bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-427: Differential effects of resveratrol-induced SIRT1 in prostate cancer: A novel therapeutic target
Authors: Li Guiming , Ghosh Rita , Kumar Addanki P. 
Published: February 2011

Abstract
Silence information regulator (SIRT1) is a Nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that regulates various biological processes including cell survival, apoptosis, metabolism and aging. Given the role for calorie restriction (CR) in delaying the onset of aging and age-related disorders including cancers, efforts are under way to develop CR mimetics as therapeutic agents. Resveratrol, a CR mimetic activates SIRT1 and has been shown to extend life span. Further, resveratrol has been shown to prevent tumor development and cancer cell proliferation in a wide variety of models including prostate. However the precise role of SIRT1 in prostate cancer development and progression remains unexplored. Towards developing SIRT1 targeted preventive approaches, we conducted studies using human prostate cancer cell lines and a preclinical animal model that develops high grade prostatic intraepithelial neoplasia (HGPIN) in response to hormone stimulation. Our studies show that androgen independent prostate cancer cell lines (DU145 and PC-3) express higher levels of SIRT1 compared to non tumorigenic RWPE-1 consistent with the published results. Resveratrol-mediated inhibition of cell proliferation was associated with reduction in the levels of pAkt (Ser473 and Thr308), SIRT1and Cyclin D1 in PC-3 cells but not in DU145. Most interestingly we did not detect SIRT1 enzymatic activation following resveratrol treatment. Further pretreatment of prostate cancer cells with known pharmacological SIRT1 inhibitor (Nicotinamide) enhanced resveratrol mediated proliferation inhibition. Dietary intervention with increasing doses of resveratrol for 3 weeks showed no protective effect on the development of PIN lesions or chronic inflammation or atrophy in rats stimulated with hormones. Our studies show for the first time that (i) SIRT1 may not be a direct target of resveratrol; (ii) combination of resveratrol and SIRT1inhibitor may provide a new approach to prevent development and progression of prostate cancer. Supported by CA 137518 (APK).
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-427.
Abstract LB-431: Randomized trial of oral melatonin supplementation in breast cancer survivors
Authors: Schernhammer Eva S. , Giobbie-Hurder Anita , Gantman Kathryn , Savoie Jennifer , Scheib Rochelle , Chen Wendy 
Published: February 2011

Abstract
Background: Night shift work has been classified by the International Agency for Research and Cancer and the World Health Organization as a probable carcinogen, presumably due to its effect on the melatonin pathway. Extensive laboratory and some human data also support that melatonin may influence breast cancer risk, although the mechanism is not clear. Both pharmacologic and physiologic doses of melatonin inhibit the growth of malignant cells of the breast in vitro and in animal models.
Study Design: 95 postmenopausal women with a prior history of Stage 0-III breast cancer who had completed active cancer treatment (including hormonal therapy) were recruited to a double-blind randomized trial of 4 months of 3 mg melatonin daily compared to placebo. Endpoints included changes in breast cancer biomarkers, sleep, hot flashes, and mood.
Results: 5 subjects on melatonin and 4 on placebo withdrew from the study or did not complete the 4 month assessment leaving 86 women (43 on placebo and 43 on melatonin) with evaluable data. Melatonin was well-tolerated without any grade 3/4 toxicity. At baseline, there was no statistical difference between the two arms for any of the endpoints or standard demographic characteristics. Mean age was 59 years (range 38-71) with mean 8 years since diagnosis. At 4 months, there were no statistically significant differences between the two groups for the biomarker endpoints (estradiol, IGF-1, IGFBP-3, or IGF-1/IGFBP-3 ratios), depressive symptoms, or hot flashes. However, subjects taking melatonin had significantly improved sleep quality, sleep duration, and total sleep scores compared with subjects taking placebo.
Conclusions: Among postmenopausal women with a prior history of breast cancer, a 4 month course of 3 mg melatonin daily did not influence IGF-1, IGFBP-3 or estradiol levels. Effects of longer courses of melatonin and among premenopausal women are unknown. However, melatonin was effective in improving sleep quality among breast cancer survivors without any significant adverse effects.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-431.
Abstract LB-45: Cancerous inhibitor of phosphatase PP2A in lung cancer
Authors: Zhou Guangbiao , Ma Liang , Wen Zhesheng 
Published: February 2011

