tbuckley/cabot-search huggingface dataset:
Abstract LB-256: Clonogenic growth of androgen receptor-overexpressing models of castration recurrent prostate cancer cells becomes insensitive to receptor ligands when their complete cellular secretory milieu is restored
Authors: Mugdha Patki, Yanfang Huang, Manohar Ratnam
Journal: Cancer Research (2016)

Abstract Evidence that androgen receptor (AR) overexpression causes castration recurrent prostate cancer (CRPC) cells to thrive on minimal residual post-castrate androgen is derived from studies of in vitro colony formation in the absence of cell-secreted factors or from studies demonstrating synergy between androgen and individual signaling pathways in isolation. We examined androgen-dependence using in vivo generated CRPC model cells overexpressing full length AR (C4-2 cells) or co-expressing a splice-variant (22Rv1 cells). The cells showed robust colony formation in conditioned media lacking androgenic activity derived from the same cells or from HEK293 fibroblasts. This effect was (i) not enhanced by androgen (ii) insensitive to blocking ligand-dependent transcriptional activity of AR, (iii) insensitive to mifepristone (iv) AR-dependent, (v) associated with AR phosphorylation and (vi) similar to androgen-stimulation in sensitivity to signaling pathway inhibitors. This ligand-insensitive response of overexpressed AR to the total cellular secretory complement may limit interventions targeting hormonal factors in CRPC. Citation Format: Mugdha Patki, Yanfang Huang, Manohar Ratnam. Clonogenic growth of androgen receptor-overexpressing models of castration recurrent prostate cancer cells becomes insensitive to receptor ligands when their complete cellular secretory milieu is restored. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-256.
Impact of the NCI Community Cancer Centers Program (NCCCP) on clinical trial (CT) activities in a community cancer center in rural Nebraska.
Authors: Mehmet Sitki Copur, Ryan C. Ramaekers, Mithat Gonen, Rebecca Hadenfeldt, Mary Gulzow, Heather Benzel, Jennifer Scott, Sarah Einspar, Mary Mickey, Max Norvell
Journal: Journal of Clinical Oncology (2014)

6511 Background: 85% of cancer patients (pts) are diagnosed/treated in the community, but only 3-5% are enrolled on CTs. Community oncologists lack adequate time, resource, infrastructure, reimbursement to engage in CTs. In July 2007, a 5-yr NCCCP contract was awarded to 16 pilot sites in diverse communities across the United States to support CTs and cancer care delivery. Methods: 5-yr prior and 5-yr after NCCCP, Saint Francis Cancer Center CT activities data, which included number/percent (pts) on CTs, percent underserved on CTs, number/type CTs available, staffing, collection/storage of tissue samples, organizational infrastructure/linkage to NCI designated cancer centers, availability of new cancer care services were gathered and compared. Results: Number/percent pts on CTs before/after NCCCP increased from 127 (5%) to 630 (23%), (p<0.001, Chi-square). All pts were rural Nebraskans, with 70% older than age 60. Number of available CTs increased four-fold with more prevention, quality of life, supportive care, cancer care delivery, biospecimen and treatment type trials after NCCCP. Non-treatment/treatment type trials both increased from an average 3/yr to 12/yr and 8/yr to 28/yr respectively (p=0.012, Wilcoxon). Average accrual per clinical trial was 13.2 before and 15.8 after NCCCP (p=0.5, Wilcoxon). CT staffing increased from an average of 1.2 to 3.9 FTEs (p=0.012, Wilcoxon). Two nurse navigators/genetic counselors, one smoking cessation counselor/outreach project coordinator were hired. Collection/storage of tissue samples increased from 24 (19%) to 330 (52%), (p<0.001, Chi-square). Affiliation with NCI designated Eppley Cancer Institute enhanced linkage to NCI programs. Conclusions: Participation in NCCCP positively impacted CT related activities with enhanced access to expanded types of CTs and cancer care services. Our data demonstrate the feasibility of implementing an expanded spectrum of CTs and programs within the rural community setting. Year Staff # Trials # Cases # Accruals % Accrual 2002 1 5 503 14 3 2003 1 8 521 21 4 2004 1 8 454 23 5 2005 1 12 542 22 4 2006 2 16 515 47 9 2007 2 19 541 56 10 2008 3 38 540 103 19 2009 5 51 528 143 27 2010 5 51 548 132 24 2011 5 40 562 196 35
Oral Valganciclovir As Preemptive Therapy for Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients
Authors: Vildan Ozkocaman, Fahir Ozkalemkas, Ridvan Ali, Yasemin Karacan, Tuba Ersal, Hilmi Erdem Gozden, Tugcan Erus, Esra Kazak, Halis Akalin
Journal: Blood (2014)
Abstract 4204: Intraarterial delivery of doxorubicin-loaded hollow gold nanospheres for photothermal ablation chemotherapy of hepatocellular carcinoma in the liver of rats
Authors: Junjie Li, Min Zhou, Chiyi Xiong, Wanqin Wang, Qizhen Cao, Xiaoxia Wen, Xin Ji, Andrew Wang, Sanjay Gupta, Chun Li
Journal: Cancer Research (2016)

