bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-386: The role of neuronal connexins in the differentiation of neuroblastoma
Authors: Sidhu Mandeep , Belliveau Daniel 
Published: February 2011

Abstract
Gap junctions are membrane channels allowing intercellular communication between adjacent cells, and regulate cellular processes such as metabolism, proliferation, and differentiation. Connexins (Cx), the constituent proteins of gap junctions, are aberrantly localized or have decreased expression in many cancers, and some connexins act as tumor suppressors when overexpressed. Connexins are also highly regulated during development and when overexpressed, some have been shown to enhance cellular differentiation. In the present study, the role of neuronal connexins, Cx36 and Cx45, in the differentiation of SH-SY5Y human neuroblastoma cells was investigated. Retinoic acid was used as the differentiating agent, as it is often employed in differentiation therapy of tumor cells. Retinoic acid induces neuritogenesis and expression of differentiation markers, such as growth associated protein 43 (Gap43), neuropeptide Y (NPY), and neuron specific enolase (NSE) in SH-SY5Y cells. Following 2, 4, and 10 days of retinoic acid induced differentiation of SH-SY5Y cells, Cx36 mRNA expression showed a significant increase compared to non-treated cells, while Cx45 mRNA expression remained stable. Cx36 was overexpressed using liposome-mediated transfection, and an increase in the mRNA levels of Gap43, NSE, and NPY was observed after 48 hours compared to control EGFP transfected cells. Cx36 overexpression also enhanced retinoic acid induced differentiation, as evidenced by the increase in mRNA expression of differentiation markers, Gap43 and NPY, following 2 days of treatment, and will now be confirmed following 4 and 10 days of treatment. Therefore, Cx36 overexpression induces and enhances the differentiation of SH-SY5Y neuroblastoma cells. Current studies involve knocking down Cx36 and Cx45 with shRNA and inducing differentiation of SH-SY5Y cells to determine whether connexin knock down diminishes neuritogenesis or differentiation marker expression. These studies provide insight into the role of connexins in the differentiation therapy approach to cancer treatment.
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 LB-386.
Abstract LB-387: MYCN dependence of tumor propagating cells in an orthotopic model of medulloblastoma
Authors: Ahmad Zai , Moore Amy , Barker Karen , Vaughan Lynsey , Popov Sergey , Pearson Andrew DJ , Chesler Louis 
Published: February 2011

Abstract
Medulloblastoma (MB) is the most common paediatric brain tumor and is a major cause of cancer death in children. MYCN expression is critical to cerebellar development, regulates the fate of neural progenitor cells (NPCs) and drives the expansion of tumor propagating cells (TPCs) thought to represent the cell-of-origin for this disease.
To examine the role of MYCN in MB tumorigenesis, we established neurosphere cell lines enriched for putative TPCs from the cerebella of GTML mice (transgenic for doxycycline-regulable overexpression of MYCN and luciferase). These mice are predisposed to anaplastic/large-cell MB (AACR abstract LB-79).
Neurospheres derived from GTML cerebella with positive luciferase imaging signals but no visible tumor tissue exhibited several characteristics consistent with enrichment for TPCs and/or NPCs. Spheroids proliferated efficiently in the absence of exogenous growth factor, exhibited self-renewal in clonal dilution assays, expressed high levels of Mycn protein and the NPC markers nestin and SOX2, and in response to serum, differentiated along neuronal and glial lineages (increased GFAP and III tubulin expression by immunofluorescence). Finally, orthotopic reimplantation at low titer (&lt;250 cells) recapitulated anaplastic/large-cell MB tumor formation with short latency (&lt;14 days) and complete penetrance.
Suppression of MYCN with doxycycline (confirmed by loss of luciferase imaging) caused growth arrest via a G1 blockade of neurospheres in vitro. Pretreatment of implanted spheres significantly reduced tumor penetrance (&lt;60%) and increased latency (2-3 months). Efficient regression of established tumors was observed with concomitant loss of nestin expression and increases in differentiated glial and neuronal markers.
Taken together, these data suggest that MYCN expression drives MB tumor formation by maintenance or expansion of a population of relatively undifferentiatedTPCs present in normal cerebella. This model represents a significant tool for further investigation of the role of MYCN in MB initiation and progression.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 LB-387.
Abstract LB-39: Development of a novel water-soluble prodrug of paclitaxel that is cleaved by prostate-specific antigen (PSA): In vitro and in vivo evaluation
Authors: Elsadek Bakheet , Graeser Ralph , Esser Norbert , Ajaj Khalid Abu , Saleem Tahia , Melegy Nagla El , Madkor Hafez , Kratz Felix 
Published: February 2011

