tbuckley/cabot-search huggingface dataset:
17. Human Adenovirus D17 Has Tropism for Endothelium Cells and Can Use Both hCAR and CD46 as Receptors
Authors: Jing Liu, Philip Boehme, Jun Fu, Wenli Zhang, Manish Solanki, Roma Yumul, Achim Schmidtko, Francis Stewart, Andre Lieber, Anja Ehrhardt
Journal: Molecular Therapy (2016)

Human adenovirus type 5-derived vectors (HAdV5) from species C were broadly explored for gene therapeutic approaches and vaccination. However, disadvantages associated with this vector type are the strong liver tropism in vivo in mice, preexisting immunity and induction of robust immune responses. There is growing interest in exploring other adenovirus types of which >69 were identified. Here we constructed a new first generation adenovirus labelled with green fluorescent protein marker based on human adenovirus D17 which was first isolated from conjunctival scrapings in 1955 and aimed at characterizing the vector in vitro and in vivo. We applied a new homologous recombineering technology to construct GFP labelled early E1 gene deleted HAdV17 and HAdV5, rescued viruses in complementary stable cell lines, and then screened a panel of different cell lines by FACS analyses and quantitative PCR. Competition assays based on soluble recombinant fiber knob blocking reagents (5knob, 17knob, JO4, Augmab) were used to characterize the receptor interaction in vitro. In vivo biodistribution analyses were performed after intravenous injection of recombinant viruses into normal and CD46 transgenic mice. We observed that HAdV17 has tropism for endothelium cells which are normally refractory to HAdV5 infection. This finding was further verified using primary human umbilical vein endothelial cells (HUVEC). Moreover, after performing competition assays we found that HAdV17 can utilize both CD46 (a membrane cofactor protein which is expressed on all nucleated cells) and CAR (coxsackievirus and adenovirus receptor) as cell attachment receptors. The endothelium tropism was CD46-dependent and could be blocked by the CD46 blocking reagent Ad35K++/Augmab. In vivo biodistribution studies showed significantly increased vector genome copies (VCN) in various organs of human CD46 transgenic mice compared to normal mice indicating involvement of CD46 as a receptor. Immunohistological analyses using cell-specific marker are ongoing. Neutralizing antibody assays revealed that there was less seroprevalence with HAdV17 compared to HAdV5. In total, we believe that HAdV17-based vectors, which can use both hCAR and CD46 as receptors, hold great promise for gene therapy in endothelial disease. The understanding of the molecular interaction between virus and host will be beneficial for vaccination and drug development.
Evaluation of molecular typing of foodborne pathogens in European reference laboratories from 2012 to 2013
Authors: Susanne Schjørring, Taina Niskanen, Mia Torpdahl, Jonas T Björkman, Eva Møller Nielsen
Journal: Eurosurveillance (2016)

In 2012, the European Centre for Disease Prevention and Control (ECDC) initiated external quality assessment (EQA) schemes for molecular typing including the National Public Health Reference Laboratories in Europe. The overall aim for these EQA schemes was to enhance the European surveillance of food-borne pathogens by evaluating and improving the quality and comparability of molecular typing. The EQAs were organised by Statens Serum Institut (SSI) and included Salmonella enterica subsp. enterica, verocytotoxin-producing Escherichia coli (VTEC) and Listeria monocytogenes . Inter-laboratory comparable pulsed-field gel electrophoresis (PFGE) images were obtained from 10 of 17 of the participating laboratories for Listeria , 15 of 25 for Salmonella , but only nine of 20 for VTEC. Most problems were related to PFGE running conditions and/or incorrect use of image acquisition. Analysis of the gels was done in good accordance with the provided guidelines. Furthermore, we assessed the multilocus variable-number tandem repeat analysis (MLVA) scheme for S. Typhimurium. Of 15 laboratories, nine submitted correct results for all analysed strains, and four had difficulties with one strain only. In conclusion, both PFGE and MLVA are prone to variation in quality, and there is therefore a continuous need for standardisation and validation of laboratory performance for molecular typing methods of food-borne pathogens in the human public health sector.
