bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 718: microRNA-29a* is a predictor for early recurrence hepatitis B virus-related hepatocellular carcinoma after surgical resection
Authors: Zhu Hai-Tao , Dong Qiong-Zhu , Sheng Yuan-Yuan , Wei Jin-Wang , Wang Guan , Zhou Hai-Jun , Ren Ning , Jia Hu-Liang , Ye Qing-Hai , Qin Lun-Xiu 
Published: August 2012

Abstract
Purpose: Early tumor recurrence after liver resection for hepatocellular carcinoma (HCC) was mainly due to intrahepatic tumor spreading. In this study, we set out to identify specific microRNA (miRNA) which might be used in predicting the possibility of early recurrence after HCC resection. Experimental Design: Taqman low density arrays were used to detect the miRNA expression levels in both the microdissected tumorous and adjacent non-tumorous liver tissues from 20 HCC patients. Quantitative real-time PCR (qRT-PCR) was used to verify the findings in 106 patients, and to develop a predictive assay. The identified miRNAs were further validated in an independent cohort of 112 patients. Results: Thirty seven selected miRNAs were validated in 106 HCC patients using qRT-PCR. A significant association was found between miR-29a* level in HCC tissues and early recurrence (P=0.0002). This association was further confirmed in the independent testing set of 112 patients (P=0.0154), in which miR-29a* level was significantly associated with both time to tumor recurrence (TTR) (P=0.0015) and overall survival (OS) (P=0.0079) of patients. In the univariate and multivariate analyses, miR-29a* was identified as an independent factor for TTR, particularly for those patients with early stage of HCC. The sensitivity and specificity of miR-29a* for the prediction of early HCC recurrence in an independent blinded validation set reached 74.2% and 68.2%, respectively. Conclusion: MiR-29a* might be a useful marker for prediction of early recurrence of HCC, particularly for those with early stage of HCC.
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 718. doi:1538-7445.AM2012-718
Abstract 72: Amino terminus of SEPT9_i1 impacts cellular localization: Implications for mammary tumorigenesis
Authors: Stanbery Laura , Petty Elizabeth M. , Merajver Sofia D. 
Published: August 2012

Abstract
Septins were first discovered in Saccharomyces cerevisiae as proteins essential for faithful cell division. They are highly conserved and found in all eukaryotes with the exception of plants. One septin, SEPT9, was cloned from a region of allelic imbalance in breast and ovarian cancers on chromosome 17q25. Further analysis showed that SEPT9 encoded multiple protein isoforms. Retroviral expression of one isoform, SEPT9_i1, promoted oncogenic phenotypes including, increased cell proliferation, invasion, motility, and genomic instability in mammary epithelial cells. In addition, abnormal nuclear localization of SEPT9_i1 was observed. SEPT9_i1 is highly expressed in many cancers including, breast, ovarian, prostate, and head and neck. SEPT9_i1 differs from other SEPT9 isoforms by 25 unique amino acids at the N terminus. SEPT9_i3, which lacks these 25 amino acids, does not exhibit the same pro-oncogenic phenotypes associated with SEPT9_i1. The goal of this study is to determine the functional relevance of these amino acids with respect to cellular localization as well as phenotypes related to mammary tumorigenesis and metastasis. First, bioinformatic analysis revealed a bipartite nuclear localization signal within the 25 unique amino acids but no other recognized functional domains. To determine the effects of these 25 amino acids on nuclear localization, FLAG-tagged deletion (ΔN)-SEPT9_i1, full-length (FL) -SEPT9_i1, and empty vector control constructs were transiently transfected into two immortalized human mammary epithelial cell lines, HME and MCF-10a. Immunofluorescence analyses of FL-SEPT9_i1 and ΔN-SEPT9_i1 localization revealed a dramatic decrease in the amount of SEPT9_i1 localized to the nucleus in the ΔN-SEPT9_i1 versus FL- SEPT9_i1 lines. Stably expressing FL-SEPT9_i1 and ΔN-SEPT9_i1 HS578t cell lines were also generated using nucleofection for examination of the effects of ΔN-SEPT9_i1 on cellular phenotypes including cell proliferation, cell motility and invasion. We present data indicating that the deletion of the N terminal 25 amino acids decreases cell motility and invasion as compared to SEPT9_i1 in HS578t cells. In addition, we show increased cell proliferation in cells expressing ΔN-SEPT9_i1 as compared to both EV and SEPT9_i1. To date our results implicate an oncogenic role for high SEPT9_i1 in mammary tumorigenesis where the unique 25 amino acids of SEPT9_i1 may impact tumorigenesis. Further investigation could provide valuable insight into developing targeted chemotherapeutic agents.
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 72. doi:1538-7445.AM2012-72
Abstract 73: The transfection of high mobility group protein AT-hook 1 (HMGA1) is associated with the development of androgen independency in prostate cancer cells
Authors: Takaha Natsuki , Takeuchi Ichiro , Kimura Yasunori , Iwata Tsuyoshi , Nakamura Terukazu , Hongo Fumiya , Mikami Kazuya , Kamoi Kazumi , Okihara Koji , Kawauchi Akihiro , Miki Tsuneharu 
Published: August 2012

