tbuckley/cabot-search huggingface dataset:
Abstract 1968: Activation of AKT negatively regulates the pro-apoptotic function of death-associated protein kinase 3 (DAPK3) in prostate cancer
Authors: Trinath P. Das, Arokya MS Papu John, Ram V. Roy, Sandhya R. Rao, Houda Alatassi, Chendil Damodaran, Murali M. Ankhem
Journal: Cancer Research (2015)

Abstract Activation of AKT plays a central role by inducing pro-survival signaling pathways, promotes cell growth and inhibits apoptosis in human malignancies including prostate cancer. Higher expression of pAKT is correlated with aggressiveness of the prostate cancer. Published evidences suggest that inhibition of survival kinases may utilize the current therapeutic modalities to sensitize the prostate cancer cells more significantly. Indeed, numbers of small molecules or peptides are being developed to inhibit either AKT or its upstream kinase PI3K to inhibit the growth of human malignances. Death-associated protein kinase 3 (DAPK3), a serine/threonine kinase governs many signaling pathways including induction of apoptosis. This lead the way to focus our research on small molecules which can inhibit AKT activation and induce DAPK mediated apoptosis in CaP cell lines. To begin with, we identified a small molecule which binds to AKT kinase domain with a predicted affinity of ∼11.0 Kcal/mol. The amino acid residues of AKT-1 within 4 Å of the best docking site of this small molecule, 6-dimethyl, dihydro pyranone (6ddp), includes ARG-4, SER-7, LEU-156, GLY-157, LYS-158, GLY-159, PHE-161, VAL-164, LYS -179, GLU-191, HIS-194, GLU-234, ASP-274, MET-281, ASP-292, GLY-294,LEU-295, and PHE-438. The hydroxyl group of 6ddp likely forms a hydrogen bond with the nitrogen on the side chain of HIS-194. 6ddp inhibited pAKT (ser473) expression which concomitantly induced DAPK1 expression resulting in the growth inhibition of CaP cell lines. Similar results were obtained when a pharmacological inhibitor of AKT was used which resulted in DAPK induced apoptosis of CaP cells. Subsequently, we examined the DAPK3 activation in prostate cancer samples, which significantly showed a higher expression in normal prostate samples. On the contrary, reduced expression with low level was observed with the progression of disease. Currently, our study focuses on the kinase and phosphatase interaction network by mass spectrometric analysis of protein complexes. Understanding the mechanism of DAPK3 mediated AKT inhibition, may strengthen the therapeutic window for prostate cancer without causing much or any toxicity Citation Format: Trinath P. Das, Arokya MS Papu John, Ram V. Roy, Sandhya R. Rao, Houda Alatassi, Chendil Damodaran, Murali M. Ankhem. Activation of AKT negatively regulates the pro-apoptotic function of death-associated protein kinase 3 (DAPK3) in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1968. doi:10.1158/1538-7445.AM2015-1968
A Contribution to the Cytogenetic Study of Plasmacytoid Dendritic Cell Acute Leukemia.
Authors: Stefanos I. Papadhimitriou, Georgios S. Paterakis, Elpiniki Kritikou-Griva, Athanassios Zomas, Aggeliki Davea, Eleni Goumakou, Anastasia A. Tsakiridou, Ioanna Gligori, Eurydike Michalis, Nikolaos I. Anagnostopoulos, Maria Georgiakaki
Journal: Blood (2004)
603. Feldan Shuttle - Advanced Protein Delivery Technology for Cell Therapy
Authors: Thomas Del'Guidice, Jean-Pascal Lepetit-Stoffaes, Joannie Roberge, Louis-Jean Bordeleau, Mario Harvey, Alain Garnier, David Guay
Journal: Molecular Therapy (2016)

Methods for maximizing the therapeutic value of human cells often involve the transfer of genetic material and use of viruses, both raising important safety and economical concerns. One promising solution to improve cell therapy processes consists on the direct delivery of active proteins into human cells. Regenerative medicine studies established powerful proofs of concept using delivery of transcription factors for cell reprogramming and differentiation; however, the lack of efficiency of current protein delivery methods slowed down the transfer of these methods toward human clinical researches. In the last years, the CRISPR/Cas9 revolution brought forward the possibility of using diverse transfection approaches to deliver Cas9 protein complexed with guide RNA, a method yielding interesting results with cationic lipid agents and electroporation systems. In a human therapy context, lipidic agents are generally not suitable because of their high cellular toxicity. As for electroporation, few systems have been approved for cell therapy; in addition, this process represents a serious concern because of its high cost, inconsistency, associated cell mortality and the fact that some cells are simply refractory to electroporation. In all, these characteristics accentuate the need for a protein delivery process suitable for human cell therapy. In order to efficiently use transcription factors, Cas9 or any other intracellular proteins in cell therapy, Feldan Therapeutics is developing a protein delivery agent, the Feldan Shuttle, explicitly designed for cell therapy. Feldan Shuttle is entirely protein-based, thus allowing cells to naturally degrade it and the delivered protein after their active use. With this novel method, Feldan Therapeutics successfully delivered fluorescent proteins as well as functionally active transcription factors and Cas9/RNA complex with high efficiency and low toxicity into multiple cell lines and human primary cells. With this new technology, Feldan Therapeutics offers an innovative method designed to efficiently and safely deliver native proteins for cell therapy applications.
Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis
Authors: Robert P. Schleimer
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost productivity, and lost time at work and leading to more than a million surgical interventions annually worldwide. The nose, paranasal sinuses, and associated lymphoid tissues play important roles in homeostasis and immunity, and CRS significantly impairs these normal functions. Pathogenic mechanisms of CRS have recently become the focus of intense investigations worldwide, and significant progress has been made. The two main forms of CRS that have been long recognized, with and without nasal polyps, are each now known to be heterogeneous, based on underlying mechanism, geographical location, and race. Loss of the immune barrier, including increased permeability of mucosal epithelium and reduced production of important antimicrobial substances and responses, is a common feature of many forms of CRS. One form of CRS with polyps found worldwide is driven by the cytokines IL-5 and IL-13 coming from Th2 cells, type 2 innate lymphoid cells, and probably mast cells. Type 2 cytokines activate inflammatory cells that are implicated in the pathogenic mechanism, including mast cells, basophils, and eosinophils. New classes of biological drugs that block the production or action of these cytokines are making important inroads toward new treatment paradigms in polypoid CRS.
377. Combined Treatment of Intrapancreatic Autologous Bone Marrow Stem Cells and Hyperbaric Oxygen in Type 2 Diabetes Mellitus Randomized Clinical Trials
Authors: Esteban J. Estrada, Jose L. Decima, Eduardo A. Nicora, Maria J. Esperanza, Gustavo Samaja, Elida B. Romero, Aldo R. Saavedra
Journal: Molecular Therapy (2015)

T2DM is a pandemic disease with a serious health complications, however stem cells therapy appear to be a new therapeutic option. This prospective, open labeled, randomized controlled clinical trial a phase I/II study, comparing the benefit of hyperbaric oxygen therapy and intra-pancreatic stem cell infusion vs. control group with standard medical treatment (insulin + metformin) for type 2 diabetes mellitus. The objective of this study was to determine whether intra-pancreatic infusion of bone marrow derived autologous stem cells in combination with hyperbaric oxygen therapy could improve metabolism in patients with type 2 diabetes mellitus. The primary endpoint was HbA1c reduction. The Patients with T2DM enrolled were 23. They were randomized and assigned, to intervention group 13 patients and 10 to control group. They were followed for 1 year. Metabolic variables included (fasting plasma glucose, C-peptide, HbA1c, and calculation of C peptide/glucose ratio) and clinical variables (BMI, insulin requirement) were measured at baseline and at 180, 270 and 365 days. At baseline there was no significance difference between groups in HbA1C, glucose, c-peptide, c peptide/glucose and insulin, BMI was greater in the intervention group than in the control group (diff=3.93, p=0.006). At 365 days in the intervention group HbA1C changes were significant (diff=-0.76, p=0.05), glucose (diff=-64.1, diff 0.001), c-peptide (diff=1.25, p< 0.001), c peptide/glucose (diff=0.01, p< 0.0001). Changes in A1c compared (both groups) to time 0 were not significant to the control group at any time during follow up, but were significantly decreased in the intervention group at 365 days (diff=-1.08, p<0.001). The conclusion of this study was that combination of autologous stem cell therapy and hyperbaric oxygen treatment could favor tissue remodeling and regeneration- expansion of insulin producing cells in the treated patients vs. patients with standard medical treatment Insulin and metformin in a randomized clinical trial.
