bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5558: The expression and characterization of up-regulated inosine monophosphate dehydrogenase type 2 (IMPDH2) in colorectal adenocarcinoma tissues by proteomic analysis
Authors: Shim Doobo , Kang Jung H. , Park Eun S. , Kang Kee R. 
Published: February 2011

Abstract
Colorectal cancer is one of the most prevalent tumors in developed countries, and the best characterized cancers with regard to genetic progression of disease. Recent improvement in methods for proteome analysis has offered the possibility of identifying disease-associated protein markers to assist in diagnosis or prognosis, and for selecting potential targets for specific drug therapy. For identification and targeting of tumor-associated marker proteins, the proteome of colorectal adenocarcinoma (CRC) and normal colorectal tissues was analyzed by 2-DE. Inosine monophosphate dehydrogenase type 2 (IMPDH2), a key enzyme of de novo purine nucleotide biosynthesis, was identified by MALDI-TOF/MS and found to be expressed at high rates in the colorectal tumor tissues. We found an increased amount of IMPDH2 mRNA in CRC compared to that observed in the normal colorectal tissues by Northern blot. Real time PCR analysis in both tissues also revealed the higher expression of IMPDH2 mRNA in CRC. Western blot analysis was carried out to confirm the elevated expression of protein level for IMPDH2 in CRC compared with normal tissues. Immunohistochemical studies denoted that tumor tissues showed higher N/C ratio, abnormal shape of gland, and darker staining in glandular area. In addition, using in situ hybridization, it was demonstrated the expression of IMPDH2 in CRC tissues was extremely high in the vicinity of mucosal gland, while IMPDH2 in the normal colorectal tissues was evenly distributed in all tissue area with lower level. These findings suggest that IMPDH2 could be a possible tumor biomarker candidate in CRC tissues. This study was supported by KOSEF grant (R13-2005-012-01003-0) and KRF grants (2006-005-J04203).
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 5558.
Abstract 5586: NK cell killer Ig-like receptor (KIR) genotype as a novel biomarker for neuroblastoma patients receiving Anti-GD2 monoclonal antibody 3F8
Authors: Venstrom Jeffrey M. , Zheng Junting , Kushner Brian H. , Modak Shakeel , Danis Karen E. , Cheung Irene Y. , Dupont Bo , Cheung Nai-Kong , Hsu Katharine C. 
Published: February 2011

Abstract
Background: Natural killer (NK) cells are regulated by inhibitory killer Ig-like receptors (KIRs) that recognize specific HLA class I ligands. KIR-HLA genotypes are tightly linked to NK cell function and clinical outcomes in allogeneic and autologous hematopoietic stem cell transplantation (HSCT). Because NK cells contribute to antibody-dependent cellular cytotoxicity, we hypothesized that specific KIR-HLA genotypes may predict NK cell responsiveness to mAb therapy, and thus, may be useful clinically to identify patients likely to respond to mAb therapy. Methods: 76 children with high risk neuroblastoma received cyclophosphamide-containing induction chemotherapy followed by murine IgG3 monoclonal antibody 3F8 against ganglioside GD2 between 1993 and 2007. HLA and KIR genotyping was performed, and patients were segregated into KIR-HLA groups based on known functional KIR-HLA ligand relationships: KIR2DL2/2DL3 with HLA-CAsn80(HLA-C1 group), KIR2DL1 with HLA-C Lys80(HLA-C2 group), and KIR3DL1 with HLA-Bw4. Overall survival and progression-free survival were estimated by Kaplan-Meier method and hazard ratios by Cox regression. No adjustments were made for multiple comparisons. Comparisons of each end point were based on the log-rank statistics. Results: 63% of the 76 children lacked at least 1 HLA ligand for his/her inhibitory KIR. At 3 years, 80% of patients lacking any KIR ligand (n=46) were alive compared with 69% of patients with all HLA ligands present (n=30) (HR 0.41; 95% CI 0.17-0.98; P=0.04). 23/23 (100%) patients specifically lacking the HLA-Bw4 ligand for KIR3DL1 were alive at 3 years compared with 34/52 (67%) patients exhibiting HLA-Bw4 for KIR 3DL1 (n=52) (HR 0.20; 95% CI 0.05-0.87; P=0.02). Conclusion: KIR-HLA immunogenetics may be a novel biomarker for neuroblastoma patients receiving chemo-immunotherapy. The milieu of HSCT may not be required for NK cells to behave according to “missing ligand,” and KIR-HLA combinations may be predictive of outcome for other malignancies similarly treated with mAb.
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 5586.
Abstract 56: Differential expression of fatty-acid-binding proteins 3 and 5 among African American and Caucasian women with breast cancer
Authors: Calderon Teleka , Singh Sharda Kalla , Leon Marino De , Leon Daisy De 
Published: February 2011