Abstract
The level of HMGA1 is low in androgen-dependent prostate cancer cell line (LNCaP), but is high in androgen-independent prostate cancer cell lines (DU145, PC-3). We have reported that the level of HMGA1 expression in prostate cancer cells is correlated with the extent of chromosomal aberrations (Can Res, 2002) and that transfection of HMGA1 into prostate cancer cell lines induces unbalanced chromosomal rearrangement and expression of matrix metalloproteinase 2 (Prostate, 2004). This suggests that HMGA1 is a strong candidate gene playing a potential role in the progression of prostate cancer. These findings have prompted us to evaluate the effect of HMGA1 on androgen independency, which is associated with the progression of prostate cancer. The androgen-dependent LNCaP cell line was induced to an androgen-independent subline (LN95) by being maintained for long term in the absence of androgen. The absence of androgen induced a 2.5-fold increase in the level of HMGA1 in the LN95 cell line. Androgen deprivation in vitro for 4 days as well as that for 8 days in vivo induced significant increase in the level of HMGA1 in parental LNCaP. On the other hand, the level of HMGA1 in normal prostate of mice 4 days and 11 days after castration as well as sham operation was almost undetectable. The cell proliferation rates of LNCaP cell transfected with HMGA1a vector (LN-H1) and LNCaP cell transfected with control empty vector (LN-EV) were determined with various concentrations (0-1nM) of dihydrotestosterone (DHT) by WST-8 assay in order to examine the effect of HMGA1 on androgen sensitivity. The expression of HMGA1 protein in LNH1 was confirmed to be 3.2-fold as high as that in LNEV. In low concentration (0-0.01 nM) of DHT, LNEV cell could not keep proliferation over day 6, while LNH1 could maintain proliferation over day 6. The cell proliferation rate at day 8 of LN-H1 grown in low concentration (0-0.01 nM) of DHT was about 2-fold higher than that of LN-EV. In contrast, both LN-H1 and LN-EV cells grew equally well in higher concentrations (0.1-1 nM) of DHT and could also keep proliferation over day6. Suppression of HMGA1 in DU145 and PC-3 by siRNA decreased cell proliferation rate and colony formation ability by 40% and 10-fold, respectively, in androgen-deprived medium. These data suggest that HMGA1 is associated with the transition of prostate cancer cells from androgen-sensitive to androgen-independent growth and plays a role in the cell growth of androgen-independent prostate cancer cells.
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 73. doi:1538-7445.AM2012-73
Abstract 730: Evaluation of micro-RNA biomarker panel on biopsies and non-invasive samples in nasopharyngeal carcinoma
Authors: ying ying Szeto Carol , KWONG Dora Lai-wan , Lee Anne , Wai-tong Ng , LEE Victor Ho-fun , Lung Maria Li 
Published: August 2012

