bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2572: Pro-resolving effects of 15-deoxy-α12,14-prostaglandin J2 through activation of Nrf2-mediated CD36 expression in murine macrophages
Authors: Kim Wonki , Lee Ha-Na , Surh Young-Joon 
Published: August 2012

Abstract
The process of resolution of inflammation is actively controlled by a series of endogenous mediators, which activate pro-resovling mechanisms. 15-Deoxy-α12,14-prostaglandin J2 (15d PGJ2), one of the terminal products of cyclooxygenase-2 (COX-2), is an endogenous lipid mediator exerting both anti-inflammatory and pro-resolving effects. Enhanced biosynthesis of 15d-PGJ2 has been suggested to contribute to resolution of inflammation. The phagocytosis of apoptotic neutrophils by macrophages, called effercytosis, is the most important step for complete resolution of inflammation. However, the molecular mechanisms underlying pro-resolving effects of 15d-PGJ2 remain not fully clarified. The phagocytic action of macrophages is known to be mediated by scavenger receptors present on the plasma membrane of these cells. CD36, one of the class B scavenger receptors, is considered to recognize phosphatidylserine on the outer membrane of apoptotic neutrophils, thereby inducing phagocytosis. Recently, NF-E2 related factor 2 (Nrf2) has been reported to be the essential transcription factor involved in the induction of CD36 expression. In the present study, we found that 15d-PGJ2 (1 μM) increased expression and nuclear translocation of Nrf2 in murine macrophage-like RAW264.7 cells. The electrophoretic mobility shift assay revealed that 15d-PGJ2 enhanced the DNA binding of Nrf2. In addition, 15d-PGJ2 upregulated the expression of CD36, thereby stimulating efferocytosis. siRNA knockdown of Nrf2 abolished 15d-PGJ2-induced CD36 expression, resulting in reduced efferocytosis. embryonic fibroblasts from Nrf2-null mice failed to up-regulate CD36 expression upon 15d-PGJ2 treatment. Moreover, unlike 15d-PGJ2, its non-electrophilic analog 9,10-ihidro-15d-PGJ2 could not induce expression of Nrf2 and CD36, suggesting that the α,β-unsaturated carbonyl group located in the cyclopenenone ring of 15d-PGJ2 is essential for Nrf2-induced CD36 expression. Taken together, these results suggest that 15d-PGJ2 might expedite resolution of inflammation by activating efferocytosis which appears to be mediated through Nrf2-induced CD36 expression in macrophages.
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 2572. doi:1538-7445.AM2012-2572
Abstract 2581: Curcubitacin B exhibits cytotoxic effects by inhibiting ILK-Paxillin signaling in breast cancer cells
Authors: Gupta Parul , Srivastava Sanjay K. 
Published: August 2012

Abstract
Integrins are known to play an important role in promotion of cell motility and survival though activation of Integrin-Linked Kinase (ILK) signaling. Therefore ILK has been an attractive target to inhibit metastasis and tumor growth. Curcubitacin B (CuB) is a steroidal class of chemical present in the plants belonging to cucurbitaceae family. CuB has shown cytotoxic potential in several cancers by causing G2/M cell cycle arrest and inhibition of JAK/STAT3 pathway. However, the exact mechanism of CuB and its role in metastasis is not known. Integrins transmit cell survival signals through ILK-Paxillin complex and further play role in activating AKT signaling. This cascade ultimately works through the activation of Rho kinases like ROCK1 and RhoA. Our results show that CuB significantly suppressed the growth of MDA-MB-231 and MCF-7 breast cancer cells in a concentration and time-dependent manner. CuB also induced apoptosis and down-regulated ILK1 expression. In addition, CuB suppressed the phosphorylation of AKT at Ser473, paxillin at Tyr118 and down-regulated ROCK1 protein expression. Previous studies have shown that heregulin, a ligand of HER2 induces paxillin expression, indicating a correlation between HER2 and paxillin. Interestingly we observed significant downregulation of paxillin in HER2 overexpressing breast cancer cells, suggesting that CuB is equally effective in HER2 overexpressing tumor cells. Taken together our results indicate the anti-cancer effects of CuB in breast cancer cells by targeting paxillin, ILK and ROCK. Further detailed mechanistic work is in progress. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute].
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 2581. doi:1538-7445.AM2012-2581
Abstract 2583: Green tea polyphenols cause stabilization and increased transcriptional activity of p53 by increasing its acetylation through inhibition of class I histone deacetylases
Authors: Thakur Vijay S. , Gupta Karishma , Gupta Sanjay 
Published: August 2012

