tbuckley/cabot-search huggingface dataset:
Self nano-emulsifying drug delivery system for Embelin: Design, characterization and in-vitro studies
Authors: Komal Parmar, Jayvadan Patel, Navin Sheth
Journal: Asian Journal of Pharmaceutical Sciences (2015)

CThe objective of the present study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing Capryol-90 as oil phase for the delivery of Embelin, a poorly water soluble herbal active ingredient. Box-Behnken experimental design was employed to optimise the formulation variables, X1 (amount of oil; Capryol 90), X2 (amount of surfactant; Acrysol EL 135) and X3 (amount of co-surfactant; PEG 400). Systems were appraised for visual characteristics for self emulsifying time, globule size and drug release. Optimised liquid formulations were formulated into free flowing granules (S-SNEDDS) by adsorption on the porous materials like Aerosil 200 and Neusilin and thereby compressed into tablet. In vitro dissolution studies of SNEDDS revealed increased in the dissolution rate of the drug. FT-IR data revealed no physicochemical interaction between drug and excipients. Solid state characterization of S-SNEDDS by DSC and Powder XRD confirmed reduction in drug crystallinity which further supports the results of dissolution studies. TEM analysis exhibited spherical globules. Further, the accelerated stability studies for 6 months revealed that S-SNEDDS of Embelin are found to be stable without any significant change in physicochemical properties. Thus, the present studies demonstrated dissolution enhancement potential of porous carrier based S-SNEDDS for poorly water soluble herbal active ingredient, Embelin.
Abstract P144: ER Stress-Mediated Reduction of SERCA2a Protein Is Not Involved in Increase in Lethal Heart Failure After Myocardial Infarction in Obese Type 2 Diabetes
Authors: Tatsuya Sato, Akifumi Takada, Takayuki Miki, Masaya Tanno, Atsushi Kuno, Hidemichi Kouzu, Takahito Itoh, Daisuke Sunaga, Tetsuji Miura
Journal: Circulation Research (2011)

Rationale: Our previous studies showed that increased endoplasmic reticulum (ER) stress in the myocardium impairs cytoprotective signaling in obese type 2 diabetes mellitus (T2DM). Objective: We examined roles of ER stress in alterations of ventricular function and mortality after myocardial infarction by T2DM. Methods and Results: SERCA2a protein level was significantly lower by 45% and Ser16- and Thr17-phosphorylated phospholamban levels tended to be lower in a rat model of T2DM (OLETF) than those in non-diabetic control rats (LETO). Treatment with an ER stress modulator, 4-phenylbutyric acid (4-PBA) or tauroursodeoxycholic acid (TUDCA), restored SERCA2a protein in OLETF to the level of that in LETO. Although left ventricular (LV) ejection fractions were comparable in OLETF and LETO, LV end-systolic elastance (1685±86 vs. 1953±68 mmHg/ml) and LVdP/dtmax (5886±337 vs. 7389±457 mmHg/s) were lower and tau was larger (12.1±0.9 vs. 8.9±0.8 msec) in OLETF. These impairments of LV function in OLETF were restored by treatment with 4-PBA (LV end-systolic elastance: 1813±58 mmHg/ml, LVdP/dtmax: 7053±546 mmHg/s and tau: 8.5±0.5 msec). Elevation of LV systolic pressure and dP/dtmax levels by dobutamine infusion was reduced, and inhibitory effects of verapamil on the dobutamine-induced positive inotropism were blunted in OLETF. In patch-clamp experiments using isolated cardiomyocytes, increase in L-type Ca 2+ channel current after isoproterenol treatment was markedly attenuated in OLETF as compared with the change in LETO. Mortality rate within 48 hrs after myocardial infarction was significantly higher in OLETF than in LETO (64.0% vs. 7.7%). Telemetric recording indicated that rapid progression of heart failure but not arrhythmia was responsible for the high mortality rate in OLETF. In contrast to the improvement of baseline ventricular dysfunction, neither 4-PBA nor TUDCA significantly reduced mortality rate after infarction in OLETF. Conclusions: ER stress plays a major role in reduction of SERCA2a by T2DM. Blunted response of cardiac L-type Ca 2+ channels to adrenoceptor activation, rather than reduced SERCA2a, may contribute to increase in lethal heart failure after myocardial infarction in T2DM.
Recombinant adenoviral human p53 gene combined with radio- and chemotherapy in treatment of advanced nasopharyngeal carcinoma: A randomized clinical study.
Authors: Guiping Lan, Yongfeng SI, Yangda Qin, Zhuoxia Deng, Chengcheng HE, Bo Huang, Jinlong LU
Journal: Journal of Clinical Oncology (2012)

