tbuckley/cabot-search huggingface dataset:
Inflammatory markers in metastatic breast cancer.
Authors: Ugur Sahin, Hilbrahim Petekkaya, Gizem Gecmez, Taner Babacan, Emir C. Roach, Saim Furkan Sarici, Cagatay Arslan, Zafer Arik, Sercan Aksoy, Kadri Altundag
Journal: Journal of Clinical Oncology (2013)

e11545 Background: The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The aim of this study is to find out the importance of serum markers as a prognostic indicator in metastatic breast cancer Methods: Women with metastatic breast cancer at the time of diagnosis were included. The study was conducted in Hacettepe University, Institute of Oncology, Department of Medical Oncology. Patient data were collected between December 2009 and January 2013. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value of &lt; 0.05 was considered statistically significant. Results: Median follow-up time was 26 months. There were 29 mortalities due to disease progression during the follow up. The levels of serum albumin, ESR and LDH were not associated with a significant effect on overall survival. Among patients with a higher serum CRP estimated median survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p = 0.49). Among patients with higher serum ferritin levels estimated median survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p = 0.01). Among patients with higher serum beta-2 microglobulin estimated median survival was 28±8 months, compared to 84±57 months for normal levels (p&lt;0.01). Conclusions: Serum CRP, ferritin and beta-2 microglobulin can be useful prognostic factors for overall survival among metastatic breast cancer patients.
a Phase I Trial of Bendamustine in Combination with Clofarabine and Etoposide in Pediatric Patients with Relapsed or Refractory Hematologic Malignancies
Authors: Sima Jeha, Monika L. Metzger, Kristine R Crews, Patrick Campbell, Raul C. Ribeiro, Cheng Cheng, Melissa Peyton, Carl Panetta, Jun Yang, Ching-Hon Pui, Deepa Bhojwani
Journal: Blood (2016)
OC-056 Long-Term Trends in Comorbidity and Risk Scores and their Influence on outcomes of upper Gastrointestinal Bleeding: Abstract OC-056 Table 1
Authors: A S Taha, E Saffouri, C McCloskey, T Craigen, W J Angerson
Journal: Gut (2013)

<h3>Introduction</h3> The prevention of upper gastrointestinal bleeding (UGIB) can be facilitated by understanding the changes in environmental and socio-pathological factors; these might not become obvious in short-term studies. We, therefore, aimed to study the changes in comorbidity and risk scores and their influence on the outcomes of UGIB over a 14-year period. <h3>Methods</h3> We analysed the clinical characteristics of all patients presenting with UGIB to a single institution, 1996–2010. The Charlson’s comorbidity and the complete Rockall scores were analysed, together with patients’ drug use and 30-day mortality. Trends with time were assessed using logistic regression analysis with year of presentation as a continuous predictor variable. Regression coefficients were expressed as odds ratios (OR), representing the relative change in odds of death or other binary dependent variables over a time interval of one year. <h3>Results</h3> A total of 2669 patients were included. The Charlson score increased significantly with time (P &lt; 0.001), the odds of a high (3+) score increasing at a relative rate of 4.4% a year (OR = 1.044, 95% CI 1.022–1.065). No significant trend with time was noted for age (p = 0.09), haemoglobin level (P = 0.47) or Rockall score (P = 0.94). The overall 30-day mortality was 4.9% and this showed no relationship with time (P = 0.28). However, when adjusted for the increasing comorbidity, the odds of death within 30 days decreased significantly at a relative rate of 4.5% per year [OR = 0.955 (0.914–0.997); P = 0.038]. Trends in the prevalence of taking potentially damaging and protective drugs are shown in Table-1, below. The rise in use of aspirin, other anti-thrombotic drugs and SSRIs [with pro-UGIB activity] was paralleled by a rise in the use of PPIs [protective activity] and beta-blockers, ACE inhibitors, and statins [being able to affect mortality. <h3>Conclusion</h3> Patients with UGIB presented with progressively increasing comorbidity over the 14-year period 1996–2010. The use of both potentially damaging and protective drugs also increased. Raw 30-day mortality was unchanged over the same period, but decreased significantly with time when adjusted for comorbidity. These observations might have clinical implications. <h3>Disclosure of Interest</h3> A. Taha Consultant for: Horizon Pharma USA; Vifor Pharma UK, E. Saffouri: None Declared, C. McCloskey: None Declared, T. Craigen: None Declared, W. Angerson: None Declared
Abstract 30: 4-PBA Prevents TAC-induced Myocardial Hypertrophy and Interstitial Fibrosis by Attenuating ER Stress in Mice
Authors: Tao Luo, Baihe Chen, Xianbao Wang
Journal: Circulation Research (2015)

