bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 173: Targeted killing of cancer stem-like cells by a novel analogue of curcumin
Authors: Bao Bin , Ali Shadan , Kong Dejuan , Sarkar Sanila H. , Wang Zhiwei , Banerjee Sanjeev , Aboukameel Amro , Padhye Subhash , Philp Philip A. , Sarkar Fazlul H. 
Published: June 2012

Abstract
The existence of cancer stem cells (CSCs) or cancer stem-like cells in a tumor mass is believed to be responsible for tumor recurrence because of their intrinsic and extrinsic drug-resistance characteristics. Therefore, targeted killing of CSCs would be a newer strategy for the prevention of tumor recurrence and/or treatment by overcoming drug-resistance. We have developed a novel synthetic compound-CDF, which showed greater bioavailability in animal tissues such as pancreas, and also induced cell growth inhibition and apoptosis, which was mediated by inactivation of NF-κB, COX-2, and VEGF in pancreatic cancer (PC) cells. In the current study we showed, for the first time, that CDF could significantly inhibit the sphere-forming ability (pancreatospheres) of PC cells consistent with increased disintegration of pancreatospheres, which was associated with attenuation of CSC markers (CD44 and EpCAM), especially in gemcitabine-resistant (MIAPaCa-2) PC cells containing high proportion of CSCs consistent with increased miR-21 and decreased miR-200. Moreover, CDF treatment showed increased protein levels of phospho-β-catenin, and decreased levels of Wnt3a, β-catenin, LEF1, and CD44. In a xenograft mouse model of human PC, CDF treatment significantly inhibited tumor growth, which was associated with decreased NF-κB DNA binding activity, COX-2, Wnt3a, and miR-21 expression, and increased PTEN and miR-200 expression in tumor remnants. These results strongly suggest that the anti-tumor activity of CDF is associated with inhibition of CSC function via down-regulation of CSC-associated signaling pathways. Therefore, CDF could be useful for the prevention of tumor recurrence and/or treatment of PC with better treatment outcome in the future.
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 173. doi:10.1158/1538-7445.AM2011-173
Abstract 1733: Therapeutic significance of ERα—PELP1 axis in blocking endocrine therapy resistance
Authors: Cortez Valerie A. , Suzuki Takayoshi , Miyat Naoki , Sood Anil K. , Vadlamudi Ratna K. 
Published: June 2012

Abstract
Breast cancer therapies target the estrogen receptor-alpha (ERα) with letrozol an aromatase inhibitor or anti-estrogens such tamoxifen to limit circulating estrogen levels and alter ERα functions. Many women suffering from recurrent or advanced disease develop resistance to current targeted endocrine treatments. Emerging data suggests therapeutic resistance is precipitated through dysfunction of ERα coregulatory proteins and crosstalk between ERα and growth factor signaling. Deregulated expression of proline-, glutamic acid- and leucine-rich protein 1 (PELP1), an ERα coregulator, was observed in a subset of human breast tumors. Recently, PELP1 was identified as an independent prognostic biomarker of shorter survival in ERα positive/luminal-like breast cancer patients. Epigenetic changes of target gene promoters are modulated by PELP1 via an interaction with lysine specific demethylase 1 (KDM1). Additionally, PELP1 promotes crosstalk between ERα and Src kinase leading to enhanced activation of extranuclear signaling pathways. Therapeutic potential of targeting the ERα-PELP1 axis in vivo was examined using a pharmacological approach in well-established preclinical models of endocrine therapy resistant breast cancer. We utilized (1) siRNA liposomes to down regulate PELP1 expression; (2) pargyline and NCL-1, KDM1 inhibitors, to block PELP1-mediated epigenetic modifications and (3) dasatinib, a Src kinase inhibitor, to prevent PELP1-mediated extranuclear actions in both pre- and post-menopausal conditions. In xenograft-based assays, treatment of ERα positive breast cancer cells with liposomes containing PELP1-siRNA, dasatinib or KDM1 inhibitors significantly reduced proliferation and tumor growth. Combinatorial therapies of letrozol or tamoxifen with PELP1 axis blockers substantially impeded xenograft tumor growth by blocking both ERα nuclear and extranuclear signaling and promoting apoptosis in therapy resistant cells. Taken together, our results suggest targeting the ERα-PELP1 axis in combination with current endocrine therapies will enhance therapeutic efficacy and may inhibit or delay development of endocrine therapy resistance.
This study is funded by Komen grant KG090447 and NIH grant CA095681.
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 1733. doi:10.1158/1538-7445.AM2011-1733
Abstract 1796: The impact of adjuvant immunochemotherapy using protein-bound polysaccharide-K on overall survival of gastric cancer
Authors: Tanaka Hiroaki , Ohira Masaichi , Muguruma Kazuya , Kubo Naoshi , Nagahara Hisashi , Kimura Kenjiro , Amano Ryosuke , Noda Eiji , Yamada Nobuya , Yashiro Masakazu , Maeda Kiyoshi , Onoda Naoyoshi , Sawada Tetsuji , Nakata Bunzo , Ishikawa Tetsuro , Hirakawa Kosei 
Published: June 2012

