bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4389: Impact of regulatory T cell depletion on dendritic cell-tumor fusion vaccine immunotherapy
Authors: Tan Chunrui , Reddy Varun , Ding Enyu , Dannull Jens , Nair Smita , Pruitt Scott K. , Lee Walter T. 
Published: August 2012

Abstract
A promising branch of research in cancer immunotherapy is the development of vaccines comprised of dendritic cells hybridized to tumor cells by electrofusion. Studies in numerous murine models have shown the efficacy of treatment with a dendritic cell-tumor fusion vaccine; however, this is critically dependent on systemic administration of 3rd signals such as IL-12 (Interleukin-12). Translation of these findings into the clinic will be difficult due to toxicity, morbidity, and mortality associated with IL-12 administration. Thus, alternative strategies to enhance the efficacy of fusion vaccines are needed. Regulatory T cells (Tregs) are known to suppress anti-tumor immunity. Treg depletion has been demonstrated to improve tumor immunotherapy in murine tumor models as well as some phase I clinical studies. We therefore investigated whether Treg depletion with the anti-CD25 monoclonal antibody PC61 would significantly improve dendritic cell - tumor fusion immunotherapy in a murine melanoma model. Experiments were conducted using six groups of animals: no treatment (negative control), isotypic monoclonal antibody alone (Y13), Treg depletion alone (PC61), fusion vaccine with Y13 (Fusion + Y13), fusion vaccine with PC61 (Fusion + PC61), and fusion vaccine with IL-12 (Fusion + IL12; positive control). Pulmonary metastases were established through intravenous tail vein injection of 0.25x106 tumor cells (Day 0). Three days later, an injection of 0.6x106 fusion hybrids was delivered intranodally. 250 µg of Y13 or PC61 monoclonal antibodies were delivered one day prior to vaccine delivery. Starting on the day of vaccination in the IL-12 group, 0.2 µg of IL-12 was given daily for 4 days. Three weeks after tumor inoculation, mice were euthanized and the pulmonary metastases were enumerated. The median number of metastases and standard deviation [SD] per group were the following: no treatment= 204 [50]; Y13= 220 [59]; PC61= 211 [49]; fusion+Y13= 126 [67]; fusion + PC61= 72 [74]; fusion + IL12= 1 [11]. Using the Mann-Whitney U test, there was a statistically significant reduction in the number of tumor metastases between both the fusion vaccine + Y13 group and the fusion + PC61 group (P=.0397) as well as PC61 alone group and fusion + PC61 group (P=.002). This suggests that Treg depletion can significantly augment dendritic cell-tumor cell fusion melanoma immunotherapy. Our results support the development of novel therapeutic modalities that include Treg depletion, or modulation, to enhance the efficacy of dendritic cell - tumor fusion cancer immunotherapy.
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 4389. doi:1538-7445.AM2012-4389
Abstract 4488: Inflammation-related biomarkers and risk of epithelial ovarian cancer
Authors: Poole Elizabeth M. , Lee I M. , Buring Julie E. , Hankinson Susan E. , Tworoger Shelley S. 
Published: August 2012

