tbuckley/cabot-search huggingface dataset:
Abstract 4599: Bile acids modulate estrogen receptor β signaling through nongenomic actions in colorectal cancer
Authors: Jesse Trujillo
Journal: Cancer Research (2016)

Abstract Bile acids deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) have contrasting effects on tumor development. DCA is measurable at increased levels in the serum of colorectal adenocarcinoma patients and is associated with disease progression. DCA is also a well-established tumor promoter. On the other hand, UDCA is a chemopreventative agent revealed to suppress the recurrence of highly dysplastic polyps in a phase III clinical trial. Remarkably, retrospective investigation of the data had shown that UDCA's efficacy as a chemopreventive mediator was gender specific. UDCA significantly lowered the recurrence of advanced lesions in males, but caused a significant increase in the recurrence of advanced lesions in females. Our lab is in pursuit of understanding the gender specific chemopreventive role of UDCA. Estrogen receptor β (ERβ) has been shown to play a significant role in controlling the development of colorectal cancer. Therefore, we hypothesized that the altered regulation of the ERβ pathway by UDCA might explain the gender specificity of this molecule. In order to assess this, we analyzed the effects of UDCA on ERβ to those of the known tumor promoter DCA in both male and female human adenocarcinoma cell lines. Female HT-29 colorectal adenocarcinoma cells induced the phosphorylation of ERβ, as well as up-regulated gene expression of estrogen response elements (EREs), showing stimulated activity of this hormonal receptor. Moreover, we found that pre-treating the cells with PD98059, a MEK 1/2 inhibitor, UDCA and DCA-induced phosphorylation of ERβ, along with increased ERE gene expression, was significantly reduced. Collectively, this data suggests that UDCA and DCA can stimulate ERβ signaling through the non-genomic MAPK signaling cascade; suggesting that UDCA's gender-specific effects may be due, in part, to signaling through hormone receptors. Citation Format: Jesse Trujillo. Bile acids modulate estrogen receptor β signaling through nongenomic actions in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4599.
Syncope While Driving in Denmark
Authors: Carol Chen-Scarabelli, Tiziano M. Scarabelli
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
P1036 : Obesity, T2DM, metabolic syndrome influence mortality in NAFLD in a cohort of Mexican patients
Authors: L.A. Perez-Arredondo, P. Cordero-Perez, G. Alarcon-Galvan, R.F. Martinez-Macias, A. Silvera-Linares, L.E. Munoz-Espinosa
Journal: Journal of Hepatology (2015)
Abstract 2267: Efficacy of pemetrexed-based chemotherapy in patients with NSCLC harboring KRAS mutations
Authors: Shunsuke Okumura, Takaaki Sasaki, Shin-ichi Chiba, Masatoshi Sado, Naoyuki Miyokawa, Hiroshi Funakoshi, Yoshinobu Ohsaki
Journal: Cancer Research (2016)

