bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1298: The effect of adipocyte-derived factors on lung cells: Exploring the protective nature of excess weight on lung cancer risk
Authors: Penney Rosalind B. , Sappington Daniel , Siegel Eric , Boysen Gunnar , Kadlubar Susan 
Published: August 2015

Abstract
Lung cancer is the second most common cancer in men and in women (not including skin cancer) and the most common cause of cancer mortality. According to several epidemiologic papers, excess weight, identified as the BMI categories of overweight and obese, lowers lung cancer risk. Despite the numerous studies describing this anomaly, the underlying mechanisms for the protective effects are still unknown. Adipose tissue is known to secrete inflammatory molecules such as IL6, IL1β, and IL12. Activated IL6- and IL1β-associated inflammatory pathways are known to promote tumorigenesis, while the activated IL12-associated pathway inhibits tumorigenesis. We hypothesize that adipocytes create an environment that prevents lung carcinogenesis through activating inflammatory pathways that inhibit tumor growth and through blocking inflammatory pathways that promote tumor growth.
To study the effect of adipocyte-derived factors on lung cells, alveolar fibroblasts (MRC5) and lung carcinoma (A549) cells were cultured in standard medium and in a 50:50 standard: adipocyte-conditioned medium (CM). In addition, cells were treated with benzo[a]pyrene (B[a]P), a known lung carcinogen. After 48 hours, mRNA expression levels of inflammatory genes were determined by RT-PCR. The data demonstrate that B[a]P treatment induced expression of IL1β, IL6 and IL12 in both cell lines. CM treatment decreased expression of IL1β and IL6 in MRC5 cells and increased their expression in A549 cells. In contrast, CM treatment decreased expression of IL12 in both cells lines. Cells treated with B[a]P plus CM had increased expression of IL12 in both cell lines, and reduced expression of IL1β and IL6 in MRC5 (2.3-fold and 6.5-fold, respectively) and A549 cells (40-fold and 11.5-fold, respectively) over B[a]P-treated cells. It was demonstrated that combined treatment increased NFκB (a transcription factor for IL1β, IL6 and IL12) mRNA expression 4-fold over control. The data suggest that conditioned medium inhibits B[a]P-induced and NFκB-mediated expression of IL1β and IL6 but increases NFκB-mediated expression IL12. This suggests that excreted factors from an adipocyte-rich environment may lead to the activation of growth-prohibiting inflammatory pathways, as opposed to growth-promoting pathways. Understanding these mechanisms and the possible discovery of biomarkers can be the foundation for new preventive techniques and treatments for lung cancer.
Citation Format: Rosalind B. Penney, Daniel Sappington, Eric Siegel, Gunnar Boysen, Susan Kadlubar. The effect of adipocyte-derived factors on lung cells: Exploring the protective nature of excess weight on lung cancer risk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1298. doi:10.1158/1538-7445.AM2015-1298
Abstract 1311: The frequency of circulating Vδ1-positive but not Vδ2-positive γ/δ T cells correlates negatively with survival in late-stage melanoma and may be increased by ipilimumab treatment
Authors: Wistuba-Hamprecht Kilian , Weide Benjamin , Martens Alexander , Pawelec Graham P. 
