bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4504: PF-04449913, a small molecule inhibitor of Hedgehog signaling, is effective in inhibiting tumor growth in preclinical models
Authors: Jackson-Fisher Amy J. , McMahon Melissa J. , Lam Justine , Li Chunze , Engstrom Lars D. , Tsaparikos Konstantinos , Shields David J. , Fang Douglas D. , Lira Maruja E. , Zhu Zhou , Robbins Michael D. , Schwab Richard , Munchhof Michael J. , VanArsdale Todd 
Published: June 2012

Abstract
Aberrant activation of the Hedgehog (Hh) signaling pathway has been implicated in several human cancers. Mutations in the Patched (PTCH1) gene are responsible for basal cell nevus syndrome, and are commonly found in sporadic basal cell carcinoma and in medulloblastoma. In this study we evaluated PF-04449913, an inhibitor of the Hh signaling pathway, in a Ptch1+/-p53 mouse model of medulloblastoma and in human patient derived xenograft models. Treatment of Ptch1+/-p53+/- or Ptch1+/-p53-/- medulloblastoma allografts with PF-04449913 produced potent dose-dependent inhibition of Hh pathway activity resulting in stable tumor regression. Using Gli1 transcript levels as a surrogate for Hh pathway activity, the pharmacodynamic effects of PF-04449913 were evaluated in medulloblastoma allografts following single dose and multi dose administrations of compound. PF-04449913 treated medulloblastoma allografts had reduced levels of Gli1 gene expression and down regulation of genes linked to the Hh signaling pathway. PF-04449913 was also effective when combined with a chemotherapeutic agent in a colon patient derived xenograft model and a pancreatic patient derived xenograft model, resulting in 63% and 73% tumor growth inhibition respectively. Collectively, our study demonstrates the therapeutic efficacy of a small molecule inhibitor of Hh pathway in preclinical models of multiple cancer types in either single or combination treatments.
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 4504. doi:10.1158/1538-7445.AM2011-4504
Abstract 4520: Targeting galectin-1 with PTX-008 inhibits invasion, tumor growth and metastasis in human carcinoma models
Authors: Astorgues-Xerri Lucile , De Groot Diane , Serova Maria , Huet Eric , Menashi Suzanne , Riveiro Maria E. , Cvitkovic Esteban , Noel Kay , Raymond Eric , Faivre Sandrine 
Published: June 2012

Abstract
Background. Galectin-1 belongs to a phylogenetically conserved family of carbohydrate binding lectins (galectins) that share a conserved carbohydrate recognition domain and are involved in tumor growth and metastasis. The aim of this study was to evaluate the effect of galectin-1 inhibition by shRNA or PTX-008, a topomimetic of antiangiogenic drug Anginex, on in vitro cancer cells invasion and on in vivo tumor growth and metastasis development.
Material and Methods. In vitro invasion was evaluated using Matrigel assay. Transfection of SQ20B head&neck cancer cells with galectin-1 shRNA was done using the Santa Cruz Biotechnology protocol. In xenograft studies, cells were injected s.c. into female nu/nu athymic mice either treated with vehicle or 10mg/kg PTX-008 i.p. daily for 3 weeks. Measurements were done twice a week, tumor volume was determined as 3.14(width2)/length.
Results. PTX-008 demonstrated potent antiproliferative effects on galectin-1 expressing SQ20B cells with IC50 of 3.8µM. Transfection of SQ20B cells with shGal1 (SQ-shGAL1) did not change proliferation of cells. In contrast, shGAL1 and PTX-008 significantly decreased invasion in matrigel assays. SQ20B and SQ-shGAL1 cells were injected in nude mice and SQ20B mice were treated continuously with PTX-008. Targeting galectin-1 with PTX-008 as well as inhibiting endogenous galectin-1 by shRNA inhibited significantly tumor growth in mice. Similar results with inhibition of tumor growth were obtained using A2780-1A9 ovarian xenografts treated with 5 and 10 mg/kg PTX-008. Subcutaneous injections of SQ20B in mice result in the development of multiple subcutaneous metastases. Interestingly, PTX-008 treated SQ20B-xenograft mice and mice with SQ-shGAL1 implanted tumors had respectively 80% and 50% decreased numbers of secondary tumors as compared to control groups. After treatment, tumors were isolated and analyzed for expression of galectin-1 by RT-PCR and western blot analysis. Interestingly, treatment with PTX-008 seems to inhibit the protein level of galectin-1 in SQ20B xenografts. In addition, tumors treated with PTX-008 expressed lower VEGFR2 and CXCR4 mRNA levels as compared to control tumors, suggesting antiangiogenic properties of PTX-008. The study of molecular mechanisms implicated in galectin-1-induced inhibition of tumor growth and metastasis development is in progress.
Conclusion. Our findings suggest that targeting galectin-1 by PTX-008 may be an effective approach to treat cancer patients and to prevent secondary tumor development.
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 4520. doi:10.1158/1538-7445.AM2011-4520
Abstract 4664: The effect of neoadjuvant androgen deprivation therapy on long-term outcome after radical prostatectomy
Authors: Payne Ondracek Rochelle D. , Hayn Matthew H. , Poch Michael A. , Ray Michael J. , Davis Warren , Curtis Alexandra , Kim Hyung L. , Morrison Carl D. , Marshall James R. , Mohler James L. 
Published: June 2012

