bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5304: Serum vascular endothelial growth factor in advanced breast cancer patients might be a key role of inhibitory effect on lymphokine activated killer cells
Authors: Suzuki Eiji , Hirose Makiko , Suzuki Noriko , Muta Mariko , Sekine Susumu , Kitagawa Dai , Horiguchi Kazumi , Aruga Tomoyuki , Ymashita Toshinari , Kuroi Katsumasa 
Published: February 2011

Abstract
Previously, we reported that serum from stage IV breast cancer patients diminished the cytotoxic activity of lymphokine activated killer cells (LAKs) (Abstract #4639 AACR in 2008). Thus, we next tested what the critical role for the inhibitory effect on LAKs was. Based on the study of protein detection in the serum using Cytokine Antibody Array (Ray Biotech), serum from stage IV patients seemed to have higher level of vascular endothelial growth factor (VEGF) as compared to early stage patients. To confirm this by more accurate way, we analyzed the serum level of VEGF by using ELISA in 24 breast cancer patients. When the serum level of VEGF was cut off by median (420 pg/ml), 11 patients with higher level of VEGF out of 12 are included in the patients whose serum inhibited the cyototoxic activity of LAKs. Therefore, we hypothesized that VEGF might be one of the key role for inhibitory effect on LAKs and neutralization of serum VEGF from the patients whose serum inhibited the cyototoxic activity of LAKs could have no inhibitory effect on LAKs. Briefly, PBMCs from a healthy volunteer were used as an effector cell for all patients’ serum incubation. After activation of the PBMCs using IL-2, LAKs were prepared and incubated with the individual patient's serum and washed. The LAKs were incubated with human breast cancer cell line MCF-7 as a target cell and LDH assay was performed to detect cytotoxicity of the LAKs. Fourteen out of 24 patients serum (serum 1) showed inhibitory effect on LAKs and we picked up these patients to test blocking study of serum VEGF. Briefly, serum from these 14 patients was incubated with neutralization antibody of VEGF (R16Y, Santa Cruz Biotechnology) (serum 2) before mix with LAKs. After incubation of serum 1 and serum 2 with LAKs, target cell cytotoxicity of LAKs from incubation with serum 1 showed 30-50% reduced level as compared to control LAKs activity. Interestingly, target cell cytotoxicity of all LAKs from incubation with serum 2 did not show such inhibitory effect (mean cell cytotoxicity of LAKs was 33.48% and 57.27%, serum 1 and serum 2, respectively, control; 55.73%). These data suggest that high level of serum VEGF in breast cancer patients might be a key role of inhibitory effect on LAKs and neutralization of the VEGF could help adoptively transferred LAKs as cancer immunotherapy in the patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5304.
Abstract 5309: Programmed Death Ligand-1 expression on the cell surface is regulated by Costimulatory Molecule CD80 expressed by cancer vaccines
Authors: Haile Samuel T. , Bosch Jacobus , Agu Nnenna , Ostrand-Rosenberg Suzanne 
Published: February 2011

Abstract
With the lack of effective treatments for metastatic cancers, the employment of immunotherapies, cell-based vaccines particularly, to activate a patient's own immune system is a promising approach for the treatment of disseminated metastatic cancer. Many tumor cells constitutively express or are induced by Interferonγ (IFNγ) to express the inhibitory molecule Programmed Death Ligand 1 (PDL1). Since many cell-based vaccines are derived from tumor cells, the expression of PDL1 could reduce the therapeutic efficacy of the vaccines. PDL1 binds to its receptor Programmed Death 1 (PD1) on T cells and can signal for either apoptosis of T cells or can prevent their activation. As determined by flow cytometry using three anti-PDL1 monoclonal antibodies (mAb) that detect distinct PDL1 epitopes, and human lung, uveal melanoma, cutaneous melanoma, and breast cancer cells, the over-expression of CD80 blocks constitutive and IFNγ-induced cell surface expression of PDL1. Quantitative analysis of CD80 and PDL1 expression indicates an inverse relationship between PDL1 and CD80. CD80+ tumor cells contain intracellular PDL1, as assessed by flow cytometry, suggesting that CD80 regulates PDL1 at the protein level. Tumor cells transfected with CD80 constructs lacking a cytoplasmic domain or with an irrelevant non-signaling cytoplasmic domain, retain the ability to block PDL1 expression at the cell surface indicating that CD80 does not modulate PDL1 transcription via intracellular signaling. These results suggest that in addition to serving as a costimulatory molecule, CD80 facilitates T cell activation by blocking coinhibitory signals and preventing T cell apoptosis.
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 5309.
Abstract 5320: Deletion of TGFß signaling in Gr-1+CD11b+ myeloid cells attenuates breast adenocarcinoma progression
Authors: Pang Yanli , Yan Hannah H. , Li Chaoyang , Achyut B. R. , Yang Li 
Published: February 2011

