bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 711: The expression of human equilibrative nucleoside transporter 1 (hENT1) is associated with overall survival in advanced biliary tract carcinoma (BTC) treated with gemcitabine
Authors: Murata Akihiro , Amano Ryousuke , Kimura Kenjiro , Yamada Nobuya , Nakata Bunzo , Nagahara Hisashi , Noda Eiji , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Yashiro Masakazu , Maeda Kiyoshi , Ohira Masaichi , Ishikawa Tetsurou , Hirakawa Kosei 
Published: August 2012

Abstract
[Introduction] The outcome of patients with unresectable and postoperative recurrent biliary tract carcinoma (BTC) is mostly miserable and most patients are possible candidates for palliative chemotherapy. Gemcitabine is a pyrimidine nucleoside analogue that is commonly used chemotherapeutic agent for advanced BTC. Gemcitabine is transported into the cell mostly by human equilibrative nucleoside transporter 1(hENT1). The hENT1 expression has been demonstrated to play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of the present study was to investigate a predictive marker for good prognosis of gemcitabine chemotherapy for unresectable and postoperative recurrent BTC. [Materials and methods] The analysis was performed on samples from 25 patients with unresectable (6 patients) and postoperative recurrent (19 patients) BTC treated with gemcitabine at the host institute between January 1997 and January 2011. The hENT1 expression levels in tumors were evaluated by immunohistochemistry. The clinical and histopathological variables were analyzed to evaluate predictive values for survival. [Results] Of the 25 tumor specimens, 18 (72%) specimens had positive hNET1 immunostaing, while 7 (28%) specimens were classified as negative. No statistical significant differences were found between the expression of hENT1 and patient characteristics (gender, age, tumor stage, lymph node stage, lymph duct invasion, vascular invasion, perineural invasion). In the univariate analysis, hENT1 expression was significantly correlated with overall survival (OS). The median OS was 15.3 versus 4.2 months, respectively in patients with positive versus negative hENT1 staining (p=0.006). As a result of multivariate analysis, hENT1 expression was useful as a predictive marker for good prognosis with significant difference (p&lt;0.001). [Conclusions] Patients with positive hENT1 expression in BTC have a significantly longer survival after gemcitabine chemotherapy than patients with negative hENT1 expression. Our results suggest that hENT1 expression in advanced BTC patients treated with gemcitabine is a prognostic predictive indicator and is useful to decide gemcitabine chemotherapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 711. doi:1538-7445.AM2012-711
Abstract 712: Parf-1A (Partner of ARF isoform 1A) promotes oxaliplatin resistance and is a new prognostic marker of survival in pancreatic ductal adenocarcinoma
Authors: Muniz Viviane P. , Zhang Xuefeng , Reed Sara M. , Tompkins Van S. , Smith Tarik , Hagen Jussara KF , Fitzgerald Matthew , Button Anna , Smith Brian , Zamba Kokou D. , Domann Frederick E. , Mezhir James J. , Weydert Jamie , Askeland Ryan A. , Quelle Dawn E. 
Published: August 2012

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an incurable malignancy with ineffective treatments and dismal median survival. The INK4a/ARF locus, which encodes the alternative reading frame (ARF) tumor suppressor, is commonly inactivated in PDAC tumors. We recently discovered Parf-1A, a novel “Partner of ARF” whose role in ARF signaling and tumorigenesis is not known. Parf-1A is highly expressed in the normal pancreas and microarray databases suggest Parf expression is altered (both up- and down-regulated) in human PDAC tumors. We generated Parf-1A specific antibodies and examined its protein levels by immunohistochemistry in PDAC tumors from patients who underwent resective surgery. Parf-1A expression was altered in 72% of tumors (33% reduced, 39% elevated) compared to adjacent normal ductal tissue. Tumors with the highest Parf-1A levels were significantly associated with poor patient outcome (median survival 6 months) while patients with undetectable Parf-1A in tumors had a dramatically extended lifespan (median survival 59 months, p=0.0037). Notably, Parf-1A knockdown in cultured PDAC cells increased the p53-independent growth inhibitory activity of ARF. Parf-1A loss also sensitized PDAC cells to oxaliplatin, a chemotherapeutic agent used in combination with gemcitabine to treat PDAC patients. This work identifies Parf-1A as a new inhibitor of ARF p53-independent activity that promotes PDAC chemoresistance in vitro and is a novel prognostic marker of survival in PDAC patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 712. doi:1538-7445.AM2012-712
Abstract 723: Detection of TIMP3 promoter hypermethylation in salivary rinse as an independent predictor of local recurrence-free survival in head and neck cancer
Authors: Sun Wenyue , Zaboli David , Wang Hao , Liu Yan , Arnaoutakis Demetri , Khan Tanbir , Khan Zubair , Koch Wayne , Califano Joseph 
Published: August 2012

