tbuckley/cabot-search huggingface dataset:
Simultaneous blockade of interacting CK2 and EGFR pathways by tumor-targeting nanobioconjugates increases therapeutic efficacy against glioblastoma multiforme
Authors: Szu-Ting Chou, Rameshwar Patil, Anna Galstyan, Pallavi R. Gangalum, Webster K. Cavenee, Frank B. Furnari, Vladimir A. Ljubimov, Alexandra Chesnokova, Andrei A. Kramerov, Hui Ding, Vida Falahatian, Leila Mashouf, Irving Fox, Keith L. Black, Eggehard Holler, Alexander V. Ljubimov, Julia Y. Ljubimova
Journal: Journal of Controlled Release (2016)

Glioblastoma multiforme (GBM) remains the deadliest brain tumor in adults. GBM tumors are also notorious for drug and radiation resistance. To inhibit GBMs more effectively, polymalic acid-based blood-brain barrier crossing nanobioconjugates were synthesized that are delivered to the cytoplasm of cancer cells and specifically inhibit the master regulator serine/threonine protein kinase CK2 and the wild-type/mutated epidermal growth factor receptor (EGFR/EGFRvIII), which are overexpressed in gliomas according to The Cancer Genome Atlas (TCGA) GBM database. Two xenogeneic mouse models bearing intracranial human GBMs from cell lines LN229 and U87MG that expressed both CK2 and EGFR at different levels were used. Simultaneous knockdown of CK2α and EGFR/EGFRvIII suppressed their downstream prosurvival signaling. Treatment also markedly reduced the expression of programmed death-ligand 1 (PD-L1), a negative regulator of cytotoxic lymphocytes. Downregulation of CK2 and EGFR also caused deactivation of heat shock protein 90 (Hsp90) co-chaperone Cdc37, which may suppress the activity of key cellular kinases. Inhibition of either target was associated with downregulation of the other target as well, which may underlie the increased efficacy of the dual nanobioconjugate that is directed against both CK2 and EGFR. Importantly, the single nanodrugs, and especially the dual nanodrug, markedly suppressed the expression of the cancer stem cell markers c-Myc, CD133, and nestin, which could contribute to the efficacy of the treatments. In both tumor models, the nanobioconjugates significantly increased (up to 2-fold) animal survival compared with the PBS-treated control group. The versatile nanobioconjugates developed in this study, with the abilities of anti-cancer drug delivery across biobarriers and the inhibition of key tumor regulators, offer a promising nanotherapeutic approach to treat GBMs, and to potentially prevent drug resistance and retard the recurrence of brain tumors.
Patterns of Care in Hospitalized Vascular Surgery Patients at End of Life
Authors: Dale G. Wilson, Sheena K. Harris, Heidi Peck, Kyle Hart, Enjae Jung, Amir F. Azarbal, Erica L. Mitchell, Gregory J. Landry, Gregory L. Moneta
Journal: JAMA Surgery (2016)

