bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3688: Role of inhibitor of apoptosis family proteins in diallyl trisulfide-induced apoptotic cell death in human prostate cancer cells
Authors: Bommareddy Ajay , Kim Su Hyeong , Singh Shivendra V. 
Published: June 2012

Abstract
Diallyl trisulfide (DATS) is a promising cancer chemopreventive constituent of processed garlic. The DATS administration not only inhibits chemical carcinogenesis in experimental rodents but also affords significant protection against cancer development in a transgenic mouse model of prostate cancer. We have shown previously that DATS inhibits growth of human prostate cancer cells by causing apoptosis, but the mechanism of cell death is not fully understood. Inhibitor of apoptosis (IAP) family proteins has emerged as critical regulators of apoptosis. In this study, we investigated the role of IAP family proteins in DATS-mediated apoptosis using PC-3 (an androgen-independent cell line lacking functional p53) and LNCaP (an androgen-responsive cell line with wild-type p53) human prostate cancer cells as a model. Protein level of X-linked inhibitor of apoptosis (XIAP) was decreased markedly upon 8-hour treatment with 20 and 40 µmol/L DATS in both PC-3 and LNCaP cells but this effect was somewhat reversible at the 16-hour time point. The DATS-mediated suppression of XIAP protein was not due to a decrease in its mRNA expression. Instead, the DATS-mediated decline in XIAP protein level was reversed in the presence of proteasomal inhibitor MG132. Ectopic expression of XIAP in PC-3 cells conferred modest yet statistically significant protection against DATS-induced apoptosis. Interestingly, the DATS treatment resulted in a marked and sustained induction of survivin protein in both cell types. The DATS-mediated induction of survivin protein correlated with an increase in its mRNA levels in PC-3 and LNCaP cells. RNA interference of survivin resulted in increased apoptosis even in absence of DATS treatment in PC-3 cells. However, the DATS-induced apoptosis was only marginally affected by siRNA knockdown of survivin. Inhibition of prostate cancer development in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice by p.o. gavage with DATS correlated with a statistically significant decrease in the levels of XIAP protein and induction of survivin protein expression. The results of the present study indicate differential effect of DATS treatment on IAP family protein expression, which may serve as biomarkers of DATS response. This study was supported by the USPHS grant 2 RO1 CA113363-06, awarded by the National Cancer Institute.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3688. doi:10.1158/1538-7445.AM2011-3688
Abstract 3692: Allyl isothiocyanate arrests bladder cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 phosphorylation
Authors: Geng Feng , Tang Li , Zhang Yuesheng 
Published: June 2012

Abstract
Allyl isothiocyanate (AITC) occurs in many common cruciferous vegetables, and was recently shown to be selectively delivered to bladder cancer tissues through urinary excretion and to inhibit bladder cancer development in an orthotopic rat bladder cancer model. Here, we show that AITC arrests human bladder cancer cells in mitosis and induces apoptosis. Mitotic arrest by AITC was associated with significant down regulation of both α-tubulin and β-tubulin which are essential for mitosis. AITC also induced mitochondria-mediated apoptosis, including cytochrome c release from mitochondria to cytoplasm, cleavage of caspase-9 and caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP) and lamin B1, and formation of TUNEL-positive cells. Both a general caspase inhibitor (Z-VAD-FMK) and a caspase-9 inhibitor (Z-LEHD-FMK) attenuated AITC-induced apoptosis. Moreover, we found that apoptosis induction by AITC resulted from mitotic arrest and was mediated via Bcl-2 phosphorylation at Ser70. Thus, AITC-induced mitotic arrest was accompanied by a strong Bcl-2 phosphorylation, while Bcl-2 expression was not affected. Pre-arresting cells in G1 phase using hydroxyurea abrogated both mitotic arrest and Bcl-2 phosphorylation in cells treated with AITC. Overexpression of a Bcl-2 mutant (loop domain deleted, removing Ser70) prevented AITC from inducing apoptosis. AITC-induced Bcl-2 phosphorylation appears to be mediated by c-Jun N-terminal kinase (JNK), as AITC activated JNK but a JNK inhibitor (SP600125) abolished Bcl-2 phosphorylation in AITC-treated cells. In summary, AITC is a highly promising agent for bladder cancer prevention and treatment, and the present study reveals a novel anticancer mechanism of AITC in human bladder cancer cell.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3692. doi:10.1158/1538-7445.AM2011-3692
Abstract 3694: Activation of ASK1 by capsaicin mediates apoptosis in pancreatic cancer cells
Authors: Pramanik Kartick C. , Srivastava Sanjay K. 
Published: June 2012

