tbuckley/cabot-search huggingface dataset:
182. Effects of Inflammation-Mediated Autophagy of Human Placental Mesenchymal Stem Cells of Fetal Origin on Their Immunomodulatory Properties and Therapeutic Potential in Bleomycin-Induced Pulmonary Fibrosis Models
Authors: Xiaoming Liu, Yongzhao Zhu, Xueyun Liang, Fei Han, Jun Wei
Journal: Molecular Therapy (2016)

Pulmonary fibrosis (PF) is an interstitial pulmonary disease caused by lung injury and inflammatory response, which is currently incurable in clinical settings. Fibroblast proliferation and extracellular matrix accumulation are the main clinical manifestation and pathogenic features of PF. An compelling number of evidence has demonstrated that mesenchymal stem cells (MSCs) pose therapeutic potentials in PF disease, owing to their strongly immunomodulatory roles in injury repair of tissues, including the lung. In this regards, the autophagy of MSCs induced by inflammatory microenvironment of pulmonary injury plays a critical role in their immunomodulatory properties. Our works have recently revealed that human placental MSCs of fetal origin (fPMSCs) have an ability to alleviate and reverse the pathological progress in a bleomycin-induced PF model. In order to better understand mechanisms underpinning the therapeutic effect of fPMSCs in pulmonary fibrosis, the inflammation-mediated MSC autophagy in murine pulmonary fibrosis model was interrogated. Our results demonstrated that the inflammatory microenvironment of PF was able to induce MSC autophagy in vitro and in vivo, implying that the inflammatory microenvironment of PF may trigger autophagy of fPMSCs, which in turn affects their therapeutic potentials to PF. These results also suggest that an interaction between autophagy of fPMSCs and PF inflammatory microenvironment may have a fundamental impact on immunomodulatory functions and therapeutic effects of fPMSCs on pulmonary. Key words: placenta; mesenchymal stem cells; cell therapy; pulmonary fibrosis; autophagy.
Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors
Authors: Shawn M Davidson, Oliver Jonas, Mark A Keibler, Han Wei Hou, Alba Luengo, Jared R Mayers, Jeffrey Wyckoff, Amanda M Del Rosario, Matthew Whitman, Christopher R Chin, Kendall J Condon, Alex Lammers, Katherine A Kellersberger, Brian K Stall, Gregory Stephanopoulos, Dafna Bar-Sagi, Jongyoon Han, Joshua D Rabinowitz, Michael J Cima, Robert Langer, Matthew G Vander Heiden
Journal: Nature Medicine (2016)
A Prospective, Self-Controlled and Randomized Study about the Optimal Timing of Leucovorin Rescue after High Dose Methotrexate Management
Authors: Tongyu Lin, Xueying Li, Tingzhi Liu, He Huang, Huangming Hong, Chengcheng Guo, Xiaohong Fu, Xiaojie Fang, Zhao Wang, Zhongjun Xia, Xiaoting Lin
Journal: Blood (2015)
Amyloidosis: Insights from Proteomics
Authors: Ahmet Dogan
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Amyloidoses are a spectrum of disorders caused by abnormal folding and extracellular deposition of proteins. The deposits lead to tissue damage and organ dysfunction, particularly in the heart, kidneys, and nerves. There are at least 30 different proteins that can cause amyloidosis. The clinical management depends entirely on the type of protein deposited, and thus on the underlying pathogenesis, and often requires high-risk therapeutic intervention. Application of mass spectrometry-based proteomic technologies for analysis of amyloid plaques has transformed the way amyloidosis is diagnosed and classified. Proteomic assays have been extensively used for clinical management of patients with amyloidosis, providing unprecedented diagnostic and biological information. They have shed light on the pathogenesis of different amyloid types and have led to identification of numerous new amyloid types, including ALECT2 amyloidosis, which is now recognized as one of the most common causes of systemic amyloidosis in North America.
Contralateral Prophylactic Mastectomy
Authors: Oluwadamilola M. Fayanju, E. Shelley Hwang
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
The Physiology of Prothrombin Gene Expression Integrates RNA Polyadenylation and Splicing in a Novel Regulatable 3′ RNP-Complex.
Authors: Sven Danckwardt, Marc Gentzel, Niels H. Gehring, Isabelle Kaufmann, Gabriele Neu-Yilik, Matthias Wilm, Matthias W. Hentze, Andreas E. Kulozik
Journal: Blood (2006)
Do diverticula provide a unique niche for microbiota which can lead to activation of the innate immune system?
Authors: Robin C Spiller, Tim J Sloan
Journal: Gut (2016)

