tbuckley/cabot-search huggingface dataset:
Abstract 416: Carbon monoxide targets Notch1 and MAPK-ERK1/2 signaling pathways to block growth of lung carcinoma
Authors: Zsuzsanna Nemeth, Eva Csizmadia, Lisa Vikstrom, Mailin Li, Kavita Bisht, Alborz Feizi, David Gallo, Leo Otterbein, Janos Fillinger, Balazs Dome, Daniel B. Costa, Barbara Wegiel
Journal: Cancer Research (2015)

Abstract We have recently shown that inhalation of low, non-toxic doses of carbon monoxide (CO) is a potential therapeutic adjuvant treatment for lung cancer and prostate cancer (Cancer Research, 2013, Wegiel B et al). We found that CO doses of 100 ppm daily or twice per week were the most effective in suppressing A549 xenograft tumors growth, Ki67 expression and increased cleaved caspase-3 staining. Additionally, we found that inhibition of xenografts and KRAS-driven lung tumor growth in response to CO was associated with increased expression of M1 macrophage markers (CD86, CD197, RANTES) and decreased M2 markers (MMR) and HO-1 blockage. We demonstrated a direct interaction between HO-1 and Notch1. Further, that CO promotes Notch 1 cleavage as well as phosphorylation of ERK1/2 in the stroma cells, which are the markers of M1 polarization. Moreover, we demonstrated a significant correlation between low HO-1 expression and high p-ERK ½ expression in primary human lung cancers (n = 30 patients). In summary, we describe a mechanism by which CO affects cancer growth through regulation of macrophage polarization via Notch1 and Erk1/2 pathways. Citation Format: Zsuzsanna Nemeth, Eva Csizmadia, Lisa Vikstrom, Mailin Li, Kavita Bisht, Alborz Feizi, David Gallo, Leo Otterbein, Janos Fillinger, Balazs Dome, Daniel B. Costa, Barbara Wegiel. Carbon monoxide targets Notch1 and MAPK-ERK1/2 signaling pathways to block growth of lung carcinoma. [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 416. doi:10.1158/1538-7445.AM2015-416
Abstract 2907: AMPK induction, lysosomal acidification and melanoma survival increased by p53 dysfunction are counteracted by inhibiting autophagy
Authors: Valery Chavez-Perez, Mary Strasberg-Rieber, Manuel Rieber
Journal: Cancer Research (2015)

Abstract BACKGROUND. In contrast to the majority of human tumors which harbour p53 mutations, melanomas preferentially have BRAF V600E or NRAS(Q61K) mutations accompanied by dysfunction of the p53 tumor suppressor gene, which may help progression from nevi to invasive melanoma. Although ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53 (Viros A. et al, Nature. 2014;511:478-82), some evidences for an anomalous wt p53 response to radiation in melanomas are a dysfunctional pro-apoptotic DNA damage response which can be enhanced by radiation sensitizers like halogenated pyrimidines (Rieber M, Rieber MS.Cancer Biol Ther. 2008;7:1561-6), and a report that p53 knockdown in melanoma cells resulted in decreased proliferation (Avery-Kiejda KA1, Bowden NA, Croft AJ, Scurr LL, Kairupan CF, Ashton KA, Talseth-Palmer BA, Rizos H, Zhang XD, Scott RJ, Hersey P.BMC Cancer. 2011;11:203) .PURPOSE. Since activation of AMPK by AMP inhibits ATP-consuming metabolic pathways during metabolic stress which may cause autophagy, we investigated the possible role of melanoma p53 status in modulating response to AMPK activators and autophagy inhibitors, in physiological 5mM glucose. EXPERIMENTAL. Genetically-matched NRAS-mutant human melanoma cells with unequal p53 mutational status were exposed to different glucose levels in the presence of AMPK inducers including autophagy modulators. Formation of autophagic vesicles were quantitated by cytometric red/gree acridine orange fluorescence Apoptosis-associated PARP cleavage was studied by specific immune blotting. RESULTS. AMPK induction in response to AICAR was greater than that of metformin and was increased in mutant p53 cells, which also showed greater resistance to autophagy inhibition. Greater AMPK activation correlated with increased lysosomal acidification in mutant p53 cells. CONCLUSIONS. Our results identify a role for a) p53 dysfunction in enhancing the response to AMPK activators and autophagy to favour tumor cell survival, b) autophagy inhibitors in counteracting pro-survival AMPK signaling. Citation Format: Valery Chavez-Perez, Mary Strasberg-Rieber, Manuel Rieber. AMPK induction, lysosomal acidification and melanoma survival increased by p53 dysfunction are counteracted by inhibiting autophagy. [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 2907. doi:10.1158/1538-7445.AM2015-2907
Inherited Bone Marrow Failure Syndromes in Children: 32 Years Experience in a Single Institution.