Abstract
Breast cancer is a major cause of mortality among middle-aged and elderly women. It is well documented that African-American (AA) patients tend to present with more advanced states of breast cancer and have lower survival rates than Caucasian-Americans (CA). Additionally, the age specific breast cancer incidence rate for AA women under age 35 is greater than twice the rate for CA of similar age, and the mortality rate is more than three times greater. Some of this disparity is due to socioeconomic factors; however, biological factors may also be involved. Altered expression of intracellular fatty-acid binding proteins (FABPs) has been implicated in the progression of breast cancer. FABP3 (heart/muscle type), also known as mammary-derived growth inhibitor (MDGI), is associated with differentiation of breast tissue, and is downregulated in breast cancer tissues. FABP5 (epidermal type) is upregulated in breast cancer tissues as a possible compensation for FABP3's decrease. Therefore, we hypothesized that AA malignant breast tissue samples would contain lower levels of FABP3, and higher levels of compensatory FABP5. We determined levels of the aforementioned proteins and the corresponding mRNA in paired breast tissue samples from AA and CA women by Western blot analysis and RT-PCR. Data was divided into three groups- ages 17-45, ages 45-65, and ages 66 and up. In ages 17-45, FABP3 protein levels were higher in AA malignant tissues relative to CA malignant, and FABP5 protein levels were similar between racial groups. Also, FABP3 levels were decreased in AA malignant tissues compared to AA normal. In ages 46-65, levels of FABP3 protein, and of FABP5 protein and mRNA, were higher in AA malignant tissues relative to CA malignant. Furthermore, FABP3 protein levels were increased in AA malignant tissues relative to AA normal tissues. In ages 66 and up, levels of both FABPs were similar between AA malignant and CA malignant tissues. However, mRNA levels of both FABPs were significantly increased in the CA malignant tissues compared to AA malignant. In addition, levels of FABP3 and FABP5 were increased in the AA malignant tissues relative to the AA normal tissues. Thus, it appears that the conventional knowledge regarding FABP3 downregulation in breast cancer may only apply to AA cancer patients below age 45. Furthermore, in ages above 66, AA breast cancer patients are at a significant disadvantage compared to their CA counterparts, as it relates to expression of FABPs 3 and 5. Further study is needed to elucidate the mechanisms involved in this differential FABP expression pattern between the racial groups, and its implication on the survival disparity.
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 56.
Abstract 5606: Preclinical and clinical development of anti-CD25 recombinant immunotoxin LMB-2 in combination with chemotherapy for the treatment of adult T-cell leukemia
Authors: Singh Rajat , Zhang Yu Jian , Pastan Ira , Kreitman Robert J. 
Published: February 2011

