tbuckley/cabot-search huggingface dataset:
Abstract 2327: Placenta-derived mesenchymal stem cells and their secreted exosomes inhibit the self-renewal and stemness of glioma stem cells in vitro and in vivo
Authors: Chaya Brodie, Edrat Buchris, Susan Finniss, Simona Cazacu, Cunli Xiang, Hae Kyung Lee, Laila Poisson
Journal: Cancer Research (2015)

Abstract Mesenchymal stromal cells (MSCs) are multipotent stem cells that can be obtained from bone marrow and adipose tissues or from other sources such as placenta and umbilical cord. The latter allow the potential use of universal, allogeneic cell therapy because to reduced antigenicity due to low expression of MHC class II molecules. MSCs can be easily expanded in vitro for therapeutic applications and their safety and therapeutic impact have been demonstrated in various pre-clinical and clinical studies. MSCs have been shown to cross the blood brain barrier and migrate to sites of experimental GBM and can deliver cytotoxic compounds that exert anti-tumor effects. In this study we examined the effects of placenta-derived MSCs and their secreted exosomes on GSCs in vitro and in vivo. Conditioned medium of placenta MSCs or their derived exosomes decreased the self-renewal, stemness markers, Sox2 and Oct4 and the migration of these cells. Similarly, intracranial administration of the MSCs decreased the tumor volume of GSC-derived xenografts and prolonged animal survival. miRNA sequencing analysis of placenta MSC-derived exosomes revealed a set of specific miRNAs that were downregulated in GSCs and that acted as tumor suppressor in these cells. We demonstrated delivery of some of these miRNAs to GSCs following treatments with MSC-derived exosomes. We further demonstrated that MSCs or exosomes that were loaded with exogenous miR-124 delivered high levels of this miRNA into glioma cells as detected by a novel quantitative miRNA reporter. Moreover, administration of placenta MSCs loaded with exogenous miR-124 exerted a strong inhibitory effect on GSC-derived xenograft growth. These results demonstrate that placenta-derived MSCs may have important clinical applications in stem cell-based glioma therapeutics. Moreover, these studies provide a novel approach for the targeted delivery of endogenous and exogenous anti-tumor miRNAs to glioma cells as a miRNA replacement therapy for GBM. Citation Format: Chaya Brodie, Edrat Buchris, Susan Finniss, Simona Cazacu, Cunli Xiang, Hae Kyung Lee, Laila Poisson. Placenta-derived mesenchymal stem cells and their secreted exosomes inhibit the self-renewal and stemness of glioma stem cells in vitro and in vivo. [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 2327. doi:10.1158/1538-7445.AM2015-2327
Organ and Tumor Specificity of Colon Mucoprotein Antigen in a Rat Model
Authors: D V Gold
Journal: JNCI Journal of the National Cancer Institute (1979)

We purified a high-molecular-weight colon mucoprotein antigen (CMA) from normal F344 rat colon and from a transplantable dimethylhydrazine-induced colon carcinoma. Chemical analysis of the mucins showed similar amino acid and carbohydrate compositions. This finding was in contrast to the major differences that occurred in the composition of human CMA as a consequence of neoplasia. Immunohistochemical techniques were used in an examination of organ and tumor specificities. A New Zealand White rabbit antiserum against purified normal rat CMA, appropriately absorbed, detected a normal colon-specific determinant(s). The organ-specific determinant was lost as a consequence of neoplasia. However, a new tumor-specific determinant was then detected. CMA may have a potential role as an organ-specific marker of the neoplastic process.
Differences in lung cancer symptom severity by tertiary cancer center vs. centers treating underserved patients
Authors: G. R. Palos, Q. C. Shi, T. Mendoza, G. Mobley, Y. Zhang, V. Valero, J. Hurley, X. S. Wang, C. S. Cleeland
Journal: Journal of Clinical Oncology (2007)

