bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4317: Low dose arsenic-induced transient p53 inhibition: A novel strategy for chemotherapy protection
Authors: Ganapathy Suthakar , Seog-Jin Seo , Ha Chul Soo , Yuan Zhi-Min 
Published: July 2012

Abstract
Because of its effectiveness in killing cancer cells, chemotherapy remains to be one of the common modalities for cancer treatment, but the resulting severe side effects often pose a significant threat to cancer patients. Recognizing p53 activation in the sensitive tissues as the primary mechanism for chemotherapy-induced acute toxicity and the universal p53 inactivation in human cancers, we exploited the use of low dose arsenic to inhibit p53 for a selective protection of normal tissues from chemotherapeutics-induced damages. Colon carcinoma cell line SW-480 was used to generate a mouse xenograft model. Treatments were initiated three weeks after implantation when the tumor size reached approximately 100 mm3. Arsenic pretreatment was carried out by feeding sex-matched mice (4-6 weeks of age) with water (1.0 mg/L) for three days. As expected, treatment of tumor-bearing mice with 5FU for 7 days resulted in 77% decrease in tumor volume when compared with the untreated group. The brief treatment with low doses of arsenic did not affect the ability of 5FU to induce tumor regression as evidenced by an 80% reduction of tumor size. However, arsenic treatment was associated with a marked alleviation of 5FU-induced systemic toxicity as demonstrated by the finding that arsenic pretreatment reduced 5FU-induced body weight loss from 25% to 4%. The protecting effect of arsenic was also clearly evident in reducing 5FU-induced damage in gastrointestinal (GI) track and hematopoietic (HP) system, two of the most sensitive tissues. Using mutant p53 expressing mice, we demonstrate that arsenic-mediated protection primarily depends on functional p53. Our preclinical study implicates that the brief use of low doses arsenic to inhibit p53 is an effective approach of chemotherapy protection. If successfully validated in clinical studies, this strategy may not only minimize side effects, but would also allow escalated therapeutic doses to improve treatment efficacy in a safe and effective approach for cancer therapy protection.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4317. doi:10.1158/1538-7445.AM2011-4317
Abstract 4320: Separate analysis of the cancer and stroma cell populations from orthotopically implanted cancer cell lines in fluorescent mice
Authors: Jacobsen Hege K. , Sleire Linda , Wang Jian , Svendsen Agnete , Pedersen Paal-Henning , Gullberg Donald , Enger Per Ø. 
Published: July 2012

Abstract
The tumour microenvironment is increasingly recognised as important in most aspects of tumourigenesis, from tumor formation, growth and invasion, to metastasis and priming of distant metastatic sites. It has been estimated that around 50% of a solid tumor mass may be of stromal origin, including cells of the immune system, endothelial cells and fibroblasts, with the latter being the most abundant. The fibroblasts recruited to a tumor are commonly known as cancer associated fibroblasts (CAFs), and are characterized by their heterogeneity of marker expression and origin, making them a challenge to study.
Therefore, we have developed a new strain of mice for the analysis of the tumour microenvironment in xenograft models. The strain was created by crossbreeding dsRed positive mice with severe combined immunodeficient (SCID) mice, and backcrossing on a SCID background until we obtained a homozygous dsRed-SCID inbred strain. As the tumor cells implanted are non-fluorescent, whereas the stromal contributions to the growing tumors are dsRed positive, the two compartments were successfully separated by Fluorescence-activated cell sorting (FACS) after mechanical and enzymatic dissociation.
The dsRed phenotype is visibly red with the naked eye, and fluoresces under a 488 nm dark reader lamp light. The organs have been confirmed dsRed positive by imaging and further confirmed and quantified by RT-PCR. The SCID phenotype was confirmed by immune phenotyping, using markers for B, T, Tc, Th and NK cells. Furthermore, the mice were confirmed immune deficient when they were orthotopicaly grafted with breast (4T1) and lung (A549) cancer cell lines.
Fibroblast enriched populations were isolated from primary A549 tumours, 4T1 tumours and 4T1 tumour metastasis to the lungs, by subsorting the dsRed positive stromal compartment, excluding cells of the immune system and endothelial cells. Preliminary data clearly show distinct tumor and stroma populations in primary breast and lung cancer, as well as in lung metastasis from breast cancer xenografts. Furthermore, when investigating the breast cancers dissociated at different time points from implantation, it is clear that the percentage of stromal cells in the overall tumour mass decreases as the tumour grows. The fibroblasts were further analyzed for marker expression, cell cycle phase distribution and in vitro growth properties. We conclude that this model provides a valuable tool for investigating the stromal compartment of xenograft tumours.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4320. doi:10.1158/1538-7445.AM2011-4320
Abstract LB-307: Hyaluronan deposition correlates with poor survival in pancreatic cancer
Authors: Whatcott Clifford J. , Jiang Ping , Watanabe April , Hostetter Galen , Hu Chengcheng , Shepard Michael , Frost Gregory , Hoff Daniel Von , Han Haiyong 
Published: July 2012