Abstract
LMB-2, previously called anti-Tac(Fv)-PE38, is a recombinant immunotoxin containing the variable domains of the anti-CD25 Mab and a truncated form of Pseudomonas exotoxin. LMB-2 binds and internalizes via CD25, and a processed toxin fragment translocates to the cytosol where catalytic ADP-ribosylation leads to cell death. LMB-2 induces complete and partial responses (CR + PR) in patients with CD25+ hairy cell leukemia, and partial responses were reported in other hematologic malignancies including adult T-cell leukemia (ATL). While nearly all ATL cells express CD25 at high levels, clinical efficacy was limited by rapid progression between cycles and immunogenicity. Recently, preclinical studies using the anti-mesothelin recombinant immunotoxin SS1P indicated that soluble receptor is ∼10-fold higher in the interstitial space of the tumor xenograft than in the serum (PNAS, 104:17099, 2007) and that gemcitabine was synergistic against the xenografts when used prior to SS1P to deplete interstitial soluble receptor (Clin Cancer Res, 13:7166, 2007). To determine if soluble CD25 (sCD25) in the interstitial space of tumors could be a limiting factor in the antitumor activity of LMB-2 in ATL, xenografts of CD25+ human ATAC-4 cells were grown subcutaneously in nude mice and harvested so that the serum and intratumoral sCD25 concentrations could be compared. Intratumoral sCD25 concentrations were 21-159 (median 43) ng/ml, compared to between undetectable and 0.33 (median 0.093) ng/ml in serum (p=0.0008, n=8). Thus, intratumoral sCD25 was 86-2200 (median 610)-fold higher than serum sCD25 in this model. To determine if chemotherapy would improve the efficacy of LMB-2 towards these tumors, groups of ATAC-4-bearing mice (tumor implantation day −3) were treated with gemcitabine on days 1 and 3, and then LMB-2 on days 3, 5 and 8. Mice treated on this schedule with gemcitabine 40 mg/Kg x2 and LMB-2 50 ug/Kg x3 had smaller tumors than mice treated with twice the dose of either agent alone, confirming in vivo synergy, with the mechanisms currently under study. A clinical trial in ATL is now underway with fludarabine and cyclophosphamide on days 1, 2, and 3 followed by LMB-2 on days 3, 5 and 7, to determine if chemotherapy can prevent immunogenicity, enhance the antitumor activity of the immunotoxin, and when possible, determine if intratumoral sCD25 is depleted.
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 5606.
Abstract 5608: Sipuleucel-T treatment results in sequential ex vivo activation of APCs and T cells during the culture step - evidence for in vivo immunological priming
Authors: Sheikh Nadeem A. , dela Rosa Corazon P. , Frohlich Mark W. , Urdal David L. , Provost Nicole M. 
Published: February 2011

Abstract
Introduction. Sipuleucel-T is an investigational autologous immunotherapy for the treatment of prostate cancer. Product potency is measured in part by antigen presenting cell (APC) expression of CD54. Previous data have shown that CD54 upregulation correlates with APC activation (Sheikh 2008). This study investigated the ex vivo activation profile of T cells from men with metastatic castrate resistant prostate cancer enrolled in a Phase 3 study (D9902B, IMPACT) evaluating the safety and efficacy of sipuleucel-T treatment. Methods. Sipuleucel-T was prepared by incubating mononuclear cells isolated from leukapheresis obtained at Wks 0, 2, and 4 with PA2024 (a recombinant fusion protein comprising prostatic acid phosphatase and GM-CSF) ex vivo for 2 days, after which washed cells were infused. 512 subjects were randomized to sipuleucel-T or placebo (2:1). As part of product characterization efforts, fresh pre- and post-culture (final product - FP) T cells were evaluated in sipuleucel-T products by flow cytometry. The culture supernatant was evaluated for the production of APC and T cell activation-associated cytokines by multiplex luminex assay. Results. APC activation as measured by CD54 upregulation increased from Wk 0 to Wk 2 (P &lt; 0.001) and persisted at the third dose (P &lt; 0.001, Wk 0 vs Wk 4). An analysis of the culture supernatant at each week showed increases in both APC activation-associated cytokines (IL-1α, IL-1β, IL-10, IL-12p70, IL-23, IFNγ, and TNFα) and T cell activation-associated cytokines (IL-2, IL-4, IL-5, IL-10, IL-17, IFNγ, and TNFα). CD134 (OX40), CD137 (4-1BB), CD278 (ICOS), and CD279 (PD-1) expression increased in both CD4+ and CD8+ T cells at Wk 2, with expression diminished at Wk 4. Conclusion. Following The Wk 0 dose, sipuleucel-T products demonstrate evidence of increased APC and T cell activation markers as well as production of T cell activation-associated cytokines. These data provide strong evidence that sipuleucel-T activates APCs ex vivo and facilitates in vivo and ex vivo priming of T cells.
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 5608.
Abstract 561: Establishment and characterization of matched pairs of human prostate stromal cells to study cancer-stromal interaction
Authors: Sun Xiaojuan , He Hui , Xie Zhihui , Qian Weiping , Yates Clayton , Marshall Fray F. , Zhau Haiyen E. , Chung Leland W. k. , Wang Ruoxiang 
Published: February 2011