19577 Background: Understanding how differences in treatment site and ethnic/racial background affect the severity and outcomes of symptoms related to advanced lung cancer is critical to providing optimal symptom management. This analysis investigated the differences in the severity of symptoms among patients receiving treatment for advanced non-small cell lung cancer (NSCLC) at three different treatment centers. Methods: We compared changes in ratings of 139 patients diagnosed with NSCLC over the course of their chemotherapy regimen for symptoms and their interference on daily activities. Eligible patients had to be diagnosed with Stage III or IV NSCLC and treated at Jackson Memorial - Dade County, LBJ - Harris County or The University of Texas M. D. Anderson Cancer Center. Data were collected using telephone and pen-paper versions of the M. D. Anderson Symptom Inventory Lung Chemotherapy Module. Mixed modeling analysis was used to examine the differences in self-reported symptom severity between black, non-Hispanic, Latino/Hispanic and white, non-Hispanic patients. Results: A total of 56 patients from all sites, matched by age and gender, were included in this sub-analysis. Because this was a relatively small sample, we combined the non-Hispanic, black (27%) and Latino/Hispanic (14%) groups to form the minority group vs. the majority group (59%). Median follow-up was 24 weeks. Inclusion of the treatment site in the model resulted in losing the effect for ethnicity for the majority of symptoms. Significant higher ratings were found for fatigue and drowsiness in white, non-Hispanic patients when compared to the minority group. We found that treatment site (tertiary vs. center treating underserved) was a significant predictor for differences in symptom severity scores. Greater symptom severity ratings were found in patients seen at centers treating the underserved for pain, sleep, fatigue, nausea, shortness of breath, appetite, drowsy, dry mouth, and numbness. Conclusions: These findings suggest that receiving treatment at a center caring for the medically underserved is associated with greater symptom burden in patients with advanced lung cancer. These results underscore the need for additional studies. No significant financial relationships to disclose.
Changing the “Working While Sick” Culture
Authors: Audrey L. Tanksley, Rachel K. Wolfson, Vineet M. Arora
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The Assessment of the Hematopoietic Reservoir After Immunosuppressive Therapy or Bone Marrow Transplantation in Severe Aplastic Anemia
Authors: Marina Podestà, Giovanna Piaggio, Francesco Frassoni, Anna Pitto, Panagiotis Zikos, Mario Sessarego, Monica Abate, Maria Teresa Van Lint, Giovanni Berisso, Andrea Bacigalupo
Journal: Blood (1998)
Isoform prefiltering improves performance of count-based methods for analysis of differential transcript usage
Authors: Charlotte Soneson, Katarina L. Matthes, Malgorzata Nowicka, Charity W. Law, Mark D. Robinson
Journal: Genome biology (2016)

RNA-seq has been a boon to the quantitative analysis of transcriptomes. A notable application is the detection of changes in transcript usage between experimental conditions. For example, discovery of pathological alternative splicing may allow the development of new treatments or better management of patients. From an analysis perspective, there are several ways to approach RNA-seq data to unravel differential transcript usage, such as annotation-based exon-level counting, differential analysis of the percentage spliced in, or quantitative analysis of assembled transcripts. The goal of this research is to compare and contrast current state-of-the-art methods, and to suggest improvements to commonly used work flows. We assess the performance of representative work flows using synthetic data and explore the effect of using non-standard counting bin definitions as input to DEXSeq, a state-of-the-art inference engine. Although the canonical counting provided the best results overall, several non-canonical approaches were as good or better in specific aspects and most counting approaches outperformed the evaluated event- and assembly-based methods. We show that an incomplete annotation catalog can have a detrimental effect on the ability to detect differential transcript usage in transcriptomes with few isoforms per gene and that isoform-level prefiltering can considerably improve false discovery rate control. Count-based methods generally perform well in the detection of differential transcript usage. Controlling the false discovery rate at the imposed threshold is difficult, particularly in complex organisms, but can be improved by prefiltering the annotation catalog.
Risks of mortality in 5 year survivors of Hodgkin’s Lymphoma (HL) in the Childhood Cancer Survivor Study (CCSS)
Authors: S. M. Castellino, J. Tooze, A. M. Geiger, W. M. Leisenring, P. Goodman, A. Mertens, M. Stovall, L. L. Robison, M. Hudson
Journal: Journal of Clinical Oncology (2008)