Abstract
Cellular signaling networks are controlled by reversible covalent phosphorylation, which depends on a precise balance between protein kinase and phosphatase activities. Recently, phosphatase has been shown to be silenced by cancerous inhibitor of phosphatase, leading to perturbation of the kinase/phosphatase balance. Here we report that at mRNA and protein levels, the expression of the cancerous inhibitor of phosphatase PP2A (CIP2A) were undetectable or very low in paratumor tissues, but was dramatically elevated in tumor samples in 33 (63.%) out of 52 patients. CIP2A enhanced clonogenic activity of human embryo lung fibroblast, while CIP2A silencing by siRNA led to inhibition of cell proliferation and induction of apoptosis of lung cancer cells. We found that LTZ010 which was a compound extracted from a traditional Chinese medicinal herb, triggered a rapid turnover of CIP2A, and increased PP2A phosphatase activity. At presence of proteasome inhibitor PS-341, aggresome was found in cytoplasm of cells treated with LTZ010, and catabolism of CIP2A was abrogated. We found that LTZ010 inhibited proliferation and cell growth of lung cancer cells, and activated caspase-9 and -8. Intriguingly, LTZ010 significantly inhibited tumor growth in vivo, but did not caused animal body weight loss. Our data suggest that CIP2A might play an important role in lung cancer tumorigenesis, and LTZ010 might have potential benefits for patients with lung cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-45.
Abstract LB-47: Resveratrol induces Apaf-1 dependent but apoptosome-independent apoptosis in cancer cells
Authors: Prabhu Varun V. , Amadori Michael , Zhang Honghao , Pitaressi Jason , Yadav Neelu , Chandra Dhyan 
Published: February 2011

Abstract
Resveratrol (Resv) selectively kills cancer cells, whereas the molecular mechanisms of Resv-induced cancer cell death are not defined. Here we show that Resv induces mitochondria-dependent but apoptosome-independent apoptosis in cancer cells. Resv inhibits cancer cell growth and proliferation, mitochondrial membrane potential, and ROS production. In contrast, Resv induces dose and time dependent caspase activation, poly (ADP-ribose) polymerase (PARP) cleavage, and thus caspase-dependent apoptosis. Mechanistic analysis reveals that recruitment and oligomerization of Bax on the mitochondria is associated with release of cytochrome c from the mitochondria. Surprisingly, the released cytochrome c fails to induce apoptosome assembly as evidenced by the lack of Apaf-1 oligomerization upon Resv treatment. Interestingly, Apaf-1 was up regulated both at transcriptional and protein levels upon Resv treatment suggesting that the levels of Apaf-1 was not a limiting factor for apoptosome assembly. Subcellular analysis reveals that catalytically active caspase-9 was mostly associated with the mitochondria in Resv-induced apoptotic cells. Reconstitution experiment using recombinant proteins and purified cytosols demonstrates that Resv inhibits apoptosome functions in a dose dependent manner. MALDI-TOF analysis indicates that inhibition of apoptosome formation was not mediated by sequestration of cytochrome c as Resv fails to interact with cytochrome c. Furthermore, Resv also induces autophagy as evidenced by the increase in the levels of LC3-II upon Resv treatment. Inhibition of autophagy either by autophagy inhibitors or by silencing of autophagy related genes (ATG-5 or Beclin-1) further increase caspase activation. Gel filtration and subcellular fractionation analyses demonstrate that caspase-independent apoptosis does not seem to be involved as AIF and endonuclease G was not released from the mitochondrial compartment upon Resv treatment. These findings indicate that Resv targets mitochondria to induce caspase-9 mediated cancer cell death and that induction of autophagy during apoptosis is an adaptive response. Therefore, inhibition of autophagy along with induction of apoptosis could represent a novel strategy for cancer therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-47.
Abstract LB-51: Correlation of expression of MDR-associated genes with outcome in primary ovarian serous carcinoma
Authors: Gillet Jean-Pierre , Calcagno Anna Maria , Varma Sudhir , Davidson Ben , Elstrand Mari Bunkholt , Ganapathi Ram , Sood Anil K. , Ambudkar Suresh V. , Seiden Michael V. , Rueda Bo R. , Gottesman Michael M. 
Published: February 2011

Abstract
We have been developing tools to reproducibly correlate the expression of multidrug-resistance (MDR)-associated genes with response to chemotherapy in primary cancers. This study reports the results of a novel MDR gene expression analysis of primary serous carcinoma of the ovary utilizing a TaqMan Low Density Array (TLDA) chip which includes 380 previously characterized multidrug resistance (MDR)-associated genes that were initially identified in cultured cancer cells. Primary tumor samples from 133 patients from 4 sites were studied. All patients were subsequently treated with standard chemotherapy and had known clinical outcome. A 13 gene signature was identified whose expression added statistical power to the risk status of the patients based on standard clinical parameters (age, CA125, and success of surgical debulking) (log-rank statistic p=0.02). When subsets of patients with defined clinical risk were studied, we found that a subset of clinically high risk patients that had low expression of the 13 gene signature had a better outcome than would be predicted by purely clinical criteria. Similarly, clinically low risk patients with high expression of the 13 gene signature had a poorer prognosis. Since the mechanism of action of the 13 MDR genes involved in the signature are well-understood, it might be possible to devise therapeutic strategies to some of these targets with the goal of improving clinical outcome.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-51.
Abstract LB-6: bHLH transcription factor Id4 plays a regulatory role in cell cycle control, apoptosis, and senescence in androgen-insensitive prostate cancer
Authors: Jason Carey P. , Chaudhary Jaideep , Evans Ashley 
Published: February 2011

