bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1880: Polymeric implants enhance bioavailability of curcumin by providing a continous (“24/7”) delivery system
Authors: Bansal Shyam S. , Kausar Hina , Aqil Farrukh , Vadhanam Manicka V. , Gupta Ramesh C. 
Published: February 2011

Abstract
Curcumin, a potent natural chemopreventive agent, has shown significant anti-oxidant, anti-inflammatory, anti-proliferative, anti-metastatic, anti-angiogenic properties and is found to be effective against many ailments of inflammatory origin. However, it has elicited only limited success in various pre-clinical and clinical studies presumably due to its poor oral bioavailability. To increase the bioavailability of curcumin, we have developed novel polymeric implants using polycaprolactone (Mol. Wt. 65,000) (P-65) to achieve continuous (“24/7”) controlled delivery of curcumin directly into the systemic circulation. In this study, we investigated rate of curcumin release from the polymeric implants and tissue levels of curcumin in vivo by subcutaneously grafting 2-cm implants containing 20% (w/w) curcumin in female rats. Animals were euthanized at different intervals, and blood, different tissues and implants were collected. Measurement of the residual curcumin in the implants showed a burst release of 4.66 (11.7%) and 7.34 mg (18.4%) after 7 and 14 days, respectively, followed by a more controlled release. After 70 weeks nearly 76% curcumin was released. In another study, implants containing 10% curcumin showed similar rate of release from the implants. The in vivo release patterns mimicked the rate of release observed in vitro under ‘sink’ conditions. A solvent extraction and HPLC methodology was developed to measure tissue levels of curcumin. After 4 days, curcumin was detected at a level of 60 ± 20 ng/g liver and declined to almost constant levels of 12-14 ng/g tissue after 22 days. Analysis of CYP1A1 and GSTM levels as the biomarkers of curcumin efficacy showed a 13- and 16-fold induction in CYP1A1 levels after 4 and 7 days, respectively. GSTM levels were also found to be increased by 3- and 4-fold after 4 and 7 days, respectively. These studies showed that polymeric implants can deliver controlled amounts of curcumin systemically over an extended period of time increasing its bioavailability and elicit modulation of phase I and phase II enzymes (Supported from the USPHS grant CA-118114 and Agnes Brown Duggan Endowment.).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1880.
Abstract 1889: Curcumin potentiates the cancer-preventive actions of selenium by inactivating selenoprotein thioredoxin reductase in prostate cancer cells
Authors: Gopalakrishna Rayudu , Schiffman Jason E. , Man Joshua , Lei Lok , Wu Adela , Gundimeda Usha 
Published: February 2011

Abstract
Our previous studies have shown that the cancer-preventive actions of selenium may be negated by an over-expression of selenoprotein thioredoxin reductase (TR). This reductase reverses selenocompound-induced sulfhydryl redox inactivation of protein kinase C (PKC), a step which is intimately involved in the cancer-preventive actions of selenium. Consistent with this observation, the TR-specific inhibitor auranofin increases the sensitivity of prostate cancer cells to methylseleninic acid (MSA). This is particularly significant for advanced prostate cancer cells which require higher concentrations of MSA than early stage cancer cells. Selenium prevents cancer in some cases but fails to do so in others. Selenium's failure in this respect may be due to the development of TR-mediated resistance to its chemopreventive actions. Therefore, there is a potential role for agents that inhibit TR and thereby sensitize cancer cells to selenium. Several studies have shown that cancer prevention by a single agent may be less effective than multiple agents administered simultaneously. Here we report that curcumin, another cancer -preventive agent, at 5 to 10 μM concentrations potentiates the action of MSA in inhibiting growth and inducing apoptosis of both androgen-dependent LNCaP cells and androgen-independent DU145 cells. Nearly 2- to 4-fold lower concentrations of MSA were needed for 50% inhibition of cell growth in the presence of curcumin than in its absence. Under these conditions, curcumin inactivated TR in these cell types. There was also a concomitant increase in MSA-induced sulfhydryl oxidative inactivation of PKC. Furthermore, we found a correlation between curcumin-induced inactivation of TR and curcumin-induced potentiation of MSA-associated growth inhibition and apoptosis. These results suggest TR may be a molecular target for cancer prevention. While auranofin, the prototypical TR inhibitor, is toxic, curcumin appears to be a safe alternative. Our results provide a mechanistic rationale to the combination of selenium and curcumin for cancer prevention. Just as resistance develops to cancer chemotherapy, cancer prevention may also be counteracted by resistance mechanisms. Similarly, a combination of agents may prevent the development of resistance in cancer prevention just as it does in chemotherapy. Instead of the random mixing of agents in an empiric manner, a mechanistically informed choice of agents as has been proposed here is a more rational approach to identify effective combination of agents for cancer prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1889.
Abstract 1892: Curcumin suppresses prostate cancer cells through modulation of β-catenin and protein kinase D1
Authors: Sundram Vasudha , Chauhan Subhash C. , Jaggi Meena 
Published: February 2011