Published: August 2015

Abstract
Recently, there has been a resurgence of interest in the possibility of using γ/δ-T cells in cancer immunotherapy, because these cells can kill melanoma cells in vitro, and IL-2 and zoledronate treatment can expand some human γδ cells in vitro and in animal models in vivo. The presence of the main subsets of γ/δ-T cells in late-stage melanoma patients and relationship with survival has not been extensively explored, although relatively lower percentages of Vδ2-positive cells has been reported in melanoma. Here, we present preliminary data on associations between the major γ/δ-T cell subsets and survival in melanoma patients, and whether baseline data are informative for predicting responses to ipilimumab treatment. We used a carefully validated set of monoclonal antibodies to assess γ/δ-phenotypes, because we found that certain commercial reagents were not behaving as specified (Wistuba-Hamprecht et al. OMIP-020: phenotypic characterization of human γδ T-cells by multicolor flow cytometry. Cytometry A. 2014; 85:522-4). Comparing a total of 39 stage IV melanoma patients with 27 controls, we found no overall differences in Vδ1 or Vδ2 T-cell frequencies, or in proportions of naïe (CD27, CD28-double positive, CD45RA+)-vs -late-differentiated (CD27,CD28-double negative, CD45RA+) γ/δ cells. However, Kaplan-Meier plots stratifying individual patients into groups with Vδ1 or Vδ2 frequencies above or below the median showed that the presence of Vδ1 but not Vδ2 cells negatively correlated with longer survival (p = 0.033 log-rank; p = 0.047 Breslow). In a subgroup of 9 patients, ipilimumab treatment resulted in an increase of peripheral Vδ1+ T-cells (p = 0.0391, Wilcoxon) but not of Vδ2+ T-cells (p = 0.375, Wilcoxon). We are currently analyzing data from a larger prospective study of ipilimumba treatment with over 100 patients, to confirm or refute these results.
Citation Format: Kilian Wistuba-Hamprecht, Benjamin Weide, Alexander Martens, Graham P. Pawelec. The frequency of circulating Vδ1-positive but not Vδ2-positive γ/δ T cells correlates negatively with survival in late-stage melanoma and may be increased by ipilimumab treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1311. doi:10.1158/1538-7445.AM2015-1311
Abstract 1343: Abcc3 up-regulation confers protection from chemotherapy to NK cells in a murine model of malignant glioma
Authors: Pellegatta Serena , Pessina Sara , Cantini Gabriele , Cazzato Emanuela , Kapetis Dimos , Finocchiaro Gaetano 
Published: August 2015

Abstract
Growing evidence suggests that chemotherapy can influence the immune response by inducing lymphopenia or enhancing immunogenicity of dying tumor cells. In a clinical trial currently active in our Institution, patients with first diagnosis of glioblastoma are treated with dendritic cells (DC) loaded with autologous tumor lysate together with standard radio and chemotherapy with temozolomide. Peripheral blood lymphocytes from 22 patients were analyzed by flow cytometry to identify immune cell activation before and after DC vaccines. The ratio of vaccine/baseline frequencies (V/B ratio) was correlated with the survival of each patient. Increased V/B ratio for NK cells was significantly associated with prolonged PFS and OS (median 15.0 vs 8.0 mo, p = 0.003; 22.0 vs 12.0 mo, p = 0.02, respectively). Using the murine malignant glioma GL261, we investigated the molecular mechanisms induced by TMZ on NK and CD8 T cells. We treated mice 9 days after intracranial implantation of GL261 cells with intraperitoneal injections of TMZ (5 mg/kg) or vehicle (control mice) for 5 days. Mice were sacrificed at different time points and tumor and peripheral blood harvested and analyzed by flow cytometry. Gene expression profiling on peripheral blood lymphocytes revealed an up-regulation of multidrug resistance genes in NK cells, but not in CD8 T lymphocytes, in TMZ-treated mice compared to controls. The increased expression of the ATP transporter gene Abcc3 was confirmed by real time PCR (4.2-fold higher than controls, P = 0.006). Using eFluxx-ID multidrug resistance (MDR) assay based on specific inhibitors, we also demonstrated that Abcc3 was functionally active during TMZ treatment. NK cell resistance to chemotherapy was accompanied by an increase in migration and homing ability into the brain at early time point and in cytotoxicity at later phases (beyond the end of TMZ treatment).
Our data show that murine NK cells are resistant to and activated by TMZ chemotherapy. Further investigations in patients treated by radio-chemotherapy with or without DC immunotherapy are warranted.
Note: This abstract was not presented at the meeting.