Abstract
Objective: To validate a panel of methylation-based salivary rinse biomarkers (P16, CCNA1, DCC, TIMP3, MGMT, DAPK, and MINT31) previously shown to be independently associated with poor overall survival and local recurrence in a larger, separate cohort of patients with head and neck squamous cell carcinoma (HNSCC). Methods: One hundred ninety-seven patients were included. All pre-treatment saliva DNA samples were evaluated for the methylation status of the gene promoters by quantitative methylation-specific PCR. The main outcome measures were overall survival, local recurrence-free survival and disease-free survival. Results: In univariate analyses, the detection of hypermethylation of CCNA1, MGMT, and MINT31 was significantly associated with poor overall survival; the detection of hypermethylation of TIMP3 was significantly associated with local recurrence-free survival; and the detection of hypermethylation of MINT31 was significantly associated with poor disease-free survival. In multivariate analyses, detection of hypermethylation at any single marker was not predictive of overall survival in patients with HNSCC; detection of hypermethylation of TIMP3 in salivary rinse had an independent, significant association with local recurrence-free survival (Hazard Ratio, 2.51, 95% CI, 1.10 to 5.68); and none of the studied markers was significantly associated with disease-free survival. Conclusions: The detection of promoter hypermethylation of the seven genes in salivary rinse as an independent prognostic indicator of overall survival in patients with HNSCC was not validated. Detection of promoter hypermethylation of TIMP3 in pretreatment salivary rinse is independently associated with local recurrence-free survival in patients with HNSCC and may be a valuable salivary rinse biomarker for HNSCC recurrence. Such a test could potentially refine our ability to identify HNSCC patients at a high risk for recurrence.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 723. doi:1538-7445.AM2012-723
Abstract 725: eIF4E/4eBP-1 as predictive factor(s) of response to EGFR targeted drug in head and neck cancer
Authors: Vergez Sébastien , Tavergnier Christelle , Rochaix Philippe , Filleron Thomas , Vagner Stéphan , Canal Pierre R. , Etienne Chatelut , Delord Jean-Pierre , Allal Ben 
Published: August 2012

Abstract
Purpose: There is a clinical need to identify predictive markers of the response to epidermal growth factor receptor (EGFR) inhibitors in patients with head and neck squamous cell carcinoma (HNSCC). In breast cancer, the resistance to targeted therapies against HER2 implicates the reactivation of the PI3K/Akt/mTOR pathway and eIF4E overexpression. The axis eIF4E/4eBP-1 is one of the major downstream effector of the PI3K/Akt/mTOR pathway. The aim of this study was to further investigate these markers in the response to preclinical and clinical EGFR inhibitors used in HNSCC, cell lines and patients. Experimental Design: We studied the effects of cetuximab using human HNSCC cell lines (CAL33 and CAL166) on proliferation, survival pathways, eIF4E and 4eBP activities and expression by western blot or immunohistochemistry in initial biopsies of patients treated for an HNSCC with cetuximab used in combination with radiotherapy or cisplatin (n=28). Results: The HNSCC cell lines have an opposite effect under cetuximab treatment. Whereas the CAL33 are not sensitive, the CAL166 shows a moderate cytostatic effect allowing us to determine an IC20 of 5,56 +/− 0.37 µg/mL. In the CAL33 cell lines cetuximab doesn't significantly modify the 4eBP phosphorylation level. On the contrary in CAL166 cetuximab induces the inhibition of the 4eBP phosphorylation level corroborating the cytostatic effect previously observed. More over, in patients the combination Cetuximab / radiotherapy or cisplatin shows, in the initial biopsie examination in the non-responder group, a significant higher level of eIF4E. Conclusion: The couple eIF4E expression levels and/or activities appeared to be determinant to discriminate the response to the EGFR targeted inhibitor in HNSCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 725. doi:1538-7445.AM2012-725
Abstract 729: Plasma EBV DNA concentration and clearance rate as good prognostic factors for metastatic nasopharyngeal carcinoma
Authors: Hsu Cheng-Lung , Huang Shiang-Fu , Chang Kai-Ping , Wang Hung-Ming 
Published: August 2012