10006 Background: Paradoxically, HL is the paradigm of treatment success, yet HL survivors are at an increased risk of premature death. We aimed to characterize risks factors associated with mortality in a cohort of HL survivors treated in childhood. Methods: The CCSS tracks long-term outcomes in childhood cancer survivors diagnosed between 1970 and 1986. This analysis explored the impact of treatment, recurrence, second malignancies, and potential adverse treatment effects on overall survival following HL. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox proportional hazards models. Results: The CCSS includes 1,927 HL survivors followed for a median of 23 years; the median age at diagnosis is 14 years and 54% are male. There have been 320 deaths at median of 31 yrs of age; 30% are due to recurrence, 26% to second malignancy, and 19% to cardiovascular events. Because treatment patterns and causes of death varied by sex, we analyzed males and females separately in models adjusted for host demographics. Overall mortality is associated with supra- and infra-diaphragmatic radiotherapy (RT) at higher doses (≥30Gy) in males (versus chemotherapy only: HR=2.7, CI=1.1–6.9), and all doses in females (versus chemotherapy only, <30Gy: HR=6.9, CI=1.4–33.5; ≥30Gy: HR=5.2, CI=1.2–22.0). Chemotherapy regimens including anthracycline significantly impact survival in males (versus radiotherapy only: HR=3.2, CI=1.8–5.6). Second malignancies decreased survival, with a stronger effect in males (HR=6.9, CI=4.0–11.7) than females (HR=5.4, CI=3.3–8.6). Grade 3–4 cardiovascular condition was also associated with mortality (males: HR= 2.5, CI=1.3–4.7; females: HR=2.1, CI=1.0–4.4). Conclusions: Childhood HL survivors who received anthracycline therapy and higher dose, extended field RT experience increased risk for premature death long after their therapy ends. The impact of treatment on mortality varies based on host sex. No significant financial relationships to disclose.
Inhibiting TNFα with etanercept in relapsed/refractory follicular lymphoma
Authors: E. Jacobsen, A. D. Van Den Abbeele, D. Neuberg, S. Li, D. C. Fisher, J. Friedberg, A. S. Barnes, J. T. Yap, J. Kutok, A. S. Freedman
Journal: Journal of Clinical Oncology (2006)