Abstract 2001: Identification of lactate dehydrogenase A (LDHA) as a potential therapeutic target for prostate cancer radiotherapy
Authors: Jingli Hao, Peter H. Graham, Lei Chang, Jie Ni, Valerie Wasinger, Julia Beretov, Joseph Bucci, Paul Cozzi, Yong Li
Journal: Cancer Research (2015)

Abstract Introduction: Radiation therapy (RT) is an important treatment option for prostate cancer (CaP) patients at both early and advanced-stage disease. Many CaP patients suffer from relapse and metastasis due to radio-resistance. In this study, we aimed to develop a radio-resistant CaP (CaP-RR) xenograft model, to identify potential protein markers associated with radio-resistance using proteomic approach, and to validate the identified biomarkers in CaP cell lines and animal xenografts. Methods: Subcutaneous (s.c) CaP animal model was established using PC3-RR and PC3-control CaP cells in NODSCID mice. Tumor xenografts were harvested 5 weeks post cell inoculation and the proteins were extracted. Using LC-MS/MS expression protein profiles from the two groups were created. Statistical analysis was performed using one-way ANOVA for all features. Mascot was employed for peptide identification. Differential protein expressions were identified by re-importing the Mascot data to Progenesis software. The protein pathways and the top KEGG terms were searched against KEGG database using ingenuity software. Selected pathway markers or modulators were validated in CaP-RR cell lines and xenograft tumors using western blotting and immunohistochemistry, respectively. Lactate dehydrogenase A (LDHA) was selected for functional studies including radio-sensitivity, apoptosis and autophagy assays. Results: We found for the first time that higher levels of vascularity, proliferation, and proteins from the glycolysis pathway are associated with CaP-RR xenograft tumors and that more than two hundred proteins were differentially expressed between CaP-RR and CaP naïve tumor xenografts. In addition, we demonstrated that the increased expressions of glycolysis markers, including LDHA, were certified in both CaP- CaP-RR cell lines and xenograft tumors. Knock-down or inhibition of LDHA combined with RT increase the radiosensitivity in PC3-RR cells, induce more apoptosis and autophagy compared to each single treatment alone. Conclusions: We have successfully identified protein signatures using a CaP-RR xenograft animal model. The glycolysis pathway protein LDHA is a promising candidate to develop combination therapy to overcome CaP radioresistance. Citation Format: Jingli Hao, Peter H. Graham, Lei Chang, Jie Ni, Valerie Wasinger, Julia Beretov, Joseph Bucci, Paul Cozzi, Yong Li. Identification of lactate dehydrogenase A (LDHA) as a potential therapeutic target for prostate cancer radiotherapy. [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 2001. doi:10.1158/1538-7445.AM2015-2001
Abstract 3768: Identification of new alternative lengthening of telomeres (ALT)-positive cancer cell lines using the C-circle assay
Authors: Andrei G. Malykh, Jonathan R. Doyle, Fang Tian, Joyce HY Lee, Jeremy D. Henson, Roger R. Reddel
Journal: Cancer Research (2015)

Abstract Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism used by approximately 10% of human cancers, including poor prognosis childhood and adult cancers for which development of better treatments is a priority. Currently there are only about ten published ALT+ cancer cell lines available for research, only four of which are available from international repositories. The development of the C-Circle Assay has made it possible to accurately and conveniently test a large number of cell lines for ALT activity. We have tested a panel of 297 cancer cell lines from the American Type Culture Collection (ATCC) with the C-Circle Assay for ALT and identified 34 new ALT+ cell lines. Importantly, we have identified for the first time ALT+ cancer cell lines derived from breast carcinoma, hepatocellular carcinoma, melanoma and leukemia. The overall proportion of ALT+ cancer cell lines was 11.4% (n = 297), which included 19.5% of leukemia (n = 46), 19.0% of melanoma (n = 21), 12.7% of non-small cell lung carcinoma (n = 53) and 3.3% of breast carcinoma (n = 37) cell lines. These results identify additional cancer cell line resources for research into the ALT mechanism, including cell lines from cancer types where ALT has not previously been studied in detail. Citation Format: Andrei G. Malykh, Jonathan R. Doyle, Fang Tian, Joyce HY Lee, Jeremy D. Henson, Roger R. Reddel. Identification of new alternative lengthening of telomeres (ALT)-positive cancer cell lines using the C-circle assay. [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 3768. doi:10.1158/1538-7445.AM2015-3768
Abstract A04: Identification of novel pancreatic cancer-specific biomarkers with organoid models
Authors: Dannielle Engle, Herve Tiriac, Rivera Keith, Michael Ludwig, Chang-il Hwang, Kenneth Yu, Darryl Pappin, David Tuveson
