bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ED01-01: Report card for chemoprevention trials: The good, the bad and the ugly-How can we do better?
Authors: Lee J. Jack 
Published: January 2014

Abstract
There is no quarrel that prevention is preferable for fighting cancer compared to treating the disease in a late stage. Prevention studies, however, can be difficult and challenging to design and to conduct due to the low incidence rate, long process of cancer development, large sample size, extended study duration, cost, and the requirement of well tolerated or little toxicity of the chemopreventive agents. In the past 30 years, much effort has been devoted to chemoprevention in breast, colon, head/neck, lung, skin, and prostate cancers, etc. An overview of the successes and failures of the chemoprevention trials will be given. In order to do better, we must make improvements in the following areas: (1) Identify high risk individuals. Individual cancer risk models are available in breast and lung cancers for example but need to be refined. (2) Focus on subjects with premalignant lesions or intra-epithelial neoplasm as they are ideal candidates for prevention trials. (3) Identify subjects with molecular targets. For targeted agent trials, selecting subjects most likely to respond based on the agent's mechanism of action can dramatically increase the study efficiency. (4) Identify and validate the intermediate or surrogate endpoints for cancer development. (5) Apply efficient and flexible designs such that correct answers can be reached with a smaller number of patients in a shorter period of time. Adaptive randomization can also allow more subjects to be treated with better treatments in the trial based on cumulative information. (6) Balance the risk benefit ratio. It is evident that all treatments come with certain side effects. Seeking favorable efficacy and toxicity tradeoff is critically important for developing successful prevention strategies. More effective chemoprevention studies can be designed and implemented through the lessons learned.
Citation Format: J. Jack Lee. Report card for chemoprevention trials: The good, the bad and the ugly: How can we do better? [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED01-01.
Abstract ED03-02: Biomarker statistical design
Authors: Feng Ziding 
Published: January 2014

Abstract
Many cancer biomarkers were put into clinical use without a proper sequence of “level of evidence” evaluation (e.g., PSA for prostate cancer screening). Furthermore, most cancer biomarkers failed on their journey to clinic use. False positive findings are rampant. Better strategies are necessary for structured phase of development parallel to the phases for drug development, and rigorous study design standards to enhance the chance of producing biomarkers with clinical utility.
As the Coordinating Center for the Early Detection Research Network (EDRN), we have proposed a 5-phase biomarker development guideline and PRoBE study design standards to address the above issues. The key elements of PRoBE principles are: (i) the Clinical Context; (ii) Performance Criteria; (iii) the Biomarker test; and (iv) Study power and termination.
Two EDRN liver cancer biomarker validation studies, a completed Phase-2 and an on-going Phase-3, were used to illustrate how these concepts can guide a more structured and systematically development of cancer biomarkers with clinical goal in mind. The Phase-2 study identified promising candidate biomarkers and produced a specimen reference set to systematically evaluate new biomarkers. The Phase-3 study is set to address the clinical question of using biomarkers to improve the early detection of HCC and to reduce unnecessary CT/MRI for patients with liver cirrhosis.
Citation Format: Ziding Feng. Biomarker statistical design. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED03-02.
Abstract ED04-01: Defining and monitoring microbial networks
Authors: Braun Jonathan 
Published: January 2014

Abstract
The composition and function of the microbiome is emerging as a susceptibility factor affecting the tumor microenvironment locally and systemically. However, the high complexity and low inter-individual overlap of intestinal microbial composition are formidable barriers to identifying microbial taxa contributing to disease susceptibility. These difficulties might be overcome by an ecologic analytic strategy to identify modules of interacting bacteria (rather than individual bacteria) as quantitative reproducible features of microbial composition in normal and IBD mucosa. Using co-occurrence and network analysis of the intestinal mucosal bacterial microbiome, we have uncovered 5 microbial modules, each detectable in all individuals, and two modules were associated with colorectal susceptibility states such as inflammatory bowel disease. Network analysis of mucosal metabolites and proteins indicates that each microbial module is associated with a distinct functional mucosal community, which can be directly visualized forming a microgeographic distribution at the mucosal surface. Systemic products produced by certain mucosal functional communities also induce remote genotoxicity associated with lymphoma formation in susceptible individuals. Microbial modules thus provide an integrative view of microbial ecology relevant to cancer, and permit quantitative and reproducible microbial monitoring by minimally-invasive sampling of the readily accessible rectal mucosa.
Citation Format: Jonathan Braun. Defining and monitoring microbial networks. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED04-01.
Abstract ED05-01: Diet, physical activity and the prevention of obesity-related breast cancer: Lessons learned from transdisciplinary research
Authors: Hursting Stephen D. 
Published: January 2014

