tbuckley/cabot-search huggingface dataset:
Abstract 2451: Cancer stem cell survival postradiation in medulloblastomas requires YAP, YB1, and IGF2
Authors: Abhinav Dey, Caroline Maier, Anshu Malhotra, Anna Kenney
Journal: Cancer Research (2016)

Abstract Sonic hedgehog (Shh)-mediated medulloblastoma growth requires IGF2 (Insulin-like Growth Factor 2) and we recently showed that Yes Associated Protein (YAP1) induces IGF2 expression by Y-box protein 1(YB1) in Shh-stimulated cerebellar granule neural precursors (CGNPs), proposed cells-of-origin for the Shh molecular subclass of medulloblastoma, and mouse Shh-medulloblastoma cells. We found elevated levels of YAP1, YB1 and IGF2 in tumor cells occupying the peri-vascular niche, a microenvironmental niche proposed to house so-called tumor re-populating cells that survive radiation and contribute to medulloblastoma recurrence, which is fatal. We have developed an ex vivo approach using organotypic brain tumor slice cultures to better understand how YAP1, YB1, and IGF2 regulate peri-vascular niche cell survival post-radiation. We observed that the perivascular niche cell population expressing stem cell markers increases markedly following exposure to radiation. Additionally, on targeting any component of the YAP1-YB1-IGF2 axis we observed increased level of cell death within the niche and compromised cancer stem cell niche expansion post-radiation. These findings strongly indicate that therapeutic approaches intended to impair the function of this pathway could be used to reduce the use of cranio-spinal radiation of medulloblastoma patients, which causes life-long side effects that drastically impair quality of life. Citation Format: Abhinav Dey, Caroline Maier, Anshu Malhotra, Anna Kenney. Cancer stem cell survival postradiation in medulloblastomas requires YAP, YB1, and IGF2. [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 2451.
Abstract LB-317: Energy distruptor 2-deoxyglucose mitigates bacterial infection responsive hyperplasia and/or colitis
Authors: Ishfaq Ahmed, Shahid Umar, Rao V. Papineni
Journal: Cancer Research (2016)

Abstract Transmissible murine crypt hyperplasia (TMCH) is a pathological outcome of Citrobacter rodentium (CR) infection, accompanied by intestinal inflammation during colitis though excessive induction of epithelial regeneration and repair mechanisms. The TMCH model, provides an excellent template to determine how alterations in intestinal stem cells promote trans-differentiation, crypt regeneration or colon carcinogenesis following bacterial infection. CR is a valuable infection model for the study of pathogenesis of the clinically significant human pathogens, enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC). During TMCH, there is a complex interplay between the Notch and Wnt/β-catenin pathways in colonic crypt hyperplasia. Blocking Notch signaling via chronic dibenzazepine (DBZ) administration inhibits both Notch and Wnt signaling, and disrupts the intestinal barrier during CR induced colitis. 2-deoxyglucose (2DG) is a glycolytic inhibitor has been used for cancer therapy exploiting the cancer cell's high metabolic state. Added, the similarity of 2DG to mannose produces improper N-linked glycosylation resulting in an unfolded protein response (UPR) slowing growth of tumors. Here, using CR infection model, we show that dietary treatment of 2DG (0.4%) mitigates C. rodentium- and Notch signaling blocker dibenzazepine (DBZ)-induced colitis in NIH:Swiss mice. The survival curve shows no loss in mice administered with 2DG, compared to 40% loss in mice with vehicle alone during CR infection together with DBZ treatment. At tissue level, 2DG dietary intervention resulted in restoration of Hes-1, and β-catenin protein levels as observed from the western analyses of the C. rodentium-infected and DBZ-treated mice crypts. Histological staining show reduced dysbiosis upon 2DG intervention, as seen from reduced infiltration of inflammatory response cells during CR infection and the therapeutic effects are further substantiated with the Ki-67 staining. Thus, the energy distruptor 2-deoxyglucose (2DG) is described for the first time here to mitigate bacterial infection and its responsive hyperplasia/colitis. The current model in this novel mechanism of action will be presented. Citation Format: Ishfaq Ahmed, Shahid Umar, Rao V. Papineni. Energy distruptor 2-deoxyglucose mitigates bacterial infection responsive hyperplasia and/or colitis. [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-317.
Proteomic Characterization of An Isogenic Multiple Myeloma Cell Line Model of Bortezomib Resistance
Authors: *Catriona A. Hayes, *Paul Dowling, Joseph Negri, Michael Henry, Leutz Buon, Jana Jakubikova, Jake E Delmore, Douglas W. McMillin, Steffen Klippel, Hannah M. Jacobs, Niels W.C.J. van de Donk, Eugen Dhimolea, Panisinee Lawasut, Paul G. Richardson, Kenneth C. Anderson, Martin Clynes, *Peter O Gorman, *Constantine S. Mitsiades
Journal: Blood (2011)
Abstract 4284: Exploratory plasma proteomic analysis in a randomized cross-over trial of aspirin among healthy individuals
Authors: Xiaoliang Wang, Yuzheng Zhang, Ali Shojaie, Paul D. Lampe, Lisa Levy, Ulrike Peters, John D. Potter, Emily White, Johanna W. Lampe
Journal: Cancer Research (2016)