Abstract [Background] Biomarkers like epidermal growth factor receptor (EGFR) gene mutations or anaplastic lymphoma kinase (ALK) rearrangement have been discovered in lung cancer, leading to targeted therapies developed in non-small cell lung cancer (NSCLC). Several oncogenes have been reported to be negative biomarkers for response to tyrosine kinase inhibitors (TKIs), for example, NSCLC with KRAS mutations are resistant to EGFR-TKIs. A preclinical study showed that KRAS mutant lung cancer cells were sensitive to pemetrexed, while a retrospective study reported that pemetrexed-based chemotherapy didn't show a favorable outcomes in patients with KRAS mutant NSCLC. We, therefore, studied efficacy of pemetrexed-based chemotherapy in patients with NSCLC, and compared the efficacy between KRAS and wild-type NSCLC. [Methods] We retrospectively studied the medical records of patients diagnosed with NSCLC between 2013 to 2015. Genomic DNA (gDNA) was extracted from FFPE tissue samples (QIAamp DNA FFPE Tissue Kit, QIAGEN). KRAS mutations were evaluated using Ion Torrent NGS systems (Ion PGM, Thermo Fischer Scientific) or PCR-rSSO. AmpliSeq Colon and Lung Cancer Research Panel v2 was used in the present study. We used Ion Reporter software for next-generation sequencing data analysis. [Results] We analyzed the data of 226 patients with NSCLC and successfully extracted gDNA from 94 tissue samples. Among them, mutation analysis by Ion PGM system was performed in 48 samples and PCR-rSSO in 46 samples. We will report response rate and progression free survival in the patients treated with pemetrexed-based chemotherapy. Citation Format: Shunsuke Okumura, Takaaki Sasaki, Shin-ichi Chiba, Masatoshi Sado, Naoyuki Miyokawa, Hiroshi Funakoshi, Yoshinobu Ohsaki. Efficacy of pemetrexed-based chemotherapy in patients with NSCLC harboring KRAS mutations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2267.
P1346 : Study protocol for a partly randomised, open-label phase IIA trial of once-daily simeprevir combined with sofosbuvir for the treatment of HCV genotype 4 infected patients with or without cirrhosis (OSIRIS)
Authors: M. El Raziky, M. Gamil, R. Hammad, M.S. Hashem, M. Hassany, M. Khairy, A. El Sharkawy, A. Gomaa, S. Keim, G. Van Dooren, R. DeMasi, I. Lonjon-Domanec, W. Doss, I. Waked
Journal: Journal of Hepatology (2015)
Abstract 3358: Expression of ALDH1, Bmi-1 and CD24 in human oral squamous cell carcinoma and its relationship with clinical factors
Authors: Tetsuya Tamatani, Natsumi Takamaru, Kenji Fujisawa, Hirokazu Nagai, Youji Miyamoto
Journal: Cancer Research (2016)

Abstract [Background] A cancer stem cell (cancer initiating cell, CSC) is considered capable of self -replication, self-differentiation, drug resistance, and immune evasion. Recently, CSC has become increasingly important in the treatment of malignant tumors. Cancer stem cells express specific molecules termed CSC marker, including aldehyde dehydrogenase (ALDH) 1, B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) and CD24, and their expression has been reported to be the potential prognostic values. However, the prognostic values of ALDH1, Bmi1, and CD24 expression in patients with oral cancer are less understood. [Purpose] The aims of present study were to evaluate the expression of ALDH1, Bmi1, and CD24 in oral squamous cell carcinoma (OSCC) and to elucidate the relationships among the CSC marker expression, clinical stages, histological differentiation, the classification of invasion mode, cerebral lymph node metastasis and disease-free survival rate. [Materials and Methods] Tissue specimens were obtains from 103 patients with OSCC after surgery or biopsy. Immunohistochemistry was used to assess ALDH1, Bmi1, and CD24 protein using at least 10% staining-positive cells as the definition of positive staining. [Results] Immunohistochemical analysis of 103 cases showed that 31 cases (30%) expressed ALDH1. There was no relationship between ALDH1 expression and clinical stages or metastasis. However, there was significant association between ALDH1 expression and histological differentiation, or classification of invasion mode or disease-free survival rate. Otherwise, 39 cases (38%) cases of 103 OSCC patients expressed Bmi-1. There was significant association between Bmi-1 expression and invasion mode or disease-free survival rate. Sixty four cases (62%) expressed CD24. There was significant association between CD24 expression and histological differentiation. [Conclusions] These findings suggested that the expression of ALDH1 and Bmi-1 as CSC markers in OSCC may be good marker indicating survival in patients with OSCC. Citation Format: Tetsuya Tamatani, Natsumi Takamaru, Kenji Fujisawa, Hirokazu Nagai, Youji Miyamoto. Expression of ALDH1, Bmi-1 and CD24 in human oral squamous cell carcinoma and its relationship with clinical factors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3358.
Extracellular vesicles released by CD40/IL-4–stimulated CLL cells confer altered functional properties to CD4+ T cells
Authors: Dawn T. Smallwood, Benedetta Apollonio, Shaun Willimott, Larissa Lezina, Afaf Alharthi, Ashley R. Ambrose, Giulia De Rossi, Alan G. Ramsay, Simon D. Wagner
Journal: Blood (2016)
Clinical activity and safety of pegylated human IL-10 (AM0010) in combination with anti-PD1.
Authors: Aung Naing, Kyriakos P. Papadopoulos, Jeffrey R. Infante, Deborah Jean Lee Wong, Karen A. Autio, Patrick Alexander Ott, Gerald Steven Falchook, Manish R. Patel, Shubham Pant, Amita Patnaik, John B Mumm, Melinda Whiteside, Ivan H Chan, Johanna C. Bendell, Todd Michael Bauer, Filip Janku, Rivka R Colen, Nizar M. Tannir, Peter Van Vlasselaer, Martin Oft
Journal: Journal of Clinical Oncology (2016)

