bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A04: Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women's Health Across the Nation
Authors: Hart Vicki , Sturgeon Susan , Reich Nicholas , Sievert Lynnette Leidy , Crawford Sybil , Gold Ellen , Avis Nancy , Reeves Katherine W.
Published: October 2015

Two previous retrospective studies reported a significantly decreased breast cancer risk among women who experienced menopausal vasomotor symptoms (VMS). It is possible that VMS are a marker of declining sex hormone levels during menopause. Elevated sex hormone levels have been associated with increased breast cancer risk, suggesting that VMS may be indicative of lower susceptibility to breast cancer. We evaluated this relationship in the prospective Study of Women's Health Across the Nation (SWAN), which includes annual data on VMS and endogenous hormone levels for 3,098 women who were pre- or early peri-menopausal at enrollment. We evaluated the effect of VMS on breast cancer risk using discrete survival analysis. Over an average 11.4 years of follow-up, 129 breast cancer cases were self-reported and approximately 50% of participants reported some VMS. Women reporting VMS at any current or previous visit had a reduced risk of breast cancer compared to those never experiencing VMS (OR 0.63, 95% CI 0.39, 1.02). Results were strengthened in the subgroup of women who fully transitioned to postmenopausal during follow-up (N=80 cases, OR 0.45, 95% CI 0.26, 0.77). Associations were unchanged upon adjustment for endogenous hormone levels. VMS appear to be a marker of reduced breast cancer risk. Future research is needed to fully understand this relationship, which does not appear to be mediated by endogenous hormone levels.

Citation Format: Vicki Hart, Susan Sturgeon, Nicholas Reich, Lynnette Leidy Sievert, Sybil Crawford, Ellen Gold, Nancy Avis, Katherine W. Reeves. Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women's Health Across the Nation. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A04.
Abstract A05: Menopausal vasomotor symptoms and mammographic density in the Study of Women's Health Across the Nation
Authors: Hart Vicki , Sturgeon Susan , Reich Nicholas , Sievert Lynnette Leidy , Crawford Sybil , Gold Ellen , Habel Laurel , Reeves Katherine W.
Published: October 2015

Background: Declines in endogenous estrogen during menopause have been linked to the onset of menopausal vasomotor symptoms (VMS) and to reduced breast cancer risk. Percent mammographic density (PMD) is viewed as a marker for breast cancer susceptibility. Establishing a relationship between VMS and PMD may justify future prospective investigations of VMS and breast cancer risk.

Methods: We investigated this association in the Study of Women's Health Across the Nation (SWAN) Mammgraphic Density Substudy (N=833). Women were pre- or perimenopausal at enrollment and followed through menopause. VMS were assessed at annual SWAN visits. PMD was ascertained from routine screening mammograms. A linear mixed effects model was used to evaluate the longitudinal association between VMS and PMD.

Results: Women contributed a total of 4,748 mammograms (2-10 per woman) over a median 5.4 years. We observed no overall association between VMS and PMD. When stratified by menopausal status, VMS was associated with lower PMD among perimenopausal women (β = -1.29%, 95%CI -2.58, -0.001) and those with unknown menopausal status due to hormone use during the study period (β = -3.62%, 95%CI -7.17, -0.07). VMS was not associated with absolute dense area in any analyses. Among women who transitioned to postmenopausal, VMS was not associated with change in PMD across the menopausal transition.

Conclusion: Although our findings do not suggest a strong association between VMS and PMD, we observed a significant effect among perimenopausal women and those using hormones during menopause.. Further prospective studies are needed to establish a relationship between VMS and breast cancer risk, and to ascertain the extent to which this relationship may be mediated by PMD.

Citation Format: Vicki Hart, Susan Sturgeon, Nicholas Reich, Lynnette Leidy Sievert, Sybil Crawford, Ellen Gold, Laurel Habel, Katherine W. Reeves. Menopausal vasomotor symptoms and mammographic density in the Study of Women's Health Across the Nation. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A05.
Abstract A34: Association of nut consumption and lung cancer risk in a large population-based case-control study
Authors: Lam Tram Kim , Consonni Dario , Pesatori Angela , Bertazzi Pier Alberto , Landi Maria Teresa
Published: October 2015

Background: Increased nut consumption has been associated with a reduced risk of major chronic diseases, including type 2 diabetes mellitus, gallstone disease, and colon cancer. However, the association between nut consumption and lung cancer risk is unclear.

Methods: We investigated the association of nut consumption (walnuts, hazelnuts, almonds, or peanuts) with lung cancer risk in the Environment And Genetics in Lung cancer Etiology (EAGLE), a population-based case-control study. Primary lung cancer cases (n= 2101) were enrolled within the Lombardy region of Italy and matched (on gender, residence, and age) to randomly selected controls (n = 2120). Diet was assessed in 1903 cases and 2073 controls. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific quintiles of intake were calculated using unconditional logistic regression, adjusted for putative confounders including smoking.

Results: Nut consumption was negatively associated with lung cancer risk (ORQ5-VS-Q1 = 0.72; 95% CI: 0.56-0.92; p-trend =0.014); the association did not change marginally after additional adjustment for consumption of fruits and vegetables (ORQ5-VS-Q1 = 0.74, 95% CI = 0.58-0.95, p-trend = 0.028).