Abstract
p53, a major tumor suppressor and transcription factor protects the cells from both internal and external stress by modulating cell cycle and apoptotic pathways. p53 is mutated in more than 50% of human cancer and in most others, its pathway is defective. p53 undergoes a number of posttranslational modifications including acetylation of lysine (Lys) residues on its C-terminal. Acetylation of p53 at Lys373 and Lys382 has been reported to decrease its degradation and increased binding to DNA, leading to increased transcription of its downstream targets such as p21/waf1 and Bax. The process of acetylation is regulated by a group of opposing enzymes histone acetyltransferase (HATs) and histone deacetylases (HDACs). Class I HDACs (HDAC 1, 2, 3 and 8) are shown to be upregulated in a variety of human cancers including prostate cancer and their inhibition by HDAC inhibitors leads to cell cycle arrest and apoptosis in cancer cells. In pursuit of safe and effective HDAC inhibitors, we earlier demonstrated that green tea polyphenols (GTP) and its major constituent, (-) epigallocatechin-3-gallate (EGCG) has ability to inhibit class I HDACs in human prostate cancer cells. Here we demonstrate that GTP and EGCG activates p53 through acetylation at the Lys373 and Lys382 residues by inhibiting class I HDACs in human prostate cancer LNCaP cells. Treatment of cells with GTP (2.5-10μg/ml) and EGCG (5-20μM) resulted in dose and time dependent inhibition of class I HDACs, albeit at varying levels. Discontinuation of treatment with GTP/EGCG resulted in the loss of p53 acetylation at both the sites in these cells. GTP/EGCG treatment also resulted in increased expression of p21/waf1 and Bax at the protein and message levels. The increased GTP/EGCG-mediated p53 acetylation enhanced its binding on the promoters of p21/waf1 and Bax, which was associated with the increase accumulation of cells in the G0/G1 phase of the cell cycle and induction of apoptosis. Taken together, our findings indicate that GTP/EGCG causes acetylation of p53 by inhibiting class I HDACs which is likely to be part of the mechanism that control the physiological activity of p53.
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 2583. doi:1538-7445.AM2012-2583
Abstract 2589: Novel chemopreventive combinatorial regimen significantly suppresses NF-kB and PI3-kinase/Akt pathways in the Syrian golden hamster pancreatic cancer model
Authors: Thakkar Arvind , Grandhi B. Karthik , Wang Jeffrey , Prabhu Sunil 
Published: August 2012

Abstract
Pancreatic cancer caused 40,000 deaths in 2010 and is currently ranked as the fourth leading cause of deaths in the United States. Due to poor prognosis of this disease, it is imperative that chemopreventive strategies be developed to control the formation of the initial neoplastic lesions. We have previously reported the effectiveness of a low dose combination regimen of aspirin, curcumin and sulforaphane (ACS) on MIA-PaCa-2 and Panc-1 pancreatic cancer cell lines. The objective of the current study was to use the ACS combination regimens in vivo to demonstrate the molecular targets responsible for prevention of pancreatic cancer in N-nitrosobis(2-oxopropyl) amine (BOP) carcinogen treated Syrian golden hamsters. BOP treated Syrian golden hamsters (n=6/group) were sacrificed after 24 weeks of treatment with a low (20+45+1.6), medium (67+150+5) and high (200+450+16) doses (in mg/kg) of ACS, respectively. Saline and BOP controls were included in the study. The pancreatic tissues were processed for isolation of nuclear and cytoplasmic proteins, and 20 mg of tissue was used for isolation of total RNA. Results from the Western blot show that low dose of ACS combined regimen down-regulated active NF-κB by inhibiting phosphorylation of IαBβ and p65. Low dose ACS also inhibited phosphorylation of Akt, needed for IKK activation. Consequently at the transcription level, low dose ACS significant down-regulated NF-κB regulated gene products TNFα, IL1α and IL6 compared to BOP controls (p&lt;0.05). Thus, low dose ACS inhibited the translocation of NF-κB into the nucleus by inhibiting the phosphorylation of IαBβ and p65. In addition, RT qPCR analysis of proliferation markers such as proliferating cell nuclear antigen (PCNA) and cyclin D1 show &gt;2 fold down-regulation in low dose regimen compared to BOP controls. With the high and medium doses, a trend similar to the low dose ACS was evident, whereby the effects were more significant at higher doses (p&lt;0.001), thus demonstrating a dose-dependent response. The significance of this work is in the demonstration of the effectiveness in gene regulation of ACS even at the low-dose level which shows its potential as a powerful combinatorial regimen for pancreatic 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 2589. doi:1538-7445.AM2012-2589
Abstract 2660: Prevalence of obesity among subjects with a personal history of cancer: A call for action among cancer survivors and care providers
Authors: Moten Ambria , Jeffers Kayin , Larbi Daniel , Smith-White Roxanne , Taylor Teletia , Wilson Lori L. , Frederick Wayne , Laiyemo Adeyinka O. 
Published: August 2012