PTH-059 The nutrition team experience in a district general hospital: a 7-year review of the impact on parenteral nutrition
Authors: R McCorry, P D Mooney, P Coulthurst, T Earley, T Shaw, Y Clarkson, R Allcock, R Fleet, C Longden, A Barnes, P L Shields
Journal: Gut (2010)

<h3>Introduction</h3> A multidisciplinary nutrition team was introduced in 2002 after an initial retrospective audit demonstrated a high rate of inappropriate parenteral nutrition (PN) use and associated complications with unregulated use. The team comprises a gastroenterologist, nutrition nurse, dietician, microbiologist, pharmacist and a biochemist. This audit was carried out to assess the role of the nutrition team since its introduction. <h3>Methods</h3> All patients accepted for PN between 2002 and 2009 were included in this prospective audit. Patient demographics, indications, duration, complications and outcomes were recorded. <h3>Results</h3> 202 patients (107 male, 95 female, mean age 62, range 16–85) received PN, for a total of 4668 PN days. Median duration of PN administration was 9 days (range 1–365). Over the study period the service has expanded, with the number of patients receiving PN increasing from 19 patients in 2002 to 56 patients in 2009. There has been a wide range of indications for PN including high output stomas, fistulae and other complex abdominal conditions. The predominant indication for PN was paralytic ileus (36%). 39 catheter related infections developed in 35 (17%) patients, giving a rate of 0.83 catheter related infection per 100 PN days. This improved from 1.82 in 2002 to 0.69 in 2009 as a result of line management training provided by nutrition nurses. Coagulase negative Staphylococcus was the most frequently cultured organism (35%). Over the same period there were 4 catheter related infections in 19 home PN (HPN) patients managed by the nutrition team. The 4 infections were observed in two patients who were both self administering PN. The rate of infection in the HPN patients was 0.06 per 100 PN days. 70 (35%) patients died while on PN, however no deaths were attributable to PN. A total of 100 (50%) patients returned to enteral feeding. <h3>Conclusion</h3> There has been a steady rise in referrals to the nutrition team. There has been more judicious PN use and those with a functioning gastro-intestinal tract are directed towards enteral feeding with bridled naso-gastric or naso-jejunal tubes, also supervised by the nutrition team. The introduction of specialist nutrition nurses has seen an improvement in the rate of catheter related infection. The significantly lower rate of catheter related infection in HPN patients suggests that line management can be improved. Further improvement may be possible with the introduction of a dedicated line management team and ring fenced nutrition beds within the surgical unit.
Evaluation of age-dependent treatment strategies for children and young adults with pineoblastoma: analysis of pooled European Society for Paediatric Oncology (SIOP-E) and US Head Start data
Authors: Martin Mynarek, Barry Pizer, Christelle Dufour, Dannis van Vuurden, Miklos Garami, Maura Massimino, Jason Fangusaro, Tom Davidson, Maria Joao Gil-da-Costa, Jaroslav Sterba, Martin Benesch, Nicolas Gerber, B. Ole Juhnke, Robert Kwiecien, Torsten Pietsch, Marcel Kool, Steve Clifford, David W. Ellison, Felice Giangaspero, Pieter Wesseling, Floyd Gilles, Nicholas Gottardo, Jonathan L. Finlay, Stefan Rutkowski, Katja von Hoff
