tbuckley/cabot-search huggingface dataset:
Abstract 1563: M402, a heparan sulfate mimetic, inhibits taxane mediated mobilization of endothelial progenitor cells and their homing to tumors in a mouse model
Authors: Birgit C. Schultes, Josephine S. D'Alessandro, Chia L. Chu, Alison Long, Christopher T. Honan, Takashi K. Kishimoto
Journal: Cancer Research (2011)

Abstract Treatment with certain anti-cancer agents, particularly taxanes and sunitinib, can lead to mobilization of pro-angiogenic factors and an acute mobilization of Endothelial Progenitor Cells (EPCs), which home to the viable tumor rim where they can enhance tumor vascularization. This phenomenon has been linked to rapid tumor regrowth following chemotherapy or treatment with specific angiogenesis inhibitors and may thus diminish the long-term efficacy of the treatment. EPCs are mobilized in response to circulating growth factors and chemokines (VEGFR, FGF, G-CSF, IL-6, SDF1α, etc.) that are induced by the drug or the progressing tumor. Many of these factors contain heparin binding domains for their anchorage to proteoglycans on cell surfaces or the extracellular matrix. We tested a novel heparan sulfate mimetic, M402, for its ability to inhibit EPC mobilization as well as EPC homing to the tumor as a result of interference with heparin-binding cytokines, chemokines and growth factors. In normal BALB/c mice, G-CSF and Docetaxel induced a significant increase in EPC within 8-24 h of dosing as compared to the saline control, while cisplatin or gemcitabine treatment did not show this effect. The docetaxel-induced EPC mobilization into the blood could be inhibited significantly by M402, similarly to an anti-VEGFR2 antibody (DC101). Analysis of the bone marrow microenvironment indicated that M402 does not inhibit the generation of EPCs but rather prevents the mobilization of EPCs from the bone marrow, likely through disruption of the SDF-1α/CXCR4 axis. M402 alone did not influence EPC mobilization in normal mice. However, in mice bearing orthotopic 4T1 breast carcinoma or Capan-2 pancreatic tumors, treatment with M402 normalized circulating EPCs otherwise mobilized by tumor-secreted factors, particularly G-CSF. Furthermore, M402 inhibited homing of EGFP labeled EPCs into SDF-1a loaded matrigel plugs or 4T1 tumors. The effect on EPCs correlated with decreased tumor angiogenesis as assessed by immuno-histochemistry and microCT. Furthermore, we observed synergistic anti-tumor activity of M402 with docetaxel in the 4T1 model. In conclusion, the experiments show that M402 could inhibit docetaxel or tumor-mediated EPC mobilization by trapping the EPCs in the bone marrow and inhibiting their recruitment into the tumor microenvironment. The data provide a scientific rationale for further studying the observed synergy of M402 with taxanes in cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1563. doi:10.1158/1538-7445.AM2011-1563
Abstract 1461: Zoledronate inhibits proliferation and invasion of inflammatory breast cancer cells
Authors: Carolyn S. Hall, Balraj Singh, Karen Tai, LaTashia R. Irving, Anthony Lucci
Journal: Cancer Research (2010)

