bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3445: C-reactive protein and lung cancer risk: a Mendelian randomization analysis
Authors: Panagiotou Orestis A. , Caporaso Neil E. , Landi Maria T. , Chatterjee Nilanjan ,   NCI Lung Cancer GWAS Group
Published: July 2016

Abstract
Background: Elevated levels of C-reactive protein (CRP) are associated with increased risk of lung cancer in observational studies. We investigated the causal relation between CRP and lung cancer using previously discovered single-nucleotide polymorphisms (SNPs) associated with CRP levels as genetic instruments.
Methods: We analyzed four lung cancer case-control studies (EAGE, PLCO, ATBC, CPSII) with available GWAS data (total 5,713 cases and 5,736 controls). We identified 21 SNPs associated with CRP levels at P&lt;10-7 in genome-wide association studies (GWAS) and constructed a weighted polygenic score (PGS) multiplying the number of CRP-increasing alleles in each locus by the GWAS-reported effect of the respective allele on CRP levels; this is the largest number of CRP SNPs used in a Mendelian randomization for lung cancer to date. We first examined whether the PGS is associated with smoking phenotypes (smoking status, cigarettes per day, pack-years, smoking duration). Subsequently, we used this PGS as an instrumental variable and estimated the odds ratio (OR) and 95% confidence interval (CI) of lung cancer per standard deviation change in the PGS using logistic regression and adjusting for age, gender, and smoking. We conducted subgroup analyses for different types of lung cancer histologies. Analyses were performed separately for each study and study-specific results were combined through random-effect meta-analysis.
Results: The PGS was not significantly associated with the number of cigarettes smoked per day (P = 0.621), pack-years (P = 0.829), smoking status (0.739), or smoking duration (P = 0.743). Overall, there was no association between PGS and lung cancer risk in EAGLE (OR = 1.02, 95% CI 0.77-1.36; P = 0.876), PLCO (OR = 0.94, 95% CI 0.68-1.31; P = 0.722), ATBC (OR = 0.80, 95% CI 0.59-1.07; P = 0.132), or CPSII (OR = 0.61, 95% CI 0.37-1.02; P = 0.059) as well as after meta-analysis (OR = 0.88, 95% CI 0.73-1.05; P = 0.149; I2 = 17.3%]. Meta-analysis results were similar for adenocarcinoma (OR = 0.94, 95% CI 0.74-1.20; P = 0.630; I2 = 9.3%), squamous cell carcinoma (OR = 1.03, 95% CI 0.79-1.34; P = .844; I2 = 0%), small-cell lung cancer (OR = 0.97, 95% CI 0.62-1.50; P = 0.882; I2 = 34.9%), and other non-small cell lung cancer (OR = 0.93 (0.53-1.65), P = 0.815, I2 = 59.2%).
Conclusions: Genetically elevated CRP levels are not associated with the risk lung cancer. Hence, our results provide no evidence of causality between CRP and lung cancer.
Citation Format: Orestis A. Panagiotou, Neil E. Caporaso, Maria T. Landi, Nilanjan Chatterjee, NCI Lung Cancer GWAS Group. C-reactive protein and lung cancer risk: a Mendelian randomization analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3445.
Abstract 3461: Smoking cessation following a limited 5A intervention in a cohort of patients with head and neck cancer attending for treatment at a regional cancer program in Ontario, Canada
Authors: Conlon Michael S.C. , Saunders Deborah P. 
Published: July 2016