Journal: Neuro-Oncology (2016)

Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors.Original prospective treatment and outcome data from international trial groups were pooled. Cox regression models were developed considering treatment elements as time-dependent covariates.Data on 135 patients with pineoblastoma aged 0.01-20.7 (median 4.9) years were analyzed. Median observation time was 7.3 years. Favorable prognostic factors were age ≥4 years (hazard ratio [HR] for progression-free survival [PFS] 0.270, P < .001) and administration of radiotherapy (HR for PFS 0.282, P < .001). Metastatic disease (HR for PFS 2.015, P = .006), but not postoperative residual tumor, was associated with unfavorable prognosis. In 57 patients <4 years old, 5-year PFS/overall survival (OS) were 11 ± 4%/12 ± 4%. Two patients survived after chemotherapy only, while 3 of 16 treated with craniospinal irradiation (CSI) with boost, and 3 of 5 treated with high-dose chemotherapy (HDCT) and local radiotherapy survived. In 78 patients aged ≥4 years, PFS/OS were 72 ± 7%/73 ± 7% for patients without metastases, and 50 ± 10%/55 ± 10% with metastases. Seventy-three patients received radiotherapy (48 conventionally fractionated CSI, median dose 35.0 [18.0-45.0] Gy, 19 hyperfractionated CSI, 6 local radiotherapy), with (n = 68) or without (n = 6) chemotherapy. The treatment sequence had no impact; application of HDCT had weak impact on survival in older patients.Survival is poor in young children treated without radiotherapy. In these patients, combination of HDCT and local radiotherapy may warrant further evaluation in the absence of more specific or targeted treatments. CSI combined with chemotherapy is effective for older non-metastatic patients.
Knockdown of MicroRNA Let-7a Improves the Functionality of Bone Marrow-Derived Mesenchymal Stem Cells in Immunotherapy
Authors: Yang Yu, Li Liao, Bingyi Shao, Xiaoxia Su, Yi Shuai, Han Wang, Fengqing Shang, Zhifei Zhou, Deqin Yang, Yan Jin
Journal: Molecular Therapy (2016)

Bone marrow-derived mesenchymal stem cells (MSCs) have been recently used in clinical treatment of inflammatory diseases. Practical strategies improving the immunosuppressive property of MSCs are urgently needed for MSC immunotherapy. In this study, we aimed to develop a microRNA-based strategy to improve MSC immunotherapy. Bioinformatic analysis revealed that let-7a targeted the 3' UTR of mRNA of Fas and FasL, both of which are essential for MSCs to induce T cell apoptosis. Knockdown of let-7a by specific inhibitor doubled Fas and Fas ligand (FasL) protein levels in MSCs. Because Fas attracts T cell migration and FasL induces T cell apoptosis, knockdown of let-7a significantly promoted MSC-induced T cell migration and apoptosis in vitro and in vivo. Importantly, MSCs knocked down of let-7a were more efficient to reduce the mortality, prevent the weight loss, suppress the inflammation reaction, and alleviate the tissue lesion of experimental colitis and graft-versus-host disease (GVHD) mouse models. In conclusion, knockdown of let-7a significantly improved the therapeutic effect of MSC cytotherapy on inflammatory bowel diseases and GVHD. With high safety and convenience, knockdown of let-7a is a potential strategy to improve MSC therapy for inflammatory diseases in clinic.
