bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 50: 2-Deoxy-2-halo-D-glucose derivatives inhibition of glycolysis in pancreatic cancer
Authors: Zielinski Rafal , Fokt Izabela , Rusin Aleksandra , Skora Stanislaw , Priebe Waldemar 
Published: July 2016

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most hypoxic and subsequently glycolytic tumors. Thus the inhibition of glycolysis appears to be an attractive therapeutic approach that should be explored.
Methods: A series of 2-deoxy analogs of D-glucose, namely, 2-deoxy-D-glucose (2-DG), 2-fluoro-D-glucose (2-FG), 2-chloro-D-glucose (2-CG), 2-bromo-D-glucose (2-BG), and 2,2-difluoro-D-glucose (2,2-diFG) were synthesized in our laboratory. The ability of 2-deoxy-2-halo-D-glucose derivatives to inhibit glycolysis in pancreatic cancer cell lines was tested using Seahorse 96 analyzer and XF Glycolysis Stress Test kit. The cellular ATP level was measured using CellTiter-Glo assay. Viability of cells cultured in normoxic and hypoxic conditions were assessed using MTS assay.
Results: 2,2-diFG and 2-FG were significantly more potent inhibitors than 2-DG of the Extracellular Acidification Rate (ECAR) of medium in oligomycin-stimulated PDAC cells (complete inhibition at &lt;12.5 mM, whereas, the 100 mM is a commonly used concentration for 2-DG in Seahorse 96 experiments). Interestingly, 2-bromo (2-BG) and 2-chloro (2-CG) analogs have a limited or no effect on glycolysis at tested concentration. Consistently, both, 2,2-diFG and 2-FG, inhibited proliferation of pancreatic cancer cell lines more potently than 2-DG in either normoxic and hypoxic conditions, with the differential effects being significantly more pronounced under hypoxia.
Conclusion: Both, 2,2-diFG and 2-FG have a superior to 2-DG ability to inhibit glycolysis in vitro and should be further evaluated in vivo in the PDAC models as a potential anticancer agents.
Citation Format: Rafal Zielinski, Izabela Fokt, Aleksandra Rusin, Stanislaw Skora, Waldemar Priebe. 2-Deoxy-2-halo-D-glucose derivatives inhibition of glycolysis in pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 50.
Abstract 5006: Docetaxel-platinum-fluorouracil (TPF) induction chemotherapy increases PD-L1 positivity and CD8+ / FOXP3+ immune infiltrates in advanced head and neck squamous cell carcinoma (HNSCC)
Authors: Leduc Charlotte , Adam Julien , Louvet Emilie , Bernard Marine , Maingot Elodie , Even Caroline , Olaussen Ken A. , Temam Stéphane , Soria Jean-Charles , Postel-Vinay Sophie 
Published: July 2016

Abstract
Introduction: Checkpoint inhibitors targeting programmed cell death-1/-ligand1 (PD-1/-L1) have demonstrated promising clinical activity in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), with overall response rates (ORR) of ≈20% in unselected patients (pts). Moreover, significant improvements have been observed when selecting pts on PD-L1 positivity, with ORR reaching 50-78%. It is therefore crucial to optimize therapeutic sequence between induction chemotherapy (Docetaxel, Platinum, Fluorouracile,TPF) and anti-PD-1/-L1 in order to maximize the number of pts that benefit from these drugs. Methods: All patients with LA-HNSCC treated at Gustave Roussy between 2006 and 2013 by induction TPF followed by surgery were considered. Only patients for who paired samples (pre and post-TPF) were available were kept for further analysis. PD-L1 expression was quantified by immunochemistry (IHC) (clone E1L3N, Cell Signaling) on a Ventana Discovery Ultra autostainer by a senior pathologist according to a validated protocol. PD-L1 IHC staining on tumor cells (TC) and tumor-infiltrating immune cells (IC) was quantified with a positivity threshold of ≥5%. The density of CD8+ and FOXP3+ lymphocytes was also assessed. Results: Out of 313 pts receiving induction TPF, 86 underwent surgery; paired samples were available for 21. Baseline PD-L1 expression was positive in only 2 and 5 samples for TC and IC respectively. An increased PD-L1 expression was observed post-TPF in 3 (14%) and 15 (71%; p = 0.0003, T-test) samples for TC and IC respectively. Tumor-infiltrating CD8+ and FOXP3+ populations also significantly increased post-TPF. Conclusion: TPF induction in LA-HNSCC increases PD-L1 positivity on tumor-infiltrating immune cells as well as CD8+ and FOXP3+ populations. This suggests that anti-PD-1/-L1 therapy might be more effective as a second-line than first-line strategy, but warrants clinical evaluation. IHC staining resultspre-TPFpost-TPFpaired samplesmedianCImedianCIT-testPD-L1 positive IC (%)2110-10100-300.0003***PD-L1 positive IC (%)2100-2010-200.08 NSCD8+ cell density (n/mm3)171194-77942653-11900.016*FoxP3 cell density (n/mm3)179126-1801774-4670.018*
Citation Format: Charlotte Leduc, Julien Adam, Emilie Louvet, Marine Bernard, Elodie Maingot, Caroline Even, Ken A. Olaussen, Stéphane Temam, Jean-Charles Soria, Sophie Postel-Vinay. Docetaxel-platinum-fluorouracil (TPF) induction chemotherapy increases PD-L1 positivity and CD8+ / FOXP3+ immune infiltrates in advanced head and neck squamous cell carcinoma (HNSCC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5006.
Abstract 5013: A meta-analysis of MSI frequency and race in colorectal cancer
Authors: Ashktorab Hassan , Ahuja Sadhna , Kannan Lakshmi , Llor Xavier , Ellis Nathan , Xicola Rosa M. , Laiyemo Adeyinka O. , Carethers John M. , Brim Hassan , Nouraie Mehdi 
Published: July 2016