Abstract Introduction: Inflammatory breast cancer (IBC) is aggressive, as approximately one third of patients present with distant metastases. Bisphosphonates are often administered to breast cancer patients for cancer-induced osteolysis. Recent evidence suggests bisphophanates may also have anti-tumor properties. This study examined the effects of the bisphosphonate, zoledronate (ZA), on the proliferation and invasive capabilities of highly aggressive IBC cell lines. Methods: The IBC cell line SUM149 was cultured utilizing both adherent and serum-free, non-adherent cancer stem cell enriching conditions. An MTT assay was used to quantify proliferation and mammosphere formation of cells. Adherent cell growth was measured at days 1-4 following 0, 0.1, 1, 5, 10, 50 and 100uM zelodronate treatment. Mammosphere formation was measured at 10 days following 0, 0.01, 0.1, 1, 10, and 100uM ZA treatment. Modified Boyden chambers were employed to assess the ability of both adherent and non-adherent cells to invade to SDF-1 (100ng/mL) following 24 hour 1uM ZA treatment. Protein expression was assessed using immunofluorescent staining, protein arrays and Western blotting. Results: ZA treatment with &amp;lt;5uM did not inhibit SUM149 adherent cell growth at any of the measured time points. ZA concentrations ≥10uM significantly inhibited SUM149 adherent cell growth at day 4 (p≤0.05). SUM 149 mammosphere formation was significantly inhibited following 10uM ZA treatment (p≤0.001). However, significantly more SUM149 non-adherent cells invaded to SDF-1 compared to adherent cells (p≤0.001). SUM 149 non-adherent cell invasion was inhibited by 24 hour 1uM ZA treatment (p≤0.001). SUM 149 non-adherent cells expressed significantly increased levels of the epithelial-mesenchymal transition (EMT) associated proteins smooth muscle actin (SMA), fibronectin, and N-Cadherin. The increased expression of SMA, fibronectin, and N-Cadherin observed in non-adherent cells returned to levels comparable to adherent cells following 24 hour 1uM ZA treatment. Conclusions: ZA inhibited the growth of IBC cells grown under adherent and non-adherent conditions. SUM 149 non-adherent cells had much greater invasive potential than adherent cells did, and their invasive capability was inhibited following low dose ZA treatment. Interestingly, ZA inhibited up-regulation of EMT associated proteins SMA, fibronectin, and N-Cadherin in SUM 149 non-adherent cells. These results indicate that some IBC cells grown under cancer stem cell enriching conditions have the potential to undergo EMT and invade. ZA may also inhibit metastases through novel mechanisms. 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 1461.
The string sign for diagnosis of mucinous pancreatic cysts
Authors: Benjamin Bick, Felicity Enders, Michael Levy, Lizhi Zhang, Michael Henry, Barham Dayyeh, Suresh Chari, Jonathan Clain, Michael Farnell, Ferga Gleeson, Michael Kendrick, Randall Pearson, Bret Petersen, Elizabeth Rajan, Santhi Vege, Mark Topazian
Journal: Endoscopy (2015)

<b>Background and study aims:</b> Pancreas cyst fluid analysis does not provide optimal discrimination between mucinous and nonmucinous cysts. The aim of this study was to assess the performance characteristics of the "string sign" – a test performed at the time of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), for the diagnosis of mucinous pancreatic cysts (branch duct intraductal papillary mucinous neoplasms [bIPMN] and mucinous cystic neoplasms). <b>Patients and methods:</b> Patients undergoing EUS-FNA of pancreatic cystic lesions at one referral center between 2003 and 2012 were included. The string sign was performed prospectively, and was considered positive if ≥ 1 cm string formed in cyst fluid and lasted for ≥ 1 second. Performance characteristics of the string sign and a sequential cyst fluid test interpretation model were assessed. <b>Results:</b> For 98 histologically proven cases, the sensitivity, specificity, positive predictive value, and negative predictive value of the string sign for diagnosis of mucinous cysts were 58 % (95 % confidence interval [CI] 44 % – 70 %), 95 % (83 % – 99 %), 94 % (81 % – 99 %), and 60 % (46 % – 72 %), respectively. When string sign results and carcinoembryonic antigen (CEA) concentration (≥ 200 ng/mL) were combined, diagnostic accuracy improved from 74 % and 83 %, respectively, to 89 % (<i>P</i> ≤ 0.03). Among bIPMN, a positive string sign was associated with gastric and intestinal epithelial subtypes. The sequential cyst fluid test interpretation model (including cytology, mucin stain, CEA, and string sign) yielded an overall sensitivity for mucinous lesions of 96 %, with a specificity of 90 %. <b>Conclusions:</b> The string sign is highly specific for diagnosis of mucinous pancreatic cysts, and improves overall diagnostic accuracy of pancreatic cyst fluid analysis. Sequential cyst fluid test interpretation yields high diagnostic sensitivity and specificity for mucinous cysts.
Retraction: Darsee JR, Heymsfield SB, Nutter DO. Hypertrophic cardiomyopathy and human leukocyte antigen linkage: differentiation of two forms of hypertrophic cardiomyopathy. N Engl J Med 1979; 300:877-82.
Authors: Donald O. Nutter, Steven B. Heymsfield, James F. Glenn
Journal: New England Journal of Medicine (1983)

Editorial from The New England Journal of Medicine — Retraction: Darsee JR, Heymsfield SB, Nutter DO. Hypertrophic cardiomyopathy and human leukocyte antigen linkage: differentiation of two forms of hypertrophic cardiomyopathy. N Engl J Med 1979; 300:877-82.
Successful endoscopic treatment of massive bleeding related to the appendiceal stump
Authors: Z. Simsek, F. Karaahmet, O. Yuksel, B. Yılmaz, S. Coban
Journal: Endoscopy (2013)