Conclusion: In summary, dietary nut consumption was associated with reduced risk of lung cancer in EAGLE.

Citation Format: Tram Kim Lam, Dario Consonni, Angela Pesatori, Pier Alberto Bertazzi, Maria Teresa Landi. Association of nut consumption and lung cancer risk in a large population-based case-control study. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A34.
Abstract A40: Multiple locations on 8q24 and 6p21-22 and rare variants associated with gastric cancer susceptibility in a Korean population
Authors: Kim Jeongseon , Park Boyoung , Lee Jeonghee , Cho Young Ae , Woo Hae Dong , Jeong Seung Hwa , Choi Il Ju , Kim Young Woo , Kim Young Woo , Kim Young Woo
Published: October 2015

To efficiently identify genetic susceptibility variants for gastric cancer, including rare coding variants, we performed an exome chip-based array study in 329 gastric cancer cases and 683 controls. We found that a linkage disequilibrium (LD) block containing 2 significant variants in PSCA gene increased the risk and two blocks that included 15 suggested variants including TRIM31, TRIM 40, TRIM 10, and TRIM26 regions, and included one suggested variant and OR2H2 gene showed protective associations with gastric cancer susceptibility. In addition, the PLEC region (rs200893203), FBLN2 region (rs201192415), and EPHA2 region (rs3754334) were associated with increased susceptibility (allele-specific odds ratios (OR)=12.65, 95% confidence interval (CI)=2.82–56.69, P=2.0×10-5; OR=7.40, 95% CI=2.43 – 22.58, P=3.8×10-5; OR=6.49, 95% CI=2.34–18.01, P=4.1×10-5, respectively). Among them, rs200893203 and rs201192415 were classified as rare variants with a minor allele frequency < 1%. 8q24 and 6p21-22 regions where aggregate LD blocks and suggested variations were possible susceptibility regions for gastric cancer and warrant further investigation.

Citation Format: Jeongseon Kim, Boyoung Park, Jeonghee Lee, Young Ae Cho, Hae Dong Woo, Seung Hwa Jeong, Il Ju Choi, Young Woo Kim, Young Woo Kim, Young Woo Kim. Multiple locations on 8q24 and 6p21-22 and rare variants associated with gastric cancer susceptibility in a Korean population. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A40.
Abstract B18: Thrombospondin-1 regulates carcinogenesis in an in vivo model of colorectal cancer
Authors: Pantoja David R. Soto , Torres Maria E. , Sipes J. Michael , Morris Nicole , Roberts David D. , Emenaker Nancy J.
Published: October 2015

According to the National Cancer Institute more than 140,000 people will be diagnosed in the United States with colorectal cancer this year alone. The adenomatus polyposis coli (APC) gene is frequently mutated in colorectal cancer, the APC-min mouse correspondingly is a widely used model for the study of this type of cancer. Studies indictate that the matricellular protein Thrombospondin 1 (TSP1) is lost during progression of colon cancer. To study the role of TSP1 in this disease we generated APC-min and TSP-/- APC-min mice. Our data indicates that expression of TSP1 in the APC-min mouse prevents the development of adenomas in the large intestine in mice fed a low fat diet. On the other hand lack of TSP1 increases tumor multiplicity in these mice, and up-regulates Ki67 in intestinal tissue. Moreover TSP-/- APC-min mice show 50% reduction in survival when compared to TSP+/+APC-min mice alone. Here we show that ADD1/SREBP1 a key transcription factor linking changes in nutritional status of certain genes that regulate systemic energy metabolism is upregulated only in the TSP null APC min/+ animals indicating and association with increased tumor aggressiveness. Together this data indicates that TSP1 regulates progression of colon carcinogenesis and define molecular targets of TSP1 in the prevention of colorectal cancer.

Citation Format: David R. Soto Pantoja, Maria E. Torres, J. Michael Sipes, Nicole Morris, David D. Roberts, Nancy J. Emenaker. Thrombospondin-1 regulates carcinogenesis in an in vivo model of colorectal cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B18.
Abstract B19: Malfunction and mutation of airway stem/progenitor cells in preneoplastic bronchial dysplasia
Authors: Ghosh Moumit , Nakachi Ichiro , Keith Robert L. , Merrick Daniel T. , Franklin Wilbur A. , Miller York E.
Published: October 2015