Authors: Guillermo I. Drelichman, Nora F. Basack, Alejandra Maro, Graciela Schwalb, Daniel H. Freigeiro, Sandra Pennesi, Lorena Moran, Ana Awdejczuk, Luis Aversa
Journal: Blood (2005)
HLA-DP Mismatches Increase the Risk of Acute GVHD after Unrelated Donor Hematopoietic Transplantation (UDT).
Authors: Marcos de Lima, Simrit Parmar, Ping Liu, Poliana A. Patah, Pedro Cano, Elizabeth J. Shpall, Chitra Hosing, Daniel Couriel, Paolo Anderlini, Sergio Giralt, Borje S. Andersson, Partow Kebriaei, Gabriela Rondon, Richard Champlin, Marcelo Fernandez-Vina
Journal: Blood (2006)
Abstract 1819: Profiling of extracellular matrix proteins in pancreatic ductal adenocarcinoma progression and metastasis
Authors: Chenxi Tian, Daniel Ohlund, Karl Clauser, Steven A. Carr, David A. Tuveson, Richard O. Hynes
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer-related death, and is characterized by accumulation of excessive extracellular matrix (ECM). Although the ECM of tumors, such as PDAC, has long been known to have major effects on behavior of both tumor and stromal cells, including invasion, angiogenesis, metastasis, and resistance to therapy, the detailed composition of the ECM in PDAC tumor progression and metastasis are not understood. To study the involvement of ECM proteins in PDAC primary tumor growth and the tissue-specific metastasis program, we modified the comprehensive ECM proteomic approach by Mass Spectrometry (MS) recently developed in our lab to profile the ECM changes during PDAC progression in both the LSL-KrasG12D/+; LSL-Trp53R127H/+; Pdx-1-Cre (KPC) mouse models of PDAC and human patient samples. We will compare ECM profiles from normal pancreas, pancreatitis, early and late pancreatic intraepithelial neoplasia (PanIN) stages, and PDAC. Initial MS identified between 100 and 140 ECM proteins in samples representing each stage. The changes identified include changes previously associated with PDAC (e.g., upregulation of Tnc, Lox) plus novel, previously unreported changes. The combination of mouse models and human samples will allow us to uncover critical ECM changes during PDAC progression and metastasis and, furthermore, to investigate and understand the functional consequences of such changes. The ongoing studies will characterize the ECM of PDAC in detail and provide novel insights into diagnosis, prognosis and treatments of this very difficult disease. Citation Format: Chenxi Tian, Daniel Ohlund, Karl Clauser, Steven A. Carr, David A. Tuveson, Richard O. Hynes. Profiling of extracellular matrix proteins in pancreatic ductal adenocarcinoma progression and metastasis. [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 1819. doi:10.1158/1538-7445.AM2015-1819
ATNT-27ASSESSING THE SAFETY OF COMBINATION THERAPY WITH BEVACIZUMAB AND OPTUNETM FOR HIGH GRADE GLIOMAS
Authors: Ashley Sumrall, Daniel Haggstrom, Tony Asher, Anthony Crimaldi, Roshan Prabhu, Scott Wait, Stuart Burri
Journal: Neuro-Oncology (2015)

