bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5401: The influences of morphine on dendritic cell-mediated immunity
Authors: Chang Ming-Cheng , Chen Yu-Li , Huang Ching-Ting , Chiang Ying-Cheng , Huang Chia-Yen , Cheng Wen-Fang , Chen Tzer-Ming 
Published: August 2012

Abstract
Morphine is a widely-used drug for analgesics and drug abuse. Previous studies have also demonstrated that the widely used as an anesthetic agent as well as adjuvant for the treatment of cancer pain and neuropathic pain, will bring harmful effects on specific immune system. Furthermore, the suppressed immune function may lead to postoperative infection and postoperative dissemination of carcinoma. Our research team has confirmed that morphine could promote tumor growth in naïve immunocompromised mice in our previous project, and morphine could suppress the proliferative ability of T lymphocytes even erased the tumor protection effects enhanced by tumor vaccines in vivo. However, these apoptotic phenomena could not explain the complete reasons that morphine induced tumor progression. The antigen processing and presenting activity enhanced by antigen presenting cells is the main cause in tumor development, especially in dendritic cells. The tumorgenesis is always associated with the low antigen presentation activity, and it results the poor recognization by cytotoxic T cells even causes the immuno-escape responses. In the present study, we confirmed that the efficiency of bone marrow monocytes differentiate into dendritic cells was significantly decreased after morphine stimulation. Under high dose morphine treatment, more than 30 % of differentiation efficiency was eliminated in 6 days incubation. Besides, the expression of co-stimulation factor CD80 and CD86 were both decrease after morphine treatment. Furthermore, cytokine expression including IL-6 and TNF-α were both inhibited, however, only IL-10 was slightly increase after morphine stimulation. Besides, the antigen processing and presenting activity of ex-vivo bone marrow-derived dendritic cells were reduced after morphine stimulation. These results suggested that morphine might reduce the process of dendritic cells maturation. These results provided the complete molecular mechanism and the correlation between morphine and immunity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5401. doi:1538-7445.AM2012-5401
Abstract 5439: Inhibition of growth and induction of differentiation of colon cancer cells by extracts from okra (Abelmoschus esculentus) and drumstick (Moringa oleifera)
Authors: Lea Michael A. , Akinpelu Taofeek , Amin Ritesh , Yarlagadda Kiranmai , Enugala Ramadevi , Dayal Bishambar , desBordes Charles 
Published: August 2012

Abstract
In previous studies we have observed that several polyphenolic molecules can inhibit growth and induce the synthesis of differentiation markers in colon cancer cells. In the present work we have sought to determine if similar activity can be observed with methanolic and ethanolic extracts from okra and drumstick. In okra, phenolic molecules and antioxidant activity were associated primarily with the seeds, whereas in drumstick the seeds had lower concentrations of phenolics and antioxidant activity than skin, pulp and seed coat. In studies with okra extracts we have concentrated on the effects of seed extracts because they were generally most inhibitory for cell proliferation as judged by protein yield, thymidine incorporation into DNA and tetrazolium salt reduction. With extracts from drumstick the greatest inhibition of growth was generally with seed coat extracts but anomalous results were obtained in assays of tetrazolium salt reduction. Inhibition was greater at low concentrations but at high concentrations the apparent effect was reversed. Studies in the absence of cells showed that a component of the drumstick seed-coat extract reacted directly to reduce the tetrazolium salt. Comparison with other parts of the drumstick indicated that this reduction was much greater with the seed coat extract. Small effects on colon cancer cell differentiation have been seen with extracts of okra seed and with pulp and seed extract from drumstick as judged by induction of alkaline phosphatase activity. In the case of okra seed extracts this effect was additive with the action of butyrate. Okra and drumstick have had a role in traditional medicine and the present data are encouraging for further studies on potential cancer chemopreventive action.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5439. doi:1538-7445.AM2012-5439
Abstract 5456: Potential role of nitric oxide in chromium-induced lung carcinogenesis
Authors: Forbes Thomas A. , Hopkins Lauren , Schneider Brent , Lazarus Lindsay , Leitenberg David , Constant Stephanie , Schwartz Arnold , Patierno Steven , Ceryak Susan 
Published: August 2012