Abstract
Protein-bound polysaccharide (PSK) has been approved as an anti-cancer agent to be used in combination with chemotherapeutic drug for adjuvant therapy against gastric cancer. Several clinical studies have demonstrated that PSK has antitumor and immunomodulating properties. However, there is little evidence about the effectiveness of PSK in clinical practice. The aim of this study was to evaluate the impact of PSK on overall survival of patients with gastric cancer and predict the suitable case selection for postoperative adjuvant immunochemotherapy. The patients with stage II/III gastric cancer who underwent surgical curative resection between 2000 and 2007 at Deptarment of Surgical Oncology, Osaka City University were included in this retrospective study. All patients received oral fluorinated pyrimidine anti-metabolites with or without PSK after surgical operation. We analyzed clinicopathological features and evaluated the impact of PSK on postoperative survival rate of resectable gastric cancer. We identified 254 patients with a median follow-up of 33 months (range, 7-110 months). 138 patients received oral anti-metabolized alone (control group) and 115 patients received anti-metabolites plus PSK (PSK group). 139 patients of the cohort experienced postoperative recurrence. No significant difference between control and PSK group in overall survival or relapse free survival was detected over the 8-year period. In patients with early tumor recurrence, PSK group increased overall survival significantly (p&lt;0.023). Among patients with pN3 lymph nodes metastasis, PSK group had better median overall survival of 28 months compared with 22 months with oral chemotherapeutics alone. After multivariate Cox regression analysis, duration of PSK administration was associated with an increased overall survival (p=0.002, HR 0.964, 95%CI 0.942 to 0.987). Our results suggested that adjuvant immunochemotherapy with PSK increased overall survival for patients with pN3 and early tumor recurrence. A population with lymph nodes metastasis might be a suitable to combine PSK with oral chemotherapeutic agents for postoperative adjuvant therapy against gastric 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 1796. doi:10.1158/1538-7445.AM2011-1796
Abstract 1798: Effective lymphoma and leukemia therapy with epratuzumab (anti-CD22 IgG) conjugated to SN-38 (Emab-SN-38), with enhanced activity in combination with veltuzumab (anti-CD20 IgG)
Authors: Sharkey Robert M. , Cardillo Thomas M. , Govindan Serengulam V. , Goldenberg David M. 
Published: June 2012

Abstract
A number of B-cell malignancies, including lymphomas (NHL) and leukemia (ALL), can be treated effectively with antibodies, but these usually are combined with chemotherapy to enhance efficacy. We conjugated SN-38, a topoisomerase I inhibitor with nanomolar potency, to an anti-CD22 IgG (6:1 SN-38:IgG) by coupling to the tert-hydroxy group on the lactone ring of SN-38. This inhibits formation of the inactive carboxylate, a common problem with irinotecan, its prodrug, but the linker allows the active SN-38 to be released slowly from the IgG (∼50% decouples every 1 to 1.5 days) in serum or in the acidic environment of the lysosome. In vitro, Emab-SN-38 had nanomolar potency against a number of human NHL and ALL cell lines. Specific (as compared to an irrelevant anti-CEACAM5-SN-38 conjugate) and enhanced anti-tumor activity were demonstrated in mice bearing Ramos (Burkitt NHL), WSU-FSCCL (follicular NHL), or 697 (ALL) when compared to the unconjugated antibody (anti-CD22 or anti-CD20) alone or when combined with irinotecan. For example, animals bearing 0.3 to 0.8 cm3 Ramos xenografts treated with 3.75 mg/kg of an irrelevant immunoconjugate (54.5 µg/kg SN-38 equivalents) progressed to 3.0 cm3 in 1.0 week (median), while Emab-SN-38-treated animals had a median time to progression (TTP) of 4.05 weeks (P = 0.003) and 3/10 cures. Increasing the Emab-SN-38 dose to 12.5 mg/kg improved TTP to &gt;12 weeks with 7/10 cures, while the irrelevant conjugate's TTP was just 3.5 wk (P = 0.023). Improvements in TTP and cures were also found for the Emab-SN-38 in FSCCL and 697. Additionally, in Ramos and FSCCL, the anti-tumor response was enhanced by co-treating animals with veltuzumab. For example, median survival in animals treated 5 days after IV implantation of FSCCL was &gt;161 days for Emab-SN-38 + veltuzumab vs. 63 days and 91 days for Emab-SN-38 alone and veltuzumab alone, respectively (untreated, 42 days). Importantly, these treatments were tolerated without toxicity, with other studies showing tolerability in mice at doses of 1500 mg/kg. These data suggest the Emab-SN-38 is a potent, minimally toxic therapeutic in both NHL and ALL, with the added value when combined with anti-CD20 antibody therapy for enhanced responses.
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 1798. doi:10.1158/1538-7445.AM2011-1798
Abstract 1807: Tumor-infilitrating lymphocytes derived from pancreatic adenocarcinoma exhibit an activated, pro-inflammatory phenotype
Authors: Hall MacLean S. , Centeno Barbara , Malafa Mokenge , Hodul Pamela J. , Weber Jeffrey S. , Pilon-Thomas Shari , Sarnaik Amod A. 
Published: June 2012