Journal: Cancer Research (2016)

Abstract Pancreatic ductal adenocarcinoma (PDA) is almost uniformly lethal and surgical intervention is the only cure. Unfortunately, the majority of patients are ineligible for resection because of the advanced stage of disease by the time of diagnosis. This is due in part to that lack of diagnostic tools, especially for families with elevated risk. Although considered an intractable and aggressive malignancy, progression from the initiating events to overt cancer requires approximately 12 years, and advancement to metastatic disease takes another 5 – 7 years. This latency indicates that there is a window for early detection and intervention. The PDA biomarker, CA19-9, is measured in the blood to follow tumor burden longitudinally, but is neither sensitive nor specific enough to be used for diagnosis. In particular, the use of CA19-9 in PDA diagnosis is problematic given the elevation of CA19-9 in benign conditions, such as pancreatitis, that have a higher incidence than PDA. To improve the diagnostic performance of CA19-9, we identified tissue- and cancer-specific protein carriers of the CA19-9 carbohydrate modification using murine and human organoid model systems of pancreatic cancer disease progression. To induce CA19-9 expression in murine organoids, two human gylcosyl transferases that were deficient in mice were ectopically expressed. CA19-9 protein carriers specific to malignancy were identified relative to normal, proliferating ductal cells. Some CA19-9 carriers that were shared between normal and malignant pancreatic ductal organoids were also detected in the sera of patients with benign pancreatic disease, highlighting their inability to distinguish malignancy from pancreatitis. Importantly, several of the tumor-specific novel CA19-9 carriers identified in organoids also discriminated between benign and malignant disease in human patient sera, and are nominated for clinical validation. Overall, organoid model systems allow identification of biomarkers that discriminate between normal proliferation and malignant conditions of multiple gastrointestinal tissues, providing a robust platform for biomarker discovery. Citation Format: Dannielle Engle, Herve Tiriac, Rivera Keith, Michael Ludwig, Chang-il Hwang, Kenneth Yu, Darryl Pappin, David Tuveson.{Authors}. Identification of novel pancreatic cancer-specific biomarkers with organoid models. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A04.
Triggering of Toll-Like Receptor-4 In Human Multiple Myeloma Cells Promotes Proliferation and Alters Cell Responses to Immune and Chemotherapy Drug Attack
Authors: Zhen Cai, Hanying Bao, Peilin Lu, Lijuan Wang, Donghua He, Hanyan Li, Yang Yang, Yi Zhao, Li Yang, Yi Li, Michael Wang, Qing Yi
Journal: Blood (2010)
Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial
Authors: Achim Rittmeyer, Fabrice Barlesi, Daniel Waterkamp, Keunchil Park, Fortunato Ciardiello, Joachim von Pawel, Shirish M Gadgeel, Toyoaki Hida, Dariusz M Kowalski, Manuel Cobo Dols, Diego L Cortinovis, Joseph Leach, Jonathan Polikoff, Carlos Barrios, Fairooz Kabbinavar, Osvaldo Arén Frontera, Filippo De Marinis, Hande Turna, Jong-Seok Lee, Marcus Ballinger, Marcin Kowanetz, Pei He, Daniel S Chen, Alan Sandler, David R Gandara
Journal: The Lancet (2016)
First visit is never forgotten
Authors: L. Bonetti, M. Ghilardi, C. Moleri, G. De Agostini, M. Cabiddu, K. Borgonovo, A. Coinu, F. Petrelli, S. Papini, A. Astori, M.E. Cavalleri, A. Aceti, E. Reali, G. Ruggieri, A. Bonardi, L. Facchetti, M. Losi, M.A. Peccati, F. Rossi, L. Ruggeri, S. Barni
Journal: Annals of Oncology (2015)
25-OH-Vitamin-D Deficiency Impairs Rituximab-Mediated Cellular Cytotoxicity and Is Associated With An Inferior Outcome Of Elderly DLBCL Patients Treated With Rituximab
Authors: Joerg Thomas Bittenbring, Bettina Altmann, Frank Neumann, Marina Achenbach, Joerg Reichrath, Marita Ziepert, Juergen Geisel, Evi Regitz, Gerhard Held, Michael Pfreundschuh
Journal: Blood (2013)
Phase II Study of Pomalidomide (Pom) in Genomically Defined High Risk Relapsed and Refractory Multiple Myeloma (RRMM)
Authors: Saad Z Usmani, Emily Hansen, Doug Steward, Sarah Waheed, Susan B. Panozzo, Nathan M Petty, Shebli Atrash, Al-Ola Abdallah, Nisar Ahmad, Antje Hoering, John Crowley, Bart Barlogie
Journal: Blood (2012)
Reduced Intensity Continuous Infusion Busulfan for Allogeneic Hematopoietic Cell Transplant Patients with Hematologic Disorders Who Are Ineligible or Inappropriate for Treatment with a More Intensive Therapeutic Regimen: LCCC 0306
Authors: Reed Friend, James Xenakis, Jonathan S Serody, Terrance Comeau, Don A. Gabriel, Stefanie Sarantopoulos, James Coghill, William A. Wood, Andrew Sharf, Julia S Whitley, Kamakshi Rao, Christine M Walko, Anastasia Ivanova, Thomas C. Shea, Paul M Armistead
Journal: Blood (2015)
Perceptions and practices of dietary cancer prevention: Comparison between physicians and patients.
