tbuckley/cabot-search huggingface dataset:
Unmanipulated, G-CSF Mobilized Peripheral Blood Stem Cells As Graft Source for Non-Myeloablative Haploidentical Transplantation: Fast Engraftment, No Evidence of Graft Rejection, and Low Incidence of Graft-Versus-Host Disease
Authors: Rocco Pastano, Giovanna Andreola, Federica Gigli, Simona Sammassimo, Mara Negri, Liptrott Jayne Sarah, Corrado Tarella
Journal: Blood (2015)
720. Triple-Negative Breast Cancer Cells and Tumor Endothelium Are Killed by Targeting Tumor Endothelial Marker 8 (TEM8)
Authors: Tiara Byrd, Kristen Fousek, Antonella Pignata, Christopher Szot, Kevin Bielamowicz, Amanda Wakefield, Steven Seaman, Bradley Fletcher, Meenakshi Hegde, Brad St Croix, Nabil Ahmed
Journal: Molecular Therapy (2015)

Triple-negative breast cancer (TNBC) refers to a subset of breast cancers that are HER2, estrogen-receptor and progesterone-receptor negative. Associated with an aggressive phenotype and high incidence of recurrence, and devoid of the aforementioned receptors, there are currently no targeted therapies for TNBC. Tumor Endothelial Marker 8 (TEM8) is one of nine gene products up-regulated in the tumor vs. normal endothelium and is overexpressed in TNBC. To investigate whether TEM8 could serve as a viable target for TNBC therapy. To validate the target antigen we conducted double immunofluorescence staining of a cohort of 6 TNBC specimens for TEM8 and the pan-endothelial cell marker (CD31). In all 6 cases TEM8 was overexpressed, when compared to normal adjacent breast tissue. TEM8 staining was not restricted to the CD31 positive cells, but also detected in tumor parenchymal cells. The immortalized TNBC cell lines (MDA-MB-231, MdA-MB-436, MDA-MB-468 and Hs578T) expressed endogenous levels of TEM8 protein as revealed by western blot. To target TNBC using T cells we designed in silico a novel TEM8-specific chimeric antigen receptor (CAR) molecule. This CAR consisted of a TEM8 recognition extracellular domain single-chain variable fragment (scFv) derived from the monoclonal antibody, L2, a connecting transmembrane chain, followed by CD28, 41BB and CD3-zeta chain intracellular signaling domains. The TEM8 CAR-encoding DNA construct was synthesized and then sequence verified. Retroviral transduction was used to integrate the TEM8 CAR transgene in HEK 293T, then on primary T cells. Over 90% of primary human T cells expressed the TEM8 specific CAR, as indicated by flow cytometry. TEM8 specific T cells recognized and killed TEM8 positive cells in standard 4 hour 51Cr release cytotoxicity assays, effectively targeting both TNBC and tumor endothelium cell lines. Further, TEM8 CAR T cells secreted immunostimulatory cytokines in coculture. In contrast, there was minimal reactivity against TEM8 negative targets or by non-transduced T cells from the same blood donor. Adoptively transferred TEM8 specific CAR T cells resulted in a significant decline in the tumor growth of vascularized orthotopic breast cancer xenografts in a murine model, compared to nontransduced T cells (p=0.03). We conclude that TEM8 specific CAR T cells could serve as a tumor and vascular targeted therapy for TNBC.