Abstract
TGFß is a very important mediator in tumor progression. However, the contribution of TGFß signaling in tumor-infiltrating inflammatory cells in this process is unclear. Gr-1+CD11b+ myeloid cells are overproduced in tumor host. They infiltrate into tumor tissues and contribute to immune suppression, tumor angiogenesis and metastasis. Data from our studies demonstrate that Gr-1+CD11b+ myeloid cells are recruited into the invasive front of breast adenocarcinomas. Tumor-infiltrating Gr-1+CD11b+ cells exhibit a significantly elevated TGFß signaling, including increased expression of TGFß type I and type II receptor, TGFß1 and TGFß3 ligands, as well as latent TGFß binding protein. They also produce a high level of multiple matrix metalloproteinases (MMPs) such as MMP13, MMP14, MMP2 and MMP9. Interestingly, genetic deletion of the gene encoding TGFß type II receptor (Tgfbr2) in Gr-1+CD11b+ cells significantly attenuates the production of MMP14 and MMP2. These in vitro studies were conducted by transduction of Gr-1+CD11b+ cells from Tgfbr2flox/flox mice (loxP-flanked Tgfbr2) with adenovirus expressing DNA recombinase. To further investigate if TGFß signaling plays an important role in Gr-1+CD11b+ myeloid cells mediated breast tumor progression, mice with conditional knockout of Tgfbr2 in Gr-1+CD11b+ cells are generated through cross breeding of Tgfbr2flox/flox mice with LysM-Cre mice expressing Cre in myeloid cells. These mutant mice are viable and appear to be normal. Southern blotting showed that Tgfbr2 deletion is restricted to bone marrow, spleen and lymph node but not other organs. Sorted Gr-1+CD11b+ myeloid cells but not T or B lymphoid cells exhibited over 85% of Tgfbr2 deletion. This specific TGF-ß inactivation in Gr-1+CD11b+ cells allows us to investigate its effect on tumor growth and angiogenesis, as well as metastasis. We observed a significantly attenuated 4T1 tumor growth in these knockout mice compared with the control littermates. We postulate that TGFß signaling in host derived Gr-1+CD11b+ cells is an important part of TGFß effect in tumor progression.
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 5320.
Abstract 5327: Upregulation of the expression of nonclassical MHC class I HLA-G antigen in human breast cancer cell lines and tissue
Authors: Jiang Xianpeng , Phillips Jeff , Head Jonathan F. , Barnett Brian , Elliott Robert L. 
Published: February 2011