BACKGROUND: The prognosis for patients with high grade gliomas remains dismal. In addition to cytotoxic therapy, the FDA has approved bevacizumab and OptuneTM (Tumor Treating Fields) for recurrent glioblastoma. Given the prognosis and multiple treatment options, many clinicians have elected to offer combined therapy. We examined our patient population at two institutions where combination therapy has been used. METHODS: We retrospectively reviewed clinical courses of all patients receiving OptuneTM who have been concurrently managed with bevacizumab or experienced prior therapy with bevacizumab. Toxicity was described for those patients. Patients who received OptuneTM for at least 4 weeks with concurrent bevacizumab were analyzed for overall survival from time of initiation of concurrent therapy. RESULTS: We identified 37 patients, 26 males and 11 females. Of those, 33 patients received concurrent therapy, and all of those patients had prior bevacizumab exposure. OptuneTM was started as single therapy in 4 patients after bevacizumab exposure and failure. 6 patients experienced contact dermatitis which did not delay therapy. 1 patient had a small skin erosion which did not delay therapy. 2 patients had small skin erosions which delayed OptuneTM therapy. 1 patient had folliculitis and skin erosions and ulcers which necessitated cessation of therapy. 1 patient had a grade 2 intracranial bleed with no clinical sequelae aside from the need to hold bevacizumab. 29 patients received this therapy for at least 4 weeks. Median duration of concurrent therapy was 4 months. Median OS from initiation of concurrent therapy was 5.3 months. CONCLUSIONS: In our dataset, there was no toxicity appreciated aside from mild skin toxicity in the majority of patients. Combining bevacizumab and OptuneTM does not appear to significantly increase risk of bleeding or stroke. The incidence and severity of skin reactions were comparable to those described previously. Additional trials to investigate this combination are ongoing.
Differential Diagnosis of Myelodisplastic Syndrome, with Flow Cytometry.
Authors: Luigi De Salvo Cardullo, Mirian C Duerto, Dalila DV De Salvo, Rodolfo J Salas-A, Jesus E Weir-M, Ana M Nuñez, Alonso A Nuñez, Zaida A Plumacher, Olga Ch Fernandez, Estela BEATRIZ Avila, Mariela J Rios, Luis S Paz, Dalida DJ Salas, Alba M Fuenmayor
Journal: Blood (2009)
Circadian Clock Protein CRY Controls B-Cell Intrinsic Tolerance
Authors: Qi Cao, Xuan Zhao, Sigal Gery, Zhengshan Chen, Ruishu Deng, Haibo Sun, De-chen Lin, Zhiqiang Zhao, Jonathan W Said, Quan-zhen Li, Markus Muschen, Ronald M. Evans, H. Phillip Koeffler
Journal: Blood (2015)
Aspirin plus medium intensity Coumadin versus aspirin alone in the prevention of reocclusion after successful thrombolysis for suspected acute myocardial infarction: Results of the APRICOT-2 trial
Authors: PJ Van Den Bergh, Rpjw Vromans, WR Aengevaeren, G Veen, JE Luijten, DP Hertzberger, AJ Van Boven, Gjh Uijen, Fwa Verheugt
Journal: Journal of the American College of Cardiology (2001)
Haploinsufficiency of NPM1 in AML Derived NPM1 Mutant (NPMc+) Expressing Cells Contributes to Aberrant C/EBPα Activity
Authors: Kathryn Czepiel, Kelly Nichol, Mason Tippy, Nirmalee Abayasekara, Jaclyn Lee, Ethan Wajswol, Anjali Khanna, Nancy Berliner, Arati Khanna-Gupta
Journal: Blood (2014)
Clinical Outcomes and Factors Predicting Development of Venous Thromboembolic Complications in Patients with Advanced Refractory Cancer in a Phase I Clinic: The M. D. Anderson Cancer Center Experience
Authors: Apostolia-Maria Tsimberidou, Sushma Vemulapalli, Lakshmi Chintala, Navjot Dhillon, Xiudong Lei, David Hong, Razelle Kurzrock
Journal: Blood (2008)
OC-090 To determine the negative predictive value of faecal calprotectin in predicting future organic gastrointestinal disease