Abstract
Nasopharyngeal carcinoma (NPC) is a prevalent malignant disease in Southeast Asia among the Chinese population. Being stable, sensitive and dysregulated in cancer, microRNAs (miRNAs) are potential biomarkers for NPC. Several screening and mechanistic studies have identified potential miRNA biomarkers from different systems, however, integrative biomarker panels including both human and EBV-encoded miRNAs are still lacking. Herein we evaluate the usefulness of a potential biomarker panel on biopsies and non-invasive samples (nasal swab and plasma) in NPC. By optimizing methodology, we can detect the expression of miRNAs in different samples (biopsies, nasal swabs, and plasma) from minimal amounts of samples. We have identified eight miRNA candidates in the literature as a testing panel and analyzed their expression levels in 20 paired tumor/normal biopsies samples. Five (EBV-mir-BART2, -BART4, -BART22, -BART7, and has-mir-34c) show significant differences in miRNA expression levels. Unbiased hierarchical clustering analysis of all eight candidates yield clusters of cases may be related to different causes and treatment outcomes of NPC. Five out of the eight miRNAs were chosen for further screening on a total of 40 paired biopsy samples to evaluate the significance of each cluster. Four (EBV-mir-BART2,-BART22, -BART7, and has-mir-34c) show significant expression (p&lt;0.05) in paired tumor/normal biopsies samples. The miRNA expression in nasal swab samples with paired biopsies was also analyzed. Expression in cell-free plasma RNAs of the miRNA candidate panel has also been examined to evaluate the usefulness of this panel as non-invasive biomarkers. Our results suggested the feasibility of utilizing a miRNA biomarker panel for diagnosis/prognosis of NPC using biopsies and of nasal swabs and plasma to minimize the invasiveness and amounts of samples needed for diagnosis. Acknowledgement: This work was supported by University Grants Council, HKSAR Area of Excellence grant AoE/M-06/08 to MLL.
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 730. doi:1538-7445.AM2012-730
Abstract 735: Metaplastic columnar lined esophagus without goblet cells show phenotypic similarities to Barrett's Esophagus
Authors: Srivastava Supriya , Liew Mei Shan , McKeon Frank , Xian Wa , Ho Khek Yu , Teh Ming 
Published: August 2012

Abstract
Aim: Barrett's esophagus (BE) is a premalignant condition, predisposing to esophageal adenocarcinoma (EAC). However, some EAC arise in columnar lined esophageal mucosa devoid of goblet cells. Therefore, the purpose of this study was to evaluate the biological properties of non-goblet columnar lined esophagus (CLE) and elucidate the relationship between BE and high grade dysplasia of esophagus (HGD). Material and Methods: Endoscopic biopsies from esophagus of 47 patients with columnar metaplasia with goblet cells (BE; n=28), columnar metaplasia with non-goblet cell (CLE; n=10), BE associated high grade dysplasia (HGD; n=9) and cardia with intestinal metaplasia (CIM; n=5) were included in the study. These groups were immunostained for, Villin (intestinal marker), CK7 (columnar epithelium marker), Claudin 3 (epithelial tight-junction marker) and MUC4 (membranous mucin). Statistical analysis between different groups was performed using the paired or unpaired t- test using SPSS v 15.0. A p value &lt;0.05 was considered significant. Results: Patients with BE, CLE and HGD showed positivity for Villin, Claudin 3 and CK7 in 79%, 93%, 54% in BE group; 60%, 100% and 80% in CLE group and 78%, 100% and 34% in HGD group respectively. In metaplastic epithelium (BE and CLE) there was no statistically significant difference in expression of these markers (p&gt;0.05). Patients with CLE without goblet cells showed immunopositive results for these markers, statistically similar to those of HGD group and also revealed significantly higher values compared to those of controls (cardia with intestinal metaplasia). MUC4 was expressed higher in 96% of BE cases as compared to 67% of HGD cases (mean, 81.85±27.74 vs 48.89±45.12). CLE without goblet cells did not express MUC4. Conclusion: Our results indicate that metaplastic columnar lined epithelium without goblet cells suggest biological properties of intestinal differentiation. It also shows that apart from BE, CLE without goblet cells may also have neoplastic potential.
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 735. doi:1538-7445.AM2012-735
Abstract 737: Hypofractionated stereotactic radiotherapy to surgical cavity after resection for brain metastasis
Authors: Yu Hsiang-Hsuan M. , Tsai Ya-Yu 
Published: August 2012