Abstract
In developed countries, prostate cancer is the second most frequently diagnosed cancer, and the third most common cause of death from cancer in men. Unfortunately, while accumulating clinical data have suggested that the taxanes may prolong the survival in a subset of men with prostate carcinoma, the dose and duration of administration of these drugs are limited by their significant systemic toxicities due to a lack of tumor selectivity. Besides prostate cancer, paclitaxel (Taxol®) is currently showing a promising antitumor activity against a variety of human tumors. In an attempt to improve both the water solubility and tumor targeting properties of paclitaxel, we set out to develop a water soluble paclitaxel prodrug that is activated specifically by prostate-specific antigen (PSA) which is solely expressed in prostate tissue and prostate carcinoma with high levels up to mg/g present in human prostate carcinoma. Using albumin as an efficient carrier for drug delivery, we describe a novel albumin-binding prodrug of paclitaxel, EMC-Arg-Ser-Ser-Tyr-Tyr-Ser-Leu-PABC-Paclitaxel [EMC: -maleimidocaproyl; PABC: p-aminobenzyloxycarbonyl] that was synthesized by reacting EMC-Arg-Ser-Ser-Tyr-Tyr-Ser-OH with H-Leu-PABC-Paclitaxel. This prodrug exhibited excellent water-solubility and was bound rapidly to the cysteine-34 position of endogenous and exogenous albumin. Moreover, incubation studies with PSA demonstrated that the albumin-bound form of the prodrug was cleaved rapidly at the P1-P‘1 scissile bond releasing the paclitaxel-dipeptide H-Ser-Leu-PABC-Paclitaxel. Above all, due to the incorporation of a PABC self-eliminating linker, this dipeptide was rapidly degraded to liberate paclitaxel as a final cleavage product within a few hours in prostate tumor tissue homogenates. Of note was that the albumin-bound form of the prodrug was approximately 4-fold more active in killing PSA-positive LNCaP cells than paclitaxel. In addition, orientating toxicity studies in mice showed that the maximum tolerated dose of the novel paclitaxel prodrug was twice that of conventional paclitaxel. Therefore, the in vivo efficacy of the prodrug (24 mg/kg paclitaxel equivalents) in comparison to free paclitaxel (12 mg/kg) is currently being evaluated in a mouse model of human prostate cancer using luciferase transduced LNCaP LN cells orthotopically implanted in SCID mice.
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 LB-39.
Abstract LB-390: Thyroid cancer incidence trends by gender and histology in Sao Paulo, Brazil, 1997-2005
Authors: Veiga Lene , Neta Gila , Ron Elaine 
Published: February 2011