Abstract
OBJECTIVE: Prostate cancer is the most commonly diagnosed cancer in males in the US. One in every 6th male will be diagnosed with prostate cancer this year. Understanding the molecular basis of prostate cancer progression can serve as a tool for early stage diagnosis and development of novel treatment strategies for this disease. Inappropriate activation of β-catenin signaling is linked to a wide range of cancers, including prostate cancer, resulting in transcription of genes involved in cancer progression such as c-Myc, c-Jun and cyclin D1. However, strategies to regulate this specific signaling pathway are very limited or not well developed. Synthetic or natural products which regulate this signaling pathway can be developed as a novel therapeutic modality for prostate cancer treatment. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular pathways. Herein, we have investigated a putative molecular mechanism involved in curcumin mediated suppression of prostate cancer cell growth and the effect of curcumin on prostate cancer cells growth and its effect on β-catenin transcription activity.
MATERIALS AND METHODS: Cellular characteristics of the C4-2 prostate cancer cells were measured using anchorage independent growth, anchorage dependent growth, motility, and proliferation assays. β-catenin/T cell factor (TCF) transcription activity was measured by luciferase reporter assays using reporter constructs Topflash or Fopflash and pRL-TK (Renilla luciferase). The Luciferase activities were assayed using the Dual Glo reagent (dual reporter assay, Promega, Madison, WI). Subcellular localization of Protein Kinase D1 (PKD1) and β-catenin was determined by confocal microscopy.
RESULTS: Our results demonstrate that curcumin effectively suppresses prostate cancer cell growth, proliferation and cellular motility. In the luciferase assays, curcumin treatment diminished β-catenin transcription activity in C4-2 prostate cancer cells. Moreover, curcumin treatment influences the translocation of β-catenin from the nucleus to the cell surface membrane. Interestingly, the suppression of β-catenin transcription activity was correlated with the modulation PKD1 expression/phosphorylation within 1-3 hrs post-curcumin treatment.
CONCLUSION: These results suggest that curcumin treatment attenuates
β-catenin transcription activity in prostate cancer cells via modulating the expression/activation of PKD1. These results suggest a novel molecular mechanism of curcumin related suppression of prostate cancer cell growth.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1892.
Abstract 190: p53 target gene expression, DNA hypomethylation, and clinical response in MDS patients undergoing decitabine therapy
Authors: Link Petra A. , Zhang Wa , Gold David , Wetzler Meir , Baer Maria R. , Karpf Adam R. 
Published: February 2011

Abstract
The myelodysplastic syndromes (MDS) are a heterogeneous group of blood disorders characterized by peripheral cytopenias, a cellular bone marrow with dysplasia and increased intramedullary apoptosis, and are associated with risk of progression to acute myelogenous leukemia (AML). MDS are often fatal due to complications from cytopenias and/or progression to AML. DNA methyltransferase inhibitors (DNMTi), including 5-azacytidine and 5-aza-2’-deoxycytidine (decitabine) have recently assumed a major role in the clinical management of MDS, and are two of only three FDA-approved treatments for these disorders. The mechanistic basis for the activity of DNMTi in MDS is unclear. We recently reported that decitabine treatment induces the expression of p53-inducible ribonucleotide reductase p53R2/RRM2B in tumor cell lines and MDS patient bone marrow (Link et al., Cancer Research 68; 9358-9366, 2008). Importantly, p53R2 induction was independent of DNA hypomethylation at its promoter region, and the level of p53R2 induction correlated with clinical response in a cohort of 13 patients. These data suggest that important pharmacodynamic responses to DNMTi may be associated with DNA damage and/or p53 activation. To better understand the overall nature of the molecular responses occurring in the bone marrow of MDS patients treated with decitabine, in the current study we examined a variety of pharmacodynamic endpoints including: p53 target gene expression, global DNA methylation, tumor antigen gene expression and methylation, and tumor suppressor gene expression. Specifically, we measured the expression of three classical p53 target genes (p21, GADD45-α, NOXA), LINE-1 repetitive element methylation, the expression and methylation of cancer-germline (CG) antigens including MAGE-A1, NY-ESO-1, XAGE-1, and CTCFL/BORIS, and the expression of the tumor suppressor genes (TSGs) p15INK4b and PDLIM4. Our data reveal that decitabine treatment causes robust induction of p53 target genes in MDS patient bone marrow, which coincides with LINE-1 hypomethylation and clinical responses. In contrast, while CG antigen genes showed some evidence for DNA hypomethylation post-therapy, this did not coincide with CG antigen gene induction. Surprisingly, TSGs were also not induced by decitabine therapy in MDS patient bone marrow. Ongoing studies seek to define p53 mutational status in MDS patients and to determine how this relates to p53 target gene induction and/or clinical response. In summary, our data reveal a connection between p53 target gene activation, global DNA hypomethylation, and clinical response in MDS patients undergoing decitabine therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 190.
Abstract 1900: Antioxidant studies on the Peruvian cherimoya fruit give an insight into the healthy lifestyle of the Incas
Authors: Elera Gaytri D. Gupta , Whitaker John , Chauca Jorge , Robison Richard A. , Neill Kim L. O’ 
Published: February 2011