Abstract
Recurrence at resection cavity after resection for brain metastasis is high; whole brain radiotherapy (WBRT) decreases this risk but may cause neurocognitive complication. Post-operative radiosurgery to resection cavity is a new technique to decrease recurrence and spare patients from WBRT, but single high-dose fraction may potentially increase radiation-induced necrosis. Hypofractionated stereotactic radiotherapy (SRT) delivers higher radiobiological dose which may potentially provide higher local tumor control, and fractionation may lower risk of radiation-induced injury. To investigate the efficacy of post-operative hypofractionated SRT after resection of brain metastasis, we retrospectively analyzed 52 consecutive patients with brain metastasis from solid tumors who underwent surgical resection followed by SRT to the resection cavity for at least one metastasis from April 2008 to March 2011. A total of 25 to 30 Gy in 5 daily fractions over 1-week period was prescribed to the resection cavity with a margin of 2 mm expansion (median dose 28.5 Gy) between 2 to 4 weeks post-operatively. Synchronous oligometastasis, if present, was treated with radiosurgery. No patients received upfront WBRT. All patients were followed up for at least 6 months. Follow-up was assessed using clinical evaluation and MR imaging every 2 to 3 months. The radiographic end point was local tumor control at resection cavity. Preliminary analyses showed the actuarial local control rate of 86% at 12 months at the resection site. For those with synchronous brain metastasis, the rates of local control at resection cavity and oligometastases were not statistically significantly different (p=0.4). Approximately 30% of the patients developed distant brain recurrence during follow-up, and 70% of these patients received salvage radiosurgery while the rest received WBRT. None of the patient developed radiation-induced injury at the resection site. Multivariate analysis showed that number of metastasis was associated with higher rate of distant brain recurrence. Hypofractionated SRT appears to be safe and effective in preventing recurrence at resection cavity following surgical resection of brain metastasis and may spare many patients from WBRT and its adverse effects.
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 737. doi:1538-7445.AM2012-737
Abstract 738: Re-irradiation for recurrent malignant glioma by boron neutron capture therapy
Authors: Kawabata Shinji , Miyatake Shin-Ichi , Hiramatsu Ryo , Kuroiwa Toshihiko , Ono Koji 
Published: August 2012

Abstract
OBJECTIVE: Boron neutron capture therapy (BNCT) is based upon the nuclear reaction that occur when non-radioactive boron-10 (10B) is irradiated with low energy neutrons to produce high energy a particles (10B[n, alpha] 7Li). In order for BNCT to be successful, a sufficient amount of 10B and neutrons must be delivered to the tumor. We have applied tumor selective particle radiation known as boron neutron capture therapy (BNCT) to malignant brain tumors. As there has been no standard treatment for recurrent gliomas so far, it has been difficult to evaluate the results of BNCT for recurrent malignant gliomas. Here we introduce the survival benefit of BNCT for recurrent malignant glioma patients, with special reference to new RPA classification recurrent malignant gliomas advocated by New Approaches to Brain Tumor Therapy CNS Consortium (NABTT, JCO 2007). METHODS: Since 2002, we have treated 27 cases of recurrent malignant gliomas with BNCT. All cases had been treated by standard treatment including radiotherapy mainly by XRT prior to BNCT. After BNCT, patients were followed by MRI and F-BPA (amino acid)-PET. Cause of death was estimated by these modalities. Also overall survival was evaluated with special reference to RPA classes advocated by NABTT as above. RESULTS: All cases showed radiographical improvement at once. The median survival time (MST) of BNCT-treated recurrent gliomas was 10 months, while that of total NABTT cases (N=333) was 7 months. MST of NABTT RPA classes were 25.7, 17.2, 3.8, 10.4, 5.6, 6.4 and 4.9 months for classes 1 to 7, respectively. The MST of BNCT-treated cases were 33, 24, 10, 9, 9, 12 and 11, for classes 1 to 7, respectively. BNCT showed good survival benefit especially for the most poor prognostic group (RPA class 3+7) from 4.4 months (NABTT) to 9.6 months. Conclusion: BNCT could prolong the survival of patients with recurrent gliomas not only for the good prognosis group but also for the poor prognosis group. Some of the prognostic factors of malignant glioma, such as KPS, tumor location, extent of surgery, are not independent factor each other. BNCT seems to have the survival benefits for such situations due to its tumor cell selectivity.
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 738. doi:1538-7445.AM2012-738
Abstract 756: Pharmacokinetics of curcumin and curcumin O-glucuronide in healthy volunteers characterized by liquid chromatography-tandem mass spectrometry
Authors: Liu Zhongfa , Chen Wei , Fan-Havard Patty , Yee Lisa D. , Mo Xiao-Kui , Stoner Gary D. , Chan Kenneth K. 
Published: August 2012

