tbuckley/cabot-search huggingface dataset:
Chimeric protein repair of laminin polymerization ameliorates muscular dystrophy phenotype
Authors: Karen K. McKee, Stephanie C. Crosson, Sarina Meinen, Judith R. Reinhard, Markus A. Rüegg, Peter D. Yurchenco
Journal: Journal of Clinical Investigation (2017)

Mutations in laminin α2-subunit (Lmα2, encoded by LAMA2) are linked to approximately 30% of congenital muscular dystrophy cases. Mice with a homozygous mutation in Lama2 (dy2J mice) express a nonpolymerizing form of laminin-211 (Lm211) and are a model for ambulatory-type Lmα2-deficient muscular dystrophy. Here, we developed transgenic dy2J mice with muscle-specific expression of αLNNd, a laminin/nidogen chimeric protein that provides a missing polymerization domain. Muscle-specific expression of αLNNd in dy2J mice resulted in strong amelioration of the dystrophic phenotype, manifested by the prevention of fibrosis and restoration of forelimb grip strength. αLNNd also restored myofiber shape, size, and numbers to control levels in dy2J mice. Laminin immunostaining and quantitation of tissue extractions revealed increased Lm211 expression in αLNNd-transgenic dy2J mice. In cultured myotubes, we determined that αLNNd expression increased myotube surface accumulation of polymerization-deficient recombinant laminins, with retention of collagen IV, reiterating the basement membrane (BM) changes observed in vivo. Laminin LN domain mutations linked to several of the Lmα2-deficient muscular dystrophies are predicted to compromise polymerization. The data herein support the hypothesis that engineered expression of αLNNd can overcome polymerization deficits to increase laminin, stabilize BM structure, and substantially ameliorate muscular dystrophy.
R702C Mutation of the MYH9 Gene Provokes Impaired Platelet Formation, Renal Focal Segmental Glomerulosclerosis, and Hearing Disability In the Mice Model
Authors: Nobuaki Suzuki, Shinji Kunishima, Makoto Ikejiri, Shoichi Maruyama, Michihiko Sone, Akira Takagi, Kanji Hirashima, Masahito Ikawa, Masaru Okabe, Tetsuhito Kojima, Hidehiko Saito, Tomoki Naoe, Tadashi Matsushita
Journal: Blood (2010)
Erratum: BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells (Cancer Research (November 15, 2004) 64, 1 (8262-8270))
Authors: T. D. Shellenberger, M. Wang, M. Gujrati, A. Jayakumar, R. M. Stricter, M. D. Burdick, C. G. Ioannides, C. L. Efferson, Adel K El-Naggar, D. Roberts, G. L. Clayman, M. J. Frederick
Journal: Cancer Research (2004)
Outcome of primary gastrointestinal compared to nodal diffuse large B cell lymphoma in a series of consecutive patients treated at a single institution
Authors: J. Romejko-Jarosinska, M. Osowiecki, E. Paszkiewicz-Kozik, A. Druzd-Sitek, K. Martyna, M. Szyman´ski, L. Targonski, J. Walewski
Journal: Annals of Oncology (2016)
A dose-escalating phase I study of biweekly docetaxel in older men with hormone refractory prostate cancer (HRPC)
Authors: J. McDevitt, R. Hauser, J. Simon, L. Balducci
Journal: Journal of Clinical Oncology (2009)

e16117 Background: Docetaxel has been shown to be effective and is used in the treatment of HRPC. This phase I study is designed to investigate the maximum tolerated dose, tolerability and activity of docetaxel administered on a biweekly schedule in older patients with HRPC. This study will also explore the feasibility of a self-report geriatric assessment tool in this population. Methods: HRPC patients with progression of metastatic disease during hormonal therapy received docetaxel q 2 wks at dose levels of 40 (level 0), 45 (level 1), 50 (level 2), or 55 mg/m2 (level 3). The trial is a conventional phase I 3+3 dose-escalation design. Treatment was continued until progression, refused further treatment, or unacceptable toxicity. Patients were given the Vulnerable Elders Survey (VES-13) for completion every 4 weeks. Results: 16 patients were enrolled in the study. All are evaluable for toxicity, 10 for response. Pts had a median (range) age 76 (72–87). Median doses administered was 6 (range 3–19). The maximum tolerated dose (MTD) was not reached in the study. No dose limiting side effects were reported for any of the dosing levels in the 8 week assessment period. Five patients had a ≥50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. Of the 10 patients with measureable disease, 2 patients (one at dose level 0 and one at dose level 3) achieved a complete response, 2 patients (one at dose level 1 and one at dose 2) achieved a partial response, and 3 patients had stable disease (one each at dose levels 1, 2, and 3). At the time of entry onto the study, 4 patients required narcotic analgesics for bone pain; after treatment, 1 (25%) discontinued their pain medications. The completion rate of the Vulnerable Elders Survey (VES-13) was 94.6%. Conclusions: Biweekly docetaxel can be safely administered in older metastatic HRPC patients and showed activity. For phase II evaluation, a bi-weekly dose of 55 mg/m2 appears to be suitable. The administration of the VES-13 was feasible in this population. [Table: see text]
