bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4654: Mitochondrial variants and clinical outcome of oral squamous cell carcinoma in Taiwan
Authors: Lai Chih Husiung , Huang Shiang-Fu , Liao Chun-Ta , Chen I-How , Wang Hung-Ming , Hsieh Ling-Ling 
Published: February 2011

Abstract
Mitochondria are essential cytoplasmic organelles, generating cellular energy in the form of adenosine triphosphate by oxidative phosphorylation. A large volume of studies have indicated that polymorphisms in the mitochondrial genome are associated with risk of various diseases, including cancer. However, only few studies examined the effect of polymorphisms on cancer outcome. To explore the possible role of mitochondrial polymorphisms on clinical outcome of oral squamous cell carcinomas (OSCCs) in Taiwan, 7 common length polymorphism (mtLP) sites and the control D-loop region of mitochondrial genome were genotyped or screened by DNA direct sequencing in 298 OSCCs. One hundred and seventy-eight single-nucleotide polymorphisms (SNPs) were found in the D-loop region and 19 SNPs were presented with a high frequency (&gt; 10%) of variant form. The frequency of variant form in the mtLP sites were quite various ranging from 3.7% to 62.8%. In total, 7 variants from 6 polymorphism sites (2 mtLPs and 4 SNPs) were associated with overall survival. Four subgroups (clusters 1 - 4) were identified by hierarchical clustering of the OSCCs based on the genotypes of these 6 polymorphism sites. We found that the overall survival was significantly different among these 4 OSCC clusters. An index score designated as the total effects of the genotypes of these 6 polymorphism sites on survival for each individual was also developed using the estimates from the Cox model. We found that individual with the higher the index score had the poorer disease-free and overall survival. In summary, the findings provide the first evidence pointing toward mitochondrial variants affect the clinical outcome in OSCC and the underlying mechanisms are worthy to investigate.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4654.
Abstract 4655: Gene expression signatures of microsatellite-stable stage III colorectal adenocarcinomas based on the p53 status
Authors: Katkoori Venkat R. , Shanmugam Chandra K. , Chen Dongquan , Bumper Harvey L. , Collens Tom , Messiaen Ludwine , Manne Upender 
Published: February 2011

Abstract
Background: Microsatellite (MS) instability and p53 mutations have been implicated in development, progression and metastasis of colorectal cancer (CRCs). Thus, to identify aggressive tumor subsets, the gene expression profiles of Stage- III MS-stable (MSS), sporadic CRCs were analyzed based on their p53 gene status.
Methods: DNA samples extracted from 136 Stage-III formalin-fixed paraffin embedded CRC tissues were analyzed for MSS and for p53 mutations. Further, mRNA samples extracted from 20 (10 each of p53-mutated and wild-type) corresponding snap-frozen Stage-III-MSS-CRCs were profiled for differential gene expression. Affymetrix Human Genome U133 Plus 2.0 arrays were used for gene expression profiling; and Affymetrix Microarray Suite (MAS 5.0), gene ontology annotation, and KEGG pathways were used for data analysis. Differentially expressed (DE) genes were confirmed by measuring mRNA levels by RT-PCR and by the quantitative nuclease protection assay.
Results: A higher incidence of p53 mutations was found in MSS (65 of 113, 58%) than in MSI (6 of 23, 30%) phenotypes. Kaplan-Meier analyses demonstrated that patients with MSS-CRCs exhibiting p53 mutations had poor overall survival when compared to p53-wt-phenotypes (log rank, p=0.031). Gene expression analyses identified 116 DE genes (73 down-regulated and 43 up-regulated). All of these passed the stringent background filter (intensity p-value ≤0.001 and intensity ≥3 SD above mean background) and DE ratio (χ2 p-value ≤0.01 & fold change ≥2.0). GBP1, PSMB9, TRIM29, BST2 and TFF1, that have prognostic value in CRCs, were up-regulated in p53-mutated-MSS-CRCs but down-regulated in p53-wt-MSS-CRCs. Further, genes that regulate cell-cycle arrest (CDKN1B) and tumor growth suppression (ACVR1B, SESN1, WFDC1 and IRF7) were down-regulated in p53-mutated-MSS-CRCs, but up-regulated in p53-wt-MSS-CRCs. The genes presented here are the top-ranked (top-5) genes in their respective groups. The mRNA expression levels of these DE genes in all 136 CRCs were confirmed on two different platforms.
Conclusion: Our findings suggest that mutant- and wt-p53 Stage-III-MSS-CRCs have distinct gene expression profiles and appear to be useful in identifying aggressive Stage III subsets and for the assessment of clinical outcomes. These studies are supported by grants from the National Institute of Health/National Cancer Institute (U54-CA118948, RO1-CA98932, and R03CA139629).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4655.
Abstract 4656: DNA repair polymorphisms as predictors of Graft-versus-Host Disease after allogeneic hematopoietic cell transplants
Authors: Thyagarajan Bharat , Lindgren Bruce , Basu Saonli , Nagaraj Sriharsha , Gross Myron , Wesidorf Daniel , Arora Mukta 
Published: February 2011

