bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1853: Piwi-like 1 and -4 gene transcript levels are associated with clinicopathological parameters in renal cell carcinomas
Authors: Al-Janabi Omar , Wach Sven , Nolte Elke , Weigelt Katrin , Rau Tilman T. , Stöhr Christine , Legal Wolfgang , Schick Stefan , Greither Thomas , Hartmann Arndt , Wullich Bernd , Taubert Helge W. 
Published: May 2015

Abstract
Background: Piwi-like gene family members (Piwil 1-4) are considered stem cell-associated genes/proteins. These are expressed predominantly in germline cells, but are re-expressed in different tumors. Piwil 1-4 gene expression has not previously been studied and correlated with clinicopathological parameters in renal cell carcinomas (RCC).
Material and Methods: The Piwil 1-4 transcript levels were analyzed by quantitative real-time PCR in 74 clear cell RCC (ccRCC) tissues and corresponding normal tissues.
Results: The transcript levels of Piwil 1, 2 and 4 were strongly and significantly correlated with each other, but not with Piwil 3, in both the tumor tissues and the normal tissues (P &lt; 0.001; Spearman's rank test). Piwil 4 gene expression was significantly higher in the ccRCC tissues than in the corresponding normal renal tissues (P &lt; 0.001; Wilcoxon signed-rank test). When the ccRCC patient cohort was divided according to the median Piwil 1-4 expression into low and high-expression groups and according to age into younger (≤ 64 years) and older patient groups (&gt;64 years), the younger patients displayed significantly higher levels of Piwil 1 mRNA in comparison to the older patients (P = 0.010; Fisher's exact test). Interestingly, Piwil 1 expression was left-right polarized in the normal tissues but not in the tumor tissues (P = 0.0005; Fisher's exact test).
Conclusions: Altogether, associations were determined between the Piwi-like family member expression levels and clinicopathological parameters of ccRCC, suggesting a potential role for these genes/proteins in ccRCC diagnostics and tumorigenesis, as well as in renal tissue embryology.
Citation Format: Omar Al-Janabi, Sven Wach, Elke Nolte, Katrin Weigelt, Tilman T. Rau, Christine Stöhr, Wolfgang Legal, Stefan Schick, Thomas Greither, Arndt Hartmann, Bernd Wullich, Helge W. Taubert. Piwi-like 1 and -4 gene transcript levels are associated with clinicopathological parameters in renal cell carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1853. doi:10.1158/1538-7445.AM2014-1853
Abstract 1863: Androgen receptor CAG repeat length and TMPRSS2:ETS prostate cancer risk: results from the Prostate Cancer Prevention Trial
Authors: Price Douglas K. , Chau Cindy H. , Figg William D. , Till Catherine A. , Goodman Phyllis J. , Cho Yonggon , Garcia Marileila , Reichardt Juergen , Tangen Catherine M. , Leach Robin J. , Bokhoven Adrie van , Kristal Alan R. , Thompson Ian M. , Lucia M Scott 
Published: May 2015

Abstract
Recent evidence suggests that genetic variations within the androgen receptor (AR) may influence the formation of TMPRSS2:ETS gene fusions, which are detected in more than half of all prostate cancers. We investigated the association between the length of the polymorphic trinucleotide CAG microsatellite repeats in exon 1 of the AR gene and risk of prostate cancer containing these fusion genes. This nested case-control study came from subjects enrolled in the Prostate Cancer Prevention Trial and included 195 biopsy-proven prostate cancer cases with known TMPRSS2:ETS status and 1344 matched controls. There was no association between CAG repeat length and risk of TMPRSS2:ETS-positive (OR=0.97, 95% CI, 0.91-1.04) or TMPRSS2:ETS-negative prostate cancer (OR=1.04, 95% CI, 0.97-1.10) and in patients with low- or high-grade disease. Our findings suggested that AR CAG repeats are not associated with TMPRSS2:ETS formation in prostate cancer.
Citation Format: Douglas K. Price, Cindy H. Chau, William D. Figg, Catherine A. Till, Phyllis J. Goodman, Yonggon Cho, Marileila Garcia, Juergen Reichardt, Catherine M. Tangen, Robin J. Leach, Adrie van Bokhoven, Alan R. Kristal, Ian M. Thompson, M Scott Lucia. Androgen receptor CAG repeat length and TMPRSS2:ETS prostate cancer risk: results from the Prostate Cancer Prevention Trial. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1863. doi:10.1158/1538-7445.AM2014-1863
Abstract 1866: Detection of early-stage lung cancer using a novel ELISA for thymidine kinase 1
Authors: Ramsden Madison K. , Alegre Melissa M. , Weyant Michael J. , Bennett Daine T. , Yu Jessica A. , Elnaggar Atif , Robison Richard A. , O'Neill Kim L. 
Published: May 2015