Abstract
BACKGROUND: African Americans(AA) are at a higher risk of colorectal cancer (CRC) and some studies report a higher frequency of microsatellite instability (MSI) in their tumors while others report lower frequency compared to Caucasians.
AIM: To determine and evaluate the association of race and clinical factors with MSI rate through meta- analysis.
METHODS: Twenty-two studies out of 15105 (1997-2015) were evaluated after a search in different literature databases, using keywords “colorectal cancer, microsatellite instability”. We used random effect meta-analysis to calculate the MSI frequency in all studies as well as in African American and Caucasian samples. Meta-regression analysis was used to assess the univariate effect of race, gender, age, tumor location and stage on MSI rate.
RESULTS: The overall MSI frequency among CRCs was 17% (95%CI: 15%-19%, I2 = 91%). The MSI rate among racial groups were 12%, 12% and 14% in AAs, Hispanics and Caucasians respectively and was not significantly different. Sub-group analysis of studies with racial information indicates MSI OR (95% CI) of 0.78 (0.58-1.06) for AAs compared to Caucasians.
CONCLUSION: CRCs demonstrate an MSI frequency of 17%. MSI frequency differences between AAs and Caucasians were not pronounced, suggesting other factors contribute to the racial disparity. There is a large variation in MSI rate between different studies. Methodology approaches and biological sources of this variation should be investigated.
Citation Format: Hassan Ashktorab, Sadhna Ahuja, Lakshmi Kannan, Xavier Llor, Nathan Ellis, Rosa M. Xicola, Adeyinka O. Laiyemo, John M. Carethers, Hassan Brim, Mehdi Nouraie. A meta-analysis of MSI frequency and race in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5013.
Abstract 5026: EGFR copy number alterations in primary tumors, metastatic lymph nodes and recurrent tumors in areca-quid associated oral squamous cell carcinoma
Authors: Huang Shiang-Fu , Chien Huei-Tzu , Cheng Sou-De , Liao Chun-Ta , Wang Hung-Ming , Hsieh Ling-Ling 
Published: July 2016