SURG-07. ENDONASAL ENDOSCOPIC EXCISION OF ORBITAL LESIONS
Authors: Awadhesh Jaiswal, Amit Kesri, Anant Mehrotra, Kuntal Das, Sushila Jaiswal, Sanjay Behari
Journal: Neuro-Oncology (2016)

Endoscope is now increasingly being used to manage orbital lesions. The aim of the paper is to report our experience of managing 7 cases of different orbital lesions by endonasal pure endoscopic approach. The study was performed by retrospective review of the medical records of the patients of orbital lesions operated in our department. Seven patients (male 5, female 2) presented with unilateral progressive proptosis (n=7), restriction of eye movement and diplopia (n=5), visual deterioration (n=1) and unilateral blindness (n=1). MRI was suggestive of intraconal (n=6) and intraconal and extraconal (n=1) lesions. The lesions were excised by pure endoscopic endonasal endoscopic approach in all the cases. Histology was suggestive of hemangioma (n=3), solitary fibrous tumor (n=1), inflammatory pseudotumor (n=1), orbital lymphoid tumor (n=1), and epidermoid (n=1). The extent of excision was total (n=6) and subtotal (n=1). Post-operatively propotosis resolved and symptoms improved in all the cases. No complication was noted in 6 cases and remaining one had visual deterioration and transient ophthalmoparesis following surgery. Endoscopic approaches to orbital lesions are minimally invasive and bear excellent outcome.
Measuring subjective improvement as well as objective response to estimate the benefit of palliative chemotherapy in women with platinum-resistant or -refractory ovarian cancer: The symptom benefit study (ANZGOG-0701/GCIG/PoCoG).
Authors: M. Friedlander, M. R. Stockler, M. King, A. M. Oza, M. Voysey, J. Martyn, K. Gillies, K. M. Sjoquist, P. Butow
Journal: Journal of Clinical Oncology (2011)

TPS241 Background: The major objective of chemotherapy in patients with platinum resistant/refractory recurrent ovarian cancer (PRR ROC) is palliation. The symptoms in patients with PRR ROC are not well documented and the impact of chemotherapy on symptom benefit unclear. The Symptom Benefit study is a 2 stage study investigating how to best measure the benefit of chemotherapy. The overall aim is to develop a better measure of benefit from palliative chemotherapy that can be used in clinical trials in this patient population. Methods: Prospective observational cohort study in women with PRR ROC about to commence palliative chemotherapy. Stage 2 will assess changes in Quality of Life (QoL) scores from baseline to post treatment assessment using both standard QoL instruments and a new measure of symptoms, the Measure of Ovarian Cancer Symptoms and Treatment Concerns (MOST), developed based on results of stage 1. The individual QoL and MOST scores will be summarized by standard descriptive statistical measures, and improvement will be assessed by calculating absolute changes from baseline for individual symptoms, domain subscales and total scores. Relative changes from baseline will also be examined. The MOST will be internally validated and compared against standard QoL instruments for common domains and symptoms. Eligibility: Stage 2 will enrol women with PRR epithelial ovarian, primary peritoneal or fallopian tube cancer with life expectancy > 3 months, ECOG PS 0-3 and about to start palliative (second- or subsequent line) chemotherapy. Trial status: Currently open in 20 centres in Australia/Canada with 121 patients enrolled in Stage 1 (at Jan 2011). Stage 2 planned to open in Feb 2011 with target recruitment 750 patients in 10 countries. Summary: This is the first study to prospectively evaluate symptom burden, toxicity and outcomes in PRR ROC. Stage 2 will assess symptom benefit from palliative chemotherapy and validate a new tool for measuring symptoms in this population. This is an important and hitherto neglected area.