Abstract
Graft versus host disease (GVHD) remains a major source of morbidity and mortality among patients undergoing hematopoietic cell transplants (HCT). Tissue damage as a result of treatment is the initiating event in the pathogenesis of GVHD and variations in DNA repair can influence the amount of tissue damage in response to treatment modalities used in HCT. Since DNA damage caused by therapeutic agents such as alkylating agents and ionizing radiation used frequently in pre- HCT conditioning regimens is commonly repaired by the base excision repair (BER) pathway we hypothesized that genetic polymorphisms in the BER pathway will be associated with GVHD after HCT. We evaluated the association between single nucleotide polymorphisms (SNPs) (n= 179) in the BER pathway with acute GVHD and chronic GVHD in a cohort of 470 recipients who underwent allogeneic HCT for treatment of hematologic malignancies at the University of Minnesota. After adjustment for donor type, diagnosis, disease status at transplant and gender mismatch, two SNPs in RFC1 (Replication Factor C) gene (rs1057807 and rs4975003) were associated with a decreased risk of grade II-IV acute GVHD (HR:0.74-0.77; p≤0.01) and one SNP, rs6844176, in RFC1 gene was associated with increased risk of grade II-IV acute GVHD (HR:1.39, p=0.001). The rs3730914 SNP in the LIG1 (Ligase I) gene was also associated with a decreased risk of grade III-IV acute GVHD (HR: 0.38; p=0.005). One SNP, rs1805410, in the PARP1 (poly ADP-ribose polymerase 1) gene was associated with increased risk of chronic GVHD (HR: 1.44; p=0.01) post HCT. These findings suggest that SNPs in the BER pathway can be used as genetic biomarkers to predict individuals at high risk for GVHD. If these findings are confirmed, modulation of pre-transplant conditioning may alter risk in these patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4656.
Abstract 466: Does body weight influence tumor-infiltrating B cells in murine pancreatic cancer
Authors: White Patrick B. , Dalbec Kathryn M. , True Eben M. , Wang Sue S. , Swartz-Basile Deborah A. , Pitt Henry A. , Zyromski Nicholas J. 
Published: February 2011

