bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B1: Heme oxygenase-1 transcription controlling GTn repeat polymorphism has contrary prognostic value in squamous cell carcinoma and adenocarcinoma of the esophagus
Authors: Effenberger Katharina E. , Vashist Yogesh K. , Uzungolu Guentac , Trump Florian , Kalinin Viacheslav , Bockhorn Maximilian , Brandt Burkhard , Pantel Klaus , Yekebas Emre F. , Izbicki Jakob R. 
Published: January 2011

Abstract
Purpose: The regulation of basal transcription of heme oxygenase-1 (HO-1) is dependent upon a GTn repeat polymorphism (GTn) in the promoter of the heme oxygenase-1 gene (HMOX-1). Here, we evaluate the role of GTn in surgically resected esophageal cancer patients without neoadjuvant or adjuvant treatment.
Patients and Methods: Genomic DNA was extracted from peripheral blood leucocytes of 297 patients. To determine the number of the GTn repeats DNA was amplified by RT-PCR and sequenced. The results were correlated with clinicopathological parameters, disseminated tumor cells (DTC) and clinical outcome.
Results: Three genotypes (SS, SL and LL) were defined based on cut-off points for short allele (“S”) with GTn repeats &lt;25 and ≥25 as long allele (“L”). Throughout all analyses a contrary role of GTn was evident in squamous cell carcinoma (SCC) and adenocarcinoma (AC) patients. In SCC patients the SS genotype patients presented with less aggressive tumors in terms of tumor size, presence of regional and non-regional lymph node metastases, DTC and lower relapse rate compared to SL and LL genotype patients. In contrast, in AC patients the SS genotype patients displayed more aggressive tumor biology with bigger tumors, a higher rate of lymph node metastases, DTC as well as tumor recurrence compared to LL and SL genotype patients. The disease-free and overall survival in SCC patients was markedly reduced in LL genotypes compared to SL and SS genotypes. To the contrary, in AC the SS genotype patients displayed the worst disease-free and overall survival.
Conclusion: GTn was identified as an independent prognostic factor with contrary prognostic value for tumor recurrence and death in the two subtypes of esophageal cancer, SCC and AC.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B1
Abstract B17: Heat shock-induced danger signals in tumor cells are crucial for a rapid differentiation of monocyte to therapeutic dendritic cells
Authors: Aguilera Raquel , Saffie Carlos , González Fermin , Tittarelli Andres , Reyes Diego , Ferrada Carlos , López Mercedes N. , Salazar-Onfray Flavio 
Published: January 2011

Abstract
Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that initiate a cell-mediated antitumor immune response. Recently, we showed that monocyte-derived DCs loaded with a heat-shocked melanoma cell lysate (TRIMEL®) induce melanoma-specific immune responses, thus prolonging patient survival. Here, we describe the rapid effect of TRIMEL on human monocytes differentiation to tumor-antigen presenting cells (TAPCells®). TAPCells showed a mature DC-like phenotype and effectively activated melanoma associated antigen (MAA)-specific CD4+ and CD8+ T lymphocytes. Moreover, heat shock (HS) pre-conditioning of TRIMEL composing cells increased calreticulin (CRT) cell surface translocation and released high-mobility group box 1 protein (HMGB1), which was closely associated to the induction of APC maturation and efficient MAAs cross-presentation. Finally, 26 out of 43 patients vaccinated with TAPCells showed a TRIMEL-specific delayed type hypersensitivity reaction (DTH) associated to anti-melanoma T cell recognition, reduced rates of progression and prolonged patient survival. Our results suggest that heat-shocked tumor cell lysates are optimal source of MAAs, inducing activated APCs with improved MAAs cross-presentation capacity and clinically effective immunogenicity.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B17
Abstract B18: Induction of Th1/Th17 and inhibition of Th3 cellular profile by DC-based immunotherapy is associated with immunological and clinical anti-tumor responses in melanoma patients
Authors: Durán Claudia , Segal Gabriela , Salazar Lorena , Pereda Cristián , Fabián Tempio , Salazar-Onfray Flavio , López Mercedes N. 
Published: January 2011