Authors: J K Moore, S West, S Kelly, G Robins
Journal: Gut (2010)

<h3>Introduction</h3> Faecal calprotectin (FC) levels can be used to predict the likelihood of relapse in patients with inflammatory bowel disease (IBD)1 and as a non-invasive marker to predict organic gastrointestinal disease (OGID)2 However, long-term follow-up of patients with low FC levels has not been done. Our aim was to determine whether patients with low FC levels develop OGID over a 5-year period. <h3>Methods</h3> York Hospital serves a population of approximately 280 000 and has measured FC where clinically indicated in patients since 2004. Records of patients with a normal FC (&lt;50 μg/g) in 2004 were examined retrospectively. Those with known OGID at the time of index FC measurement were excluded. Primary outcome was diagnosis of an OGID (eg, colorectal cancer or polyps &gt;1 cm, IBD) in the 5 years subsequent to the index FC measurement. The assay used was the PhiCal Calprotectin Elisa kit with a clinical sensitivity of 74% and specificity of 84% at 50 μg/g.3 <h3>Results</h3> 118 patients (39 male and 79 female) were identified. The mean age was 40.4 years (SEM 1.3); median age was 41 years (range 15–83). The mean FC level was 13.95 μg/g (SEM 1.04). The median was 10 μg/g (range 5–48). 84 patients were diagnosed with Functional Bowel Disease. No patients during the 5-year follow-up period developed OGID. <h3>Conclusion</h3> A normal FC has an extremely high negative predictive value for developing OGID over the subsequent 5 years.
First line treatment in patients with luminal-like metastatic breast cancer: a propensity score-matched analysis
Authors: M. Bonotto, L. Gerratana, G. Arpino, M. Di Maio, C. De Angelis, D. Iacono, M. Cinausero, M. Milano, P. Gargiulo, C. Fontanella, C. Bozza, S. Moroso, A.M. Minisini, M. Mansutti, G. Fasola, S. De Placido, F. Puglisi
Journal: Annals of Oncology (2015)
Genome-Wide Profiling of DNA Copy Number Variation in CLL Cases Lacking 17p- (TP53) or 11q- (ATM) Abnormalities Selected from the CLL4 Study
Authors: Sarah L Hockley, David Gonzalez, Vasantha Brito-Babapulle, Monica Else, Paola E Leone, Brian A Walker, Estella Matutes, Claire E Dearden, Daniel Catovsky, Gareth J Morgan
Journal: Blood (2008)
Abstract 3335: Targeting Egr1 selectively radioprotects normal tissues while killing cancer cells
Authors: Diana Yi Zhao, Keith M. Jacobs, Dennis E. Hallahan, Dinesh Thotala
Journal: Cancer Research (2015)

Abstract Radiotherapy is a common therapeutic modality for a wide range of malignancies. Normal tissue toxicity reduces the therapeutic index of radiotherapy and decreases the quality of life for cancer survivors. Apoptosis is a key element of the radiation response in normal tissues like the hippocampus and small intestine, and results in neurocognitive disorders and intestinal malabsorption. The Early Growth Response 1 (Egr1) transcription factor mediates radiation-induced apoptosis since it activates the transcription of pro-apoptosis genes in response to ionizing radiation (IR). Therefore, we hypothesized that the genetic abrogation of Egr1 and the pharmacological inhibition of its transcriptional activity could attenuate radiation-induced apoptosis in normal tissues. We demonstrated that Egr1 null mice had less apoptosis in the hippocampus and intestine following irradiation as compared to their wild-type