Abstract
HLA-G is a nonclassical MHC class I molecule with immunotolerant properties. HLA-G is normally expressed by trophoblastic cells during pregnancy and protects the fetus from the maternal immune system. HLA-G is also overexpressed in tumors and plays a role in immune evasion of cancer. In this study, we used RT-PCR and immunohistochemistry (IHC) to examine HLA-G expression in normal mammary epithelial and breast cancer cell lines, normal breast tissue, and human breast cancer tissue. RT-PCR showed that normal epithelial MCF-12A cells had no HLA-G mRNA expression, while the breast cancer cell lines MCF-7, T47D and MDA-MB-231, and drug-resistant cell line NCI/Adr-Res had various levels of HLA-G mRNA expression. Furthermore, three mRNA isoforms were expressed in breast cancer cell lines. Twelve normal breast tissues from plastic surgery and 38 breast cancer tissues from mastectomy were examined by IHC. While 60.5% (23 of 38 samples) of breast cancers had medium to strong staining to HLA-G, only 33% (4 of 12 samples) of normal breast tissues had weak staining, the difference was significant (p&lt;0.05). HLA-G staining was diffusely distributed in the membrane and cytoplasm of the cancer cells and mammary epithelia. Rare staining was found in fibroblasts, vascular endothelia or inflammatory cells. In conclusion, breast cancer cells over-express HLA-G mRNA and protein in cell lines and tumors. The role of HLA-G over-expression in breast cancer-related immune evasion remains to be determined.
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 5327.
Abstract 5330: Phosphatidylserine-targeting antibody enhances survival benefit of androgen deprivation therapy in mice bearing syngeneic prostate cancer
Authors: Yin Yi , Kavlie Anita , Thorpe Philip E. 
Published: February 2011

Abstract
Purpose: Androgen deprivation therapy (ADT) remains the cornerstone treatment for advanced prostate cancer despite being principally palliative in nature. New treatment strategies aimed at enhancing tumor immunogenicity and damaging tumor vasculature could potentially improve prostate cancer response to ADT. We recently showed that targeting phosphatidylserine by antibodies resulting in enhanced tumor immunogenicity and tumor vascular damage. Bavituximab, a chimeric version anti-phosphatidylserine antibody, is being tested in clinic trails for different cancers. Here we tested the hypothesis that the fully human anti-phosphatidylserine antibody 1N11 can enhance the antitumor properties of ADT in prostate cancer
Experimental Design: Efficacy of ADT and 1N11 against prostate cancer was assessed in C57BL/6 mice bearing syngeneic RM1 prostate tumor by using castration and mouse chimeric 1N11(mch1N11). Effects on mouse survival were assessed. In vivo localization of 1N11,effects on immune cell infiltration, vasculature density were also estimated by histology.
Results: Our data showed that castration of RM1 tumor bearing mice increased the percentage of tumor vessels with exposed phosphatidylserine from 60% to 93%. Castration, when combined with mouse chimeric 1N11, led to significant survival befit versus individual treatments. The mean survival time was 16 days with control antibody. The prolongation in survival was 15 days with the combination, as compared with 3 days with mch1N11, 5 days with castration alone. Toxicity to the mice was not observed. A dramatic enhancement of tumor infiltration by a variety of immune cells and disruption of vasculature implied the combination to be more immunostimulatory and antivasculitic.
Conclusion: Combined treatment with 1N11 and ADT improves survival of mice bearing prostate cancer. These results provide the foundation for using ADT plus fully human 1N11, or bavituximab, to treat prostate cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5330.
Abstract 5333: Novel Ab treatment tool for CRC
Authors: Shapira Shiran , Kraus Sarah , Kazanov Dina , Stahel Rolf , Benhar Irai , Arber Nadir 
Published: February 2011

Abstract
Background: We have shown that CD24, a cell surface molecule, is overexpressed early in the multistep process of colorectal neoplasia (Gastroenterology, 2006) hence, it can serve as a target for early detection and immunotherapy. The anti-CD24 murine SWA11 Mab (generous gift from Prof. Sthal, Zurich University) binds to CD24 and inhibits tumor cell growth, in vitro and in vivo, in a time- and dose-dependent manner (Cancer Research, 2008). However, murine Mabs have limitations because of their xenogeneic nature and due to the human anti-mouse antibody (HAMA) response.
Aim: To produce an improved, chimeric form of the SWA11 Mab.
Methods: Mammalian vector pMAZ-IgH for human γ1 heavy-chain and pMAZ-IgL for human κ light chain expression were designed. The variable region genes encoding the murine anti-CD24 SWA11 MAb were cloned for expression as chimeric γ1/kappa antibody into the mammalian pMAZ-IgH and pMAZ-IgL expression vectors and co-transfected into HEK293 cells. Stable clones were screened and selected for IgG production, analyzed by whole-cell and antigen-based ELISA, and Western blotting.
Results: The new chimeric IgG derivative of the anti-CD24 SWA11 Mab possesses similar affinity and specificity (ELISA and Western blot), but has improved activity in inhibiting cell growth.
The chimeric Mabs also have the ability to induce complement-dependent cytotoxicity, causing up to 60% cell lysis in the presence of complement. Conclusions: We had successfully generated a chimeric IgG derivative of the anti-CD24 SWA11 Mab that can serve as a novel therapeutic tool for cancer cells harboring CD24.
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 5333.
Abstract 5337: Phase 1 study of bavituximab in advanced solid tumor malignancies: Final results
Authors: Ibrahim Nuhad , Wong Lucas , Stopeck Alison , Rosen Lee S. , Gerber David E. , Shan Joseph S. 
Published: February 2011