Abstract
Certain hexavalent chromium [Cr(VI)] compounds are well established human respiratory toxins and carcinogens of occupational and environmental relevance. Our recent studies have shown that intranasal (IN) exposure of Balb/c mice to particulate zinc Cr(VI) compounds leads to pronounced innate inflammation in the lung, which we postulate plays a significant role in pulmonary tumorigenesis. Nitric oxide (NO) has been shown to be induced via inflammatory response mediators, and has been implicated in the progression of different cancers, including lung. Moreover, NO-induced tumor invasiveness has been correlated with enhanced matrix metalloproteinase (MMP) expression in lung tumor cell lines. Of particular relevance to the present study is the finding that in vitro exposure of human lung cells to Cr(VI) in culture led to increased NO production. The aim of the present study was to explore the role of NO in chromium-induced lung tumorigenesis. BALB/c mice received weekly IN delivery of either saline or 10 ug particulate basic zinc chromate, which is an intermediately water soluble chromate typically encountered in mining/chromate production facilities and which is also present as an environmental atmospheric contaminant in urban areas surrounding ferrochrome production facilities. After 9 weeks, immune cells, cytokines, NO, MMPs and pathologic features of lung injury and inflammation were measured in airway lavage fluid and lung tissue, at both 24h after the final Cr(VI) dose, as well as 1 week later. As previously shown, repetitive Cr(VI) exposure induced a neutrophilic inflammatory airway response 24h after treatment. Neutrophils were subsequently replaced by increasing numbers of macrophages 1 week after treatment. Peribronchiolar inflammation was observed in chromate-exposed mice, and was accompanied by a 100-fold increase in pro-MMP9 release into the airways. Notably, airway NO was significantly increased ∼ 1.9 fold in Cr(VI)-exposed mice as compared to their saline-treated counterparts at both time points following final exposure. Moreover, immunoreactivity of induced nitric oxide synthase (iNOS) was markedly increased in airways exposed to Cr(VI), with staining localized to infiltrating immune cells. In conclusion, repetitive exposure to particulate chromate induces an inflammatory environment in the lung, accompanied by enhanced NO production, which we postulate may promote Cr(VI) carcinogenesis. Supported by NIH grants CA107972 and ES017334 to SC and ES017307 to SRP.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5456. doi:1538-7445.AM2012-5456
Abstract 558: Bortezomib induction of the unfolded protein response mediates Epstein-Barr virus lytic activation but is separable from bortezomib-induced cytotoxicity
Authors: Shirley Courtney , Kalu Nene , Shamay Meir , Ambinder Richard F. 
Published: August 2012

Abstract
Epstein-Barr virus (EBV) is associated with many human cancers. Several therapeutic strategies involving the pharmacologic activation of the EBV lytic cycle for tumor killing have been described (1-2). We previously identified bortezomib, a proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma, as a potent activator of EBV lytic gene expression. The mechanism of action of bortezomib as either a viral lytic activator or an anticancer drug remains poorly understood. However, induction of the unfolded protein response (UPR) has emerged as a central theme in both areas of investigation (3). In order to further evaluate the role of the UPR in lytic activation, we treated lymphoid and epithelial tumor cell lines with bortezomib and assessed induction of the UPR and EBV lytic gene expression. We found dose-dependent parallel induction of UPR and EBV lytic infection across cell lines. However, an EBV-immortalized lymphoblastoid cell line was relatively resistant to both bortezomib-induced UPR and induction of EBV lytic gene expression, but not resistant to bortezomib-induced cell killing. To further investigate, we assessed induction of the UPR by thapsigargin which leads to depletion of Ca2+ in the ER. Thapsigargin induced the UPR and EBV lytic gene expression across all the cell lines tested. Blocking ER stress and UPR activation, by cycloheximide treatment or by BiP knockdown, diminished EBV lytic gene expression but had no effect on cellular toxicity. Additionally, regulated knockdown of UPR associated transcription factors (XBP1(s), c-Jun) blocked lytic activation by both agents. Taken together, these results suggest that induction of the UPR by bortezomib is tightly linked to EBV lytic activation but may be separable from the cytotoxic effects of bortezomib. References: 1. Fu DX, Tanhehco Y, Chen J, Foss CA, Fox JJ, Chong JM, Hobbs RF, Fukayama M, Sgouros G, Kowalski J, Pomper MG, Ambinder RF. Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors. Nat Med. 2008; 14(10):1118-22. 2. Feng WH, Hong G, Delecluse HJ, Kenney SC. Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. J Virol. 2004; 78(4):1893-902. 3. Shirley CM, Chen J, Shamay M, Li H, Zahnow CA, Hayward SD, Ambinder RF. Bortezomib induction of C/EBPα mediates Epstein-Barr virus lytic activation in Burkitt lymphoma. Blood. 2011; 117(23):6297-303.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 558. doi:1538-7445.AM2012-558
Abstract 5598: Interaction between BRAF inhibitor PLX-4720 and CDK inhibitors can sensitize melanoma cells with BRAF V600E mutation
Authors: Tortelli Tharcísio Citrângulo , Chammas Roger , Chellappan Srikumar 
Published: August 2012