Abstract
Prostate stromal cells may play binary roles in the process of prostate cancer development. Being the first to be encountered by infiltrating prostate cancer cells, prostate stromal cells form the first defense line against prostate cancer progression and metastasis. On the other hand, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival. To establish an experimental system for studying the interaction between cancer and stromal cells, we isolated three matched pairs of normal and cancer-associated human prostate stromal cells. The specimens were from three prostate cancer patients who underwent radical prostatectomy in the Department of Urology, Emory University School of Medicine. From each prostate, a cube of prostate tissue was dissected from a histologically normal region distal to the tumor, and another cube was dissected from a cancer-affected zone. Live cells in single cell preparation were cultured in low density for isolation of stromal clones. In contrast to the LNCaP prostate cancer cells, the isolated prostate stromal clones exhibited large fibroblastic morphology with slow growth rate. Growth and survival of the stromal clones were not affected by androgens and were highly resistant to serum starvation. In contrast to the normal counterparts, the cancer-associated stromal clones exhibited differentiated survival ability, as determined by colony formation assay following serum starvation. In direct co-culture, the prostate stromal cells inhibited growth of the LNCaP cells and made the production of Prostate Specific Antigen (PSA) less sensitive to androgen deprivation. Importantly in co-culture experiments, the stromal cells protected some LNCaP prostate cancer cells from death by serum starvation, and cancer-associated stromal clones showed more protection. The surviving LNCaP clones showed features of androgen-independent PSA expression similar to the lineage-related androgen-independent C4-2 cells, suggesting that cancer cells acquired increased malignancy through interaction with the stromal cells. The results from this study indicate that matched stromal cell pairs may serve as models for comparative analysis of molecular changes in the tumor microenvironment. These cells can also be used in co-culture with prostate cancer cells to simulate cancer-stromal interaction in the tumor microenvironment in order to define the role of prostate stromal cells in prostate cancer progression and metastasis.
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 561.
Abstract 5612: Pretreatment with chemotherapy can enhance the immunogenicity of tumors by promoting adaptive immune responses
Authors: Liu Wai M. , Fowler Daniel W. , Smith Peter , Dalgleish Angus G. 
Published: February 2011

Abstract
Cancer patients are typically immuno-compromised, and it has been long felt that immune-intervention is not compatible with standard chemotherapies. However, evidence suggests that standard chemotherapy drugs may stimulate beneficial changes in both the immune system and tumour. We have assessed the impact of chemotherapy agents (cyclophosphamide, oxaliplatin and gemcitabine (GEM)) on the potential immunogenicity of tumour cells (A549, Caki2, HCT116, MCF7 and PC3), and investigated the interactions between supernatants derived from these stressed cells and cells of the immune system, by studying the activities between dendritic cells and T-cells. Results showed that some chemotherapy agents can increase total MHC class I expression on tumour cells, even when expression is low. For example, expression on MCF7 cells was increased by ∼4-fold upon treatment with GEM (133 ± 31 vs. 33 ± 7.8 in untreated cells; p&lt;0.001). The increases in expression were associated with enhanced killing by cytotoxic T-cells (e.g. in HCT116, the MTT reading for GEM pre-treated tumour cells cultured with T-cells was 0.17 ± 0.011 vs. 0.12 ± 0.0096 in untreated tumour cells with T-cells added; p=0.007), which were negated by HLA1-blockade. Results also showed that the supernatants derived from tumours treated with chemotherapy augmented DC-maturation as indicated by increases in the maturation markers CD80/CD83/CD86. Furthermore, DC function was enhanced as confirmed by an increase in DC-mediated proliferation of CFSE-loaded T-cells. For example, the percentage of CD3+/CD4+ cells with a reduced CFSE content (indicating proliferation) was higher in cells exposed to supernatants derived from GEM treated A549 cells (12 ± 2.1% vs. 5.2 ± 1.4% in controls where the supernatant was from untreated tumours; p=0.028). In summary, there is evidence that a facet of immune surveillance can be restored by appropriate chemotherapy agents. Also, tumours exposed to some chemotherapy may deliver signals that can mature DCs, which ultimately enhances T-cell responses.
This work was supported by the Cancer Vaccine Institute.
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 5612.
Abstract 5627: Antitumor activity of soluble beta-1,3/1,6 glucans: Structure matters
Authors: Vasilakos John P. , Bose Nandita , Chan Anissa SH. , Danielson Michael E. , Elmasry Natalie , Gorden Keith B. , Guerrero Faimola O. , Magee Andy , Maristany Carolyn M. , Walsh Richard M. , Will Paul M. , Wurst Lindsay R. 
Published: February 2011