Acrometastasis of Neuroblastoma to the Great Toe Revealed by MIBG Scan
Authors: Kun Zheng, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2017)

A 3-year-old boy with history of neuroblastoma underwent I-MIBG scan. The whole-body images showed relatively normal tracer distribution except for mild activity in the right foot, which was located in the first metatarsal on SPECT/CT images. The subsequent MRI scan of the right foot showed infiltration of the metatarsal of the right first toe. The findings were consistent with solitary acrometastasis of neuroblastoma to the great toe.
Inhibition of PI3K/Akt and Erk Signaling Pathways by BCR-ABL Tyrosine Kinase Inhibitors up-Regulates the Immunosuppressive Receptor Osteoactivin in Monocyte-Derived Dendritic Cells
Authors: Michael Gutknecht, Simone Joas, Lothar Kanz, Helmut R Salih, Susanne M Rittig, Frank Gruenebach
Journal: Blood (2012)
Circulating MUC1 Levels (CA15.3) in Myeloproliferative Disorders (MPD)
Authors: Aurelia Rughetti, Angelo Fama, Silvia von Mensdorff-Pouilly, Federica Taurino, Hassan Rahimi, Michela Ribersani, F. Natalino, G.M. D’Elia, L. Bizzoni, Roberto Latagliata, Massimo Breccia, Robin Foà, Giuliana Alimena, Gabriella Girelli, Luigi Frati, Marianna Nuti, Agostino Tafuri
Journal: Blood (2008)
Redox Signaling in Adult Stem Cell Biology: A New Target Controlling Pluripotency and Differentiation. What about Iron Chelators?.
Authors: Tiziana Tataranni, Francesca Agriesti, Carmela Mazzoccoli, Vitalba Ruggieri, Fiorella D'Auria, Franca Falzetti, Mauro Di Ianni, Pellegrino Musto, Nazzareno Capitanio, Claudia Piccoli
Journal: Blood (2012)
STIMULI: A randomised open-label phase II trial of consolidation with nivolumab and ipilimumab in limited-stage SCLC after standard of care chemo-radiotherapy conducted by ETOP and IFCT
Authors: D. De Ruysscher, J.-L. Pujol, S. Popat, M. Reck, C. Le Pechoux, A. Liston, D. Speiser, G. Coukos, R. Kammler, O. Dafni, Z. Tsourti, H. Roschitzki, M. Finlayson, A.-C. Piguet, B. Ruepp, R. Maibach, R.A. Stahel, S. Peters
Journal: Annals of Oncology (2016)
Increased choline uptake in androgen receptor (AR) copy number gain castration-resistant prostate cancers (CRPC)
Authors: V. Conteduca, V. Casadio, P. Caroli, E. Scarpi, C. Lolli, C. Menna, E. Bianchi, G. Schepisi, S. Testoni, G. Gurioli, S. Salvi, D. Amadori, G. Paganelli, F. Matteucci, G. Attard, U. De Giorgi
Journal: Annals of Oncology (2016)
GENT-05. DELETION OR AMPLIFICATION OF MUTANT IDH1 IS ASSOCIATED WITH EXTREME DNA HYPOMETHYLATION AND MALIGNANT PROGRESSION
Authors: Tali Mazor, Llewellyn Jalbert, Aleksandr Pankov, Chibo Hong, Josie Hayes, Ivan Smirnov, Roxanne Marshall, Arie Perry, Sarah Nelson, Susan Chang, Andrew Bollen, Annette Molinaro, Henrik Bengtsson, Adam Olshen, Joanna Phillips, Joseph Costello
Journal: Neuro-Oncology (2016)

Mutations in IDH1 are the most common genetic alteration in low-grade gliomas (LGGs) and lead to overproduction of the oncometabolite 2-hydroxyglutarate (2HG) and altered DNA methylation (glioma CpG island methylator phenotype or G-CIMP). While mutant IDH1 likely initiates tumorigenesis, its role in tumor progression is less clear. We and others have previously found that mutations in IDH1 are maintained at recurrence, but several case reports have noted the loss of either the mutant or wild-type allele of IDH1 in vitro and in vivo. We therefore undertook a longitudinal analysis of copy number at the IDH1 locus in a cohort of 50 patients with