Abstract
BRAF V600E mutation happens in 60% of all melanomas cases and this mutation is responsible to poor prognosis of the disease. BRAF is part of the MAPK signaling pathway and the V600E mutation of BRAF confers full activation of this survival pathway. Several clinical trials are being conducted using mutated BRAF as a target but so far, all this trials works during a certain moment but soon, melanoma cells becomes resistant to treatment by activating some survival pathways that can continues the signal initialized in the MAPK pathway. Our objective is to evaluate if the combination of BRAF inhibitors and CDKs inhibitors can suppress the acquired resistance of V600E melanoma cells to BRAF inhibitors. Two melanoma cell lines were used in this study. The SKMel 28 cell line, which has BRAF V600E mutation, and the SKMel 02, which is wild type to BRAF. Olomoucine and Roscovitine were the CDKs inhibitors used in this study, while PLX-4720 was BRAF inhibitor. Western blot and Real time PCR were used to verify some survival pathways, like the MAP3K8 and the PRKD3 pathway, that are overexpressed after BRAF inhibition and MTT assay was used to verify cell viability with both treatments combined. The combination of Olomoucine and PLX-4720 or Roscovitine and PLX-4720 could sensitize the BRAF V600E mutated melanoma cell line SKMel 28, but not the BRAF wild type melanoma cell line SKMel 02. Two survival pathways (MAP3K8 and PRKD3) which are activated after BRAF inhibition by PLX-4720 were downregulated in the presence of the CDKs inhibitors in the SKMel 28 melanoma cell line. Also, the retinoblastoma protein was not phosphorylated when the SKMel28 melanoma cell line was treated with the BRAF inhibitor together with the CDKs. The treatment with the BRAF inhibitor and the CDKs inhibitors can sensitize BRAF V600E melanoma cells by decreasing cell viability, downregulation of survival pathways induced by the BRAF inhibitor and preventing Rb phosphorylation. This strategy may overcome the acquired resistance of BRAF-mutated melanoma after treatment with its inhibitors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5598. doi:1538-7445.AM2012-5598
Abstract LB-217: Lycopene and gene expression in benign prostate: a phase II randomized trial
Authors: Gann Peter H. , Dai Yang , Giangreco Angeline Antonio , Deaton Ryan , van Breemen Richard , Lu Yi , Rueter Erika Enk , Nonn Larisa 
Published: August 2012

Abstract
Previous research indicates that lycopene and associated compounds in tomato foods could have cancer chemopreventive properties in the prostate. Pre-clinical and clinical studies provide support for mechanisms involving androgen or IGF-1 regulation, oxidative stress response, inflammation and DNA repair. We undertook a 6-month repeat biopsy trial in men with HGPIN, randomly assigned to consume placebo or LycoMato® capsules, a tomato oleoresin containing 30 mg/day of lycopene. Benign epithelium from fixed prostate biopsy sections (pre- and post-treatment) was laser capture microdissected and RNA was extracted. We reverse transcribed RNA and pre-amplified for 92 target and 4 housekeeping (HK) genes. Pre-amped RNA was loaded unto custom Taqman® Low Density Arrays for qPCR quantitation. For each gene, Ct values were standardized to the mean HK gene values and fold-change (RV, relative value) in expression between baseline and follow-up was determined. Evaluable data was obtained from 16 lycopene subjects and 22 placebo controls. Serum lycopene increased by 83.3% on average in the active group and declined by 35.0% in the placebo group, although changes varied considerably across subjects. Individual gene comparisons by assigned group revealed statistically significant relative downregulation of DDB1, SOD3, and CXCL12 in the lycopene group. Expression changes in GCLC a rate-limiting enzyme in glutathione synthesis and an NRF2 oxidative stress response gene - were positively correlated with serum lycopene changes (Spearman R = 0.42, P = 0.009). Ongoing gene set analysis, by sum of Wilcoxon signed-rank and permutation tests, thus far suggest non-significant trends for treatment effects in the androgen, DNA repair and oxidative stress response gene groups. Initial results from unsupervised hierarchical clustering and principal components analysis for 34 genes with the highest variance showed evidence for classification by treatment group. Among all subjects, baseline serum lycopene was inversely correlated with baseline expression of AMACR, XRCC1, ERCC3, and OGG1 (R −0.32 to −0.38, P &lt; .05). Follow-up studies on protein expression of key targets using immunohistochemistry are underway. The results from this small but unique trial demonstrate the feasibility of this approach and so far indicate that long-term lycopene status may be associated with down-regulation of DNA repair genes in benign prostate and that a 6-month intervention could cause changes in expression of genes and gene sets selected a priori.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-217. doi:1538-7445.AM2012-LB-217
Abstract LB-295: Targeted therapy of human osteosarcoma cell lines
Authors: Yu Yan , Ibrahim Nuha , Walsh William R. , Yang Jia Lin 
Published: August 2012