5558 Background: Studies showed p53 gene therapy could enhance the anti-tumor effect of both chemo- and radiotherapy. The anti-tumor function of p53 gene is associated with up-regulated expression of p21 and Bax. Here, we investigate the beneficial role of recombinant adenoviral human p53 gene (rAd-p53) combined with chemoradiotherapy in treatment of advanced nasopharyngeal carcinoma (NPC), and p21 and Bax protein expression in pre- and post-treatment tumor tissues. Methods: Sixty-three patients with historically-diagnosed advanced NPC, with ECOG performance status less than 2, life expectancy greater than 3 months and adequate organ function tests, were randomly assigned into two groups: 32 in experimental group (EG) and 31 in control group (CG). EG received intratumoral injection of 1×10 12 rAd-p53 viral particles (VP) per 3 days for 6-8 times, carboplatin 300 mg/m 2 on day1 and continuous infusion of a total dose of 2000 mg/m 2 of 5-Fu on day1-5 for 3 cycles, and radiotherapy at a dose of 2Gy/fraction for a total dose of 70-76 Gy/35-38f. CG received the same chemo- and radiotherapy. Pre- and post-treatment tissue samples were analyzed for Bax and p21 protein levels. Results: The median follow-up time was 28 months. EG achieved a complete response rate (CR) of 62.5% and overall response rate (RR) of 90.6%, both rates being statistically significantly higher than that of CG (CR=35.5%, RR=74.2%). One-year of overall survival (OS) was 100.0% for EG and 90.3% for CG, and one year of progress free survival (PFS) was 96.7% and 77.4% for EG and CG, respectively. Two-year OS was 95.7% and 86.4% for EG and CG, respectively, and two-year of PFS was 79.6% and 73.5% for EG and CG, respectively. After treatment, both Bax and p21 protein levels in EG increased significantly. In CG, both proteins levels also increased after treatment but not significantly. The main side effects of rAd-p53 were self-limited fever, occurring in all of EG patients. Conclusions: RAd-p53 as a component of the comprehensive therapy for advanced NPC contributes significant beneficial effects. Increased levels of Bax and p21proteins after treatment represent two mechanisms of p53 anti-tumor activities.
A closer look at next generation sequencing (NGS) in breast cancer: A retrospective analysis.
Authors: Bahar Laderian, ANA CRISTINA Sandoval Leon, Loulwa Alsharhan, Dorraya El Ashry, Marc E. Lippman
Journal: Journal of Clinical Oncology (2017)

e13023 Background: Targeted cancer therapy has been posited to revolutionize treatment paradigms in oncology. There are, a paucity of data regarding the use of NGS in breast cancer (BC). Herein we report our experience with NGS in a consecutive series of BC patients. Methods: Using an IRB approved protocol, we retrospectively identified patients with BC treated at the Sylvester Comprehensive Cancer Center (UMMSOM) who underwent NGS. Data were collected on demographics, tumor characteristics, genomic mutation profiles, and subsequent response to targeted therapy after 3 months. Results: Between January 2013 and April 2016, 101 BC patients underwent NGS. The mean age at diagnosis was 49. Ninety-one percent were stage IV, 6% were stage III, 2% were stage II, and 1% were stage I. Fifty percent had estrogen receptor (ER)+, HER2- tumors, 31% had triple-negative tumors, 13% had HER2+, ER+ tumors, and 6% had HER2+, ER- tumors. Ninety-six percent had at least one mutation, of which 78% had a targetable mutation. Sixteen patients received targeted therapy (TT). The average time between NGS and TT was 5 months ranging 0-22 months, during which seven patients received other systemic therapy. The most common reasons for not receiving TT were no actionable mutations (24%), not meeting criteria for an available clinical trial (14%), stable disease (SD) (13% ), lost to follow up (11%), physician decision (11%). Of the 16 patients who received TT, 7 patients had progression of disease, 3 died before response could be evaluated and presumably had no benefit, 2 discontinued TT due to side effects, 1 had SD, 1 had a partial response, and 2 were too early to be assessed. Conclusions: The majority of BC patients in our series had actionable mutations. However, TT was not offered to a significant number of patients for a multiplicity of reasons and the clinical benefit in those patients treated according to NGS findings was dismal. While NGS is surely a promising technology that should be utilized in combination with molecular tumor board, a host of reasons limit its usefulness at this time and its expense may well not justify its use outside of clinical trials.
LncRNA ODRUL Contributes to Osteosarcoma Progression through the miR-3182/MMP2 Axis
Authors: Kun-Peng Zhu, Xiao-Long Ma, Chun-Lin Zhang
Journal: Molecular Therapy (2017)