Abstract
Contrary to current dogma, which maintains that pancreatic adenocarcinoma (PA) is infiltrated by predominantly inhibitory, regulatory CD4+ T cells (Treg), we demonstrate expansion of activated, pro-inflammatory tumor-infiltrating lymphocytes (TILs) from PA that could be used for adoptive cell therapy. TILs were grown in vitro in high-dose IL-2 from fragments of primary or metastatic PA. Pancreatic TILs were successfully expanded in 9 of 10 tumors and were phenotyped by flow cytometry. CD3+ TILs were predominantly CD4+ (mean frequency 76%, range 37-97%). CD4+ TILs were assessed for Treg frequency by CD25 and FoxP3 co-expression as a percent of total CD3+ TILs. Tregs were found to comprise the minority of CD3+ TILs (mean=3.1%, range=0.36-6.6%). We assessed CD4+ TIL expression of CD69, a known marker of T cell activation, and found a relatively high percentage of CD4+ TILs expressed CD69 (mean=25%, range=9-46%), which was significantly higher than the mean percent of Treg (p=0.0006). To confirm pro-inflammatory function, bulk TILs were stimulated in vitro by PMA/ionomycin, and expression of the pro-inflammatory cytokine IFNγ and the cytolytic marker CD107a was assessed. CD4+ TILs demonstrated a relatively high level of expression of IFNγ (mean=35%, range=20-47%) and CD107a (mean=19%, range=10-26%). Despite a low relative frequency, CD8+ TILs (mean=17%, range=1.8-41%) also expressed CD69 (mean=46%, range=17-83%) and exhibited a pro-inflammatory function upon stimulation as demonstrated by IFNγ (mean=43%, range=31-61%) and CD107a (mean=42%, range=22-69%) expression. After CD4 depletion, CD8-enriched TILs were effectively expanded with α-CD3 and maintained an activated, pro-inflammatory phenotype. This is the first report demonstrating that CD4+ TILs derived from PA have a predominantly pro-inflammatory phenotype. CD8+ TILs, though in the minority, also displayed an activated phenotype and preserved this phenotype throughout selective expansion. Further work is ongoing to support a phase I clinical trial involving adoptive TIL therapy in PA.
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 1807. doi:10.1158/1538-7445.AM2011-1807
Abstract 1826: Obesity as a therapeutic target for preventing recurrence and mortality in prostate cancer survivors: A meta-analysis of 29 cohort studies
Authors: Song Yong Sang , Kim Hee Seung , Kim Mi-Kyung , Lee Sangchul , Gong Seung Pyo , Kim Yong Beom , Lee Eunsik 
Published: June 2012