Abstract Background: Long-term use of aspirin is associated with lower colorectal cancer (CRC) incidence; however, the mechanism of the chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Methods: We assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized, double-blinded, placebo-controlled, cross-over trial of 44 healthy non-smoking men and women, aged 21-45 years. Plasma proteomics was analyzed on an antibody microarray with ∼3,000 full-length antibodies, printed in triplicate. Moderated paired t-test was performed on individual antibodies, and gene set analyses were performed for KEGG and GO pathways. Results: Among the 3,387 antibodies, significant differences in plasma protein levels were observed for 267 antibodies (p&amp;lt;0.05), the most significant protein being a transcription-factor regulator belonging to a steroid receptor family and found to be differentially expressed in colon cancer cells. Other significant proteins are involved in multiple oncogenic pathways related to colon tumorigenesis. In the pathway analysis, 4 KEGG (among 138) and 69 GO (among 1,089) pathways were found to be significant (p&amp;lt;0.05), including natural killer (NK) cell-mediated cytotoxicity, butanoate metabolism and Wnt signaling pathways. Pathways that modulate cellular protein binding to steroid receptors were also significantly different between aspirin treatment and placebo (p&amp;lt;0.05). None of the results remained statistically significant after correction for multiple testing. Conclusion: Several proteins and pathways, which have previously been reported as playing a role in colorectal carcinogenesis in vitro were found to be differentially expressed after aspirin treatment vs. placebo in healthy human subjects. This study suggests several chemopreventive mechanisms of aspirin; however, larger, confirmatory studies are needed. Citation Format: Xiaoliang Wang, Yuzheng Zhang, Ali Shojaie, Paul D. Lampe, Lisa Levy, Ulrike Peters, John D. Potter, Emily White, Johanna W. Lampe. Exploratory plasma proteomic analysis in a randomized cross-over trial of aspirin among healthy individuals. [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 4284.
Using technology to improve quality metric adherence.
Authors: Paul B. Jacobsen, Michele Gaguski, Kathryn A Thomas, Amanda Hathaway, Karina I. Halilova, Carrie Tompkins Stricker, Karen Hammelef, SarahLena Panzer, Douglas W. Blayney, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2016)