Abstract
Hyaluronan (HA) is an extracellular matrix component that plays an important role in a diverse range of cellular processes including proliferation, tissue hydration, cell motility, inflammation, angiogenesis, and malignancy. Increased HA deposition is a characteristic of many desmoplastic tumors. High HA levels have been correlated with poor prognosis in some cancer types, including gastric, colorectal, breast, ovarian, and bladder cancers. Considering the high desmoplastic stromal content of pancreatic tumors, we hypothesized that high HA levels may contribute to poor prognosis or survival in pancreatic cancer. Utilizing a biotinylated HA binding protein-based staining method in a tissue microarray constructed from resected pancreatic tumor tissues, we assessed HA-specific staining in 43 pancreatic ductal adenocarcinoma samples for which patient survival had been followed for more than eight years. We observed HA staining primarily in the peritumoral, or stromal, compartment of the tumor tissue samples. 100% of the patient tumors stained positive in at least some fraction of the tissue area (stroma) for HA. The staining was scored according to the percentage area of HA-positivity, relative to total tissue area. We observed low (&lt;40%) and high (≥40%) levels of stromal HA in 11 and 32 patient samples, respectively. We tested our hypothesis with the log-rank test and found that the survival rate was significantly lower among patients with high HA (P&lt;0.05). The median survival among those patients with high HA was 299 days, and 738 days for those with low HA (the difference in median survival between the two patient groups is 439 days). These results suggest that HA levels in pancreatic adenocarcinoma patients may be predictive of survival. Because HA functions in maintaining high tumoral interstitial fluid pressure, resulting in vascular compression and limited tumor-drug access, our results also suggest that HA may serve as a potential therapeutic target in pancreatic cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-307. doi:10.1158/1538-7445.AM2011-LB-307
Abstract LB-308: Hypoxia affects gene expression and proteome of prostate cancer cells
Authors: Gomez Christian R. , Knutson Gaylord J. , Schreiber Claire A. , Kosari Farhad , Vasmatzis George , Vuk-Pavlovic Stanimir 
Published: July 2012

Abstract
Tumor-associated hypoxia facilitates malignant progression, metastasis and poor prognosis in prostate cancer (CaP); however, effects of oxygen tension (pO2) in CaP are just beginning to be investigated. To establish mechanisms whereby hypoxia enhances malignant properties and survival of CaP and to identify pO2-regulated tumor-associated macromolecules, we propagated CaP cell lines LnCaP, VCaP and DU145 in hypoxia (pO2=2 kPa) and compared them with normoxically grown cells (pO2=20 kPa); hypoxic cells proliferated faster and secreted more vascular endothelial growth factor (p&lt;0.05). Transcriptome studies revealed different gene expression in cells grown in hypoxia relative to those in normoxia. Interestingly, in hypoxic cells transcripts associated with cancer and urologic disease were overexpressed in comparison to normoxic cells (p&lt;0.001) suggesting an association of low pO2 and aggressive features of CaP. Further, we analyzed the transcriptome in primary CaP cells isolated by laser-capture microdissection (LCM) and whole CaP tissue. We compared the data to those from CaP cells cultured at pO2=20 kPa or pO2=2 kPa. Notably, hypoxia increased transcript levels for pyruvate dehydrogenase kinase isozyme 1, nuclear prelamin A recognition factor, glucose phosphate isomerase, and glyceraldehyde-3-phosphate dehydrogenase in all three cell lines (p&lt;0.05) to levels comparable to those found in primary bulk tissue and LCM isolated cells (p&lt;0.005). This finding suggests that gene expression in hypoxically cultured cells is more akin to that in tumor cells in situ than are cells grown normoxically. By 2D-gel electrophoresis, we found that change in pO2 affected the proteome mostly quantitatively (i.e., by change in spot intensity). Our results suggest that hypoxia affects transcriptome and proteome in CaP cells. In addition, we screened 20 patient sera and 20 healthy control sera for spontaneous antibodies cross-reactive with VCaP cells and found that the sera reacted with numerous proteins, some previously reported to elicit an immune response in CaP patients (e.g., nucleoporin 62 and transitional endoplasmic reticulum ATPase). By this method we detected numerous novel autoantigens (under validation). Currently we are clarifying the pO2 effects on the relationship of transcriptome, proteome and tumor-associated antigens in CaP cells. Support: DOD PC094680 (CRG), Minnesota Partnership for Biotechnology and Medical Genomics, Mayo Clinic Prostate SPORE 5P50CA091956 (FK); Mrs. Adelyn L. Luther, Singer Island, Florida and Mayo Clinic Cancer Center (SV-P).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-308. doi:10.1158/1538-7445.AM2011-LB-308
Abstract LB-31: A snapshot of the expression signature of androgen receptor splicing variants and their distinctive transcriptional activities
Authors: Hu Rong , Isaacs William B. , Luo Jun 
Published: July 2012