Recent findings have shown that lncRNA dysregulation is involved in many cancers, including osteosarcoma (OS). In a previous study, we reported a novel lncRNA, ODRUL, that could promote doxorubicin resistance in OS. We now report the function and underlying mechanism of ODRUL in regulating OS progression. We show that ODRUL is upregulated in OS tissues and cell lines and correlates with poor prognosis. ODRUL knockdown significantly inhibits OS cell proliferation, migration, invasion, and tumor growth in vitro and in vivo by decreasing matrix metalloproteinase (MMP) expression. A microarray screen combined with online database analysis showed that miR-3182 is upregulated and MMP2 is downregulated in sh-ODRUL-expressing MG63 cells and that miR-3182 harbors potential binding sites for ODRUL and the 3' UTR of MMP2 mRNA. In addition, miR-3182 expression and function are inversely correlated with ODRUL expression in vitro and in vivo. A luciferase reporter assay demonstrated that ODRUL could directly interact with miR-3182 and upregulate MMP2 expression via its competing endogenous RNA activity on miR-3182 at the posttranscriptional level. Taken together, our study has elucidated the role of oncogenic ODRUL in OS progression and may provide a new target in OS therapy.
Anti-tumor activity of PEGylated human IL-10 (AM0010) in patients with pancreatic or colorectal cancer.
Authors: Kyriakos P. Papadopoulos, Aung Naing, Jeffrey R. Infante, Karen A. Autio, Patrick Alexander Ott, Deborah Jean Lee Wong, Gerald Steven Falchook, Manish R. Patel, Shubham Pant, Melinda Whiteside, John B Mumm, Ivan H Chan, Johanna C. Bendell, Drew W. Rasco, Kent C. Shih, Milind M. Javle, Todd Michael Bauer, Rivka R Colen, Peter Van Vlasselaer, Martin Oft
Journal: Journal of Clinical Oncology (2016)

3082 Background: IL-10 induces activation of STAT3 in CD8 T cells leads to increased survival, proliferation and cytotoxicity of CD8 T cells. In preclinical studies, PEG-IL-10 induces CD8 mediated tumor rejection and synergizes with cytotoxic chemotherapies. Anti-tumor activity of AM0010 alone was established in the ongoing phase 1 basket trial. Objective responses were observed in pts with renal cell cancer (RCC; 4 of 15pts), uveal melanoma and cutaneous T cell lymphoma. Methods: Pts with advanced pancreatic cancer (PDAC) were treated daily with AM0010 alone (n = 24) or in combination with FOLFOX (5), capecitabine (5) or gemcitabine/nab-paclitaxel (6). Pts with colorectal cancer (n = 16) were treated with AM0010 alone. Tumor responses were monitored following irRC. Immune responses were monitored through analysis of serum cytokines, activation of blood derived T cells, immunosequencing for peripheral T cell clonality and immunohistochemistry for the infiltration of tumors by CD8 T cells. Results: In 24 PDAC pts and 16 CRC pts treated with AM0010 monotherapy (1-20 mg/kg), G3/4 TrAEs were observed in 16 pts, including anemia (5), thrombocytopenia (9), fatigue (2) rash (3) and transaminitis (1). Most TrAEs were transient, only one patient discontinued treatment due to anemia. Colitis, pneumonitis or endocrine abnormalities were not observed. In 16 pts with PDAC treated with AM0010 plus chemotherapy, TrAEs were observed in 11 pts, including thrombocytopenia (10). At 8 weeks, 8 of 17 pts with PDAC and in 4 of 15 pts with CRC on AM0010 alone had stable disease (SD). 11 of 15 PDAC pts had a reduction of CA 19-9. 4 patients (3 PDAC, 1 CRC) had prolonged PFS > 6 months. The median overall survival of PDAC was 5.1 months (n = 20), and CRC was 15.4 months (n = 13; observation > 15mo). 13 of 15 PDAC pts treated with AM0010 and chemotherapy had SD, 2 had a PR. AM0010 increased PD-1+ activated CD8 T cells and the de-novo oligoclonal expansion of T cell clones in the blood. AM0010 increased tumor infiltrating Phospho STAT3+, Granzyme+ and PD1+ CD8+ T cells in tumors. Conclusions: The preliminary clinical activity and the mechanistic data indicating enhanced immune stimulation encourages continued exploration of AM0010 in “immune resistant” cancers. Clinical trial information: NCT02009449.
Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring
Authors: Margareta H. Lejonklou, Linda Dunder, Emelie Bladin, Vendela Pettersson, Monika Rönn, Lars Lind, Tomas B. Waldén, P. Monica Lind
Journal: Environmental Health Perspectives (2017)