257 Background: Many barriers to adherence to quality standards exist, including patient, provider, and system barriers to delivery and documentation of timely, evidence-based care. Gaps in clinician knowledge about care standards likely contribute to non-adherence. Methods: Prior to an intervention study, providers completed a questionnaire assessing their knowledge of and ability to influence institutional attainment of specific QOPI metrics. Providers’ ability to influence meeting each of 9 QOPI metrics was measured on a 1-4 scale from “not at all” to “significantly” able to influence. Providers also identified barriers to meeting each metric. Results: 28 providers completed surveys; 43% from a university based cancer center and 57% from a community based cancer center. Respondents include oncology MDs (43%), NPs (7%) and RNs (46%). Perceived ability to influence 9 quality metrics are detailed in the Table below. Providers felt the least able to influence metrics related to fertility preservation with 32% reporting no influence. 21% credited ‘lack of visibility into current data’ to be a main barrier. Providers reported limited ability to address emotional well-being with 36% reporting a ‘lack time to assess/manage’. Providers felt most able to influence physical symptoms such as pain. Conclusions: The most frequently cited barriers to meeting study-specific quality metrics included lack of a) current knowledge/latest evidence and, b) time to assess/manage. Employing methods to address these barriers may improve quality care. In part 2 of this study providers engage with the Carevive Care Planning System, designed to address these barriers by assessing patient needs at the point of care and providing evidence-based recommendations for treatment. [Table: see text]
Physical trauma recorded in primary care is associated with the onset of psoriatic arthritis among patients with psoriasis
Authors: Stefán Már Thorarensen, Na Lu, Alexis Ogdie, Joel M Gelfand, Hyon K Choi, Thorvardur Jon Love
Journal: Annals of the Rheumatic Diseases (2016)

To evaluate the risk of psoriatic arthritis (PsA) among patients with psoriasis exposed to physical trauma.A matched cohort study was performed using data from The Health Improvement Network (THIN). Patients with psoriasis exposed to trauma were randomly matched to up to five unexposed psoriasis controls based on gender, age, duration of psoriasis and the date of entry into THIN. Trauma exposure was stratified into subgroups of joint, bone, nerve and skin trauma. Cox proportional hazard models were used to estimate the HRs for developing PsA. For comparison, an identical analysis was performed in the entire THIN population evaluating rheumatoid arthritis (RA) risk following physical trauma.Patients with psoriasis exposed to trauma (N=15 416) and matched unexposed patients (N=55 230) were followed for a total of 425 120 person-years during which 1010 incident PsA cases were recorded. Adjusting for potential confounders, patients with psoriasis exposed to trauma had an increased risk of PsA compared with controls, with a multivariate HR of 1.32 (95% CI 1.13 to 1.54). In our subset analysis, bone and joint trauma were associated with multivariate HRs of 1.46 (95% CI 1.04 to 2.04) and 1.50 (95% CI 1.19 to 1.90), respectively; while nerve and skin trauma were not associated with a statistically significant increase in risk compared with controls. Patients exposed to trauma in the entire THIN population did not have an increased risk of developing RA: HR 1.04 (95% CI 0.99 to 1.10).Patients with psoriasis exposed to physical trauma are at an increased risk of developing PsA.
Abstract 1616: Galectin-4 interferes with the integrin β4/Src/FAK cascade and attenuates metastasis in urothelial carcinoma
Authors: Li-Fang Lin, Meei-Maan Wu, Te-Chang Lee
Journal: Cancer Research (2016)

Abstract Galectin-4 (Gal-4), a multifunctional lectin, is presented at both intracellular and extracellular sites. Recent studies have shown that Gal-4 plays certain role in attenuating cancer progression and metastasis. We have also observed that patients with urothelial carcinoma (UC) with the lower Gal-4 expression were at higher grade and stage. In addition, the Gal-4 expression is inversely associated with lymph node invasion and prognosis. Since how Gal-4 attenuates the cancer metastasis in UC has not been well investigated, the goal of the present study is to understand the role of Gal-4 in UC progression. We ectopically expressed Gal-4 in UC cells and found that increased Gal-4 significantly inhibits cell proliferation, colony formation, migration, and invasion. We also demonstrated that Gal-4 overexpression leads to a significant decrease the adhesion of UC cells to the basement membrane substrate laminin. Mechanistically, we found that Gal-4 overexpression significantly reduces the expression of the laminin receptor integrin α6β4. Besides to downregulation of integrin β4, Gal-4 overexpression also reduces phosphorylation of Src and focal adhesion kinase (FAK) and promotes anoikis. Together, the present results revealed that Gal-4 reduces the metastasis activity of UC cells by interfering integrin β4/Src/FAK cascade, which are of essential to prevent the suspended cells from anoikis. These results suggest that Gal-4 could be considered as a pivotal factor in the migration and invasion of UC cells. Key words: Galectin-4, integrin β4, migration, invasion, metastasis, anoikis, urothelial cancer Citation Format: Li-Fang Lin, Meei-Maan Wu, Te-Chang Lee. Galectin-4 interferes with the integrin β4/Src/FAK cascade and attenuates metastasis in urothelial carcinoma. [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 1616.
Abstract 2281: DNA methyl transferase inhibitors (DNMTis) upregulate NY-ESO expression in several human primary cells: implications for co-therapy with engineered adoptive T-cell therapies
Authors: Bruno Laugel, Alexandra Sevko, Karen Howe, Zoltan Ferjentsik, Tiago Ferronha, Miguel Maroto, Joanna Brewer, Bent Jakobsen, Gwendolyn Binder-Scholl
Journal: Cancer Research (2016)