Abstract
Id4 belongs to a family of genes that are dominant negative regulators of basic helix-loop-helix (bHLH) transcription factors. Id4 expression shows an inverse correlation to Id1-3 expression in advanced metastatic prostate cancer which act as tumor promoter genes. Recent Id4 promoter hypermethyation data suggests that Id4 may act as a tumor suppressor in prostate cancer, and loss of Id4 expression may correlate with androgen insensitive prostate cancer progression. The inhibitory role of Id4 is characterized by inhibition of cancer progression and up regulation of tumor suppressor genes. In the DU145 prostate cancer cell line, Id4 down regulation is responsible for increased cell survival, metastasis and decreased apoptosis. Id4 absent/androgen-independent prostate cancer cell line DU145 was used to ectopically express Id4 mRNA and protein. This allowed for a novel identification of the role Id4 plays in cell cycle control, apoptosis and proliferation in an advanced prostate cancer model. FACS analysis highlighted the role of Id4 in cell cycle maintenance. Apoptosis assays support the tumor suppressor role of Id4 in DU145 cell lines. Senescence assays were also conducted on in Id4 expressing DU145 cells. RT-PCR and western blot analysis were used to study gene expression of downstream apoptosis and cell cycle control genes E-cadherin, p21, p27, p53, MDM2, E2F1 and, Androgen receptor. Du145 + Id4 prostate cancer cells have significantly decreased proliferation due to an S-phase arrest possibly associated with E2F-1 down regulation. The increased expression of E-cadherin, p27, p21 and p53 strengthens the hypothesis of Id4 as a tumor suppressor by regulating key cell cycle control and apoptosis associated genes. A functional androgen receptor was also induced in this androgen insensitive prostate cancer model. Id4 ectopic expression resulted in a significant decrease in Id1 and Id3, which are known contributors to metastasis and cell survival. This suggests that Id4 may inhibit bHLH transcription factors involved in proliferation, and metastasis of prostate cancer cells. Id4 induces apoptosis whether dependent/independent of the mutated p53 gene in DU145 cells. The presence of senescent cells in Id4 transfected cell lines suggest that Id4 may also play a role in autophagic cell death. We conclude that the mechanism by which Id4 may act as a tumor suppressor is by influencing a hierarchy of cellular processes at multiple levels including, apoptosis, senescence and S-phase mediated cell cycle arrest, which results in changes to cell morphology, and androgen receptor response.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-6.
Abstract LB-7: Epigenetic silencing of IRF8 expression is associated with myeloid leukemia escape from cancer immunosurveillance
Authors: Hu Xiaolin , Liu Kebin 
Published: February 2011

Abstract
Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease (MPD) that comprises 15-20% of human hemapoietic cancers. Exciting advances in molecular mechanism-based strategies have yielded imatinib mesylate/STI571/Gleevec, which has proven to be effective in many human patients with CML. Unfortunately, Gleevec is not effective in some human CML patients, whereas some CML patients become refractory to Gleevec due to the development of drug resistance caused by mutations in abl. Furthermore, Gleevec becomes significantly less effective if the CML evolves to blast crisis. Therefore, elucidating the molecular mechanisms underlying CML pathogenesis is of significance for the development of more effective molecular target-based therapy for CML patients. In this study, we demonstrated that the IRF8 expressed is decreased in human CML/AML cells and the IRF8 promoter is methylated in human CML/AML cells and in PMBC derived from human CML patients. Ectopic expression of IRF8 in myeloid cells suppressed tumor development in mice in vivo. We further demonstrated that IRF8 regulates Fas and FLIP expression in myeloid leukemia cells to mediated Fas-mediated apoptosis. Taken together, our data suggest that myeloid leukemia cells use DNA methylation to silence IRF8 expression to acquire a Fas-resistant phenotype to escape from cancer immunosurveillance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-7.
Abstract LB-72: Rapid detection and profiling of breast cancer cells in blood applied to arrays of carbon nanotube thin film biosensors
Authors: Panchapakesan Balaji , Velasco Vanessa , Jing Rui-Yan , Talati Pooja , Zibelli Allison M. , Wickstrom Eric 
Published: February 2011