Abstract
Neoadjuvant androgen deprivation therapy (NADT) was championed for men treated with radical prostatectomy (RP) for high risk prostate cancer (CaP) in the early 1990s. Although NADT improved neither surgical margin positivity nor progression-free survival, it continues to be part of some clinical trials. The effect of NADT on long term outcome was evaluated using modern aggressiveness and failure criteria among 720 patients treated with RP at Roswell Park Cancer Institute between 1993 and 2005. Among RP patients, 125 received NADT. NCCN pre-surgery risk categories were low in 36 (29%), intermediate in 54 (43%), and high or very high in 35 (28%). Clinical and pathological aggressiveness indicators included clinical Gleason sum, clinical tumor stage (2002 TNM), highest preoperative PSA, pathological Gleason sum, pathological tumor stage (2002 TNM) and surgical margin status. Ten post-RP recurrence definitions were considered: 1) at least 1 detectable PSA, 2) at least 2 detectable PSAs, 3) PSA&gt;0.2 ng/ml, 4) PSA&gt;0.4 ng/ml, 5) at least 1 post RP treatment (chemotherapy, hormone, radiation), 6) PSA doubling time &lt;9 months, 7) NCCN definition of failure, 8) AUA definition of failure, 9) development of metastatic CaP, 10) death from CaP. In bivariate analysis, men treated with NADT were 105% (p&lt;0.0001) more likely to fail using the AUA definition, 202% (p=0.004) more likely to develop metastatic CaP, and 673% (p=0.001) more likely to die of CaP. The increased risk of recurrence persisted for NADT in multivariate analysis, despite control for all clinical and pathological parameters; the table shows data for clinical and pathological parameters that have been associated with RP failure. Analysis of hazards regression for AUA failure across NCCN risk category demonstrated that NADT was detrimental for men treated with RP, regardless of any level of 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 4664. doi:10.1158/1538-7445.AM2011-4664
Abstract 4710: p53 regulates epithelial-mesenchymal transition (EMT) and stem cell properties through modulation of miRNAs
Authors: Chao Chi-Hong , Chang Chun-Ju , Xia Weiya , Yang Jer-Yen , Xiong Yan , Li Chia-Wei , Hung Mien-Chie 
Published: June 2012