Abstract Purpose: We sought to use combretastatin A-4 phosphate disodium (CA4P) to enhance the tumor uptake of doxorubicin (Dox)-loaded, polyethylene glycol (PEG)-coated hollow gold nanospheres (HAuNS; Dox@PEG-HAuNS) for improved photothermal ablation (PTA)-chemotherapy of hepatocellular carcinoma (HCC) in rats under image guidance. Materials and Methods: Two groups of 10 HCC-bearing rats each received intrahepatic arterial (IA) injection of either PEG-HAuNS/Lipiodol alone or CA4P followed by PEG-HAuNS/Lipiodol 5 min later. Each group was subdivided, and the Au content of tumors and tissues excised at 1 h or at 24 h was quantified using neutron activation analysis (n = 5/time point). Five rats received CA4P plus PEG-[64Cu]-HAuNS/Lipiodol and underwent μPET/CT. Therapeutic effects were compared among 3 groups of 6 rats each that received IA injection of saline (control group), CA4P plus Dox@PEG-HAuNS/Lipiodol (chemotherapy group), or CA4P plus Dox@PEG-HAuNS/Lipiodol plus near-infrared irradiation (PTA-chemotherapy group). Findings were verified with postmortem histopathology and/or autoradiography. Results: PEG-HAuNS uptake in CA4P-pretreated tumors was significantly higher than that in non-CA4P-pretreated tumors at both 1 h (P&amp;lt;0.05) and 24 h (P&amp;lt;0.01). The tumor-to-liver PEG-HAuNS uptake ratios at 1 h and 24 h were 5.63±3.09 and 1.68±0.77, respectively, in the CA4P-treated group and 1.29±2.40 and 0.14±0.11, respectively, in the non-CA4P-treated group. μPET/CT clearly delineated the tumors, enabling quantitative imaging guidance. Tumor volumes 10 d after therapy were 1.68±1.01, 3.96±1.75, and 6.13±2.27 cm3 in the PTA-chemotherapy, chemotherapy, and control groups, respectively, with significant differences between the PTA-chemotherapy group and other groups (P&amp;lt;0.05). Conclusion: CA4P pretreatment causes a higher concentration of Dox@PEG-HAuNS to be trapped inside the tumor, thereby enhancing the anti-HCC efficacy of μPET/CT-guided PTA-chemotherapy in rats. (Supported in part by the John S. Dunn Foundation) Citation Format: Junjie Li, Min Zhou, Chiyi Xiong, Wanqin Wang, Qizhen Cao, Xiaoxia Wen, Xin Ji, Andrew Wang, Sanjay Gupta, Chun Li. Intraarterial delivery of doxorubicin-loaded hollow gold nanospheres for photothermal ablation chemotherapy of hepatocellular carcinoma in the liver of rats. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4204.
’Idiopathic’ Eosinophilia with an Occult T-Cell Clone: Prevalence, FIP1L1-PDGFRA Status, and Clinical Course.
Authors: Animesh Pardanani, Christos Vaklavas, Joseph Butterfield, Rhett Ketterling, Srdan Verstovsek, Hagop Kantarjian, Ayalew Tefferi
Journal: Blood (2006)
Serum Vitamin D and Prostate Cancer Prognosis: The Story Continues
Authors: Elisa Roca, Francesca Valcamonico, Vito Amoroso, Alessandro Antonelli, Chiara Foroni, Claudio Simeone, Alfredo Berruti
Journal: Journal of Clinical Oncology (2016)