Abstract
Purpose: To investigate the pretreatment copy number and the clearance rate of plasma EBV DNA as novel prognostic outcome markers for metastatic nasopharyngeal carcinoma (NPC) Experimental Design: Nineteen newly diagnosed and fifty-four relapsed metastatic NPC patients were treated at outpatient department (i.v. or i.v. plus oral chemotherapy followed by local irradiation boost where applicable). Multiple blood samples were collected before and during the first 6 weeks of chemotherapy. Plasma EBV DNA concentrations and half-life values of plasma viral clearance rates, t1/2, were determined by a real-time quantitative PCR. The association between the copy number of plasma EBV DNA, t1/2, and clinical outcome were analyzed. Results: Treatment response evaluated after 3-6 months of treatment showed the best response of 18 complete responses (CR)(24.7%), 21 partial responses (PR)(28.8%) and overall response rate was 53.5%. The pretreatment plasma EBV DNA concentrations and the t1/2 of plasma EBV DNA clearance rates had significant effects on treatment response and overall survival prediction. In the chemotherapy regimen, gemcitabine plus cisplatin had better treatment outcome than cisplatin plus oral UFT and calcium folinate based regimen. Multivariate analysis revealed both pretreatment EBV DNA load and t1/2 of plasma EBV DNA clearance rates but not chemotherapy regimen had significant effects on overall survival. Conclusions: The pretreatment plasma EBV DNA copy number and their clearance rates are significant predictors for NPC treatment outcome. In low copy number group, the t1/2 in the first 6 weeks may provide the physician to choose a tailored regimen for the patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 729. doi:1538-7445.AM2012-729
Abstract 732: Overexpression of the basic helix-loop-helix protein DEC1 induces cellular senescence and is related to better survival in esophageal squamous cell carcinoma
Authors: Xu Qing , Ma Peiqing , Hu Chenfei , Chen Lechuang , Xue Liyan , Wang Zaozao , Liu Mei , Zhu Hongxia , Xu Ningzhi , Lu Ning 
Published: August 2012

Abstract
Objective: Human differentiated embryo chondrocyte expressed gene 1 (Dec1), also known as Bhlhb2/Stra13/Sharp-2, is a basic helix-loop-helix transcription factor that involves in cell proliferation, differentiation, apoptosis, and cellular senescence. In this study, the expression, function, diagnosis and prognostic impact of DEC1 in normal esophageal epithelia, esophageal squamous cell carcinoma (ESCC) and its precursor lesions (intraepithelial neoplasia) were investigated. Methods: ESCC combined with adjacent precursor tissues from 241 patients were collected to construct tissue microarray (TMA) blocks. DEC1 expression among normal epithelia, introepithelial neoplasia and ESCC was analyzed by immunohistochemistry (IHC), and the correlations between Dec1 and clinicopathological parameters were also analyzed statistically. In vitro study, DEC1 was transient transfected into ESCC cell line EC9706, and then cellular senescence was analyzed by senescence associated β-galactosidase (SA-α-Gal) activity. Fresh esophagectomy tissues from ESCC patients were embedded and fixed, and tissue sections were detected by immunohistochemistry of DEC1 and SA-α-Gal activity. Results: Compared with normal epithelia, DEC1 expression was significantly increased in intraepithelial neoplasia and DEC1 expression was significantly decreased in ESCC in comparison with intraepithelial neoplasia. DEC1 overexpression both induced cellular senescence in EC9706 cell line and correlated to more senescent cells in fresh tissue sections. Kaplan - Meier method analysis revealed that DEC1 expression levels were significantly correlated with the survival of ESCC patients after surgery. The expression levels of DEC1 were also correlated with the tumor embolus, depth of invasion of ESCC, lymph metastasis status and pTNMs. Conclusions: These results suggest that DEC1 overexpression is a protective mechanism by inducing cellular senescence in ESCC progression, and DEC1 is a potential prognostic marker of ESCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 732. doi:1538-7445.AM2012-732
Abstract 741: Sunitinib plus hormone ablation and radiation therapy for patients with high-risk localized prostate cancer: Results from a multi-institutional phase I study
Authors: Corn Paul G. , Song Danny , Heath Elisabeth , Maier Jordan , Meyn Raymond , Kuban Deborah , DiPetrillo Thomas , Mathew Paul 
Published: August 2012

Abstract
Background: Novel strategies are needed to improve the long-term outcomes of patients (pts) with high-risk prostate cancer treated with hormonal ablation and external beam radiation therapy (XRT). Preclinical data suggest that angiogenesis inhibitors normalize vasculature, reduce hypoxia, and improve the therapeutic index of XRT. To assess the feasibility of combined VEGFR/PDGFR inhibition in combination with XRT, a Phase I study with sunitinib was initiated. Methods: Seventeen men with adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or PSA &gt; 20ng/ml received initial hormonal ablation (leuprolide 22.5mg every 12 weeks + oral bicalutamide 50mg daily) for 4-8 weeks prior to oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks post XRT (prostate and proximal seminal vesicles received 75.6 Gy in 42 fractions with at least 50 Gy for the distal seminal vesicles). A 3+3 sequential dose-escalation design was employed to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose (MTD) of sunitinib. Results: The first 4 pts enrolled on 37.5 mg experienced a DLT during lead-in. *With 2 pts unexpectedly experiencing Grade 3 neutropenia and a third experiencing Grade 3 thrombocytopenia, a drug-interaction with bicalutamide was suspected. The protocol was revised to replace these pts and omit concurrent bicalutamide. Of these first 4 pts, 3 were dose reduced to 25 mg and successfully completed full treatment, while 1 pt withdrew. Of the next 3 pts subsequently enrolled at 37.5 mg, 2 of 3 on concurrent therapy have experienced DLTs (G3 diarrhea with concomitant sunitinib-induced thyrotoxicosis; G3 proctitis). Conclusions: Using a daily dosing regimen and a lead-in phase, the MTD of concurrent sunitinib, hormonal ablation and XRT was 37.5mg daily. The recommended Phase 2 dose of sunitinib for further study is 25mg daily.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 741. doi:1538-7445.AM2012-741
Abstract 742: Comparison of commercially available phosphorylated ERK antibodies for immunohistochemical biomarker analysis
Authors: Jeffers Michael , Dauffenbach Lisa M. , Pena Carol , Lathia Chetan , Bhargava Ajay , Kerfoot Christopher A. 
Published: August 2012