Establishment and Characterization of a Novel Human Myeloma Cell Line, AMU-MM1, From a Multiple Myeloma Patient Involving Central Nerve System After Treatment with Bortezomib
Authors: Ichiro Hanamura, Mayuko Goto, Hisao Nagoshi, Tomohiko Taki, Norikazu Imai, Kazuto Suganuma, Mineo Goto, Shohei Mizuno, Miyuki Takahashi, Hidesuke Yamamoto, Akihito Hiramatsu, Motohiro Wakabayashi, Masaya Watarai, Masato Shikami, Akira Imamura, Hidetsugu Mihara, Shinsuke Iida, Ryuzo Ueda, Masafumi Taniwaki, Hiroshi Miwa, Masakazu Nitta
Journal: Blood (2010)
Dasatinib 140 Mg Once Daily (QD) Demonstrates Equivalent Efficacy and Improved Safety Compared with 70 Mg Twice Daily (BID) in Patients with Chronic Myeloid Leukemia in Blast Phase (CML-BP): 2-Year Data from CA180-035
Authors: Giuseppe Saglio, Hagop M. Kantarjian, Andreas Hochhaus, Yeow Tee Goh, Tamas Masszi, Ricardo Pasquini, Frederic Maloisel, M. Brigid Bradley-Garelik, Chao Zhu, Herve Dombret
Journal: Blood (2008)
PWE-028 Thiopurine-induced neutropaenia in IBD patients with normal TPMT levels: a warning for gastroenterologists
Authors: S Cherian, V Saxena, M Foxton, A McNair
Journal: Gut (2010)

<h3>Introduction</h3> Myelotoxicity occurs in approximately 3% of patients receiving Azathioprine (AZA) or Mercaptopurine (MP). Manufacturers recommend weekly blood testing for the first 8 weeks of therapy but BSG guidelines state that “less frequent monitoring (within 4 weeks) may be sufficient”. Some gastroenterologists elect to monitor patients with normal thiopurine methyl transferase (TPMT) levels less intensively, believing that neutropaenia is less frequently encountered in this group. We performed a retrospective review to determine the proportion of IBD patients on our unit with AZA/MP-induced neutropaenia who had low TPMT levels. <h3>Methods</h3> We reviewed the medical records of our IBD patients who had become neutropenic on AZA/MP over the last 2 years. Patients received standard recommended doses: 2–2.5 mg/kg AZA, 1–1.5 mg/kg MP. TPMT had been measured prior to therapy in all patients. All patients had blood tests done at fixed intervals according to a local protocol to monitor myelotoxicity. <h3>Result</h3> Over the last 2 years, 8 patients were identified, who had developed myelosupression on AZA/MP therapy. Five patients had Ulcerative colitis. Average age at start of AZA/MP was 51.8 years (range 31–74 years). Average disease duration prior to immunosuppression was 8.7 years (range 1–21 years). MP was used in 7 patients. Only one of the patients had a low TPMT level 24 (normal range 26–50 PM/h/mgH). Mean time to myelosupression was 4.7 weeks (range 2–7 weeks). Lowest recorded WCC ranged from 0.6–2.7×10<sup>9</sup>/L (median-1.8×10<sup>9</sup>/L) and neutrophils ranged from 0–1.4×10<sup>9</sup>/L (median 0.75×10<sup>9</sup>/L). <h3>Conclusion</h3> The majority (7 of 8) of our patients with thiopurine-induced myelotoxicty had normal TPMT levels. Half of our patients developed neutropaenia within 4 weeks of treatment. The results of TPMT level should not influence the frequency of blood test monitoring in the first 8 weeks of therapy. The current BSG guidelines should be amended to emphasise the importance of frequent blood test monitoring. We advise caution when using thiopurine and suggest weekly FBC for the first 8 weeks, even if the TPMT is normal.
Comparison of Cyclosporine and Methotrexate with Cyclosporine and Mycophenolate Mofetil for Gvhd Prophylaxis in Myeloablative Allogeneic Bone Marrow Transplantation.
Authors: Robert Dean, Lisa Rybicki, Ronald Sobecks, Edward Copelan, Matt Kalaycio, Steven Andresen, Shawnda Sungren, Mary Serafin, Brian J. Bolwell
Journal: Blood (2008)
Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-line therapy for advanced NSCLC: KEYNOTE-021 cohort G
Authors: C. Langer, S.M. Gaddgeel, H. Borghaei, V.A. Papadimitrakopoulou, A. Patnaik, S. Powell, R.D. Gentzler, R.G. Martins, J.P. Stevenson, S.I. Jalal, A. Panwalkar, J.C.-H. Yang, M.A. Gubens, L.V. Sequist, M.M. Awad, J.J. Fiore, Y. Ge, H. Raftopoulos, L. Gandhi
Journal: Annals of Oncology (2016)
Electrocardiograms of 25 Marathon Runners before and after 100 Meter Dash
Authors: Kimiaki Nakamoto
Journal: Circulation (1969)

ECG characteristics of well-trained endurance athletes who are in state of training vagotonia were investigated in comparison with male and female controls of the same age group. The effects of sympathicotonia on these ECG characteristics of training vagotonia were also investigated by recording ECG immediately after 100 meter dash in endurance athletes. Thus, ECG charcteristics of endurance athletes could be divided into 2 groups, an cute and a chronic effect of maximal exercise. On the basis of these observations and inferences the athletic heart was clssified into 5 stages, and their probable ECG manifestations were reasoned.
