bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 471: A case of bone-metastatic breast cancer resulted in complete remission 5 years after the comprehensive treatment including autologous formalin-fixed tumor vaccine.
Authors: Kuranishi Fumito , Ohno Tadao 
Published: August 2014

Abstract
Introduction: All cases, so far we have experienced,of bone-metastatic breast carcinoma patients show the downhill course to a tragic ending despite of intensive chemo-radiation therapy. We here report a case of advanced breast cancer that has been additively treated with autologous formalin-fixed tumorvaccine (AFTV) (Clin Cancer Res 10: 1574-9 2004). Case : A 53 years old female was diagnosed bearing a bone metastasis of breast cancer at vertebra Th7 by bone scintigraphy,
MRI and SPECT. The breast was operated, irradiated according to palliative radiation therapy with 36 Gy, vaccinated with AFTV, and then chemotherapy (CEF) was done as the last step of adjuvant therapy. Afterwards aromatase inhibitor and zoledronic acid hydrate was used for maintenance therapy. Five years later, the bonemetastasis has disappeared and she was diagnosed complete remission. Tumor markers have been in normal level . QOL of this patient is good at present.
Conclusion: Complete remission of bone metastasis of breast carcinoma is very rare. In this case, the preceded use of AFTV and radiation to the chemotherapy may have contributed to the cure. Additional use of AFTV should be considered in a larger scale clinicaltrial to improve therapeutic efficacy in bone-metastatic breast carcinoma.
Citation Format: Fumito Kuranishi, Tadao Ohno. A case of bone-metastatic breast cancer resulted in complete remission 5 years after the comprehensive treatment including autologous formalin-fixed tumor vaccine. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 471. doi:10.1158/1538-7445.AM2013-471
Abstract 4724: No-lyse no-wash immunophenotyping.
Authors: Bradford Jolene A. , Kerndt Rick 
Published: August 2014

Abstract
Immunophenotyping whole blood is a primary application in the study of blood cell populations and their functions. Red blood cells have traditionally been removed during sample preparation by lysis methods or density-gradient selection to enable the study of nucleated cell populations. This processing of whole blood has its draw backs due to the potential loss of cells of interest thru inadvertent lysis and unintentional selection of fragile and rare cells including blast cells, cancer cells, and cancer stem cells. The application of a No-Lyse No-Wash protocol in human whole blood samples benefit from a streamlined protocol that reduces cell loss. Testing of mouse whole blood presents additional challenges for cancer researchers due to the limited sample volume available (≤100 μL/day/animal), particularly in longitudinal studies. Specifically, these small volumes limit the ability to perform immunophenotyping experiments with required controls. This work describes a No-lyse No-wash method which takes advantage of acoustic focusing technology. Immunophenotyping panels are shown for both human and mouse whole blood. A total of 10μL of whole blood is stained in a 50 μL total volume and then diluted 400-fold in PBS. A fluorescence threshold is used to distinguish the white blood cell populations from the more abundant red blood cell population. In the mouse immunophenotyping example, CD45 is used to threshold on white blood cells. For the human immunophenotyping example, a cell permeable nucleic acid stain is used to threshold on all nucleated cells. At this dilution, the coincidence of the target population with red blood cells is reduced sufficiently so scatter signals are reliable for population identification. The significantly higher sample collection rates available with acoustic cytometry allows for the acquisition of high quality data utilizing a No-lyse No-wash protocol in a timely manner. Difficult-to-collect and precious samples like mouse blood can be stained and diluted without washing or performing RBC removal procedures. Loss of cells due to sample preparation is essentially eliminated, and ability to detect the cells of interest is enabled.
Citation Format: Jolene A. Bradford, Rick Kerndt. No-lyse no-wash immunophenotyping. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4724. doi:10.1158/1538-7445.AM2013-4724
Abstract 4725: High expression of TLR4 in hepatocellular carcinoma promotes proliferation and drug resistance.
Authors: Tseng Ping-Hui , Liu Yi-Ting , Cheng Yi-Chen 
Published: August 2014