Abstract
A &lt;20% survival rate for metastatic and recurrent osteosarcoma reflects the inadequacy of available therapies. We aimed to [1] investigate the therapeutic effect of a multikinase inhibitor (sorafenib, gift from Bayer) alone or as a radiosensitizor in human osteosarcoma cell lines, [2] establish a 143B orthotopic mouse model of human osteosarcoma with lung metastasis to identify ras down stream signaling pathways, and [3] assess effect of blocking specific pathway on 143B invasion using a MEK/ERK inhibitor (U0126). Osteosarcoma cell lines, 143B (HOS cell line with k-ras oncogene transformation), HOS and U-2 OS were used in an in vitro experiments. The 143B was also used to set up an orthotopic osteosarcoma mouse model. Clonogenic assay was used to assess the anti-cell growth and anti-colony formation effects of sorafenib and/or radiotherapy (Therapax 3 System) respectively. Immunohistochemistry was used to measure ras down stream signaling factors from both local tumor and lung secondaries of the mouse model. A Matrigel assay was used to assess 143B invasion under interference. IC50s for sorafenib (µg/ml) and x-ray (Gy) were 14.98 and 2.72 (143B), 6.52 and 1.48 (HOS) and 7.72 and 1.49 (U-2 OS) respectively. Ras transformed 143B was relatively insensitive to sorafenib monotherapy. Sorafenib can enhance x-ray treatment in HOS (5-26%) and U-2 OS (4-26%), but not in 143B. The 143B was then used to be injected into the left tibia of 15 nude mice and showed tumor mass at both local area and lung. Detection of ras down stream signaling factors, we found that total MEK, Akt, p38 and phosphorylated MEK (p-MEK), but not p-Akt and p-p38 were positive in both local tumors and lung secondaries. Leiomyosarcoma controls expressed p-Akt and p-MEK, but not p-p38. The 143B cells treated with U0126 had significantly lower in vitro invasion ability compared with controls. Our results indicated that sorafenib may enhance radiotherapy in vitro in some of the osteosarcoma cell lines without overexpression of k-ras gene. The Ras/Raf/MEK/ERK, may play an important role in osteosarcoma lung metastasis, and the targeting MEK/ERK by its specific inhibitor may have a potential use in the effective treatment of osteosarcoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-295. doi:1538-7445.AM2012-LB-295
Abstract LB-425: An NF-κB pathway mediated positive feedback loop amplifies Ras activity to pathological levels in mice
Authors: Ji Baoan , Daniluk Jaroslaw , Liu Yan , Deng Defeng , Huang Haojie , Wang Huamin , Logsdon Craig D. 
Published: August 2012

Abstract
Elevated Ras activity is critical for Ras induced tumorigenesis. However, the underlying mechanisms that lead to pathological levels of Ras activity are unclear. Here, we found that stimulation of Ras signaling by typical inflammatory stimuli was transient and had no long term sequelae in wild-type mice. In contrast, these stimuli generated prolonged Ras signaling and led to chronic inflammation and precancerous lesions (PanINs) in mice expressing endogenous levels of oncogenic K-Ras. The effects of inflammatory stimuli on oncogenic Ras expressing mice were disrupted by deleting IKK2 or inhibiting Cox-2. Likewise, the expression of active IKK2 or Cox-2, or treatments with LPS generated chronic inflammation and PanINs only in mice expressing oncogenic Ras. The data support that in the presence of oncogenic Ras, inflammatory stimuli trigger an NF-κB mediated positive feedback mechanism involving Cox-2 that amplifies Ras activity to pathological levels. Because a large portion of the adult human population possesses Ras mutations in tissues including colon, pancreas, and lung, disruption of this positive feedback loop may be an important strategy for cancer prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-425. doi:1538-7445.AM2012-LB-425
Abstract LB-46: Advocacy & Action
Authors: McIntyre Katherine E. 
Published: August 2012

Abstract
These powerful core statements communicate our purpose and express the heart and soul of all we do, and why we do it. Mission Rooted in God's love; we treat illness and promote wellness for all people. Vision Our vision is to set the standards of excellence in delivery of health care throughout the regions we serve. Values The following values are represented by the six brush strokes preceding our name in the logo. They serve as a reminder to ourselves and our community that our values precede-literally and figuratively-everything we do. - Compassion: Showing empathy and concern for everyone and responding with kindness, and sensitivity. - Quality: Optimizing talents, skills and abilities to achieve excellence in meeting and exceeding our patients’ expectations - Integrity: Adhering without compromise to high moral principles of honest, loyalty, sincerity and fairness - Courtesy: Demonstrating polite, cooperative and respectful behavior; showing consideration and care for each person - Accountability: Using material good wisely; being conscious of the environment; being accountable for prudent use of our talents and financial resources. -Team Work: Working together to accomplish task and goals; recognizing the interdependence of one another and cache person's unique gifts. Navigators Three patient navigators are employed at Lewis Cancer & Research Pavilion. The LCRP also employs patient resource navigators (social workers).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-46. doi:1538-7445.AM2012-LB-46