Abstract
The ability of DCs to induce a primary immune response makes them ideal candidates for cancer vaccines against tumors. Recently, in a serie of phase I/II clinical studies, we showed the effectiveness of autologous DCs loaded with a conditioned allogeneic melanoma cell lysate named TRIMEL. Our results demonstrated a correlation between positive tumor-specific delayed type hypersensitivity (DTH) reaction induced by DC-vaccination, and improved long-term patient survival in late-stage melanoma patients. In fact, 60% of patients showed a positive DTH reaction showing a three-fold prolonged survival compared to non-responder patients (33 and 11 months respectively). Herein, we investigated whether cellular and cytokine profiles in patients PBL before and after vaccination reflects differential responses associated to the clinical outcome. Analysis of T cell populations in blood showed that melanoma patients (n=28) have an increased proportion of Th3 (CD4+TGF-β+) regulatory T lymphocytes (2.64 % ± 0.16) compared to normal donors (n=14) (1.72 % ± 0.22). However, we didn't observed differences in TGF-β concentrations at serum level. Moreover, we analyzed vaccine effect on cytokine and cellular responses in PBL. Interestling, although there was not differences in Th3 population proportions between responder (n=14) and non-responder patients (n=14) before vaccination, after treatment responder patients showed a three-fold reduction of CD4+TGf-β+ T cells compared to non-responders (1.65 % ± 0.19 and 5.54 % ± 0.28 respectively). Furthermore, our results show that DC-vaccination resulted in a three-fold augment of IFN-γ releasing by Th1 population and a two-fold increase of IL-17 producing Th17 lymphocyte population in responder patients, but not in non-responders. A direct correlation between IFN-γ and IL-17 production in responder patients blood was observed (p &lt; 0.0001) suggesting that those cytokines may favour an anti melanoma response. Taken together our results indicates that despite undetectable differences in the cellular and cytokine profiles in melanoma patients before DC-vaccination, immunization resulted in two different pattern of response associated to the immunological and clinical outcome. Our study may contribute to a better understanding of clinical immunological responses and to an earlier prognosis of patient outcome.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B18
Abstract B2: Patterns of serum biomarkers for lung cancer are different for men and women
Authors: Streeper Robert , Izbicka Elzbieta , Campos David , Diaz Armando , Baek Sung , Mussman Rhys 
Published: January 2011

Abstract
Introduction: Lung cancer has one of the highest mortality rates among all human cancers. Higher mortality has been noted in the past in men with the history of smoking but no significant differences in mortality exist in never smoking men and women. Some gender differences to date have been linked to genes located on sex chromosomes.
Methods: We quantified levels of 57 cytokines, chemokines and growth factors using multiplexed immunoassays to determine patterns of serum biomarkers in men and women with non-small cell lung cancer (NSCLC; 250 men, 116 women) and compared these with serum marker patterns in subjects with asthma (AST; 68 men, 132 women) and normal controls (NOR; 250 men, 116 women). Data were reduced using inter-pathology comparisons with statistical significance determined using the Kruskall-Wallis U test with p &lt; 0.05 considered significant. Scalar sums of inter-pathology percentage differences (NSCLC vs. NOR, AST vs. NOR and NSCLC vs. AST) in marker expression were used for hierarchically ranking the markers. We selected markers based on at least one statistically significant difference was present for a given marker; those showing marginally significant differences were discarded.
Results: The markers showed unique gender- and disease specific patterns. For unisex analysis of NSCLC, we identified 36 markers with the 25% change cutoff threshold and 32 markers with the 50% cutoff. For women, we found 32 markers with the 25% cutoff and 30 with the 50% cutoff. For men, 39 markers were found at the 25% cutoff and 37 at the 50% cutoff. Expression of four markers was unique for women with NSCLC compared to NOR: IL-8 and serum amyloid P (downregulated), serum amyloid A and C-reactive protein (all upregulated). Five markers were unique for men with NSCLC compared to NOR: Insulin (downregulated), matrix metalloproteinases-7 and -8, resistin and hepatocyte growth factor (all upregulated). Three markers showed opposite patterns of expression; VEGF was downregulated in women and upregulated in men with NSCLC compared to NOR. Leptin was upregulated in women and downregulated in men and MIP-1α were upregulated in men and downregulated in women with NSCLC compared to NOR.
Conclusion: Our study has revealed surprisingly large qualitative and quantitative differences in biomarker expression patterns and levels in serum specimens from men and women suffering from NSCLC. The markers appear to be products of genes residing on several chromosomes and are not limited to sex chromosomes. Our findings may have implications for the diagnosis of non-small cell lung cancer, early detection of the disease through simple blood tests, characterization of disease progression and differentiation among the pathologies. It may find application in discovery and development of novel therapeutic strategies for human diseases.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B2
Abstract B25: Autocrine action of VEGF/VEGFR pathway in human Glioblastomas in addition to the paracrine angiogenic role
Authors: Martinez Juan-Carlos , Campo Leticia , Val Toledo Maria , Sacristan Silvia , Gatter Kevin C. 
Published: January 2011

