bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4610: NO-NSAIDs inhibit colon tumor cell growth by a cGMP-independent mechanism
Authors: Gurpinar Evrim , Sun Yanjie , Keeton Adam , Tinsley Heather , Gary Bernard , Butler Braeden L. , Binkowski Brock F. , Kopelovich Levy , Athar Mohammad , Piazza Gary A. 
Published: June 2012

Abstract
Nitric oxide-releasing NSAIDs (NO-NSAIDs) were originally developed as prodrugs to reduce the gastrointestinal toxicity of conventional NSAIDs and were found to have improved potency to inhibit tumor growth compared with the parent NSAID. Although different mechanisms have been proposed for their potent anticancer properties, the role of the NO-moiety has not been clearly defined. We have investigated whether the NO group contributes to the anticancer properties of NO-NSAIDs by inducing soluble guanylyl cyclase and elevating intracellular cGMP levels, effects that are associated with the activity of NO donors. We confirmed the increased potency of the NO-derivatives of sulindac, aspirin (o-, p- and m- isomers), exisulind and naproxen with respect to the parent compounds for inhibiting growth of HCT116, SW480 and COLO741 human colon tumor cells. The two derivatives with the lowest IC50 values, NO-sulindac (16.50 µM) and NO-ASA(o) (8 µM) were also tested for cGMP elevation using a novel cGMP biosensor assay in live cells. In brief, HEK293 cells were transfected with a biosensor construct containing cGMP binding domains fused to the modified firefly luciferase gene (Promega) which produces bioluminescence in the cGMP-bound or ‘activated’ state. Cells were treated with NO-Sulindac, NO-ASA(o) and known NO-donors, NOR-3 and SNP as positive controls. Chemiluminescence was measured over a period of 1h. A strong and sustained signal was obtained with the NO-donors, SNP and NOR-3 (50 µM), although no induction was observed with NO-NSAID treatment (50 µM). In addition, SW480 colon tumor cells were treated with 50 µM NO-Sulindac, NO-ASA(o) or NOR-3 and levels of phosphorylated vasoactivator stimulated phosphoproteins (p-VASP), an intracellular marker of cGMP signaling activity, were measured by Western Blotting. NOR-3 caused a time-dependent increase in p-VASP expression, whereas the NO-NSAIDs had no such effect. Since sulindac and certain derivatives have previously been reported to inhibit cGMP-phosphodiesterase (PDE) and inhibit tumor cell growth by a mechanism involving cGMP elevation, we also determined if NO-NSAIDS can inhibit cGMP PDE activity. NO-NSAIDs did not inhibit cGMP hydrolysis by either recombinant PDE5 or in lysates from colon tumor cells, although sulindac sulfide was an effective inhibitor as previously reported. These results suggest that mechanisms other than cGMP elevation explain the anticancer properties of NO-NSAIDs. Funding provided by NIH/NCI grants CA131378 and CA148817.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4610. doi:10.1158/1538-7445.AM2011-4610
Abstract 4614: The organic panic
Authors: Jensen Jacob , Garrett Andrew , O'Neill Kim , Robison Richard 
Published: June 2012