As individuals living a Western lifestyle age, the prevalence of diverticulosis steadily rises reaching around 50% over the age of 75 years.1 While for most this is a harmless ageing change reflecting weakening of colonic connective tissue, around 30% suffer recurrent abdominal pain, often with diarrhoea,2 and 1–4% will be hospitalised with diverticulitis.3 As our population steadily ages this represents a substantial health burden, however, we know surprisingly little about the underlying mechanisms of this disease.

Heritability of symptomatic diverticular disease is around 40%,4 however, studies of immigrants from low-risk areas to high-risk countries show that environmental factors are equally important.3 Once hospitalised with diverticulitis the risk of further hospitalisation is around 1% per year but the majority continue to suffer pain or bowel disturbance, at least for the 1st year after discharge.5 Diverticulitis is associated with inflammation, tissue destruction and remodelling which includes striking muscular hypertrophy and morphological abnormalities of the enteric nerves thought to be responsible for symptoms.6 However the mechanisms whereby diverticulosis leads to diverticulitis remains unclear though dietary factors such as meat eating, obesity and low fibre intake play a role. One way these could act is by altering the microbiota.7 This might also account for reports that antibiotics8 probiotics9 or the anti-inflammatory agent mesalazine10 can reduce symptoms, though in most cases the number needed to treat is high.

The current paper11 represents a start in our attempts to understand this phenomenon. The authors hypothesised that the presence of diverticula creates a unique environment which leads to important changes in microbiota with potential effects on the gut immune system and hence symptoms. Controls (n=14) and 16 patients with asymptomatic diverticulosis (termed ‘diverticulosis’) were compared with 8 patients with …
High Response Rates to Pomalidomide and Dexamethasone in Patients with Refractory Myeloma, Final Analysis of IFM 2009-02
Authors: Xavier Leleu, Michel Attal, Bertrand Arnulf, Philippe Moreau, Catherine Traulle, Mauricette Michalet, Gerald Marit, Claire Mathiot, Marie Odile Petillon, Margaret Macro, Murielle Roussel, Brigitte Pegourie, Brigitte Kolb, Anne-Marie Stoppa, Sabine Brechiniac, Laurent Garderet, Bruno Royer, Cyrille Hulin, Lotfi Benboubker, Olivier Decaux, Denis Caillot, Martine Escoffre-Barbe, Jean Paul Fermand, Hervé Avet-Loiseau, Thierry Facon
Journal: Blood (2011)
Intratumoral neutrophils, plasmacytoid dendritic cells, and pSTAT3 in AJCC stage I/II melanoma prognosis.
Authors: T. O. Jensen, H. Schmidt, H. J. Moller, F. Donskov, M. Hoyer, P. Sjoegren, I. J. Christensen, T. Steiniche
Journal: Journal of Clinical Oncology (2011)

8553 Background: Interactions between tumor cells and host immune cells play a key role in carcinogenesis. Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer and is believed to be an important mediator of tumor-induced immuno-suppression. We studied the prognostic role of neutrophil and dendritic cell infiltration in primary melanomas and their association with activated STAT3 (pSTAT3) in primary melanoma cells. Methods: Formalin-fixated, paraffin-embedded primary melanomas from 187 stage I/II melanoma patients treated with surgical resection in 1997 to 2000 were included. Infiltrating neutrophils (CD66b+), dendritic cells (CD123+ and DC-LAMP+), and melanoma cell expression of pSTAT3 were studied by immunohistochemistry and evaluated as present or absent. Study endpoints were: Relapse-free survival, melanoma-specific and overall survival. Results: After a median observation time of 9.5 years (range 7.0-11.4 years), 39 deaths (21%) were observed, of which 31 (17%) were melanoma-specific. In a multivariate Cox proportional hazards model including ulceration and melanoma thickness, neutrophil- and CD123+ dendritic cell infiltration were independently associated with poor prognosis (CD66b+: HR=3.14 95% CI, 1.31-7.54 P=0.010; CD123+: HR=2.56 95% CI, 1.16-5.64 P=0.020). There was a strong association between melanoma cell pSTAT3 expression and neutrophil/CD123+ dendritic cell infiltration. pSTAT3 expression and DC-LAMP infiltration were not independently associated with poor prognosis. Conclusions: Neutrophil infiltration and CD123+ dendritic cell infiltration in primary melanoma are independently associated with poor prognosis. Melanoma cell expression of pSTAT3 is strongly associated with neutrophil and CD123+ dendritic cell infiltration.
Plerixafor (Mozobil ®)Plus G-CSF Is Effective in Mobilizing Hematopoietic Stem Cells in Patients with Concurrent Thrombocytopenia Undergoing Autologous Hematopoietic Stem Cell Transplantation.
Authors: Ivana N Micallef, Eric Jacobsen, Paul Shaughnessy, Sachin Marulkar, Purvi Mody, Frits van Rhee
Journal: Blood (2009)
Abstract 4405: Tumor-targeted nanotherapeutics
Authors: Olga B. Garbuzenko, Andriy Kuzmov, Justin E. Sapiezynski, Oleh Taratula, Vatsal Shah, Min Zhang, Ronak Savla, Shali John, Lorna Rodriguez-Rodriguez, Tamara Minko
Journal: Cancer Research (2015)