A 43-year-old man was admitted to the hospital with a 2-day history of rectal bleeding. His medical history included uncomplicated appendectomy 7 days previously because of acute phlegmonous appendicitis. Physical examination findings were normal. Hemoglobin concentration was 7.8 g/dL (normal range 13.6 – 17.2 g/dL) and other laboratory tests showed unremarkable findings. Emergent colonoscopy was performed after blood transfusion and bowel preparation with polyethylene glycol. Colonoscopy revealed much fresh blood in all the colonic lumen and wall but no evidence of any inflammatory lesion or mass. No active bleeding was observed from the terminal ileum, but there was some reflux of fresh blood from the cecum to the terminal ileum. Intermittent bleeding from the appendiceal orifice was identified ([Fig. 1]). Endoscopic hemostasis was performed using hemoclips (EZ Clip; Olympus, Tokyo, Japan) and successful hemostasis was confirmed ([Fig. 2]). The patient was discharged 4 days after the colonoscopic clipping, and was doing well at follow-up.
Dietary management of hepatic encephalopathy
Authors: C. A Seymour, K. Whelan
Journal: BMJ (1999)

The mode of anaesthesia used during pneumoencephalography has a significant effect on the size of the cerebral ventricles 24 hours after the procedure. Post-encephalographic ventricular enlargement is less marked in patients examined under nitrous oxide anaesthesia. This appears to be related to passage of the gas into the ventricles during the encephalogram, and subsequent diffusion outwards. Variations in arterial carbon dioxide tension during the anaesthesia do not contribute significantly to changes in ventricular size. However, both hyperventilation and inhalation of nitrous oxide may cause apparent increase in size of the cerebral sulci.
Abstract 2041: PDGF inducible microRNAs regulate gene expression in cancer cells
Authors: Minghai Shao, Simona Rossi, Bhadrani Chelladurai, Obiageli Ntukogu, Mircea Ivan, George Calin, Daniela Matei
Journal: Cancer Research (2010)

Abstract Background: Platelet derived growth factor (PDGF)-regulated signaling plays a critical role in oncogenesis. By binding to the PDGF receptors, the Akt, Src and MAPK pathways are activated to regulate genes expression and cellular physiological processes. There are subtle functional differences between the effects of specific PDGF ligands (e.g. AA, BB), which are incompletely understood. MicroRNA(miR)s are single-stranded, 21-23 nucleotide regulatory RNAs that repress target gene expression either by inhibiting protein translation or by promoting target mRNA degradation. The hypothesis tested in this study was that PDGFs regulate genes expression by modulating microRNAs level in cancer cells. Methods: MicroRNA microarrays were performed to identify miR alterations after treatment of U118 glioblastoma cells with PDGF-AA and BB. Several time points were tested: 2, 6, 12, and 24 hour. Significance Analysis of Microarrays (SAM) was performed to compare expression level between different time points. Q-PCR was conducted to confirm the microarrays data. Pre-miR probe/miRCury LNA probe were transfected into cancer cells to over-express/knock down selected miRs. Western blots were used to detect miRs’ target proteins. Results: Candidate PDGF-inducible/repressible miRs were identified based on significant change in expression level after AA/BB treatment (p-value &amp;lt;0.01). Expression levels of 7 miRs were altered by PDGF AA and expression levels of 14 miRs were altered after PDGF BB treatment. By Q-PCR we showed that let 7d was repressed by PDGF-AA, but not by PDGF-BB in cancer cells (U118, C272 and U87) and in fibroblasts (WI38). Cyclin D1 is a known target of let7d. By overexpression and knock-down strategies we show that PDGF-AA induced cyclin D1 expression is mediated via repression of let7d. Q-PCR confirmed that miR-146b and miR-106b are inducible by PDGF-BB, but not by PDGF-AA in cancer cells (U118, C272 and U87) and in fibroblasts (WI38). MiR-146b induction by PDGF-BB is modulated via MAPK-dependent induction of Fos. A Fos binding element was identified in the promoter region of miR146b and Fos binding to this region in the presence of PDGF-BB was confirmed by chromatin immunoprecipitation. Several targets of miR146b are altered by PDGF in cancer cells. Conclusions: Our data demonstrate for the first time that PDGF signaling regulates expression of several critical oncogenic miRs which in turn alter target gene expression and function. 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 2041.
Abstract 1172: <i>RARB</i> is a biomarker of poor prognosis in prostate carcinomas
Authors: Flavia C M C Alves, Sandra A. Drigo, Cláudia A. Rainho, João L V Camargo, Francisco P. Fonseca, Fernando A. Soares, José C S Trindade-Filho, Maria A C Domingues, Silvia R. Rogatto
Journal: Cancer Research (2010)