Abstract
Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase (MAPK) kinase kinase family plays an essential role in reactive oxygen species (ROS) induced cellular response. Thioredoxin (Trx), a redox sensitive protein binds to ASK1 and inhibits its activation. In our previous study, we have shown that capsaicin induced apoptosis in pancreatic cancer cells was associated with the generation of ROS and persistent disruption of mitochondrial membrane potential. In the present study, we evaluated the interaction of thioredoxin/ASK1 in pancreatic cancer cells. In a concentration dependent study, we observed that capsaicin treatment down regulated thioredoxin and increased the phosphorylation (activation) of ASK1 at Thr845 in AsPC-1 and BxPC-3 cells. ASK1 has been shown to activate JNK, which in turn activates MKK4/7 resulting in the cleavage of caspase-9, and caspase-3. In agreement, our results reveal that capsaicin treatment activated JNK, MKK4/7, caspase-9 and caspase-3. Interestingly, treatment of cells with antioxidants such as tiron or catalase blocked the activation of ASK1 cascade by capsaicin and protected the cells from apoptosis indicating the involvement of ROS in the activation of ASK1. To confirm the interaction of Trx/ASK1 and the dissociation of ASK1 by capsaicin in our model, BxPC-3 cell were transiently transfected with contructs encoding ASK1 fused to C-terminal hemaggutinin (HA) and flag tagged Trx. Our results reveal that Trx over expression suppressed the effects of capsaicin whereas ASK1 over expression enhanced the apoptosis-inducing effects of capsaicin. Taken together, our results suggest that ROS generated by capsaicin reduce Trx expression resulting in the activation of ASK1 and downstream effectors leading to apoptosis in pancreatic cancer cells. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute].
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3694. doi:10.1158/1538-7445.AM2011-3694
Abstract 3732: Inflammatory breast cancer rates among different ethnic and racial groups in the United States
Authors: Reihani Sharareh , Akushevich Igor , Schildkraut Joellen , Il'yasova Dora 
Published: June 2012

Abstract
Inflammatory breast cancer (IBC) is considered to be the most aggressive form of breast cancer. In the US, the proportion of incidences of IBC cases ranges from 2% to 5%. Understanding the determinants of IBC rates among different populations may help to design prevention strategies. Internationally, IBC rates have been linked to socioeconomic status (SES). In the US, the analysis of the National Cancer Institute Surveillance Epidemiology and End Results (SEER) data for the period of 1988-2000, and data for 1994-1998 from the North American Association of Central Cancer Registries demonstrated greater IBC rates among Blacks compared to Whites and similar rates among Whites and Hispanics. However, the Hispanic population in the US has grown significantly in the last decade and its SES status is generally lower compared to non-Hispanic Whites. Therefore, we hypothesized that IBC rates in Hispanics have increased since the reported rates from 1994-1998 and are higher than among Whites.
We used the SEER database to estimate age-adjusted and age-specific rates of IBC among ages 20-84 in three racial/ethnic groups: Whites, Blacks, and Hispanics (including both Whites and Blacks). IBC cases were categorized using Common Stage Extension Codes 71-73. Age-specific IBC rates were estimated for three age-groups: 20-45 (pre-menopausal), 45-60 (peri-menopausal), and 60-84 (post-menopausal).
During 2004-2007, a total of 3107 IBC cases were diagnosed among the 20-84 year old population covered by the SEER registries. Among them, 2436 cases were diagnosed in Whites, 470 in Blacks, and 403 in Hispanics. Age-adjusted rates among Blacks were ∼ 1.4-fold greater than in Whites, whereas rates among Hispanics were ∼1.4-fold lower than Whites and ∼2-fold lower than Blacks. Age-specific rates among Blacks were greater than among Whites at all ages. Age-specific rates among Hispanics in pre- and peri-menopausal groups were similar to Whites, but became lower after menopause, which could account for overall lower age-adjusted rates among Hispanics.
In summary, our analysis indicates different IBC rates in Whites, Blacks, and Hispanics. New information about lower IBC rates among Hispanics poses a question of what accounts for these differences. Further investigations of the ethnic/racial rates disparities may elucidate the underlying risk factors for IBC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3732. doi:10.1158/1538-7445.AM2011-3732
Abstract 3735: Mathematical modeling of the inflammatory breast cancer age-patterns indicates its unique biology
Authors: Il'yasova Dora , Akushevich Igor , Siamakpour-Reihani Sharareh , Spector Neil , Schildkraut Joellen 
Published: June 2012