Abstract
A smoking cessation intervention at the time of cancer treatment is an important opportunity to improve patient quality of life, treatment outcome, and survival in people with cancer. This prospective observational study was designed to assess intention to quit, motivation to quit, smoking characteristics and interest in smoking cessation, and assessment of cessation following a standardized smoking cessation intervention. The intervention was a limited clinical 5A intervention offered by trained health professionals and occurred within a dental oncology clinic that offered regular follow-up and any needed pharmacotherapy through the course of cancer treatment. The cohort was composed of head and neck cancer patients who were self-reported ever-smokers at enrolment and who attended the Northeast Cancer Centre, a regional cancer centre in Northeastern Ontario, Canada, for cancer treatment. There were 377 cancer patients who participated in study, with 35.8% (n = 135/377) self-reporting as current smokers. Most current smokers had high nicotine dependence, with 82.2% (n = 111/135) reporting a time to first cigarette (TTFC) of 30 minutes or less; 84.4% (n = 114/135) were interested in quitting smoking. By 1 year post intervention 10 patients had died and 28 patients were lost to follow-up; of the remainder 29 smokers had cessated yielding a cessation rate of 29.9% (n = 29/97); or 23.2% (n = 29/125) conservatively assuming those lost to follow-up remained current smokers. Offering comprehensive smoking cessation during the course of cancer treatment yields long term smoking cessation benefits in a cohort of patients with smoking associated cancers.
Citation Format: Michael S.C. Conlon, Deborah P. Saunders. Smoking cessation following a limited 5A intervention in a cohort of patients with head and neck cancer attending for treatment at a regional cancer program in Ontario, Canada. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3461.
Abstract 347: Developing a novel immunotoxin that targets cells overexpressing ErbB2
Authors: Shen Luqun , Weigel Kelsey , Thomas Clayton , Drapalik Lauren , Schafer Zachary T. , Lee Shaun 
Published: July 2016

Abstract
Immunotoxins are chimeric proteins comprising a specific cellular targeting domain linked to a cytotoxic factor. Here we describe the design and use of a novel, peptide-based immunotoxin that can initiate selective cytotoxicity on ErbB2-positive cells. ErbB2 is a receptor tyrosine kinase that is overexpressed in the tumor cells of approximately 30% of breast cancer patients. Immunotoxin candidates were designed to incorporate a targeting ligand with affinity for ErbB2 along with a membrane lysin-based toxin domain. The use of a membrane lysin as the toxin domain distinguishes our immunotoxins from numerous others in that internalization of the toxin is not required to induce cell death. One particular peptide candidate, NL1.1-PSA, demonstrated selective cytotoxicity towards ErbB2-overexpressing cell lines. We utilized a bioengineering strategy to show that recombinant NL1.1-PSA immunotoxin expression by Escherichia coli also conferred selective cytotoxicity towards ErbB2-overexpressing cells. Our findings hold significant promise for the use of effective immunotoxins in cancer therapeutics. While Herceptin treatment has been effective in patients with ErbB2 positive breast cancer, our novel immunotoxin may ultimately prove to be a novel and efficacious addition to the arsenal of approaches used to eliminate Herceptin-resistant breast cancer cells.
Citation Format: Luqun Shen, Kelsey Weigel, Clayton Thomas, Lauren Drapalik, Zachary T. Schafer, Shaun Lee. Developing a novel immunotoxin that targets cells overexpressing ErbB2. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 347.
Abstract 3476: Factors related to cervical cancer screening differences between regions around Bagamoyo, Tanzania
Authors: Rooney Brianna , Cummings Autumn , Soliman Amr , Kahesa Crispin 
Published: July 2016

Abstract
Background: With cervical cancer being among the most common cancers in East Africa among women, it is important to look at the factors related to referral differences in Tanzania, especially in rural areas where there is little to no access to cervical cancer screening clinics (CCS). Cervical cancer is related to HIV because a woman is 13.3 times more likely to develop cervical abnormalities if she is HIV positive. There are more HIV-positive women that attend CCS than HIV-negative women. This leads to more research to discover the variation in screening rates between HIV-positive and HIV-negative patients within the same village, as well as the variation in the screening rates between different villages.
Purpose: This study aims to determine the multi-level factors related to differences in cervical cancer screening frequencies between villages in Bagamoyo, Tanzania, and providers’ perception of barriers to screening at the Bagamoyo District Hospital (BDH). Factors identified that influence CCS attendance are HIV prevalence, distance to BDH, number of clinics, and female population.
Methods/Design: This mixed method design includes data obtained from the Tanzania Ministry of Health, the Bagamoyo District Medical Officer, and BDH medical records, as well as additional data from questionnaires conducted with health care providers, doctors or nurses, employed at BDH. The questionnaires included written informed consent. Data obtained from CCS medical records were used to estimate the frequency of women screened from 42 villages. ANOVA analysis was used to compare the percent of women screened from each village to the identified risk factors, HIV prevalence, distance, access to clinics, and population. Chi-square analysis was conducted in order to determine associations between type of health care provider and previously identified barriers to screening.
Discussion: This is the first study to examine providers’ perceived barriers to screening in relation to previously identified factors related to differences in cervical cancer screening rates. Further analysis of patient perceived barriers to screening should be conducted in order to better understand differences in screening rates.
Funding: Funding was received from the National Cancer Institute through the Cancer Epidemiology Education in Special Populations program.
Citation Format: Brianna Rooney, Autumn Cummings, Amr Soliman, Crispin Kahesa. Factors related to cervical cancer screening differences between regions around Bagamoyo, Tanzania. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3476.
Abstract 3477: Graduate public health students as health educators: A pilot project to promote cancer health in Puerto Rico
Authors: Moreno Laura , Vélez Himilce , Jiménez Julio , Vadaparampil Susan , Muñoz-Antonia Teresita , Torres José , Quinn Gwendolyn 
Published: July 2016

