tbuckley/cabot-search huggingface dataset:
187. AAV Delivery of Tafazzin for the Correction of Mitochondrial Dysfunction in Barth Syndrome Using IPS Differentiated Cardiomyocytes
Authors: Amy L. Donate, Meghan Soustek, Skylar A. Rizzo, Katherine Santostefano, Bennett J. Gosiker, Alfred S. Lewin, Naohiro Terada, Todd Cade, Barry J. Byrne, Christina A. Pacak
Journal: Molecular Therapy (2015)

Barth Syndrome (BTHS) is caused by a single gene mutation affecting mitochondria and resulting in dilated cardiomyopathy, growth delay, neutropenia and severe exercise intolerance. This gene, Tafazzin (TAZ) located at Xq28, is responsible for cardiolipin (CL) remodeling in the inner mitochondrial membrane. Mutation/s in TAZ result in altered remodeling of CL and increasing Monolysocardiolpin (MLCL): CL ratios. This imbalance leads to abnormal mitochondrial cristae formation and decreased oxidative phosphorylation resulting in decreased ATP production and energy metabolism. Since BTHS is the result of a single gene defect, it is an ideal candidate for treatment by gene therapy. Therefore, we hypothesized that delivery of TAZ by adeno-associated virus (AAV) should increase TAZ gene expression and function, correcting the CL remodeling. Preliminary data, using fibroblasts directly differentiated to muscle resulted in increased gene expression of TAZ and a return to normal levels of CL. To further evaluate this gene therapy for effectiveness in the heart, we utilized patient derived induced pluripotent stem cells (IPSC) which were differentiated to cardiomyocytes. Upon confirmation of differentiation, control and diseased cells were treated with either AAV-TAZ or sham. TAZ gene and protein expression were measured as well as TAZ function through CL analysis. Muscle weakness and exercise intolerance have been described by patients, therefore to further stress the cardiomyocytes, cells were placed in hypoxia under nutrient limiting conditions and ATP production measured after 24 hours. Additional studies are being performed to evaluate mitochondrial activity as well as preclinical in vivo analysis.
NF1 Alterations Are Common In AML with Complex Karyotype and Correlate with Specific Genomic Imbalances
Authors: Frank G. Rücker, Lars Bullinger, Frank Stegelmann, Carmen Blersch, Peter Lichter, Jürgen Krauter, Brigitte Schlegelberger, Arnold Ganser, Richard F. Schlenk, Hartmut Döhner, Konstanze Döhner
Journal: Blood (2010)
Abstract 1579: Circulating cell-free DNA as a diagnostic marker for epithelial ovarian cancer and an association with epithelial-mesenchymal transition
Authors: Yu-Jin Koo, Kyung-Jin Min, Jin-Hwa Hong, Jae-Kwan Lee
Journal: Cancer Research (2015)

Abstract Objectives: Although technologies continue to develop, there are still many limitations on detecting circulating tumor cells in blood. In addition, the great genetic heterogeneity in ovarian cancer is one of the major concerns. Therefore, we aimed to investigate the cell-free DNA (cfDNA) as a diagnostic marker for epithelial ovarian cancer (EOC) and evaluate the cfDNA level of epithelial-mesenchymal transition markers. Methods: Blood was preoperatively collected from women who were assigned to surgery for pelvic mass. DNA was extracted using Qiagen DNA Mini kit and quantification of total cfDNA was performed using real-time PCR with TaqMan Assay with primers directed to the following genes: GAPDH, β-globin, β-actin, E-cadherin, and fibronectin. Results: A total of 32 patients with EOC and 17 patients of benign ovarian disease (controls) were included. The median cfDNA level of β-globin was 0 (range, 