3018 Background: IL-10 has anti-inflammatory properties but stimulates the cytotoxicity and proliferation of CD8 T cells. The observation that T cell receptor mediated activation induces the expression of IL-10 receptors and PD1 on CD8 T cells, provides the mechanistic rationale for combining AM0010 and anti-PD1 in the clinic. Tolerability and anti-tumor activity of AM0010 alone was established in the ongoing phase 1 study. Objective responses were observed in pts with uveal melanoma, cutaneous T cell lymphoma and in 4 of 15 pts with RCC. Methods: Pts with advanced melanoma, RCC or NSCLC were treated with AM0010 (daily SC) and Pembrolizumab (q3wk IV). Tumor responses were monitored following irRC. Immune responses were measured by analysis of serum cytokines, activation of blood derived T cells, peripheral T cell clonality and immunohistochemistry of tumor infiltrating CD8 T cells. Results: In 19 pts, AM0010 10 mg/kg (n=13) or 20 mg/kg (n=6) in combination with anti-PD1 (2mg/kg) was well tolerated (observation period 10-15 months). All TrAEs were transient and DLTs or TrAEs leading to study discontinuation were not observed. There was no colitis, pneumonitis, or endocrine disruptions. G3/4 TrAEs were observed in 7 of 19 pts and included pruritus (1), anemia (3), thrombocytopenia (3) and malaise (1). Objective responses (PR/CR) were observed in 4 of 8 RCC pts, 2 of 5 NSCLC pts and 2 of 6 melanoma pts. 2 additional melanoma pts had tumor increase followed by decrease (pseudoprogression). AM0010 / anti-PD1 increased Th1 cytokines (IL-18, IFNg, IL-7) and the number and proliferation of PD1+ activated CD8 T cells while decreasing the proliferation of FoxP3+ Tregs and TGFb in the blood. AM0010 / anti-PD1 induced de-novo oligoclonal expansion of T cell clones in the blood without affecting total lymphocyte counts. AM0010 / anti-PD1 increased the number of tumor infiltrating Granzyme+ PD1+ CD8+ T cells in tumor biopsies of treated patients. Conclusions: AM0010 in combination with anti-PD1 is well-tolerated. The clinical activity and the observed CD8 T cell activation encourages the continued exploration of AM0010 in combination with anti-PD1. Clinical trial information: NCT02009449.Best Response SD PR CR CBR (SD, PR, CR: > 24 weeks) RCC (n=8) 4 3 1 5 NSCLC (n=5) 3 2 - 4 Melanoma (n=6) 2 2 - 2 (NR)
Surgeon is suspended for altering dead patient’s notes retrospectively
Authors: Clare Dyer
Journal: BMJ (2016)

A UK consultant surgeon has been suspended for four months after a fitness to practise tribunal found that he had retrospectively added a line to a patient’s notes after she died, then claimed it was contemporaneous to deflect criticism.

Jose Mullerat was also found to have falsely told grieving relatives that he had ordered blood tests on Lyn O’Reilly, 57, of Tilbury, Essex, when she was still reporting pain a week after gastrointestinal surgery, at a time when she should have been ready for discharge.

O’Reilly died of peritonitis from a burst abscess after being found …
Preliminary product parameter and safety results from NeuACT, a phase 2 randomized, open-label trial of DN24-02 in patients with surgically resected HER2+ urothelial cancer at high risk for recurrence.
Authors: Dean F. Bajorin, Leonard G. Gomella, Padmanee Sharma, Elizabeth R. Plimack, Peter H. O'Donnell, Jean H. Hoffman-Censits, Thomas W. Flaig, David I. Quinn, Dwayne Campogan, Heather Haynes, Candice McCoy, Johnathan Maher, Todd DeVries, Nadeem A. Sheikh, Seth P. Lerner
Journal: Journal of Clinical Oncology (2014)