Abstract 4342: Differential expression of novel PKD1 related biomarker panel in African American men with prostate cancer
Authors: Bita Nickkholgh, Xiaolan Fang, Shira M. Winters, Nora Fino, KC. Balaji
Journal: Cancer Research (2015)

Abstract Background: Prostate Cancer (PCa) exhibits striking racial disparity and is presented more aggressively in African Americans (AAs) than Caucasians (CAs). We have previously reported that the dysregulation of PKD1-centered signaling in primary AA prostate cancer cell line E006AA is akin to more aggressive Caucasian cell line C4-2. As PKD1 plays a central role in several cellular mechanisms that contribute in aggressive malignant phenotype, we defined a PKD1 related biomarker panel consisting of 11 biomarkers and explored whether PKD1 centered signaling would be differentially regulated in AA compared to CA PCa. Methods: PKD1 related biomarker panel consisted of PKD1, AR, HSP27, N-Cadherin, Snail, Vimentin, MMP-2, MMP-9, MT-1, E-cadherin, beta-Catenin. The validity of the PKD1 related biomarker panel in PCa was evaluated on available microarray databases (cbioportal.org). The differential expression of the biomarker panel was quantified on PCa tissue samples from15 AA and 15 CA men with matching Gleason score obtained from tumor tissue bank of Comprehensive Cancer Center of Wake Forest University. Results: The cbioportal consisted of six different PCa databases with approximately 662 human PCa samples in total. In average, PKD1 related biomarker panel was altered 47.7% in available cases. Quantification of the PKD1 related biomarker panel regarding gene expression demonstrated a trend toward higher expression of majority of biomarkers in AA samples in compare to CAs. However, only variances in expression of MMP2 (P&amp;lt;0.0001) and MT1A (P = 0.03) were significantly different between AAs and CAs. The results obtained from human PCa samples showed a moderate correlation with previously reported cell line data which showed significantly higher expression of EMT markers N-Cadherin, Vimentin and Snail in AA cell line in compare to CA cell lines. Conclusion: The differential expression of PKD1 related biomarker panel in AAs in compare to CAs suggests a biological basis for disparity in PCa. Besides, relatively high altered PKD1 related biomarker panel in available microarray databases suggests the potential of the panel as a tool in diagnosis of aggressive phenotype in PCa. Citation Format: Bita Nickkholgh, Xiaolan Fang, Shira M. Winters, Nora Fino, KC. Balaji. Differential expression of novel PKD1 related biomarker panel in African American men with prostate 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 4342. doi:10.1158/1538-7445.AM2015-4342
PO50AN AUDIT OF THE USE OF POST-OPERATIVE IMAGING FOLLOWING GLIOMA RESECTION
Authors: Alona Weir, John Leach
Journal: Neuro-Oncology (2015)

INTRODUCTION: Gliomas are by far the most common type of primary brain tumour in adults. High grade gliomas are often managed surgically, with maximal debulking, followed by concomitant chemo-radiotherapy and adjuvant chemotherapy. There is increasing evidence that maximal surgical debulking confers a survival advantage. After surgical debulking, early post-operative MRI scanning is an accurate means by which to assess the extent of residual tumour and may highlight the need to perform second-look surgery prior to oncology treatment. Local protocol implemented at Salford Royal Foundation Trust proposes that all patients should be scanned within 24 to 72 hours subsequent to intended gross macroscopic removal of glioma. METHOD: We performed a retrospective audit of 100 consecutive patients undergoing glioma debulking surgery in 2012/3. The attempted degree of glioma resection, time interval from surgery to scan, and MRI scan reports were assessed. The number of patients returning to theatre for further debulking surgery following attempted total resection was recorded. RESULTS: 47% of patients had an MRI scan within 72 hours following attempted total resection. Of these, 9% returned to theatre for subsequent debulking prior to chemo-radiotherapy. CONCLUSION: A significant proportion of patients having early post-operative imaging are returning to theatre for second surgeries to complete maximal tumour resection. Reasons for second surgery are discussed. Patients not having early post-operative imaging may be missing an opportunity for maximal surgical debulking prior to oncological treatment. A significant rate of return to theatre for second surgery may indicate the need for an intra-operative MRI scanner.
Proteomic-Based Approach for Biomarker Discovery to Predict Silent Cerebral Infarct in Patients with Sickle Cell Disease.