There is limited literature reporting circumstances surrounding end-of-life care in vascular surgery patients.To identify factors driving end-of-life decisions in vascular surgery patients.In this cohort study, medical records were reviewed for all vascular surgery patients at a tertiary care university hospital who died during their hospitalization from 2005 to 2014.Patient, family, and hospitalization variables potentially important to influencing end-of-life decisions.Of 111 patients included (67 [60%] male; median age, 75 [range, 24-94] years), 81 (73%) were emergent vs 30 (27%) elective admissions. Only 15 (14%) had an advance directive. Of the 81 (73%) patients placed on comfort care, 31 (38%) had care withheld or withdrawn despite available medical options, 15 (19%) had an advance directive, and 28 (25%) had a palliative care consultation. The median time from palliative care consultation to death was 10 hours (interquartile range, 3.36-66 hours). Comparing the 31 patients placed on comfort care despite available medical options with an admission diagnosis-matched cohort, we found that more than 5 days admitted to the intensive care unit (odds ratio [OR], 4.11; 95% CI, 1.59-10.68; P < .001), more than 5 days requiring ventilator support (OR, 9.45; 95% CI, 3.41-26.18; P < .001), new renal failure necessitating dialysis (OR, 14.48; 95% CI, 3.69-56.86; P < .001), and new respiratory failure necessitating tracheostomy (OR, 23.92; 95% CI, 2.80-204; P < .001) correlated with transition to comfort care.Palliative care consultations may be underused at the end of life. A large percentage of patients were transitioned to comfort measures despite available treatment, yet few presented with advance directives. In high-risk patients, discussions regarding extended stays in the intensive care unit, prolonged ventilator management, and possible dialysis and tracheostomy should be communicated with patients and families at time of hospitalization and advance directives solicited.
CD161 Expression Identifies a Distinct Subset Of Drug-Effluxing Viral-Specific Memory CD4+ T Cells That Preferentially Survive Cytotoxic Chemotherapy
Authors: MD Muharrem Muftuoglu, Abdullah Alsuliman, Ahmad Khoder, Yong-Oon Ahn, Enli Liu, Claude Chew, Amir Hamdi, Takuya Sekine, Anushruti Sarvaria, Nichola Cooper, Hugues de Lavallade, David Marin, Kate Stringaris, Michael R. Verneris, Elizabeth J Shpall, Katayoun Rezvani
Journal: Blood (2013)
Advanced Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) in Children and Adolescents : Retrospective Study from Sfce and Ukccssg
Authors: Roques Gaelle, Ananth Shankar, Thierry Leblanc, Claudine Schmitt, Janis Hayward, Helene Pacquement, Anne Lambilliotte, Nathalie Aladjidi, Stephanie gorde-Grosjean, Hewitt Martin, Stephanie Haouy, Samuel Abbou, Dominique Plantaz, Genevieve Plat, Georgina Hall, Judith Landman-Parker
Journal: Blood (2014)
Targeting Btk in Lymphoma: PCI-32765 Inhibits Tumor Growth in Mouse Lymphoma Models and a Fluorescent Analog of PCI-32765 Is an Active-Site Probe That Enables Assessment of Btk Inhibition In Vivo.
Authors: Lee A. Honigberg, Ashley M. Smith, Jun Chen, Patti Thiemann, Erik Verner
Journal: Blood (2007)
PWE-245 Oral neostigmine treatment in recurrent resistant intestinal pseudo-obstruction: Abstract PWE-245 Table 1
Authors: NM Mirza, A Akram, K Konrad
Journal: Gut (2015)

<h3>Introduction</h3> Chronic intestinal pseudo-obstruction is a syndrome of disordered intestinal motility. It is generally considered to be more prevalent in elderly patients so incidence is expected to rise in developed countries with ageing population. Chronic pseudo-obstruction can be difficult to treat and has significant morbidity. Neostigmine has been reported to effectively relieve acute colonic pseudo-obstruction. Reported recurrence after initial use of neostigmine is up to 30%. Neostigmine enhances excitatory parasympathetic activity by competing with acetylcholine for attachment to acetylcholinesterase at sites of cholinergic transmission and enhancing cholinergic action. We studied use of oral neostigmine treatment for six months in patients with recurrent resistant pseudo-obstruction when other treatments failed and surgery was not considered a safe option due to co-morbidities. <h3>Method</h3> Three patients with clinical and radiological evidence of pseudo-obstruction were treated conservatively. All reversible causes were corrected and two patients had multiple flatus tube inserted for colonic decompression with recurrence of pseudo-obstruction. After deemed, unsafe for surgical intervention secondary to co-morbidities, patients were treated with 2.5 mg intramuscular neostigmine and then maintenance dose of oral Neostigmine 30 mg twice daily was initiated. Regular ECG was carried out pre and post treatment to look for cardiac arrhythmias. Patients were monitored for side effects and recurrence of symptoms. <h3>Results</h3> Clinical resolution of large bowel dilatation occurred in all three patients within twenty four hours after initiating treatment with intramuscular neostigmine. Maintenance oral Neostigmine 30mg twice daily was continued for six months with no further recurrence of pseudo-obstruction. No side effects or complications were noted. <h3>Conclusion</h3> We have shown that oral Neostigmine is safe and effective treatment option in selective group of patients with recurrent resistant pseudo-obstruction when other conservative treatment options are ineffective. <h3>Disclosure of interest</h3> None Declared.
The DAC Inhibitor, LBH589, Is Highly Effective in Both Rituximab-Sensitive and Rituximab-Resistant Lymphomas and Enhances the Anti-Tumor Activity of Bortezomib, Other Chemotherapy Agents, and Anti-CD20 Monoclonal Antibodies.
Authors: Francisco J Hernandez-Ilizaliturri, Cory Marvis, Ilir Maraj, Mohammad M Chisti, John Gibbs, Myron S Czuczman
Journal: Blood (2009)
Authors’ reply to Lamont
Authors: Sarah J Stock, Khaled M K Ismail
Journal: BMJ (2016)