Abstract Directing anticancer agents specifically to tumors and/or cancer cells by targeting specific extracellular receptors fulfills the following three most important tasks: (1) preventing or at least substantially limiting adverse side effects on healthy tissues, (2) enhancing drug internalization by cancer cells, and (3) overcoming (at least in part) resistance mechanisms that are based on the active efflux of exogenous drugs from cancer cells. We developed several tumor-targeted nanoscale-based formulations: various nanocarriers (liposomes, lipid nanoparticles, dendrimers, polymers, quantum dots, mesoporous silica and supermagnetic iron oxide nanoparticles); different anticancer drugs (doxorubicin, paclitaxel, camptothecin, and cisplatin); suppressors of cellular drug resistance and tumor grows (antisense oligonucleotides or siRNA targeted to BCL2, MDR1, MRP1, HIF1A, CD44 mRNA); and tumor-targeting agent - luteinizing hormone-releasing hormone (LHRH). The proposed nanotherapeutics were tested in vitro and in vivo using established lung and ovarian cancer cell lines and highly metastatic cancer cells isolated from malignant intraperitoneal ascites from patients with advanced ovarian carcinoma. These cells were used to initiate orthotopic models of lung and ovarian cancers in nude mice that were often accompanied by the development of metastases. Tumor-targeted nanoscale-based drug formulations were delivered intravenously and intraperitoneally (for ovarian cancer) or intravenously and by inhalation (for lung cancer). Treatment with the developed therapeutics led to the suppression of targeted proteins, efficient induction of cell death, effective tumor shrinkage, prevention the development of metastases and limitation of adverse side effects. Acknowledgements: The work was supported by R01CA100098, R01CA111766, and R01CA138533 grants from NIH. Note: This abstract was not presented at the meeting. Citation Format: Olga B. Garbuzenko, Andriy Kuzmov, Justin E. Sapiezynski, Oleh Taratula, Vatsal Shah, Min Zhang, Ronak Savla, Shali John, Lorna Rodriguez-Rodriguez, Tamara Minko. Tumor-targeted nanotherapeutics. [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 4405. doi:10.1158/1538-7445.AM2015-4405
Infected Urachal Cyst
Authors: Nicholas Potisek, James Weihe
Journal: New England Journal of Medicine (2016)

A 19-month-old girl presented with abdominal pain. The initial examination was normal, but within 24 hours the umbilicus became protuberant and erythematous. The white-cell count was elevated. CT revealed a cystic mass extending from the umbilicus to the dome of the bladder.
424. AAV Re-Administration Following Pediatric Application: Effect of Age at First Administration
Authors: Kimberly L. Pietersz, Sander J. vanDeventer, Harald Petry, Valerie Ferreira
Journal: Molecular Therapy (2016)

