bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract CN15-02: Gut microbiota and colorectal adenoma
Authors: Keku Temitope 
Published: May 2012

Abstract
CN15-02
The human body is home to about 10 -100 trillion commensal bacterial organisms, of which about 70% reside in the gut. Growing evidence from animal and human studies suggest that these bacteria may contribute to the etiology of diseases such as colorectal cancer, a leading cause of cancer mortality in the United States. Although epidemiologic studies have implicated genetic factors and diet in the etiology of colorectal cancer, the findings from dietary studies have been inconsistent. It is reasonable that the inconsistencies in these dietary studies are related to the influence of the gut microbiota, a mostly understudied component. We hypothesize that the gut microbiota may contribute to the pathogenesis of colorectal cancer through interactions with diet, changes in community composition, production of toxic substances that lead to DNA damage and inflammation. Recent advances in molecular techniques make it possible to describe the gut bacterial communities and evaluate associations with diseases such as colorectal cancer. The presentation will review evidence for the role of gut bacteria in colorectal cancer, discuss potential mechanisms for the link between the gut bacteria and colorectal cancer and identify areas for future investigations.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN15-02.
Abstract CN15-03: Targeting APC-deficient cells for apoptosis: a therapeutic approach for colorectal cancer prevention
Authors: Wu Xiangwei 
Published: May 2012

Abstract
CN15-03
Cancer prevention is generally perceived as long-term process and inevitably associated with adverse effects. Here we report the development of a procedure that specifically targets premalignant tumor cells for apoptosis, potentially making cancer prevention work like therapy. This procedure is based on our finding that deficiency in the adenomatous polyposis coli (APC) gene and subsequent activation of β-catenin leads to repression of cFLIP expression through activation of c-Myc. Independently, retinoid (RA) upregulates tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL) death receptors and suppresses decoy receptors. Combination of TRAIL and RA results in specific killing of APC-deficient cells without harming normal cells. We further show that co-treatment with TRAIL and RA in APC+/Min mice induces apoptosis specifically in intestinal polyps and strongly inhibits tumor growth. Since mutations in the APC tumor suppressor gene are frequently associated with early stages of colorectal cancer (CRC), these results provide a therapeutic approach for chemoprevention of CRC by targeting APC-deficient cells for apoptosis.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN15-03.
Abstract ED01-01: Use of natural products as the scaffolds for the design of molecularly targeted agents for cancer treatment and prevention
Authors: Wang Shaomeng 
Published: May 2012

Abstract
ED01-01
Natural products have played a major role in the development of anticancer therapies for both treatment and prevention of human cancers. Approximately 70% of the current anticancer drugs are natural products per se or semi-synthetic analogues of natural products. In addition, natural products can be also used as the inspiration for the design of molecularly targeted anticancer drugs. In this presentation, we describe the use of natural products to design a scaffold for a new class of small-molecule inhibitors to target the MDM2-p53 protein-protein interaction and to activate p53 for both cancer treatment and potentially prevention. We have designed the spiro-oxindole scaffold, which is embedded in a number of diverse natural products to mimic one key binding element in p53 using a computational structure-based design approach. Using the spiro-oxindole scaffold as the starting point, we have obtained a class of highly potent and specific small-molecule inhibitors of the MDM2-p53 interactions. Our lead compound (MI-219) binds to MDM2 with an affinity &gt;1000-times more potent than the natural p53 peptide and demonstrates greater than 100,000-fold selectivity to MDMX, a close homologous protein of MDM2. MI-219 effectively induces p53 activation in both cancer and normal cells with wild-type p53. Activation of p53 leads to cell cycle arrest and apoptosis in cancer cells but only cycle arrest in normal cells. MI-219 achieves an excellent oral bioavailability. MI-219 activates p53 in both normal and tumor tissues. While MI-219 achieves strong antitumor activity in xenograft models of human cancer, it does not cause damage to normal tissues. Our data suggest that MI-219 should be investigated as a novel treatment and prevention agent in the clinic.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):ED01-01.
Abstract ED01-02: Sphingolipid biodiversity and cancer: an endless source of surprises in cell regulation and novel strategies for cancer chemoprevention and chemotherapy
Authors: Merrill Alfred 
Published: May 2012