We thank Lamont for highlighting the well established link between infection and preterm birth and the lack of strong evidence on the ability of antibiotics to prevent preterm birth or improve neonatal outcomes.1 2 The remit of our article was to discuss interventions for prevention of preterm birth in women at high risk due to previous preterm birth, late miscarriage, cervical treatment, or a short cervix. We focused …
<scp>RHS</scp>6 coordinately regulates the Th2 cytokine genes by recruiting <scp>GATA</scp>3, SATB1, and <scp>IRF</scp>4
Authors: S. S. Hwang, S. W. Jang, K. O. Lee, H. S. Kim, G. R. Lee
Journal: Allergy (2016)

Abstract Background Asthma is a Th2 cell‐driven inflammatory disease and a major public health concern. The cis ‐acting element Rad50 hypersensitive site 6 ( RHS 6) in the Th2 locus control region is essential for regulation of the Th2 cytokine genes; however, its role in allergic airway inflammation and underlying molecular mechanisms of the regulation by RHS 6 are poorly understood. Objective We sought to understand the role of RHS 6 in the development of allergic airway inflammation and its molecular mechanism for Th2 cytokine expression. Methods We used an ovalbumin‐induced allergic inflammation model with RHS 6‐deficient mice to examine the role of RHS 6 in this process. To examine molecular mechanism of RHS 6 for Th2 cytokine expression, we used DNA affinity chromatography and mass spectrometry, quantitative RT ‐ PCR , ELISA , intracellular cytokine staining, chromatin immunoprecipitation, and co‐immunoprecipitation. Results Deletion of RHS 6 caused a dramatic resistance to allergic airway inflammation. RHS 6 recruited transcription factors GATA 3, SATB 1, and IRF 4, which play important roles in expression of all three Th2 cytokine genes. RHS 6 deficiency caused inhibition of transcription factor‐induced Th2 cytokine gene expression. Conclusion RHS 6 is a critical regulatory element for allergic airway inflammation and for coordinate regulation of Th2 cytokine genes by recruiting GATA 3, SATB 1, and IRF 4.
Everolimus and Cyclosporine in Combination with 2Gy TBI as Pre- and Posttransplant Immunosuppression in a Canine Transplantation Model.
Authors: Sandra Lange, Susanne Rathsack, Rainer Wacke, Simone Altmann, Volker Weirich, Heike Vogel, Bernd Drewelow, Mathias Freund, Christian Junghanss
Journal: Blood (2007)
Comparison of COBAS 4800 <i>KRAS</i>, PCR TaqMan, and PCR high-resolution melting assays for the detection of <i>KRAS</i> somatic mutations in formalin-fixed paraffin-embedded colorectal tumors.
Authors: Alexandre Harle, Jean-Louis Merlin
Journal: Journal of Clinical Oncology (2012)