Authors: Lisa M. Williams, Zongming Fu, Pratima Dulloor, William J Savage, Emily Barron-Casella, John J. Strouse, Michael R. DeBaun, Jennifer Van Eyk, Allen Everett, James F. Casella
Journal: Blood (2009)
Burden of Morbidity in 10+ Year Survivors of Hematopoietic Cell Transplantation (HCT): A Report From the Bone Marrow Transplant Survivor Study (BMTSS)
Authors: Can-Lan Sun, John H. Kersey, Liton Francisco, K. Scott Baker, Saro H. Armenian, Daniel J. Weisdorf, Forman Stephen, Smita Bhatia
Journal: Blood (2011)
Abstract 3481: Sigma-2 ligands sensitize triple negative breast cancer cells to PARP inhibitor treatment
Authors: Chenbo Zeng, Julia Mankoff, Robert H. Mach
Journal: Cancer Research (2015)

Abstract Triple-negative breast cancer (TNBC) accounts for 15-25% of breast cancer cases. Effective targeted treatment for TNBC is lacking. Poly (ADP-ribose) polymerase (PARP) is a key enzyme involved in single-strand DNA break repair. PARP inhibitors have been used in combination with various chemotherapeutic agents in TNBC with limited success. The sigma-2 receptor is associated with cellular proliferation and quiescence and has been used as the target for imaging solid tumors by positron emission tomography. The sigma-2 receptor has been identified as progesterone receptor membrane component 1 (PGRMC1) protein complex. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target. In this study we looked for potential synergy between PARP inhibitors and sigma-2 ligands using a triple negative breast cancer cell line, MDA-MB231. We showed that the sigma-2 ligand, SW43, and a PGRMC1 ligand, AG205, induced cell toxicity and caspase 3 activation in a dose-dependent manner. The combination of SW43 and PARP inhibitor, Olaparib, resulted in additive cytotoxicity by cell viability assay and colony forming assay. Olaparib inhibited PARP activity in MDA-MB231 cell line, suggesting that the single-strand DNA break repair may be inhibited. SW43 and AG205 treatment decreased PGRMC1 and EGFR protein levels, suggesting that sigma-2/PGRMC1 ligands reduce growth factor signaling. In conclusion, SW43 and Olaparib induce cell death by separate signaling pathways. Sigma-2 ligands may selectively sensitize tumors to PARP inhibitor treatment in triple negative breast cancer patients. Citation Format: Chenbo Zeng, Julia Mankoff, Robert H. Mach. Sigma-2 ligands sensitize triple negative breast cancer cells to PARP inhibitor 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 3481. doi:10.1158/1538-7445.AM2015-3481
Impact of Smoking on Circulating Cardiac Troponin I Concentrations and Cardiovascular Events in the General Population
Authors: Magnus Nakrem Lyngbakken, Julia Brox Skranes, James A. de Lemos, Ståle Nygård, Håvard Dalen, Kristian Hveem, Helge Røsjø, Torbjørn Omland
Journal: Circulation (2016)

Both tobacco smoking and circulating cardiac troponin I (cTnI) levels are associated with the risk of acute myocardial infarction, heart failure, and cardiovascular death. However, whether cTnI levels differ according to smoking status and whether smoking modifies the prognostic relationship between cTnI and outcomes remain unclear.Using data from a large, population-based cohort, we assessed the association between smoking and cTnI and the impact of smoking on the associations between cTnI levels and the incidence of acute myocardial infarction, heart failure, and cardiovascular death. cTnI was measured with a high-sensitivity assay in 3824 never smokers, 2341 former smokers, and 2550 current smokers participating in the prospective observational HUNT Study (Nord-Trøndelag Health Study). All subjects were free from known prior cardiovascular disease and diabetes mellitus at baseline.The age of the participants ranged from 19 to 94 years; 55.5% were women. Current smokers exhibited significantly lower levels of cTnI (median, 2.9 ng/L; interquartile range, 2.0-4.1 ng/L) than never smokers (3.2 ng/L; interquartile range, 2.2-4.7 ng/L; P<0.001) and former smokers (3.4 ng/L; interquartile range, 2.3-5.0 ng/L; P<0.001). This association remained significant after adjustment for potential confounders (B=-0.098; 95% confidence interval, -0.129 to -0.068). We observed an association between increasing concentrations of cTnI and clinical end points in the total study cohort (adjusted hazard ratio per log unit increase in cTnI, 1.41; 95% confidence interval, 1.29-1.54). This association was attenuated for current smokers (hazard ratio, 1.17; 95% confidence interval, 0.98-1.40) and was significantly weaker than in never/former smokers (P for interaction=0.003). Prognostic accuracy, as assessed by C statistics, was significantly lower in current smokers than in never smokers (P<0.001). In addition, cTnI provided no incremental prognostic information to the Framingham Cardiovascular Disease risk score in current smokers (P=0.08).Current smoking is associated with lower concentrations of cTnI, suggesting that substances in tobacco smoke may affect cardiomyocyte injury. The association between cTnI levels and cardiovascular end points is stronger in never/former smokers than in current smokers, compatible with the theory that the detrimental cardiovascular impact of current smoking is mediated via mechanisms other than subclinical myocardial injury.