Abstract
Angiogenesis is an important determinant for glioma growth and there is a growing interest in anti-angiogenic therapies as a way of blocking glioma development.
To get insights into brain tumor angiogenesis, we have addressed the expression of a panel of angiogenesis regulatory proteins in 34 human Glioblasotmas (GBs) specimens.
Methods: Immunohistochemistry (IHC) detection of Vascular endothelial growth factor (VEGF), Phosphorylated VEGF Receptor (PKDR), Hypoxia Inducible Factor (HIF-1) and the hypoxia marker Carbonic Anhydrase IX (CAIX).
Results & Discussion: VEGF & PKDR cytoplasmic staining of variable intensity in tumoral cells and vascular endothelium was observed in all cases. The highest levels were seen around necrotic foci and in areas of endothelial proliferation. However, VEGF & PKDR expression by tumoral cells was shown also in non-hypoxic areas far away from necrotic foci.
Hypoxia induces FIH expression, which in turn activates VEGF expression by tumoral cells. This is followed by diffusion, and interaction through a paracrine process with endothelial VEGF Receptors (VEGFR).
Interaction between VEGF and VEGFR, induces activation and phosphorylation of VEGFR, triggering angiogenesis by the emission of vascular sprouts.
Our finding of high levels of PKDR by neoplastic cells indicates that interaction and activation of the VEGF/VEGFR pathway can be as well an autocrine process. As VEGF is a powerful growth factor, this support that in addition to angiogenic induction, VEGF may play an active role in neoplastic cell growth. The strong expression of VEGF & PKDR in non-hypoxic areas suggests that VEGF may be induced by other stimulus than hypoxia.
This possibility my have a therapeutic influence in that treatment with VEGF blockers and or inhibitors, aimed at an antiangiogenic effect, could additionally act against neoplastic proliferation on neoplastic cells themselves.
Supported by Grant to JCM, Fundación de Investigación Mutua Madrileña.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B25
Abstract B26: The role of G alpha12 and thromboxane receptor beta interaction in bladder cancer progression
Authors: Woolworth Julie Ann , Desouki Mohamed , Halushka Perry , Watson Dennis , Smith Michael T. , Moussa Omar 
Published: January 2011

Abstract
In the United States, it is predicted that there will be over 70,000 new cases of bladder cancer this year. Bladder cancer is the fourth most common cancer in men and eighth in women. Our lab has previously identified Thromboxane receptor-β (TP-β) as potentially playing a role in bladder cancer progression. TP-β is a G-protein coupled receptor that is over-expressed in bladder cancer tumors and high levels of TP-β in bladder cancer patients correlate with decreased survival. G-proteins are involved in second messenger cascades that influence a variety of cellular functions, including transcription and motility. In multiple cellular systems TP-β has been found to interact with multiple G proteins such as Gαi, Gαs, Gα12, and Gα13. We found high levels of mRNA and protein expression of the G-protein, Gα12, in bladder cancer cell lines. We also observe high levels of Gα12 expression in human bladder cancer tissues. Studies using a constitutively active Gα12 mutant, suggest that signaling through Gα12 can contribute to oncogenic transformation. In this study we aim to elucidate the TP-β associated Gα12 dependent pathways that contribute to bladder cancer progression. We found that TP agonist U46619 increases cell migration and that treatment with TP antagonist blocks this increase in cell migration induced by U46619. TP agonist stimulation also increases the phosphorylation of extracellular regulated kinase (ERK) and U46619-induced phosphorylation of ERK is blocked with TP agonist treatment. Using a shRNA to knockdown Gα12 we observe a reduction in U46619-induced cell migration and ERK phosphorylation. Together our results suggest that TP-β mediated cell migration and the MAPK signaling pathway is in part regulated through Gα12. This work could have clinical implications by targeting the TP-β and Gα12 interaction as a potential therapeutic approach for bladder cancer treatment.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B26
Abstract B41: Antitumoral and angiostatic activities in skin secretion of frog Phyllomedusa bicolor
Authors: van Zoggel Hanneke , Hamma-Kourbali Yamina , Galanth Cécile , Ladram Ali , Nicolas Pierre , Courty José , Amiche Mohamed , Delbé Jean 
Published: January 2011