Squamous cell lung cancer (SCC) is the second leading cause of lung cancer death in the US with a 5-year survival rate of 16.8%. Since most SCC is diagnosed at a late stage, chemoprevention or early detection could improve survival. SCC develops through a series of histological alterations including dysplasia and carcinoma in situ. Previous studies have identified genetic changes in epithelial progenitor cells in dysplastic lesions. The goal of this project is to establish a correlation between specific genetic changes in epithelial progenitors and their function. A tissue stem cell is a progenitor cell that is capable of long-term self-renewal as well as differentiation to all the cell-types that make up a specific tissue and therefore is multipotential. Because the normal function of a progenitor cell is to repair and regenerate a native epithelium after injury, histologic changes in dysplasia led us hypothesize that “normal function of airway progenitors is altered in dysplasia”. To address this hypothesis we purified and established clonal cultures of basal progenitors from normal, moderate and severely dysplastic biopsies and compared their self-renewal and differentiation abilities. These analyses revealed that the self-renewal capacity of progenitor cells decreased as dysplasia grade increased. The progenitors from normal biopsies differentiated to all three cell-types (basal, secretory or mucin-secreting and ciliated) of the airways. In contrast, progenitors from dysplasia generated increased numbers of basal cells (p<0.05) and lacked secretory (p<0.001) and ciliated cells (p<0.001), suggesting that multipotential differentiation is impaired in dysplasia. Genetic analyses of dysplastic lesions and cultured dysplastic progenitors (n=4, histology grade ≥ 5.5) identified several mutations (p53, Notch 1, 2 and 3, FBXW7, and FGFR1) that have been previously reported in SCC. Thus, we demonstrate that we are able to culture airway stem/progenitor cells that recapitulate both the phenotypic and mutational characteristics of the lesions from which they originate. We propose that understanding the effect of these mutations in altered progenitor function will help to devise prevention as well as early detection strategies.

Citation Format: Moumit Ghosh, Ichiro Nakachi, Robert L. Keith, Daniel T. Merrick, Wilbur A. Franklin, York E. Miller. Malfunction and mutation of airway stem/progenitor cells in preneoplastic bronchial dysplasia. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B19.
Abstract B27: RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1α-mediated mitochondrial oxidative phosphorylation and glycolysis
Authors: Chen Wenshu , Wang Qiong , Bai Lang , Chen Weijie , Wang Xia , Tellez Carmen S. , Leng Shuguang , Padilla Mabel T. , Nyunoya Toru , Belinsky Steven A. , Lin Yong
Published: October 2015

In the presence of ample oxygen, cancer cells prefer glycolysis to mitochondrial respiration for energy supply. This metabolic alteration, known as the Warburg effect or aerobic glycolysis, has been shown to contribute to cancer cell proliferation. However, how this glucose metabolism pathway is precisely regulated remains elusive. Receptor-interacting protein 1 (RIP1) is an important cellular signaling molecule that plays a pivotal role in the regulation of cell death, survival and proliferation. However, the role of RIP1 in cell metabolism is unclear. To investigate the function of RIP1 in lung cancer cell proliferation, we established stable RIP1 knockdown lung cancer cell lines using lentivius-mediated shRNA expression. RIP1 knockdown inhibited the proliferation of lung cancer cells, which was associated with DNA damage-induced p53 activation. Compared with control cells, the RIP1 knockdown cells had higher glucose consumption and lactate production, indicating a higher glycolytic rate. The increased glycolysis lowered the cellular level of nicotinamide adenine dinucleotide (NAD+), a cofactor essential for DNA damage repair. By microarray profiling and promoter reporter assays, we determined that RIP1 positively regulates the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a key factor involved in the regulation of mitochondrial function. The downregulation of PGC-1α reduced the expression of components of electron transfer chain that impaired oxidative phosphorylation, which underlays the increased glycolysis in RIP1 knockdown cells. Moreover, RIP1 knockdown cells were more sensitive to both DNA damage anticancer agents and glycolysis inhibitors. Our data suggest that while aerobic glycolysis within a certain range favors cancer cell proliferation, excessive glycolysis may cause cytostasis. Thus, maintenance of glycolysis by RIP1 is critical to cancer cell energy homeostasis and DNA integrity, which may be exploited for anticancer therapy.

Citation Format: Wenshu Chen, Qiong Wang, Lang Bai, Weijie Chen, Xia Wang, Carmen S. Tellez, Shuguang Leng, Mabel T. Padilla, Toru Nyunoya, Steven A. Belinsky, Yong Lin. RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1α-mediated mitochondrial oxidative phosphorylation and glycolysis. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B27.
Abstract CN05-02: Exploiting aspirin's mechanism of action for combination chemoprevention
Authors: Chan Andrew T.
Published: October 2015

In human populations, aspirin has emerged as the agent with the most consistently observed chemopreventive effect on cancer, particularly of the colorectum. Remarkably consistent data demonstrating aspirin's efficacy have accumulated from prospective studies and randomized controlled trials conducted for the prevention of polyp recurrence, hereditary colorectal cancer, cardiovascular disease, and overall cancer. In addition, there are now convincing data supporting an association between aspirin use and lower risk of metastases and improved survival among colorectal cancer patients. This substantial evidence base has stimulated interest in the molecular underpinnings of aspirin's mode of action. Although a complete understanding of aspirin's anti-cancer mechanism remains elusive, several interrelated biological pathways have been uncovered which appear to, at least in part, mediate aspirin's effect on both tumor initiation and progression. These include fundamental pathways of prostaglandin synthesis and Wnt signaling, offering additional molecular targets for chemopreventive intervention that may enhance aspirin's effectiveness and/or reduce its associated toxicities. In this presentation, we will provide an update on investigation into the mechanistic basis of the effect of aspirin on cancer with a focus on potential molecularly-targeted strategies for combinatorial chemoprevention.