Abstract
Thyroid cancer incidence has been increasing steadily in much of the developed world, but there is limited information on trends in the developing world. The overall rise in thyroid cancer incidence varies by gender, race/ethnicity, and geographic location, with the largest increases found among women and white non-Hispanics. Where histology is available, this increase has been accompanied by a change in the distribution of histological types, with a particular increase in papillary thyroid cancer. Sao Paulo, Brazil is the largest registry in Brazil and covers has one of the ten highest rates of thyroid cancer incidence worldwide, and has the highest rate among Brazilian registries. The Sao Paulo Registry covers about 15 million people in the region. Approximately 1000 new thyroid cancer cases are documented each year in Sao Paulo. This large number of cases presents the opportunity to evaluate trends in thyroid cancer incidence in a Latin American population. Using 12,495 cases reported between 1997 and 2005 to the Sao Paulo Cancer Registry, we analyzed thyroid cancer incidence patterns by gender and histology using Joinpoint analysis to calculate the annual percentage change (APC) in incidence, adjusting for age (standard world population). We found that females made up the vast majority of cases (87%) compared with males (13%). Papillary was the most common histology (74.7%), followed by follicular (17.3%), medullary (4%), and other (4%) among 77% of cases with histological confirmation. Overall incidence rates increased for both males and females, with a larger APC for females (+7.7%) compared with males (+6.6%). The greatest increases were seen for papillary and follicular histologies for both sexes. Rates increased most for females and males greater than 50 years of age compared with those 50 years or younger. Mortality rates remained relatively constant. These findings suggest that incidence rates of thyroid cancer are increasing in Sao Paulo, following a similar trend as seen in many developed countries. Further research looking at tumor stage and size could help to understand the potential causes of this increase.
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 LB-390.
Abstract LB-392: Ethnic/racial differences in bladder cancer risk: the Multiethnic Cohort
Authors: Setiawan Veronica W. , Henderson Brian E. , Wilkens Lynne R. , Kolonel Laurence N. , Marchand Loic Le 
Published: February 2011

Abstract
Few studies have examined differences in bladder cancer risk among ethnic groups in the United States. We investigated racial/ethnic differences in bladder cancer risk and cancer stage and risk factors for bladder cancer among 189,998 African-American, Japanese-American, Latino, Native Hawaiian, and White men and women in the Multiethnic Cohort Study. We included 880 incident cases of bladder cancer (685 males and 195 females) identified in the cohort over an 11-year period, between baseline (1993 through 1996) and 2004. Data on known/potential risk factors for bladder cancer were obtained from the baseline questionnaire. Among many potential risk factors examined, only cigarette smoking-related variables (e.g. cigarette dose, years of smoking, pack-years, and years since quitting) were significantly associated with risk of bladder cancer in both men and women; the associations were observed in all five racial/ethnic groups. Racial/ethnic differences in bladder cancer risk were observed in men (P&lt;0.0001) and women (P=0.001). Whites, by far, had the highest risk of bladder cancer compared to other racial/ethnic groups; the relative risks (RRs) (vs. Whites) were 0.65 [95% confidence intervals (CI): 0.53, 0.80] for African Americans, 0.63 (95%CI: 0.46, 0.86) for Native Hawaiians, 0.59 (95%CI: 0.49, 0.69) for Japanese, and 0.41 (95%CI: 0.33, 0.50) for Latinos. After adjustment for cigarette dose, the RRs were 0.69 (95%CI: 0.56, 0.85) for African Americans, 0.65 (95%CI: 0.47, 0.89) for Native Hawaiians, 0.62 (95%CI: 0.52, 0.73) for Japanese, and 0.48 (95%CI: 0.38, 0.59) for Latinos. Similar results were obtained when other smoking variables were considered for adjustment. Although Whites had the highest risk of developing bladder cancer, African-American (P=0.007) and Latino (P=0.008) women were more likely to be diagnosed with advanced disease. Among current and former cigarette smokers, regardless of their smoking dose, Whites were more susceptible to bladder cancer than African Americans, Hawaiians, Japanese, and Latinos. Results from this study suggest that differences in self-reported smoking characteristics among men and women of different races/ethnicities do not fully explain interethnic differences in bladder cancer risk.
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 LB-392.
Abstract LB-399: Use of metformin and the risk of cancer in the EPIC-Italy centers
Authors: van Veldhoven Karin , Sacerdote Carlotta , Ricceri Fulvio , Russo Alessia , Krogh Vittorio , Panico Salvatore , Palli Domenico , Tumino Rosario , Berrino Franco , Matullo Giuseppe , Vineis Paolo 
Published: February 2011