Abstract
In today's market place organic foods have become a very popular topic of discussion. Some studies have compared the different benefits of organic foods vs. conventional foods in disease prevention, including cancer. Although differences have been examined, no broad or concrete conclusions have been reached. Studies have shown that consumption of antioxidants can decrease the risk of oxidative damage, degenerative conditions, and cancer. In this study, antioxidant levels between organic blueberries and conventional blueberries were analyzed and compared in their skin, seed, and juice using the Oxygen Radical Absorbance Capacity assay (ORAC). Data indicate that, in each sample category, conventional samples showed higher antioxidant activities overall when compared to organic samples. 15 organic samples and 15 conventional samples were taken for measurement of antioxidant activity. All values are reported as Trolox Equivalents per 100 grams sample (TE/100g). Conventional blueberry skin revealed highest overall antioxidant activity (7258 TE/100g, s=1024), while organic blueberry seed revealed the lowest (494 TE/100g, s=160). Conventional skin (7258 TE/100g, s=1024) revealed higher values than organic skin (3891 TE/100g, s=288). Conventional seed (1308 TE/100g, s=597) revealed higher values than organic seed (494 TE/100g, s=160). Conventional juice (5077 TE/100g) revealed higher values than organic juice (2205 TE/100g, s=276). Student's t-test analysis revealed statistically significant differences between conventional and organic samples in all three groups (organic vs. conventional skin, p=1.3×10-5, organic vs. conventional seed, p=0.008; organic vs. conventional juice, p=0.022). Data from this study suggest that consumption of organic fruits may not provide higher antioxidant protection when compared to consumption of conventional samples; consumption on conventional blueberries may prove to be most beneficial. Further studies on other fruit samples may provide additional insight on the antioxidant benefits of organic and conventional fruits and vegetables.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4614. doi:10.1158/1538-7445.AM2011-4614
Abstract 4618: Oral administration of bitter melon extract prevents initiation of prostate cancer in TRAMP model
Authors: Ray Ratna B. , Ru Peng , Steele Robert , Oshima Kikyoko , Phillips Nancy , Nerurkar Pratibha 
Published: June 2012

Abstract
Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting progression of the disease to a hormone refractory state. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. We have recently discovered an anti-proliferative effect of bitter melon extract (BME) in a number of cancer cell lines, including prostate, without affecting normal cell growth. Treatment of prostate cancer cells with bitter melon extract modulated Bax expression and induced poly(ADP-ribose) polymerase cleavage. TRAMP (transgenic adenocarcinoma of mouse prostate) male mice display prostatic intraepithelial neoplasia (PIN) at 10-12 weeks of age. We examined whether oral administration of BME as a dietary compound inhibits or delay the conversion of normal prostate to PIN in these mice. We have observed prevention of PIN in BME-fed mice as compared to untreated control. Further tissues analyses for mechanism of cancer prevention are in progress and the results will be discussed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4618. doi:10.1158/1538-7445.AM2011-4618
Abstract 463: The role of cysteinyl leukotriene receptors and tumour associated macrophages in colon cancer progression
Authors: Zhang Yuan , Sime Wondossen , Sjölander Anita 
Published: June 2012

Abstract
The pro-inflammatory cysteinyl leukotrienes (CysLT) have been implicated to play a role in colon cancer. The biological effects of CysLTs are mainly mediated through two different G-protein coupled receptors CysLT1 and CysLT2. We have shown that LTD4 signaling via CysLT1 receptors is linked to tumourigenic processes in cancer cells1. On the other hand, signaling via CysLT2 receptors is involved in cancer cell differentiation2. Colon cancer patients with high CysLT1R and low CysLT2R expression demonstrate poor prognosis3. Tumor-associated macrophages (TAMs, M2 phenotype, CD68+) are not only a source of CysLTs in tumor tissue, but also promote cancer cell invasion. High macrophage content is associated with poor patient prognosis in many tumors. In breast carcinoma, EGF is secreted by activated macrophages, but not by normal or malignant epithelial cells4. CD47, expressed on tumor cells, is capable of interacting with its receptor Signal-regulatory protein α (SIRPα) on macrophages to negatively regulate phagocytosis.
Our aim is to investigate how TAMs affect tumor behavior, and to investigate the role of CysLT1 and CysLT2 receptor-switch, which might be caused by EGF, in cancer progression.
Our preliminary data shows that TAMs are the source of EGF in cancer patient tissue. EGF up-regulates CysLT1R and downregulates CysLT2R expression. Migration of colon cancer cell is enhanced by M2 compared to M1 macrophages in wound healing-assay. Boyden Chamber-assay shows that conditioned medium from colon cancer cells cultured enhances migration of M2 (150%) but not M1 macrophages. We are now investigating the influence of the CysLT1R activity on phagocytosis and proliferation.
These findings suggest TAMs secret various molecular factors, which potentially influence the overall process of tumor initiation. TAMs may also change the balance between CysLT1R and CysLT2R, and there by play an important role in colon cancer progression.
References
1 Öhd JF, Nielsen CK, Campbell J, Landberg G, Löfberg H, Sjölander A. Gastroenterology. 2003 124:57-70.
2 Magnusson C, Ehrnstrom R, Olsen J, Sjölander A. Cancer Res 2007 67:9190-8.
3 Magnusson C, Mezhybovska M, Lörinc E, Fernebro E, Nilbert M, Sjölander A. Eur J Cancer. 2010 46:826-35.
4 O'Sullivan C, Lewis CE, Harris AL, McGee JO. Lancet. 1993 342:148-9.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 463. doi:10.1158/1538-7445.AM2011-463
Abstract 4645: Decreased CD4+ naive and effector memory T cell counts, and CD8+ naïve T cell counts, are associated with trichloroethylene exposure
Authors: Hosgood H. Dean , Zhang Luoping , Tang Xiaojiang , Vermeulen Roel , Shen Min , Smith Martyn , Qiu Chuangyi , Ge Yichen , Ji Zhiying , Xiong Jun , Reiss Boris , Hao Zhenyue , Liu Songwang , Xie Yuxuan , Guo Weihong , Galvan Noe , Li Laiyu , Rothman Nat , Huang Hanlin , Lan Qing 
Published: June 2012