0-0.35)GE/ml in EOC and 0.41 (range, 0-33.5)GE/ml in control (p = 0.04). The sensitivity of β-globin cfDNA (&amp;gt;0.4 GE/ml) was 51.9%, which was lower than that of CA-125 (96.3%, if CA-125 &amp;gt;35IU/ml). cfDNA was significantly higher in advanced stage of EOC than early stage EOC (p = 0.02). Plasma E-cadherin level was significantly related with β-globin cfDNA (coefficient 0.886, p&amp;lt;0.001). However, there was no significant association with cfDNA amount and survival outcomes. Conclusions: Circulating cfDNA can be a promising target for early detection of EOC. The levels of epithelial-mesenchymal transition markers showed a different pattern in plasma and were associated with other cfDNA amounts. Citation Format: Yu-Jin Koo, Kyung-Jin Min, Jin-Hwa Hong, Jae-Kwan Lee. Circulating cell-free DNA as a diagnostic marker for epithelial ovarian cancer and an association with epithelial-mesenchymal transition. [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 1579. doi:10.1158/1538-7445.AM2015-1579
Secondary Myelodysplasia-Associated Metaphase Cytogenetic Abnormalities in Newly Diagnosed Multiple Myeloma Treated On Total Therapies 2 &amp; 3– Influence of Cumulative Dosing of Maintenance Drugs
Authors: Saad Z Usmani, Adam Rosenthal, Rachael Sexton, Antje Hoering, Zeba N Singh, Sarah Waheed, Al-Ola Abdallah, Jameel Muzaffar, Nathan M Petty, John Crowley, Jeffrey Sawyer, Joshua Epstein, Frits van Rhee, Bart Barlogie
Journal: Blood (2012)
Abstract 409: Docetaxel induced-JNK2/PHD1 signaling pathway increases cell death in cancer cells under hypoxia through the degradation of HIF-1α
Authors: Eun-Taex Oh, Min-Jeong Song, Hyemi Lee, Yun-Jeong Choi, Heon Joo Park
Journal: Cancer Research (2015)

Abstract HIF-1α has been shown to regulate the expression of more than 70 genes involved in angiogenesis, tumor growth, metastasis, chemoresistance and radioresistance. There has been a growing interest in using HIF-1α inhibitors as anticancer drugs. Recently, docetaxel, which has been approved by the FDA for treatment of various cancers, has been reported to enhance the degradation of HIF-1α, but its molecular mechanism is unclear. In this study, we investigated the molecular mechanism underlying the docetaxel-induced degradation of HIF-1α and cell death in cancer cell under hypoxia. Pretreatment of docetaxel increased the polyubiquitination and proteasome mediated-degradation of HIF-1α and cell death in cancer cells under hypoxia. Under hypoxia, pharmacological inhibitors or siRNAs for PHD1 (prolyl hydroxylase 1) effectively prevented HIF-1α degradation and cancer cell death through inhibiting docetaxel-mediated activation of PHD1. In addition, siRNA-mediated knockdown of JNK2 blocked docetaxel-induced degradation of HIF-1α and cancer cell death through inhibiting the activation of PHD1. Through a luciferase reporter assay, we observed that the inhibition of the JNK2/PHD1 signaling pathway significantly suppressed the transcriptional activity of HIF-1α. Our results collectively show that, under hypoxia, docetaxel contributes to cause apoptotic cell death under hypoxia by triggering the JNK2/PHD1 signaling pathway, thereby increasing the degradation of HIF-1α. Citation Format: Eun-Taex Oh, Min-Jeong Song, Hyemi Lee, Yun-Jeong Choi, Heon Joo Park. Docetaxel induced-JNK2/PHD1 signaling pathway increases cell death in cancer cells under hypoxia through the degradation of HIF-1α. [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 409. doi:10.1158/1538-7445.AM2015-409
Oncological outcomes of cryoablation for renal tumors: The Johns Hopkins experience.