Gene therapy delivery in pediatric patients may prevent or reduce the deleterious impact of disease long-term. However, due to the cellular turn-over and growth of some target organs such as the liver re-administration of AAV vectors will have to be considered. The goal of our study is to determine the time frame after birth in which AAV can be delivered without the development of an immune response against capsid, but with a proper transgene expression, thereby permitting re-administration and a continuous transgene expression. Mice were administered with AAV1-hAAT-hSEAP intraperitoneally at 2, 7, 14, 21 days and adult mice were used as controls. Two weeks after administration SEAP concentration was measured in plasma as a measure for transgene activity. Initial transgene expression was higher in mice injected at two and seven days of age than in mice injected at 14 or 21 days; As expected, transgene expression decreased over time in all mice. At week 8 SEAP concentrations in plasma of all mice were similar. AAV1 neutralizing antibody (NAB) responses were assessed at 9 weeks following primary administration. Mice administered at 21 days of age had a NAB titer slightly above PBS level; while the other age groups of 2, 7, and 14 days were similar to PBS. Mice of all groups were re-administrated 9 weeks after primary administration with AAV1-LP1-hFIX in order to assess the effect of NAB induction on the expression of a novel transgene. Mice primed at 21 days of age had 67% less FIX than adult control mice. In the other groups that were primed at 2, 7 or 14 days of age the second administration generated the same FIX plasma levels as measured in adult controls. With this study, we show that AAV1 can be effectively used for pediatric application up to 14 days after birth without inducing an immune response. This strategy prevents the formation of neutralizing antibodies, and the same serotype can be used for re-administrated later in life.
Clinical Follow-up Demonstrates Differential Accuracy of Flow Cytometry and Cytomorphology for the Detection of Hematologic Malignancy in Hypercellular Body Cavity Fluids.
Authors: Clara Cesana, Catherine Klersy, Barbara Scarpati, Bruno Brando, Elisabetta Volpato, Giambattista Bertani, Maurizio Faleri, Annamaria Nosari, Silvia Cantoni, Ursula Ferri, Linda Scampini, Claudia Barba, Giuliana Lando, Enrica Morra, Roberto Cairoli
Journal: Blood (2009)
437. Biosafety After the Injection of Carrier Cells Infected With Oncolytic Adenovirus
Authors: Katsuyuki Hamada, Kazuko Takagi, Hiroshi Itoh, Kenzaburo Tani, Akihiro Nawa
Journal: Molecular Therapy (2015)

Although replication-competent viruses have been developed to treat cancers, their cytotoxic effects are insufficient, since infection with them is inhibited by generation of neutralizing antibodies. To address this limitation, we developed a carrier cell system to deliver a replication-competent adenovirus. Carrier cells infected with oncolytic adenovirus were injected into syngeneic subcutaneous ovarian tumors after immunization with adenovirus and induced complete tumor regression by the induction of antiadenoviral and antitumoral CTL responses. To start clinical trial, toxicity and biodistribution study were carried out in nude mice, rabbits and beagle dogs. Acute toxicity and distribution test were carried out after the single injection of carrier cells into ovarian tumor in nude mice. Chronic toxicity test was carried out by 8 injections of carrier cells into rabbits for 4 weeks. Excretion study was carried out to determine whether oncolytic adenovirus was excreted from the beagle dogs after the single injection of carrier cells. Acute toxicity test did not show any lethal side effects in nude mice. In biodistribution test, single injection of carrier cells into ovarian tumor induced the peak levels of oncolytic adenovirus the next day but did not show any significant levels of that in nude mice 14 days after injection. In chronic toxicity test, 8 injections of 1.25×107 cells/kg or less did not show any significant toxicity in rabbits. In excretion test, oncolytic adenovirus was not excreted into the urine and the stool of beagle dogs. This oncolytic adenovirus-infected carrier cell system might prove effective and safe in the preclinical efficacy and the biosafety test, respectively. Clinical trial is being scheduled to treat recurrent solid cancers.
Abstract 4976: Inhibition of eIF4B suppresses the growth and induces the apoptosis of Bcr-Abl positive cells
Authors: Ke Chen, Jian-Ling Yang, Guijie Guo, Jilong Chen
Journal: Cancer Research (2015)