Abstract
Toll-like receptors (TLRs) expressed in hematopoietic cells have emerged as sensors for pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), and are critical for innate immunity. Meanwhile, TLRs, especially TLR4, are also found to be expressed in various tumor cells. In hepatocellular carcinoma (HCC), TLR4 in marcorphages and hepatic stellate cells has been shown to be involved in promoting tumorigenesis. It has also been reported that hepatocytes with hepatitis B or C virus infection, the risk factor for HCC, lead to up-regulation of TLR4. However, the association between TLR4 in hepatocytes and HCC has not been well-studied. Here, the hepatotic cells with different TLR4 expression from human cancer cell lines and DEN-induced mouse HCCs were investigated. The results demonstrated that proliferation and colony formation in cells with higher TLR4, but not in those with low TLR4, was enhanced in response to LPS. Additionally, Akt activation, cyclinD1 induction, IL-6 production and STAT3 activation were detected in LPS-sensitive cancer cells. We also found that HCC with LPS pretreatment was resistant to anti-tumor drug-induced cell death. In xenograft model, the results were also in line with in vitro experiments. Briefly, TLR4 expressed in liver cancer cells provide advantage in growth and survival in the present of PAMPs and DAMPs. Better understanding of TLR activation in HCC might help the development of novel therapeutic approaches.
Citation Format: Ping-Hui Tseng, Yi-Ting Liu, Yi-Chen Cheng. High expression of TLR4 in hepatocellular carcinoma promotes proliferation and drug resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4725. doi:10.1158/1538-7445.AM2013-4725
Abstract 473: Long term clinical and biochemical outcomes following immunotherapy with an novel autologous immunomodulated vaccine in patients with prostate cancer.
Authors: Kreutz Fernando T. , Schroeder Gustavo , Berger Milton 
Published: August 2014

Abstract
Background: VAP is an new autologous immunomodulate vaccine, that was previously demonstrate to be safe in an initial phase I trial with local advance prostate cancer patients. The extension of this initial trail into a Phase IIb is now been reported. The primary endpoint of the study reported here is clinical response (PSA and survival) in local advance (T2 and T3) prostate cancer patients, with safety and immunologic responses as secondary endpoints.
Methods: Tumor cells from 107 prostatectomy patients were collected (HCPA - Porto Alegre - Brazil). 48 (45%) patients with T3 or T2 with co-morbidity factors were enrolled. 22 patients received the vaccine and 26 were in the control group. Vaccine was given by intradermal injections (4x weekly, 2x monthly and after 3 months). First two doses also ontained BGC as adjuvant. DTH was measured 48 hours after the vaccine doses that did not contained BCG. PBMCs and were collected via apheresis at baseline and D+54 for Tcell proliferation assay in some patients. Clinical flow up was performed and all standard care was given to all patients.
Results: The overall follow up was 7.4 years. No grade 3 or 4 toxicity attributable to vaccine was noted. Side effects were largely limited to grade 1 or 2 injection site reactions. DTH was positive (= or higher than 5 mm) in 73% of the vaccinated patients. Cancer related mortality was 9% (2/22) on the vaccinated group and 19% (5/26) on the non-vaccinated group. PSA was undetectable (less than 0.04 ng/ml) in 85% (17/20) of the vaccinated patients and in 48% (10/21) of the non-vaccinated patients after 5 years of follow up.In vitro specific T cell proliferation was demonstrated in vaccinatedpatients.
Conclusions: VAP is safe and well tolerated vaccine. There is evidence of clinical activity and immune changes in selected patients. Further studies to confirm these results are warranted. (Financial support from FINEP - Brazilian Innovation Agency)
Citation Format: Fernando T. Kreutz, Gustavo Schroeder, Milton Berger. Long term clinical and biochemical outcomes following immunotherapy with an novel autologous immunomodulated vaccine in patients with prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 473. doi:10.1158/1538-7445.AM2013-473
Abstract 4731: Discovering cancer biomarkers using a novel cytokine screening panel.
Authors: Manimala Joseph , Gupte Prachi , Swaminathan Ashok , Tituana Jorge P. , Hansen Caitlin , Mathew Anu , Stewart David , Oberoi Pankaj , Wohlstadter Jacob 
Published: August 2014

