bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 469: Functional imaging of the hypoxic tumor microenvironment in metastatic progression
Authors: Iglesias Pablo , Fraga Maximo , Costoya Jose A. 
Published: February 2011

Abstract
In the last years, the need for visualization of tumoral processes has become a high-top priority in molecular imaging. This is especially true for those methods dedicated to functional imaging that focus on revealing phenomena associated with biological processes such as hypoxia to cancer. Among them, optical imaging methods such as fluorescence are provided with a broad range of proteins and dyes used to visualize many types of these biological processes widely used in cell biology studies. Although the best-known example of these fluorochromes is the green fluorescent protein (GFP), tissue autofluorescence and signal dispersion raise doubts about its suitability as an in vivo tracer. However, a number of groups have recently developed several NIR fluorescent proteins that enable real-time imaging free of autofluorescence interference thus making possible to take a deep view into the tissues. With all of this in mind, we devised a novel fluorescence-bioluminescence genetically encoded biosensor activated by the neoangiogenesis-related transcription factor HIF-1α, which appears upregulated in growing tumors. At the same time, by fusing a fluorescent to a bioluminescent protein we obtained a bioluminescence resonance energy transfer (BRET) phenomenon turning this fusion protein into a new class of hypoxia-sensing genetically encoded biosensor. We also tested the inducibility and performance of this hypoxia sensor by imaging artificially activated cells both in culture (in vitro) and inside an animal model (in vivo). Finally, the breast cancer cell line MDA-MB 231, which is known by its invasiveness and ability to metastasize, was modified to carry the hypoxia sensor and subsequently injected intravenously in live mice. Metastases were detected in lung and brain by fluorescence and/or bioluminescence. In conclusion, we have described the designing and development of a functional dual hypoxia-sensing system able to display BRET activity between the firefly luciferase and the NIR fluorochrome. In addition a metastatic tumoral cell line was genetically modified to demonstrate that the biosensor is able to detect hypoxic conditions in metastasis in vivo, yielding valuable functional information about the tumor besides size and spatial localization.
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 469.
Abstract 4693: Maternal GSTP1 Ile105Val polymorphism and petrochemical exposure in relation to the childhood leukemia in southern Taiwan
Authors: Liu Chen-yu 
Published: February 2011

Abstract
We conducted a population-based case-control study in an industrial city of southern Taiwan to investigate childhood leukemia risk in relation to the association of maternal and offspring polymorphisms with residential petrochemical exposures. A total of 109 leukemia cases and 220 controls younger than 20 years were recruited between November 1997 and December 2005. A procedure using geographic information system tools was used to estimate individual-level exposure by accounting for subjects’ mobility, length of stay at each residence, distance to petrochemical plant(s), and monthly prevailing wind direction. Multivariate logistic regression was used to assess the effects of petrochemical exposures, maternal and offspring's GSTP1 genotypes, and their joint roles on offspring's leukemia risk. No main effect of residential petrochemical exposure was observed, yet the exposure association was influenced by maternal GSTP1 genotypes alone as well as by the combined maternal and offspring genotypes (P for interaction=0.02 and 0.01, respectively). Among the subjects with both mothers and offspring carrying the GSTP1 105Val variant allele(s), the adjusted odds ratio was 1.34 (95 percent confidence interval: 1.02, 1.76) for each unit of increase in the log-transformed exposure opportunity score. In conclusion, this study suggests that the childhood leukemia risk is associated with the residential petrochemical exposures, modified by both offspring's and maternal GSTP1 genotypes.
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 4693.
Abstract 4716: Mitochondrial DNA variants in colorectal adenomatous polyps
Authors: Aikhionbare Felix O. , Akwe Joyce A. , Mehrabi Sharifeh , Tah Sahil C. , Okoli Joel 
Published: February 2011