Abstract
Lung cancer is the number one cause of cancer mortality and early detection will increase the survival of this disease. Thymidine kinase 1 (TK1) is a biomarker indicative of cell proliferation that is elevated in numerous malignancies including lung cancer. TK1 has been found to be elevated early in the development of lung cancer and therefore is an ideal target as an early detection biomarker. We have developed an enzyme-linked immunosorbent assay (ELISA) to detect TK1 in serum. Forty patients with pulmonary nodules and 18 healthy control individuals had serum collected under standard conditions, prior to operative removal of any lesions. All serum samples were analyzed using TK1 radioassay to measure TK1 activity, and TK1 ELISA to measure TK1 concentration. TK1 was significantly elevated in all patients with confirmed lung cancer. This was true even in stage IA, where patients (n=16) had significantly higher TK1 levels than controls. The clearest cut-off was 4.9 nM with an area under the curve of 0.792 for early stage lung cancer. The corresponding sensitivity and specificity was 82.4 and 83.3, respectively. TK1 concentration was a more sensitive and accurate indicator of lung cancer than TK1 activity. Overall, TK1 is significantly elevated in serum of lung cancer patients. This TK1 ELISA is sensitive and specific for detection of lung cancer and further trials with a larger patient base can confirm the potential of this method of detection.
Citation Format: Madison K. Ramsden, Melissa M. Alegre, Michael J. Weyant, Daine T. Bennett, Jessica A. Yu, Atif Elnaggar, Richard A. Robison, Kim L. O'Neill. Detection of early-stage lung cancer using a novel ELISA for thymidine kinase 1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1866. doi:10.1158/1538-7445.AM2014-1866
Abstract 1891: Mutations in polymerase ϵ as key molecular alteration of the novel ultramutator phenotype do not define a clinically distinct entity of colorectal cancer
Authors: Stenzinger Albrecht , Volker Endris , Pfarr Nicole , Penzel Roland , Jansen Lina , Herpel Esther , Roth Wilfried , Bläker Hendrik , Chang-Claude Jenny , Brenner Hermann , Hoffmeister Michael , Weichert Wilko 
Published: May 2015

Abstract
Background: Recent molecular profiling studies reported a new class of ultramutated colorectal cancers (CRC), which are likely caused by exonuclease domain (END) mutations in DNA polymerase ϵ (POLE). However, data on the clinical implications of these biological findings as to whether these mutations in analogy to endometrial cancer define a unique CRC entity with distinct clinical outcome is entirely lacking.
Methods: We performed Sanger sequencing of the POLE END in 431 well annotated microsatellite stable (MSS) CRCs of a population-based epidemiological case-control study (DACHS). Mutation data were correlated with major epidemiological, clinical, genetic and pathological parameters including overall and disease-specific survival.
Results: In 373 out of 431 MSS CRC all exons of POLE END were analyzable. 47 mutations in the END of POLE were identifiable in 41 of these samples (11%). Besides already reported mutations affecting the codons 459, 411 and 286, we found many new mutations in exons 13 and 14 (corresponding to codons 411-491 of the END) as well as in exon 12 (corresponding to codons 268-301 of the END), which have not been reported yet. However, we found no associations of POLE END mutations with clinicopathological parameters, including sex, age, tumor location and tumor stage, CIMP, RAS and BRAF mutations. Survival analysis by cox regression revealed adjusted (for sex, age, tumor location and therapy) HRs of 1.38 and 1.44 for disease-specific and overall survival indicating slightly impaired survival of patients with mutations in POLE END, however, these differences were not statistically significant. This was also true for the subgroups of different exons, known/new, potentially damaging/non-damaging mutations and the type of mutation.
Conclusions: In contrast to endometrial cancer, somatic POLE mutations do not appear to define a clinically strongly distinct disease entity in CRC.
Citation Format: Albrecht Stenzinger, Endris Volker, Nicole Pfarr, Roland Penzel, Lina Jansen, Esther Herpel, Wilfried Roth, Hendrik Bläker, Jenny Chang-Claude, Hermann Brenner, Michael Hoffmeister, Wilko Weichert. Mutations in polymerase ϵ as key molecular alteration of the novel ultramutator phenotype do not define a clinically distinct entity of colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1891. doi:10.1158/1538-7445.AM2014-1891
Abstract 1906: FOXC1 regulates cancer stem cells properties via inducing SMO-independent Gli activation and confers anti-Hedgehog drug resistance in basal-like breast cancer
Authors: Han Bingchen , Jin Yanli , Bose Shikha , Zhang Xiao , Qu Ying , Karlan Beth Y. , Giuliano Armando E. , Cui Xiaojiang 
Published: May 2015