Abstract
Objectives: Multiple androgen receptor (AR) splicing variants implicated in ligand-independent AR signaling have been characterized. These variants are expressed in hormone naïve prostate cancers, and elevated in castration-resistant prostate cancers (CRPC), supporting their potential as biomarkers and therapeutic targets for advanced prostate cancer. The diversity and complexity of AR splicing variants however are not fully understood, raising the need to generate a comprehensive expression signature of AR variants, and to address the relative importance of the individual variants that may confer the castration resistant phenotype.
Methodology: A modified RNA amplification method, termed selective linear amplification of sense RNA (SLASR), was developed to amplify all AR transcripts containing AR exon 3. Amplified AR transcripts from CRPC specimens were profiled using expression microarrays with probes tiled across the human AR gene locus. Primers corresponding to novel expression peaks in the AR locus were designed to amplify and decode the splicing junctions. Coding sequences for a subset of selected AR variants were cloned into expression vectors and assessed for their transcriptional activities. Quantitative RT-PCR was used to determine their in vivo expression patterns in an expanded set of clinical specimens.
Preliminary data: Tiling microarray results revealed a molecular portrait of both canonical and cryptic AR exons across the human AR locus. In addition to expression peaks in AR intron 3, a novel AR exon, termed exon 9, was discovered. Exon 9 was spliced into multiple novel AR variants. Different AR splicing variants were functionally distinctive, with some demonstrating constitutive activity while others were conditionally active. Conditionally active AR-Vs may activate AR signaling depending on the cellular context. AR variant functions however did not appear to depend on the full-length AR. AR variants demonstrated patterns of expression change in clinical prostate tumor specimens consistent with their role in castration-resistant progression. This study provided the first unbiased snapshot of the AR variant signature consisting of multiple AR variants with distinctive functional properties. Our results suggest that some AR variants previously considered to be inactive may confer the castration resistance phenotype depending on the cellular context. If further confirmed, the aggregate function of multiple AR variants may compensate for the low abundance of individual variants in clinical specimens relative to the full-length AR.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-31. doi:10.1158/1538-7445.AM2011-LB-31
Abstract LB-310: FISH-based determination of HER2 status in circulating tumor cells isolated with the microfluidic CEE™ platform
Authors: Mayer Julie A. , Pircher Tony J. , Mikolajczyk Stephen D. , Cotter Philip D. , Bischoff Farideh Z. 
Published: July 2012

Abstract
Purpose: Determination of HER2 status by immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH) in patients with breast cancer is considered standard practice for selection of treatment options. Though patients presenting with recurrent and/or metastatic disease are often re-evaluated for HER2, biopsy is not often feasible. Thus, circulating tumor cells (CTCs) are an attractive alternative source of tumor tissue for determining HER2 status to enable a more effective course of treatment.
Experimental Design: Twenty to thirty ml of peripheral blood was collected prospectively from 54 patients diagnosed with late stage metastatic/recurrent breast cancer. CTCs were isolated using the microfluidic CEE™ platform. CTC capture was achieved using a cocktail of capture antibodies, followed by detection with an expanded anti-cytokeratin (CK) cocktail mixture and anti-CD45. HER2 amplification was subsequently assessed by FISH on captured CK+/CD45− and CK−/CD45− cells.
Results: CK+/CD45− cells were detected in 43 of 54 cases (80%). Among the 43 cases in which CK+ cells were detected, high concordance (93%) in HER2 status between primary tumor (by IHC and FISH) and CTCs (by FISH) was observed. An overall sensitivity of 95% and a specificity of 92% were obtained using the OncoCEE-BR™ assay.
Conclusions: Recovery of CTCs from peripheral blood using the CEE™ platform is shown to be efficient and suitable for FISH-based testing. In addition, HER2 FISH on recovered CTCs is proven to be sensitive and accurate.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-310. doi:10.1158/1538-7445.AM2011-LB-310
Abstract LB-313: Development of a non-invasive, multi-analyte assay for the triage of patients presenting with hematuria
Authors: Fernandez Cecilia A. , Millholland John M. , Zwarthoff Ellen C. , Loughlin Kevin R. , Feldman Adam , Karnes R. Jeffrey , Shuber Anthony P. 
Published: July 2012