Abstract
Introduction: Chronic inflammation caused by ovulation-related wound healing is theorized to cause ovarian carcinogenesis. We examined associations between three plasma biomarkers of inflammation, CRP, IL-6, and TNFαR-2, and risk of epithelial ovarian cancer in a nested case-control study of ovarian cancer cases and controls from the Nurses’ Health Study (NHS) and NHSII as well as in the Women's Health Study (WHS) cohort (CRP only). We further performed a meta-analysis with previously published studies of these biomarkers and ovarian cancer. Methods: Associations between quartiles of CRP, IL-6, and TNFαR-2 and risk of epithelial ovarian cancer were calculated using unconditional logistic regression (NHS/NHSII) or Cox proportional hazards regression (WHS); NHS/NHSII and WHS were combined using random effects meta-analysis. All analyses were adjusted for age, menopausal status/post-menopausal hormone use, duration of oral contraceptive use, tubal ligation, parity, and body mass index. The NHS/NHSII analyses were additionally adjusted for blood draw characteristics (fasting status, time of day and month of draw). Random effects meta-analysis was used to combine these results with previously published results. Results: In the NHS/NHSII (n=218 cases) and WHS (n=159 cases), a 59% increased ovarian cancer risk was observed in the 4th quartile of CRP compared to the 1st quartile (95% CI: 1.08-2.34). Further, CRP &gt;10mg/L compared to &lt;1 mg/L, was associated with a 2.21-fold increased ovarian cancer risk (95% CI: 1.29-3.80). In meta-analyses with previously published studies, the 3rd compared to the 1st tertile of CRP was associated with a 41% increased risk (95% CI: 1.14-1.74) (Table). There were no statistically significant associations between quartiles of IL-6 or TNFαR2 and ovarian cancer risk in the NHS/NHSII or in a meta-analysis with a previous publication. Conclusion: Our results suggest that higher levels of circulating CRP, but not IL-6 or TNFαR2, are associated with increased risk of ovarian cancer.

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 4488. doi:1538-7445.AM2012-4488
Abstract 4497: Biomarkers of HPV in head and neck squamous cell carcinoma
Authors: Liang Caihua , Marsit Carmen J. , McClean Michael D. , Nelson Heather H. , Christensen Brock C. , Haddad Robert I. , Clark John R. , Wein Richard O. , Grillone Gregory A. , Houseman E. Andres , Halec Gordana , Waterboer Tim , Pawlita Michael , Krane Jeffrey , Kelsey Karl T. 
Published: August 2012

Abstract
Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC) and patients with HPV-associated disease have a favorable prognosis. Currently there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV. We measured DNA-based and serological markers in a single population-based study to assess their associations with disease outcome and to determine the most relevant biomarker for clinical use. HPV16 serology was determined using an immunoassay for the capsid protein L1, and multiplex serology based on the capsid protein L1 and the early oncoproteins E6/E7 for 488 patients. Immunohistochemical detection of p16 expression in tumors was performed in a subset of 233 cases, and we used two different methods to assess the presence of HPV16 DNA in a subset of 179 cases’ tumors. Seropositivity for the E6 and E7 proteins (individually) was significantly associated with enhanced survival (HRE6 or HRE7=0.3, 95%CI=0.2-0.5). Neither the presence of HPV16 DNA or p16 overexpression was associated with significant enhanced overall survival (HRDNA=0.8, 95%CI=0.5-1.3; HRp16=0.8, 95%CI=0.5-1.4). However the combination of HPV positive DNA and E6/E7 serology was associated with similarly enhanced overall survival (HRDNA+/E6+/E7+=0.1, 95%CI=0.01-0.6), while E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HRDNA+/E6-/E7-=1.2, 95%CI = 0.7-2.2). Further, the combination of p16 staining and early gene seropositivity showed a favorable survival (HRp16+/E6+/E7+=0.3, 95%CI=0.1-0.9), while those who were p16 positive and early gene seronegative had significantly increased hazard of death (HRp16+/E6-/E7-=2.1, 95%CI=1.1-4.2). Determination of only HPV16 DNA status or p16 immunostaining is not an effective prognostic biomarker for HNSCC. However the combination of measurement of HPV16 DNA and p16 immunostaining with E6/E7 antibodies has high predictive clinical value, strongly suggesting that a combined biomarker approach is necessary for the assessment of the prognosis of HNSCC 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 4497. doi:1538-7445.AM2012-4497
Abstract 4511: The effect of obesity-related adipokines at diagnosis on breast cancer survival
Authors: Lee Sang-Ah , Noh Dong-Young , Choi Ji-Yeob , Ahn Sei-Hyun , Kang Deahee 
Published: August 2012