Abstract
Randomized clinical trials, observational epidemiologic studies, behavioral intervention studies, and basic animal and cellular/molecular research have complementary and synergistic roles in advancing knowledge on food, nutrition, physical activity and cancer prevention. In most cases, a single study (of any type) is unlikely to provide sufficient evidence of causal associations, and the entire available body of data from various perspectives and disciplines is necessary to provide the best evidence for the relationship between a dietary factor and cancer risk. One way to accelerate research progress in this area is to form transdisciplinary teams to approach a research problem on a multilevel basis. As but one example, the convergence of evidence supporting obesity and obesity-related biomarkers as risk factors for cancer, based on both human and animal studies, supports the recommendations from multiple agencies that persons “be as lean as possible, within the normal range of body weight”. However, with nearly 7 in 10 US adults currently at an unhealthy weight, and given the established associations between excess weight and many cancers s well as the difficulty many have in losing weight, new evidence-based targets and strategies are necessary to break obesity-cancer links. This presentation will discuss lessons learned from a transdiciplinary approach that bridges animal model and mechanistic studies with randomized breast cancer prevention trials.
Citation Format: Stephen D. Hursting. Diet, physical activity, and the prevention of obesity-related breast cancer: Lessons learned from transdisciplinary research. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED05-01.
Abstract FO02-02: What are the hurdles for moving approved drugs into the prevention setting?
Authors: Munster Pamela N. 
Published: January 2014

Abstract
Most anticancer agents are initially tested in patients with metastatic disease. Early dose finding studies evaluate the tolerability and safety of such agents, and the recommended Phase II dose is most commonly derived from toxicity assessments in the first 3-6 weeks of treatment. An acceptable maximally tolerated dose allows dose-limiting toxicities in at least one of 6 patients or &lt;33% of the treated patients. Dose limiting toxicities are typically defined as grade 3 non-hematological toxicities and grade 4 hematological toxicities occurring in the first 3-4 weeks of treatment. Hence, most agents that receive approval from trials in metastatic patients are derived from studies with a relatively short exposure time and allow a considerable negative impact on quality of life. Similarly, novel anti-cancer agents that are tested and approved in the adjuvant setting are usually administered for a limited time span. Cytotoxic agents have therefore rarely been considered as chemopreventive agents.
The emergence of more effective targeted agents or biologics are of great interest as potential chemoprevention agents.
However, the motivation of treatment adherence and the acceptance of severe side effects of agents is higher when treating metastatic disease or when preventing a recurrence after a diagnosis of limited stage disease. Many of the targeted agents and biologics are developed similar to cytotoxic agents based on the maximally tolerated dose rather than optimal biological dose.
In contrast, cancer prevention agents may have to be given over prolonged periods to patients who have an elevated risk of developing cancer solely based on genomic testing or population studies. The uncertainty of the individual risk and potential benefit has to be weight against toxicities and impact on quality of life. The acceptance of grade 3 and 4 toxicities in this population is very limited.
The use of a targeted or biologic agent originally approved for metastatic disease in the prevention setting, will require a reassessment of what are acceptable doses for long-term use based on lower grade toxicities. Furthermore, a more in depth understanding of the effective biological and molecular concentrations and the development of predictive biomarker will be paramount.
Citation Format: Pamela N. Munster. What are the hurdles for moving approved drugs into the prevention setting? [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr FO02-02.
Abstract PL01-01: The role of telomeres and telomerase in aging and cancer
Authors: Shay Jerry W. 
Published: January 2014