Abstract
Cytokines and chemokines that are produced in the tumor micro-environment play major roles in tumorigenesis, tumor progression, and apoptosis. They are involved in the modulation of angiogenesis and consequently, in tumor growth and metastases. Cytokine/chemokine expression by tumor cells leads to tumor proliferation and enhances tumor cell survival. Profiling these biomarkers may be useful for cancer diagnosis. For example, biomarkers such as IFNγ, TNFα, IL-1β, MCP-1, and IL-8 are overexpressed in breast carcinoma; IL-2, IL-4, IL-6, IL-8, IL-10, IL-16, and TARC are associated with prostate cancer; and increased expression levels of TNFα, IL-6, and IL-1β are implicated in colon cancer.
We have developed and validated multiplexed panels of 30 assays that allow users to simultaneously detect cytokines and chemokines with high precision and accuracy in different human matrices. These panels detect IFNγ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNFα, IL-5, IL-7, GM-CSF, IL-1α, IL-17A, IL-15, IL-16, IL-12/IL-23 p40, TNFβ, and VEGF MIP-1α, MIP-1β, Eotaxin, Eotaxin-3, IP-10, TARC, IL-8 (high abundance), MDC, MCP-1, and MCP-4.
The MSD® platform has the ability to quantitate these biomarkers in multiple sample types with superior sensitivity and performance, quantifying many low abundance analytes at levels below 0.5 pg/mL.
A challenge with current multiplex assays is a lack of analytical validation and lot-to-lot reproducibility. These new multiplex panels were developed with highly characterized and qualified reagents, and the assays were developed in accordance with industry guidelines. The panels demonstrated suitable spike recovery and dilution linearity performance in different biological matrices. Diluents, other kit components, and an optimized assay protocol are provided to achieve optimum performance. Each assay in the panel is well characterized and shows low non-specific binding. Each has been evaluated for potential assay and analytical interference. Controls are available for each panel.
These panels are suitable tools for accurately quantitating cytokines and chemokines in various tumor samples. Data are presented for samples from normal subjects as well as samples from benign prostatic hyperplasia and prostate cancer patients (serum), cirrhosis and liver cancer patients (serum), kidney cancer patients (plasma), and colon cancer patients (serum).
Citation Format: Joseph Manimala, Prachi Gupte, Ashok Swaminathan, Jorge P. Tituana, Caitlin Hansen, Anu Mathew, David Stewart, Pankaj Oberoi, Jacob Wohlstadter. Discovering cancer biomarkers using a novel cytokine screening panel. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4731. doi:10.1158/1538-7445.AM2013-4731
Abstract 4738: TLR8 stimulation enhances cetuximab-mediated natural killer cell lysis of head and neck cancer cells and dendritic cell cross priming of EGFR-specific CD8+ T cells.
Authors: Stephenson Ryan M. , Lim Chwee Ming , Matthews Maura , Dietsch Gregory , Hershberg Robert , Ferris Robert L. 
Published: August 2014