Background: Recently, 4-phenylbutyric acid (4-PBA) has been recognized as a potent ER stress inhibitor and a histone deacetylase inhibitor, but its therapeutic effect in cardiovascular diseases is still not fully understood. Our previous study indicated that attenuation of ER stress by administration of low dosage of 4-PBA (20 mg/kg/d) prevented post-infarction-induced cardiac rupture and remodeling through modulating both cardiac apoptosis and fibrosis in the mouse model of myocardial infarction. However, little is known whether the administration of 4-PBA is effective for hypertrophic heart disease. The aim of this study is therefore to test the therapeutic effect of 4-PBA on pressure-overload induced myocardial hypertrophy. Methods and Results: Transverse aortic constriction (TAC) was used to produce pressure-overload in C57BL/6 male mice for 4 weeks. After surgery, 4-PBA (20mg/kg/d) or 0.9% NaCL was intraperitoneally injected daily. At the end of 4 weeks, the survivals were underwent high-resolution echocardiographic imaging observation. The results showed that the left ventricular posterior wall thickness at end systole (LVPWs) and left ventricular posterior wall thickness at end diastole (LVPWd) were increased in TAC group. Administration of 4-PBA ameliorated this hypertrophic effect. Autopsy also confirmed the anti-hypertrophic effect of 4-PBA. Masson-staining found that there was no difference in perivascular fibrosis between TAC and TAC+4-PBA groups. However, myocardial interstitial fibrosis and collagen deposition were significant decreased by 4-PBA. We finally detected the ER stress and histone acetylation using western blotting. Our results showed that 4-PBA, at the dosage of 20 mg/kg/day, decreased the expression of CHOP and had no effect on histone 3 acetylation. Conclusion: These findings indicate that attenuating ER stress by 4-PBA maybe a promising therapeutic strategy to prevent pressure-overload induced myocardial hypertrophy and interstitial fibrosis.
The Authors' reply
Authors: G. Grazzini, M. Zappa, L. Ventura, T. Rubeca, S. P. Halloran
Journal: Gut (2010)

The Authors' reply It is likely that Dr Guittet and colleagues1 are correct in their assertion that a reduction in haemoglobin (Hb) concentration due to in vitro degradation will have a disproportionately large effect on the detection of the small bleeds characteristic of intermediate and high-risk adenomas.2

As the impetus for worldwide …
Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy
Authors: Nicholas D. James, Johann S. de Bono, Melissa R. Spears, Noel W. Clarke, Malcolm D. Mason, David P. Dearnaley, Alastair W.S. Ritchie, Claire L. Amos, Clare Gilson, Rob J. Jones, David Matheson, Robin Millman, Gerhardt Attard, Simon Chowdhury, William R. Cross, Silke Gillessen, Christopher C. Parker, J. Martin Russell, Dominik R. Berthold, Chris Brawley, Fawzi Adab, San Aung, Alison J. Birtle, Jo Bowen, Susannah Brock, Prabir Chakraborti, Catherine Ferguson, Joanna Gale, Emma Gray, Mohan Hingorani, Peter J. Hoskin, Jason F. Lester, Zafar I. Malik, Fiona McKinna, Neil McPhail, Julian Money-Kyrle, Joe O’Sullivan, Omi Parikh, Andrew Protheroe, Angus Robinson, Narayanan N. Srihari, Carys Thomas, John Wagstaff, James Wylie, Anjali Zarkar, Mahesh K.B. Parmar, Matthew R. Sydes
Journal: New England Journal of Medicine (2017)

Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design.
Prediction of treatment response in subtypes of non-Hodgkin's lymphoma by in vivo <sup>31</sup>P MR spectroscopy before treatment
Authors: F. Arias-Mendoza, M. O. Leach, J. A. Koutcher, J. R. Griffiths, A. Heerschap, J. D. Glickson, O. A. O'Connor, T. R. Brown
Journal: Journal of Clinical Oncology (2009)