Abstract
Basal-like breast cancer (BLBC), an aggressive subtype of breast cancer, are usually associated with high histologic grade, high recurrence rate, short recurrence-free survival, younger patient age, poor outcome, and a propensity to metastasize to the brain and lung. So far, developing targeted therapies against BLBC still remains a great challenge. Uncovering the underlying molecular events and identify therapeutic target becomes highly urgent. Forkhead Box C1 (FOXC1), a biomarker for BLBC, is associated with poor prognosis in patients with BLBC. Here, we found that FOXC1 increases cancer stem cells (CSCs) properties in BLBC cells in vitro and in vivo. FOXC1 activates SMO-independent non-canonical Hedgehog (Hh) signaling pathway, which mediates the effects of FOXC1 on CSCs properties in BLBC cells. Further study showed that the N-terminal of FOXC1 bind directly to the Gli2 transcription factor, which has the highest transcriptional activity in Hh signaling pathway. Here we also found that the elevated expression of FOXC1 induces anti-Hh pathway drug resistance. All of these data demonstrate a novel mechanism underlying the regulation of CSC properties and the poor prognosis of BLBC patients, and may provide new insight into anti-CSC therapy resistance. Thus, our study provides a strong rationale for developing FOXC1-targeted therapy for treating BLBC patients.
Citation Format: Bingchen Han, Yanli Jin, Shikha Bose, Xiao Zhang, Ying Qu, Beth Y. Karlan, Armando E. Giuliano, Xiaojiang Cui. FOXC1 regulates cancer stem cells properties via inducing SMO-independent Gli activation and confers anti-Hedgehog drug resistance in basal-like breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1906. doi:10.1158/1538-7445.AM2014-1906
Abstract 1913: C/EBPdelta links hypoxia and inflammation to the promotion of tumor cell stemness through inhibition of FBXW7: A molecular target for HDAC inhibitor action
Authors: Balamurugan Kuppusamy , Summers Glenn H. , Sharan Shikha , Sterneck Esta 
Published: May 2015

Abstract
Hypoxia and inflammation are linked to progression of epithelial cancers by promoting epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). A better understanding of the mechanisms by which these conditions augment tumor progression is necessary to combat metastases and treatment resistance. The transcription factor C/EBPδ promotes hypoxia adaptation and inflammatory signaling by inhibiting expression of FBXW7, which targets many oncoproteins (e.g. Notch, c-myc) and also C/EBPδ for degradation (Balamurugan et al., EMBO J, 2010; Nature Commun 2013). FBXW7 is also known to regulate self-renewal, differentiation and quiescence of neural and hematopoietic stem cells. Therefore, we hypothesized that C/EBPδ supports the development of CSCs through inhibition of FBXW7 and that this pathway has potential as therapeutic target.
We investigated the roles of C/EBPδ and FBXW7 through overexpression and silencing approaches in human breast tumor cell lines and primary mouse mammary tumors; followed by gene expression analyses and assays for stem cell-like functions under hypoxia and in response to interleukin 6 (IL-6). We found that C/EBPδ augments _ while FBXW7 inhibits _ hypoxia- and IL-6-induced formation of mammospheres, a surrogate assay for stem cell function, and expression of markers for EMT and CSCs. Furthermore, C/EBPδ was necessary for hypoxia-induced expression of IL-6, providing a link between these pathways. Indeed, silencing of C/EBPδ delayed the outgrowth of MCF-7 xenograft tumors, indicating that C/EBPδ supports CSC development.
Because C/EBPδ can interact with histone deacetylases (HDACs), we tested the effect of HDAC inhibitors (HDACi) that are in clinical trials for breast cancer (e.g. SAHA). HDACi inhibited C/EBPδ expression and induced FBXW7 expression. Furthermore, HDACi reduced mammosphere formation specifically under hypoxia, and this effect could be partially reversed by FBXW7 knockdown. These results suggest a therapeutic benefit of HDACi for breast cancer through activation of FBXW7 and inhibition of C/EBPδ followed by reduction in CSCs. Future investigations will explore drug combinations with HDACi to maximize the effectiveness of the FBXW7 tumor suppressor pathway under hypoxia and inflammatory conditions.
Citation Format: Kuppusamy Balamurugan, Glenn H. Summers, Shikha Sharan, Esta Sterneck. C/EBPdelta links hypoxia and inflammation to the promotion of tumor cell stemness through inhibition of FBXW7: A molecular target for HDAC inhibitor action. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1913. doi:10.1158/1538-7445.AM2014-1913
Abstract 1957: Slug regulates SOX9 stability in lung carcinoma and its involvement in the regulation of cancer stem cells and lung metastasis
Authors: Luanpitpong Sudjit , Wang Liying , Rojanasakul Yon 
Published: May 2015