Abstract
Introduction: Community health workers, known as promotores de salud in Spanish, have been recognized as an effective communication channel to promote health education among marginalized groups. However, cancer education programs often cease efforts when funding ends. This can be particularly problematic in Puerto Rico (PR), where cancer is the leading cause of death. In an effort to identify new ways to provide sustainable cancer health education programs, the NCI-funded PACHE partnership between Moffitt Cancer Center and Ponce Health Sciences University (PSHU) trained graduate public health students to disseminate cancer education to PR communities. This was achieved by developing a culturally adapted version of “Cancer 101: A Cancer Education and Training Program” (Cancer 101) to the PR community. A pilot study was conducted to test students’ ability to: I) deliver the educational intervention, charlas, in the community; II) utilize a specific module from the curriculum, “Cancer in PR”, which focused on current island data and statistics, and definitions of the cancer and its various types; and III) to measure community members’ cancer knowledge before and after the charla.
Methods: Students enrolled in the class Principles of Health Education in Practice (n = 15) participated in a two-day Cancer 101 training session. Upon completion, students were divided into 5 teams (n = 3 per team), each delivering the “Cancer in PR” charla to a community group of their selection. Cancer knowledge was assessed before and after the charla via a 10-item true or false questionnaire. Items were summed to create an overall knowledge score (range: 0-10).
Results: A total of 201 participants attended the community educational intervention at 10 different locations in PR (Salinas Elderly, Guancha, Hogar San Jose, etc.). Participants pre and post-test mean score (SD) were 4.54 (2.31) and 7.65 (2.28) respectively, with a 3.1 (2.79) point increase in overall cancer knowledge (p&lt;.000). Students reported the Cancer 101 toolkit was feasible and appropriate for each of the communities in which they delivered the intervention.
Conclusion: Results from this pilot project suggest public health students are an innovative and sustainable way to improve cancer health communication and a novel strategy for reducing cancer health disparities.
Citation Format: Laura Moreno, Himilce Vélez, Julio Jiménez, Susan Vadaparampil, Teresita Muñoz-Antonia, José Torres, Gwendolyn Quinn. Graduate public health students as health educators: A pilot project to promote cancer health in Puerto Rico. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3477.
Abstract 348: Small molecule Axl Ig1-Gas6 inhibitors block Gas6-inducible Axl signaling and suppress tumorigenicity
Authors: Bansal Nitu , Kimani Stanley , Singh Kamlendra , Comollo Thomas , Kumar Sushil , Kholodovych Vladyslav , Peng Youyi , Welsh William , Joseph Bertino , Birge Raymond B. 
Published: July 2016