Citation Format: Andrew T. Chan. Exploiting aspirin's mechanism of action for combination chemoprevention. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN05-02.
Abstract CN08-01: Air pollution and cancer: Implications of IARC's causal classification
Authors: Samet Jonathan M.
Published: October 2015

This presentation will identify the main lessons learned from the extensive analysis and discussion of the carcinogenicity of outdoor air and describe potential areas for future research. The IARC classification of “outdoor air pollution” and “particulate matter air pollution” as carcinogenic to humans are based on a broad research foundation, but nonetheless there are important gaps to be addressed. For example, research is needed to understand more specifically the components of the air pollution mixture that drive cancer risk, in part to develop useful indicators for control and tracking. Further information is needed on potential determinants of susceptibility to lung cancer caused by air pollution and on the combined effect of smoking and air pollution. Most importantly, this presentation will also cover the implications of the IARC evaluation for public health, including regulatory, societal, and personal actions that, collectively, could improve global public health. Outdoor air pollution now constitutes a cause of cancer to which most people are exposed, and understanding of underlying mechanisms implies that there is no threshold below which there is no risk. Risk assessment will likely play a critical role in considering air quality standards to protect the public from the cancer risk posed by outdoor air pollution.

Citation Format: Jonathan M. Samet. Air pollution and cancer: Implications of IARC's causal classification. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN08-01.
Abstract CN12-03: Epigenetic targets of sulforaphane and epigallocatechin gallate in cancer prevention
Authors: Tollefsbol Trygve , Li Yuanyuan
Published: October 2015

Interest in cancer epigenetics has arisen from the fact that epigenetic processes affect many aspects of tumor formation and progression. The reversibility of epigenetic changes that may arise in early tumorigenesis is an important aspect of their potential in approaches for cancer prevention. Many of the components of the human diet have bioactive effects that lead to reversal of epigenetic aberrations in cancer. We have found that both (-)-epigallocatechin-3-gallate (EGCG) from green tea and sulforaphane (SFN) from cruciferous vegetables are able to down-regulate telomerase in breast cancer cells. This occurs through epigenetic modifications of the promoter region of hTERT, the gene that encodes the catalytic subunit of telomerase. Since telomerase promotes tumor formation and is active in about 90% of cancers, this epigenetic inhibition of its catalytic subunit gene may have considerable potential in breast cancer prevention. Our studies also indicate that these bioactive dietary compounds are able to convert estrogen-receptor (ER)-negative breast cancer cells to ER-positive breast cancer cells and to prevent the formation of highly lethal ER-negative breast cancer. This occurs through epigenetic modifications of the ERalpha gene in response to EGCG and SFN. These findings have significance in that ER-positive cells are amenable to breast cancer prevention or therapy with compounds such as tamoxifen while ER-negative cells confer few preventive or treatment options for patients. Moreover, our studies have also indicated that EGCG and SFN have additive or synergistic epigenetic effects on cancer prevention and that the oral administration of green tea polyphenols and SFN-rich broccoli sprouts inhibits the formation of breast cancer in mice. These results are important because the combination of these dietary products may have potential in lowering their efficacious consumption and increase their utility for breast cancer prevention in humans.

Citation Format: Trygve Tollefsbol, Yuanyuan Li. Epigenetic targets of sulforaphane and epigallocatechin gallate in cancer prevention. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN12-03.
Abstract PL01-01: Meet your microbiome: An introduction to the who, what, and how of mixed microbial communities
Authors: Hollister Emily B.
Published: October 2015

The human microbiome is comprised of the bacteria, archaea, fungi, protists, and viruses that live in and on our bodies. It is estimated that the microbial cells that comprise your individual microbiome outnumber your own cells by a factor of 10 and that their collective gene content outnumbers your own by a factor of 100. Although scientists and physicians have appreciated the diversity of our “fellow travelers” for decades, our ability to count, study, and categorize our microbes was long limited by the challenges associated with their culture in the laboratory. The utilization of high-throughput sequencing platforms, development of new and improved bioinformatics resources, and the introduction of other ‘omics technologies have shed new light on the composition and function of the human microbiome. The NIH-sponsored Human Microbiome Project characterized the microbial communities of hundreds of healthy individuals in an attempt to define the “healthy” microbiome at various sites throughout the body, and other projects have examined the human microbiome under varying states of disease and health. Microbiome and metagenomic studies have revealed that microbes may contribute to metabolic disorders, inflammatory bowel disease, heart disease, and cancer; and emerging evidence from mouse models suggests a strong link between gut microbiome composition and brain development and behavior. Microbiome and metagenomic studies have also demonstrated that our microbiota may confer protective or beneficial effects, and the depletion or loss of these “good” microbes may leave us susceptible to disease or infection. This talk will introduce the concept of the human microbiome, discuss the techniques that are used to characterize the structure and function of mixed microbial communities, and highlight recent findings from the literature.