AbstractOne of the fundamental differences in the behavior of human normal versus tumor cells is that most normal cells divide for a limited number of times (Hayflick Limit) whereas tumor cells can proliferate indefinitely (one of the hallmarks of cancer). It is widely believed that the biological function of cellular aging (senescence) is to serve as a mechanism for restricting cancer progression. It is now established that almost all advanced cancers express telomerase, and this provides the molecular mechanism for the bypass of both telomere-associated senescence. The following topics/questions will be discussed in this lecture.1. Evidence that the telomere-based mechanism of cellular aging in human cells has held the test of time2. The role of telomerase in bypassing telomere-based replicative senescence proves that the growth arrest of human cells with critically short telomeres is a key molecular basis of human cell aging3. Progress in using telomerase inhibitors in targeting cancer4. Development of accurate methods to quantitatively measure the shortest telomeres5. Methods for safely using telomerase or telomerase activators for identifying and treating telomere diseases associated with aging?Goals and Objectives1. To review the evidence that telomeres are a biomarker that is important in human aging and cancer.2. To review the evidence that introduction of telomerase into normal cells does not lead to an increased risk of cancer and inhibition of telomerase can lead to cancer cell death3. To review human diseases associated with telomere dysfunction and approaches to identifying and treating telomeropathiesCitation Format: Jerry W. Shay. The role of telomeres and telomerase in aging and cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr PL01-01.
Abstract PL02-02: Helicobacter gastritis, metaplasia, and gastric cancer
Authors: Merchant Juanita L. 
Published: January 2014

Abstract
Helicobacter pylori is one of the primary reasons that the gastric epithelium becomes chronically inflamed. As with other epithelial tissues, chronic inflammation can lead to hyperproliferation, metaplasia and eventually gastric cancer. The hedgehog (Hh) pathway is required for embryonic development including development of the gastrointestinal tract. In the pancreas, Hh signaling is extinguished after birth but becomes re-activated by chronic inflammation and when sustained contributes to pancreatic cancer. However, the contribution of Hh signaling in gastric cancer has been less clear. Components of the Hh pathway are elevated in human gastric cancer cell lines, and on this basis, its contribution to gastric cancers have been implicated. Unlike the pancreas, the gastric corpus produces abundant amounts of the Sonic Hedgehog (Shh) ligand. Recent studies have indicated that Shh expressed in the acid-producing parietal cells is required to recruit myeloid cells to the stomach during the initial phase of a Helicobacter infection. We will present evidence showing that the canonical Hh target gene Gli1 is required for the Helicobacter-induced inflammatory response as well as the subsequent development of mucous cell metaplasia, a pre-neoplastic lesion in the stomach.
Citation Format: Juanita L. Merchant. Helicobacter gastritis, metaplasia, and gastric cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr PL02-02.
Abstract PL03-03: The LKB1-AMPK pathway coordinates metabolic reprogramming with growth control
Authors: Shaw Reuben J. 
Published: January 2014

Abstract
The serine/threonine kinase LKB1 is a tumor suppressor gene mutated in the familial cancer condition Peutz-Jeghers syndrome (PJS), as well as in 30% of sporadic non-small cell lung cancer (NSCLC). One of the critical substrates of LKB1 is the AMP-activated protein kinase (AMPK). AMPK is a highly conserved sensor of cellular energy status found in all eukaryotic cells that restores metabolic homeostasis following stress. Thus LKB1 is a unique energy-state sensitive regulator of growth and metabolic reprogramming via its effects on AMPK. Our laboratory has performed a three-pronged screen to identify novel substrates of AMPK that may mediate its effects on metabolism and growth control. These studies have led to the identification of components of the mTOR signaling pathway (raptor, TSC2), the autophagy pathway (ULK1), and transcriptional regulators of metabolism (Srebp1, HDAC4/5/7) all as direct substrates of AMPK. Collectively, these studies uncovered novel conserved effectors of LKB1 and AMPK that mediate their role as a metabolic checkpoint coordinating cell growth with energy status. The connection of AMPK to tumor suppression has also led many to examine whether compounds that normally serve to activate AMPK, may in fact exhibit anti-cancer activities. Notably, the most widely used type 2 diabetes therapeutic in the US and worldwide, metformin, is a mitochondrial OXPHOS inhibitor which activates AMPK. We have therefore examined the potential anti-cancer effects of metformin and its more potent analog phenformin, in the context of genetically engineered mouse models of lung cancer. Whereas cells containing an intact LKB1-AMPK pathway respond to this metabolic stress by undergoing growth arrest, cells lacking LKB1 are unable to sense the damage and continue to divide ultimately undergoing apoptosis. Thus we examined whether this class of compounds may show selective therapeutic efficacy in preclinical trials in Kras-dependent lung cancer mouse models with loss of LKB1 as compared to those bearing loss of p53.
Citation Format: Reuben J. Shaw. The LKB1-AMPK pathway coordinates metabolic reprogramming with growth control. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr PL03-03.
Dissociable Neuroanatomical Correlates of Subsecond and Suprasecond Time Perception
Authors: Hayashi Masamichi J. , Kantele Moona , Walsh Vincent , Carlson Synnöve , Kanai Ryota 
Published: January 2014