Abstract
Most solid tumors including lung carcinoma are believed to contain cancer stem cells (CSCs) that are responsible for tumor initiation, progression, and metastasis. Understanding how CSCs are regulated at the molecular level may lead to novel strategies for cancer therapy. We have identified two proteins, Slug and SOX9, which determine the CSC state of human lung cancer epithelial cells. Inhibition of either Slug or SOX9 sufficiently blocks CSCs in human lung carcinoma cell lines, as determined by side population and tumor sphere assays, and attenuates lung metastasis in vivo in a xenograft mouse model. Coexpression of Slug and SOX9 is detected in the majority of lung tissues with advanced stage carcinoma. Here we found for the first time that Slug regulates SOX9 stability. Loss of Slug results in SOX9 degradation through ubiquitin-proteasomal pathway, and overexpression of Slug conversely prevents SOX9 degradation. Together, our results provide a direct evidence for the control of CSCs and tumor progression by Slug and SOX9, and unveil a novel role of Slug in SOX9 stabilization. These findings provide a mechanistic insight to the pathogenesis of metastasis in advanced lung carcinoma.
Citation Format: Sudjit Luanpitpong, Liying Wang, Yon Rojanasakul. Slug regulates SOX9 stability in lung carcinoma and its involvement in the regulation of cancer stem cells and lung metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1957. doi:10.1158/1538-7445.AM2014-1957
Abstract 1959: Lgr5 marks an enriched population of fetal mammary stem cells
Authors: Trejo Christy L. , Spike Ben , Wahl Geoff 
Published: May 2015

Abstract
Basal-like breast cancers have unique characteristics that may contribute to their particularly poor prognosis. These include a high degree of genomic instability, intra-tumor heterogeneity, and gene expression profiles similar to those of normal mammary stem cells. These characteristics may arise through the aberrant propagation of normal stem cells. Alternatively, mutations commonly found in this subtype may be the dominant determinant of tumor phenotype. In order to explore these possibilities, pure populations of stem cells need to be isolated and analyzed. Our lab has identified a population of fetal mammary stem cells (fMaSCs) in the mouse whose gene expression profiles show a striking enrichment for those of human basal tumors. When fMaSCs were targeted with a p53 mutation, commonly found in human basal cancer, a tumor arose within 5 weeks- the shortest latency we have observed from any cell type. This suggests that fMaSCs are particularly prone to tumorigenesis and may likely be a source of basal-like tumors in the adult. Mammary stem cell activity becomes detectable at a defined time in late embryonic development, peaks right before birth, diminishes rapidly at birth, and remains low in the adult. We have since identified Lgr5 to be highly expressed in fMaSCs at the peak of their stem cell activity. We have gone on to use it to isolate the most pure population of fMaSCs measured yet by in vitro means. When plated in 3D culture containing 2% matrigel, up to 50% of Lgr5-expressing fetal mammary cells formed correctly polarized mammospheres.
Using three independent methods, we will determine how Lgr5 expression tracks with stem cell activity throughout development and use this marker to test for the persistence of fetal-like stem cells in the adult mammary gland. We will develop comprehensive gene expression profiles from Lgr5+ cells throughout development to identify molecular correlates of the stem cell state. The relative contributions of developmental state of cell of origin or mutational status to tumor phenotype are poorly understood. We will test the capacity of stem cells at various stages of development to give rise to tumors when targeted with mutations commonly found in human basal tumors. A thorough analysis of tumors will reveal links between development, tumor initiation and progression, and provide insight into strategies to treat basal breast cancers.
Citation Format: Christy L. Trejo, Ben Spike, Geoff Wahl. Lgr5 marks an enriched population of fetal mammary stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1959. doi:10.1158/1538-7445.AM2014-1959
Abstract 1964: Masitinib antagonizes ATP-binding cassette subfamily c member 10-mediated paclitaxel resistance: a preclinical study
Authors: Kathawala Rishil , Sodani Kamlesh , Chen Kang , Patel Atish , Abuznait Alaa , Anreddy Nagaraju , Sun Yue-Li , Kaddoumi Amal , Ashby Charles R. , Chen Zhe-Sheng 
Published: May 2015