Authors: J. Goyal, P. Verma, A. Sidana, C. Georgiades, R. Rodriguez
Journal: Journal of Clinical Oncology (2011)

e15085 Background: We sought to compare intermediate-term oncological outcomes of patients undergoing percutaneous with those undergoing open or laparoscopic cryoablation for renal tumors. Methods: After Institutional Review Board approval, we retrospectively evaluated the medical records of 182 patients treated with cryoablation for 196 renal tumors at Johns Hopkins Hospital between 1997 and 2008. Patient demographics, tumor characteristics, peri-operative data and the course of disease were studied. Uni- and multivariate Cox proportional hazard analysis was done to identify predictors for all cause mortality (ACM), cancer specific mortality (CSM) and recurrence. Results: Cryoablation was done percutaneously in 130 patients (Group 1), and using a laparoscopic or open approach in 52 patients (Group 2). The mean follow up was 23.2 (±17.1) months in Group 1 and 30.3 (±28.6) months in Group 2. Group 1 was significantly associated with posterior tumors (p<0.0001) and with a higher mean number of intra-operative cryoprobes (p<0.0001). Group 2 was associated with a higher post-operative glomerular filtration rate (GFR) (p=0.03). Group 1 had a significantly shorter duration of hospital stay (p<0.0001) as well as a lower estimated blood loss (EBL) (p=0.04). 5-year overall survival (OS) was 75.6% and 70% in Group 1 and Group 2 respectively. 5-year cancer specific survival (CSS) in the two groups was 93.1% and 100% respectively. Recurrence free survival (RFS) at 5 years was 82.7% and 92.4% respectively. Metastases free survival (MFS) at 5 years in the two groups was 97.2% and 100% respectively. On log-rank test, no statistical differences were observed in OS (p=0.23), CSS (0.29), MFS (0.29) and RFS (p=0.3) between the two groups. Treatment approach was not found to be a predictor of recurrence, ACM or CSM. On multivariate analysis, EBL was found to be an independent predictor of ACM (p=0.04). Also, EBL and metastases on follow-up were found to be independent predictors of CSM (p=0.001). Conclusions: Both groups provide safe and effective oncological control for a renal mass with similar OS, CSS, RFS and MFS. The only independent factor predicting all cause mortality was EBL during surgery.
PAPILLOPHAR: Impact of the human papillomavirus (HPV) status in the prognosis of oropharynx squamous cell carcinoma (OSCC).
Authors: J. Lacau Saint Guily, J. Pretet, G. Agius, A. Rousseau, B. Barry, X. Dufour, S. Perie, M. Lefevre, P. Birembaut, C. Mougin, T. Simon, C. Clavel
Journal: Journal of Clinical Oncology (2011)

TPS198 Background: According to retrospective series, HPV-positive OSCC would have a better overall and specific prognosis. Nevertheless, there is currently no evidence-based indication to modify treatment according to the HPV status. Methods: Papillophar is a multicentric (15 clinical, 5 biological centers) prospective study. The aim is to study the role of HPV characteristics in OSCC prognosis. With a clinical database (including follow-up), tumor and serum collections are constituted to analyse virological parameters of HPV positive tumors (HPV genotype, variants, load, DNA integration, E6-E7 transcript expression, L1 gene methylation, HPV serology), molecular tumor markers (EGFR, Kras, PTEN, PI3KCA, c-MET mutations), immunohistochemistry analysis (p16, p53, pRb, markers of EMT (vimentin, E-cadherine, beta-catenin) expression). Primary endpoint is Disease Free Survival (DFS) at 2 years according to HPV status. Secondary endpoints are: Overall Survival at 2 years; virological characteristics in HPV-positive tumors; molecular tumor characteristics in HPV positive vs negative tumors. We hypothesized that DFS in HPV-negative cancer is similar to DFS in OSCC (about 40%). To detect at least a 20% difference in DFS at 2 years, 324 patients are needed (25% HPV positive patients, 80% power, alpha equals 5%, two-sided). No interim analysis is planed. Prognosis value of HPV status on endpoints will be assessed using Cox regression hazard model independently from baseline characteristics. Patients are treated according to the usual multidisciplinary approach in each center and followed according to the recommendations of the French Otolaryngology head neck surgery Society. At least 2 years of follow-up after the completion of the treatment will be required. Major eligibility criteria are: invasive OSCC confirmed histologically in adult patients, all TNM stages and first head and neck cancer. SCC of other localization, non-invasive neoplasia and synchronous head and neck carcinomas are excluded. Enrollment has begun in May 2009. At this time (January 2011), 198 OSCC patients have been included and 34 % have reached 12 months of follow-up. Clinical trial registry number: NCT00918710.