Abstract
Background: Although a number of experimental studies have suggested the effect of obesity-related adipokines in breast cancer progression, limited numbers of epidemiological studies have examined the relationship between the adipokines and breast cancer survival. Patients and methods: Preoperative serum levels of obesity-related adipokines including leptin, adiponectine and hepatocyte growth factor (HGF) were measured in 370 breast cancer patients recruited between 2004 and 2007. We examined the association between those adipokines and disease-free survival (DFS) using Cox proportional hazard regression model. Results: There was no difference in age distribution, menopausal status, BMI, PR status, tumor size, and lymph node status between survivor and recurrence or death subjects. On the other hand, the TNM stage, ER status and histological grade were observed the association with breast cancer survival. Elevated adiponectin were associated with reduced DFS of breast cancer (P for trend = 0.047) with adjustment for age, ER/PR status, histological grade, nuclear grade and TNM stage among patient with less than 4 year survival time. There was no association of leptin and HGF with the breast cancer survival. Conclusions: Our study suggests that the elevated levels of adiponectine at diagnosis are associated with breast cancer survival, but the leptin and HGF level in blood not associated.
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 4511. doi:1538-7445.AM2012-4511
Abstract 4521: Differential whole genome methylation profile in a responder and a non-responder to chemotherapy in colorectal cancer patients
Authors: Ashktorab Hassan , Tbaishat Rana , Rahi Hamed , Lee Edward , Smoot Duane T. , Ajayi Olaide , Sun Xueguang , Jia Xi-Yu , Chung Hunter , Bacon Eliza , Leavitt Ron , Brim Hassan 
Published: August 2012

Abstract
Background: Colorectal adenoma (CRA) to cancer (CRC) progression involves in epigenetic changes including DNA methylation. Here we performed whole genome Bisulfite Next-Generation sequencing (WGBSNGS) on a normal, a tubular adenoma and a tumor patients’ tissue DNA to elucidate epigenetic drivers in normal to cancer progression. Patients and Methods: Genomic DNA was isolated from fresh frozen tissues from a patient with normal colon, from a tubular adenoma lesion (&lt;0.5 cm) and from a carcinoma. A WGBSNGS at &gt;20X depth was performed on these DNA samples., Alignment, mapping and CpG methylation analyses were done. Pyrosequencing and immunohistochemistry (IHC) was used to confirm selected CpG methylation. Results: We identified 94 unique CpG sites hypermethylated in 4 novel genes in adenoma compared to normal and 180 unique CpG sites in 7 genes in cancer. Ingenuity pathway analysis (IPA) showed that the methylated genes including a novel gene ATXN7L1 were involved in WNT pathway, ubiquotlation process and cross-talk with B-catenin, in the adenoma. Three of the hypermethylated genes in cancer were, Loc100506436: a novel gene with 17 unique CpG sites (EGFR pathway, cRNA CpG site hypermethylated is part of MEK1/2), GPNMB with 7 unique CpG sites (a G protein) and TNFAIP2 with 8 unique CpG sites (its role was noted in Head and neck cancer). IHC confirmed the lack of expression in cancer. Conclusion: This work provides insight into differential CpG island methylation profiles in CRA, CRC vs. normal colon tissue and provides a window into the more complex factors, including alteration of known and novel genes as a multiple CpG methylation drivers in colorectal carcinogenesis. Investigations into the possible roles of the novel gene targets in the context of early and prognostic methylation biomarker are underway.
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 4521. doi:1538-7445.AM2012-4521
Abstract 4530: A novel blood-based method for evaluating KRAS in circulating microvesicles from colorectal cancer patients
Authors: Yeatts Kimberly , Millis Meredith , Smith Shannon , Duncan Janet , Moran Brittany , Ortiz Gerri , Little Tanya , Conrad Amber , Spetzler David B. , Pawlowksi Traci 
Published: August 2012