Abstract Alterations in translation are associated with various human malignancies, but the precise pathogenic processes and mechanistic underpinnings remain to be better understood. The oncogenic tyrosin kinase Bcr-Abl, which is believed to induce chronic myelogenous leukemia (CML), could cause the dysregulation of mRNA translation initiation by activating a series of signal pathways. Eukaryotic initiation factor 4B (eIF4B), a critical element in the assembly of translation initiation complex, has been shown to anticipate in Bcr-Abl-mediated tumorigenesis. eIF4B is activated through Ser422 phosphorylation by several pathways including JAK/STAT/Pim and PI3K/AKT/mTOR. Such redundant activation provides mechanistic bases for the less potent antitumor consequences under single-pathway targeted therapy. Interestingly, profound synergy was observed against cell survival and tumor growth and greater decrease of eIF4B Ser422 phosphorylation was detected upon the combination of Pim and mTOR inhibitors. Knockdown of eIF4B would increase the dependence of Bcr-Abl positive cells on Pim and mTOR signaling and then sensitize cells to the synergistical effect mediated by the combined inhibition. In addition, inhibiting mTOR pathway by shRNA targeting AKT or mTOR renders cells dependent on Pim pathway and knockdown Pim1 would sensitize cells to mTOR inhibitor. Thus, eIF4B acts as a prominent role in Bcr-Abl-driven pathogenesis by playing as the convergent point of these pathways which are active in Bcr-Abl positive tumors. Our results reveal a novel mechanism by which Bcr-Abl-induced cellular transformation can be blokced and provides a rationale for combination therapy targeting the dysregulation of translation for CML. Note: This abstract was not presented at the meeting. Citation Format: Ke Chen, Jian-Ling Yang, Guijie Guo, Jilong Chen. Inhibition of eIF4B suppresses the growth and induces the apoptosis of Bcr-Abl positive cells. [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 4976. doi:10.1158/1538-7445.AM2015-4976
A case of SIADH following cisplatin and 5-fluorouracil chemotherapy in a patient with esophageal cancer
Authors: Hongmei Lu, Rumiko Okamoto, Naoko Kumagai, Norikazu Miyamoto, Satoshi Monno, Naoshi Minamidate, Masaaki Hamada, Tatsuhiko Takahama
Journal: Annals of Oncology (2015)
A phase III study exploring various doses of imatinib (IM) or IM in combination for newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) patients (pts): Results of an interim analysis of the SPIRIT trial of French CML group
Authors: F. E. Nicolini, F. X. Mahon, J. Guilhot, A. Buzyn, M. Tulliez, C. Berthou, B. Christian, D. Guyotat, C. Preudhomme, F. Guilhot
Journal: Journal of Clinical Oncology (2009)

7058 Background: IM 400 mg daily is the front-line treatment of CP CML, but provides only 50% major molecular responses (MMR) at 18 months (Mo). We designed a phase III randomized multicenter open-label prospective trial comparing IM 400 mg/d (n=159) with 3 experimental arms: IM 600 mg/d (n=160), IM 400 mg/d + s/c cytarabine (Ara-C), (20 mg/m 2 /d, d15–28 of 28-day cycles) (n=158) and IM 400 mg/d + s/c Peg-IFN2a (90 μg/wk) (n=159). Pts were allocated at a 1.1.1.1 ratio, stratified by Sokal risk groups. Molecular assessments were centralized and blinded. An interim analysis of 636 pts was planned based on an IS BCR-ABL/ABL ratio &lt;0.01% (Optimal Molecular Response, OMR) at 1 year (α=0.85%, β=10%). Results: 636 pts were recruited between 9/2003 and 10/2007, median age 51 (18–78) yrs, 62% males, median follow-up for alive pts 36 (12–62) Mo. At 3 Mo, 88% of pts achieved complete hematologic response. Complete cytogenetic response (CCyR), MMR and OMR rates are presented (Table). MMR rates at 6 and 12 Mo were higher for IM-PegIFN as compared to IM-400 (p&lt;10 -3 ). At 18 Mo the cumulative OMR rates were 22% (IM-400), 28% (IM-600), 25% (IM-Ara-c), 43% (IM-PegIFN). Grade 3/4 neutropenia and/or thrombocytopenia occurred during the first year in 8% IM-400, 14% IM-600, 41% IM-Ara-C and 40% IM-PegIFN arms respectively. Grade 3/4 non-hematological toxicities occurred in 19% IM-400 (edemas, muscle cramps), 30% IM-600, 27% IM-Ara-C (diarrhea) and 31% IM-PegIFN pts (skin rashes, asthenia). Within the first 12 Mo, discontinuation of experimental treatment occurred in 8% IM-600, 39% Ara-C and 45% PegIFN pts. Conclusions: Although a significant number of pts reduced or stopped PegIFN within the first year, significant improvements in molecular response rates were observed in the IM-Peg IFN arm and may translate into survival benefit. [Table: see text] [Table: see text]