Treatment Effect of Rituximab Plus Chemotherapy Is Obtained by Improving Survival from Non-Germinal Center-Type Untreated Diffuse Large B-Cell Lymphoma.
Authors: Bungo Saito, Eisuke Shiozawa, Takako Usui, Hidetoshi Nakashima, Takashi Maeda, Norimichi Hattori, Daisuke Adachi, Toshiko Yamochi-Onizuka, Masafumi Takimoto, Tsuyoshi Nakamaki, Hidekazu Ota, Shigeru Tomoyasu
Journal: Blood (2006)
68. Development of Thioaptamers and X-aptamers Targeting Human Ovarian Cancer Cells
Authors: Hongyu Wang, Weiguo He, Miguel A. Elizondo-Riojas, Xin Li, Lokesh G. Rao
Journal: Molecular Therapy (2015)

Aptamers are oligonucleotide or peptide molecules that bind to a specific target with high affinity and specificity. A diverse range of modifications have been reported for either enhancing aptamers' nuclease resistance or expanding their chemical functionalities. We created a combinatorial DNA aptamer library that had been modified with thio substitution of the phosphate backbone (thioaptamer, TA) at selected 5'dA positions for cell and tissue based selections. Based on morphological assessment of the tissue, we used an image-directed laser microdissection (LMD) technique to dissect Regions of Interest (ROIs) bound with thioaptamers, and further identified the targeted proteins. Using a Next Generation Sequencing (NGS) approach and alignments by our recently developed Aptaligner program, we are able to select tissue specific TAs in a more representative way from the TA libraries. We have successfully identified TAs that bind specifically to tumor endothelial cells and characterized the lead candidate TA, Endo28, as an Annexin A2-specific TA that allows for selective delivery to the tumor vasculature. Based on the primary sequences of several of the previously selected TAs and observed variations, we developed an X-aptamer (XA) library by conjugating drug-like ligands (X) to the DNA bases in a random fashion. We were able to select an XA with high affinity to CD44 hyaluronic acid binding domain (HABD) from a large combinatorial TA library modified with a drug (N-acetyl-2,3-dehydro-2- deoxyneuraminic acid, ADDA). The selected CD44 X-aptamers (amine form and ADDA form) show enhanced binding affinities with ADDA to CD44 over-expressed on human ovarian cancer IGROV cells. Using a systems biology approach that combines the use of 15 mm bead-based XA libraries with flow cytometry sorting and mass spectrometry, we collected beads binding to proteins labeled with different fluorescence dyes and identified their associated XA sequences by PCR and NGS. The differentially expressed proteins can be identified by an XA beads pulldown experiment to discover the potential biomarkers for ultimately TA or XA targeted nanoparticle delivery of drugs to tumors.
Computed Tomography (CT) Predicts Response Duration in Patients with Chronic Lymphocytic Leukemia (CLL) in Complete Response (CR) by Conventional, NCI-Working Group, Criteria.
Authors: Francesc Bosch, Ana Muntañola, Ana Ferrer, Marcos González, Eva Gine, Eugenia Abella, Santi Gardella, Javier Briones, Eva González-Barca, Lourdes Escoda, Elena Pérez-Ceballos, Antoni Asensi, Maria José Sayas, Joan Besalduch, Emili Montserrat
Journal: Blood (2006)
Rituximab-CHOP Versus CHOP with or without Maintenance Rituximab in Patients 60 Years of Age or Older with Diffuse Large B-Cell Lymphoma (DLBCL): An Update.
Authors: Thomas M. Habermann, E. Weller, V. A. Morrison, P. A. Cassileth, J. Cohn, S. Dakhil, R. D. Gascoyne, B. Woda, R. Fisher, B. A. Peterson, S. J. Horning
Journal: Blood (2004)
Exon-12 Nucleophosmin (NPM) Mutation and Aberrant Cytoplasmic Expression of NPM Protein in Leukemia Cell Line OCI-AML3.