Abstract
Paclitaxel displays clinical activity against a wide variety of solid tumors. However, resistance to paclitaxel significantly attenuates the response to chemotherapy. The ABC transporter subfamily C member 10 (ABCC10), also known as multi-drug resistance protein 7 (MRP7) efflux transporter, is a major mediator of paclitaxel resistance. In this study, we show that masitinib, a small molecule stem-cell growth factor receptor (c-Kit) tyrosine kinase inhibitor, at non-toxic concentrations, significantly attenuates paclitaxel resistance in HEK293 cells transfected with ABCC10. Our in vitro studies indicated that masitinib (2.5 μM) enhanced the intracellular accumulation and decreased the efflux of paclitaxel by inhibiting the ABCC10 transport activity without altering the expression level of ABCC10 protein. Furthermore, masitinib, in combination with paclitaxel, significantly inhibited the growth of ABCC10-expressing tumors in nude athymic mice in vivo. Masitinib administration also resulted in a significant increase in the levels of paclitaxel in the plasma, tumors and lungs compared to paclitaxel alone. In conclusion, the combination of paclitaxel and masitinib could serve as a novel and useful therapeutic strategy to reverse paclitaxel resistance mediated by ABCC10.
Citation Format: Rishil Kathawala, Kamlesh Sodani, Kang Chen, Atish Patel, Alaa Abuznait, Nagaraju Anreddy, Yue-Li Sun, Amal Kaddoumi, Charles R. Ashby, Zhe-Sheng Chen. Masitinib antagonizes ATP-binding cassette subfamily c member 10-mediated paclitaxel resistance: a preclinical study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1964. doi:10.1158/1538-7445.AM2014-1964
Abstract 1967: A-803467, a sodium channel blocker, reverses ABCG2-mediated MDR
Authors: Anreddy Nagaraju 
Published: May 2015

Abstract
The ATP-binding cassette, subfamily G, isoform 2 protein (ABCG2) is a vital member of the ABC transporter superfamily, which has been involved in multidrug resistance (MDR) in cancer. Its diverse range of substrates includes many antineoplastic agents such as doxorubicin and mitoxantrone. ABCG2 expression has been significantly increased in some solid tumors and hematologic malignancies, which is correlated to poorer clinical outcomes. In addition, ABCG2 expression is a distinguishing feature of cancer stem cells, whereby this membranous transporter imparts resistance to the chemotherapeutic drugs. To enhance the chemosensitivity of cancer cells, attention has been focused on MDR modulators. In this study, we investigated the ability of sodium channel blocker, A-803467 to reverse ABCG2-mediated MDR. We found that A-803467 at non-toxic concentration could significantly increase the cellular sensitivity to ABCG2 substrates in drug-resistant cells overexpressing either wild-type or mutant ABCG2. Mechanistic studies indicated that A-803467 (7.5 μM) significantly increased the intracellular accumulation resulted from inhibition of the efflux of mitoxantrone by inhibiting the transport activity without altering expression level of ABCG2 protein. Furthermore, ATPase analysis indicates that A-803467 stimulates the ATPase activity in membranes overexpressing ABCG2. Our findings suggest that A-803467 has the potential to be used in combination with ABCG2 chemotherapeutic substrates to augment the response in drug resistant cancers.
Citation Format: Nagaraju Anreddy. A-803467, a sodium channel blocker, reverses ABCG2-mediated MDR. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1967. doi:10.1158/1538-7445.AM2014-1967