Abstract
Colorectal tumors mostly arise from sporadic adenomas (polyps). Polyps are defined as a mass of cells that protrudes into the lumen of the colon. Adenomatous polyps are benign neoplasms that, by definition display some characteristics of dysplasia and it has been well documented that polyps were benign tumors that may undergo malignant transformation. Adenomatous polyps have been classified into three histologic types, with increasing malignant potential; tubular, tubulovillous, and villous. The ability to differentially diagnose these colorectal adenomatous polyps is important for therapeutic intervention. To date, most efforts to identify genetic changes involved in adenomatous polyps have been focused on the nuclear genome. This study was designed to examine the relevance of mitochondrial genome alterations in the three adenomatous polyps. Using high resolution restriction endonucleases and PCR-based sequencing, fifty-seven primary fresh frozen tissues of adenomatous polyps (12 tubular and 5 matched surrounding normal tissues; 11 tubulovillous and 6 matched surrounding normal tissues and 14 villous and 9 matched surrounding normal tissues) obtained from the southern regional Cooperative Human Tissue Network (CHTN) and Grady Memorial Hospital at Atlanta were screened with three mtDNA regional primer pairs. Results from our data analyses revealed the presence of forty-seven variants in these mitochondrial genes; COX I, II, ATPase 6, 8, CYT b and ND 5. Six of the 49 variants detected were previously unreported and the MITODAT database [#J01415] was used as a sequence reference. Notably, a somatic variant C8515G/T in the MT-ATP 8 gene was observed at a frequency of 100% (12/12) in tubular adenomas and a germline variant 8327delA in the ATP 8 gene was observed at a frequency of 100% (47/47) among the tissue samples of the three adenomatous polyps. A germline variant G9055A in the MT-ATP 6 gene had a frequency of 100% (34/34) in tubular and villous adenomas; no corresponding variant was in tubulovillous adenomas. Furthermore, variant A9006G at MT-ATP 6 gene was observed at 74% (6/23) frequency of villous adenomas only. Interestingly, the A9006G variant was absent in six of the villous tissue samples that were clinicopathological designated as “polyvillous adenomas”. Our current data provide a basis for continued investigation of certain mtDNA variants as predictors of the three adenomatous polyps in a larger number of clinicopathological tissue specimens.
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 4716.
Abstract 4757: CancerVaccine: Novel proteinase treatment of melanoma cancer cells produces a cancer vaccine with enhanced protective adaptive immune response
Authors: Drewe John A. , Qian Yong , Shi Jin , McClurg Michael , Li Weidong , Campbell Tom 
Published: February 2011

Abstract
To facilitate the development of whole cell cancer vaccines, harmless derivatives or variants of cancer cells, BioMedicure reports here the development of a specific proteinase treatment to produce a whole cell melanoma cancer vaccine that induced specific adaptive or acquired immune responses against cancer cells specifically. The melanoma CancerVaccine was derived by treatment in vitro of B16 melanoma cells with a proteinase formulation, TumoraseTM (T101, BioMedicure, San Diego, CA). Studies show that the resultant preparation is nonviable in vitro and that upon injection into wild type or nude mice does not initiate tumors. In contrast, the same B16 cancer cells treated with other proteinases, as an example trypsin, readily replicate in vitro and elicit tumors in vivo. Wild-type mice vaccinated subcutaneously at day 1 and 15 were protected against subsequent challenge by living B16 cancer cells, with most attaining a normal lifespan. In contrast, animals that were not vaccinated or those vaccinated with TumoraseTM -treated normal cells grew large tumors and had to be sacrificed within 30 days due to large tumor burden. Major breakthroughs for the melanoma CancerVaccine are enhanced recognition by the immune system as foreign as shown by the almost complete protection. Proposed is that the TumoraseTM -treated non viable cancer cells are now recognized as foreign enhancing the antigen presentation process thus promoting engulfment by macrophage and dendritic cells for the antigen presentation process. Preserved are most, if not all, intracellular antigens that are general to heterogeneous cancer cells as well as specific to the cancer type all at their natural copy number. As more antigen species proceed through the antigen presentation process, the immune system sorts out the highly antigenic epitopes. The procedure does not introduce new antigens that may confuse the immune system since there is no molecular manipulation of the cells. Simple production with potential improved and consistent quality can be achieved during the manufacturing of this vaccine. With the TumoraseTM -treated B16 melanoma cells CancerVaccine antigens are presented on surfaces of professional antigen presenters without interference of self-recognition molecular patterns giving a good immune response and robust protection from tumor challenge. All of these advantages lead to more potent immune responses covering a wide range of cancer cell mutations. Therefore, CancerVaccine is expected to be an improvement over other whole cell cancer vaccines including gamma-ray irradiated whole cell cancer vaccines.
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 4757.
Abstract 476: Mammary tumors in lipocalin-2 deficient MMTV-PyVT mice grow faster but show decreased metastasis to lung
Authors: Chow Heiman , Fan Pengcheng , Xu Aimin , Hsiao Wen Laun Wendy , Wang Yu 
Published: February 2011