RTHP-10. PHASE II STUDY OF HYPO VS. CONVENTIONAL -FRACTIONATED RADIOTHERAPY WITH TEMOZOLOMIDE IN NEWLY DIAGNOSED GLIOBLASTOMA: EARLY COMPLIANCE AND TOLERANCE
Authors: Supriya Mallick, Kunhi parambath Haresh
Journal: Neuro-Oncology (2016)

To compare possibility of delivering radiation in shorter course of time by hypo-fractionation in newly diagnosed GBM. This phase II study intended to compare treatment outcome in newly diagnosed GBM patients, age ≥16 and ≤60 treated with conventional fractionated radiotherapy (60 Gy in 30 fractions) to hypo-fractionated radiotherapy (60 Gy in 20 fractions) with concurrent and maintenance Temozolomide after a maximal safe surgical resection. 50 patients were planned to randomize 1:1 in each of the study arm. The primary endpoints are response rate in each arm. Secondary endpoints are PFS, OS, and Toxicity ad compliance. 30 patients have been randomized so far. Median age was 38.5 years (Range: 16-59). Male: Female ratio was 2:1. 12(30%) patients had seizure at presentation. Median symptom duration was 2.5 months. 22 patients underwent a gross total resection whereas 8 patients underwent subtotal resection. Median MIB labeling index was 30% (Range: 8-95%). p53 deletion was noted on 50%, 20% patients had IDH-1 mutation, and 23% loss of ATRX immuno-expression. Only one patient required hospitalization for features of raised intracranial tension during radiation. All patients tolerated both the fractionation schedule without any treatment break. None of the patients had grade III or higher hematological toxicity both during the concurrent and adjuvant treatment with Temozolomide. At a median follow up of 8.31 months (Range: 3.97-24.89 months), 5 patients experienced local progression. However, none of the patients has a documented radio necrosis as of now. Hypofractionated radiation appears to be well tolerated with no treatment interruption. However, longer follow up of the study will be able to conclude the possibility of incorporating hypo fractionation in regular treatment of newly diagnosed GBM.
Abstract 3061: In vivo role of miR-32 in prostate cancer
Authors: Leena Latonen, Mauro Scaravilli, Fuping Zhang, Pekka Ruusuvuori, Matti Poutanen, Tapio Visakorpi
Journal: Cancer Research (2015)

Abstract The androgen receptor (AR) signaling pathway is central to the emergence of castration-resistant prostate cancer (CRPC). We set out to identify androgen-regulated microRNAs (miRNAs) that may contribute to the development of CRPC. We found miR-32 to be an androgen regulated miRNA which is differentially expressed in CRPC compared to benign prostatic hyperplasia (BPH) and able to provide a significant growth advantage to LNCaP cells by reducing apoptosis To study how increased miR-32 expression contributes to prostate cancer formation and/or progression in vivo, and to search for in vivo targets of miR-32 in the prostate tissue, we have established transgenic mice expressing miR-32 specifically in the prostate. FVB/N mouse strain was used to create transgenic mice with probasin promoter (ARR2PB) driving expression of miR-32 androgen-responsively in prostate epithelium post-puberty. The mice develop and breed normally, and express the transgene specifically in the ventral and dorsolateral lobes of the prostate, with no transgene expression detected in anterior prostate or seminal vesicles up to six months of age. To provoke lesions in prostate epithelium, the miR-32 mice were cross-bred with mice heterozygous for tumor suppressor Pten. Histological analysis of the prostates of ARR2PB-miR-32xPten+/- mice shows increased number of prostatic intraepithelial neoplasia (PIN) lesions in the dorsal prostate compared to Pten+/- mice. In addition, transgenic miR-32 can induce goblet cell metaplasia in prostate epithelium in lateral to ventral prostate, in addition to stromal responses, in the prostate in the Pten+/- background. In search for in vivo targets of miR-32, we have performed a gene expression microarray analysis comparing the wild type and ARR2PB-miR-32 prostate tissue. Several candidate targets have been identified, and will be discussed further for their potential cancer relevance. We find that miR-32 is potentially an important gene in the progression of prostate cancer and a putative drug target. We are currently analyzing histology of the miR-32 transgenic mouse prostates further, and assessing tissue targets of miR-32. With the transgenic mouse model, we aim to determine whether miR-32 is an oncomiR for prostate cancer in vivo, and will assess the potency of miR-32 as a therapeutic target. Citation Format: Leena Latonen, Mauro Scaravilli, Fuping Zhang, Pekka Ruusuvuori, Matti Poutanen, Tapio Visakorpi. In vivo role of miR-32 in prostate 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 3061. doi:10.1158/1538-7445.AM2015-3061
Hematological Testing Is Not Required with Every Dose of Bortezomib In Patients with Adequate Blood Counts at the Start of Each Cycle
Authors: Pooja S. Raibagkar, Paul G Richardson, Pieter Sonneveld, Michael W. Schuster, David Irwin, Edward A. Stadtmauer, Thierry Facon, Jean-Luc Harousseau, Dina Ben-Yehuda, Sagar Lonial, Hartmut Goldschmidt, Donna E. Reece, Jesus F San Miguel, Joan Blade, Mario Boccadoro, Rachel Neuwirth, Dixie-Lee Esseltine, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2010)
Cotransplantation of HLA-Identical Mesenchymal Stem Cells and Hematopoietic Stem Cells in Chinese Patients with Hematologic Diseases.