Authors: Hilmar Quentmeier, Maria P. Martelli, Wilhelm G. Dirks, Niccolo Bolli, Arcangelo Liso, Roderick A.F. MacLeod, Ildo Nicoletti, Roberta Mannucci, Alessandra Pucciarini, Barbara Bigerna, Massimo F. Martelli, Cristina Mecucci, Hans G. Drexler, Brunangelo Falini
Journal: Blood (2005)
High Intra-Individual Variability In Systemic Exposure To 6 Mercaptopurine (6MP) In Children With Acute Lymphoblastic Leukemia (ALL) Contributes To ALL Relapse: Results From a Children’s Oncology Group (COG) Study (AALL03N1)
Authors: Smita Bhatia, Wendy Landier, Lindsey Hageman, Can-Lan Sun, Heeyoung Kim, Nancy Kornegay, William E. Evans, Bruce C. Bostrom, Jacqueline Casillas, Anne Angiolillo, Glen Lew, Kelly Maloney, Leo Mascarenhas, Jane Meza, A. Kim Ritchey, Amanda Termuhlen, William L. Carroll, F. Lennie Wong, Mary V. Relling
Journal: Blood (2013)
BiRD (Biaxin®/Revlimid®/Dexamethasone) Combination Therapy (Rx) Results in High Complete Remissions (CR) and Overall Responses in Myeloma (MM) with Poor Prognostic Features.
Authors: Ruben Niesvizky, K. Pekle, U. Gelbshtein, F. Zafar, S. Ostrow, R. Pearse, H. Cho, J. Tepler, S. Ely, R. Lent, D. Jayabalan, T. Shore, J. Harpel, M. Schuster, L. Lyons, R. Furman, J. Leonard, S. Chen-Kiang, M. Coleman
Journal: Blood (2005)
Predicting the future from the past
Authors: Alvar Agustí
Journal: European Respiratory Journal (2017)

Like everyone else I am getting older, and I am being asked to talk more and more about the future (a coincidence?). By definition, these talks are speculative (there is no evidence for the future) and they reflect, almost exclusively, a personal view, which in turn arises from my own by definition restricted vital experiences. While preparing one of these talks, I thought that nobody would have been able to predict what was about to happen (the future) in the nearly 40 years that followed my graduation from medical school in 1979. Below I list a number of things that have occurred from then until now. To some extent, this is a sort of experiment where, knowing de facto what has occurred, we ask ourselves if we would ever have been able to predict these events ( i.e. can we predict the future from the past?). I believe that this exercise illustrates well the difficulties in predicting the future, since the answer to this question is almost certainly no. The list, not meant to be exclusive or prioritised, includes several very significant advances. Is it possible to leverage medical advances from the last 40 years to predict future changes? <http://ow.ly/A1zw305H5a5> I thank Rosa Faner, Guillaume Noell and Paco Pozo for critical reading and helpful suggestions and the high-speed train from Madrid to Barcelona that gave me enough time and a quiet atmosphere to think about the content of this paper.
Abstract 1233: Impairment of TFF3 induces cellular apoptosis in prostate cancer cell lines and overexpression of TFF3 may be a prognostic biomarker in human prostate cancers
Authors: So-Youn Kim, Ji-Ying Liu, Yeun-Jun Chung
Journal: Cancer Research (2015)

Abstract Background: Human trefoil factor 3(TFF3)/ Intestinal trefoil factor(ITF) is originally known well as an essential regulator for epithelial restitution in gastrointestinal tract and also suggested as a potential cancer marker in serum. Furthermore, the aberrant overexpression of TFF3 has been reported in various human cancers, majorly colorectal cancers, suggesting that TFF3 may play a critical role in tumor growth. However, its molecular signaling pathway remains unclear. Objective: To clarify whether TFF3 is related to survival/anti-apoptotic cell signaling pathways, and to determine that tff3 could be a molecular marker in prostate cancers. Design, Setting, and Participants: TFF3 gene was silenced by using siRNA in prostate cancer two kinds of cell lines, LNCap and PC3, following investigation of genes related to apoptosis and cell migration. The expression of TFF3 was analyzed