Abstract
Background: Recent epidemiological studies suggest a reduced cancer incidence and mortality among metformin users. Some studies also assessed treatment with other anti-diabetic drugs, such as insulin, and found an increased risk of cancer.
Our aim is to investigate in a large prospective study the possible association between metformin use and other anti-diabetic drugs and the risk of cancer. In order to disentangle the protective effect of metformin from the possible increased risk of other anti-diabetic drugs we will compare diabetic patients treated with metformin to diabetic patients treated with other anti-diabetic drugs and to non-diabetic subjects.
Methods: We have requested data on diabetic patients and non-diabetic subjects from 5 different centers in Italy (about 40000 volunteers enrolled), participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. We expect to have approximately 1500 incident and 1000 prevalent diabetic patients. We will adjust our analyses for anthropometric, dietary, and lifestyle factors.
Preliminary analyses have been performed on the Turin cohort, including 473 incident and 214 prevalent diabetic patients. We calculated odds ratios (ORs), adjusting for age and sex for diabetic patients developing cancer using metformin compared to diabetic patients not using metformin.
Results: Among both incident and prevalent diabetic patients we found a decreased risk of cancer for metformin users versus non-metformin users: OR=0.89, 95%CI=0.25-3.14 and OR=0.61, 95%CI=0.22-1.69 respectively, however, these results were not statistically significant.
Conclusion: The results seem to suggest a protective effect of metformin, although it is not statistically significant. Using data from all EPIC-Italy centers will increase our power. This will be the largest prospective cohort study investigating the possible association between the use of metformin and other anti-diabetic drugs, and cancer incidence, comparing diabetics to non diabetics and adjusting for different possible confounding factors.
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 LB-399.
Abstract LB-40: Inhibition of anchorage-independent growth of melanoma cell lines using Riluzole in combination with PI3 kinase pathway inhibitors
Authors: Goydos James S. , Salehomoum Negar M. , Rosenberg Steve , Chan Joseph L-K , Wen Yu 
Published: February 2011

Abstract
We previously reported that the majority of human melanomas express metabotrophic glutamate receptor 1 (GRM1), a cell surface glutamate receptor. We recently completed a Phase 0 trial of Riluzole, a glutamate release inhibitor, in patients with advanced melanoma and showed a clinical response of 34%. We have also shown that Riluzole, can effectively block invasion and migration of melanoma cells in vitro. In our in vitro studies it was observed that the efficacy of Riluzole treatment on anchorage independent growth was attenuated in melanoma lines harboring activated BRAF/NRAS mutations or a PTEN deletion. We have continued our pre-clinical studies by further examining the effects of Riluzole in combination with inhibitors of specific signaling molecules of the PI3 kinase pathway. Specifically, we tested the AKT inhibitor API-2 and the mTOR inhibitor Rapamycin. These inhibitors were used alone or with Riluzole on C8161 (grm1+, braf/nraswt, ptenwt), HT144(GRM1+, BRAFV600E, PTENdel) SKMEL-2(grm1+, nrasq61r) and UACC930(grm1-,brafv600e, ptendel) melanoma cell lines. When treating the GRM1+ cell lines with the individual agents, there was a moderate reduction in the number of colonies relative to the control. However, the combination of Riluzole with API-2 or Rapamycin had a more robust reduction in colony formation. This inhibition was not observed in the GRM1- UACC930 melanoma line where Riluzole in combination with either API-2 or Rapamycin did not induce a significant decrease in colony formation over single treatment with either agent. In addition to the effect on the number of colonies, the combinational treatments had a significant inhibitory effect on the size of the colonies relative to single agent treatments. The monolayer growth assays also demonstrated increased inhibition of growth with the combinational treatments versus single agent treatments. We conclude that the combination of glutamate signaling blockade combined with inhibition of PI3K signaling with either Rapamycin or API-2 is more effective at inhibiting GRM1 expressing melanoma cell proliferation than treatment with any of the agents alone. Combination therapy with Riluzole and either Rapamycin or API-2 may prove a more effective therapy than Riluzole alone in patients with melanoma.
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 LB-40.
Abstract LB-430: Chemopreventive effect of beta-cryptoxanthin on smoke-induced lung inflammation and lesions in ferrets
Authors: Liu Chun , Bronson Roderick T. , Wang Xiang-Dong 
Published: February 2011