Abstract
TAM receptors (Tyro-3, Axl, and Mer) are a family of three homologous receptor tyrosine kinases (RTKs) expressed predominantly on myeloid-derived hematopoietic cells and epithelial cells which function as inhibitory receptors that dampen inflammatory responses and maintain tissue tolerance. Additionally, all three TAMs have been implicated in various human malignancies, where level of expression is often associated with more aggressive staging of the cancers, poorer predicted patient survival, as well as drug-resistant cancers. Over the past several years, considerable effort has been made to generate small molecule tyrosine kinase inhibitors and biological therapeutics (such as monoclonal antibodies and soluble extracellular receptor traps) targeting TAM receptors in human cancers. Early preclinical studies show promising anti-tumor activities using either kinase inhibitors or monoclonal antibodies against Axl and Mer, although cross-reactivity with other tyrosine kinase inhibitors is associated with off-target specificities. Here, we report the development and characterization of a series of small molecule inhibitors that target the interface between the Ig1 domain of Axl and Gas6, and inhibit native receptors and Axl reporter lines with sub-micro-molar affinities. Additionally, these compounds inhibit Gas6 inducible motility and invasion in Axl-expressing cell lines, and suppress tumor growth in xenograft models of non small cell lung cancer. Together, these observations demonstrate that Axl can be targeted by small molecules that bind to the Ig1 domain/Gas6 interaction, and validate Ig1 inhibitors as novel agents for treatment of cancer.
Citation Format: Nitu Bansal, Stanley Kimani, Kamlendra Singh, Thomas Comollo, Sushil Kumar, Vladyslav Kholodovych, Youyi Peng, William Welsh, Bertino Joseph, Raymond B. Birge. Small molecule Axl Ig1-Gas6 inhibitors block Gas6-inducible Axl signaling and suppress tumorigenicity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 348.
Abstract 3482: Inhibition of glucose metabolism in neuroendocrine tumors by lanreotide, sunitinib, and rapamycin
Authors: Rubinek Tami , Shabtay-Orbach Ayelet , Hesin Arkadi , Rubinstein Tammi , Wolf Ido 
Published: July 2016

Abstract
Background: Neuroendocrine tumors (NETs) represent a heterogeneous family of neoplasms, which may develop from different endocrine glands or endocrine cells dispersed throughout the digestive and respiratory tracts. Lanreotide is a somatostatin analog approved for the treatment of NETs. While Lanreotide extends survival of patients and slows tumor growth, controversy exists regarding its mechanism of action. We hypothesized that lanreotide can interfere with the metabolic activity of NETs, and compared its effect to that of rapamycin and sunitinib.
Methods: The pancreatic carcinoid BON-1 cells and pulmonary carcinoid NCI-H727 cells were used. Viability was tested using colony formation assay. mRNA levels of the glycolytic enzymes hexokinase 2 (HK2), lactate dehydrogenase (LDH) and pyruvate kinase M2 (PKM2) was tested using real-time PCR. Phosphorylation levels of AMP-activated kinase (AMPK) and acetyl CoA carboxylase (ACC) were tested using Western blot. The activity of HK2 was tested using HK enzymatic assay. Lactate secretion was tested in the routine biochemistry laboratory of our institution.
Results: Lanreotide, rapamycin and sunitinib significantly decreased colony formation. They also reduced relative expression levels of HK2, LDH and PKM2 24 and 48h after treatment and decreased HK2 activity after 24h. An increase in the phosphorylation levels of AMPK and ACC was observed shortly after treating the cells with lanreotide and rapamycin. All three agents also decreased lactate concentration in the media.
Conclusions: These data indicate tumor metabolism as an attractive target for therapies against NET, and a novel mechanism of action of somatostatin analogs, namely, alteration of tumor metabolism.
Citation Format: Tami Rubinek, Ayelet Shabtay-Orbach, Arkadi Hesin, Tammi Rubinstein, Ido Wolf. Inhibition of glucose metabolism in neuroendocrine tumors by lanreotide, sunitinib, and rapamycin. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3482.
Abstract 3485: Estrogen receptor ligands and their responses in de novo and tamoxifen resistant cell models
Authors: Gutgesell Lauren M. , Thatcher Gregory R. J. , Patel Hitisha , Xiong Rui 
Published: July 2016