Citation Format: Emily B. Hollister. Meet your microbiome: An introduction to the who, what, and how of mixed microbial communities. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL01-01.
Abstract PL05-02: Current therapies for diabetes - will they reduce cancer risk?
Authors: Gallagher Emily Jane
Published: October 2015

Type 2 diabetes has been associated with an increase in the incidence and mortality from many cancers. Understanding the mechanisms underlying Type 2 diabetes, has contributed to the discovery of the potential anti-cancer effects of diabetes treatments. Insulin resistance and hyperinsulinemia precede the development of hyperglycemia and Type 2 diabetes, and may be key factors contributing to the increased cancer risk. Other factors including hyperglycemia, steroid hormonal bioavailability (estrogen and testosterone), insulin-like growth factors, adipokines (leptin and adiponectin) and cytokines may also contribute to cancer progression in the setting of Type 2 diabetes. The main classes of pharmacological treatments for Type 2 diabetes include insulin-sensitizing therapies, insulin secretagogues, exogenous insulin and incretin based therapies. While some previous epidemiological studies suggested that exogenous insulin therapy may increase breast cancer mortality, recent human studies have not supported these findings. Our studies have shown that high doses of the insulin analogs currently in clinical use do not increase murine breast cancer growth or metastases in a mouse model of pre-diabetes. However, insulin-sensitizing therapies, including metformin and thiazolidinediones may have anti-cancer effects. One potential mechanism by which these agents may reduce tumor progression, is by improving the metabolic abnormalities associated with Type 2 diabetes; improving insulin sensitivity, decreasing endogenous insulin levels. Reducing insulin levels has been shown to reduce cancer growth in previous animal studies. In addition, or alternatively, these agents may act directly on the tumor cells. Metformin is taken up into cells by organic cation transporters, and is an activator of AMPK, which may reduce cell proliferation and tumor metastases. Thiazolidinediones are peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists that also improve insulin resistance, and are effective in reducing the progression from pre-diabetes to Type 2 diabetes. While these agents demonstrated potential as anti-cancer agents in animal and in vitro studies, however, some epidemiological studies reported that these agents may increase bladder cancer risk, subsequent studies have not corroborated these findings. Therefore, Type 2 diabetes is associated with an increase in cancer incidence and mortality, understanding the mechanisms underlying this association has led to the potential use of anti-diabetic agents in the prevention and treatment of cancer.

Citation Format: Emily Jane Gallagher. Current therapies for diabetes - will they reduce cancer risk? [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL05-02.
Abstract PL06-03: Role of the circadian clock in skin cancer prevention and sunburn erythema
Authors: Gaddameedhi Shobhan , Sancar Aziz
Published: October 2015

Epidemiological studies of humans and experimental studies with mouse models suggest that sunburn apoptosis and erythema as a result of exposure to excessive UV light and damage to DNA confers an increased risk for melanoma and non-melanoma skin cancer. The early inflammatory response to UV exposure, sunburn, follows molecular and cellular responses including DNA repair and apoptosis. Previous reports have shown that nucleotide excision repair, the sole pathway for removing UV-induced DNA damage, as well as DNA replication, are regulated by the circadian clock in mouse skin. Furthermore, more skin carcinogenesis was observed in mice exposed to UV in the early morning, when repair activity was low, and replication activity was high, as compared to mice exposed in the late afternoon. Because sunburn and skin cancer are causally related, we investigated UV-induced sunburn apoptosis and erythema in mouse skin as a function of circadian time. Interestingly, sunburn apoptosis, inflammatory cytokine induction, and erythema were maximal following an acute early morning exposure to UV, and minimal following an afternoon exposure. We find that the circadian rhythmicity of erythemal response was correlated with greater UV-induced stabilization and activity of p53 protein in the early morning as compared to the late afternoon. These data provide the first evidence that the circadian clock plays an important role in the erythemal response. Furthermore, modulating either the circadian clock or the time of the day when exposure occurs may be effective in mitigating the risk for sunburn, skin cancer development and photo aging.

Citation Format: Shobhan Gaddameedhi, Aziz Sancar. Role of the circadian clock in skin cancer prevention and sunburn erythema. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL06-03.
Minimally Invasive Techniques and Hybrid Operations for Esophageal Cancer
Authors: Wullstein Christoph , Ro-Papanikolaou Hye-Yoen , Klingebiel Christoph , Ersahin Koray , Carolus Rene
Published: October 2015

Background: Minimally invasive esophagectomy (MIE) is slowly gaining acceptance due to advantages in short-term outcome. While evidence is slowly increasing, the discussion about MIE is still controversial. Methods: A literature review was performed to compare MIE with open esophagectomy (OE). Current studies are summarized in view of short- and long-term outcome as well as oncological accuracy. Results: The majority of studies show that MIE is associated with a significant reduction of pulmonary complications, blood loss, and shorter length of stay on the intensive care unit. Pulmonary complications are reduced by 14-65%. MIE shows an improved quality of life 6 weeks after surgery. There is some evidence that the endoscopic reintervention rate may be higher after MIE than after OE. Mortality rates do not differ. Regarding oncological results, the rate of R0 resections is comparable between MIE and OE, as is the number of retrieved lymph nodes. Long-term survival seems to be comparable. A few single center trials suggest oncological advantages of MIE over OE concerning the number of lymph nodes, R0 resection rate, and 1-year survival. Conclusion: Current evidence supports that MIE has advantages over OE in the short-term outcome. Oncological results are comparable to those achieved by OE. As a result, MIE has already been included in current guidelines for the treatment of esophageal cancer.
Neuroprotective Effects of Crocin against Oxidative Stress Induced by Ischemia/Reperfusion Injury in Rat Retina
Authors: Chen Li , Qi Yun , Yang Xinguang
Published: October 2015