Abstract
Background: High intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers in epidemiological studies. However, there are no available data from well-controlled animal studies to examine the effect of beta-cryptoxanthin on smoke-induced lung lesions and potential biological mechanisms by which beta-cryptoxanthin affects lung carcinogenesis. Using a ferret animal model, we evaluated the effect of beta-cryptoxanthin supplementation in both low-and high-dose (7.5 mcg/kg body weight per day vs. 37.5 mcg/kg body weight per day in ferrets which are equivalent to 104 mcg/day vs. 520 mcg/day, respectively, in the humans) on the cigarette smoke-induced pro-inflammatory cytokine TNF alpha, inflammation and squamous metaplasia in the lung.
Methods: Thirty six male ferrets were assigned to one of six groups (n = 6 in each group) for 9 weeks as follows: 1) control; 2) cigarette smoke exposed; 3) low-dose beta-cryptoxanthin (7.5 mcg/kg body weight per day); 4) high-dose beta-cryptoxanthin (37.5 mcg/kg body weight per day); 5) cigarette smoke-exposed plus low-dose beta-cryptoxanthin; and 6) cigarette smoke-exposed plus high-dose beta-cryptoxanthin. Lung TNF alpha was measured by immunohistochemical staining. Lung inflammation and squamous metaplasia were quantified by histopathological evaluations.
Results: Beta-cryptoxanthin supplementation dose-dependently increased plasma and lung beta-cryptoxanthin levels in ferrets. Cigarette smoke exposure lowered plasma and lung beta-cryptoxanthin levels. Treatment with beta-cryptoxanthin substantially reduced the cigarette smoke-elevated TNF alpha levels in bronchial/bronchiolar epithelial cells, alveolar epithelial cells, airway serous/mucous glands and lung macrophages. Beta-cryptoxanthin at both doses also significantly decreased the cigarette smoke-induced lung inflammation. In addition, both doses of beta-cryptoxanthin significantly lowered the incidence of lung squamous metaplasia induced by cigarette smoke exposure. There were no detectable squamous metaplasia in the groups treated with beta-cryptoxanthin alone and in the control group.
Conclusions: Beta-cryptoxanthin may provide a beneficial effect against the smoke-induced lung inflammation and lung lesions.
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 LB-430.
Abstract LB-434: Colorectal, prostate, and skin cancer screening among Hispanic and white non-Hispanic men, 2000-2005
Authors: Jing Zhou , Enewold Lindsey , Peoples George E. , McLeod David G. , Potter John F. , Steele Scott R. , Clive Kevin S. , Stojadinovic Alexander , Zhu Kangmin 
Published: February 2011

Abstract
One of the most effective means of reducing cancer-specific mortality is early detection via cancer screening; however, Hispanic men continue to have lower colorectal, prostate and skin cancer screening rates than White non-Hispanic men. To combat this disparity and educate men and women aged 50 and older about the importance of regular colorectal cancer (CRC) screening, the Screen for Life campaign, which included directed intervention materials in Spanish as well as in English, was launched by the Center for Disease Control and Prevention (CDC) in 1999. We hypothesized that CRC screening rates would increase overtime among Hispanics and non-Hispanics as a result of this campaign and that prostate and skin cancer screening would also increase due to screening recommendations and raised awareness and necessity of cancer screening. The objective of this study was to assess whether CRC, as well as prostate and skin cancer screening rates among Hispanic and White non-Hispanic men changed between 2000 and 2005 using the National Health Interview Survey (NHIS) data. Our results showed that Hispanic men were less likely to comply with cancer screening guidelines for these three common malignancies than White non-Hispanic men. However, significant increases in CRC endoscopic screening were observed in both ethnic groups. It increased 2.1-fold and 2.4-fold for Hispanic and White non-Hispanic men, respectively (P&lt;0.05). In contrast, the use of home fecal occult blood tests remained stable among Hispanics and decreased significantly among White non-Hispanics. PSA screening remained stable, while the use of skin cancer screening tended to increase among both ethnic groups. Our study suggests that a targeted public education program that is culturally sensitive and linguistically appropriate may be effective in increasing CRC screening rates.
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 LB-434.