Abstract Purpose: Despite the advances in prostate carcinomas (PCa) management, about 30% of the patients who undergo radical prostatectomy presented biochemical recurrence (BCR). BCR is considered an unfavorable prognostic factor followed by clinical disease progression. The current prognostic markers in PCa are unable detect correctly who is at risk for BCR. Hypermethylation at RARB and RASSF1A genes have been associated with worse prognosis in PCa. The current study aimed to evaluate RARB, and RASSF1A hypermethylation frequencies in prostate carcinoma (PCa) and to correlate these alterations with down-regulation at transcriptional and protein levels and with clinical outcome. Methods: Methylation patterns of RARB and RASSF1A were determined by methylation-specific PCR in 68 PCa samples and 27 non-neoplastic prostate tissues. Gene expression was evaluated by quantitative RT-PCR in 73 PCa, 15 adjacent non-neoplastic prostate tissues (AdjP) and two normal prostate (N). Protein expression was evaluated in an independent PCa cohort (n=141) with long-term follow-up period. The findings were associated with clinicopathological parameters and BCR-free survival (BRFS). Results: RARB and RASSF1A genes were hypermethylated in PCa (P &amp;lt;0.0001 and P = 0.0017, respectively). RASSF1A mRNA and protein levels were similar in PCa and AdjP samples. Down-expression of RARβ in transcript (P=0.001) and protein (P=0.0007) levels were detected in PCa. Lower mRNA levels were associated with RARB hypermethylation. Nuclear and cytoplasmic RARβ protein expression was detected in tumor tissues. Multivariate analysis demonstrated that cytoplasmic RARβ immunostaining was independently associated with decreased BRFS (P=0.005, HR=2.314). Conclusions: RARB hypermethylation seems to be one of the mechanisms involved in RARβ down-expression in PCa. Cytoplasmic RARβ protein is an independent predictor of poor prognosis that may be considered a new biomarker in prostate cancer providing, therefore, relevant information for patient management. 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 1172.
Abstract 4979: Multidimensional crosstalk regulates myeloid cell hyperplasia, immune escape, and tumor progression.
Authors: Ibrahim H. Younos, Alicia J. Dafferner, Holly Britton, James E. Talmadge
Journal: Cancer Research (2013)

Abstract Myeloid-derived suppressor cells (MDSCs) encompass a heterogeneous class of cells in different maturation states that proliferate and accumulate in tumors, secondary lymphoid organs and some epithelial organs during tumor growth. Tumor secretion of growth factors and chemokines regulate myeloid cell proliferation, apoptosis, differentiation, circulation and biodistribution both locally and systemically. There is a reciprocal interaction that occurs between tumor and myeloid cells, which can facilitate tumor growth and metastasis and myeloid cell proliferation and survival via unique and tumor specific arrays of growth factors and chemokines. The tumor microenvironment, a complex, highly dynamic environment composed of host-derived MDSCs, endothelial cells, and fibroblasts; contributes to the microenvironmental crosstalk regulating host immunity and tumor progression. However, the macroenvironment is also a critical to myeloid cell expansion, tumor invasion and immune escape and tumor progression. The primary site of MDSC expansion and immune suppression is splenic extramedullary hematopoiesis, which is regulated by growth factors secreted by the distant primary tumor cells. Similarly, regulation of tumor infiltration by myeloid cells is by tumor secretion of CCL2; however, this occurs at the macroenvironmental level as CCL2/CCR2 blockade inhibits medullary myeloid cell mobilization and recruitment from secondary lymphoid organs and not at the tumor. Further, regulatory crosstalk is bidirectional with tumor-secreted factors differentially upregulating myeloid and lymphoid cell growth factors and enzymes (G-CSF, CXCL1, CCL2, arginase) by medullary myeloid cells and splenic lymphocytes. In tumor bearing, mice the tumor-secreted growth factors support hematopoietic stem/progenitor cell proliferation, limit their apoptosis and inhibit T-cell function. Conversely, leukocyte-secreted cytokines limit immune and hematopoietic growth factor transcript levels by tumor cells (G-CSF, IL-23, CXCL1 and NOS-2) with associated effects on tumor malignancy and leukocyte proliferation and differentiation. In summary, tumors form both local and systemic, bidirectional, regulatory loop(s) between metastatic tumor cells and MDSCs that regulates their proliferation and differentiation supporting tumor metastasis and systemic and regional T-cell suppression. Citation Format: Ibrahim H. Younos, Alicia J. Dafferner, Holly Britton, James E. Talmadge. Multidimensional crosstalk regulates myeloid cell hyperplasia, immune escape, and tumor progression. [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 4979. doi:10.1158/1538-7445.AM2013-4979
TR-04 * NANOPARTICLE siRNA DELIVERY VEHICLES INHIBIT DNA REPAIR AND SENSITIZE PEDIATRIC BRAIN TUMOR CELLS TO RADIATION THERAPY
Authors: F. Kievit, Z. Stephen, K. Wang, C. Dayringer, J. Silber, R. Ellenbogen, M. Zhang
Journal: Neuro-Oncology (2015)