littermates. Alternatively, mice treated with Mithramycin A, a drug that prevents binding of Egr1 to target promoters, also displayed reduced apoptosis following irradiation in the intestine as compared to mice treated with vehicle. In cell culture based studies, shRNA-mediated silencing of Egr1 expression dampened apoptosis and enhanced the clonogenic survival of irradiated HT22 hippocampal neuronal cells and IEC6 intestinal epithelial cells. Mechanistically, these events involved an abrogation of p53 induction by IR and an increase in the ratio of Bcl-2/Bax expression. In contrast, targeted silencing of Egr1 in two cancer cell lines (GL261 glioma cells, HCT116 colorectal cancer cells) was not radioprotective, since it reduced their growth while also sensitizing them to radiation-induced death. These results strongly support the potential of targeted silencing of Egr1 in order to improve the therapeutic index of radiotherapy and minimize the normal tissue complications associated with radiation therapy. Note: This abstract was not presented at the meeting. Citation Format: Diana Yi Zhao, Keith M. Jacobs, Dennis E. Hallahan, Dinesh Thotala. Targeting Egr1 selectively radioprotects normal tissues while killing cancer cells. [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 3335. doi:10.1158/1538-7445.AM2015-3335
OP24ASSESSING 'SECOND-LOOK' TUMOUR RESECTABILITY IN CHILDHOOD EPENDYMOMA - A CENTRALISED REVIEW PANEL AND CLASSIFICATION TOOL FOR THE SIOP EPENDYMOMA II TRIAL
Authors: Christopher P. Millward, Conor Mallucci, Tim Jaspan, Donald Macarthur, Richard G. Grundy
Journal: Neuro-Oncology (2015)

INTRODUCTION: Complete surgical resection is significantly associated with survival in most, but not all clinical trials in Ependyoma, and varies significantly due to surgical strategy. To improve imaging quality and discussion of surgical resection status in the forthcoming SIOP Ependymoma II trial, a central review of imaging and resection status will be offered prior to treatment stratification. We present a review of surgical decision-making from the UKCCSG/SIOP Ependymoma trial along with a primary surgical classification system for Ependymoma II. METHOD: Imaging of 89 patients enrolled in the UKCCSG/SIOP Ependymoma trial was independently reviewed by 3 experienced paediatric neuro-oncology surgeons (44 incomplete, 45 complete). 6 incomplete resections were supratentorial and data was incomplete for 10. Pre and post op imaging was only available for 28 posterior fossa cases. Location of residual disease, decision to offer 'second-look' surgery, perceived chance of complete resection, and risk to cranial nerves was assessed. Review panel retrospective recommendation for 'second-look' surgery was compared with actual 'second-look' surgery for patients with incomplete resections after initial surgery. RESULTS: 28 patients with incomplete resections were reviewed. 13 patients had 'second-look' surgery at some point. Of the remaining 15 patients, the surgical review panel would have offered 'second-look' surgery in 9 of these, and 18 overall. CONCLUSION: Based on scans alone a surgical panel would have offered 'second-look' surgery to an additional 53% of patients. The benefit of a surgical review panel and classification system will be assessed in the forthcoming Ependyoma II trial to maximise complete resection whilst minimising surgical morbidity.