Citation Format: Serena Pellegatta, Sara Pessina, Gabriele Cantini, Emanuela Cazzato, Dimos Kapetis, Gaetano Finocchiaro. Abcc3 up-regulation confers protection from chemotherapy to NK cells in a murine model of malignant glioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1343. doi:10.1158/1538-7445.AM2015-1343
Abstract 1358: Generation of induced pluripotent stem cells from tumor-infiltrating lymphocytes
Authors: Saito Hidehito , Okita Keisuke , Fusaki Noemi , Sabel Michael , Chang Alfred , Ito Fumito 
Published: August 2015

Abstract
Human induced pluripotent stem cells (iPSCs) derived from somatic cells of patients hold great promise for autologous cell therapies. One of the possible applications of iPSCs is to use them as a cell source for producing autologous lymphocytes for cell-based therapy against cancer. Tumor-infiltrating lymphocytes (TILs) were found to have tumor-reactive T cells and have been used for adoptive cell therapy for metastatic melanoma. The objective in this study is to generate iPSCs from TILs and assess their pluripotency. Under the approved protocol by the Institutional Review Board and the Human Pluripotent Stem Cell Research Oversight Committee, we obtained melanomas from a patient who provided informed consent for tissue procurement and generation of iPSCs. TILs were reprogrammed by Sendai virus (SeV) vector encoding four pluripotency transcription factors (Oct3/4, Klf4, Sox2 and c-Myc). TIL-derived iPSCs (TIL-iPSCs) were characterized by their pluripotency. Within 3 weeks of infection with SeV to deliver pluripotency transcription factors, we identified colonies that resembled embryonic stem cells (ESCs) among the T cell derivatives. TIL-iPSCs displayed typical stem cell morphology and had a normal karyotype. Alkaline phosphatase and immunofluorescence staining with stem cell surface markers, OCT3/4, SSEA3, SSEA 4, TRA1-81 and TRA1-60 proteins suggested pluripotency of colonies. RT-PCR analyses revealed that TIL-iPSCs expressed pluripotent stem cell markers such as NANOG, OCT3/4 at levels comparable to those in ESCs. T cell receptor (TCR) gene rearrangement analysis in TIL-iPSCs confirmed that they originated from mature T cells and retained diversity of TCR gene rearrangement. In conclusion, human iPSCs with diverse TCR gene rearrangement can be generated from TILs efficiently by SeV encoding four pluripotency transcription factors. Future work will explore their differentiation potential to T cells for cancer immunotherapy. We acknowledge in DNAVEC Corporation for kindly providing Sendai virus vectors. This study was supported by the University of Michigan Start-up fund, American College of Surgeons and Central Surgical Association.
Note: This abstract was not presented at the meeting.
Citation Format: Hidehito Saito, Keisuke Okita, Noemi Fusaki, Michael Sabel, Alfred Chang, Fumito Ito. Generation of induced pluripotent stem cells from tumor-infiltrating lymphocytes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1358. doi:10.1158/1538-7445.AM2015-1358
Abstract 1361: The decoy receptor interleukin-1 receptor type 2 acts as an angiogenic factor in human colorectal cancer
Authors: Mar Ai-Chung 
Published: August 2015

Abstract
We previously demonstrated that interleukin-1 receptor type 2 (IL1R2), an IL-1 decoy receptor that inhibits exogenous IL-1 signaling, intracellularly activates the expression of several pro-inflammatory cytokines. In this study, we observed that IL1R2 was overexpressed in human colon cancer cells (CRC) compared to normal colon cells. In addition, we observed that the IL1R2 level was higher in late-stage clinical CRC patients and that a high level of IL1R2 was associated with a poor 5-year survival rate in CRC patients. Furthermore, we observed that the levels of IL1R2 and IL-6 were strongly correlated in 40 CRC patients. To elucidate the oncogenic roles of intracellular IL1R2, we modulated its expression levels in human CRC cell lines. We verified that the intracellular level of IL1R2 was correlated with the migration ability of CRC, cells. We observed that the VEGF-A and IL-6 levels were significantly increased in conditioned media harvested from IL1R2-overexpressing cells, and these elevated VEGF-A and IL-6 levels enhanced the proliferation, migration, and tube formation of cultured endothelial cells. We further demonstrated that intracellular IL1R2 levels were positively associated with tumor growth and microvessel density in xenograft mouse models. Furthermore, we observed that IL1R2 formed a complex with c-Fos. This complex bound to the AP-1 site at the IL-6 and VEGF-A promoters. Together, these results reveal that intracellular IL1R2 acts with c-Fos to enhance the transcription of IL-6 and VEGF-A, which promotes tumor malignancy and angiogenesis.