Abstract
Objective: The role of body mass index (BMI) remains unclear for disease recurrence and survival in patients with prostate cancer. To evaluated the role of BMI in prostate cancer survivors, we performed a meta-analysis for comparing biochemical recurrence-free survival (BCRFS), progression-free survival (PFS) and overall survival (OS) among normal weight (BMI &lt;25 kg/m2), overweight (BMI 25 – 29.9 kg/m2) and obesity (BMI ≥30 kg/m2).
Methods: After the extensive literature search till July 2010, we analyzed 29 relevant cohort studies where the role of BMI was investigated for BCRFS, PFS and OS in prostate cancer survivors. We used the fixed-effect model for the meta-analysis because of no observed heterogeneity among all relevant studies (Higgins I2 ≤50%).
Results: Although there was no difference in BCRFS between BMI &lt;25 kg/m2 and ≥25 kg/m2 (HR, 1.02, 95% CI, 0.98 to 1.09), BMI ≥30 kg/m2 showed poor BCRFS when compared with BMI &lt;30 kg/m2 (HR, 1.56, 95% CI, 1.48 to 1.65). In sub-analyses for BCRFS, BMI 25 – 29.9 kg/m2 showed poor BCRFS, compared with BMI &lt;25 kg/m2 (HR, 1.08; 95% CI, 1.03 to 1.14), and BMI ≥30 kg/m2 was also associated with poor BCRFS, compared with BMI 25 – 29.9 kg/m2 (HR, 1.20; 95% CI, 1.12 to 1.29). Furthermore, BMI ≥30 kg/m2 was related with PFS (HR, 1.65; 95% CI, 1.43 to 1.91) and OS (HR, 1.73; 95% CI, 1.63 to 1.97) when compared with BMI &lt;30 kg/m2, whereas there were no differences in them between BMI &lt;25 kg/m2 and ≥25 kg/m2 (PFS and OS; HR, 1.01 and 1.05; 95% CI, 0.85 to 1.20 and 0.88 to 1.26). In sub-analyses for PFS and OS, BMI ≥30 kg/m2 also decreased PFS (HR, 1.45; 95% CI, 1.23 to 1.71) and OS (HR, 1.49; 95% CI, 1.29 to 1.72) when compared with BMI 25 – 29.9 kg/m2 in spite of no differences in them between BMI &lt;25 kg/m2 and BMI 25 – 29.9 kg/m2 (PFS and OS; HR, 1.05 and 0.99; 95% CI, 0.88 to 1.26 and 0.88 to 1.11). Finally, these meta-analytic results showed no publication bias among all relevant studies.
Conclusion: These findings suggest that overweight (BMI 25 – 29.9 kg/m2) and obesity (BMI ≥30 kg/m2) may be associated with early biochemical recurrence, whereas obesity (BMI ≥30 kg/m2) may influence on clinical poor prognosis such as PFS and OS in prostate cancer survivors.
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 1826. doi:10.1158/1538-7445.AM2011-1826
Abstract 1842: Vitamin D compounds induce BRCA1 expression and inhibit breast stem cells
Authors: Kakarala Madhuri , Dubey Shiv K. , Dobry Craig J. , Peng Xinjian , Murillo Genoveva , Parikh Satyam R. , Amarasinghe Chintaka , Mehta Rajendra , Brenner Dean E. 
Published: June 2012

Abstract
Background: Basal breast cancer which occurs in women with BRCA1 mutations has been suggested to arise from arrested differentiation of stem/luminal progenitor cells, whose gene profile includes Vitamin D receptor prominently. In addition to DNA repair, BRCA1 enhances luminal differentiation of breast stem cells. Vitamin D compounds have long been known to have differentiating function. We hypothesized that Vitamin D receptor exists on stem cells and that vitamin D treatment induces differentiation of stem/progenitor cells, in part due to increased BRCA1 expression.
Methods: We treated normal human breast epithelial cells and MCF-7 breast cancer cells with 10 or 100 nM 1, 25 dihydroxyvitamin D3 or the less hypercalcemic vitamin D5 analogue (1alpha(OH)D5) in suspension culture in stem cell media to assess: 1) stem cell self renewal using the mammosphere assay; 2) inhibition of stem cell percentage; 3) induction of BRCA1 mRNA and 4) induction of BRCA1 protein.
Results: Teatment with 100nM 1alpha(OH)D5 inhibited stem cell self renewal as assessed by mammosphere formation assay from 23spheres/high power field (HPF) to 1 per HPF at 7 days; inhibited of percentage of stem cells from 17% in vehicle control to 7% with vitamin D5. Both vitamin D3 and D5 caused an 8 fold induction of vitamin D target CYP24 gene expression; 4 fold increase in BRCA1 mRNA by real time PCR; and 4 fold increase in BRCA1 protein expression by western blot compared to actin control.
Conclusion: Vitamin D3 and D5 analogue induce BRCA1 expression and inhibit stem cell percentage in normal breast cells.
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 1842. doi:10.1158/1538-7445.AM2011-1842
Abstract 2155: The origins and functional consequences of ETS gene fusions in prostate cancer
Authors: Mani Ram S. , Tomlins Scott A. , Brenner Chad J. , Wang Lei , Iyer Matthew , Yu Jindan , Cao Qi , Callahan Kaitlin , Ghosh Aparna , Nyati Mukesh K. , Varambally Sooryanarayana , Palanisamy Nallasivam , Chinnaiyan Arul M. 
Published: June 2012