Abstract 12976: Malignant Type of Electrical Storm in Patients With an Implantable Cardiac Shock Device: Results From the Nippon Storm Study
Authors: Takashi Noda, Takashi Kurita, Takashi Nitta, Hiroshi Frushima, Naoki Matsumoto, Takeshi Toyoshima, Akihiko Shimizu, Hideo Mitamura, Tohru Ohe, Yoshifusa Aizawa
Journal: Circulation (2015)

Introduction: Electrical storm (ES) referred to as multiple device therapies is an important clinical problem in patients (pts) with an implantable cardiac shock device (ICSD), such as implantable cardioverter-defibrillator or cardiac resynchronization therapy device with defibrillator. Detailed clinical aspects of ES, however, remain unclear in the Asian large population. Methods: We analyzed the data of the Nippon Storm Study which was a prospective observational study and consisted of 1570 pts enrolled from 48 Japanese ICSD centers designed to clarify the clinical aspects of ES. The study population included 493 (31%) pts with ischemic heart disease (IHD) and 357 (23%) pts with dilated cardiomyopathy (DCM). They had a mean LVEF of 43±19 %. Results: ES occurred in 96 (6.4%) pts during a median follow-up of 28 (23-33) months. Compared to pts without ES, pts with ES showed a significantly lower left ventricular ejection fraction (43% vs 38 %, respectively, p=0.005). No significant difference regarding ES incidence was observed between pts with IHD and pts with DCM (log-rank p=0.77). A sub-analysis of the ES characteristics revealed that the mortality in patients with shock therapy during the first ES episode and those with the incidence of multiple episodes of ES during the follow-up was significantly higher than those without (12/18 vs 30/78; p=0.03, 12/18 vs 26/78, p&lt;0.01, respectively, Table). Conclusions: Shock therapy during the first ES episode and multiple episodes of ES were related to significantly higher mortality in pts with ICSD. There can be a malignant entity of ES.
Development of Efficent Gene Therapy for the Treatment of Erythrocyte Pyruvate Kinase Deficiency.
Authors: Nestor W. Meza, Maria Eugenia Alonso, Susana Navarro, Guillermo Guenechea, Oscar Quintana-Bustamante, Maria Garcia-Gomez, Juan A. Bueren, Jose M. Bautista, Jose C. Segovia
Journal: Blood (2007)
Abstract POSTER-BIOL-1341: MUC16 (CA125) knockdown as a potential strategy to decrease tumor growth
Authors: Mildred Felder, Arvinder Kapur, Alexander L. Rakhmilevich, Xiaoyi Qu, Joseph Connor, Manish S. Patankar
Journal: Clinical Cancer Research (2015)

Abstract MUC16 (CA125), a membrane spanning mucin, promotes proliferation and metastasis of ovarian cancer cells. Here, we demonstrate that MUC16 protects cancer cells from cytolysis by NK cells and macrophages. SCID mice implanted with MUC16-positive and MUC16-knockdown human ovarian tumors have a median survival of 75 and 181 days, respectively. Animals bearing MUC16-positive tumors developed ascites fluid and were moribund because of high tumor volume. In contrast, none of the mice with MUC16-knockdown tumors developed ascites. Decreased growth of MUC16-knockdown tumors correlated with increased cytolysis by murine splenocytes from naïve and anti-CD40 antibody treated mice. Murine NK cells showed a 2.5-fold higher preference for MUC16-knockdown cells. Unstimulated and LPS or IFN-γ-activated peritoneal macrophages from SCID mice also preferentially inhibited proliferation of MUC16-knockdown targets. Even in SCID/Beige mice, where cytolysis by resident NK cells is impaired, median survival MUC16-positive tumor-bearing animals was 75 days as compared to 189 days for animals with MUC16-knockdown tumors. All ten SCID/Beige mice with MUC16-knockdown tumors showed significant macrophage infiltration throughout the tumor nests and only two of the ten developed ascites. In contrast, 80% of SCID/Beige mice with MUC16-positive tumors had significant ascites and macrophages were predominantly found in the stroma. Finally, knockdown of MUC16 increased the susceptibility of cancer cells to natural cytotoxic responses of human NK cells, and increased their susceptibility to ADCC and lysis in the presence of immunocytokines. Therefore, strategies that decrease the expression of immunosuppressive MUC16 coupled with NK or macrophage-based immunotherapies should be investigated for the treatment of ovarian cancer. Citation Format: Mildred Felder, Arvinder Kapur, Alexander L. Rakhmilevich, Xiaoyi Qu, Joseph Connor, Manish S. Patankar. MUC16 (CA125) knockdown as a potential strategy to decrease tumor growth [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1341.