Abstract
Background: Cetuximab is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) that prolongs survival in the treatment of head and neck cancer (HNC), but only in 10-20%. An immunological mechanism of action including natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) has been suggested. We investigated the effects of activating toll-like receptor (TLR)-8 to enhance activity of cetuximab-stimulated, FcγR bearing cells.
Objective: To determine the capability of TLR8-stimulation to enhance the activation and function of NK cells and dendritic cells (DC) in the presence of cetuximab-coated HNC cells.
Methods: Peripheral blood mononuclear cells (PBMC), NK, DC and CD8+ T cells were isolated and analyzed using 51Cr release ADCC, flow cytometry analysis, cytokine ELISA, and EGFR853-861 tetramer staining.
Results: TLR8 stimulation of unfractionated PBMC led to enhanced cetuximab-mediated ADCC in healthy donors (p=0.01) and HNC patients (p&lt;0.05), which was dependent on NK cells. Secretion of Th1 cytokines TNFα(p&lt;0.0001), IFNγ(p&lt;0.0001), and IL-12p40(p&lt;0.005) was increased. NK cells in TLR8 stimulated PBMC showed higher degranulation marker CD107a expression after incubation with cetuximab-treated HNC cells (p&lt;0.001). TLR8 stimulation enhanced DC maturation markers CD80, CD83, and CD86 in co-culture with NK cells and cetuximab-treated HNC cells. Stimulation of DC using TLR8 agonist plus cetuximab-activated NK cells significantly increased EGFR-specific CD8+ T cell induction, compared to either condition alone (p&lt;0.01).
Discussion: VTX-2337 and cetuximab combination therapy can activate innate and adaptive anti-cancer immune responses. Further investigation in human trials will be important for determining the clinical benefit from this combination, and for determining biomarkers of response.
Citation Format: Ryan M. Stephenson, Chwee Ming Lim, Maura Matthews, Gregory Dietsch, Robert Hershberg, Robert L. Ferris. TLR8 stimulation enhances cetuximab-mediated natural killer cell lysis of head and neck cancer cells and dendritic cell cross priming of EGFR-specific CD8+ T cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4738. doi:10.1158/1538-7445.AM2013-4738
Abstract 4748: Therapy model for advanced intracerebral B16 mouse melanoma using radiosurgery combined with immunotherapy.
Authors: Smilowitz Henry M. , Sasso Dan , Lee Edward W. , Micca Peggy , Goh Gyuhyeong , Dilmanian F Avrahamn 
Published: August 2014

Abstract
A reproducible therapy model for advanced intracerebral B16 melanoma is reported. Implanted tumors (D0), suppressed by a single 15 Gy radiosurgical dose of 100 kVp X-rays (D8) were further suppressed by a single ip injection of a Treg depleting Mab given two days prior to the initiation (D9) of four weekly then eight bi-monthly sc injections of GMCSF-transfected, mitotically disabled B16 cells. The results of seven independent experiments were similar to the combined result: the Median (Days) [SD/Total N] of survival went from 15[1.09/62] (No Treatment Control) to 35.8[8.8/58] (Radiosurgery-Only) to 52.5[13.5/57] (Radiosurgery Plus Immunotherapy); Radiosurgery-Only and Radiosurgery Plus Immunotherapy groups were highly distinct from Controls as well as from one another (p&lt;0.0001). Within two weeks after immunization, tumors in mice receiving Radiosurgery Plus Immunotherapy were significantly smaller than tumors in mice treated only with Radiosurgery. Splenocytes and lymph node cells from immunized mice showed increased interferon Y production when cultured with syngenic tumor cells. We hypothesize that our model will be useful for the development and testing of novel combination therapies for brain tumors.
Citation Format: Henry M. Smilowitz, Dan Sasso, Edward W. Lee, Peggy Micca, Gyuhyeong Goh, F Avrahamn Dilmanian. Therapy model for advanced intracerebral B16 mouse melanoma using radiosurgery combined with immunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4748. doi:10.1158/1538-7445.AM2013-4748
Abstract 4750: Maximising the activity of immune checkpoint blockade through rational combination.
Authors: Mullins Stefanie R. , Watkins Amanda , Morrow Michelle , Vallee Theresa La , Robbins Paul , Stewart Ross , Wilkinson Robert 
Published: August 2014