Abstract
Epithelial mechenchymal transition (EMT) has recently been linked to stem cell phenotype. However, the molecular mechanism involving regulation of EMT and stemness remains elusive. Here, using unbiased genomic approaches, we discovered that tumor suppressor p53 plays a critical role in regulating both EMT and EMT-associated stem cell properties through transcriptional activation of miR-200c. p53 transactivates miR-200c through direct binding to miR-200c promoter. Loss of p53 in human mammary epithelial cells leads to decreased expression of miR-200c and activates EMT program, accompanied by increased mammary stem cell population. Re-expressing miR-200c suppresses gene targets that mediate EMT and stemness properties and thereby converts mesenchymal/stem cell-like phenotype caused by loss of p53 to differentiated epithelial cell phenotype. Furthermore, loss of p53 negatively correlates with miR-200c level but positively with increased expression of EMT and stemness markers as well as high tumor grade in a cohort of breast cancer samples. Together, this study elucidates a novel role of p53 in regulating EMT/MET and stemness/differentiation plasticity and reveals a potential therapeutic implication to suppress EMT associated-cancer stem cells through activation of p53-mediated miR-200c pathway
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 4710. doi:10.1158/1538-7445.AM2011-4710
Abstract 4834: Microarray gene expression analysis on formalin-fixed, paraffin embedded material is feasible and the resulting profiles are comparable to profiles from fresh frozen matched material
Authors: Mittempergher Lorenza , de Ronde Jorma J. , Nieuwland Marja , Kerkhoven Ron M. , Simon Iris , Wessels Lodewyk FA , Van ‘t Veer Laura J. 
Published: June 2012

Abstract
Formalin Fixed Paraffin Embedded (FFPE) samples represent a valuable resource for cancer research and clinical setting. However, the discovery and development of new cancer biomarkers often requires fresh frozen (FF) samples. In this study, we profiled, in duplicate, 20 FFPE breast cancer tissues and 20 matched FF tissues and evaluated the concordance of the gene expression results from FFPE and matched FF material using the whole Genome (WG) DASL assay. We show that clinically relevant biomarkers developed on FF samples can be applied to FFPE samples. We show that after proper normalization, all FFPE and FF pairs exhibited a high level of similarity (Pearson correlation &gt; 0.7), significantly larger than the similarity between non-paired samples. Interestingly, the probes showing the highest correlation had a higher G/C content percentage and were enriched for cell cycle genes. Predictions of gene expression signatures developed on frozen material (Intrinsic subtype, Genomic Grade Index, 70 gene prognosis signature) show a high level of concordance between FFPE and FF matched pairs. Predictions based on a 60 gene DASL list (best match with the 70 gene signature) show very high concordance with MammaPrint® results. We demonstrate that data generated from FFPE material with the DASL assay, if properly processed, are comparable to data extracted from the FF counterpart. This opens up the possibility of using both FFPE and FF material in gene expressions analyses, leading to a vast increase in the potential resources available for cancer research.
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 4834. doi:10.1158/1538-7445.AM2011-4834
Abstract 485: Hypoxia increases the expression of stem-cell markers and promotes cell invasion in prostate cancer cells
Authors: Bae Kyungmi , Dai Yao , Vieweg Johannes , Siemann Dietmar 
Published: June 2012