Abstract
Immunohistochemical (IHC) analysis of ERK phosphorylation is commonly performed on pre- and post-treatment cancer biopsies as part of pharmacodynamic biomarker assessments for targeted oncology therapeutics. The current study was performed to assess the specificity and sensitivity of four commercially-available pERK antibodies for IHC analysis, which included three monoclonal antibodies (clones 20G11, MAPK-YT, D13.14.4E) and one polyclonal antibody. To facilitate this analysis, the HEPG2 liver cancer cell line was grown in the presence or absence of inhibitors of the RAF/MEK/ERK pathway (U0126 or sorafenib). Cell lysates were prepared for analysis via Western blotting and formalin-fixed, paraffin-embedded cell pellets were prepared for analysis via IHC. All antibodies produced bands at 44 and 42 kDa, the expected molecular weights of ERK1/2, when used for Western analysis of untreated cells and demonstrated a reduction or ablation of these bands following treatment of cells with inhibitors of the RAF/MEK/ERK pathway. When examined via IHC, the monoclonals demonstrated nuclear and cytoplasmic staining in HEPG2 cells with increased sensitivity relative to the polyclonal antibody. The monoclonals also demonstrated greatly reduced staining in HEPG2 cells treated with inhibitors of the RAF/MEK/ERK pathway. These antibodies were further characterized for reactivity in human tumor specimens representing breast cancer, colon cancer, lung cancer, melanoma, and ovarian cancer. Melanoma tissues were stained with a red chromogen; all others were stained with DAB. Differences in the frequency of expression, percentage of expression, and protein localization were identified between the three monoclonals. In summary, this work has identified commercially-available antibodies that appear to be of suitable specificity and sensitivity for use in IHC assays.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 742. doi:1538-7445.AM2012-742
Abstract 752: The effect of food on the pharmacokinetics of tivozanib
Authors: Cotreau Monette M. , King Thomas , Massmanian Lisa , Strahs Andrew , Slichenmyer William , Vargo Dennis 
Published: August 2012

Abstract
Background: Tivozanib, a potent, selective, long-half-life tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, has demonstrated antitumor activity in a Phase II study in patients with renal cell carcinoma (RCC), and is currently being studied in clinical trials in patients with RCC and other solid tumors. The goal of this study was to investigate the effect of food on the pharmacokinetics (PK) of a single 1.5 mg dose of tivozanib in healthy subjects. Methods: This was a single-center, open-label, randomized, two-period, crossover Phase I trial. Subjects were admitted to the clinical research unit (CRU) 1 day before dosing, fasted ∼10 hours, and were randomized to fed (standard high-fat breakfast)/fasted or fasted/fed sequence. In each phase of the sequence, subjects received a single oral dose of tivozanib 1.5 mg with a 6-week washout period between doses. Subjects remained at the CRU for at least 48 hours post dose for blood sample collection and safety monitoring, and were assessed on an outpatient basis for up to 504 hours post dose. PK data were analyzed by non-compartmental methods. The effect of food on PK was assessed using standard criteria for bioequivalence based on the exposure parameters AUC0-α and Cmax. If the 90% confidence intervals for the fed/fasted AUC0-α and Cmax fell within the range of 80% to 125%, it was concluded that food had no effect on exposure. Results: Thirty healthy volunteers were enrolled (19M/11F; mean age 39 years [range 22-53 years]). There was no significant difference in AUC0-α of serum tivozanib between the fed and fasted states (107.4%; Table 1). Food caused a significant decrease in serum tivozanib levels vs fasted state (Cmax: 77.5%). Conclusions: These results indicate that dosing tivozanib with food decreases maximal concentrations by ∼ 23%, but does not affect overall exposure. As tivozanib is dosed chronically in oncology patients and accumulates ∼6 to 7 times single-dose levels when at steady-state, these results are not likely to affect dosing.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 752. doi:1538-7445.AM2012-752