Abstract
Background: Studies have suggested that obesity is a risk factor for many common cancers and has a negative impact on the prognosis of those with cancer. Aim: To determine the prevalence of overweight and obesity among cancer survivors. Methods: We used the 2007 Health Information National Trends Survey (HINTS) data and identified those with (n = 966) and without (n = 6,093) a personal history of cancer. We calculated responders’ body mass index (BMI) using self-reported height and weight data and formed 3 categories: BMI &lt; 25 kg/m*2 (normal); BMI 25 - 29 kg/m*2 (overweight); and BMI ≤ 30 kg/m*2 (obese). We used multinomial regression models to evaluate the association of personal history of cancer with BMI categories and calculated risk ratios (RR) and 95% confidence interval (CI). Results: The mean age of responders was 54.2 years and 60.5% were females. Cancer survivors were older (65.4 versus 52.4 years; P value &lt;0.001), but there were no differences by sex or education level. After adjusting for age, sex, education, smoking, race, income, marital status and health insurance status, cancer survivors were as likely to be obese as responders without a history of cancer (Table). Conclusion: In this nationally representative sample of US adults, there is a high prevalence of obesity among cancer survivors. Maintenance of healthy weight should be an integral part of routine care of cancer survivors.

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 2660. doi:1538-7445.AM2012-2660
Abstract 2661: Healthcare utilization by race and sex among a nationally representative sample of adults with and without a personal history of cancer
Authors: Burnside Clinton D. , Williams Mark D. , Hudson Tamaro , Caldera Ricardo , Freeman Clyde , Ricks-Santi Luisel , O'Neal Patricia , Laiyemo Adeyinka 0. 
Published: August 2012

Abstract
Background: Men and minorities suffer higher burdens from cancer. Healthcare utilization differences may contribute to this major public health problem. Aim: To compare utilization of healthcare services by race and sex among adults with and without a history of cancer as measured by having at least one doctor's visit within the last 12 months. Methods: We analyzed data from 7,229 responders to the 2007 Health Information and National Trends Survey (HINTS). We identified participants with and without a personal history of cancer and compared them by race and sex with having a doctor's visit within the previous 12 months. We used logistic regression models to calculate Odd Ratios (OR) and 95% confidence intervals (CI). Results: The mean age of respondents was 54.1 years, 38.8% males, 76.1% whites, 9.4% blacks, and 8.6% Hispanics. Of the respondents, 88.8% had health insurance (92.5% whites, 78.9% blacks, and 69.1% Hispanics; P value &lt;0.001). Although there was no difference in health insurance coverage by sex (P value = 0.506), men were less likely to have seen a doctor within the previous 12 months (OR=0.40; 95% CI: 0.31-0.51). Cancer survivors were more likely to have seen a doctor (OR=2.70; 95% CI: 1.68-4.36), but there was no difference by race. After adjusting for age, education, race, income and insurance status, men were less likely to have seen a doctor if they did not have a personal history of cancer (Table). Conclusion: Our study suggests that men improve in their compliance to doctors’ visits only after cancer diagnosis. Targeted interventions to promote use of preventive care services by men are needed. Table: Comparison of doctors’ visit within the previous 12 months by personal history of cancer