Abstract
Trichloroethylene (TCE) is a volatile chlorinated organic compound that is commonly used in the workplace as a degreaser for metal parts and general-purpose solvent for lipophilic compounds. Although TCE is considered an animal carcinogen, its carcinogenic potential in humans is uncertain. Occupational exposure to TCE has been associated with increased risk of kidney cancer and non-Hodgkin lymphoma in some studies, but findings are not fully consistent. We have carried out a cross-sectional study of 80 workers exposed to TCE and 96 unexposed controls matched on age and sex in Guangdong, China to study TCE's early biologic effects. We previously reported that the total lymphocyte count (but not the granulocyte count) and each of the major lymphocyte subsets (i.e., CD4+ T cells, CD8+ T cells, natural killer (NK) cells, and B cells) were decreased in TCE-exposed workers compared to controls. These findings suggested a selective effect of TCE exposure on lymphoid progenitors and/or lymphocyte survival. To further study which subsets of lymphocytes are affected specifically, we investigated the effect of TCE exposure on the numbers of CD4+ naïve and memory T cells, CD8+ naïve and memory T cells, and regulatory T cells by FACS analysis. Linear regression using the natural logarithm (ln) of each subset was used to test for differences between exposed workers and controls adjusting for potential confounders such as age, sex, smoking status, alcohol consumption, recent infections, and body mass index. We observed that CD4+ and CD8+ naïve T cell counts were about 8% (p = 0.056) and 17% (p = 0.0002) lower, respectively, among exposed workers. Strikingly, CD4+ effector memory T cell counts were decreased by about 20% among TCE exposed workers compared to controls (p = 0.001) whereas the CD4+ central memory T cell population was not significantly changed. Intriguingly, the numbers of CD4+ central memory T cells, and CD8+ memory T cells including central and effector memory population, as well as regulatory T cells were not significantly different between the controls and exposed workers. Thus, TCE selectively targets CD4+ naïve and CD4+ effector memory T cells, and CD8+ naïve T cells. These findings provide further insights into the biologic response of human immune cells upon exposure to TCE, which may include immunosuppression through reduced capacity to respond to antigens.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4645. doi:10.1158/1538-7445.AM2011-4645
Abstract 4649: Association between serum 25-hydroxyvitamin D and risk of female thyroid cancer in Korea
Authors: Shin Myung-Hee , Chung Jae Hoon , Kim Jung Han , Son Young-Ik 
Published: June 2012