Citation Format: Ai-Chung Mar. The decoy receptor interleukin-1 receptor type 2 acts as an angiogenic factor in human colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1361. doi:10.1158/1538-7445.AM2015-1361
Abstract 1390: Combination of carbon ion beam and gemcitabine causes unrepairable DNA damage and death of radioresistant pancreatic cancer stem-like cells in vitro and in vivo
Authors: Sai Sei , Wakai Toshifumi , Vares Guillaumes , Yamada Shigeru , Kamijo Takehiko , Kim Eun Ho , Kamada Tadashi , Shirai Toshiyuki 
Published: August 2015

Abstract
Purpose
To elucidate whether carbon ion beam alone or in combination with gemcitabine has advantages over X-ray irradiation in targeting putative human pancreatic cancer stem cells (CSCs).
Materials and Methods
Human pancreatic CSCs sorted from PANC1 and PK45 cells were treated with carbon ion beam, X-ray alone or in combination with gemcitabine, and then colony, spheroid and tumor formation assays, RT Profiler PCR Array assay, immunofluorescence γH2AX foci assay as well as in vivo tumor control analysis were performed.
Results
The colony, spheroid formation as well as tumorigenicity assays confirmed that CD44+/ESA+ cells exactly have CSC properties compared to CD44-/ESA- cells. CSCs were more highly enriched after X-ray or gemcitabine compared to carbon ion beam alone, but extremely enhanced either X-ray or carbon ion beam in combination with gemcitabine. The number of colony and spheroid formed from CSCs after carbon ion beam was significantly reduced compared to that of X-ray, and it was extremely suppressed when combined with gemcitabine. The relative biological effectiveness (RBE) values for the carbon ion beam relative to X-ray at the D10 levels for CSCs were 2.13-2.78. RT Profiler PCR Array analysis showed that expressions of apoptosis-related genes (Bax, Cytochrome c), autophagy-related genes (LC3, p62), and senescence-related gene p21 were remarkably induced after carbon ion beam combined with gemcitabine compared to carbon ion beam alone or X-ray combined with gemcitabine. Immunofluorescence assay showed that not only the number but also the size of γH2AX foci in CSCs were lager 24 h after carbon ion beam combined with gemcitabine compared to carbon ion beam alone or X-ray combined with gemcitabine. Xenograft tumor control analysis showed that the tumors were not completely controlled even treated with 60 Gy of X-ray, but it was destroyed with 25 Gy of carbon ion beam combined with 50 mg/kg gemcitabine.
Conclusions
Carbon ion beam combined with gemcitabine has superior potential to kill pancreatic CSCs via unrepairable clustered DSB, and multiple cell death pathways at relatively lower doses compared to carbon ion alone or X-ray combined ith gemcitabine.