Abstract The DNA methyl transferase inhibitors 5-aza-2’-deoxycytidine (decitabine or DECI) and 5-azacytidine (azacitidine or AZA) have recently been approved for the treatment of a variety of hematologic malignancies. These cytidine analogues remove repressive epigenetic DNA methyl marks and induce the transcription of numerous genes normally silenced during the processes of cellular differentiation or transformation. DNMTis have a net anti-neoplastic activity through the up-regulation of tumor-suppressor genes involved in the induction of apoptosis, cellular differentiation and cell cycle arrest. In addition, DNMTis promote the expression of several cancer testis antigens (CTAs) by tumor cells, including NY-ESO and MAGE-A1/A3. These observations suggest that the combination of DNMTis with immunotherapeutic modalities may provide some clinical benefit. Adoptive immunotherapies using autologous CD4+ and CD8+ T cells expressing an affinity optimized NY-ESO TCR are in clinical trials and show robust clinical responses in patients across several indications including synovial sarcoma, multiple myeloma or melanoma. DNMTis were previously shown to induce the expression of NY-ESO in antigen-low or -negative tumor cells and consequently enable the activation of NY-ESO-specific T-cells. While there is compelling evidence for the combination of DNMTis with T cells containing engineered affinity-enhanced TCRs recognizing NY-ESO-1, safety data supporting this approach are lacking. Initial tests into the safety of combining these treatments investigated the effects of DECI and AZA on NY-ESO and LAGE-1 expression in a panel of primary adult human cells of different tissue origins. Our data demonstrate that treatment with either compound resulted in a significant up-regulation of NY-ESO transcription in a subset of primary cells tested. The magnitude of increase in transcript expression varied between cell types and, in some cases, was sufficient to activate T cells expressing an affinity-optimized NY-ESO-specific TCR. These findings raise important safety concerns with regards to the potential combination of DNMTi compounds with NY-ESO T-cell therapy and suggest that such co-therapies may result in on-target off-tumor toxicities. Citation Format: Bruno Laugel, Alexandra Sevko, Karen Howe, Zoltan Ferjentsik, Tiago Ferronha, Miguel Maroto, Joanna Brewer, Bent Jakobsen, Gwendolyn Binder-Scholl. DNA methyl transferase inhibitors (DNMTis) upregulate NY-ESO expression in several human primary cells: implications for co-therapy with engineered adoptive T-cell therapies. [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 2281.
Leukemic T Cells Are Specifically Enriched In a Unique CD3dimCD7low Subpopulation of CD4+ T Cells In Acute-Type Adult T Cell Leukemia
Authors: Yamin Tian, Seiichiro Kobayashi, Nobuhiro Ohno, Masamichi Isobe, Mayuko Tsuda, Yuji Zaike, Nobukazu Watanabe, Kenzaburo Tani, Arinobu Tojo, Kaoru Uchimaru
Journal: Blood (2010)
Abstract 1729: Withaferin A blocks formation of IFN-γ-induced metastatic cancer stem cells through inhibition of the CXCR4/CXCL12 pathway in the UP-LN1 carcinoma cell model
Authors: Andy Shau-Bin Chou, Li-Lei Ting, Chin-Hsuan Hsieh, See-Tong Pang, Shuen-Kuei Liao
Journal: Cancer Research (2016)