Abstract
Background: Bavituximab, a novel human chimeric IgG1 monoclonal antibody which targets the membrane phospholipids, phosphatidylserine complexed with β2-glycoprotein I on tumor vasculature, produces host effector cell-mediated destruction of tumor vasculature and enhancement of anti-tumor immunity (He et. al. Clin Cancer Res 2009). We are reporting on an open label dose escalation Phase 1 trial to examine the safety, pharmacokinetics and pharmacodynamics of bavituximab in adults with refractory advanced solid tumor malignancies. Methods: Patients received bavituximab monotherapy, intravenously, up to 4 doses of either 0.1, 0.3., 1 or 3 mg/kg. 26 patients with a median age of 57.6 yrs (range of 37-80 yrs) who had metastatic breast cancer (n=13), colorectal cancer (n=4), pancreatic cancer (n=3), or other solid tumors (n=6), were treated with a total of 86 doses of bavituximab. Results: 6 serious adverse events were observed in 5 patients, with 1 drug-related SAE (pulmonary embolism) at the 3 mg/kg dose. The most common AEs seen in ≥15% of patients were: nausea, fatigue; headache, constipation, dizziness cough, dyspnea, anemia, and chest pain. Pharmacokinetic measures indicated T1/2 of bavituximab ranged from 28 to 47 hrs, and Cmax on Day 0 ranged from 2 to 56 ug/ml with no accumulation seen following multiple dose administration. Coagulation testing revealed no platelet or factor abnormalities, D-dimer levels were elevated in the majority of patients at baseline and increased with disease progression. The presence of a lupus anticoagulant-like activity (prolonged aPTT or DRVVT-an in vitro test artifact) was observed only in patients treated at the highest dose tested of 3 mg/kg. Overall, 8/26 patients showed stable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) (4/14 subjects at 0.1 and 0.3 mg/kg and 4/12 subjects in 1 and 3 mg/kg dose groups). Conclusions: Bavituximab was safe and well tolerated when given as monotherapy. Based on pharmcokinetics, the maximum recommended dose for Phase II trials will be weekly at 3 mg/kg, intravenously.
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 5337.
Abstract 5346: A novel immunotoxin comprising quadruple RNase tethered to an internalizing anti-TROP-2 humanized MAb shows potent cytotoxicity against diverse solid tumors in vitro
Authors: Cardillo Thomas M. , Rossi Edmund A. , Arrojo Roberto , Chan Eric , Goldenberg David M. , Chang Chien-Hsing 
Published: February 2011