data that hypovitaminosis D is a reliable prognostic parameter or that the outcome of patients with PC might be improved by vitamin D supplementation. Several drawbacks hamper the clinical interpretation of serum vitamin D levels in cancer: the hormonal activity of vitamin D is mediated by its binding to vitamin D receptor (VDR) within the cell nuclei, and both VDR expression and VDR polymorphisms reflect the individual susceptibility to vitamin D action 3 ; and hypovitaminosis D is associated with secondary hyperparathyroidism, which could have contributed tothe negative prognostic features observed. Parathyroid hormone (PTH), in fact, is similar to PT-related peptide, which is a potent growth factor, and both PTH and PT-related peptide interact with the same receptor that is expressed by PC cells. 4 In the study by Nyame et al, 1 neither tissue VDR and its relevant polymorphisms nor serum PTH were measured; therefore, information on the interaction between vitamin D status and these important biologic parameters is lacking. Moreover, the assays to determine serum vitamin D levels are not standardized, and a significant variability among methods and laboratories was reported. 5 This further complicates the application of the results of the Nyame et al 1 study to clinical practice. In their discussion, Nyame et al 1 stated that patients with PC with intermediate risk may benefit, in terms of disease outcome, from the normalization of vitamin D levels. In principle, we agree with the authors that future studies are warranted to assess the efficacyofvitaminD supplementationin terms ofPC aggressiveness. However, caution should be taken in administering vitamin D to patients with PC outside a clinical trial. In fact, the results of a prospective phase III clinical trial testing the efficacy of high-dose calcitriol plus docetaxel versus single-agent docetaxel in men with castrate-resistant metastatic PC showed a shorter survival in the vitamin D arm compared with the control arm. 6
Capecitabine in the treatment of metastatic colorectal cancer refractory to 5-fluorouracil chemotherapy
Authors: T. Salek, J. Mardiak, M. Mego, Z. Hlavata, J. Obertova, Z. Sycova-Mila, T. Minarik, J. Sufliarsky, L. Bohunicky, Z. Thalmeinerova, I. Koza
Journal: Journal of Clinical Oncology (2005)

3689 Background: The oral fluoropyrimidines have therapeutic advantages over intravenous 5-fluorouracil such as tumor selectivity and inhibition of resistance mechanisms. Capecitabine is an oral tumor-activated fluoropyrimidine, that yields response rates of 23% to 27% in untreated metastatic colorectal cancer (CRC). The objective of the study was to evaluate the efficacy and safety of capecitabine in patients (pts) with CRC demostrating progression on 5-fluorouracil based therapy. Methods: Thirty one pts (13F/18M) with metastatic CRC, who progressed on 5-fluorouracil based therapy (median: 3 regimen; range: 2 - 7) were enrolled. Median age was 67 years (36 - 68), ECOG 0 (0 - 2). Five pts were also pretreated with oxaliplatin and 15 pts with irinotecan-based therapy. Median interval between 5-FU and capecitabine administration was 3 months (range: 0 - 23 months). The treatment schedule consisted of capecitabine 1250mg/m2 bid (day 1 to 14, every 3 weeks). Results: Median number of 5 cycles (range: 1 - 13) were administered. No objective response was observed. Nine patients (29%; 95%CI, 12 to 46) showed disease stabilisation for more than 6 months. Median time to treatment failure was 4,3 months (95%CI, 2,6 to 5,5 months, range, 1 to 13 months), median overall survival was 14,6 months (95% CI, 12,5 - 18,3 months, range, 2 to 28 months). The length of 5-FU free interval has no influence on capecitabine treatment Results: The main Gr3–4 toxicity was hand-foot syndrome, which experienced 11% pts. Conclusions: Despite easy administration and good tolerability the effectivity of capecitabine is unsatisfactory in patients with metastatic CRC refractory to 5-FU containing chemotherapy. Based on the obtained results we suggest that length of interval between 5-FU and capecitabine administration has no clinical impact. No significant financial relationships to disclose.
Abstract 740: Silica promotes anchorage-independent growth of human bronchial cells via activation of NF-êB1 p50
Authors: Motoo Katabami, Ichiro Kinoshita, Yasushi Shimizu, Satoshi Takeuchi, Hirotoshi Dosaka-Akita
Journal: Cancer Research (2016)