Abstract
The skin secretions of neotropical and South American frogs contains large amounts of a wide range of biological active peptides. Commonly studied are small peptides with antimicrobial activities as the Dermaseptin family. These peptides constitute a primitive immune defence mechanism and are able to disrupted the membranes of microbes and, subsequently, to inhibit their growth leading to cell death. Some of these antimicrobial peptides also present an antitumoral activity whereby they use a similar disrupting mechanism on the plasma membrane of the tumoral cells [1]. Therefore, intense research is now performed on the secretions from amphibian skin to discover new pharmacological agents, especially useful for drug-based cancer treatments.
In this study we have postulated that the skin secretions from the South American frog Phyllomedusa bicolor contain such molecules and we reported antitumoral and angiostatic activities from a crude extract of these secretions [2]. After a two steps chromatography procedure, we have identified one of the bioactive compounds in this crude extract as Dermaseptin B2 (Drs B2) [3]. Drs B2 is a well known antimicrobial peptide which is 33-amino acid residues long. This natural α-helical peptide consist of a cationic NH2-terminal part (residues 1 to 23) predicted to form an amphipathic α-helix that is followed by a hydrophobic tail (residues 24 to 33).
A synthetic Drs B2 peptide was prepared and tested for its antitumoral and angiostatic activities. Results obtained with this synthetic molecule were equal to those obtained by testing the crude extract in vitro. Thus, Drs B2 inhibited the growth of different human tumoral cell lines like the prostatic adenocarcinoma cell line PC3 and the mammary carcinoma cell line MDA-MB231 when cultured on plastic or in soft agar with an EC50 of 1–2 μM. Drs B2 was also able to inhibit non adherent human tumoral cells like the Raji and LB-EBV lymphoma cell lines with the same efficiency. It is noteworthy that Drs B2 showed an inhibitory effect on non tumoral cells like NIH-3T3 and primary mouse embryonic cells but only when concentrations higher than 10 μM where used. Furthermore, Drs B2 was evaluated for its effect on endothelial cells growth and was able to inhibit to growth of the adult bovine aortic endothelial cells (ABAE) in vitro. Moreover, Drs B2 could also block the capillary network formation induced by FGF-2 of these cells when cultured on collagen in a Montesano model.
In conclusion, Drs B2 could represent a new interesting pharmacological leader molecule against the proliferation of human tumoral cells that now need to be evaluated on different cancer cell types in vitro but also in vivo in animal models. Besides that, also the mechanism of action of Drs B2 on tumoral cells has to be clear before further pharmacological development.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B41
Abstract B43: Gene expression in breast tissue associated with mammographic density in healthy women
Authors: Haakensen Vilde D. , Biong Margarethe , Lingjærde Ole Christian , Holmen Marit Muri , Frantzen Jan Ole , Ying Chen , Navjord Dina , Romundstad Linda , Solvang Hiroko K. , Vessela Kristensen N. , Ursin Giske , Børresen-Dale Anne-Lise , Helland Åslaug 
Published: January 2011