Dose-finding and efficacy phase II study of inecalcitol, a new VDR agonist, in combination with docetaxel-prednisone regimen for patients (pts) with castration-resistant prostate cancer (CRPC).
Authors: J. Medioni, J. Ferrero, G. Deplanque, T. Maurina, J. P. Rodier, E. Raymond, J. Allyon, S. Renaux, J. Dufour-Lamartinie, S. Oudard
Journal: Journal of Clinical Oncology (2011)

4605 Background: Inecalcitol is a novel vitamin D receptor (VDR) agonist which shows high antiproliferative effects in human cancer cell lines and a 100-fold lower hypercalcemic activity than calcitriol the natural ligand of VDR. Methods: Escalating dosages of inecalcitol were combined to chemotherapy in naive metastatic CRPC patients. Safety and efficacy were evaluated in groups of 3-6 patients receiving inecalcitol every other day, daily or twice a day on a 21-day cycle in combination with docetaxel (75mg/m2 q3w) and oral prednisone (5mg bid). Patients received up to six cycles unless unacceptable toxicity or disease progression. Primary endpoint was dose limiting toxicity (DLT) defined as G3 hypercalcemia within the first cycle. Efficacy endpoint was PSA response defined as ≥30% decline within 3 months. Results: Eight dose levels from 40 to 8,000 µg have been evaluated in 54 pts; 87 % had bone metastases, 13% had visceral disease only. Median age was 71 years [range, 49-87], median Gleason score (Gs) 7 and mean PSA 75 ng/mL±146.92. DLT occurred in 2/4 patients receiving 8,000 µg/day after 1 and 2 weeks of treatment. Calcemia normalized in few days after interruption of treatment. The 2 other experienced only G2 and were stepped down to 4,000 µg. After dose reduction, calcemia remained within normal ranges and G1.The maximum tolerated dose is defined at 4,000 µg qd. Most of adverse events reported were grade 2. G3-4 were mainly hematological toxicity. 85% and 76% of the patients had ≥30% PSA decline within 3 months of treatment and ≥50% PSA decline any time on study respectively. Historical data published with docetaxel as a single agent showed 67% and 48% of responder respectively. PSA decline ≥30% was observed after 1 cycle of treatment in 43% of the treated patients. Conclusions: High antiproliferative daily dose of inecalcitol, a new VDR, agonist has been safely used in combination with docetaxel in CRPC patients. This combination treatment shows encouraging PSA response (> 30% PSA response: 85% - (> 50% PSA response: 76%). A multicenter randomized double blind phase III study is forecasted to confirm these results.