Authors: V. W. Li, J. Ko, W. W. Li
Journal: Journal of Clinical Oncology (2011)

1536 Background: Patients frequently ask their physicians for dietary recommendations with anti-cancer activity. Population and scientific studies form the basis for such advice, but the actual use of information has not been previously examined. Methods: We conducted a survey of perceptions and practices about anti-cancer dietary recommendations. A questionnaire was delivered via the Internet to 9,654 healthy subjects, cancer patients, oncologists and GPs, with N=285 respondents for analysis. Results: Among healthy individuals, 91% were open to changing dietary habits. Respondents were convinced of the beneficial activity of dietary factors for which data exists (green tea, berries, tomatoes, Omega-3 PUFA, vitamin D) but also for dietary factors for which data does not exist. Respondents were 32% more willing to add than reduce dietary factors. Half (48%) of the cancer patients did not feel their physicians were adequately knowledgeable about diet and cancer. Most (83%) physicians reported that patients ask about dietary approaches to cancer. 66% of physicians acknowledged none or less than one week of formal education on diet and disease prevention. 94% of oncologists believed dietary factors can reduce cancer risk, but only 54% have reviewed the supporting data; 7% did not believe there is a link. A third of oncologists reported they do not make any recommendations to their patients, despite familiarity with data. Physicians reported obstacles to implementing dietary-based cancer prevention: lack of guidelines; lack of data; inadequate education; too much information with insufficient interpretation. Many physicians (34% oncologists, 40% GPs) believed randomized placebo-controlled clinical trials would be necessary to convince them to recommend dietary factors for their patients. Conclusions: In summary, there is strong interest and belief in cancer risk reduction through dietary factors. Patients frequently query their physicians but most do not receive advice, despite the existence of supportive data. This study suggests the need for well-designed clinical studies and improved physician training on the impact of dietary factors on cancer to address patient-centered needs.
Several Immune Cell Subsets Are Associated with Outcome in the Microenvironment of Follicular Lymphoma.
Authors: Björn Engelbrekt Wahlin, Mohit Aggarwal, Santiago Montes-Moreno, Luis Francisco Gonzalez, Giovanna Roncador, Lydia Sanchez-Verde, Birger Christensson, Birgitta Sander, Eva Kimby
Journal: Blood (2009)
High Dose Intravenous Busulfan (BU) and Melphalan (MEL) Followed by Bortezomib (BTZ) as Conditioning with Autologous Peripheral Blood Stem Cell Transplantation (ASCT) for Patients with Multiple Myeloma (MM)
Authors: Tulio E. Rodriguez, Patrick J. Stiff, Scott E. Smith, Jonathan L. Kaufman, Mary Lee, Mala Parthasarathy, Zachary M. Earley, Sagar Lonial, David H. Vesole
Journal: Blood (2010)
T-Cell Receptor Complementarity Determining Region Analysis of Peripheral Blood and Bone Marrow T-Lymphocyte Subsets and Quantitative Evaluation of T-Regulatory Cells in Patients with Chronic Idiopathic Neutropenia
Authors: Michael Spanoudakis, Antonia Antoniou, Maria Velegraki, Katerina Pyrovolaki, Maria Ximeri, George D. Eliopoulos, Kostas Stamatopoulos, Helen A. Papadaki
Journal: Blood (2008)