Abstract
Introduction: Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, high MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of MD are virtually unknown.
Methods: Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) recruited through mammographic centres and 64 newly diagnosed breast cancer patients. MD percentage was determined using a previously validated, computerized method on scanned mammograms. Unsupervised hierarchical clustering was used to investigate the presence of subgroups of samples within the normal biopsies. Significance analysis of microarrays (SAM) was performed to identify genes associated with MD.
Results: Hierarchical clustering of normal biopsies on the basis of the gene expression data split the individuals into two main groups. These were not significantly associated with MD or BMI. SAM identified 24 genes differentially expressed between high and low MD in the healthy women. Several single nucleotide polymorphisms (SNPs) associated with the expression of these 24 genes were identified.
Conclusions: Breast biopsies from healthy women show substantial variation in their gene-expression profiles. Twenty-four genes associated with MD and SNPs associated with their expression were identified. Several of these genes have previously been found to be linked to breast biology and oestrogen metabolism. Validation and further analysis of these genes is ongoing.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B43
Abstract B44: Value of 1H-magnetic resonance spectroscopy chemical shift imaging (CSI) for detection of anaplastic foci in diffusely infiltrating gliomas with non-significant contrast-enhancement
Authors: Widhalm Georg , Krssak Martin , Minchev Georgi , Woehrer Adelheid , Traub-Weidinger Tatjana , Czech Thomas , Asenbaum Susanne , Marosi Christine , Knosp Engelbert , Hainfellner Johannes A. , Prayer Daniela , Wolfsberger Stefan 
Published: January 2011

Abstract
Objective: In diffusely infiltrating gliomas (DIG), positron emission tomography (PET) imaging is a clinically powerful method for detection of anaplastic foci. Recently, 1H-magnetic resonance spectroscopy chemical shift imaging (CSI) using choline/creatine (Cho/Cr) or choline/N-acetylaspartate (Cho/NAA) ratios has emerged as new non-invasive and widely available alternative. We therefore correlated CSI with 11C-methionine (MET)-PET data in a series of DIG with non-significant contrast-enhancement (CE).
Methods: Thirty-two patients with DIG were examined with CSI on 3T MRI scanner and MET-PET. Maximum pathologic intratumoral ratios of CSI (=CSImax) and maximum tumor-to-normal-brain PET ratios (=PETmax; T/N ratio) were determined. Co-registration of MRI with CSI and PET was performed and the topographic overlap of CSImax and PETmax was analyzed. Cell proliferation rate in tumor samples inside and outside of CSImax was assessed by MIB-1 labeling index (LI).
Results: CSI showed a pathologic ratio in all patients, whereas PET demonstrated a pathologic T/N ratio in 21/32 patients. Topographical correlation of CSImax and PETmax revealed a ≥50% overlap in 18/21 and &lt;50% overlap in 3/21 patients, respectively. Cho/Crmax and Cho/NAAmax showed a ≥50% overlap in 24/32, a &lt;50% overlap in 8/32 patients. MIB-1 LI was significantly higher inside than outside the CSImax (13.6% versus 6.9%, p&lt;0.001).
Conclusion: Our results indicate that CSI is a promising method for detection of anaplastic foci within DIG with non-significant CE. Intraoperative use of CSI by multimodal neuronavigation may increase the reliability of detection of malignant areas in glioma surgery and therefore optimize allocation of patients to adjuvant treatments.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B44
Abstract B47: Biomarker discovery and evaluation of response to anticancer therapeutics in breast cancer using a novel nanofluidic immunoassay
Authors: Iacovides Demetris C. , Johnson Aimee B. , Gray Joe 
Published: January 2011

Abstract
Cancer subtype specific molecular variations dramatically affect patient responses to already existing treatments. For example, the phosphorylation status of many proteins that are involved in signal transduction pathways perturbed in cancer cells is extremely important in determining whether these cells are susceptible to killing by available cancer therapeutics. Therefore, differentially phosphorylated protein isoforms can be a particularly useful prognostic biomarker of drug response in the clinic. However, accurate detection and quantitative analysis of cancer-related phosphoproteins in tumors is limited by current technologies.
Using a novel, fully automated nanocapillary electrophoresis technology (CB1000TM) designed to separate protein molecules based on their isoelectric point, we are currently developing highly sensitive assays for reliable assessment of the phosphorylation status of cancer-related phosphoproteins in tumors, before and during drug treatment. We have already developed and optimized assays measuring all AKT, ERK and MEK isoforms and their respective phosphoisoforms using a single detection reagent method. Using these assays, we were able to measure levels of activated MEK1/2, ERK1/2 and AKT1/2/3 in cancer cell lines, mouse xenografts and patient FNAs using protein extracted from as few as 125 cells. We have already measured and characterized changes in the phosphorylation states of these targets before, during and after treatment with inhibitors of the PI3K pathway in breast cancer, and based on this data we are currently developing molecular profiles that predict response to available therapeutics.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):B47