Abstract
Introduction: Inflammatory breast cancer (IBC) is the most fatal form of breast cancer (BC) with unknown etiology. IBC is characterized by rapid onset (3-6 month) with unusual clinical presentation (redness, edema, warmth, and pain), sometimes without an underlying tumor mass, whereas non-inflammatory BC most often presents as painless breast mass. IBC also presents with higher nuclear grade, more frequent involvement of lymph nodes, and negative hormone receptor status than non-inflammatory locally-advanced BC (NI-LABC). Finally, the incidence age-pattern of IBC has been shown to be distinctly different from NI-LABC. The differences in the cancer incidence age-patterns, as hypothesized by Armitage and Doll, reflect different number of successive cellular transitions necessary for the development of a clinically significant malignancy. We used extended Armitage-Doll model and SEER data for 2004-2007 to describe age-patterns of IBC and NI-LABC incidence and to estimate the number of cellular transitions involved in the development of these two BC types. Also, it was important to compare earlier described IBC age-patterns to the most recent as coding of IBC has been changed since 2004.
Methods: Using SEER data for 2004-2007, we estimated age-specific incidence rates of IBC and NI-LABC for ages 20-84. IBC cases were defined as having Common Stage Extension Codes 71-73. Incidence rates were modeled using extended Armitage-Doll model with four parameters reflecting the baseline hazard, the number cellular transitions, and properties of the distribution of individual predisposition.
Results and Conclusions: As expected, IBC incidence age-pattern was distinctly different from that of NI-LABC and similar to the earlier described by Hance et al. Specifically, the IBC incidence increased with age and peaked between ages 50 and 60 with obvious deceleration after 60. In contrast, NI-LABC incidence continued to increase after 50 years of age without a peak or deceleration. The number of estimated cellular transitions was ∼7 for IBC and ∼ 9 for NI-LABC; this difference in cellular transition number was statistically significant. In theory, each transition represents a distinct stage with a rate-limiting event. We discuss different interpretations of the lower transition steps estimated for IBC in light of its unique presentation and age-pattern. Finally, the similarity of age-patterns with the previously published analysis of SEER data confirms the validity the new definition of IBC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3735. doi:10.1158/1538-7445.AM2011-3735
Abstract 3740: Low carbohydrate diets, DASH-style diet and risk of post-menopausal breast cancer
Authors: Fung Teresa , Hu Frank , Hankinson Susan , Willett Walter , Holmes Michelle 
Published: June 2012