Abstract
Oxygen is an essential regulator of cellular metabolism, survival, and proliferation. Cellular responses to oxygen levels are monitored, in part, by the transcriptional activity of the hypoxia inducible factors (HIFs). The existence of hypoxic microenvironment is a common occurrence in many solid tumors including prostate. Previous studies from our laboratories have shown that in human prostate cancer models, cancer stem cells expressing the embryonic stem cell markers SOX2 and OCT3/4 were highly invasive and, importantly, were capable of altering their E-cadherin expression during the process of invasion. In contrast, non-tumorigenic cells which minimally express SOX2 or OCT3/4 were found to be poorly invasive. Furthermore, targeted knockdown of SOX2 or OCT3/4 markedly suppressed the invasion of prostate cancer cells, suggesting an indispensible role of these two stem cell markers in invasiveness. In the present study, we examined the impact of oxygen deprivation on cell invasiveness and stemness in both stem cell enriched and non-stem cell populations in PC3 and DU145 prostate cancer cells. Moreover, the impact of Notch signaling, which has been shown as a critical regulator of prostate cancer development, progression and metastasis, was examined. When cells were exposed to 1% oxygen for 24 h, the invasive capacity of both the stem- and non-stem cell subpopulations increased. Interestingly the non-stem cell subpopulation showed the most striking increase (&gt; 10-fold) in invasion under hypoxic conditions. The expression of several important stem cell factors, including OCT3/4, SOX2, Nanog and c-Myc, also was upregulated under hypoxia in both subpopulations. In addition, the expression of Notch1, Notch2 and their target genes Hey1, Hey2 and HeyL were increased in both subpopulations that had experienced oxygen deprivation (1% O2, 24 h). These findings suggest that although cancer stem cells per se exhibit significantly greater invasive capacity, aberrant microenvironmental conditions such as hypoxia may dramatically enhance the ability of non-stem cells to invade. Consequently, both the stem and non-stem cell subpopulations of tumors may be potential targets for the development of suitable therapeutic interventions designed to inhibit prostate cancer cell invasion.
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 485. doi:10.1158/1538-7445.AM2011-485
Abstract 4863: Pathway-focused cancer mutation profiling with somatic mutation PCR arrays
Authors: Long Samuel , You Min , Wang Liang , Jiang Xiaofang , Cheng Jie , Wang Yexun 
Published: June 2012

Abstract
Recent advances in sequencing technologies have led to significant increases in the number of known cancer somatic mutations. Translating such information into therapeutic benefits requires molecular characterization of all major human tumor types and the advent of research tools that enable interrogation of multiple mutations in multiple cancer genes simultaneously, with high accuracy and scalability. As an increasing number of important signal transduction pathways, such as the EGFR-RAS-RAF pathway, are implicated in a variety of cancers, the utility of pathway-focused mutation analysis arrays has increased. This study examined the use of real-time PCR somatic mutation detection arrays that target all known functionally important mutation sites within an entire signal transduction pathway. Each array contains 80 to 90 ARMS® primers and 5’ hydrolysis probe-based qPCR assays that allow simultaneous detection of the most frequent and functionally important mutations for multiple genes in a specific pathway.
In this study, different cancer sample types (fresh-frozen or FFPE samples from cancer cell lines and tissues) were profiled on qPCR arrays. To establish methodology validity, pyrosequencing was used as a performance benchmark. FFPE tissue sections of lung adenocarcinoma originating from different sources and with dramatically different DNA quality were tested to examine the tolerance of qPCR-based mutation detection to sample quality variation. Finally, data analysis algorithms were developed to maximize the accuracy of mutation/genotype calls.
Results indicated that allele-specific PCR amplification combined with probe detection can achieve sufficient analytical specificity and sensitivity for detecting as little as 1% mutant alleles in a background of wild type genomic DNA. In addition, the method can detect mutations in FFPE samples over a wide range of quality (i.e. with differing extents of DNA degradation), and the mutations detected were verified by pyrosequencing analysis. Interestingly, multiple mutations across different genes within the EGFR pathway, and more than one mutation within the EGFR gene, were detected in lung adenocarcinoma samples, indicating either acquisition of multiple mutations by the same cell population or sample heterogeneity.
In conclusion, it was demonstrated that somatic mutation profiling in the context of a pathway can be easily accomplished by using qPCR arrays and can be applied to biomarker development for a variety of human cancers.
Disclaimer: The applications presented here are for research use only. Not for use in diagnostic procedures.
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 4863. doi:10.1158/1538-7445.AM2011-4863
Abstract 5123: A platform for examining the molecular basis for targeted therapy selection in colon cancer
Authors: Chen Yi , Wood Elizabeth R. , Chen Yian A. , Coppola Domenico , Siegel Erin , Shibata David , Koomen John M. 
Published: June 2012