Abstract
Background: We have developed a murine model of pancreatic cancer in congenitally obese (LepOb and LepDb) mice where tumors grow larger, metastasize, and decrease survival. Obese mice also had altered splenic T and B cells as well as downregulation of B cell and immunoglobulin genes and reduced numbers of B cells in the tumors. The question remained, however, whether alterations in tumor-infiltrating lymphocytes were a reflection of body weight or leptin metabolism. Therefore, we designed an experiment to determine whether diet-induced weight gain would alter systemic and tumor-infiltrating lymphocytes.
Methods: Thirty lean C57 female mice were fed either a control 10% fat (n=10) or a 60% fat diet (n=20) starting at 6 weeks of age. At 11 weeks, all mice were inoculated with 2.5x105 PAN02 murine pancreatic cancer cells. After 6 weeks tumors that developed in 18 mice, the spleen (n=12), and the sera were harvested. Mice were categorized as Lean or Overweight if they weighed less or more than the mean final weight of the 60% fat animals (23.1g). Tumors in Lean (n=10) and Overweight (n=8) mice were sectioned and stained for B and T cells. Two observers blinded to animal weight graded cell density on a scale of 0-4 in 10 high-powered fields. Flow cytometry was performed on the spleen from Lean and Overweight mice for B, T, activated T and B (ACT), natural killer (NK) cells, and macrophages (MACRO). Serum leptin was measured. ANOVA and Student's t-test were applied.
Results: Tumors were larger (1.33 vs. 0.54g, p=0.03) and leptin levels were higher (3.1 vs. 1.4ng/ml, p=0.05) in Overweight mice. Mean tumor-infiltrating lymphocyte (TIL) scores and spleen lymphocyte data are presented in the table.
Conclusion: The data suggest that 1) both B and T cells are present in the pancreatic cancer microenvironment and 2) TIL and splenic lymphocyte populations do not differ between lean and overweight mice. We conclude that obesity, as opposed to overweight, is required to alter systemic and tumor microenvironment lymphocyte populations. B Cell TILT Cell TILB Cell (%) SpleenT Cell (%) SpleenACT (%) SpleenNK (%) SpleenMACRO (%) SpleenLean0.7±0.12.2±0.264±244±32.3±0.72.3±0.71.6±0.2Overweight0.7±0.12.0±0.258±139±51.5±0.31.4±0.41.4±0.3
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 466.
Abstract 4661: Decreased epidermal growth factor receptor plasma levels as an indicator for head and neck squamous cell carcinoma case status and disease progression
Authors: Egloff Ann Marie , Kelly Lori , Panelli Monica , Davis Autumn Gaither , Siegfried Jill M. , Grandis Jennifer R. , Argiris Athanassios 
Published: February 2011

Abstract
The epidermal growth factor receptor (EGFR), c-Met and G-protein-coupled receptor signaling pathways contribute to head and neck squamous cell carcinoma (HNSCC) growth. To assess these pathways in HNSCC patients, we measured plasma levels of EGFR, the EGFR ligands transforming growth factor alpha (TGF-α) and amphiregulin (AR), the c-Met ligand hepatocyte growth factor (HGF) and COX-2, a component of prostaglandin production, in HNSCC patients (n=22) and cancer-free controls (n=32) enrolled through an Early Detection Research Network- (EDRN-) sponsored effort. Analytes were measured using a multiplex enzyme-linked immunosorbent assay. Differences in analyte levels between cases and controls and the prognostic potential of each analyte were evaluated.
EGFR plasma levels were significantly decreased (P=0.04, rank sum test (RST)) and HGF plasma levels significantly increased (P&lt;0.01, RST) in HNSCC cases compared to cancer-free controls. TGF-α levels tended to be higher in HNSCC cases (P=0.07, RST) while AR and COX-2 levels did not differ between cases and controls (P=0.32 and 0.32, respectively RST). Area under the Receiver Operating Characteristic (ROC) curve for HGF levels in subjects with low EGFR plasma levels was 0.92. EGFR plasma levels were significantly reduced in HNSCC cases who were former or active smokers compared to never smokers (P = 0.009, Kruskal-Wallis test (KWT)), but no difference in EGFR plasma levels by smoking status was observed among cancer-free controls (P = 0.97, KWT). HGF plasma levels tended to be lower in HNSCC cases who were never smokers (P=0.06 KWT) but did not differ by smoking status among cancer-free controls (P=0.16, KWT). Low EGFR plasma levels were associated with significantly reduced progression-free survival (PFS) in EDRN HNSCC cases (P = 0.03, log rank test); no other analyte tested was associated with PFS. We noted a negative correlation between EGFR plasma levels in EDRN HNSCC cases and previously reported EGFR tumor levels assessed by immunohistochemical staining that was not significant (Spearman's rho=-0.41, P=0.10, n=17).
Plasma EGFR and HGF levels may provide indications of HNSCC cancer status, and EGFR plasma levels may be a valuable prognostic indicator for patients with HNSCC. Decreased plasma EGFR levels in HNSCC patients were likely not due to general effects related to smoking and instead may reflect tissue characteristics specific to tobacco-related cancers. We found EGFR plasma levels in HNSCC patients were not positively correlated with EGFR tumor levels.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4661.
Abstract 4663: Markers of anaerobic glycolysis as predictive factor in neoadjuvant chemoradiotherapy of rectal cancer
Authors: Shim ByoungYong , Jung Ji Han , Lee Kang-Moon , Kim Hyung Jin , Hong Sook Hee , Kim Sung Whan , Sun Der Sheng , Kim Hoon-Kyo , Cho Hyun Min 
Published: February 2011