Aims: Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been reported to be useful in the treatment of oxidative stress injury. In the present study, we investigated the antioxidative effect of crocin and the change of the ERK signaling pathway on rat retina induced by ischemia/reperfusion (IR) injury. Methods: Crocin was pretreated 30 min before and once daily after retinal IR injury by intraperitoneal injection. The retinal morphological damage was observed by hematoxylin and eosin (HE) staining. The number of retinal ganglion cells (RGCs) was counted by Brn-3a immunofluorescence staining. The antiapoptotic effect of crocin was determined by detecting cleaved caspase-3 protein levels by means of Western blot and immunohistochemical analysis. Furthermore, retinas were also used for the determination of malondialdehyde (MDA) levels, glutathione (GSH) levels, total superoxide dismutase (T-SOD), and reactive oxygen species (ROS). The phosphorylated ERK (p-ERK) protein level was determined by Western blot and immunohistochemical analysis. Results: Our results showed that crocin treatment (50 mg/kg) significantly inhibited the decrease of retinal thickness through HE staining and protected RGCs from decreasing. Compared with the IR + vehicle group, crocin treatment significantly decreased cleaved caspase-3 and p-ERK protein expression by Western blot analysis and immunohistochemistry. Immunohistochemical staining for cleaved caspase-3 and p-ERK in the retinal sections showed positive cells were present in the RGC layer and inner nuclear layer after IR injury. Similarly, crocin (50 mg/kg) treatment also significantly increased the level of activity of GSH, enhanced the activity of T-SOD, and decreased the activity level of ROS and MDA after IR injury. Conclusions: These findings demonstrated that crocin treatment could notably protect the retina from damage induced by IR. It might be related to crocin antioxidant and antiapoptotic properties in the retina.
Diagnostics and Early Diagnosis of Esophageal Cancer
Authors: Meves Volker , Behrens Angelika , Pohl Jürgen
Published: October 2015

In the esophagus two different kinds of primary neoplasias may arise: squamocellular carcinomas (SCC) and esophageal adenocarcinomas (EAC). Although both types of carcinoma are rare diseases, especially the incidence of EAC rose in the last years. The management of esophageal cancer is challenging. There are no specific symptoms of early esophageal cancers. Due to this fact, most of the esophageal cancers are found incidentally, and only 12.5% of esophageal tumors are endoscopically resectable. Gastroscopy is the gold standard for the diagnosis of esophageal cancer. The sensitivity of detecting early-stage carcinoma may be improved by adjunct techniques such as chromoendoscopy, virtual chromoendoscopy, magnification endoscopy, and other advanced endoscopic imaging techniques. The diagnosis of esophageal cancer can be verified with targeted biopsies. Accurate staging information is crucial for establishing appropriate treatment choices for esophageal cancer, while the depth of the tumor determines the feasibility of therapy. In terms of staging, endosonography, abdominal ultrasound, and computed tomography scan of the thorax and abdomen should thus be performed before initiation of therapy.
Bet v 1- and Bet v 2-Associated Plant Food Sensitization in Uganda and Germany: Differences and Similarities
Authors: Odongo Leo , Mulyowa Grace , Goebeler Matthias , Trautmann Axel
Published: October 2015

Background: Birch pollen allergy and concomitant plant food sensitization are well documented in Europe. However, there are currently no data available on pollen-associated plant food sensitization or even pollen allergy in tropical Africa. Our study aimed to investigate Bet v 1- and Bet v 2-associated plant food sensitization in atopic patients from Uganda and compare it with sensitization rates in German patients. Methods: Sera from 83 Ugandan and 97 German atopic patients were analysed using UniCAP100™ for allergen-specific IgE against the birch tree pollen allergens Bet v 1 and Bet v 2 as well as the plant foods hazelnut, apple, kiwi, pea, peach, cherry, litchi, peanut, and soy. Results: As expected, sensitization to Bet v 1 and cross-reactive plant food allergens was more common in German atopic patients. In contrast, the prevalence of sensitization against Bet v 2 was remarkably similar in Ugandan and German patients. Interestingly, in Ugandan patients we found IgE-mediated sensitization against plant foods such as hazelnut, pea, peach, cherry, and litchi that are neither cultivated nor consumed in Uganda. Conclusions: For Ugandan atopic patients, sensitization against the Bet v 2 allergen (a plant profilin) may explain cross-reactivity to several plant foods which are not consumed in Uganda. Additionally, it is probable that sensitization of Ugandan atopics to alder pollen (Alnus acuminata, plant family Betulaceae) caused serological cross-reactivity with Betula verrucosa-related allergens.
Comparison of Completion Thyroidectomy and Primary Total Surgery for Differentiated Thyroid Cancer: A Meta-Analysis
Authors: Li Yu-Jie , Wang Yao-Zong , Yi Zhan-Bo , Chen Liang-Liang , Zhou Xiao-Dong
Published: October 2015