624. Immunovirotherapy Combined with Immune Checkpoint Inhibitors for Treating Glioblastoma
Authors: Dipongkor Saha, Robert L. Martuza, Samuel D. Rabkin
Journal: Molecular Therapy (2015)

Glioblastoma, the most common primary brain tumor in adults, is invariably fatal despite all current therapies, with a median survival of about 15 months. Glioblastoma contains cancer stem cells or tumor-initiating cells, a subpopulation of cancer cells that are thought to be important in tumor initiation, progression, heterogeneity, recurrence and resistance to therapy, and thus critical targets for therapy. We have established a mouse syngeneic glioblastoma stem cell (GSC) tumor model using 005 GSCs, isolated from activated H-Ras and Akt gliomas induced in Tp53+/- C57Bl/6 mice, which recapitulates the hallmarks of human glioblastoma. Immunovirotheray takes advantage of the natural inflammatory responses to virus infection and oncolytic virus-induced cancer cell death to drive antitumor immunity. Oncolytic herpes simplex viruses (oHSVs) are genetically-engineered to selectively replicate in cancer cells without harming normal tissue. In this study, we test G47Δ-mIL12, an oHSV expressing murine IL-12, a critical cytokine involved in adaptive and innate immune responses as well as anti-angiogenesis. G47Δ-mIL12 increases the survival of immunocompetent mice bearing 005 GSC-derived intracerebral tumors, compared to non-cytokine expressing G47Δ-empty. Immune checkpoints, especially co-inhibitory molecules like PD-1 and its ligand PD-L1, play a critical role in regulating immune responses and suppressing antitumor immune effector cells. PD-1 is expressed on immune cells, as is PD-L1, which is also expressed on endothelial and tumor cells. PD-L1 is expressed on a minority of 005 GSCs in vitro, but is induced by IFNγ in almost all 005 GSCs. Blocking antibodies to these molecules have been shown to be very effective at unleashing antitumor immunity. Therefore, we hypothesized that oHSV, which induces antitumor immune responses, should synergize with checkpoint inhibitor antibodies in inhibiting glioblastoma growth. Mice with established 005 GSC-derived tumors were treated with a single intratumoral injection of G47Δ-mIL12 or PBS, followed by systemic anti-PD-1, anti-PD-L1, or control antibody. Single treatments had a small but significant impact on survival, compared to mock treatment. The combination further extended survival, compared to virus or anti-PD-1 alone. We are examining the immunologic effects of treatment in order to understand the mechanism of action and how to improve outcomes. Combining local delivery of oncolytic viruses (immunovirotherapy) with systemic blockade of immune checkpoints is a promising strategy to target cancer stem cells.
A Pilot Study of Genasense® (Oblimersen Sodium, Bcl-2 Antisense Oligonucleotide), Fludarabine and Rituximab in Previously Treated and Untreated Subjects with Chronic Lymphocytic Leukemia.
Authors: Asher Alban Chanan-Khan, Blanche Mavromatis, Kanti R. Rai, Philomena Casey, Steven Novick, Loretta M. Itri
Journal: Blood (2004)
Significant Suppression of the Colony Forming Capacity of Erythroid Progenitors by Iron Overload in Patients with MDS and Sequential Anlyses of BFU-E Under Chelation Therapy.
Authors: Julia Hartmann, Ursula Sinzig, Gerald Wulf, Lorenz Trümper, Frank Konietschke, Stephanie Fischer, Detlef Haase
Journal: Blood (2009)
Genome-Wide Analysis by High-Resolution SNP Array Identifies Novel Genomic Alterations in Acute Promyelocytic Leukemia (APL).
Authors: Ilaria Iacobucci, Emanuela Ottaviani, Federica Salmi, Viviana Guadagnuolo, Nicoletta Testoni, Annalisa Lonetti, Cristina Papayannidis, Stefania Paolini, Daniela Cilloni, Michele Malagola, Carmen Baldazzi, Francesca Messa, Anna Candoni, Francesca Arruga, Giuseppe Visani, Giuseppe Saglio, Michela Rondoni, Fabrizio Pane, Hasan Syed Khizer, Michele Baccarani, Giovanni Martinelli, Francesco Lo Coco
Journal: Blood (2009)
Seek and You Shall Find – but Then What Do You Do? Cold Agglutinins in Cardiopulmonary Bypass, and a Single Center Experience with Cold Agglutinin Screening Before Cardiac Surgery
Authors: Michael D Jain, Keyvan Karkouti, Terence M. Yau, Jacob M Pendergrast, Christine Cserti-Gazdewich
Journal: Blood (2012)