103 Background: Colorectal cancer (CRC) is the 2nd most common cancer with more than one million new cases diagnosed every year. From 2006 to 2008, several studies showed the importance of the KRAS oncogene in the treatment of metastatic CRC (mCRC) and response to anti-EGFR therapies like cetuximab or panitumumab. KRAS is a small G protein which can bear activating mutations in 40% cases of mCRC. Numerous methods have been described for the detection of KRAS mutations in FFPE tissues. Direct sequencing is the gold standard but the most sensitive methods are real time PCR assays based. The new COBAS4800 KRAS developed by Roche Diagnostics is a CE IVD validated assay using real time PCR and TaqMelt technology. This assay is validated for the detection of 19 KRAS somatic mutations on exon 2 (codons 12/13) and exon 3 (codon 61) in specimen containing at least 5% of mutated tumoral cells. Methods: We compared COBAS with previously validated PCR TaqMan and PCR High Resolution Melting (HRM) assays. The PCR TaqMan and HRM are a real time PCR based assays. TaqMan can detect accurately 0.5 to 1% of mutated tumoral DNA on codon 12 (G12A, G12C, G12D, G12R, G12S and G12V) and on codon 13 (G13D). HRM can detect 5 to 10% of tumoral DNA on codon 12 and 13. 80 FFPE samples of colorectal tumors resections or biopsies have been collected and processed with the 3 assays. Results have been compared using kappa statistics. Results: On 80 samples, 69 were interpretable with COBAS and TaqMan and 62 with COBAS and HRM. No statistically significant difference between COBAS and TaqMan was found (k=0.942 ; p&lt;0.001). Only 2 discordant cases were found mainly regarding codon 61 mutations not detected with TaqMan. No statistically significant difference between COBAS and HRM was found (k=0.903 ; p&lt;0.001). Three discordant cases were found two regarding codon 61, not detected with HRM and one G12S mutation (detected by COBAS and TaqMan). Conclusions: The 3 assays can detect accurately KRAS mutations. Less ininterpretable results were found with COBAS and TaqMan assays. A pre screening with COBAS and mutation characterization with TaqMan seem to be a good scheme for routine diagnostic of KRAS mutations.
PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation
Authors: Guo Zhu, Sherri L. Rankin, Jon D. Larson, Xiaoyan Zhu, Lionel M.L. Chow, Chunxu Qu, Jinghui Zhang, David W. Ellison, Suzanne J. Baker
Journal: Cancer Research (2016)

Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into the effect of its loss on outcomes in the brain, we conditionally inactivated the murine Pten gene in neonatal neural stem/progenitor cells. Pten inactivation created an abnormal perivascular proliferative niche in the cerebellum that persisted in adult animals but did not progress to malignancy. Proliferating cells showed undifferentiated morphology and expressed the progenitor marker Nestin but not Math1, a marker of committed granule neuron progenitors. Codeletion of Pten and Trp53 resulted in fully penetrant medulloblastoma originating from the perivascular niche, which exhibited abnormal blood vessel networks and advanced neuronal differentiation of tumor cells. EdU pulse-chase experiments demonstrated a perivascular cancer stem cell population in Pten/Trp53 double mutant medulloblastomas. Genetic analyses revealed recurrent somatic inactivations of the tumor suppressor gene Ptch1 and a recapitulation of the sonic hedgehog subgroup of human medulloblastomas. Overall, our results showed that PTEN acts to prevent the proliferation of a progenitor niche in postnatal cerebellum predisposed to oncogenic induction of medulloblastoma. Cancer Res; 77(1); 123-33. ©2016 AACR.
The need for surgery after endoscopic treatment of colorectal neoplasms is the most important outcome criterion
Authors: Peter Rolny
Journal: Endoscopy (2016)