Abstract
The ability to estimate durations varies across individuals. Although previous studies have reported that individual differences in perceptual skills and cognitive capacities are reflected in brain structures, it remains unknown whether timing abilities are also reflected in the brain anatomy. Here, we show that individual differences in the ability to estimate subsecond and suprasecond durations correlate with gray matter (GM) volume in different parts of cortical and subcortical areas. Better ability to discriminate subsecond durations was associated with a larger GM volume in the bilateral anterior cerebellum, whereas better performance in estimating the suprasecond range was associated with a smaller GM volume in the inferior parietal lobule. These results indicate that regional GM volume is predictive of an individual's timing abilities. These morphological results support the notion that subsecond durations are processed in the motor system, whereas suprasecond durations are processed in the parietal cortex by utilizing the capacity of attention and working memory to keep track of time.
Displaying Contextual Information Reduces the Costs of Imperfect Decision Automation in Rapid Retasking of ISR Assets
Authors: Rovira Ericka , Cross Austin , Leitch Evan , Bonaceto Craig 
Published: January 2014

Objective: The impact of a decision support tool designed to embed contextual mission factors was investigated. Contextual information may enable operators to infer the appropriateness of data underlying the automation’s algorithm. Background: Research has shown the costs of imperfect automation are more detrimental than perfectly reliable automation when operators are provided with decision support tools. Operators may trust and rely on the automation more appropriately if they understand the automation’s algorithm. The need to develop decision support tools that are understandable to the operator provides the rationale for the current experiment. Method: A total of 17 participants performed a simulated rapid retasking of intelligence, surveillance, and reconnaissance (ISR) assets task with manual, decision automation, or contextual decision automation differing in two levels of task demand: low or high. Automation reliability was set at 80%, resulting in participants experiencing a mixture of reliable and automation failure trials. Dependent variables included ISR coverage and response time of replanning routes. Results: Reliable automation significantly improved ISR coverage when compared with manual performance. Although performance suffered under imperfect automation, contextual decision automation helped to reduce some of the decrements in performance. Conclusion: Contextual information helps overcome the costs of imperfect decision automation. Application: Designers may mitigate some of the performance decrements experienced with imperfect automation by providing operators with interfaces that display contextual information, that is, the state of factors that affect the reliability of the automation’s recommendation.
Oropharyngeal Carcinoma in Young Adults: An Alarming National Trend
Authors: Gayar Omar H. , Ruterbusch Julie J. , Elshaikh Mohamed , Cote Michele , Ghanem Tamer , Hall Francis , Siddiqui Farzan 
Published: January 2014

ObjectivesTo assess the incidence, treatment methods, and outcomes of oropharyngeal squamous cell carcinoma (OPSCC) in patients younger than 45 years.Study DesignRetrospective population based.SettingSurveillance Epidemiology End Results (SEER) 9 database.Subjects and MethodsThe SEER 9 database was queried from 1973 to 2009 for OPSCC patients <45 years of age.ResultsThere were 1603 patients with OPSCC younger than 45 years. The incidence in patients between 36 and 44 years increased from 0.79 to 1.39 (per 100,000). In the same time period, there was an increase in the rate from 0.20 to 0.42 in whites and a decrease in the rate in African American (AA) patients from 0.67 to 0.32. The proportion of grade III/IV tumors also steadily increased from 28% in 1973 to 1979 to 43% in 2000 to 2009 (P <. 0001). Surgery alone was performed in 220 patients (13.72%) and in combination with radiation therapy in 734 patients (45.79%). Five‐year survival for the study cohort is 54%. Compared with white patients, AA patients had worse survival (P <. 0001). Patients who had surgery, either alone (localized stage patients) or in combination with radiation, had the highest 5‐year survival followed by those who had radiation.ConclusionsThere was an increase in OPSCC in the study patients within the past 4 decades, particularly in those aged 36 to 44 years. Interestingly, the incidence in whites increased and in AA patients it decreased. It is important to note that most of these patients were treated with surgery, either alone or with radiation therapy. The rising incidence within recent decades is thought to be related to human papillomavirus transmission and changes in sexual practices.