Abstract
Background: Low carbohydrate diets and the DASH-style diet have not been evaluated for their association with breast cancer.
Methods: We prospectively examined the association between the DASH score, overall, animal, and vegetable low carbohydrate diet scores and risk of postmenopausal breast cancer in 86,621 women in the Nurses’ Health Study. Diet scores were calculated from up to 7 food frequency questionnaires (FFQ) during up to 26 years of follow-up. We also examined the association with major plant food groups. Analysis was separately conducted for estrogen receptor status (ER) positive and negative tumors.
Results: We ascertained 5,522 incident cases of breast cancer, including 3,314 ER+ and 826 ER- cancers. After adjusting for potential confounders, the DASH score was associated with a lower risk of ER- cancer (RR comparing extreme quintiles=0.80, 95% CI=0.64-1.01, p trend=0.02). However, this is largely explained by higher fruits and vegetables intake. An inverse association was also observed with the vegetable low carbohydrate score (corresponding RR=0.81, 95% CI=0.65-1.01, p trend=0.03). Total fruits and low protein vegetables were association with a lower risk of ER- cancer (RR comparing extreme quintiles=0.71, 95%CI=0.55-0.90, p trend=0.005).
Conclusion: A diet high in fruits and vegetables, such as one represented by the DASH score was associated with a lower risk of ER- breast cancer. In addition, a diet high in plant protein and fat and moderate in carbohydrate content is also associated with a lower risk of ER- cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3740. doi:10.1158/1538-7445.AM2011-3740
Abstract 3745: IL-10 polymorphisms, smoking, and Helicobacter pylori infection on the risk of noncardia gastric cancer in Koreans
Authors: Kim Jeongseon , Cho Young Ae , Shin Aesun , Cho Soo-Jeong , Kim Chan Gyoo , Lee Jong Yeul , Kim Young-Woo , Choi Il-Ju 
Published: June 2012

Abstract
Background: Genetic variations of interleukin-10 (IL-10) and environmental factors are assumed to influence inflammation and gastric carcinogenesis. Therefore, we aimed to investigate the association between IL-10 polymorphisms, smoking, and Helicobacter pylori (H. pylori) infection on the noncardia gastric carcinogenesis in Koreans.
Methods: We genotyped 3 promoter polymorphisms (−1082 A&gt;G, -819T&gt;C, -592A&gt;C) on the IL-10 gene in 495 noncardia gastric cancer patients and 495 sex- and age-matched controls. Multiple logistic regression models were used to detect the effects of IL-10 genetic variants, smoking, and H. pylori infection on gastric cancer risk, stratified by histological type of gastric cancer.
Results: The IL-10-819C allele and -592C allele are in complete linkage disequilibrium, and IL-10-819C/-592C carriers are associated with a higher risk of noncardia gastric cancer, particularly with a risk of intestinal type cancer (OR [95% CI] = 1.50 [1.08−2.08]), than those with the wild type homozygote genotypes. Compared to nonsmokers carrying the wild type homozygotes, current smokers carrying IL-10-1082G and -819C/-592C showed 4.91 (95% CI = 2.49−9.69) and 6.82 (95% CI = 2.94−15.84) times increased risk of intestinal type gastric cancer, respectively. In addition, smokers with H. pylori infection were in the highest risk of intestinal gastric cancer compared with non-smokers without H. pylori infection, and this association was particularly stronger among IL-10-1082G carriers than AA carriers (OR [95% CI] = 15.54 [5.52−43.72]).
Conclusion: Inflammation-related genetic variants may interact with smoking and H. pylori infection on the risk of noncardia gastric cancer, particularly intestinal type. Therefore, high risk group may reduce the risk of gastric cancer by modifying their lifestyles.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3745. doi:10.1158/1538-7445.AM2011-3745
Abstract 3749: Polymorphisms in metabolism genes may mediate the effect of dietary intake on pancreatic cancer risk
Authors: Jansen Rick , Robinson Dennis , Stolzenberg-Solomon Rachael , Bamlet William , Cunningham Julie , Rider David , Oberg Ann , Hammer Traci , Rabi Kari , Anderson Kristin , Olson Janet , Sinha Rashmi , Petersen Gloria 
Published: June 2012