Abstract
Introduction
The presence of blood in the urine (hematuria) is one of the hallmark symptoms of bladder cancer. Thus, the current best practice policy suggests that patients with hematuria undergo cystoscopic examination. However, hematuria can be present in healthy individuals as well as in individuals with various non-life threatening conditions such that a majority of patients with blood in the urine (∼95%) who are screened by cystoscopy do not have bladder cancer. In addition, recent studies have found that a majority of patients with hematuria are not referred on to a specialist for further invasive tests, despite the guidelines. This suggests that the prevalence of cancer in this population may be lower than 5%, making screening by cystoscopy inefficient and, in a large number of cases, unnecessary. We are developing a non-invasive diagnostic assay utilizing urinary protein and DNA biomarkers to triage those patients who do not have cancer from those who should go on to be existing invasive screening modalities.
Methods
Urine samples were obtained from 48 cancer patients and 256 patients who were evaluated for hematuria but who did not have cancer upon cystoscopic evaluation (Hem+/Cysto−). Twist1 and Nid2 methylation status was assessed using methylation-specific PCR primers and FGFR3 mutational status was determined by quantitative PCR. Matrix Metalloproteinases (MMPs) levels were determined by ELISA.
Results
Using a novel combination of these DNA and protein markers we identified with high confidence (99% negative predictive value) those patients who do not have cancer and who could be excluded from further testing. Cutoffs could be adjusted such that at 94% sensitivity, 65% of patients who do not have cancer could be excluded.
Conclusions
The Multi-Analyte Diagnostic Readout (MADR) assay described here combines the best performance characteristics of protein and DNA biomarkers into one assay for optimal clinical performance. Using this approach, the detection of FGFR3 mutations and Twist1 and Nid2 methylation in the urine of hematuria patients undergoing screening for bladder cancer effectively increases the sensitivity and negative predictive value at an established MMP protein cutoff. This non-invasive urinary diagnostic assay could lead to the more efficient triage of hematuria patients by identifying those patients who do not have cancer and could be excluded from receiving invasive procedures.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-313. doi:10.1158/1538-7445.AM2011-LB-313
Abstract LB-316: Association of Bcl2 family gene polymorphisms with response to and toxicity of platinum-based chemotherapy in non-small-cell lung cancer patients in a Chinese population
Authors: Qian Ji , Han Wu Qi , Ru Lu Da , Yi Wei Qing 
Published: July 2012

Abstract
PURPOSE: The Bcl2 family members have dual functions in apoptosis. Platinum agents cause genetic lesions and cell death that may be modulated by the normal pathway of apoptosis regulated by the Bcl2 family genes. We hypothesized that genetic polymorphisms of these genes have an impact on the outcome of platinum-based chemotherapy. The aim of our research was to assess whether single nucleotide polymorphism (SNPs) of BAD, BAX, PUMA, BID, and BCL2 in a pathway of regulating apoptosis affect the response to and toxicity in patients with NSCLC treated with platinum-based chemotherapy.
METHODS AND METERIALS: We genotyped 64 SNPS of 5 genes by Illumina Custom Designed Chip in 1004 patients with advanced NSCLC treated with platinum-based chemotherapy. We investigated the response and the toxicity of patients after platinum-based chemotherapy. The genotyping data were analyzed by the Sofeware of SPSS12.0, PHASE2.1 and Haploview.
RESULTES: A SNP of BID (rs5746474) was significantly associated with the hematological toxicity. Compared with the wild-type GG genotype, the variant AA genotype was associated with significantly increased risk to hematological toxicity (adjusted OR: 2.4344, 95%CI=1.4084–4.2077, p=0.0014) in a recessive model (adjusted OR: 2.5241, 95% CI = 1.4839–4.2933, P=0.0006). In the allelic analysis, a SNP of BCL2 (rs8099575) showed an effect on gastrointestinal toxicity (adjusted OR: 0.3041, 95% CI=0.1524–0.6.68, P=0.0007). Several haplotypes of these genes were associated with the response and toxicity; however, after Bonfernoni correction, no association between haplotypes and clinical outcome remained.
CONCLUSION: Genetic polymorphisms in the BID and BCL2 genes may have an impact on the response to and toxicity of platinum-based chemotherapy in patients with NSCLC, which may be prognostic biomarkers of chemotherapy in NSCLC patients, if validated in larger studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-316. doi:10.1158/1538-7445.AM2011-LB-316