Abstract
The incidence of female thyroid cancer is rapidly increasing in Korea. However, factors that would account for this increase are unclear other than the increase in frequency of screening. Vitamin D has shown anticarcinogenic effect on many cancers in experimental studies. Dietary and circulating vitamin D have shown inconclusive, yet promising, inverse associations with colorectal, breast, and prostate cancer in epidemiological studies. Evidences on the association between circulating vitamin D and thyroid cancer are rare. We investigated the association between serum 25-hydroxyvitamin D3 (25(OH)D3) and the risk of thyroid cancer among Korean women. A total of 158 incident thyroid cancer and 144 non-cancer control patients from one large hospital in Seoul were interviewed on their life-style factors between April, 2006 and December, 2007. Among the total participants, 91 cancer (all thyroid papillary cancer) and 105 control patients who agreed to donate their blood were included in this study. The blood of cancer patients was collected at the inpatient wards while the patients were admitted for the operation. The blood of control patients was collected at the inpatient wards or outpatient clinics of four different clinical departments. All blood samples were centrifuged within 1 hour of collection and the serum vials were stored in -80 °C. Serum 25(OH)D3 concentration was measured using radioimmunoassay (RIA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression adjusted for the month of blood collection, body mass index, physical exercise, breast feeding, and menopausal status. The OR of thyroid cancer for the highest quintile (17.2-30.1ng/ml) of serum 25(OH)D3 concentration compared to the lowest quintile (4.0-8.7ng/ml) was 0.30 (95%CI = 0.10-0.85, ptrend=0.04). The inverse association between serum 25(OH)D3 and risk of thyroid cancer was observed in both premenopausal (OR=0.50, 95%CI=0.09-2.68) and postmenopausal women (OR=0.24, 95%CI=0.05-1.09) although statistical significance was not reached in both groups. Women with lower BMI (&lt;23kg/m2) or with no history of breast feeding showed stronger association between serum 25(OH)D3 and risk of thyroid cancer. Our results suggest higher serum 25(OH)D3 may reduce the risk of thyroid papillary cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4649. doi:10.1158/1538-7445.AM2011-4649
Abstract 465: Alternatively activated bone marrow-derived macrophages enhance tumor growth and metastasis in a 4T1 mammary cancer model
Authors: Cho Han Jin , Lim Do Young , Jung Jae In , Her Song , Park Jung Han Yoon 
Published: June 2012

Abstract
Tumor microenvironment consists of a number of components including malignant cells, stromal cells, endothelial cells, infiltrating immune cells, and extracellular matrix. Because inflammation plays an important role in cancer development and progression, tumor-associated macrophages (TAMs) can be one of key regulators of tumor microenvironment. Recent evidence has shown that TAM is associated with poor prognosis in a variety of cancers, including breast, lung, and pancreatic cancer. TAMs account for up to 50% of the total tumor mass, resemble M2-macrophages, and exhibit a number of pro-tumoral functions, including the expression of growth factors and matrix proteases, the promotion of angiogenesis, and the suppression of adaptive immunity. In the present study, we examined the effect of M2 macrophages on the development of and metastasis of mammary cancer using a 4T1-orthotopic tumor model. Monocytes were isolated from mouse bone marrow and treated with IL-4 to induce differentiation into an M2 phenotype. In order to determine whether or not M2 microphages stimulate mammary cancer growth and progression, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pad of syngeneic BALB/C mice, either alone or coupled with bone marrow-derived alternatively-activated macrophages (BMDAM). Co-injection of 4T1 cells with BMDAM increased solid tumor volumes (at 2 weeks after inoculation) and lung metastasis (at 3 weeks after inoculation). We prepared 4T1-luc cells that stably express firefly luciferase which allows for direct examination of tumor growth in animals by estimating the luciferase activity of 4T1 cancer cells via an in vivo imaging system. Luminescence was quantified, and the results demonstrated that the accumulation of 4T1-luc cells was significantly more pronounced when 4T1 cells were co-injected with BMDAM. Immunohistochemical staining of tumor tissues revealed that the proportion of Ki67 (proliferation index)-positive cells was increased in tumor tissues when 4T1 cells were co-injected with BMDAM. We also observed that co-injection of BMDAM with 4T1 cells increased the expression of hypoxia-inducible factor-1α and CD31 (a glycoprotein expressed on endothelial cells and in platelets)-positive cells. These results indicate that TAM increases the proliferation of mammary tumor cells, which may lead to the stimulation of lung metastasis in the 4T1 mammary carcinoma model.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 465. doi:10.1158/1538-7445.AM2011-465
Abstract 4656: Relationship of nicotine and carcinogen biomarkers to lung cancer risk among smokers in the Shanghai cohort study
Authors: Murphy Sharon E. , Berg Jeannette Zinggeler , Wang Renwei , Wickham Katherine M. , Gao Yu-Tang , Hecht Stephen S. , Yuan Jian-Min 
Published: June 2012