IDH1-mutant LGG and patient-matched recurrences of all grades. We identified six cases (12%) in which the ratio of the mutant to wild-type allele was altered. Deletion or amplification of the mutant allele both coincided with malignant progression and resulted in decreased 2HG. While G-CIMP was uniformly maintained, there was extreme DNA hypomethylation outside CpG islands. The clonal expansion of tumor cells in the absence of mutant IDH1 and 2HG suggests that initially IDH1-mutant LGG can undergo malignant progression without mutant IDH1. These results have implications for therapeutic inhibition of mutant IDH1, and provide evidence that a driver of gliomagenesis may not be required for malignant progression in vivo.
Significant and Rapid Improvement in Survival After Unrelated Donor (URD) Hematopoietic Cell Transplantation (HCT): Analysis of National Marrow Donor Program (NMDP) Facilitated Transplants From 2000 to 2009
Authors: Navneet S. Majhail, Pintip Chitphakdithai, Ying Shan, Roberta King, Bernadette Anton, Robyn Ashton, Ruth Bakken, Bette Braem, Steven M. Devine, Gregory A. Hale, Robert J Hartzman, Chatchada Karanes, Ginna G Laport, Rebecca Lewis, Eneida R. Nemecek, Susan Rossmann, Nawraz Shawir, Edward L. Snyder, Galen E. Switzer, Willis H. Navarro, John P. Miller, Dennis L Confer, John E. Levine
Journal: Blood (2012)
MNGO-18. MANAGEMENT OF MULTIPLE MENINGIOMAS
Authors: Georgios Tsermoulas, Mazda Turel, Jared Wilcox, David Shultz, Richard Farb, Gelareh Zadeh, Mark Bernstein
Journal: Neuro-Oncology (2016)

Multiple meningiomas are sporadic, radiation-induced or familial and account for 1-10% of meningiomas. Their management is more challenging from single tumors as patients may require multiple treatments. OBJECTIVE: To describe the management of patients with multiple intracranial meningiomas. We reviewed our practice on the management for patients with two or more spatially separated synchronous or metachronous meningiomas. Patients with neurofibromatosis type 2 were excluded. We collected clinical, imaging and treatment data in order to analyze epidemiological aspects of the disease and outcomes of active treatment and surveillance. Over the last 25 years we managed 133 consecutive patients, with total of 395 synchronous and 53 metachronous meningiomas. 106 patients had sporadic disease, 26 radiation-induced and 1 had familial menigniomatosis. In 66 cases the tumors were initially asymptomatic. At presentation, about half of the patients had two tumors, 67% were small (≤2cm) and 11% were large (>4cm). Fifty-four patients had up front treatment and 18 of them underwent treatment of a different meningioma after a mean of 5 years. Thirty-one patients required treatment during surveillance, on average 4 years after diagnosis. Overall, 64% of the patients had treatment for 142 tumors; 67 with surgery and 18 only with radiotherapy. One in four patients had two or more meningiomas treated. The mean follow-up period was 7 years and 13% of the treated patients had salvage therapy. Multiple meningiomas are often asymptomatic, probably because two thirds of them are small tumors. About two thirds of patients with multiple meningiomas require treatment, two thirds up front and one third during surveillance. However, two thirds of meningiomas do not require active treatment. We recommend treatment for the symptomatic tumors, or those that grow at a rate that may cause symptoms during the patient’s expected lifespan.