Abstract
Circulating microvesicles (cMV) are lipid-encapsulated bodies that are secreted from various tissues and can be detected in a number of body fluids, including plasma. Once collected from plasma, they can be exploited diagnostically for their protein and RNA signatures. Mutations in KRAS are diagnostically important for predicting response to chemotherapy and prognosis. A blood-based method of assessing KRAS mutation status would be helpful for patients with colorectal cancer (CRC). Traditional methods of KRAS detection examine the genomic DNA sequence. We developed a method to sequence exon 3 from KRAS using Pyrosequencing. The limit of detection for the assay was 0.78 ng/uL of mutant cDNA for both Pyrosequencing and Sanger sequencing. To further enhance mutation detection, we sorted cMV from CRC patients by first capturing cMV with a CRC associated membrane protein and then sorting for CD63 and CD24 positive events. A Taqman gene expression assay was not sensitive enough to detect KRAS in the sorted samples. However, Pyrosequencing was sufficient to identify mutant and wild-type sequences in patient plasma samples.
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 4530. doi:1538-7445.AM2012-4530
Abstract 4569: Amplicon-targeted ultra-deep sequencing for the detection of KRAS, BRAF, and PIK3CA actionable mutations
Authors: Donahue Amber C. , Sferruzza Anthony D. 
Published: August 2012

Abstract
Background: Next-generation deep sequencing techniques have the potential to revolutionize clinical testing, especially in the arena of mutation detection. Molecular diagnostic testing for KRAS, BRAF, and PIK3CA mutations has become an integral part of clinical practice for the determination of treatment eligibility for anti-EGFR therapy. Purpose: Here we investigate the feasibility of ultra-deep advanced sequencing with the 454 GS Junior instrument (454 Life Sciences/Roche, Branford CT) for the simultaneous detection of actionable mutations in KRAS, BRAF, and PIK3CA in formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissue. Methods: Advanced sequencing with a 4-amplicon panel was performed on 17 de-identified residual FFPE colorectal cancer biopsy specimens originally submitted for mutation analysis of one or more genes by standard sequencing. The 4-amplicon panel was multiplexed for up to 4 samples through “barcoding” with molecular identifier (MID) sequences, for a total of 16 amplicons per run. Results: Sequence analysis with ultra-deep coverage of 3000-5000 reads detected KRAS mutations in 5 (29%) tumor specimens, BRAF mutations in 3 (18%), and PIK3CA mutations in 4 (24%). Ten cases had a single mutation and one had two: PIK3CA E545K and BRAF D594G. Coverage was equivalent for each of the four amplicons, and in both the forward and reverse directions, providing a high level of confidence for each mutation detected. Sequencing data was obtained for each sample tested. When sample quantity allowed, Sanger sequencing and/or castPCR (Life Technologies, Grand Island, NY) were performed as method comparisons, and results were concordant. Conclusions: The use of MIDs with ultra-deep advanced sequencing allowed the simultaneous detection of mutations in multiple amplicons from multiple patients in a single sequencing run. This proof-of-concept study confirmed that using advanced sequencing to simultaneously test for multiple biomarkers in one FFPE sample is feasible, and that amplicon-based advanced sequencing is a robust and high-throughput platform for the detection of clinically actionable mutations.
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 4569. doi:1538-7445.AM2012-4569
Abstract 4579: The novel MEK Inhibitor GSK1120212b inhibits HMCL growth in vitro and synergises with a range of conventional and novel anti-myeloma therapies
Authors: Khong Tiffany T. , Leow Christopher , Monaghan Katherine , Spencer Andrew 
Published: August 2012