Abstract As our understanding of cancer stem cell (CSC) biology improves, there is an urgent need to search for inhibitory agents of CSCs and metastatic CSCs (mCSCs) positive for CXCR4. Withaferin A (WA), a withanolide extracted from the medicinal plant Withania somnifera, has been shown to exhibit anti-cancer effects through multiple mechanisms. Whether WA could selectively target CSCs, mCSCs, or non-CSCs of a gastrointestinal (GI) carcinoma tumor remains unclear. Side population analysis, flow cytometric phenotyping and sorting, non-invasive imaging in conjunction with xenotransplantation, and immunohistology were used in this investigation. Using the lymph node metastatic GI cancer cell line UP-LN1, consisting of CD44high/CD24low grape-like floating (F) and CD44low/CD24high adherent (A) cell subsets, this study demonstrated that, as compared with parental UP-LN1 cells or A cells, WA preferentially reduced F-cell proliferation, tumor sphere formation, and side population cells in vitro in greater efficiencies by apoptosis. This action was mechanistically mediated via the down-regulation of CXCR4/CXCL12 and STAT3/IL-6 pathways, both of which are instrumental in the acquisition of metastatic ability. Attenuation of IFN-γ-induced CXCR4 expression in F cells by knockdown with siRNA or blocking with anti-CXCR4 antibody, followed by Western blot analysis, showed significantly reduced metastatic potential in vitro. The extent of in vitro anti-invasive effect of WA on the IFN-γ-treated F cells was significantly greater than on the F cells without WA treatment, or F cells treated with control siRNA or with control IgG antibody. The observed in vitro effects of WA on the CSC and mCSC targeting were validated by data obtained with non-invasive imaging in NOD/SCID mouse xenotransplantation. We conclude that WA could efficiently block the formation of both CSCs and mCSCs in the UP-LN1 cell line, suggesting that WA may be considered an effective therapeutic agent for GI malignancies exhibiting grape-like tumor sphere. Citation Format: Andy Shau-Bin Chou, Li-Lei Ting, Chin-Hsuan Hsieh, See-Tong Pang, Shuen-Kuei Liao. Withaferin A blocks formation of IFN-γ-induced metastatic cancer stem cells through inhibition of the CXCR4/CXCL12 pathway in the UP-LN1 carcinoma cell model. [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 1729.
To be in pain (or not): a computer enables outpatients to inform their physician
Authors: W.H. Oldenmenger, F.E. Witkamp, J.E.C. Bromberg, J.L.M. Jongen, P.J. Lieverse, F.J.P.M. Huygen, M.A.G. Baan, L. van Zuylen, C.C.D. van der Rijt
Journal: Annals of Oncology (2016)
American Cancer Society questions study claiming increase in metastatic prostate cancer
Authors: Jeanne Lenzer
Journal: BMJ (2016)

A study claiming a rise in metastatic prostate cancer has been questioned, and the American Cancer Society posted a response after calls from journalists.1 2

The study, led by Edward Schaeffer, professor of urology at Northwestern University in Chicago, examined the records of 767 550 men with prostate cancer diagnosed from 2004 to 2013. They found that cases of metastatic disease increased from 1685 in 2004 to 2890 in 2013.

Publication of the study was preceded by a press release from Northwestern University,3 headed, “Metastatic prostate cancer cases skyrocket: increase may be due to more lax screening or more aggressive disease.” The news release cited a 72% rise in metastatic disease and quoted Schaeffer as saying that the increase was “probably” caused, at least in part, by lax screening after the 2012 United States Preventive …
Cross-talk between the dipeptidyl peptidase-4 and stromal cell-derived factor-1 in stem cell homing and myocardial repair: Potential impact of dipeptidyl peptidase-4 inhibitors
Authors: Marko Anderluh, Gordana Kocic, Katarina Tomovic, Radivoj Kocic, Marina Deljanin-Ilic, Andrija Smelcerovic
Journal: Pharmacology & Therapeutics (2016)