Abstract Although crystalline silica (hereafter silica) was judged as carcinogen by IARC, the mechanism of silica-induced carcinogenesis remains elusive. As limited studies have been reported to support the direct carcinogenic effect of silica on human lung epithelial cells, silica-induced inflammatory microenvironment may be postulated to facilitate lung neoplastic transformation. To test this hypothesis, we investigate the growth of immortalized human lung bronchial epithelial cell lines NL20, BEAS-2B and 16HBE14o-, following incubation with conditioned media collected 48h after exposed to silica (Silica CM) in each cell line. All cell lines promoted anchorage-independent growth in each Silica CM, compared with those in CM without silica exposure. All the bronchial cell lines in Silica CM increased DNA binding activity of NF-êB1 p50. After incubated with Silica CM, culture supernatants of NL20 and BEAS-2B kept higher concentration of EGF, and those of 16HBE14o- contained higher concentration of TNFá and IGF1, respectively. Recombinant EGF, TNFá and IGF1 are all sufficient to promote anchorage-independent growth of each bronchial cell line, and to increase DNA binding activity of NF-êB1 p50. Neutralizing human EGF and TNFá antibodies dampened the growth of each bronchial cell line. NF-êB inhibitor Bay11-7082 suppressed the growth of all bronchial cell lines incubated with Silica CM. Taken together, silica promoted anchorage-independent growth of human lung epithelial cells via silica-induced secretion of soluble factors, followed by activation of NF-êB1 p50 in an autocrine manner. The present study supports the hypothesis that silica-induced inflammatory microenvironment may be actively involved in the potential carcinogenic effect of silica. Citation Format: Motoo Katabami, Ichiro Kinoshita, Yasushi Shimizu, Satoshi Takeuchi, Hirotoshi Dosaka-Akita. Silica promotes anchorage-independent growth of human bronchial cells via activation of NF-êB1 p50. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 740.
Abstract 5105: Exosomes secreted by proinflammatory macrophages modulate breast cancer
Authors: Robert Bronislaw Bednarczyk, Neha Y. Tuli, Ghada Ben Rahoma, Rachana Maniyar, Abraham Mittelman, Raj K. Tiwari
Journal: Cancer Research (2016)

Abstract Multiple cell types reside within the tumor microenvironment (TME) including cancer stem cells, stromal cells, and inflammatory cells. Cellular crosstalk is initiated between these cells through a variety of secreted biomolecules such as cytokines, growth factors, and exosomes. The role of inflammation and numerous secretory factors within the TME have been implicated in the development and progression of various cancers including breast. In this study, we wanted to evaluate the effect of macrophages (a major constituent of inflammation) on breast cancer development. Our study focused on macrophage secreted exosomes which are membraneous nanovesicles that contain various miRNA, mRNA, and proteins. We hypothesized that macrophage secreted exosomes will modulate breast cancer phenotype. An in vitro cell culture system was used in this study to examine macrophage exosome treatments on breast cancer cell lines MCF-7 (ER+) and MDA-MB 231 (ER-, PR-, HER2/neu-). Human monocytic THP-1 monocytes were activated with a common phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) and conditioned media (CM) was collected following 48 h. Exosomes were isolated from THP-1 CM via the use of an exosome isolation reagent and standard centrifugation. Breast cancer cells were then treated with THP-1 exosomes and cell morphology, proliferation, MEK/ERK and PI3K/AKT signaling pathways, and cell cycle were evaluated. MCF-7 and MDA-MB 231 exhibited round and spindle-like morphologies as well as a significant decrease in proliferation at 24 h treatments. Furthermore, MDA-MB 231 displayed increased p-ERK, while MCF-7 showed increased p-MEK following Western blot analysis. Both cell lines exhibited decreased p-AKT and p-S6 kinase expression. Cell cycle analysis showed that MCF-7 and MDA-MB 231 arrested at G2/M at 24 h exosome treatments. THP-1 exosome treatments led to a significant increase in MDA-MB 231 senescence as determined by a senescence assay looking at senescence-associated beta-galactosidase. Increased p21 and decreased Cdc2/Cyclin B1 was also observed which indicates a G2/M arrest. We conclude that specific macrophage secreted exosomes may induce breast cancer cell senescence and affect breast cancer progression. Citation Format: Robert Bronislaw Bednarczyk, Neha Y. Tuli, Ghada Ben Rahoma, Rachana Maniyar, Abraham Mittelman, Raj K. Tiwari. Exosomes secreted by proinflammatory macrophages modulate breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5105.
Direct retrograde cholangioscopy with a new prototype double-bending cholangioscope
Authors: Torsten Beyna, Harald Farnik, Christoph Sarrazin, Christian Gerges, Horst Neuhaus, Jörg Albert
Journal: Endoscopy (2016)