Abstract
Individuals who develop lung cancer are predominantly tobacco users and further risk profiling within this group is important to better understand cancer susceptibility and could be used to target interventions. A nested case-control approach was used to evaluate risk factors for lung cancer in a population of Chinese men from Shanghai, China (317 cases and 317 controls). All participants were current smokers at baseline and controls were matched for age, neighborhood, and date of biospecimen collection. Biomarkers assessed in urine were nicotine and its major metabolites, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a tobacco carcinogen), and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT, a biomarker of polyaromatic hydrocarbons). The odds ratio for developing lung cancer were greatest for men with the highest versus lowest quintile of urinary cotinine (cotinine + cotinine glucuronide), OR (95% CI); 8.79 (4.42-17.47) unadjusted, and 5.26 (2.39-11.57) adjusted for years of smoking, cigarettes per day, NNAL, and PheT. Cotinine levels are influenced both by nicotine exposure and metabolism. Nicotine and cotinine are metabolized by cytochrome P450 2A6 which is polymorphic and ∼15% of the Chinese population carry low activity alleles. In contrast, nicotine equivalents is a biomarker of exposure that is less influenced by metabolism as it is the sum of nicotine and its metabolites excreted in urine. Higher odds ratios of lung cancer were also observed for increasing nicotine equivalents but this was a weaker biomarker compared to cotinine in this population, OR (95% CI); 4.86 (2.72-8.69) unadjusted, and 2.58 (1.32-5.03) adjusted for years of smoking, cigarettes per day, NNAL, and PheT. The ratio of trans-3′-hydroxycotinine to cotinine per nicotine equivalents was evaluated as a biomarker of oxidation phenotype. Previously the ratio of trans-3′-hydroxycotinine to cotinine has been used to phenotype individuals for P450 2A6 activity, and to account for variation in nicotine dose during smoking the ratio was expressed per nicotine equivalents. Unexpectedly, the highest quintile of the metabolite ratio was associated with a decreased risk of lung cancer compared to the lowest quintile, OR (95%CI); 0.26 (0.15-0.47). This group would include individuals who have a low nicotine metabolism phenotype and smoke an average-to-high amount. Higher urinary NNAL and PheT were also risk factors for lung cancer albeit the odds ratios were lower than for cotinine.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4656. doi:10.1158/1538-7445.AM2011-4656
Abstract 466: Bone marrow and cancer cells mutually affect each other
Authors: Suetsugu Atsushi , Hassanein Mohamed K. , Osawa Yosuke , Nagaki Mashito , Saji Shigetoyo , Moriwaki Hisataka , Bouvet Michael , Hoffman Robert M. 
Published: June 2012

Abstract
Kaplan et al (Nature 438, 820-827, 2005) demonstrated that bone marrow cells can home to tumor-specific pre-metastatic sites thereby providing a permissive niche for incoming metastatic cells. In the present study, bone marrow cells, which were harvested from tumor-bearing mice, were able to form a strong niche compared to bone marrow cells which were harvested from non-tumor-bearing mouse upon co-implantation with cancer cells. When GFP-bone marrow cells from non-tumor-bearing mice, RFP-bone marrow cells from tumor-bearing mice and dual color MMT mouse breast cancer cells expressing GFP in the nucleus and RFP in the cytoplasm were co-transplanted in the spleen of nude mice, much more RFP-bone marrow cells were observed in liver metastases formed by the breast cancer cells compared to GFP-bone marrow cells. Thus bone marrow derived from tumor bearing animals appeared to play a role in metastasis formation compared to bone marrow derived from naïve animals. The results suggest that bone marrow and cancer cells mutually affect each other.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 466. doi:10.1158/1538-7445.AM2011-466