Abstract
EGFR and downstream signaling pathway plays important roles in the tumorigenesis in oral squamous cell carcinoma (OSCC). Gene copy number alteration is one the mechanism overexpressing the EGFR protein. We previously demonstrated that EGFR gene amplification was related with lymph node metastasis, tumor invasion and perineural invasion. We appraise the hypothesis that the EGFR gene copy number alteration in the primary tumor can predict that in recurrent tumors or in lymph node metastatic foci. Of 167 primary OSCCs, fluorescence in-situ hybridization (FISH) study showed EGFR polysomy in 19 (11.4%) patients and amplification in 33 (19.8%) patients. EGFR gene amplification was related with lymph node metastasis (χ2 trend test: P = 0.018) Of 57 metastatic lymph nodes, 9 (15.8%) had EGFR polysomy and 14 (24.6%) had EGFR gene amplification. The concordance rate of EGFR gene copy number in primary tumor and lymph node metastasis was 68.4% (McNemar test: P = 0.389). Of 41 recurrent tumors, 5 (12.2%) had EGFR polysomy and 5 (12.2%) had gene amplification. The concordance rate of EGFR gene copy number between primary tumor and recurrence tumor was 65.9% (McNemar test: P = 0.510). From our results, we can predict two-thirds of the EGFR gene copy number alteration in the lymph node metastasis or the recurrent tumor from the analysis of primary tumor. In clinical scenario, for OSCC patients that the lymph nodes or the recurrent tumors are unavailable for EGFR gene copy number analysis, studies from the primary tumors could provide part of the EGFR clonal information in the metastatic or recurrent lesions.
Citation Format: Shiang-Fu Huang, Huei-Tzu Chien, Sou-De Cheng, Chun-Ta Liao, Hung-Ming Wang, Ling-Ling Hsieh. EGFR copy number alterations in primary tumors, metastatic lymph nodes and recurrent tumors in areca-quid associated oral squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5026.
Abstract 5036: Elucidating an oncogenic role of an extracellular matrix protein, Agrin, in hepatocellular carcinoma
Authors: Chakraborty Sayan , Hong Wanjin 
Published: July 2016

Abstract
Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. Despite offering poor survival advantage, broad spectrum receptor tyrosine kinase inhibitors are the sole chemotherapeutic treatments for advanced stages of HCC. Hence, there is a pressing clinical need to broaden the scope of HCC treatments through the systematic identification of suitable candidate(s) overexpressed in liver cancer. Therefore, we performed a SILAC based quantitative proteomics of cell surface proteins in HCC lines and identified proteoglycan Agrin to be overexpressed and secreted in HCC. Our systematic cell biological analysis indicated a role of Agrin in maintaining focal adhesion integrity through stimulation of focal adhesion kinase (FAK). We showed that Agrin functions in cellular migration, invasion and tumor growth. However, the exact mechanisms by which Agrin's mediates liver tumorigenesis remain unknown. The present study dissects how Agrin mediated signals from the extracellular matrix are sensed by tumor cells. Our evidences reveal that Agrin binds to its co-receptor(s) Lrp4 and subsequently activates MuSK to mediate oncogenic effects through activating focal adhesions. Additionally, integrins and focal adhesions collaborate closely with Agrin in communicating ECM signals to intracellular components in multiple HCC cell lines, thereby stimulating their invasive, migratory and growth capabilities. More importantly, Lrp4-MuSK as well as integrin-FAK pathways are crucial downstream signaling axes of Agrin's functions in liver tumorigenesis. The signal transduction network initiated by Agrin activates the oncogenic program in liver by negatively regulating tumor suppressor pathways. These novel insights will have profound impact on the possibility of targeting Agrin mediated oncogenesis in HCC.
Citation Format: Sayan Chakraborty, Wanjin Hong. Elucidating an oncogenic role of an extracellular matrix protein, Agrin, in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5036.
Abstract 5037: Upregulated superoxide dismutase 2 by specificity protein 1 mediates temozolomide resistance in glioma stem cells
Authors: Chuang Jian-Ying , Liu Jr-Jiun , Chou Shao-Wen , Chang Wen-Chang , Chang Kwang-Yu 
Published: July 2016

Abstract
The resisitant mechanism of glioblastoma mutliforme (GBM) to the standard chemotherapy temozolomide (TMZ) can be attributed to methylguanine methyltransferase (MGMT) expression in only half of the clinical cases. For the other half, it is not fully understood. To elucidate the mechanism, MGMT-negative GBM cell lines, U87MG and A172, were used to develop the TMZ-resistant variants. The variants showed reduced reactive oxygen species (ROS) accumulation by TMZ treatment comparing to the parental one. Further analysis of the cells revealed enhanced expression of superoxide dismutases 2 (SOD2), an antioxidative enzyme, as well as the stem cell-like properties. The protein was shown to associate with glioma stem cells (GSC). Notably, inhibition of SOD2 by diethyldithiocarbamate attenuated the stemness properties and the viability of the resistant variants. Further investigation of the promotor binding study suggested specificity protein 1 (Sp1) as the key factor of the SOD2 response. Moreover, Sp1 expression was even enhanced in the spheroid cells and the TMZ-resistant U87MG cell line. Conversely, treatment with Sp1 inhibitor mithramycin A attenuates SOD2 expression and the stemness properties of the resistant variants. In summary, our results suggested a novel role of SOD2 in TMZ resistant mechanism of GBM. Further study of Sp1-SOD2 pathway as a therapeutic target to restore susceptibility of chemotherapy is therefore warranted.
Citation Format: Jian-Ying Chuang, Jr-Jiun Liu, Shao-Wen Chou, Wen-Chang Chang, Kwang-Yu Chang. Upregulated superoxide dismutase 2 by specificity protein 1 mediates temozolomide resistance in glioma stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5037.
Abstract 5039: Co-targeting polo-like kinase 1(Plk1) and the Wnt/β-catenin signaling pathway in castration-resistant prostate cancer
Authors: Li Jie , Liu Xiaoqi 
Published: July 2016