Abstract
Beta-glucan is a pathogen-associated molecular pattern recognized by a variety of innate immune cells. Beta-1,3/1,6 glucans possess numerous immune potentiating activities. In particular, antitumor activity has been demonstrated with the soluble beta glucan Imprime PGG used in combination with complement-activating antitumor monoclonal antibodies (MAb) in several tumor models. Structurally, beta-1,3/1,6 glucans can vary on the basis of chain length, types of linkages, branching, and tertiary structure. Previously, the antitumor activity of soluble beta-1,3/1,6 glucans in combination with antitumor MAb has only been reported using beta glucans derived from yeast. The primary objective of this study was to compare the antitumor activity of three structurally distinct soluble beta-1,3/1,6 glucans in vivo in a mouse syngeneic lymphoma model. Tumor-bearing mice were administered antitumor MAb plus beta glucan 2x/week for 4 weeks. Antitumor activity was based on inhibition of tumor growth at the tumor implantation site and enhanced long-term survival. In addition, critical innate immune cells responsible for antitumor activity were identified focusing on the role of neutrophils. Also, characterization of relevant human immune cells and their beta glucan receptors will be shown focusing on complement receptor 3 (CR3) and dectin-1. Beta glucan binding to immune cells and identification of relevant receptors were determined by flow cytometry using beta glucan-specific antibody and fluorescently-labeled beta glucans. Key findings are that soluble beta glucans, which differ structurally, do not induce similar antitumor activity, and antitumor activity is abrogated in granulocyte-deficient mice. Finally, soluble glucans bind to human neutrophils in a CR3-dependent manner.
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 5627.
Abstract 5640: KRAS and BRAF in rectal cancer treated with preoperative chemoradiotherapy
Authors: Gaedcke Jochen , Grade Marian , Jung Klaus , Wolff Hendrik A. , Beissbarth Tim , Becker Heinz , Ried Thomas , Ghadimi Michael 
Published: February 2011

Abstract
KRAS and BRAF are mutated in 35% and 10% of colorectal cancers, respectively. However, data for locally advanced rectal cancer patients specifically are scarce and the frequency of KRAS mutations in codons 61 and 146 remains to be established. Therefore DNA was isolated from pretherapeutic biopsies of 94 patients who were treated within the clinical trials receiving preoperative chemoradiotherapy. Mutation status of KRAS exon 1-3 as well as BRAF exon 15 was established using ABI PRISM Big Dye Sequencing Kit and subsequently correlated with clinical parameters. KRAS was mutated in 49 patients (52%). 29 mutations (64%) were located in codon 12, ten (22%) in codon 13, and three (7%) in each codons 61 and 146. No V600E BRAF mutation was detected. The presence of KRAS mutations was not correlated with tumor response or lymph node status after preoperative chemotherapy. When KRAS exon 1 mutations were separated based on the amino acid exchange, we again failed to detect significant correlations (p=0.052). However, G12V mutations appeared to be associated with higher rates of tumor regression than G13D mutations (p=0.0124). We are therefore the first to report the mutation status of KRAS and BRAF in pretherapeutic biopsies. The high number of KRAS mutations in codons 61 and 146 emphasizes the importance to expand current mutation analyses whereas BRAF mutations are not relevant for carcinogenesis. Although KRAS mutation status was not correlated with response, the subtle difference between G12V and G13D mutations warrants analysis of a larger patient population.
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 5640.