4541^ Background: DN24-02 is an investigational HER2-targeted autologous cellular immunotherapy (ACI) based on the same manufacturing platform as sipuleucel-T, an ACI approved by the FDA and EMA for certain patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. DN24-02 consists of antigen presenting cells (APC) cultured with BA7072, a recombinant HER2-derived antigen (HER500) linked to GM-CSF. NeuACT (N10-1; NCT01353222) compares the efficacy and safety of adjuvant DN24-02 to surveillance in HER2+ urothelial cancer (UC) pts at high risk of relapse after resection. Preliminary product potency, immune response and safety data are reported. Methods: Pts randomized to DN24-02 received 3 infusions at 2 week intervals. Primary endpoint is overall survival. Secondary objectives include disease-free survival, antigen-specific immune response, product potency (measured by APC activation) and safety. Results: As of November 2013, 38 pts completed DN24-02 infusions and were assessed for product potency. APC activation was observed for each infusion and the profile was indicative of a prime boost effect, with a greater magnitude at infusions 2 (median 15.26; range: 6.42–23.97) and 3 (14.69; 7.38–30.86) than 1 (6.73; 3.47–14.34). T-cell associated cytokines were greater at infusions 2 and 3 than 1. Following treatment, significant increases were observed in peripheral immune responses (p<0.01), and were comparable in pts with and without neoadjuvant chemotherapy. Adverse events (AEs) occurring in >15% of 48 pts receiving ≥1 leukapheresis were fatigue (41.7%), chills (37.5), nausea (25.0), pyrexia (18.8) and headache (16.7). Three pts had treatment-related grade ≥3 AEs or SAEs. No clinically significant changes were reported in left ventricular ejection fraction. Conclusions: This preliminary analysis suggests a pattern of DN24-02 APC activation and T-cell cytokines consistent with immunological prime-boost similar to that of sipuleucel-T. DN24-02 appears well-tolerated in UC pts, and the most common AEs are similar to those reported with sipuleucel-T. Clinical trial information: NCT01353222.
What Should Be the Target Blood Pressure in Elderly Patients With Diabetes?
Authors: Anna Solini, Ehud Grossman
Journal: Diabetes Care (2016)

Hypertension is very common in elderly subjects with type 2 diabetes. The coexistence of hypertension and diabetes can be devastating to the cardiovascular system, and in these patients, tight blood pressure (BP) control is particularly beneficial. Little information is available regarding the target BP levels in elderly hypertensive patients with type 2 diabetes, and therefore extrapolation from data in the general population should be done. However, it is difficult to extrapolate from the general population to these frail individuals, who usually have isolated systolic hypertension, comorbidities, organ damage, cardiovascular disease, and renal failure and have a high rate of orthostatic and postprandial hypotension. On the basis of the available evidence, we provide arguments supporting the individualized approach in these patients. Target BP should be based on concomitant diseases, orthostatic BP changes, and the general condition of the patients. It is recommended to lower BP in the elderly patient with diabetes to &amp;lt;140–150/90 mmHg, providing the patient is in good condition. In patients with isolated systolic hypertension, the same target is reasonable providing the diastolic BP is &amp;gt;60 mmHg. In patients with coronary artery disease and in patients with orthostatic hypotension, excessive BP lowering should be avoided. In elderly hypertensive patients with diabetes, BP levels should be monitored closely in the sitting and the standing position, and the treatment should be tailored to prevent excessive fall in BP.
Standardised surveillance of Clostridium difficile infection in European acute care hospitals: a pilot study, 2013
Authors: Sofie M van Dorp, Pete Kinross, Petra Gastmeier, Michael Behnke, Axel Kola, Michel Delmée, Anastasia Pavelkovich, Silja Mentula, Frédéric Barbut, Agnes Hajdu, André Ingebretsen, Hanna Pituch, Ioana S Macovei, Milica Jovanović, Camilla Wiuff, Daniela Schmid, Katharina EP Olsen, Mark H Wilcox, Carl Suetens, Ed J Kuijper
Journal: Eurosurveillance (2016)

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a ‘minimal’ option (aggregated hospital data), a ‘light’ option (including patient data for CDI cases) and an ‘enhanced’ option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe.
RAMÓN Y CAJAL
Journal: JAMA (1962)

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
Review of<i>Antiepileptic Drugs</i>
Authors: Mohammad Tabaeizadeh
Journal: JAMA Neurology (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 Neurology 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 Neurology journal