Abstract
Purpose: To develop and validate a liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for simultaneous quantification of curcumin and curcumin O-glucuronide (COG) in human plasma, and to characterize the pharmacokinetics (PK) of curcumin and COG in healthy volunteers after separate oral administrations of Curcumin C3 Complex (CC3C) and nano-emulsion Curcumin (NEC) using this method. Methods: The study was conducted at The Ohio State University (OSU) with the approval of the OSU Institutional Review Board. CC3C and NEC were administered orally to four healthy volunteers and plasma levels of curcumin and COG were determined by a validated LC-MS/MS method. The pharmacokinetic parameters were calculated using WinNonlin computer software. Clinical safety assessment included vital signs and biochemical measurement on the day of each PK study and three weeks following each PK study to monitor potential toxicity. A mixed effect model was used for comparing the concentration of curcumin or COG at each time point after the oral consumption of CC3C or NEC across each donor using SAS 9.2 software. Results: An LC-MS/MS method for simultaneous quantification of curcumin and COG in human plasma with the lower limit of quantification of 2 ng/mL was established. The within-day and between-day validation parameters were consistent with the Food and Drug Administration's (FDA) criteria for Good Laboratory Practice analytical methods. A cross-over pharmacokinetic study in the four healthy volunteers revealed that 2g NEC delivered much higher plasma concentrations of free curcumin (1.5-8.0 ng/mL vs. non-detectable, p&lt;0.001, paired t-test) and COG (550-3300 ng/mL vs. 3.0-167 ng/mL, p&lt;0.05, paired t-test) when compared to 4g of CC3C. The total drug exposure of curcumin and COG from NEC in human volunteers is 26 to 350-fold higher than that of CC3C. No adverse events were noted following administrations of CC3C and NEC. No abnormalities were noted on the hematologic, clinical chemistry, and metabolic profiles at prescreening, and at 3 weeks following CC3C and NEC administration. Conclusion: NEC represents a novel formulation of curcumin with enhanced oral absorption of curcumin and is worthy of evaluation for future clinical applications. Supported by NIH-NCI-R21 CA135478 [ZL], UL1RR025755 [NCRR] and the BioMedical Mass Spectrometry Laboratory [KC & ZL].
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 756. doi:1538-7445.AM2012-756
Abstract 764: Multiple testing in a phase II trial design for the detection of tumor subtypes
Authors: Roberts John D. , Ramakrishnan Viswanathan 
Published: August 2012

Abstract
Tumor subtypes may be especially responsive to a particular treatment. Phase II designs that incorporate tumor subtypes typically require prospective tumor subtyping and stratified patient enrollment. These features are cumbersome, discourage patient and investigator participation, and select for patients with relatively indolent disease who can wait for subtyping results. Previously we described a two stage phase II design that permits tumor subtyping at the end of stage 1 and that does not require stratified enrollment (Clin Cancer Res 2011;17:5538). In this design results from stage 1 are used to select an appropriate stage 2 objective. The stage 2 objective may be either to estimate the response rate of either the tumor or a subtype or a formal test of the hypothesis that the response rate for a subtype is greater than the overall response rate. Previously, although our design accommodated multiple subtypes in stage 1, it allowed further testing of only a single subtype in stage 2. Here we expand upon the previous design by describing a method to evaluate multiple tumor subtypes in stage 2 with appropriate adjustments for multiple testing. As there are practical limits on sample size, these adjustments tend to reduce power. We identify strategies to limit loss of power by taking advantage of tumor biology. For example, when tumor subtypes are mutually exclusive or nested, some comparisons can be made without further “alpha spending”. We explore the promise of our approach for the efficient identification of clinically significant tumor subtypes more responsive to a specific targeted therapy.
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 764. doi:1538-7445.AM2012-764