Abstract
ED01-02
Sphingolipids are found in essentially all eukaryotes and some prokaryotes and viruses where they influence cell structure, signaling, and interactions with the extracellular environment. The structural diversity of sphingolipids is mind-bogglingly complex due to the combinatorial possibilities for subspecies variation in the lipid backbones (sphingoid base and N-acyl-derivatives, i.e., “ceramides”) and headgroups.
Early comparisons of the glycosphingolipids of normal and transformed cells found differences that prompted speculation that “the structural remodeling of glycolipids and glycoproteins are undoubtedly a key to open a secret box of malignancy” (Hakomori and Murakami,1968). This hypothesis can be reexamined using conventional and “bio-imaging” mass spectrometry, which can be combined with gene expression data for tumors and cancer cell lines to explore the molecular basis for this diversity, and possibly to identify new biomarkers.
The lipid backbones of sphingolipids are additionally interesting because they serve as intracellular and extracellular signals for a wide spectrum of pathways that are important in cancer. This has provided new leads for pharmacologic intervention as well as better understanding of how some chemotherapeutic drugs, and some componsnts of the diet, affect cancer. However, because sphingolipids affect a large number of signaling pathways, it is difficult to interpret and optimize their effects using the typical paradigm of drug discovery (i.e., as agents that are active against a single molecular target). Nonetheless, as an understanding of this complexity has evolved, it has become likely that sphingolipids suppress cancer by modulation of multiple interrelated signaling pathways--in essence, behave like a multi-drug combination. It will probably be necessary to employ the tools of “omics” and systems biology to understand, and capitalize on, the exceptional promise of sphingolipids for cancer detection, chemotherapy and prevention.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):ED01-02.
Abstract ED03-03: CXC chemokines in cancer
Authors: Strieter Robert 
Published: May 2012

Abstract
ED03-03
The biology of CXC chemokines in cancer has expanded beyond their role in mediating migration of specific subsets of leukocytes. CXC Chemokines have been found to display pleiotropic effects for enhancing immunity to tumor associated antigens, regulating angiogenesis, promoting proliferation/anti-apoptosis of tumor cells; and mediating tumor cell invasion and trafficking in an organ-specific manner that leads to metastases. In this presentation, we will discuss the importance of CXC chemokines in regulating angiogenesis and promoting metastases; and demonstrate why they can be seen as important therapeutic targets for intervention in a variety of cancers.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):ED03-03.
Abstract ED04-02: The role of genes in protecting against age-related disease in cancer
Authors: Barzilai Nir 
Published: May 2012

Abstract
ED04-02
Despite evidence for a substantial genetic component, the inherited biological factors that promote extended life span (longevity) in humans remain unknown. We have comprehensively characterized over 450 Ashkenazi Jewish families with exceptional longevity (survival in good health to at least age 95) and have identified several biological markers that may be causative in their longevity. These subjects and their offspring have 2-3 fold increases in rates of polymorphism in 3 genes all validated by other in other studies. Two genes are regulating lipoprotein--cholesterol ester transfer protein (CETP) and apolipoprotein C-3 (APOC-3)--and decrease in plasma levels CETP and APOC-3. Another gene is Adiponectin (ADIPOQ) regulating insulin action and inflammation. We have also demonstrated that these genotypes and phenotypes are associated with less hypertension (HTN), cardiovascular disease (CVD) and metabolic syndrome (MS), and improved cognitive function. However, these genes have not been shown yet to protect against cancer.
Modulation of GH/IGF-1 axis is conferring longevity in mamalians and low IGF-1 levels is associated with decreased rates of cancers in humans. We demonstrated a gender-specific increase in serum IGFI associated with a smaller stature in female offspring of centenarians. Sequence analysis of the IGF1 and IGF1 receptor (IGF1R) genes of female centenarians showed overrepresentation of heterozygous mutations in the IGF1R gene among centenarians relative to controls that are associated with high serum IGFI levels and reduced activity of the IGFIR as measured in transformed lymphocytes. Thus, genetic alterations in the human IGF1R that result in altered IGF signaling pathway confer an increase in susceptibility to human longevity, suggesting a role of this pathway in modulation of human lifespan, possibly by protecting against cancer.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):ED04-02.
Abstract ED05-03: The development of tractable mouse models to study therapeutic response
Authors: Hemann Michael 
Published: May 2012