Abstract
Ribonucleases (RNase) are potential anti-tumor agents, and their potency can be enhanced by recombinant fusion or chemical conjugation with tumor-targeting antibodies, as have been demonstrated for ranpirnase (Rap), an amphibian RNase, conjugated to LL2, a murine anti-CD22 MAb (Newton et al., Blood 2001; 97: 528-35) or fused to a humanized anti-CD74 MAb (Chang et al., Blood 2005; 106: 4308-14). We have now applied the Dock-and-Lock (DNL) method to link four copies of Rap site-specifically to the carboxyl termini of a panel of tumor-targeting humanized antibodies, in particular, hRS7, an internalizing, humanized, anti-TROP-2 MAb. We combined Rap-DDD2, a fusion protein comprising Rap and the dimerization and docking domain (DDD) of cAMP-dependent protein kinase (PKA), with hRS7-IgG-AD2, a fusion protein comprising two AD2 peptides derived from A-kinase anchoring proteins (AKAPs) having each AD2 appended to the carboxyl terminus of the heavy chain. Since Rap-DDD2 is isolated as a dimer, the resulting DNL complex, designated E1-Rap, contains four copies of Rap tethered to a bivalent hRS7 IgG. In the present study, we compared the in vitro growth inhibitory properties of E1-Rap against a variety of carcinoma cell lines. In breast (MDA-MB-468), cervical (ME-180), and pancreatic (BxPC-3 and Capan-1) tumor lines, all of which express high levels of TROP-2, E1-Rap was very potent, showing EC50 in the subnanomolar range (5 to 890 pM), which was 1,000- to 100,00-fold higher than untargeted Rap or the combination of Rap and hRS7. In cell lines expressing moderate levels of TROP-2, such as the three prostate cancer lines (PC-3, DU 145, and LNCaP), E1-Rap was less potent, but still showed EC50 in the nanomolar range (1 to 890 nM). The cell binding data obtained for these solid cancer cell lines suggest that the sensitivity of a cell line to E1-Rap appears to correlate with its TROP-2 expression on the cell surface. No toxicity was observed for E1-Rap in the prostate cancer line, 22Rv1, which fails to bind hRS7. Based on these results, further in vivo studies are warranted to better determine the efficacy of E1-Rap for future development as a new candidate therapeutic for TROP-2-positive solid tumors, including breast, cervical, pancreatic, and prostatic carcinomas.
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 5346.
Abstract 5351: Human papillomavirus prevalence in bladder cancer: Molecular and pathological analysis
Authors: Shigehara Kazuyoshi , Kawaguchi Syohei , Mizokami Atsushi , Sasagawa Toshiyuki , Maeda Yuji , Konaka Hiroyuki , Kumaki Misako , Namiki Mikio 
Published: February 2011

Abstract
Objective: We preformed a molecular and pathological analysis to elucidate the prevalence of human papillomavirus (HPV) in bladder cancer.
Patients and Methods: 72 cases of bladder cancer treated at Kanazawa University Hospital were enrolled in this study. As a negative control, 10 tissue samples including pathologically normal transitional cell (TC) epithelium were used. DNA was extracted from each frozen sample, and DNA quality was confirmed by amplifying the β-globin gene using PCR. Samples were tested for HPV-DNA by modified GP5+/6+ PCR, and the genotype was determined using a Hybri-Max HPV genotyping kit. Moreover, in situ hybridization (ISH) was performed to confirm presence of HPV-DNA in tumor tissue using the paraffin-embedded tissue of each sample. We compared the categorical characters such as patient's age, gender, tumor grade and tumor stage between HPV positive group and negative group.
Results: Mean age of 72 patients (58 men and 14 women) was 65.2 years. 15 cases were grade1 (G1), 49, grade2 (G2) and 8, grade3 (G3). β-globin gene could be amplified by PCR test in all bladder cancer samples and normal TC epithelium. HPV-DNA was detected in 14 cases (19%) of bladder cancer samples, and was not detected in all normal TC epithelium. The grade of HPV-positive tumor indicated that 7 cases were G1 and 7 cases were G2. HPV genotypes indicated high-risk type in all cases, as follow; HPV16: 6 cases, HPV18: 4 cases, HPV33: 3 cases and HPV56: 1 case. On ISH analysis, high-risk HPV genome signals were observed in the nuclei of most of the tumor cells in all HPV positive cases. On the other hands, high-risk HPV signals were not observed in the HPV negative cases and normal TC epithelium. Type 6/11 genome signals were not shown in all samples.
We compared the categorical characters between HPV positive cases and HPV negative cases. HPV-DNA was detected frequently in younger age and low grade (G1) tumor (p&lt;0.05).
Conclusions: HPV-DNA was detected in 19% of bladder cancer. Especially, HPV-DNA was frequently detected in low grade bladder cancer generated in the younger patients. In these cases, we demonstrated HPV-DNA was presented in the tumor tissue by ISH. We consider HPV infection can be one of etiological factors of bladder tumor.
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 5351.