Abstract
Improved therapeutic interventions over the past decade has led to prolonged survival rates of patients with multiple myeloma (MM) but unfortunately, the subsequent development of progressive disease is inevitable. As such, the identification of novel compounds and strategies that improve therapeutic response is essential. GSK1120212b, a novel orally bio-available MEK inhibitor, has been shown to inhibit tumour growth and induce cell cycle arrest in some cancer cells. Here we report the efficacy of GSK1120212b in human myeloma cell lines (HMCL) and primary myeloma cells when used as a single agent and in combination with conventional and novel anti-myeloma therapies. HMCL response to variable doses of GSK1120212b (10nM-5µM) was determined by MTS assay. FACS and cell cycle analysis were used to evaluate the profiles of the cells post-MEK inhibition. Mechanistic studies using Western analysis with antibodies against p-MEK, MEK, p-ERK and ERK were performed. Subsequently, the anti-MM activity of GSK1120212b was evaluated in HMCL co-cultured with the human stromal cell line HS5. Primary samples from relapsed/refractory MM patients were subjected to GSK1120212b treatment and the level of apoptosis in CD45negCD38pos myeloma cells was assessed by Apo2.7-PE. Finally, combination studies with conventional and novel anti-MM therapies were also performed. GSK1120212b demonstrated an IC50 of 10-5000nM against 3 HMCL at 72h hours. Induction of both apoptosis and accumulation of cells in the G0/G1 phase occurred in a dose dependent manner. Western Blot analysis revealed increased p-MEK activity while total MEK levels decreased. Moreover, a decrease in p-ERK was observed with no change in total ERK levels. GSK1120212b demonstrated variable ability to induce HMCL apoptosis in stromal cell (HS5) co-culture, with or without transwells. Finally, GSK1120212b exhibited synergism with a variety of conventional and novel anti-MM therapies but was most pronounced when used in combination with GSK2110183b (Akt inhibitor) or LBH589 (HDAC inhibitor). Considering the potent anti-MM effects of GSK1120212b and its ability to synergise with other anti-MM agents, MEK inhibition demonstrates a promising future avenue for the management of MM and warrants further investigation.
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 4579. doi:1538-7445.AM2012-4579
Abstract 4586: Use of triple combination array analysis to identify STEAP family member 4 (STEAP4), a novel tumor related gene in hepatocellular carcinoma
Authors: Nomoto Shuji , Hishida MItsuhiro , Hayashi Masamichi , Inokawa Kuniyoshi , Kodera Yasuhiro 
Published: August 2012

Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common cancers world-wide, but the molecular mechanisms underlying hepatocarcinogenesis are not clear. Array technology has made it possible to identify novel genes with alterations in liver cancer. In this study, we performed triple combination array analysis, expression profiling, karyotyping analysis using SNP array, and array-based DNA methylation profiling in the same HCC sample and attempted to find a novel tumor related gene as a prognostic marker. Materials & Methods: A 68-year-old woman with chronic hepatitis C was diagnosed with HCC. The excised tumor and corresponding normal tissues were used for extraction of DNA and RNA. SNP array experiments were performed using the DNA. mRNA expression profiles were determined using the total RNA by Affimetrix HGU133A and B Gene-Chips. Bisulphite-converted genomic DNA was analyzed using Illumina's Infinium Human Methylation27 Beadchip Kit. We consequently analyzed the identified gene using quantitative RT-PCR, methylation and un-methylation-specific PCR in nine HCC cell lines and in 48 primary HCC tissues and corresponding non-cancerous tissues collected at Nagoya University Hospital, and then compared these results with clinico-pathological data. Results: STEAP4 gene, is located on 7q21.12, and expression was decreased at a Log2 ratio of –4.2 to –2.0 in cancerous tissue. There were two copies of 7q21.12, indicating no loss of heterozygosity (LOH) in the SNP array. The methylation value (0-1.0) in the tumor sample was 0.870 compared to 0.160 in non-cancerous tissue, indicating high methylation in tumor tissue in the Methylation array. Re-activation of STEAP4 expression was seen after 5-aza-dC treatment in HCC cell lines. Moreover, we found that 32 of 48 (67%) HCC samples showed promoter hypermethylation. In 32 methylated cases, the expression values of STEAP4 gene in tumor tissues by real-time RT-PCR were significantly decreased compared to corresponding normal samples (p&lt;0.0001). In addition, methylated cases were significantly correlated with worse recurrence free survival (p&lt;0.0001) and overall survival (p=0.0093). Conclusion: The Promoter hypermethylation of STEAP4 gene was a marker of worse prognosis in HCC. The triple combination array was a useful technique to identify the novel tumor related gene in 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 4586. doi:1538-7445.AM2012-4586