Abstract
Breast cancer is the most frequently diagnosed cancer in women. Developing breast cancers shed transformed cells into the blood. More malignant breast cancer cells appear in the blood at later stages. Early detection of circulating breast cancer cells might improve diagnosis of early breast cancer and ultimately might reduce deaths from breast cancer. We hypothesized that nanotube-antibody arrays could detect circulating human breast cancer cells in a drop of blood. Breast cancer cell surfaces show high levels of insulin-like growth factor 1 receptor (IGF1R), human epidermal growth factor receptor 1 (Her1, EGFR), and Her2 (Erb-B2, neu), among others. We have previously demonstrated antibody-specific nanodevice detection of ER+/Her2- MCF7 and ER+/Her2+ BT474 breast cancer cells suspended in a physiological buffer, and in fresh human blood. We discovered significant changes in conductance of single wall carbon nanotube-monoclonal antibody nanodevices upon exposure to human breast cancer cells in 2-5 microliter drops of physiological buffer or fresh donor blood. The nanodevices detected the cancer cells within 60 seconds and stabilized by five minutes. Control cells did not change nanodevice conductance. Breast cancer cells did not perturb the conductance of nanodevices with adsorbed anti-PSMA or nonspecific antibodies. Hence, the conductance change required a specific antigen-antibody complex between the live, intact breast cancer cell and the nanotube surface in blood. We postulate that sensing of breast cancer cell binding is due to cooperative stress on the surface of the nanotubes due to cellular binding to multiple antibodies. The stress on the nanotube is then thought to change its electron transport properties. Five microliter drops of blood from patients with metastatic breast cancer changed nanodevice conductance similarly to 10-100 MCF7 cells. Comparable circulating tumor cell numbers were obtained from 7.5 mL blood draws from the same patients analyzed by EpCAM bead capture and anti-cytokeratin staining. Single wall carbon nanotube-monoclonal antibody nanodevices provide the simplest and quickest method for direct detection of live cancer cells circulating in blood. Supported by a grant from the Breast Cancer Alliance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-72.
Abstract LB-73: Nuclear S100A4 is a novel prognostic marker in colorectal cancer
Authors: Boye Kjetil , Nesland Jahn M. , Sandstad Berit , Mælandsmo Gunhild M. , Flatmark Kjersti 
Published: February 2011

Abstract
Background and Aims: Current staging classifications in colorectal cancer are not able to accurately predict patient outcome, and the need for novel prognostic markers is evident. S100A4 is a Ca2+-binding protein which promotes metastasis in several tumor types, and the aim of the present study was to investigate the prognostic impact of S100A4 expression in colorectal cancer.
Methods:
242 patients with curatively resected adenocarcinoma of the colon or rectum were prospectively included in the study at the time of surgery. S100A4 expression was analyzed by immunohistochemistry, and associations with clinicopathological variables and patient outcome were investigated.
Results: Nuclear expression of S100A4 was observed in 29% and cytoplasmic expression was observed in 64% of the tumors. In univariate analysis, nuclear S100A4 was a significant predictor of metastasis-free (P= .006) and overall survival (P= .01), whereas cytoplasmic S100A4 was not associated with patient outcome. In multivariate analysis, nuclear localization was associated with metastasis-free (P= .03) and overall survival (P= .02). Interestingly, the prognostic impact was largely confined to TNM stage II, and stage II patients with tumors expressing nuclear S100A4 had a similar prognosis as stage III patients.
Conclusions: Nuclear expression of S100A4 is a novel prognostic marker in colorectal cancer, and the prognostic value in TNM stage II suggests that nuclear S100A4 could be used in the stratification of stage II patients for adjuvant treatment.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-73.
Abstract LB-81: Purification and characterization of a human urinary compound with potent anticancer activity
Authors: Antakly Tony , Chen Ling , Lafaille Francine , Toma Emil , Menezes José , Emwas Abdul-Hamid , Brox Alan 
Published: February 2011

Abstract
Historically, the urine, considered as a blood filtrate has been recognized as a source of medicinal products and important constituents of widely used drugs. However, various molecules in human urine such as growth factors, hormones, and their metabolites have not yet been thoroughly characterized. A group of low molecular weight compounds named HIP's (HCG-like Inhibitory Proteins), was discovered in our laboratories while investigating the hormonal regulation of a skin cancer, Kaposi's sarcoma (KS). Following extraction from the urine of pregnant women, HIP was found to inhibit the growth and kill KS cancer cells by apoptosis both in vitro and in vivo. Initial results following intralesional injection with HIP, revealed a marked reduction in the number of neoplastic cells in the tumor. We are presently testing this product in clinical trials on KS patients in a double blind placebo controlled study. Preliminary results reveal HIP to be safe and well tolerated with no adverse or unexpected reactions. More recently, two other tumors types were demonstrated to be sensitive to HIP and are under further investigation. Following the use of gene microarrays and RT-PCR, the principal target genes for HIP were identified as belonging to a growth factor receptor family. Further purification and biochemical characterization is underway using proteomics and NMR spectroscopy. Overall, the present studies further establish HIP as a urinary compound with potent anti-cancer activity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-81.