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 2661. doi:1538-7445.AM2012-2661
Abstract 2670: Genetic variants in human epidermal growth factor receptor (HER) family gene predict tumor recurrence in breast cancer
Authors: Zhang Henry(Xiong Jia) , Paez David , Giamas Georgios , Filipovic Aleksandra , Yang Dongyun , Bohanes Pierre , Ning Yan , Gerger Armin , LaBonte Melissa J. , Stebbing Justin , Lenz Heinz-Josef 
Published: August 2012

Abstract
Background: Epidermal growth factor receptor (EGFR or HER) family is composed of 4 members: HER1 (EGFR), HER2 (neu), HER3 and HER4. In breast cancer, besides HER2, other HER family members may also overexpressed and their dimerization may contribute to chemo-resistance. Single nucleotide polymorphisms (SNPs) in HER family genes have been associated with breast cancer risk and outcome. We tested 7 functional SNPs in HER family genes (HER1-4) (HER1 rs2227983, HER2 rs1136201, HER3 rs2271189 and HER4 rs4673628, rs839523, rs707284, rs6735267) in a cohort of Estrogen receptor (ER) positive breast cancer patients to determine their association with clinical outcome. Method: Tissue samples of 221 patients with ER positive primary invasive breast cancer (median age=56 years; range=28-90 years), who had undergone surgery at Charing Cross Hospital, London, UK between 1981 and 2003, were analyzed. The median follow-up was 6.5 years and 96 of 221 patients (43%) had tumor recurrence with a 5-year probability of recurrence of 40%. Genomic DNA was extracted from formalin fixed paraffin embedded (FFPE) tissue samples and SNPs were analyzed using direct DNA-sequencing or PCR-RFLP. Results: In univariable analysis, EGFR R497K (rs2227983), and HER2 I655V (rs1136201) were associated with time to tumor recurrence (TTR)(log-rank P=0.007 and 0.041, respectively). In multivariable analysis, EGFR R(G)497K(A) remained significantly associated with TTR. Patients with EGFR 497 AA genotype (n=15) had a shorter median TTR 4.8 years (95%C.I 0.9-6.3 years) compared to those harboring AG or GG genotype (n=201), had median TTR=6.9 years (95%C.I 5.3-8.4 years). (Wald test p value = 0.041 in the Cox model adjusting for lymph node status, tumor size and HER2 staining). Conclusion: Genetic variants in the HER family gene may be potential molecular markers to predict tumor recurrence in advanced ER positive breast cancer. Further large, prospective trials are needed to confirm our preliminary findings.
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 2670. doi:1538-7445.AM2012-2670
Abstract 2680: Characterization of cultured circulating melanoma cells for individualized therapy
Authors: Kolostova Katarina , Hroncova E. , Liberko M. , Hoffman Robert M. , Arenbergerova M. , Rossmeislová L. , Romzova M. , Bobek Vladimir 
Published: August 2012

Abstract
In the presented study circulating melanoma cells (CMSs) have been isolated from a B16 mouse melanoma model and from melanoma patients. Culture of CMCs has enabled us to perform drug sensitivity testing on them. The main hypothesis was to compare drug sensitivity of primary tumor cells grown in culture with the sensitivity of CMCs grown in vitro after capture. B16 murine melanoma was implanted i.p. in mice. Fourteen days after peritoneal injection, mice were sacrificed and blood obtained by cardiac puncture for CMCs-capture. The CMCs were captured either by immunomagnetic separation (Adnagen, AdnaTest Melanoma Select™, Germany) and/or blood added to culture flask containing growing medium. Sensitivity to cisplatin (CDDP) was tested with the MTT-assay at different concentrations. Primary melanoma and disseminated tumor cells (DTCs) were also cultured and tested. The DTCs were isolated from peritoneal washing (ascites like cells), lymph nodes and peritoneal fat tissue. CMCs and DTCs were found less sensitive to CDDP than primary melanoma cells. The ability to capture and culture CTCs enabled these studies which can be used for individualized therapy design.
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 2680. doi:1538-7445.AM2012-2680
Abstract 2688: Color-coded imaging of the pre-metastatic niche in the lung and liver indicates the involvement of cancer-associated fibroblasts
Authors: Suetsugu Atsushi , Momiyama Masashi , Osawa Yosuke , Moriwaki Hisataka , Bouvet Michael , Saji Shigetoyo , Hoffman Robert M. 
Published: August 2012

