sensitizing breast cancer cells to low ritonavir concentrations. Conclusions Ritonavir inhibits breast cancer growth in part by inhibiting Hsp90 substrates, including Akt. Ritonavir may be of interest for breast cancer therapeutics and its efficacy may be increased by sustained exposure or Hsp90 RNA interference.Item CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis(BioMed Central, 2006-10-24) Sheridan, Carol; Kishimoto, Hiromitsu; Fuchs, Robyn K.; Mehrotra, Sanjana; Bhat-Nakshatri, Poornima; Turner, Charles H.; Goulet Jr., Robert; Badve, Sunil; Nakshatri, Harikrishna; Anatomy and Cell Biology, School of MedicineIntroduction A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells has the unique ability to invade, home, and proliferate at sites of metastasis. Methods CD44 and CD24 expression was determined by flow cytometry. Northern blotting was used to determine the expression of proinvasive and 'bone and lung metastasis signature' genes. A matrigel invasion assay and intracardiac inoculation into nude mice were used to evaluate invasion, and homing and proliferation at sites of metastasis, respectively. Results Five among 13 breast cancer cell lines examined (MDA-MB-231, MDA-MB-436, Hs578T, SUM1315, and HBL-100) contained a higher percentage (>30%) of CD44+/CD24- cells. Cell lines with high CD44+/CD24- cell numbers express basal/mesenchymal or myoepithelial but not luminal markers. Expression levels of proinvasive genes (IL-1α, IL-6, IL-8, and urokinase plasminogen activator [UPA]) were higher in cell lines with a significant CD44+/CD24- population than in other cell lines. Among the CD44+/CD24--positive cell lines, MDA-MB-231 has the unique property of expressing a broad range of genes that favor bone and lung metastasis. Consistent with previous studies in nude mice, cell lines with CD44+/CD24- subpopulation were more invasive than other cell lines. However, only a subset of CD44+/CD24--positive cell lines was able to home and proliferate in lungs. Conclusion Breast cancer cells with CD44+/CD24- subpopulation express higher levels of proinvasive genes and have highly invasive properties. However, this phenotype is not sufficient to predict capacity for pulmonary metastasis.