Abstract
Background: The role of dietary fruit, vegetable, fiber, and whole grain intake is implicated as a potential protective factor against pancreatic cancer, but studies are inconsistent. A possible explanation for the variability is that individuals who carry constitutional metabolism gene variants (minor alleles) may differentially benefit compared to those who are homozygous for the major allele, which over a life-time could lead to altered pancreatic cancer risk. Methods: We genotyped 70 SNPs that tag ten candidate metabolism genes (CAT, GAA, GCK, MT1E, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2B4, and UGT2B7) involved in the metabolism of components of fruits, vegetables, fibers, and whole grains to test if differential associations exist with pancreatic adenocarcinoma. We used a clinic-based case-control design, excluding participants who reported changing their diet within 5 years prior to entering the study. Three hundred eighty-four rapidly ascertained cases and nine hundred eighty-three non-cases from a primary care clinic (frequency matched on age at recruitment (+ 5 years), race, sex, and region of residence) provided blood samples for DNA and completed epidemiologic surveys plus a 144-item food frequency questionnaire developed by the National Cancer Institute. We used a dominant model to code SNPs and split dietary intake categories based on the sex-specific median intake level among non-cases. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals, adjusted for age, sex, family-history of pancreatic cancer, smoking (never/ former/ current), body mass index, energy intake, and alcohol consumption. The reference group was defined as carriers of no minor alleles in the lowest intake category. Results: The greatest benefit was observed for carriers of no minor alleles, for rs11032702 (CAT) with higher insoluble dietary fiber intake (OR [95%CI]: 0.515 [0.37, 0.71]); for rs735670 (GCK) with higher soluble dietary intake (0.473 [0.34, 0.67]); for rs2070971 (GCK) and rs2268569 (GCK) with higher fruit intake not from citrus, melon, and berries (0.513 [0.36, 0.73] and 0.554 [0.40, 0.78]); and for rs17832252 (GCK) with higher whole grain intake (0.530 [0.37, 0.76]); all comparisons had a reference group of no minor alleles with low dietary intake and a p-value for interaction &lt;0.001. Conclusions: Inter-individual variation in metabolism of fruits, vegetables, fiber, and whole grain via metabolism gene variants may influence pancreatic cancer risk.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3749. doi:10.1158/1538-7445.AM2011-3749
Abstract 3776: Bone marrow stromal cell paracrine signaling and IL-6 induce autophagy in bone metastatic prostate cancer cells
Authors: Delk Nikki A. , Farach-Carson Mary C. 
Published: June 2012

Abstract
Prostate cancer (PCa) is the second leading cause of death in North American men, where 80% of PCa mortality is due to bone metastasis. It is imperative to understand the biology of PCa cells in bone, especially as related to the role of the microenvironment in cellular adapation. Our lab recently published data revealing that bone marrow stromal cell (BMSC) paracrine signaling induces apoptosis in co-cultured bone metastatic PCa cells. However, a subpopulation of the bone metastatic PCa cells can avoid apoptotic cell death and undergo neuroendocrine differentiation (NED), a phenotype that contributes to tumor growth and is correlated with poor prognosis. One process that mediates cell survival and differentiation is autophagy, a process of sequestering cytoplasmic components for degradation and recycling to maintain cellular homeostasis. Autophagy provides a long term survival and growth advantage for cancer cells by relieving metabolic stress. Neuronal differentiation with cytoplasmic reduction is one adaptive response that can involve autophagy. Thus, we hypothesize that autophagy is a cytoprotective mechanism for PCa cell survival and NED in the bone microenvironment. To address this, we assessed the paracrine effect of BMSC on bone metastatic PCa cell autophagy and identified interleukin-6 (IL-6) as a BMSC paracrine factor that can induce PCa autophagy. We provide experimental data showing that IL-6 can protect PCa cells from apoptosis and simultaneously induce PCa NED. Current experiments are underway to determine if IL-6-induced autophagy functions upstream of bone metastatic PCa cell survival and NED and to dissect the IL-6 signaling pathway responsible for autophagy induction in PCa cells. These studies will identify IL-6 pathway components as molecular targets to attenuate cytoprotective autophagy in PCa cells in the bone microenvironment, providing new avenues for long term treatment of bone lesions in PCa patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3776. doi:10.1158/1538-7445.AM2011-3776