Background: Bisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive. Objectives: The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring. Methods: Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to 0.5μg/kg BW/d (BPA0.5; n=21) or 50μg/kg BW/d (BPA50; n=16), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (n=26). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring. Results: Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels (0.81±0.10 mmol/L compared with 0.57±0.03 mmol/L, females BPA50 p=0.04; 0.81±0.05 mmol/L compared with 0.61±0.04 mmol/L, males BPA0.5 p=0.005) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls (68.2±4.4 number of adipocytes/HPF compared with 55.9±1.5 number of adipocytes/HPF; p=0.03) and by 123% in BPA0.5 females compared with BPA50 animals (68.2±4.4 number of adipocytes/high power field (HPF) compared with 55.3±2.9 number of adipocytes/HPF; p=0.04). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals (69.9±5.1 number of adipocytes/HPF compared with 54.0±3.4 number of adipocytes/HPF; p=0.03). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex. Conclusions: Developmental exposure to 0.5μg/kg BW/d of BPA, which is 8–10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of 4μg/kg BW/d and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at 0.5μg/kg BW/d were compared with the offspring of unexposed controls. https://doi.org/10.1289/EHP505
NHS bosses soften cost cutting plans in response to concerns
Authors: Gareth Iacobucci
Journal: BMJ (2017)

NHS bosses have softened controversial cost cutting plans that could have forced hospitals to delay operations and close wards, after warnings that patients would suffer from the scale of the cuts.

The sector regulator NHS Improvement (NHSI) and NHS England recently ordered 14 financially stricken areas of England to submit radical cost savings plans in a bid to bring their budgets under control. Earlier this month the Health Service Journal reported that closing wards, extending …
Two-step endoscopic radiofrequency ablation for metastatic cholangiocarcinoma
Authors: Monica Saumoy, Enad Dawod, Ming Xu, Michel Kahaleh
Journal: Endoscopy (2017)

A 58-year-old woman with cholangiocarcinoma previously treated with partial hepatectomy with Roux-en-Y gastric bypass, presented with worsening jaundice. Despite chemotherapy, the patient was diagnosed with tumor obstructing the hepaticojejunostomy and associated intrahepatic biliary ductal dilation. She was referred for endoscopic retrograde cholangiopancreatography (ERCP) with intraductal radiofrequency ablation (RFA). However, conventional ERCP failed because of her altered anatomy. She was offered two-step RFA therapy ([Video 1]).
RETRACTED: The YY1-HOTAIR-MMP2 Signaling Axis Controls Trophoblast Invasion at the Maternal-Fetal Interface
Authors: Yan Zhang, Feng Jin, Xiao-Cui Li, Fu-Jin Shen, Xiao-Ling Ma, Fan Wu, Si-Ming Zhang, Wei-Hong Zeng, Xiao-Rui Liu, Jian-Xia Fan, Yi Lin, Fu-Ju Tian
Journal: Molecular Therapy (2017)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the editors. After investigating concerns of image duplication raised by a reader, evidence for image duplication in identical or altered fashion in Figures 2D, 3H, and 5C was identified. This reuse (and in part misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. Retraction Notice to: The YY1-HOTAIR-MMP2 Signaling Axis Controls Trophoblast Invasion at the Maternal-Fetal InterfaceZhang et al.Molecular TherapyMarch 02, 2022In Brief(Molecular Therapy 25, 2394–2403; October 2017) Full-Text PDF Open Archive
ERCP Service Provision – An Analysis of South Eastern Referral Patterns
Authors: D Prichard, G Cullen, AR Aftab, G Courtney
Journal: Endoscopy (2006)

Background: There is a dearth of information on the uptake of ERCP services or the occurrence of choledocholithiasis or pancreaticobiliary cancer by region and county in Ireland, which would be important in planning service provision nationally.
A permanent US-Mexico border environmental health commission. Council on Scientific Affairs
Journal: JAMA (1990)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Prognostic but not predictive: focus on stage II right-sided colorectal cancer tumors
Authors: Andrea Palloni, Aurelia Barbera Maria, Giorgio Frega, Manuela Ferracin, Maria Massucci, Francesca Abbati, Veronica Mollica, Giovanni Brandi, Guido Biasco, Ingrid Garajová
Journal: Annals of Oncology (2017)
An Evaluation of Lower Oesophageal Sphincter Dynamics during Intraluminal Oesophageal Manometry
Authors: SM Taylor, P Byrne, P Lawor, P Moran, P MacMathuna
Journal: Endoscopy (2006)

Aims: To characterize LOS dynamics. Lower oesophageal sphincter (LOS) pressure during routine intraluminal oesophageal manometry (IOM) varies within the same individual. This may be related to catheter orientation and / or intrinsic variability over time.
Acupuncture and the Complex Connections Between the Mind and the Body
Authors: Josephine P. Briggs, David Shurtleff
Journal: JAMA (2017)

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