by immunohistochemistry in 109 prostate cancer and 106 normal prostate tissues. Results and Limitations: TFF3 silenced prostate cancer cell lines exhibited increased annexin V binding and the activation of caspase-9 and caspase-3 which are crucial for programmed cell death, consistent with an increased rate of apoptosis, reduced rate of proliferation and migration. In human prostate cancer tissue microarray, TFF3 was positive in 54.7% (49.1%, 2+; 5.6%, 1+) of cancer cases (59/108) and 2.8% (1.9%, 2+; 0.9%, 1+) of morphologically normal tissue cases (3/106), P&amp;lt;0.0001. Conclusions: The results suggest that TFF3 expression seems play a role in promoting cell survival and be a potential useful marker in prostate cancers. In these contexts, TFF3 in human prostate cancers deserves further investigation to exploit as a cancer marker and anticancer drug. Citation Format: So-Youn Kim, Ji-Ying Liu, Yeun-Jun Chung. Impairment of TFF3 induces cellular apoptosis in prostate cancer cell lines and overexpression of TFF3 may be a prognostic biomarker in human prostate cancers. [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 1233. doi:10.1158/1538-7445.AM2015-1233
Surface Topography and Mechanical Strain Promote Keratocyte Phenotype and Extracellular Matrix Formation in a Biomimetic 3D Corneal Model
Authors: Wei Zhang, Jialin Chen, Ludvig J. Backman, Adam D. Malm, Patrik Danielson
Journal: Advanced Healthcare Materials (2016)

The optimal functionality of the native corneal stroma is mainly dependent on the well-ordered arrangement of extracellular matrix (ECM) and the pressurized structure. In order to develop an in vitro corneal model, it is crucial to mimic the in vivo microenvironment of the cornea. In this study, the influence of surface topography and mechanical strain on keratocyte phenotype and ECM formation within a biomimetic 3D corneal model is studied. By modifying the surface topography of materials, it is found that patterned silk fibroin film with 600 grooves mm-1 optimally supports cell alignment and ECM arrangement. Furthermore, treatment with 3% dome-shaped mechanical strain, which resembles the shape and mechanics of native cornea, significantly enhances the expression of keratocyte markers as compared to flat-shaped strain. Accordingly, a biomimetic 3D corneal model, in the form of a collagen-modified, silk fibroin-patterned construct subjected to 3% dome-shaped strain, is created. Compared to traditional 2D cultures, it supports a significantly higher expression of keratocyte and ECM markers, and in conclusion better maintains keratocyte phenotype, alignment, and fusiform cell shape. Therefore, the novel biomimetic 3D corneal model developed in this study serves as a useful in vitro 3D culture model to improve current 2D cultures for corneal studies.
Slamf-1/CD150 Is a Signaling Receptor Expressed by a Subset of Chronic Lymphocytic Leukemia Patients Characterized by a Favorable Prognosis
Authors: Cinzia Bologna, Roberta Buonincontri, Sara Serra, Tiziana Vaisitti, Valentina Audrito, Davide Brusa, Davide Rossi, Marta Coscia, Gianluca Gaidano, Cox Terhorst, Silvia Deaglio
Journal: Blood (2012)
A phase I trial of paclitaxel, cisplatin, and veliparib in the treatment of persistent or recurrent carcinoma of the cervix: an NRG Oncology Study (NCT#01281852)
Authors: P.H. Thaker, R. Salani, W.E. Brady, H.A. Lankes, D.E. Cohn, D.G. Mutch, R.S. Mannel, K.M. Bell-McGuinn, P.A. Di Silvestro, D. Jelovac, J.S. Carter, W. Duan, K.E. Resnick, D.S. Dizon, C. Aghajanian, P.M. Fracasso
Journal: Annals of Oncology (2016)
Phase I/II Study of Myeloablative Anti-CD20+ Radioimmunotherapy with I-131-Rituximab in High-Risk CD20-Positive Non Hodgkin Lymphoma
Authors: Kathleen Schwarz, Wagner Julia, Susanne Schreiber, Burkhard Schmidt, Alexander Hoellein, Mareike Verbeek, Markus Schwaiger, Christian Peschel, Klemens Scheidhauer, Christoph von Schilling, Ulrich Keller
Journal: Blood (2012)