Endoscopic submucosal dissection (ESD) is known to provide superior results in terms of en bloc and/or R0 resection compared with endoscopic mucosal resection. Therefore, ESD is also expected to provide superior clinical outcomes in terms of the need for supplementary surgery after endoscopic treatment. However, whether or not the clinical gain to the patient is sufficiently large to justify the cost and risk of ESD remains to be further evaluated.
NCO-15PREDICTION OF SUBJECTIVE MEMORY ABILITY BEFORE RESECTION OF HIGH GRADE GLIOMA
Authors: Allison S. Verhaak, Jeffrey S. Wefel, Consuelo A. Arbona, Susan X. Day
Journal: Neuro-Oncology (2015)

OBJECTIVE: A significant relationship between subjective reports of cognitive function and objective neuropsychological test data is often absent in medical populations. Sociodemographic and clinical predictors of subjective memory ability are largely unknown in glioma patients. METHODS: Patients (n = 146) with high-grade glioma completed neuropsychological assessment preoperatively, including the Hopkins Verbal Learning Test-Revised (HVLT-R), the Functional Assessment of Cancer Therapy-Brain (FACT-Br), and the Beck Depression Inventory-Second Edition (BDI-II). Linear regression analyses were conducted with sociodemographic (age and sex), clinical (tumor location and lateralization), and neuropsychological variables (HVLT-R and BDI-II) as predictors of subjective memory ability (“I can remember new things”) from the FACT-Br. Three linear regression analyses were conducted to examine differences between the HVLT-R subtests (Immediate Recall, Delayed Recall, Delayed Recognition) in predicting subjective memory ability. RESULTS: FACT-Br subjective memory ability was significantly correlated with HVLT-R Immediate Recall, r(144) = .31, p < .001, Delayed Recall, r(136) = .26, p < .01, and Delayed Recognition, r(136) = .18, p < .05. Better subjective memory ability was predicted by a model (p < .001, R2 = .21) that included younger patient age (β = -.20; p = .018), better HVLT-R Immediate Recall (β = .19; p = .018), and less depressive symptomatology (β = -.24; p = .002). Separate models including HVLT-R Delayed Recall (p < .001, R2 = .20) and Delayed Recognition (p < .001, R2 = .20) did not find these subtests to be predictive of subjective memory ability; however, younger patient age (β = -.24; p = .006; and β = -.26; p = .002, respectively) and less depressive symptoms (β = -.25; p = .002; and β = -.26; p = .001, respectively) were predictive of better subjective memory ability. CONCLUSION: Subjective memory ability and objective memory test performance were modestly correlated in newly diagnosed patients with high-grade glioma. Multivariate analysis highlighted the additional importance of patient age and depressive symptoms in predicting subjective memory ability. Results underscore the importance of considering sociodemographic and clinical variables when patients self-report memory difficulties.
Excellent Prognosis of Late Relapses of ETV6/RUNX1 Childhood Acute Lymphoblastic Leukemia: Lessons From the FRALLE 93 Protocol
Authors: Virginie Gandemer, Sylvie Chevret, Arnaud Petit, Christiane Vermylen, Thierry Leblanc, Gerard Michel, Claudine Schmitt, Odile Lejars, Jean-Pierre Vannier, Francois Demeocq, Brigitte Bader-Meunier, Francoise Bernaudin, Yves Perel, Marie-Francoise Auclerc, Jean Michel Cayuela, Guy Leverger, Andre Baruchel
Journal: Blood (2011)
NCCN Guidelines Insights: Older Adult Oncology, Version 2.2016
Authors: Noam VanderWalde, Reshma Jagsi, Efrat Dotan, Joel Baumgartner, Ilene S. Browner, Peggy Burhenn, Harvey Jay Cohen, Barish H. Edil, Beatrice Edwards, Martine Extermann, Apar Kishor P. Ganti, Cary Gross, Joleen Hubbard, Nancy L. Keating, Beatriz Korc-Grodzicki, June M. McKoy, Bruno C. Medeiros, Ewa Mrozek, Tracey O'Connor, Hope S. Rugo, Randall W. Rupper, Dale Shepard, Rebecca A. Silliman, Derek L. Stirewalt, William P. Tew, Louise C. Walter, Tanya Wildes, Mary Anne Bergman, Hema Sundar, Arti Hurria
Journal: Journal of the National Comprehensive Cancer Network (2016)