17525 Background: Follicular dendritic cells (FDC) support the survival of follicular lymphoma (FL). TNFα is overexpressed by FL cells and TNFα plays a central role in the development and maintenance of normal FDCs. TNFα may be an ideal target for therapy due to its pleotropic effects on FDCs. Inhibition of TNFα is possible with the decoy receptor, etanercept. Methods: Patients with relapsed/refractory FL received 8 weeks of etanercept, 25 mg SC on day 1 and 4 of each week. Patients with any response or stable disease (SD) received 16 more weeks of etanercept at the same dose/schedule. 7 patients enrolled from April 2002 to September 2005. Median age was 63. All patients had stage III/IV disease and had received multiple chemotherapy regimens (median 3); 2 had prior autologous stem cell transplant. FDG-PET was performed at baseline and after 8 (scan 1, n = 7 patients) and 24 weeks on therapy (scan 2, n = 3 patients). Maximum standardized uptake values (SUVmax) were measured in up to 3 lesions per patient (n = 17 lesions for scan 1; 7 lesions for scan 2). The summation SUVmax of all lesions was calculated at each time point. The percentage (%) change in SUVmax in individual lesions and the summed SUVmax for each patient was calculated relative to baseline. The % metabolic response (mR) was assessed using EORTC thresholds for % SUVmax change (mPR ≤ −25% &lt; mSD &lt; +25% ≤ PD). Results: All patients completed at least 8 weeks of etanercept. 2 patients completed 24 weeks. 5 patients had minor or mixed responses. At the 8 week evaluation 5 patients had SD and 2 had progressive disease (PD). Of the 5 with SD, 2 progressed at 9 and 12 weeks of therapy and 3 progressed by 24 weeks. PET scan 1 showed mPR in 5/7 pts, SD in 2/7 and no PD. PET scan 2 showed mPR in 2/3 pts, mSD in 1/3 and no mPD.All patients are alive at a median of 20+ months after therapy. 1 grade 3 toxicity (lymphopenia) and 3 grade 1/2 toxicities (rhinitis/URI and 2 injection site reactions) were reported. Conclusions: Etanercept was well tolerated and minor clinical responses were observed. By EORTC criteria for metabolic response, mPR occurred in 5/7 pts, mSD in 2/7 and there was no mPD. The significant number of metabolic PR’s suggest that targeting the microenvironment with agents like etanercept may be a novel treatment approach for FL. No significant financial relationships to disclose.
The genomic basis of parasitism in the Strongyloides clade of nematodes
Authors: Vicky L Hunt, Isheng J Tsai, Avril Coghlan, Adam J Reid, Nancy Holroyd, Bernardo J Foth, Alan Tracey, James A Cotton, Eleanor J Stanley, Helen Beasley, Hayley M Bennett, Karen Brooks, Bhavana Harsha, Rei Kajitani, Arpita Kulkarni, Dorothee Harbecke, Eiji Nagayasu, Sarah Nichol, Yoshitoshi Ogura, Michael A Quail, Nadine Randle, Dong Xia, Norbert W Brattig, Hanns Soblik, Diogo M Ribeiro, Alejandro Sanchez-Flores, Tetsuya Hayashi, Takehiko Itoh, Dee R Denver, Warwick Grant, Jonathan D Stoltzfus, James B Lok, Haruhiko Murayama, Jonathan Wastling, Adrian Streit, Taisei Kikuchi, Mark Viney, Matthew Berriman
Journal: Nature Genetics (2016)

Taisei Kikuchi, Mark Viney, Matthew Berriman and colleagues report the genome sequences of six species of nematodes from the Strongyloides clade of nematodes, including human and animal pathogens, facultative parasites and a free-living species. They find that expansions of the astacin and SCP/TAPS gene families are associated with parasitism in these species. Soil-transmitted nematodes, including the Strongyloides genus, cause one of the most prevalent neglected tropical diseases. Here we compare the genomes of four Strongyloides species, including the human pathogen Strongyloides stercoralis, and their close relatives that are facultatively parasitic (Parastrongyloides trichosuri) and free-living (Rhabditophanes sp. KR3021). A significant paralogous expansion of key gene families—families encoding astacin-like and SCP/TAPS proteins—is associated with the evolution of parasitism in this clade. Exploiting the unique Strongyloides life cycle, we compare the transcriptomes of the parasitic and free-living stages and find that these same gene families are upregulated in the parasitic stages, underscoring their role in nematode parasitism.
Factors influencing outcome in advanced stage, low-grade follicular lymphoma treated at MD Anderson Cancer Center in the rituximab era
Authors: C.Y. Cheah, D. Chihara, M. Ahmed, R.E. Davis, L.J. Nastoupil, K. Phansalkar, F.B. Hagemeister, L.E. Fayad, J.R. Westin, Y. Oki, M.A. Fanale, J.E. Romaguera, M.L. Wang, H. Lee, F. Turturro, F. Samaniego, M.A. Rodriguez, S.S. Neelapu, N.H. Fowler
Journal: Annals of Oncology (2016)
Conditioned media from BMSC attenuate endoplasmic reticulum stress in alveolar epithelial cells invitro
Authors: Izabela Nita, Amiq Ur Rahman Gazdhar, Katrin Hostettler, Zhong Jun, Micheale Roth, Thomas Geiser
Journal: European Respiratory Journal (2014)