Abstract
The purpose of this study is to unravel the cellular mechanisms underlying the oncogenic ETS gene fusions, which are a hallmark of prostate cancer development. Recurrent gene fusions involving the 5’untranslated region of the androgen-regulated gene TMPRSS2 and the ETS family genes are observed in a majority of prostate cancers. Among the ETS family gene fusions, the TMPRSS2-ERG fusions involving the 5’untranslated region of TMPRSS2 with the ERG gene are the most common and found in approximately 50% of prostate cancers. However, the origins and functional consequences of ETS gene fusions are not clear. Using dual color fluorescence in situ hybridization (FISH), we demonstrate that stimulation with dihydrotestosterone (DHT) induces proximity between TMPRSS2 and ERG genomic loci in LNCaP cells, which are androgen sensitive and lack the TMPRSS2-ERG gene fusions. This effect was dependent on androgen receptor (AR). Importantly, androgen did not induce proximity between the TMPRSS2 and ERG loci in DU145 human prostate cancer cells, which are androgen insensitive. Further, a combination of androgen signaling and genotoxic stress that induces DNA double strand breaks results in the formation of TMPRSS2-ERG gene fusions in LNCaP cells. Interestingly, we observe that the ERG protein formed as a result of gene fusion binds to the promoter of wild type ERG and activates its transcription. The VCaP cell line that endogenously harbors the TMPRSS2-ERG gene fusion has high levels of wild type ERG. Treatment with androgens induces the expression of both the TMPRSS2-ERG and wild type ERG transcripts in VCaP cells. Lenti virus mediated stable over expression of TMPRSS2-ERG in PC3 cells results in an increase in the expression levels of wild type ERG. This auto-activation of wild type ERG is observed in about 50% of clinically localized and 25% of metastatic prostate cancers harboring the TMPRSS2-ERG gene fusions, but not in ETS negative prostate cancers. Taken together, our studies provide a mechanistic framework for the up-regulation of ERG transcription in prostate 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 2155. doi:10.1158/1538-7445.AM2011-2155
Abstract 2158: Increased expression of NuSAP gene in recurrent prostate cancer is mediated by E2F
Authors: Gulzar Zulfiqar G. , Brooks James D. 
Published: June 2012

Abstract
Increasing evidence suggests prostate cancer is over diagnosed and over treated. Identification of prognostic biomarkers would aid in treatment selection. To define prognostic biomarkers for aggressive prostate cancer, we carried out gene expression profiling of 100 prostate tumors and normal prostate tissue samples with detailed clinical annotation and a median follow up of 5 years. Using Significance Analysis of Microarrays (SAM) we identified 28 transcripts significantly associated with recurrence after radical prostatectomy, including several that have been reported previously. Several transcripts were noted to function in mitotic assembly including NuSAP, which encodes for a protein that binds DNA to the mitotic spindle. NuSAP was found highly prognostic in 3 independent datasets. To characterize the role and regulation of NuSAP in prostate cancer, we studied the expression of NuSAP in the LNCaP and PC3 human prostate cancer cell lines. Using siRNA, we found that post transcriptional silencing of the NuSAP gene severely hampers the ability of PC3 to invade and proliferate in vitro. We cloned 431bp of human NuSAP promoter to understand its regulation. Sequence analysis of the promoter region suggests that NuSAP promoter contains 2 CCAAT boxes, Sp1 box and binding sites for several proteins including proliferation master regulator E2F. E2F has previously been shown to be over-expressed during prostate cancer progression. Transient transfection of E2F and the NuSAP promoter with a luciferase reporter construct identify E2F as a powerful regulator of NuSAP expression. Promoter deletion experiments demonstrate that E2F directly binds to NuSAP promoter at nt -243 to drive expression. Deletion of the E2F binding site negates the effects of E2F on NuSAP expression. NuSAP is a novel biomarker for prostate cancer recurrence after surgery and its over-expression might be largely driven by E2F activation.
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 2158. doi:10.1158/1538-7445.AM2011-2158