Abstract
Annona cherimola, known as “cherimoya” was grown as an essential crop in the Incan empire, and was believed to prevent disease. Indigenous to Peru and Ecuador, this “pearl of the Andes” is consumed mainly for its exceptional taste. American writer Mark Twain called the cherimoya “the most delicious fruit known to men.” Recent interest in this fruit stems from its high concentration of acetogenins, which are bioactive polyketides. Recent research has accredited beneficial effects to acetogenins, including the exhibition of cytotoxic and anti-tumorous activity, particularly in mammary, pancreatic and colon cancer cells (Cheng et. al 1998). This project explores the health benefits of cherimoya consumption by examining the antioxidant effect of its components, including: skin, flesh and juice. These components were analyzed for antioxidant concentrations using the Oxygen Radical Absorbance Capacity (ORAC) assay.
A cellular model was also established that evaluated the antioxidant capacity of cherimoya components in the presence of Raji cells, a Burkitt lymphoma cell line, and HT-29 cells, a colon cancer cell line. After incubation with the cherimoya components, cell lysate samples were assessed for antioxidant capacity using the ORAC assay. Results for Raji cell lysate exposed to media, juice, skin and flesh were as follows: 886 Trolox Equivalents per Liter (TE/L), 1238 TE/L, 1018 TE/L, and 1045 TE/L respectively. Results for HT-29 cell lysate exposed to media, juice, skin and flesh were: 294 TE/L, 924 TE/L, 505 TE/L and 627 TE/L respectively. These data shows that cells treated with cherimoya juice exhibited a higher antioxidant uptake.
An alternate cellular model was established in which Raji cells and HT-29 cells were pre-exposed to oxidant AAPH, 2,2’-azobis-(2-amidinopropane) dihydrochloride, and then treated with cherimoya juice, skin and flesh. Results for Raji cells exposed to AAPH and then treated with media, juice, skin and flesh were as follows: 1054 TE/L, 1363 TE/L, 1183 TE/L, and 1254 TE/L respectively. Results for HT-29 cells exposed to AAPH and then treated with media, juice, skin and flesh were: 1075 TE/L, 1528 TE/L, 1350 TE/L and 1374 TE/L respectively. These data indicated that when cells were pre-exposed to an oxidant, thus simulating cells under oxidative stress, antioxidant cell uptake increased for both cell lines. These results suggest that cells can sense oxidative stress in their environment and can increase their ability to uptake available antioxidants.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1900.
Abstract 1905: Inhibition of hypoxia-inducible factor 1 (HIF-1) in tumor can augment anti-tumor immune responses in tumor-bearing mouse through suppression of transforming growth factor-beta (TGF-β)
Authors: Teramoto Koji , Kawaguchi You , Hori Tetsuo , Kitamura Shoji , Hanaoka Jun , Tezuka Noriaki , Kontani Keiichi 
Published: February 2011