Abstract
We report here a color-coded imaging model in which the development of pre-metastatic niches in the lung and liver can be identified. The transgenic green fluorescent protein (GFP)-expressing mouse was used as the host which expresses GFP in all organs but dimly in the parenchymal cells of the liver. Mouse breast cancer cells (MMT), expressing red fluorescent protein (RFP), were injected in the tail vein of GFP nude mice to establish a lung metastasis model and in the spleen of GFP nude mice to establish a liver metastasis model. Niche formation in the lung and liver metastasis was observed using the Olympus OV100, IV100, and FV1000 imaging systems. In the lung, GFP host- mouse cells accumulated around a single RFP cancer cell. In addition, GFP host cells were observed to form circle-shaped niches in the lung even without RFP cancer cells, which was possibly a niche in which future metastasis could be formed. In the liver, as with the lung, GFP host cells could form circle-shaped niches without RFP cancer cells. The accumulation of host GFP cells before metastasis formation was observed in the live mouse, enabling cancer-cell niche-interaction to be observed as well as the premetastatic niche in real time. The liver and lung metastases were removed surgically and cultured in vitro. MMT-RFP cells and GFP cancer-associated fibroblasts (CAFs) were observed in the dish, suggesting that CAFs initiated the premetastatic niche. This is in contrast with previous studies which suggested that bone marrow cells initiated the premetastatic mice (Nature 438, 820-827, 2005).
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 2688. doi:1538-7445.AM2012-2688
Abstract 2694: The impact of curcumin plus docetaxel on neuroendocrine features, or not, in castration-resistant prostate cancer: A prospective study
Authors: Planchat Eloïse , Eymard Jean-Christophe , Curé Hervé , Durando Xavier , Barthomeuf Chantal , Gadéa Emilie , Abrial Catherine , Thivat Emilie , Chollet Philippe , Mahammedi Hakim 
Published: August 2012

Abstract
Background &Aims: Curcumin, a polyphenol derived from Curcuma Longa is known for his anti-cancer activity and may exert synergic effects with cytotoxic agents. In parallel, neuroendocrine differentiation in castration-resistant prostate cancer provides an aggressive phenotype to disease. In this prospective phase II study, we assessed the impact of a new combination, docetaxel plus curcumin, in patients with or without neuroendocrine features. Methods: In this phase II study, thirty patients received docetaxel 75 mg/m*2 (perfusion given every 3 weeks) in combination with curcumin orally at 6 g/day (day-4 to day+2 of docetaxel). Neuroendocrine features were determined by serum chromogranin A and neuron-specific enolase, before each cycle. Variations were divided in 3 groups: an increase &gt; 25%, a decrease of 50% or greater and stability. Treatment response were measured by PSA &gt;50% decrease (PSA response) and objective response rate on evaluable metastatic lesions. Results: Initially, 53% of patients had an elevated chromogranin A and 33% an elevated neuron-specific enolase. During treatment, 7% performed a &gt; 50% chromogranin A decrease and 30% a neuron-specific enolase decrease. PSA response was observed in 59% of patients and 40% out of patients with evaluable targets had a partial response. PSA and objective response rate were identical whatever neuroendocrine feature. A positive correlation was found between chromogranin A and PSA, age, weight and palliative radiotherapy. Conversely, neuron-specific enolase was negatively correlated with PSA and patients'age. Conclusions: Curcumin and docetaxel had a global action on tumors with or without neuroendocrine features. Chromogranin A was the best neuroendocrine marker in correlation with clinical parameters. This association delivered then remarkable results on neuroendocrine differentiation of castration-resistant prostate cancer, in comparison with pivotal study data with docetaxel alone (TAX 327).
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 2694. doi:1538-7445.AM2012-2694