Abstract
Lipocalin-2, an iron and lipid binding glycoprotein, has been previously found to be abnormally expressed in malignant human cancers. In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT) transgenic mice, with reduced or depleted lipocalin-2 expressions were established, for evaluating the stromal effects of lipocalin-2 deficiency on mammary tumor development. When compared to MMTV-PyVT control mice, lacking of lipocalin-2 delayed tumor onset but promoted the rate of tumor progression. However, lipocalin-2 deficiency led to a significantly reduced tumor metastasis to lungs. Mechanistic studies revealed that there was a reduced level of 12-Hydroxyeicosatetrenoate (12-HETE), a lipoxygenase metabolite positively related to tumor cell metastatic potential, in the tumor lysates of lipocalin-2 deficient mice. Replacement with lipocalin-2 by adenovirus based overexpression approach enhances mammary tumor metastasis through selectively upregulating the arachidonic acid metabolic pathway. Our findings, on the one hand support previous findings that lipocalin-2 is a pro-oncogenic factor in breast tumor development; on the other hand, the results also suggest that apart from its effect on matrix metalloproteinase activity, lipocalin-2 exacerbates tumorigenesis and metastasis through disrupting the lipid homeostasis in the tumor microenvironment.
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 476.
Abstract 4770: Cell-to-cell transfer of Ras proteins from cancer cells to lymphocytes at the immunological synapse is augmented upon antigenic specificity
Authors: Vernitsky Helly , Rechavi Oded , Nagar Meital , Kloog Yoel , Goldstein Itamar 
Published: February 2011

Abstract
Immune cells establish dynamic adhesive cell-cell interactions at a specific contact region, termed the immunological synapse (IS). Important features of the IS are the formation of cell-cell membrane fusions and bridges and the intercellular transfer of selected proteins. In previous studied we found that upon IS formation, a variety of Ras super-family members transfer intact from B cells to T and NK cells, and consequently transmit signals across cell boundaries. Mutations in Ras proto-oncogenes are rather common in human cancers, including melanoma, and moreover immunosurveillance is particularly important for the elimination of malignant melanoma. Thus, it was of interest to study whether mutated constitutively active Ras proteins transfer from HLA-2+ melanoma cells (MEL526) to patients-derived tumor infiltrating lymphocytes (TILs), and whether they can serve as a stimulatory ‘danger’ signal. Using an ex vivo co-culture system we found that TILs_as opposed to polyclonal T cells_efficiently and rapidly acquired intact H-Ras-G12V-GFP from MEL526 transfectants. Importantly, the adopted Ras was incorporated into the plasma membrane of the TILs in the correct in-out orientation. To study the functional consequences of the ‘non-autonomously translated’ H-Ras-G12V in the adopting TILs, we analyzed its effect on ERK1/2 activation and a variety of T cell effector functions. We found that the adopted H-Ras-G12V increased p-ERK1/2 levels in the adopting lymphocyte. Moreover, H-Ras-G12V-GFP+ TILs specifically produced more IFN-g and showed increased cytotoxic activity. In conclusion, our findings show a hitherto unobserved mode of intercellular signal transfer between T cells and cancer cells that may play an important role in the complex process of cancer immunoediting.
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 4770.
Abstract 4772: Hyperphosphorylated Paratarg-7, the first autosomal-dominantly inherited risk factor for hematological neoplasias: hyperphosphorylation by PKCzeta
Authors: Preuss Klaus-Dieter , Fadle Natalie , Regitz Evi , Grass Sandra , Klotz Markus , Pfreundschuh Michael 
Published: February 2011

Abstract
Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins might play a role in the pathogenesis of these neoplasms. By screening a commercially available recombinant human cDNA expression macroarray we identified paratarg-7 as the antigenic target of the paraprotein from 14% (35/252) of all patients analyzed (Preuss et al. Int J Cancer 2009). The high frequency of hyperphosphorylated paratarg-7 as the antigenic target of paraproteins from MM/MGUS patients suggests that the modified protein is involved in the development of sporadic and familial MGUS/MM by acting as a chronic antigenic stimulus for the respective B-cell clones. With a relative risk of 7.9, the carrier state of hyperphosphorylated paratarg-7 (pP-7) is the strongest risk factor for the development of MGUS/MM. Moreover, the analysis of consanguineous relatives of MM/MGUS patients with an anti-paratarg-7 specific paraprotein showed that pP7 is inherited in a dominant fashion (Grass et al., Lancet Oncology, 2009). Here we present data showing that the hyperphosphorylation of paratarg-7 is due to an additional phosphorylation of this protein at the identical phosphorylation site when compared to normal paratarg-7. We identified protein kinase C zeta as responsible for this hyperphosphorylation which specifically occurs on Ser17 which is part of the 15 amino acid region identified as the paraprotein-binding epitope in all paratarg-7-immunopositive patients. In additional experiments no DNA modification of PKCzeta was detected. As shown by Western blot experiments and quantitative PCR no overexpression or copy number variation of PKCzeta was shown, suggesting that other not yet identified enzyme(s) must be involved in the process of paratarg-7 hyperphosphorylation or the maintenance of the hyperphosphorylated state.
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 4772.
Abstract 4779: Circulating and tumor-infiltrating CD4+IL-17+ T-cells in mice bearing orthotopic and heterotopic prostate tumors
Authors: Hung Tzong-Tyng , Russell Pamela J. , Power Carl A. 
Published: February 2011