Abstract
Harnessing the power of the immune system to identify and eliminate cancer is a promising area of development in cancer therapy. Increasing T-cell activation, in particular, is now a clinically validated approach to the treatment of cancer. Cytotoxic T-lymphocyte antigen 4 (CTLA-4, CD152) and B7-H1 (PD-L1, CD274) are part of a complex system of receptors and ligands that are involved in limiting T-cell activation through the delivery of inhibitory signals. MedImmune is currently developing tremelimumab (anti-CTLA4) and MEDI4736 (anti-PD-L1), for the treatment of advanced or metastatic solid tumours. Both of these antibodies antagonise T-cell inhibition signals with the aim of enhancing anti-tumor T cell activity, and tremelimumab has demonstrated benefit in a sub-set of patients with melanoma (Ribas, 2010).
Published studies characterising the immunogenic nature of some existing cancer therapeutics provide reason to believe that a combination strategy, utilising checkpoint blockade together with current standard of care, or novel therapeutics, could result in increased activity. We have established and characterised a panel of syngeneic mouse tumor models and employed these to explore the immune effects of a number of existing cancer therapies using pharmacodynamic (PD) and tumor growth inhibition (TGI) endpoints. In addition mouse cross reactive anti-CTLA-4 and PD-L1 antibodies were used to assess the potential for combination with these existing therapeutics and the effect of schedule on PD and TGI activity.
Citation Format: Stefanie R. Mullins, Amanda Watkins, Michelle Morrow, Theresa La Vallee, Paul Robbins, Ross Stewart, Robert Wilkinson. Maximising the activity of immune checkpoint blockade through rational combination. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4750. doi:10.1158/1538-7445.AM2013-4750
Abstract 4760: Evaluation of the progesterone receptor status using three different antibodies: A comparison by Allred score system.
Authors: Madeira Klesia P. , Daltoe Renata , Carvalho Alex , Rezende Lucas , Silva Ian , Rangel Leticia 
Published: August 2014

Abstract
Abstract:
Breast cancer (BC) hormonal receptors (progesterone, PgR and estrogen) status is assessed by immunohistochemistry (IHC), a specific, sensitive, and accessible method that guide BC treatment. We evaluated PgR expression in 53 BC cases using 3 anti-PgR antibodies (AB): monoclonal (SP42 and RP636) and polyclonal ab62621.
Methods:
Primary BC cases (with signed informed consent) were used to generate tissue microarray platforms, where PgR expression was accessed by IHC and evaluated by the Allred score. Categorical and quantitative data are shown in percentage and mean, respectively. Concordance (CON) and correlation among ABs were analyzed by Kappa factor (K), Spearman's correlation coefficient (ρ) or intraclass correlation coefficient. Staining patterns of each AB were compared by paired T-Test.
Findings:
We noted poor CON and K between ab62621 vs SP42 (CON=64.1%; K=0.247), and ab62621 vs RP636 (CON=62.3%; K=0.204), but higher CON between SP42 vs RP636 (CON 90.6%; K =0.738). Data were corroborated by Mc Nemar statistical test (p=0.019, p=0.014 and p&gt;0.05, respectively). Regarding staining intensity among PgR+ samples, we found higher proportion of weak staining and lower IS for ab62621 (48.3%; mean IS=1.6), when compared to SP42 (20.0%, mean IS=2.1, T-test p&lt;0.01) and RP636 (2.3, 21.9%, T-test p&lt;0.01). Within the entire sample, similar results were observed following ρ: SP42 vs RP636 (ρ=0.8103); ab62621 vs SP42 (ρ=0.3524); ab62621 vs RP636 (ρ=0.4075). As for proportion of stained cells and PS, among PgR+ samples, the mean values for ab62621 (75.4%; 4.8) were significantly higher than those of SP42 (56.3%, 4.3; T-test p&lt;0.01) and RP636 (60.1%; 4.2; T-test p&lt;0.01). Similar data were found after analyzing PS for the entire sample: SP42 vs RP636 (ρ=0.8588); SP42 vs ab62621(ρ=0.4832); RP636 vs ab62621(ρ=0.4050).
Interpretation:
Our data indicate that anti-PgR monoclonal ABs, RP636 and SP42, are, unlike ab62621, equally suitable to test BC PgR status by IHC due to their higher accuracy. Therefore, we suggest their clinical use during BC diagnosis; thus, enabling more precise therapeutic decisions to treat BC.
Citation Format: Klesia P. Madeira, Renata Daltoe, Alex Carvalho, Lucas Rezende, Ian Silva, Leticia Rangel. Evaluation of the progesterone receptor status using three different antibodies: A comparison by Allred score system. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4760. doi:10.1158/1538-7445.AM2013-4760
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.