Cancer is the leading cause of death in older adults aged 60 to 79 years. Older patients with good performance status are able to tolerate commonly used treatment modalities as well as younger patients, particularly when adequate supportive care is provided. For older patients who are able to tolerate curative treatment, options include surgery, radiation therapy (RT), chemotherapy, and targeted therapies. RT can be highly effective and well tolerated in carefully selected patients, and advanced age alone should not preclude the use of RT in older patients with cancer. Judicious application of advanced RT techniques that facilitate normal tissue sparing and reduce RT doses to organs at risk are important for all patients, and may help to assuage concerns about the risks of RT in older adults. These NCCN Guidelines Insights focus on the recent updates to the 2016 NCCN Guidelines for Older Adult Oncology specific to the use of RT in the management of older adults with cancer.
Shp2 promotes liver cancer stem cell expansion by augmenting β‐catenin signaling and predicts chemotherapeutic response of patients
Authors: Daimin Xiang, Zhuo Cheng, Hui Liu, Xue Wang, Tao Han, Wen Sun, Xiaofeng Li, Wen Yang, Cheng Chen, Mingyang Xia, Na Liu, Shengyong Yin, Guangzhi Jin, Terence Lee, Liwei Dong, Heping Hu, Hongyang Wang, Jin Ding
Journal: Hepatology (2016)

Src-homology 2 domain-containing phosphatase 2 (Shp2) has been reported to play an important role in the maintenance and self-renewal of embryonic and adult stem cells, but its role in cancer stem cells (CSCs) remains obscure. Herein, we observed high expression of Shp2 in both chemoresistant hepatocellular carcinomas (HCCs) and recurrent HCCs from patients. A remarkable increase of Shp2 was detected in sorted epithelial cell adhesion molecule-positive or cluster of differentiation 133-positive liver CSCs and in CSC-enriched hepatoma spheroids from patients. Up-regulated Shp2 facilitated liver CSC expansion by promoting the dedifferentiation of hepatoma cells and enhancing the self-renewal of liver CSCs. Mechanistically, Shp2 dephosphorylated cell division cycle 73 in the cytosol of hepatoma cells, and the dephosphorylated cell division cycle 73 bound β-catenin and facilitated the nuclear translocation of β-catenin, which promoted the dedifferentiation of hepatoma cells. Shp2 increased β-catenin accumulation by inhibiting glycogen synthase kinase 3β-mediated β-catenin degradation in liver CSCs, thereby enhancing the self-renewal of liver CSCs. Blockage of β-catenin abolished the discrepancy in liver CSC proportion and the self-renewal capacity between Shp2-depleted hepatoma cells and control cells, which further confirmed that β-catenin is required in Shp2-promoted liver CSC expansion. More importantly, HCC patients with low Shp2 levels benefited from transcatheter arterial chemoembolization or sorafenib treatment, but patients with high Shp2 expression did not, indicating the significance of Shp2 in personalized HCC therapy.Shp2 could promote HCC cell dedifferentiation and liver CSC expansion by amplifying β-catenin signaling and may be useful in predicting patient response to chemotherapeutics. (Hepatology 2017;65:1566-1580).
Cyclophosphamide, Vincristine, Myocet and Prednisone ± Rituximab (COMP±R) Regimen Is Safe and Effective as First Line or Salvage Therapy in Elderly Non Hodgkin Lymphoma (NHL): Preliminary Data of Single Centre Experience.
Authors: Elsa Pennese, Claudio Cristofalo, Michelina Dargenio, Maria Rosaria De Paolis, Pasquale Forese, Rosella Matera, Giorgio Pugliese, Giovanni Reddiconto, Antonio Valacca, Carolina Vergine, Nicola Di Renzo
Journal: Blood (2009)