Abstract
Background: Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to resistance of radiotherapy and chemotherapy. We investigate the relationship between biomarkers related to anaerobic glycolytic metabolism (glucose transpoter-1(GLUT-1), lactate dehydrogenase (LDH)-5 and pyruvate dehydrogenase kinase (PDK)-1) and prognosis.
Methods: GLUT-1, LDH-5, PDK-1 expression determined by immunohistochemistry were assessed in 109 patients with rectal cancer treated with 5 flurouracil and leucovorin neoadjuvant chemoradiotherapy.
Results: This study included 74 male and 35 female patients with a median age of 63 (range 53-70 years). Stage I, II and III accounted for 7.3%, 43.1% and 49.5%. All patients had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (425 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33 and surgery was done on 7 to 10 weeks after completion of all therapies. The down staging rate of this neoadjuvant therapy was 53% and pathologic complete response rate is 18.3%. High expression of GLUT-1, LDH-5, PDK-1 was observed in 34 (31.2%), 62 (56.9%) and 45 (41.3%) patients, respectively. A negative GLUT-1 was associated with a significantly higher rate of pathologic complete response compared to positive GLUT-1 (25.3% vs. 0.02%, p=0.006). LDH-5, PDK-1 was not correlated with down staging and complete response of chemoradiotherapy.
Conclusions: The GLUT-1 expression is the predictive factor of pathologic complete response in rectal cancer patients treated with 5 flurouracil and leucovorin neoadjuvant chemoradiotherapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4663.
Abstract 4665: A combined IHC/Western method to measure phosphorylated histone H3 in skin biopsies as potential biomarker for anticancer drug action
Authors: Graeser Ralph , Birkle Marianne , Rentzsch Christine , Schaechtele Christoph 
Published: February 2011

Abstract
In recent years there has been a rapid increase in targeted tumor therapy approaches. Hand in hand with these novel approaches, the need has arisen to monitor specific target inhibition by the drug. In contrast to classic chemotherapy, which non-specifically targets proliferating cells, these novel approaches attempt to specifically interfere with some process thought to be crucial for the tumor cell survival. Nevertheless, despite extensive validation, an immediate effect of target interference on tumor growth may not necessarily be expected. Thus, in order to demonstrate activity of anti-cancer drugs, a marker known to be modified upon inhibition of the target may serve as a surrogate to tumor inhibition. Ideally, tumor biopsies would be analysed for monitoring of drug-induced effects. However, taking in consideration the difficulties to perform sequential tumor biopsies, the use of surrogate tissues like blood or skin is being explored instead. Blood is relatively easily accessible, but unlike skin tissue, blood may not reflect the fact that drugs have to penetrate multiple layers of tissue in order to reach their target in the tumor. Also, to monitor the effects of anti-mitotic drugs, the investigated specimen must exhibit proliferating features, which is given only in a very poor manner blood samples, as peripheral blood cells have typically exited the cell cycle. However cells in the dermis still proliferate, albeit to a small percentage.
Therefore, considering these issues, we set out to develop a method to analyse drug effects in skin biopsies. Traditionally, most analyses of skin biopsies have relied on immunohistochemistry (IHC) studies. However, the quantification of such results is time-consuming and error-prone. Western Blot analyses are easier to quantify, but require a considerable amount of protein lysate of sufficient concentration. We developed a protocol that reproducibly allows the detection and quantification of phosphorylated histone H3 in Western Blots from a single half of a skin biopsy. For normalization, the total amount of histone H3 present in the lysate is determined. The other half of the skin biopsy may be used for IHC analysis of phosphorylated histone H3, allowing the comparison to other studies relying solely on IHC.
We will present data on the measurement of phosphorylated histone H3 via Western Blots and IHC from skin biopsies of healthy donors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4665.
Abstract 4666: Identification of cancer stem cell-like fractions in cultured oral squamous cell carcinoma and expression of keratin 15 as a putative cancer stem cell marker
Authors: Isobe Tomohide , Yamamoto Gou , Tsunoda Yuko , Sasaki Akiko , Tachikawa Tetsuhiko 
Published: February 2011