Background: The aim of this study was to compare the complication rates between completion thyroidectomy and primary total thyroidectomy for differentiated thyroid cancer (DTC). Methods: PubMed, the Web of Knowledge, and the China Journal Net were searched for studies concerning the treatment of DTC published in 1990-2014. A meta-analysis was performed to compare the effects of different treatments. Results: 7 studies with a total of 1,208 patients were included. There were no statistically significant differences regarding the presence of temporary recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, temporary hypocalcemia, permanent hypocalcemia, hematoma, and wound infection. Conclusions: Completion thyroidectomy can be performed with acceptable morbidity in select cases of DTC who could not be properly diagnosed perioperatively or who recurred after less than total thyroidectomy.
Partição gástrica para o tratamento paliativo de pacientes com tumores gástricos distais obstrutivos e irresecáveis
Authors: Coimbra Brian Guilherme Monteiro Marta , Ramos Marcus Fernando Kodama Pertille , Yagi Osmar Kenji , Jacob Carlos Eduardo , Cecconello Ivan , Zilbertein Bruno
Published: October 2015

O câncer gástrico é uma afecção que ainda se mostra muito prevalente. Como agravante, a maioria dos pacientes apresenta-se em estágios avançados da doença, frequentemente com tumores distais obstrutivos e irressecáveis, demandando tratamento paliativo, cujo objetivo é dar ao doente maior qualidade de vida. Dentre as opções terapêuticas, tradicionalmente se opta pela gastroenteroanastomose. Entretanto, devido às altas taxas de complicações desse procedimento, passou-se a empregar a técnica da partição gástrica. Frente aos resultados em estudos comparativos entre essas duas técnicas, nosso serviço passou a realizar a partição gástrica em casos de pacientes portadores de câncer gástrico avançado distal obstrutivo e irressecável, e analisamos retrospectivamente os resultados do emprego dessa técnica em 29 pacientes, em termos de sobrevida e qualidade de vida. Toda a população se apresentava com ECOG performance status de 0, 1 ou 2 e 53,9% dos doentes apresentavam, sob a classificação de obstrução gástrica de GOOSS, graus 0 ou 1. A duração operatória média foi de 169 minutos. No pós-operatório, sob a classificação de complicações de Clavien-Dindo, houve 4 pacientes em grau II e 2 em grau V (dois óbitos, correspondendo a uma mortalidade operatória de 6,9%). O tempo médio para se atingir GOOSS 2 foi de 5 dias e, ao longo do seguimento, 96,15% da população atingiu GOOSS 2 ou 3. A sobrevida média foi de 213 dias. Considerando os resultados satisfatórios obtidos, a técnica de partição gástrica é efetiva e segura, proporcionando sobrevida, manutenção de dieta via oral e qualidade de vida para os pacientes. 
Modelo experimental de doença pleural maligna induzida por células LLC (Lewis Lung Carcinoma)
Authors: Hashizume Pedro Henrique Shimiti , Acencio Milena Marques Pagliarelli , Teixeira Lisete Ribeiro
Published: October 2015

Derrame pleural maligno (DPM) é um fator de mau prognóstico em pacientes com câncer de pulmão avançado. Sua patogênese ainda é pouco compreendida e as opções terapêuticas são limitadas. Modelos animais de DPM podem demonstrar novos aspectos fisiopatológicos desta doença. Stathopoulos et al. em 2006 (Am J Respir Cell Mol Biol. 2006;34:142-50) descreveram um modelo de DPM com 1,5 x105 células de LLC injetadas diretamente no espaço pleural de camundongos. Os autores relataram carcinomatose com derrame pleural, tumores pleurais e 100% de mortalidade após 17 dias. [...]
Liga de Prevenção à Cegueira – 29 anos de ensino, pesquisa e assistência em oftalmologia
Authors: Kato Juliana Mika , Ohnishi Luis Felipe Yassuki , Higashi Alex Haruo , Nagai Ahlys Ayumi , Carricondo Pedro Carlos
Published: October 2015

Uma parcela significante das doenças sistêmicas mais prevalentes em nosso meio vem acompanhada de acometimento ocular e muitas doenças oftalmológicas exigem atendimento imediato e cuidados específicos para evitar-se a cegueira. O curso de Oftalmologia da graduação abrange os temas essenciais à adequada formação do médico generalista, porém carece de treinamento prático e cirúrgico. A fim de suprir tal deficiência, a Liga de Prevenção à Cegueira foi fundada em 1985 como alternativa para aprofundar os conhecimentos na área, aproximar-se da prática oftalmológica e atender indagações profissionais futuras. [...]
Aneurisma gigante de artéria poplítea
Authors: Kinoshita Jennifer Naomi , Gabriel Sthefano Atique , Camargo Junior Otacilio De , Chrispim Antonio Claudio Guedes
Published: October 2015