Authors: Xiaoyan Zhang, Jianyong Li, Kejiang Cao, Hanxin Wu, Hua Lu, Peng Liu, Sixuan Qian, Wei Xu, Wenyi Shen, Yu Zhu
Journal: Blood (2007)
OP21IDENTIFICATION OF NOVEL SMALL MOLECULE INHIBITORS OF THE FANCONI ANAEMIA DNA REPAIR PATHWAY AS A MEANS TO SENSITISES GLIOBLASTOMAS TO CHEMOTHERAPEUTIC AGENTS
Authors: A.A. Patil, P. Hua, M.A. Sellwood, D.A. Jellinek, T.A. Carroll, B. Chen, S.J. Collis
Journal: Neuro-Oncology (2015)

INTRODUCTION: The treatment of glioblastoma (GBM) remains a significant challenge, highlighting a critical need for the development of novel targets and agents to improve GBM treatment. We have previously shown that unlike normal brain tissue, GBMs re-express an active Fanconi Anaemia (FA) DNA repair pathway that confers resistance to Temozolomide. Additionally, we have demonstrated that drug-like small molecule disruption of the FA pathway renders GBMs more sensitive to the cytotoxic effects of Temozolomide. Our previous findings therefore highlight a potential exploitable therapeutic window to improve the clinical management of GBM and patient survival. This prompted us to develop rationally developed specific and potent small molecule inhibitors of the FA pathway for potential future clinical assessment. METHOD: In silico chemical docking, cell-based immunofluorescence and western blot analyses in various GBM cell models were used to identify novel small molecule inhibitors of the FA pathway. RESULTS: A novel chemical series of approximately 2000 compounds was interrogated both in silico and in vitro for the ability to disrupt the activity of the FA pathway. From these analyses 3 compounds were selected for further study. All 3 compounds showed a specific and potent ability inhibit the FA pathway in established and primary GBM cell models. Importantly, pre-treatment of GBM cells with these compounds conferred a potent increased sensitive to Temozolomide. CONCLUSION: We have identified novel small molecule inhibitors of the FA pathway that can be pre-clinically and clinically developed as a means to augment the anti-cancer effects of Temozolomide in GBM through an exploitable therapeutic window.
Atypical Serum Immunofixation Pattern (ASIP) Development during Induction Therapy with BiRD for Newly Diagnosed Multiple Myeloma Correlates with a High Rate of Complete Remission.
Authors: Tomer Mark, David Jayabalan, Roger N. Pearse, Y. Lynn Wang, Richard Lent, Paul J. Christos, Joong W. Lee, Yashpal P. Agrawal, Susan Matthews, Scott Ely, Madhu Mazumdar, Ethel Cesarman, April Rambo, John P. Leonard, Morton Coleman, Selina Chen-Kiang, Ruben Niesvizky
Journal: Blood (2007)
Allogeneic Stem Cell Transplantation after Reduced Intensity Conditioning (RIC) Is Effective for Long-Term Disease Control in High-Risk AML Patients in First Complete Remission.
Authors: Philipp G. Hemmati, Gero Massenkeil, Theis H. Terwey, Stefan Neuburger, Philipp le Coutre, Lam Vuong, Bernd Dorken, Renate Arnold
Journal: Blood (2007)