Abstract
Although it is well known that one of the intermediate filament proteins cytokeratin 15 (CK15) can be a marker for not only epithelial stem cells but also cutaneous neoplasm and sebaceous tumors, the expression of CK15 in oral squamous cell carcinoma has not been reported. In this study, we investigated the expression of CK15 in different stages of epithelial dysplasia, carcinoma in situ (CIS) and squamous cell carcinoma (SCC) by immunohistochemical analysis and genetic analysis. Only basal cells in normal epithelia showed strong positive staining for CK15. Which was spread to basal cells and parabasal cells in epithelial dysplasia. In CIS and SCC, however, no reactivity was observed for CK15 except for the peripheral part of carcinoma nest in SCC. On the other hand, CK15 expression in chemoresistant SCC showed overall positive staining. In contrast to CK15 expression, transcription factor P63 which is known to putative keratinocyte stem cell marker showed different staining patterns from those of CK15. These observations seem to indicate that CK15 staining in combination with P63 could be a useful marker for pathologic diagnosis in terms of predicting malignant change and chemoresistance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4666.
Abstract 4678: KIAA1199 depletion targets the wnt/beta catenin signaling pathway and impairs migration and proliferation of human colon cancer cells
Authors: Birkenkamp-Demtroeder Karin , Maghnouj Abdel , Mansilla Francisco , Thorsen Kasper , Andersen Claus L. , Hahn Stephan , Ørntoft Torben F. 
Published: February 2011

Abstract
In a previous study KIAA1199 was found to be upregulated in colon adenomas. A depletion of beta-catenin resulted in silencing of KIAA1199, suggesting a potential role in wnt/beta signaling. Aim of this study was to correlate KIAA1199 expression with patient outcome, to identify KIAA1199 downstream target genes and to elucidate its function and pathway association. Here we show by transcript profiling of &gt;400 colon adenocarcinomas that KIAA1199 is strongly increased in &gt;75% of colon adenocarcinomas compared to normal mucosas. Immunohistochemical analyses with a monospecific antibody identified the protein to be expressed in the nucleus and the cytoplasm of adenocarcinomas, and a strong upregulation of the KIAA1199 protein compared to normal, as also seen in several other types of cancer. Cloning identified a splice isoform lacking exon 28 resulting in a truncated KIAA1199 protein. Microarray profiling of SW480 cells transiently overexpressing, or stably depleted from, KIAA1199 identified genes involved in cell cycle regulation, cell signaling, cellular movement and cell to cell interaction. In vitro functional analyses indicated that cells depleted from KIAA1199 showed reduced cellular adhesion, a decreased proliferation rate and migrated less than control cells. KIAA1199 silencing affected the expression of eighteen genes, known to be involved in the wnt/beta catenin signaling pathway. The identified target genes correlated with KIAA1199 expression in normal colon mucosa and adenocarcinomas of stage II and III (Pearson 0.7-0.9). In conclusion, our data provide evidence that KIAA1199 is a regulatory part of the wnt/beta catenin signaling, sited downstream of beta-catenin and upstream of the stem cell marker ASCL2.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4678.