Abstract
ED05-03
Many human cancers fail to respond to chemotherapy, and cancers that initially respond frequently acquire drug resistance and relapse. While chemoresistance has been observed since the earliest chemotherapeutic application, relatively little is known about the genetic determinants of drug response. Thus, chemotherapy is commonly administered without regard to the specific constellation of genetic alterations present in a given tumor. This current clinical reality is problematic for a number of reasons. First, patients are frequently given chemotherapies that have little or no chance of success. Second, potential tumor vulnerabilities conferred by specific genetic lesions are rarely considered prior to therapeutic administration, so the “right therapy” is generally not matched with the “right tumor”. Third, combination therapies are currently assembled by random trial and error, rather than through a genuine understanding of the basis for drug synergy in a given tumor. Finally, potentially effective drugs frequently fail in clinical trials due to an inability to genetically define small subsets of tumors in which these drugs have significant efficacy. Thus, new approaches to define patient populations most likely to benefit from a particular drug and to identify potentially effective drug combinations are urgently needed. Our lab combines emerging RNA interference technologies with tractable mammalian cancer models to identify genes that influence the action of conventional and molecularly targeted therapies. Specifically, we have performed highly parallel in vivo genetic screens to identify short hairpin RNAs (shRNAs) capable of enhancing or reducing the sensitivity of cancer cells to select anticancer agents, with the objective of finding potential biomarkers that may be used for patient selection, pathways required for drug action, and strategies for effective combination therapy. Importantly, these screens are carried out in vivo, in mammalian systems that more closely approximate the pharmacokinetic, pharmocodynamic, microenvironmental and immunological setting encountered in the treatment of human cancers. It is our expectation that these approaches will provide powerful preclinical test systems that can be used to identify therapies that circumvent traditional drug resistance mechanisms or test novel ‘targeted’ therapeutics.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):ED05-03.
Abstract PL03-01: Role of Stat3 in the tumor microenvironment
Authors: Yu Hua 
Published: May 2012

Abstract
PL03-01
An essential role of immune cells as extrinsic tumor suppressor has been demonstrated. However, immune cells in the tumor microenvironment not only fail to mount an effective antitumor immune response, but also interact intimately with the transformed cells to promote oncogenesis actively. We and others have demonstrated that Stat3, a key oncogenic transcription factor constitutively activated in diverse cancer cells and important for tumor cell survival and invasion, is also activated in tumor stromal immune cells and potently immunosuppressive. Constitutively-activated Stat3 inhibits the expression mediators necessary for immune activation against tumor cells. Moreover, Stat3 activity promotes the production of immunosuppressive factors that activate Stat3 in diverse immune cell subsets. Among the immunosuppressive factors regulated by Stat3 are IL-6, IL-23 and IL-17, which are elevated in cancer, promote chronic inflammation, and cancer progression. Many of these immunosuppressive factors are also Stat3 activators. Our recent results further demonstrate that activated Stat3 in tumor myeloid cells, including macrophages and myeloid-derived suppressor cells, is important for mediating tumor angiogenesis. As such, Stat3 propagates several levels of crosstalk between tumor cells and the tumor microenvironment, leading to tumor-induced immunosuppression, tumor survival and tumor angiogenesis.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PL03-01.
Abstract PL05-01: Mechanistic targets for preventing obesity-related cancers
Authors: Hursting Stephen 
Published: May 2012

Abstract
PL05-01
The prevalence of obesity, an established risk factor for many cancers (1), has risen steadily for the past several decades in the US and many other countries (2). Unfortunately, the mechanisms underlying the obesity and cancer connection are not well understood, and new targets and strategies for offsetting the impact of obesity on cancer risk are urgently needed. Several hormones and growth factors have been implicated as potential mediators of the energy metabolism -carcinogenesis relationship. These include insulin-like growth factor-1 (IGF-1), insulin, several adipokines, and inflammatory/ oxidative stress factors. Calorie restriction (CR), the most commonly recommended dietary strategy for preventing or reversing obesity, has been shown to inhibit spontaneous, transplanted and chemically induced tumors in a variety of animal models (3). In contrast, diet-induced obesity enhances tumorigenesis in many of these same models (3-6). We have also shown in a series of transgenic model systems and microarray studies that the insulin and insulin-like growth factor signaling pathways appear central to many of the anti-cancer effects of CR, as well as the pro-cancer effects of obesity (3). Using AZIP/F1 transgenic mice, which lack white adipose tissue but have high levels of insulin, IGF-1 and inflammatory markers, we have reported that elevated IGF-1 and insulin, as well as increased inflammatory factors (which typically accompany obesity), independent of the adipose tissue per se, appear to be the important dietary targets for disrupting the obesity-cancer link (4). In addition, biochemical and molecular analyses of tissues from lean, overweight and obese mice, as well as IGF-1 deficient mice, established that the Akt and mTOR pathways provide an important target for disrupting the obesity-cancer link via dietary energy balance (5,6).
The other side of the energy balance equation is energy expenditure, which includes the energetics of growth, metabolism, thermoregulation and physical activity (the only truly modulatable aspect of energy expenditure). Epidemiologic studies have established that increased physical activity is associated with reduced risk of colorectal cancer and postmenopausal breast cancer (7). In addition, there is limited but encouraging epidemiologic data suggesting that increased physical activity may be associated with reduced risk of several other cancers as well (7). Physical activity also exerts anticancer effects in several of our transgenic models, but apparently through very different mechanisms than CR (7). For example, the protective effects of exercise appear to be dependent on p53 gene dosage and independent of IGF-1, based on studies in Apc min mice and Wnt-1 transgenic mice (7,8). A better understanding of the mechanisms underlying the energy balance-cancer link will facilitate the development of novel prevention and treatment strategies for offsetting the effects of obesity on cancer.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PL05-01.
Abstract PL05-02: Antioxidants and nutritional intervention in aging and age-associated disease
Authors: Meydani Mohsen 
Published: May 2012