Impact of Cytogenetics on Outcome of Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation for Adults with AML.
Authors: Martin Tallman, Gordon Dewald, Hillard Lazarus, Sharavi Gandham, Gene Nelson, Brent Logan, Jacob Rowe, Mark Litzow, Armand Keating, Jayesh Mehta, Meir Wetzler, Tanya Warren, Daniel Weisdorf
Journal: Blood (2004)
Sodium taurocholate cotransporting polypeptide is the limiting host factor of hepatitis B virus infection in macaque and pig hepatocytes
Authors: Florian A. Lempp, Ellen Wiedtke, Bingqian Qu, Pierre Roques, Isabelle Chemin, Florian W. R. Vondran, Roger Le Grand, Dirk Grimm, Stephan Urban
Journal: Hepatology (2017)

Infections with the human hepatitis B virus (HBV) and hepatitis D virus (HDV) depend on species‐specific host factors like the receptor human sodium taurocholate cotransporting polypeptide (hNTCP). Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV, indicating the requirement of additional HBV‐specific factors. As an essential premise toward the establishment of an HBV‐susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals. Primary hepatocytes from mice, rats, dogs, pigs, rhesus macaques, and cynomolgus macaques were transduced with adeno‐associated viral vectors encoding hNTCP and subsequently infected with HBV. Cells were analyzed for Myrcludex B binding, taurocholate uptake, HBV covalently closed circular DNA formation, and expression of all HBV markers. Sodium taurocholate cotransporting polypeptide (Ntcp) from the respective species was cloned and analyzed for HBV and HDV receptor activity in a permissive hepatoma cell line. Expression of hNTCP in mouse, rat, and dog hepatocytes permits HDV infection but does not allow establishment of HBV infection. Contrarily, hepatocytes from cynomolgus macaques, rhesus macaques, and pigs became fully susceptible to HBV upon hNTCP expression with efficiencies comparable to human hepatocytes. Analysis of cloned Ntcp from all species revealed a pronounced role of the human homologue to support HBV and HDV infection. Conclusion : Ntcp is the key host factor limiting HBV infection in cynomolgus and rhesus macaques and in pigs. In rodents (mouse, rat) and dogs, transfer of hNTCP supports viral entry but additional host factors are required for the establishment of HBV infection. This finding paves the way for the development of macaques and pigs as immunocompetent animal models to study HBV infection in vivo , immunological responses against the virus and viral pathogenesis. (H epatology 2017;66:703–716).
Lenalidomide Combined with R-CHOP (R2CHOP) Overcomes Negative Prognostic Impact of ABC Molecular Subtype in Newly Diagnosed Diffuse Large B-Cell Lymphoma
Authors: Grzegorz S. Nowakowski, Betsy R. Laplant, Levi Pederson, Matthew J Maurer, William R. Macon, Rebecca L King, James Storhoff, Shannon Dennis, Anita K. Gandhi, Anjan Thakurta, Patrick R. Hagner, Lisa Rimsza, Thomas M. Habermann, James R Cerhan, Thomas E. Witzig
Journal: Blood (2016)
Myeloablative Allogeneic Stem Cell Transplantation for Relapsed Composite Low and Intermediate Grade Lymphoma Is Not Superior to Autologous Stem Cell Transplantation - Reduced Relapse Risk Is Offset by Higher Treatment Related Mortality.