Abstract
Hypoxia is one of distinctive features of the tumor microenvironment. In the tumor tissues under hypoxia, a transcription factor, hypoxia-inducible factor 1 (HIF-1) plays a critical role in regulating expressions of various genes associated with tumor growth. In order to understand the immunobiology of hypoxic tumor microenvironment, it is of great interest to elucidate the anti-tumor immune responses regulated by HIF-1. From these points of view, we focused on a relationship between HIF-1 and an immunosuppressive cytokine, transforming growth factor-beta (TGF-β) in the tumor. TGF-β which is derived from either tumor cells or tumor stromal cells has been reported to suppress anti-tumor immune responses in tumor-bearing hosts. In this report, we hypothesized that inhibition of HIF-1 would eliminate expression of TGF-β in tumor tissue and decreased level of TGF-β would contribute to augmentation of anti-tumor immune responses. We examined the possibilities in tumor-bearing mice models. C57BL/6 mice were inoculated subqutaneously with syngeneic Lewis lung carcinoma cell LLC. Five days after tumor inoculation, mice were administrated HIF-1 siRNA into the established tumor twice at 2-day interval. Three to 7 days after the last administration of HIF-1 siRNA, anti-tumor immune responses elicited in the mice were examined. As results, HIF-1 siRNA into the established tumor contributed to low expression of TGF-β mRNA as well as low level of TGF-β protein. In the tumor-draining lymph nodes, tumor antigen-specific CD8+ cells producing IFN-γ were increased and CD4+CD25+Foxp3+ (Treg) cells were decreased by administration of HIF-1 siRNA. Enhancement anti-tumor immune responses were associated with antigen-specific cytotoxic activity in spleen. Subsequently, tumor growth was effectively suppressed in mice administrated HIF-1 siRNA. Inhibition of HIF-1 in the tumor can eliminate expression of TGF-β there, and anti-tumor immune responses are augmented through eliminated TGF-β-mediated immunosuppression. These results demonstrate that hypoxia in the tumor tissue is associated with TGF-β-mediated immunosuppression and HIF-1 inhibitors can improve anti-tumor immune responses in tumor-bearing hosts. Our mouse models provide a new rationale with the molecular-targeting therapy for HIF-1.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1905.
Abstract 1910: Infiltration of ovarian carcinoma by altered plasmacytoid dendritic cells could contribute to local immune tolerance
Authors: Labidi-Galy Sana Intidhar , Ray-Coquard Isabelle , Sisirak Vanja , Treilleux Isabelle , Meeus Pierre , Mithieux François , Cassignol Alexandre , Bouchard François , Gabelle Philippe , Guastalla Jean-Paul , Ménetrier-Caux Christine , Caux Christophe , Bendriss-Vermare Nathalie 
Published: February 2011

Abstract
Ovarian carcinomas are usually considered as immunogenic tumors, as they are capable of inducing tumor-associated antigen immunity. However, immune system fails to eradicate established tumors partly due to alteration of immunosurveillance and induction of an active process of « tolerization » by the tumor microenvironment. We prospectively collected blood, tumors, and ascites samples from 38 patients with ovarian carcinomas (localized and advanced stages) and 35 healthy donors that gave written informed consent. Lin−CD4+CD11c−CD123+BDCA2+ pDC are the most abundant DC subset within ovarian carcinomas and neoplasic ascitis while they are profoundly depleted in peripheral blood of ovarian carcinoma patients compared to healthy donors. The depletion of pDC in patient's blood is partially restored when they are in complete remission (after chemotherapy and surgery). These observations suggest preferential pDC recruitment into tumor tissues that may involve CCR7 and CD62L which are downregulated in Tumor-associated (TA)-pDC compared to ascitis or blood pDC. Furthermore, TApDC express a partially mature phenotype compared to patient's blood and ascitis pDC that may reflect an in situ activation. Importantly, ex vivo TApDC produce lower amounts of IFN-α, TNF-α, IL-6 and RANTES in response to TLR ligands than ascitis or healthy donor pDC, suggesting a specific inhibition by ovarian tumor environment. In vitro, tumor or ascitis-derived surnageants (SNTUM) induce inhibition of the production of IFN-α and TNF-α by healthy pDC in response to TLR activation, suggesting the implication of soluble factors in this functional inhibition. In addition, TApDC but not ascitis pDC or healthy donors pDC direct allogeneic naive CD4+ T lymphocytes to produce high amounts of IL-10. Thus, TApDC may contribute to the tumor environmental immunosuppressive network. Elucidation of the mechanisms of dysfunctions of TApDC could have clinically relevant implications for future therapeutic strategies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1910.
Abstract 1916: Robust pro-inflammatory cytokine secretion by tumor-infiltrating t cells despite altered Stat1/Stat3 signaling responses
Authors: O'Donnell Erika A. , Nolan Garry P. , Engleman Edgar G. , Mende Ines 
Published: February 2011

Abstract
The mechanisms whereby tumors reap the pro-growth benefits of an inflammatory context while still evading the immune response are not fully understood. Using phospho-specific flow cytometry, we demonstrate differential biasing of STAT phosphorylation responses within the tumor microenvironment, with B16 and CT26 cancer cells responding preferentially to pro-inflammatory IL-6 and IFN-γ and tumor-infiltrating T cells responding preferentially to anti-inflammatory IL-10. Investigation of cytokine responsiveness biasing within tumor-infiltrating T cells revealed that the intratumoral T cell population is shaped by non antigen-specific accumulation of CD62L− T cells, which lack responsiveness to pro-inflammatory cytokines despite their robust secretion of these factors. The unchecked production of pro-inflammatory factors by antigen-experienced T cells within the tumor suggests a novel role for these cells in supporting tumor growth by contributing to the inflammatory milieu within the tumor microenvironment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1916.