Introduction Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive lung disorder of unknown etiology. Evidence of endoplasmic reticulum (ER) stress has been found in IPF patients. In this study we investigate possible effects of Bone Marrow Stromal Cell conditioned media (BMSC-cm) on ER stress and wound healing in alveolar epithelial cells line (AEC) and IPF primary cells. Methods ER stress was induced by growing A549 cells in Tunicamycin (TN) 3µg/ml for 24 h. Continuous the cells were treated with BMSC-cm or control media for 24h. qRT PCR was performed for analysis of ER stress markers: Grp78, XBP1 and CHOP and the wounds were measured at 0h, 24h. IPF primary cells were treated with BMSC-cm or control media and analyzed. BMSC-cm was treated by blocking HGF antibody and the analysis was repeated. Results Gene expression level of Grp78 in A549 was reduced after BMSC-cm treatment at 24h compared to controls (3.03±0.36 vs 4.86±0.76). Similarly, the spliced variant of XBP1 (4.07±0.41vs 5.42±0.51) and CHOP levels (10.13±1.39 vs 1.74±1.07) were diminished after BMSC-cm compared to controls. Furthermore, the percentage of alveolar wound repair was increased in presence of BMSC-cm in ER stressed cells as compared to controls at 24h (48.50%±5.1 vs 20.34%±2.51). In primary IPF cells similar reduction in gene expression of ER stress markers was observed. Conclusions BMSC-cm increases alveolar epithelial wound healing, possibly by reducing ER stress in AEC. Since ER stress predisposes to AEC dysfunction and subsequent lung fibrosis, our study emphasize that ER stress inhibition may serve as important therapeutic target in IPF, perhaps by BMSC-cm and probably by rHGF involved.
Abstract 18125: Left Ventricular Radial Strain Improvement After Surgery for Ebstein’s Anomaly
Authors: Krong-on Pinyoluksana, Garvan Kane, Benjamin Eidem, Hector Villarraga, Joseph Dearani, Heidi Connolly, Naser Ammash
Journal: Circulation (2013)

Background: Impact of right ventricular (RV) overload on left ventricular (LV) performance has been demonstrated in Ebstein’s anomaly (EA). We have shown that LV radial strain (RS) in 83 EA patients was significantly less than in controls. We subsequently sought to evaluate LV strain after EA surgery. Methods: Systolic strain, strain rate (SR) and early diastolic strain rate (SRe) were retrospectively performed, using velocity vector imaging, in 24 repaired EA patients (age 35 ±12 years; 67% women) with LV ejection fraction &gt;50%, preoperatively (median 5 days [1-145 days]) and postoperatively within 5 years at sequential follow-up (6 months-3 years). Repair of EA included tricuspid valve repair, valve replacement and bidirectional cavopulmonary anastomosis. A slope of change postoperatively was estimated for each subject using linear regression. A one-sample t-test of the mean slope=0 assessed average change per year. Results: Mean (standard deviation) and median (range) of preoperative LV RS was 36.5 +/- 11.4% and 36.3% (16.8-59.8) respectively. LV strain analyses are summarized in tables 1 and 2. Conclusions: LV RS improved significantly after EA surgery whereas circumferential strain (CS), SR and radial SR did not. This may reflect the change in RV and subsequently LV geometry after resolution of tricuspid regurgitation with EA surgery. Ongoing evaluation with deformational imaging may help to characterize if these changes are compensatory or maladaptive and may determine optimal timing for surgery. In the subgroup with the lowest RS, significant improvement postoperatively was not seen. This may suggest that surgery was performed too late to allow favorable remodeling.
Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins
Authors: E.J. Giamarellos-Bourboulis, N. Tziolos, C. Routsi, C. Katsenos, I. Tsangaris, I. Pneumatikos, G. Vlachogiannis, V. Theodorou, A. Prekates, E. Antypa, V. Koulouras, N. Kapravelos, C. Gogos, E. Antoniadou, K. Mandragos, A. Armaganidis
Journal: Clinical Microbiology and Infection (2016)

The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26–0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p <0.0001). Results favour the use of IgGAM as an adjunct to antimicrobial treatment for the management of septic shock caused by MDR Gram-negative bacteria. A prospective randomized trial is warranted.