Radiotherapy (RT) is an integral component of the treatment for medulloblastoma (MB) and the only effective adjuvant therapy for ependymoma (EP), two of the most common pediatric brain tumors. However, survival is frequently accompanied by one or more radiation-induced adverse developmental and psychosocial sequelae. Therefore, strategies that enhance the tumoricidal action of RT while sparing adjacent normal brain are expected to reduce the amount of radiation required to generate a therapeutic effect in these tumors. The multifunctional DNA repair protein Ape1/Ref-1 has been implicated in conferring radiation resistance in pediatric brain tumors. However, inhibiting Ape1 activity in the clinic has been hindered by the lack of safe and effective drugs and siRNA delivery vehicles. Here, we used our nanoparticle delivery vehicles to deliver siRNA against Ape1 (siApe1) and improve cell kill after RT. Nanoparticles were loaded with siApe1, or siGFP as a control, and used to treat UW228 (MB) and Res196 (EP) cells. Ape1 expression and activity were measured using PCR, Western blot, and an abasic endonuclease activity assay. DNA repair and clonogenic survival were assessed after exposure to 137Cs-γ-rays. We found that nanoparticle-mediated siApe1 delivery reduced Ape1 expression and activity by greater than 80%, which was accompanied by a greater abundance of DNA damage. This diminished the shoulder of resistance in survival curves decreasing survival to ∼50% at 1 Gy. Sensitization was specific to abasic site generating treatments as response to paclitaxel was not affected. Therefore, nanoparticle-mediated inhibition of Ape1 may help enhance the therapeutic effect of RT in pediatric brain tumor patients and reduce treatment-induced morbidity.
A4.10 The comparison of osteoclastogenic potential of blood and bone marrow plasma from rheumatoid arthritis (RA) and osteoarthritis (OA) patients
Authors: A Radzikowska, M Plebanczyk, W Kurowska, T Burakowski, A Nowakowska-Plaza, R Gasik, P Gluszko, W Maslinski
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Alterations of OPG/RANKL ratio are critical in bone pathology in RA. Therefore the aim of this study was to investigate the osteoclastogenic potential of RA and OA blood and bone marrow plasma. <h3>Materials and methods</h3> Bone marrow samples were obtained during routine total hip replacement surgery. Levels of soluble RANKL, osteoprotegerin (OPG) and sclerostin in plasma were evaluated by ELISA. To compare the osteoclastogenic potential of RA and OA blood and bone marrow plasma, adherent PBMCs isolated from healthy blood donors were cultured for 15–21 days in the presence of heat inactivated plasma. Osteoclasts (OCs) differentiation was examined by TRAP staining and calcified matrix resorption activity. <h3>Results</h3> Significantly higher levels of soluble RANKL in blood and bone marrow plasma from RA than from OA were observed, which correlated with disease activity. OPG levels were comparable between RA and OA. A tendency to higher osteoclastogenic potential of RA blood plasma was reflected by stronger resorptive activity of osteoclasts in comparison to OA. Interestingly, RA blood plasma promoted enhanced differentiation of monocytes into large osteoclasts (≥10 nuclei), whereas OA plasma induced mainly small osteoclasts (less than 10 nuclei). This phenomenon was not observed for bone marrow plasma. Both RA and OA bone marrow plasma stimulated differentiation of osteoclasts. The osteoclastogenic potential was comparable between OA and RA, despite higher level of soluble RANKL in RA bone marrow plasma. Bone marrow soluble RANKL may originate from membrane form shed during inflammation, as monocytes and T-lymphocytes exert significantly lower RANKL surface expression. Sclerostin concentrations in OA, but not RA, bone marrow plasma correlated with resorption activity of OCs. <h3>Conclusions</h3> RA blood plasma has stronger osteoclastogenic property than OA. Bone marrow plasma promotes osteoclastogenesis without significant differences between RA and OA.