O aneurisma de artéria poplítea é o aneurisma periférico mais frequente, podendo corresponder a 70% dos mesmos, sendo mais prevalente no sexo masculino onde é encontrado em torno de 95% dos casos. Estes aneurismas são de incidência bilateral em mais de 50% dos casos, podendo ter também uma associação de mais de 50% com aneurisma de aorta abdominal. A complicação mais comum do aneurisma de artéria poplítea é a embolização distal sendo a complicação mais grave a trombose com risco alto de perda do membro. A rotura do aneurisma de poplítea é rara com uma incidência de menos de 3%, porem, dependendo do tamanho a rotura pode representar um risco maior para o paciente.[...]
Gamificação, elementos de jogos e estratégia: uma matriz de referência
Authors: Costa Amanda Cristina Santos , Marchiori Patrícia Zeni
Published: October 2015

Situando-se as pesquisas de gamificação – entendida como a utilização de elementos de design de jogos em contextos que não são de jogos – nas discussões referentes à arquitetura de informação, o estudo apresenta uma matriz de referência para aplicações de gamificação a partir da sistematização de elementos de jogos (dinâmicas, mecânicas e componentes) e da busca de relações com segmentos/áreas de aplicação da gamificação. Além da pesquisa bibliográfica exploraram-se técnicas da Teoria Fundamentada nos Dados (Grounded Theory) para coleta, preparação e análise de dados. Matrizes intermediárias permitiram discutir aspectos relativos aos componentes, mecânicas e dinâmicas de jogo e os distintos segmentos/áreas identificados. A matriz principal pode servir de modelo de referência para aplicações de gamificação destacando-se que diferentes elementos de jogos podem ser combinados de diversas maneiras, e que cada segmento/área apresenta um potencial de combinações que dependem da clareza dos objetivos de negócio. Um exemplo nesta direção seria o uso da dinâmica de “narrativas” no segmento Educação e Treinamento devido ao estímulo, motivação e engajamento que estas podem promover no processo de ensino/aprendizagem. No contexto da arquitetura de informação, as mecânicas de jogo são elementos críticos para o engajamento, pois estruturam o estilo do jogo e atuam diretamente na percepção do usuário. Estudos futuros podem agregar a esta matriz informações prévias dos usuários - as quais afetariam o desenvolvimento das aplicações de gamificação - assim como informações derivadas da atividade dos jogadores, enquanto recortes voltados a uma proposta estratégica mais ampla.
The Shape of Morality in the Gospel of Mark: An Experiment in Hermeneutics
Authors: Wheaton Gerry
Published: October 2015

The following work draws from the philosophical hermeneutics of Hans-Georg Gadamer to form an inquiry into the moral vision of the Gospel of Mark. The metaphor of slavery is identified as a central component of the moral instruction of Jesus to his disciples. Following a brief analysis of the metaphor in Greco-Roman literature to identify its basic import in Mark’s Gospel, a dialogue is developed between the second Gospel and the moral philosophy of Zygmunt Bauman. Three lines of thought are isolated in the work of Bauman and utilized to illuminate and elaborate the moral vision of Mark that emerges from the metaphor of slavery: the conceptualization of morality as responsibility for others; the rooting of moral action in emotion; and the location of morality at the center of what it means to be human.
Theological Reflections on the Oracles against the Nations
Authors: Chae Moon Kwon
Published: October 2015

This paper illuminates the positive theological value of the oracles against the nations (oans) in the Old Testament. Tracing the historical development of the oan tradition, I propose that the oan tradition originated in a war or a cultic setting and went through three stages of transformation: first, the shift from salvation oracles for Israel to oracles against Israel by the 8th century prophets Amos and Isaiah: second, the shift from a realistic depiction of enemies to a more cosmic depiction of them during the exilic period: third, the inclusion of the nations into the future restoration in the postexilic period. The trajectory of the development of the oan tradition shows how Israel’s self-understanding and attitude toward foreign nations changed with a strong emphasis on Yahweh’s kingship. The emphasis on Yahweh’s kingship over Israel’s special status provides a ground for the inclusion of foreign nations into Yahweh’s plan. By prioritizing Yahweh’s kingship, his people can avoid the danger of self-elevation and embrace the other people into the community.
A “rediscovered” record of Ainsliaea brandisiana (Asteraceae) from Thailand and its biogeographic significance
Authors: Nie Bao , Zhang Guo-Jin , Inta Angkhana , Gao Tian-Gang
Published: October 2015

Ainsliaea brandisiana was regarded as distributed only in southeastern Myanmar. Koyama once reported the occurrence of A. brandisiana in Thailand in 1983, whereas Tseng thought it was a new species and described it as A. spnocephala in 1988. This treatment was accepted by Freire in 2007. Thus, the record of A. brandisiana from Thailand reported by Koyama was not valid. However, during a field trip in Phu Soi Dao National Park of northeastern Thailand, we found a remarkable species of Ainsliaea growing in mountain forests at the elevation of 1600 m. After detailed and comprehensive examination, we determined that it was A. brandisiana. This “rediscovered” record of A. brandisiana suggested a close phytogeographical connection between the mountain forests flora of southeastern Myanmar and that of northeastern Thailand, although they were separated by the lowlands rain forests of Thailand peninsula. We proposed a new hypothesis that there might be a plant migration route connecting southeastern Myanmar, northeastern Thailand and the Hengduan Mountains. Here, we described and illustrated A. brandisiana and provided photographs of its live specimens in the field, its habitat, morphological details of its floret, its distribution map and a key to all the known species of Ainsliaea from Thailand.