Abstract
Helper T-cells expressing interleukin-17 are classified as TH17 cells, which are important in autoimmune disease and inflammatory responses. However, there are limited studies on their role and effects on cancer development and progression. Here we used a syngeneic murine model for prostate cancer, RM1(BM)-B4H7-Luc, to evaluate the proportion of TH17 cells in various organs (spleen, lymph nodes, prostate) and peripheral blood of tumour-bearing mice compared to normal mice. The number of tumour-infiltrating TH17 cells in tumours located at different sites (subcutaneous and prostate) were also compared. The proportion of TH17 cells in the peripheral blood of prostate tumour-bearing mice was significantly higher than in age-matched control mice (p&lt;0.05) or mice bearing subcutaneous tumours (p&lt;0.05). Additionally, an increase in the proportion of tumour-infiltrating CD4+ T cells expressing IL-17 was observed in both subcutaneous (9.28%) and prostate tumours (10.2%) compared to lymphoid organs (spleen and lymph node, &lt;1%) from these mice, suggesting sequestration of these cells within the tumour. In addition, significantly higher numbers of TH17 cells were detected in prostate tumours compared to normal prostates (p=0.0357). Finally, the percentage TH17 in the peripheral blood of mice with prostate tumours correlated with the size of the tumour ((R2=0.84, p=0.0014). In conclusion, in our model, we show that TH17 cells are a significant proportion of tumour infiltrating T-cells and, as proposed in recent studies, they are likely to be involved in the anti-tumour immunity/tumour rejection. Importantly, the number of circulating TH17 cells correlates with tumour size for prostatic tumours, but not subcutaneous tumours. Thus, assessment of peripheral blood TH17 cells may be an effective tool for diagnosis/prognosis of prostate cancer. This relationship does not hold if subcutaneous models are used for preclinical studies.
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 4779.
Abstract 4780: CD4 T-lymphocyte responses to the human telomerase reverse transcriptase (hTERT) in patients (pts) with advanced non small cell lung cancer (NSCLC)
Authors: Fabre Elizabeth , CAZES Aurelie , Ravel Patrice , Medioni Jacques , Dosset Magali , Leviennois Emeline , Tartour Eric , Meyer Guy , Riquet Marc , Adotevi Olivier 
Published: February 2011

Abstract
Background: hTERT is a potential target for cancer immunotherapy because it is highly expressed in tumor cells. To assess the applicability of hTERT-based immunotherapy in NSCLC, we aimed to analyse the natural anti-hTERT CD4 T-lymphocyte responses in advanced NSCLC pts. Methods: We included in a prospective, monocentric study chemonaive NSCLC pts. Pts were required to present stage III or IV tumor, without any immune deficiency or immunosuppressive drug. Before start of chemotherapy, the anti-hTERT T-lymphocyte responses were assessed in whole blood by ELISPOT test. We evaluated the presence or absence of hTERT-specific CD4 T lymphocytes. Thereafter, we analyzed its link with age (&lt; 70 vs. ≥ 70 yrs), ECOG performance status PS (0-1 vs. 2-3), tumoral stage (IIIA vs. IIIb + IV), histological subtype (adenocarcinoma vs. other) and smoking status (never smoker vs. smoker). Statistical analysis was performed using chi-Square or Fischer test. Results: Between February 2008 and October 2009, fifty-one NSCLC pts were included. They presented a stage IIIa (n = 5), IIIb (n = 5) or IV (n = 41) disease. Median age was 66 yrs [39-89]. Nineteen pts presented anti-telomerase CD4 T lymphocytes (37 %); among them we found 14 stage IV (73 %), 13 pts &lt; 70 yrs (68 %), 12 pts with PS 0/1 (63 %), 18 adenocarcinoma/undifferentiated carcinoma (94 %), 13 pts with stable disease/ partial response (68%). Furthermore, all non smokers have anti-telomerase immune response. Conclusions: These preliminary results demonstrate that natural anti-hTERT immune response exists in NSCLC pts, even in case of advanced disease. However the presence of immune response is more frequently found in pts less than 70 yrs with good PS, in non squamous cell carcinoma and in pts with non progressive disease. The study is ongoing to evaluate if baseline anti-hTERT immune response could be used as selection criteria for telomerase vaccination in NSCLC.
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 4780.