Abstract
PL05-02
Aging is a complex and multifactorial biological phenomenon that is commonly manifested by the decline of many physiological functions and is often associated with chronic diseases such as cancer, cardiovascular disease, obesity, diabetes, arthritis, cataract, osteoporosis, neuronal diseases, and infections. Nutrition has been recognized to play an important role in the aging process and age-associated diseases. Changes in bodily functions with aging, together with malnutrition associated with advancing age, also increase the risk of developing a number of age-related diseases. Free radicals and oxidative stress have been recognized as important factors in the biology of aging and many age-associated degenerative diseases. In this regard, the modulation of oxidative stress by calorie restriction in animal models has been suggested to be one mechanism that helps to slow aging and the decline of bodily functions. Our human studies also indicate a reduction of oxidative stress by lowering caloric intake. Experimental and epidemiological data suggest that dietary interventions with micronutrients such as B vitamins, calcium, zinc and antioxidants such as carotenoids, vitamins E and C, selenium as well as specific phytochemical components in grains, fruits, and vegetables contribute to healthy aging through the primary prevention of age-related decline of bodily functions and associated disorders. In summary, nutrition is a critical determinant of the quality of life in the elderly and may have a significant impact on longevity. Supported by USDA-58-1950-7-707
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PL05-02.
Abstract PR-10: Poverty, insurance status, and colorectal cancer in Colorado: 1995-2006.
Authors: Palisoc Alma , Byers Tim , Miller Sara , Finch Jack 
Published: May 2012

Abstract
PR-10

Background
Poverty in Colorado is an important factor that lowers the advantages of being diagnosed with colorectal cancer (CRC) at the earlier stage of disease and decreases survival due to CRC. Health insurance status can also lead to disparities in early detection of CRC.

Methods
Data from the Colorado Central Cancer Registry in the Colorado Department of Public Health and Environment and information from the 2000 U.S. census were used to determine the proportions of Colorado residents with CRC residing in areas designated as “less than 10% poverty” or wealthier areas, “10-19% poverty” or middle poverty areas, and “20+% poverty” or poorest areas. Since income was not reported to the cancer registry, the poverty level of the census block group area, obtained through the 2000 U.S. Census, where each cancer case resided was used to assign the poverty level for that case. The analyses presented included CRC cases over a 12-year period, from 1995-2006, in order to compare early stage diagnosis by area poverty level and age (less than 65 vs. 65 and older). Early stage at CRC diagnosis and insurance status by area poverty level for 1998-2006 and five-year cause-specific survival among Colorado CRC cases from 1999-2002 were also analyzed.

Results
Among the 21,212 colorectal cancer cases reported to the cancer registry from 1995-2006, 64.5% resided in wealthier areas, 24.8% were from middle poverty areas, and 10.7 % were from the poorest areas of the state. The proportion of early stage diagnosis was lower among the CRC cases from the poorest areas (42.0%) compared to those from the wealthier areas (44.2%). Among those less than aged 65, there was a substantial decrease in early stage at CRC diagnosis as poverty level increased (42.0% from wealthier areas vs. 37% from poorest areas). This is in contrast to those aged 65 and older (45.5% from wealthier areas vs. 44.4% from the poorest areas). In addition, of those younger than age 65 whose insurance status was available from the cancer registry for 1998-2006 (n=5,288), having no insurance or only Medicaid coverage was a disadvantage for early stage diagnosis compared to those with private insurance in all three poverty groups. More importantly, five-year cause-specific survival decreased as poverty level increased (64.1% from wealthier areas, 58.1% from middle poverty areas, 50.8% from the poorest areas of the state). This association between survival differences and socioeconomic status was apparent in those younger than 65 (67.8%, 66.9%, 48.7%) and in those 65 and older (61.5%, 53.9%, 51.9%).

Conclusions
Poverty and lack of health insurance are disadvantages that lead to disparities in early detection of and survival from colorectal cancer.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-10.