Abstract
Approximately 75% of breast cancer incidences are Estrogen Receptor positive (ER+). Tamoxifen, a selective estrogen receptor modulator (SERM), is the standard of care for many of these ER+ breast cancer patients. Unfortunately, tamoxifen resistance occurs in almost 50% of patients within 5 years of treatment, and endocrine-independence accompanying resistance negates the effects of aromatase inhibitors. Paradoxically, estradiol (E2) has shown clinical efficacy in patients with resistant breast cancer. Understanding the antiproliferative role of E2 and ER signaling in resistant ER+ cell lines is essential to gain a better understanding of paradoxical clinical efficacy and for the appropriate biomarker-assisted selection of endocrine therapy for various stages of ER+ breast cancer. We have discovered ER ligands, based upon a single chemical scaffold with a diverse set of pharmacological responses, which can be used to better understand the role of ER signaling in resistance and therapy: selective ER modulators (SERMs), selective ER downregulators (SERDs), selective estrogen mimics (SEMs), and selective human ER partial agonists (ShERPAs). These compounds were initially classified using an ERE luciferase reporter assay and affinity for ER confirmed by biochemical assays. The effects of these novel ER-directed chemical probes on cell viability were further examined in multiple 2D and 3D spheroid models of tamoxifen resistance. Finally, ERα localization upon administration of these ligands in tamoxifen-sensitive and tamoxifen-resistant cells was studied. While SERDs and SEMs showed growth inhibition in tamoxifen resistant cell lines, both molecules had different responses and mechanisms of growth inhibition. ERα was localized to extranuclear sites upon administration of E2, SEMs, and ShERPAs, an observation specific to the resistant phenotype and mechanistically associated with spheroid disintegration. SERDs inhibited the antiproliferative actions of E2, but were antiproliferative in resistant cell lines. Further dissection of the role of ER in resistance and survival is needed to define the appropriate ER-directed, endocrine therapy in ER+ breast cancer.
Citation Format: Lauren M. Gutgesell, Gregory R. J. Thatcher, Hitisha Patel, Rui Xiong. Estrogen receptor ligands and their responses in de novo and tamoxifen resistant cell models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3485.
Abstract 3492: Differential sensitivity of normal liver and hepatocarcinoma tissues to tBid induced apoptosis is determined by the abundance of VDAC2
Authors: Naghdi Shamim , Roy Soumya Sinha , Walter Ludivine , Hajnoczky Gyorgy 
Published: July 2016

Abstract
A conserved step in extrinsic apoptosis is the outer mitochondrial membrane (OMM) permeabilization by truncated Bid (tBid) that is generated from Bid upon cleavage by Caspase-8 activated at death receptors. tBid directly or indirectly activate proapoptotic proteins i.e. Bak in OMM and/ or Bax in cytosol which is followed by a change in their conformation and oligomerization, leading to a pore formation in the OMM. To better understand the mitochondrial phase of this pathway we applied tBid to semi-permeabilized cells and isolated mitochondria. We monitored cytochrome c release, and the ensuing mitochondrial membrane potential collapse, using immunoblotting and fluorimetry as the markers for mitochondrial cell death. We found that normal liver tissue and normal hepatocytes (Rat, Mouse or Human) are unexpectedly resistant to tBid, whereas hepatocellular carcinoma (HCC) tissues and cell lines (e.g. PLC, Huh7) are greatly sensitized. Considering that the effect of tBid is most effectively mediated through Bak, its abundance in the mitochondria was tested. Bak level is significantly higher in tumor tissue/cell lines, whereas OMM-bound tBid and Bax levels are similar in both cancerous and normal tissue. Since we have recently found that voltage dependent anion channel 2 (V2), a pore forming OMM protein, is specifically required for Bak targeting to OMM, the abundance of V2 was also measured. V2 showed significant upregulation in HCC tissue/cell lines. Rescue studies using V2 sensitized normal hepatocytes and liver mitochondria to tBid. We propose that V2 might be the main regulator for the differential tBid sensitivity in normal liver and hepatocellular carcinoma.
Citation Format: Shamim Naghdi, Soumya Sinha Roy, Ludivine Walter, Gyorgy Hajnoczky. Differential sensitivity of normal liver and hepatocarcinoma tissues to tBid induced apoptosis is determined by the abundance of VDAC2. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3492.