Direct retrograde cholangioscopy (DRC) enables high quality video imaging of the bile ducts and allows intraductal treatment with optical control. We evaluated the feasibility, success, and complications of a new third-generation prototype cholangioscope.All consecutive patients from two tertiary endoscopy centers who had undergone DRC with the prototype were included. Indications for DRC were: evaluation of indeterminate strictures, filling defects, and complex bile duct stones. Technical success was investigated in terms of indication and treatment performed. All adverse events were recorded.DRC with the prototype was performed in 74 patients. Therapeutic interventions included laser or electrohydraulic lithotripsy and stone removal, among others. The papilla was entered in 72/74 patients (97 %). The targeted bile duct segment was reached in 62 /74 patients (84 %), with an anchoring balloon catheter needed in 21/74 (28 %). Mean investigation time was 21 minutes (15 - 27 minutes)DRC using the prototype is feasible, safe, and attains access to the bile ducts in almost all patients, with less need of an anchoring balloon catheter compared with the standard technique and short investigation and fluoroscopy times.
Efficient in vivo transfection and safety profile of a CpG-free and codon optimized luciferase plasmid using a cationic lipophosphoramidate in a multiple intravenous administration procedure
Authors: Mattias F. Lindberg, Tony Le Gall, Nathalie Carmoy, Mathieu Berchel, Stephen C. Hyde, Deborah R. Gill, Paul-Alain Jaffrès, Pierre Lehn, Tristan Montier
Journal: Biomaterials (2015)
Abstract 3814: Synthetic lethal approaches targeting E-cadherin-deficient cancers
Authors: Augustine Chen, Bryony J. Telford, Andrew Single, Henry Beetham, Kaylene J. Simpson, Parry Guilford
Journal: Cancer Research (2016)

Abstract E-cadherin is a cellular adhesion protein that is frequently mutated in lobular breast cancer and diffuse gastric cancer. The E-cadherin protein which is encoded by the CDH1 gene has key roles in establishing and maintaining cell polarity and differentiation, the organization of cell migration and architecture and the mediation of signaling through various proliferation and survival pathways. E-cadherin also has a tumor suppressor role and its loss in cancer cells would preclude drug targeting by conventional therapy. To circumvent this, we have taken a synthetic lethal approach to exploit any vulnerability created by the loss of E-cadherin. In the therapeutic setting, synthetic lethality refers to a combination of a mutated gene and a drug targeted at a second gene or protein causing cell death (specifically in cancer cells). To identify the vulnerabilities created by E-cadherin loss, we performed a genome-wide siRNA knockdown screen in isogenic MCF10A cell lines with and without E-cadherin expression. From the functional screen, we identified broad classes of G-protein-coupled receptor (GPCR) signaling proteins and families of cytoskeletal proteins which were highly enriched among the synthetic lethal candidates. Indeed, we identified drug classes with linkages to several of the GPCR and cytoskeletal targets that showed evidence of E-cadherin synthetic lethality when we performed a 4,057 known drug screen. These included certain PI3K inhibitors (PI-103), anti-glucocorticoid (mifepristone), tyrosine kinase inhibitor (saracatinib) and multiple histone deacetylase inhibitors (vorinostat and entinostat). Interestingly, the combination of saracatinib and mifepristone gave a synergistic effect (combination index &amp;lt; 1.0) in targeting E-cadherin-deficient MCF10A cells. These results demonstrate that E-cadherin loss creates druggable vulnerabilities that have the potential to improve the management of both of sporadic and familial lobular breast cancer and diffuse gastric cancer. Citation Format: Augustine Chen, Bryony J. Telford, Andrew Single, Henry Beetham, Kaylene J. Simpson, Parry Guilford. Synthetic lethal approaches targeting E-cadherin-deficient cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3814.
A Combined Score of Minimal Residual Disease (MRD) Assessment by Flow Cytometry, Cytogenetic and Molecular Markers As Well As Age Predicts Outcome and Can Potentially Guide MRD-Based Therapy in Acute Myeloid Leukemia
Authors: Thomas Köhnke, Daniela Sauter, Katharina Ringel, Jan Braess, Wolfgang Hiddemann, Karsten Spiekermann, Marion Subklewe
Journal: Blood (2011)