Abstract
The Wnt/β-catenin signaling pathway has been identified as one of the predominantly upregulated pathways in castration-resistant prostate cancer (CRPC). However, whether targeting the β-catenin pathway will prove effective as a CRPC treatment remains unknown. Polo-like kinase 1 (Plk1) is a critical regulator in many cell cycle events and is significantly elevated upon castration of mice carrying xenograft prostate tumors. Indeed, inhibition of Plk1 has been shown to inhibit tumor growth in several in vivo studies. Here, we show that Plk1 is a negative regulator of Wnt/β-catenin signaling. Plk1 inhibition or depletion enhances the level of cytosolic and nuclear β-catenin in human prostate cancer cells. Furthermore, inhibition of Wnt/β-catenin signaling significantly potentiates the anti-neoplastic activity of the Plk1 inhibitor BI2536 in both cultured prostate cancer cells and CRPC xenograft tumors. Mechanistically, Axin2, a negative regulator of the β-catenin pathway, serves as a substrate of Plk1 and Plk1 phosphorylation of Axin2 facilitates the degradation of β-catenin by enhancing the binding between GSK3β and β-catenin. Plk1 phosphorylated Axin2 also exhibits resistance to Cdc20-mediated degradation. Overall, this study identifies a novel Plk1-Wnt signaling axis in prostate cancer, offering a promising new therapeutic option to treat CRPC.
Citation Format: Jie Li, Xiaoqi Liu. Co-targeting polo-like kinase 1(Plk1) and the Wnt/β-catenin signaling pathway in castration-resistant prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5039.
Abstract 504: Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are superior to CA 15-3 in predicting tumor burden, patients response to treatment and overall survival (OS) rates in metastatic breast cancer patients from Egypt
Authors: Zekri Abdel-Rahman N. , Bahnassy Abeer A. 
Published: July 2016

Abstract
Background: Monitoring of tumor burden in patients with metastatic breast cancer (mBC) is crucial to determine response to treatment. In addition to radiological procedures and serological biomarkers, circulating, tumor cells (CTCs) are now used to assess the tumor burden and patients’ response to treatment. The circulating cell-free tumor DNA (ctDNA) harboring tumor-specific aberrations has not been properly assessed yet.
Methods: 100 Egyptian patients with locally mBC were assessed for CA 15-3 levels, CTCs number by flowcytometry (FCM) confirmed by RT-PCR (CK and mammaglobin expression), and for ctDNA. The results of the three techniques were compared to the radiographic imaging of tumors, patients response to treatment and overall survival (OS) rates. Paraffin blocks for 40 tumor samples, obtained from the studied patients (20 non-responders and 20 responders) were used to detect p53 gene mutations exons 5-9. CA 15-3 levels and CTC numbers were measured at the same time intervals.
Results: Somatic mutations of p53 were detected in 23/40 (57.5%) sequenced tumors. ctDNA showing the identified mutations in tumor samples, was detected in 78 cases (78%) with high dynamic range. CTCs&gt;4/7.5ml blood were present in 57 out of the 78 (73.1%) ctDNA positive cases, and CA 15-3 was detected in 30 (38.5%) cases. Changes in ctDNA levels and CTCs&gt;4 correlated significantly with the tumor burden (p = 0.034), patients response to treatment (p&lt;0.01), and lower OS rates (p = 0.034&p = 0.01; respectively). CTCs number and ctDNA levels showed higher correlation with changes in tumor burden, compared to CA 15-3 (p&lt;0.001 versus p = 0.046). However, ctDNA provided the earliest measure of treatment response in most of the patients (53%).
Conclusions: ctDNA is an informative, highly sensitive and specific biomarker that could be used to monitor tumor burden in mBC. Together with enumeration of CTCs they can predict tumor response and OS in mBC patients with high accuracy.
Citation Format: Abdel-Rahman N. Zekri, Abeer A. Bahnassy. Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are superior to CA 15-3 in predicting tumor burden, patients response to treatment and overall survival (OS) rates in metastatic breast cancer patients from Egypt. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 504.
Abstract 5046: High-throughput chemical screening for sensitization of bladder cancer to gemcitabine and cisplatin chemotherapy
Authors: Kita Yuki , Kobayashi Takashi , Masuda Norihiko , Sawada Atsuro , Matsui Yoshiyuki , Inoue Takahiro , Kamba Tomomi , Ogawa Osamu 
Published: July 2016