Authors: Khaled M. Ramadan, Joseph M. Connors, Abdulwahab J. Al-Tourah, Randy D. Gascoyne, Kevin Song, Michael J. Barnett, Stephen H. Nantel, Thomas J. Nevill, John D. Shepherd, Heather J. Sutherland, Julye Lavoie, Donna L. Forrest, Donna E. Hogge, Nicholas J. Voss, Clayton A. Smith, Cynthia L. Toze
Journal: Blood (2006)
STMC-30. TRAFFICKING AND EFFECT ON SURVIVAL OF BEVACIZUMAB IN GLIOBLASTOMA
Authors: Gaelle Muller-Greven, Cathleen Carlin, Steven Toms, Manmeet S. Ahluwalia, Markus Bredel, Justin Lathia, Jeremy Rich, Petra Hamerlik, Candece Gladson
Journal: Neuro-Oncology (2016)

Most patients with recurrent glioblastoma (GBM) are treated with bevacizumab, a humanized monoclonal antibody (mAb) that binds VEGF-A and inhibits its binding to VEGFR. Approximately 30% of GBM patients are non-responsive to bevacizumab and the underlying mechanism for the lack of response is unknown. It has been assumed that bevacizumab solely targets circulating VEGF-A. We hypothesized that bevacizumab and human IgGs in general gain access to the perivascular niche that contains cancer stem cells (CSCs) in GBM. We found that bevacizumab gains access to the perivascular tumor area through leaky blood vessels and was internalized by tumor cells in an orthotopic established xenograft mouse model of GBM. In vitro, CSCs (CD133+) from GBM rapidly internalized bevacizumab into membrane protrusions that contained actin and internalization was significantly inhibited by a macropinocytosis inhibitor (EIPA), suggesting CSCs internalize bevacizumab via macropinocytosis. Furthermore, bevacizumab or human IgG were largely detected in the Rab4+ “fast” recycling compartment at 5 min, and in the LAMP1+ compartment (late endosome/lysosome) at 3 hr in the CSCs. We observed similar trafficking patterns for bevacizumab in our in vivo model. CSCs from GBM do not express the neonatal Fc receptor, the canonical pathway for recycling of IgG. Bevacizumab induces autophagy in CSCs due to VEGF deprivation and this mechanism is blocked with the addition of growth factors. Taken together, our data show that in GBM, bevacizumab gains access to the perivascular tumor space, is macropinocytosed by CSCs where it is trafficked to a recycling compartment or to the late endosome/lysosome, and that it induces autophagy promoting survival of these tumor cells. These data suggest that alterations in endocytosis or recycling in the CSCs could impact the fate of therapeutic IgGs like bevacizumab and ultimately influence a patients’ response to GBM therapy.
Adhesion G Protein–Coupled Receptors as Drug Targets
Authors: Ryan H. Purcell, Randy A. Hall
Journal: The Annual Review of Pharmacology and Toxicology (2017)

The adhesion G protein–coupled receptors (aGPCRs) are an evolutionarily ancient family of receptors that play key roles in many different physiological processes. These receptors are notable for their exceptionally long ectodomains, which span several hundred to several thousand amino acids and contain various adhesion-related domains, as well as a GPCR autoproteolysis–inducing (GAIN) domain. The GAIN domain is conserved throughout almost the entire family and undergoes autoproteolysis to cleave the receptors into two noncovalently-associated protomers. Recent studies have revealed that the signaling activity of aGPCRs is largely determined by changes in the interactions among these protomers. We review recent advances in understanding aGPCR activation mechanisms and discuss the physiological roles and pharmacological properties of aGPCRs, with an eye toward the potential utility of these receptors as drug targets.
Dasatinib Promotes Osteoprogenitor Differentiation and Inhibition of Osteoclastogenesis: Rationale for Treatment of Myeloma Bone Disease.
Authors: Antonio Garcia-Gomez, Mercedes Garayoa, Enrique M. Ocio, Edvan Crusoe, Diego Fernández, Teresa Paíno, Laura San Segundo, Juan C. Montero, Stela Álvarez-Fernández, Juan F. Blanco, Fermin M. Sanchez-Guijo, Felix T. Garzon, Atanasio Pandiella, Jesús F. San-Miguel
Journal: Blood (2009)
Follow-up of chemotherapy induced changes in anti-Mullerian hormone, antral follicle number and ovary volume in premenopausal breast cancer patients
Authors: F. Elbuken, C. Ordu, D. Sarsenov, S. Ilgun, K. Pilanci, Z. Erdogan, F. Agacayak, G. Alco, A. Ozturk, Y. Eralp, B. Baysal, V. Ozmen
Journal: Annals of Oncology (2016)