Citation Format: Sei Sai, Toshifumi Wakai, Guillaumes Vares, Shigeru Yamada, Takehiko Kamijo, Eun Ho Kim, Tadashi Kamada, Toshiyuki Shirai. Combination of carbon ion beam and gemcitabine causes unrepairable DNA damage and death of radioresistant pancreatic cancer stem-like cells in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1390. doi:10.1158/1538-7445.AM2015-1390
Abstract 1407: Identification of sialylated glycoproteins in doxorubicin-treated hepatoma cells with glycoproteomic analyses
Authors: Miyoshi Eiji , Azuma Kanako , Takamatsu Shinji , Terao Naoko , Serada Satoshi , Naka Tetsuji , Kamada Yoshihiro 
Published: August 2015

Abstract
Sialylation is one of the most important types of glycosylation involved in carcinogenesis and establishment of cancer stemness. We previously showed that increased sialylation is a characteristic glycan change in cancer stem cells (CSCs) from hepatocellular carcinoma (Cancer Science 2011, Moriwaki et al). However, the identities of glycoproteins targeted for sialylation remain unknown. CSC fraction is too small to identify target proteins with glycol-proteomics analyses. In the present study, we identified glycoproteins targeted for sialylation in doxorubicin (DXR)-treated hepatocarcinoma cell line, Huh7, using glycoproteomic analyses. Since CSCs constitute a small subset of cells within carcinoma cell lines, it is difficult to identify sialylated proteins using general glycoproteomic strategies. It is known that treatment with anti-cancer drug can condense CSCs, we used DXR to concentrate CSCs. In DXR-treated Huh7 cells, isobaric tag for relative and absolute quantitation (iTRAQ) analysis identified 17 sialylated glycoproteins. Most of the identified glycoproteins were cancer-associated proteins. Furthermore, two proteins of approximately 70 kDa were detected using Sambucus sieboldoana agglutinin (SSA) blot analysis and identified as beta-galactosidase and alpha-2-HS-glycoprotein (fetuin-A) by SSA precipitation followed by liquid chromatography-tandem mass spectrometry analyses. Sialylation levels of fetuin-A were increased in DXR-treated Huh7 cell lysates. Furthermore, intracellular localization of fetuin A with sialylation was changed in DXR-treated Huh7 cells under observation with confocal microscopy These changes in sialylation of glycoproteins might be involved in the establishment of cancer stemness.
Citation Format: Eiji Miyoshi, Kanako Azuma, Shinji Takamatsu, Naoko Terao, Satoshi Serada, Tetsuji Naka, Yoshihiro Kamada. Identification of sialylated glycoproteins in doxorubicin-treated hepatoma cells with glycoproteomic analyses. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1407. doi:10.1158/1538-7445.AM2015-1407
Abstract 1409: Whole-cell and local viscoelasticity of stem-like and non-stem-like breast cancer cells
Authors: Alipour Amina , Burdick Monica M. , Tees David F.J. 
Published: August 2015

Abstract
It has been shown that the mechanical properties of pathological cells are different from healthy ones. Therefore, mechanical characterization of cells may be useful for investigating mechanisms and progression of diseases. In the case of cancer, the finding that cancerous cells are considerably more deformable than normal ones provides the motivation for investigating rheological differences between stem-like and non-stem-like cancer cells. In this study, the viscoelastic properties of six breast cancer cell lines, three of which have been regarded (based on surface markers) as stem-like and three considered less stem-like, were measured using micropipette aspiration and particle tracking microrheology. In micropipette experiments, cancer cells were aspirated one-by-one at controlled pressures into small glass micropipettes and the length of the aspirated section of the cells was tracked as a function of time. The applied pressure was either increased linearly or increased suddenly to different levels and then held constant. The homogeneous elastic half-space model was used to interpret the viscoelastic properties of the different cell lines. The effect of pressure loading rate on cell viscoelasticity was examined by applying three different aspiration pressure rates of 9, 6, and 3 Pa/s. The apparent Young's modulus was found to depend on pressure loading rate, which suggests a more complex rheology than a standard viscoelastic solid. Above a threshold force level, cells were also found to enter the micropipette continuously in a fashion that is analogous to white blood cells, i.e. as a liquid drop with constant cortical tension. A comparison between the Young's moduli showed that at least some of the stem-like breast cancer cell lines were less stiff than less stem-like cell lines and more likely to exhibit the liquid drop-like behavior. The reduction in stiffness and change in rheological regime might be the result of lower actin filament density which allowed the stem-like cancer cells to be more deformable while undergoing extravasation and intravasation during the metastatic process. Regional rheological differences were also found using particle tracking microrheology. Our hypothesis is that the differences in the rheological properties might help to distinguish between stem-like cancer cells and non-stem-like ones, which could eventually lead to a new detection and diagnostic method in cancer research.
Citation Format: Amina Alipour, Monica M. Burdick, David F.J. Tees. Whole-cell and local viscoelasticity of stem-like and non-stem-like breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1409. doi:10.1158/1538-7445.AM2015-1409