Abstract
Background
Gemcitabine and cisplatin chemotherapy (GC) is the current standard regimen for locally advanced and metastatic bladder cancer (BC). Despite a relatively high initial response rate, some cases do not regress (intrinsic resistance) and the remaining cases often show regrowth after initial shrinkage (acquired resistance). To identify novel therapeutic agents for overcoming these resistances, we applied a high-throughput screening of chemicals administered in combination with GC.
Methods and Findings
As a high-throughput screening, 2100 compounds were administered alone or in combination with GC to human BC cell lines (J82, UMUC-3). Cell viability was determined after 3-day incubation and chemicals that enhanced inhibitory effect of GC were screened. The initial screening identified 26 compounds and further validation narrowed them into the most synergistic agent disulfiram (DSF), an FDA-approved drug for alcoholism. Combination index assay showed synergistic effects of DSF with cisplatin but not with gemcitabine in J82, UMUC-3, T24, HT1197 and HT1376 cells. Co-administration of DSF significantly enhanced apoptosis by GC treatment in UMUC-3 and T24 cells, with significant increase of reactive oxygen species (ROS) production. DSF-induced apoptosis was attenuated in the presence of N-acetyl L-cysteine and Trolox, ROS scavengers. Use of DSF in combination with GC (GCD) significantly inhibited tumor growth of UMUC-3 subcutaneous xenograft on athymic mice (by 39% compared with GC alone, p = 0.02). GCD regimen was as tolerable as GC and no significant differences were observed in body weight of treated mice between the two regimen.
Conclusion
Repositioning of DSF to a chemotherapy sensitizer is a promising treatment strategy, which can be translated rapidly in the future.
Citation Format: Yuki Kita, Takashi Kobayashi, Norihiko Masuda, Atsuro Sawada, Yoshiyuki Matsui, Takahiro Inoue, Tomomi Kamba, Osamu Ogawa. High-throughput chemical screening for sensitization of bladder cancer to gemcitabine and cisplatin chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5046.
Abstract 5051: Docosahexaenoic acid inhibits cancer cell invasion and migration by modifying focal adhesion complex structure and signaling
Authors: Mouradian Michael , Bains Palvinder K. , Pardini Ronald S. 
Published: July 2016

Abstract
The extracellular matrix (ECM) is responsible for the regulation of many cellular processes, including survival, proliferation, migration and invasion. Cellular-ECM contact induces a coordinated process recruiting functional protein complexes, consisting of scaffold, adapter, linking and docking proteins, to form focal adhesion (FA) structures. Once formed, FA complexes then recruit signaling proteins to activate downstream cellular pathways. Aberrations in FA structure and signaling have shown to contribute to cancer initiation, progression and cellular motility. Studies investigating the molecular mechanisms accounting for FA structure and function in cancer cells have demonstrated unique growth behavior and migratory properties in vitro. While docosahexaenoic acid (DHA), an omega-3 PUFA, has been shown to inhibit growth of a number of cancer cell lines, the effects of DHA on FA dynamics and signaling have not been investigated. In the present study, we show that DHA induced changes in the morphological growth phenotype in cancer cell lines grown in Matrigel™. DHA treatment also inhibited planar cell movement (cell migration) and amoeboid motility (invasion) in breast and lung cancer cell lines. Associated with the observed morphological changes and inhibited growth, were changes in the expression of a number of proteins involved in the FA complex. Upon further characterization, cell line specific changes in protein expression levels and protein localization of FAK, e-cadherin, paxillin and vinculin were observed with DHA treatment, which suggests that DHA is modifying FA complex structure. Additionally, changes in the phosphorylation patterns of major signaling pathways associated with the FA complex, like EGFR, ERK and c-Myc, were also observed with DHA treatment. Overall, these results provide new insight into FA activation and signaling and demonstrate a new mechanism for DHA treatment in cancer.
Citation Format: Michael Mouradian, Palvinder K. Bains, Ronald S. Pardini. Docosahexaenoic acid inhibits cancer cell invasion and migration by modifying focal adhesion complex structure and signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5051.