Abstract
Introduction: The quantitative evaluation of expression and post-translational modification of receptor tyrosine kinase targets in tumor tissues may enable the development of a molecular profile for the selection of targeted therapy in colon cancer.
Experimental Procedures: Colon cancer cell lines are used to develop peptide-based quantitative assays for receptor tyrosine kinase protein expression and post-translational modification using SDS-PAGE protein fractionation prior to in-gel digestions and liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM). Additional downstream signaling proteins are also investigated. The sensitivity of each assay is tested using serial dilutions of cell lysate before translation to individual frozen tissue sections, which are bookmatched to hematoxylin and eosin stained slides for histology. A classification scheme for selection of targeted therapy is devised based on the amounts of protein expression and modification detected by LC-MRM.
Data Summary: LC-MRM assays have been previously developed to monitor components of the beta catenin signaling pathway have been translated to measure protein expression in individual frozen tissue sections. Using the same methodology, LC-MRM assays have been developed for receptor tyrosine kinases (RTKs), including EGFR, Met, VEGFR, and IGF1R, as well as selected RTK interacting proteins and downstream signaling components. Implementing these novel assays in parallel with those already existing, an analysis of multiple signaling pathways in frozen section of colon tumors is conducted to enable a view of the tumor biology and assess the relevance of treatment with RTK inhibitors. Conclusions: The ability to examine cancer-related pathways in human tumors with quantitative mass spectrometry will produce improved understanding of the processes involved in tumor development and progression as well as elucidate the mechanisms of cancer cell response to chemotherapy. The coupling of quantitative proteomics with medical history and histology for comprehensive analysis of tumor tissues represents a promising step toward the ultimate goal of establishing a molecular basis for personalized medicine. This effort will demonstrate the feasibility of creating a quantitative proteomics method for tumor evaluation that could be used to translate basic science hypotheses into clinical samples and build a systems biology tool for patient assessment.
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 5123. doi:10.1158/1538-7445.AM2011-5123
Abstract 5204: PP2A- STAT3 pathway mediates suspension survival in colon cancer stem cells
Authors: Chang Chia Chien , Wang Jir-You , Hung Shih-Chieh 
Published: June 2012

Abstract
Cancer stem or initiating cells (CSCs) which share similarity with normal stem cells are a small population of cells in tumor with the abilities of self-renewal, multi- potent differentiation, and tumor initiation. CSCs also contribute to the resistance of tumor to chemotherapy or irradiation therapy. Therefore, targeting CSCs could be a hopeful way in treating cancer.
Involvement of constitutive phosphorylation of STAT3 at Tyr705 in tumorigenesis of CSCs was implicated in many types of cancers. However, the role of Ser727 phosphorylation in STAT3 activation and CSCs tumorigenesis remains unknown. In this study, we are trying to figure out whether Ser727 phosphorylation of STAT3 plays a role in the characteristic properties of colon CSCs. Efforts will also be made to shed light on the upper signaling pathway and downstream targets of Ser727 phosphorylation of STAT3.
Our preliminary data demonstrate enriched CSCs increase in the capacity for suspension survival both in vitro and in vivo. After enrichment of CSC population by spheroid culture, the phosphorylation of STAT3 at Ser727 but not Tyr705 was increased and localized at nucleus. The increase of Ser727 activation is also associated with down-regulation of PP2A activity, a serine/threonine phosphatase candidate of STAT3. We further proved PP2A formed immunoprecipitated complex with STAT3 and regulated STAT3 activation at Ser727 by treating the cells with PP2A inhibitor in normal culture or PP2A activator in spheroid culture. Overexpression of wild-type PP2A or Ser727 point mutated STAT3 reduced the survival ability in CSC. In contrast, knock down of PP2A activity or gain of function mutation at Ser727 of STAT3 increased the survival ability in nCSC. Taken together, our current data indicate enriched CSCs increased the capacity of suspension survival through the activation of PP2A-STAT3 pathway.
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 5204. doi:10.1158/1538-7445.AM2011-5204