8565 Background: To determine if the intracellular tumor marker of phosphoethanolamine plus phosphocholine normalized by nucleotide triphosphates (PPN) monitored non-invasively by phosphorus MR spectroscopy ( 31 P-MRS) correlate with indicators of treatment response in non-Hodgkin's lymphoma (NHL) subtypes. Methods: The PPN value was obtained in 33 diffuse large B-cell lymphomas (DLBCL), 18 follicular lymphomas (FL) and 16 other types (OT) of NHL using in vivo 3D-localized, 1 H-irradiated 31 P-MRS prior to standard treatment. Results: The PPN values (mean ± standard error) for complete responses (CR) and not complete responses (NCR) in DLBCL were significantly different (CR: 1.42±0.10, n=19 and NCR: 2.25±0.15, n=14; p&lt;0.00002). A Fisher test with a cutoff maximizing PPN sensitivity and specificity (1.78) showed a p&lt;0.004 (sensitivity=0.6, specificity=1.0). Further, when the PPN was combined with the international prognostic index (IPI) to predict treatment response, the Fisher test increased significance (p&lt;0.0002; sensitivity and specificity=0.9). In addition, the two groups dichotomized by the PPN-IPI combination showed a significant difference for drug-free survival (p&lt;0.0001)with one group with survival below 20 months. FL patients did not show PPN significance (CR: 1.40±0.16, n=4 and NCR: 1.75±0.15, n=14). Although this could be due to the lower number of patients, the mean PPN value of the NCR group of FL was significantly lower than that of DLBCL (p&lt;0.01). In the OT group there was only one CR observation but the PPN of its NCR cases was 2.51±0.25, n=13. This value was not significantly different from that of DLBCL but was against that of FL (p&lt;0.007). Conclusions: Our results show that: 1) the pretreatment PPN can predict treatment response in DLBCL identifying a group of DLBCL patients with DFS below 20 months; 2) FL and DLBCL showed distinctive metabolic behaviors; and 3) the number of CR cases was low for FL and OT limiting analysis of PPN until larger cohorts of patients are accrued. No significant financial relationships to disclose.
Human Subjects Protection and Cancer Surveillance Research: Revised Regulations, Expanded Opportunities
Authors: Robert H. McLaughlin, Scarlett Lin Gomez, Dennis Deapen, Marta Induni
Journal: Cancer Research (2017)

On January 19, 2017, the United States federal government issued revisions to the Common Rule under which scientists who receive federal funding conduct research involving human subjects. The revised Common Rule expressly addresses public health surveillance in relation to scientific research and the protection of human subjects, and its impacts are anticipated to contribute to the efficiency of activities, including cancer registration and surveillance, and research that uses cancer registry data. Cancer Res; 77(12); 3140-3. ©2017 AACR.
Toward Molecularly Driven Precision Medicine in Lung Adenocarcinoma
Authors: David Liu, Natalie I. Vokes, Eliezer M. Van Allen
Journal: Cancer Discovery (2017)

Abstract Summary: Assessing the benefit of routine panel-based genomic sequencing of tumor tissue remains a critical need in clinical oncology. Jordan and coauthors report on 860 patients with metastatic or recurrent lung adenocarcinoma from a single institution with prospectively sequenced tumors using a targeted gene panel of &amp;gt;300 genes to guide therapy. Their results suggest that early prospective tumor sequencing, including non–standard-of-care predictive biomarkers combined with careful clinical annotation, can guide therapy, improve clinical outcomes, and accelerate the development of biomarkers and drugs. Cancer Discov; 7(6); 555–7. ©2017 AACR. See related article by Jordan et al., p. 596.
High cytoplasmic relative to membranous Met is a prognostic indicator in early stage colon cancer.
Authors: Michael Montalto, Sudeshna Adak, Ali Can, Michael Gerdes, Robert Filkins, Melinda Larsen, Ginty Fiona
Journal: Clinical Cancer Research (2007)

B2  The measurement of receptor tyrosine kinases (RTK) by standard immunohistochemistry (IHC) has several limitations including the lack of sub-cellular compartmental measurements which can be indicative of intracellular signaling. Simultaneous and automated measurement of membranous, cytoplasmic and nuclear levels of RTKs would offer a superior approach to traditional IHC and may be useful for the elusive molecular stratification of various cancers. The RTK hepatocyte growth factor receptor (Met) is believed to play a role in the progression of colon cancer, however the association of Met expression and survival has not been well established for colon cancer. We performed fluorescent-based immunohistochemistry for Met in 583 colon cancer patients in a tissue microarray format. Using novel curvature and intensity based image analysis, the membrane, nuclear and cytoplasm were segmented, and the epithelial tissue was automatically separated from the stromal tissue. Probability distributions of Met within each compartment were determined, and an automated scoring algorithm was generated. An optimal cut point was selected using 500-fold cross validation of a training and test data set. In univariate Cox analysis, high cytoplasmic relative to membranous values were a significant predictor of survival in stage I (hazard ratio (HR) 0.16; p=0.006) and in stage II patients (HR 0.34 p = 0.0005). Similar results were found with multivariate analysis. The value of Met in the membrane alone was not a significant predictor of outcome in all patients or within stage. This is the first report to show sub-cellular distribution of Met is a predictive molecular biomarker and our data support the use of automated algorithms for the molecular stratification of early stage colon cancer. Further, these algorithms have general applicability to RTKs that are known to have complicated intracellular signaling patterns.
Olanzapine vs Haloperidol for Treatment of Schizophrenia
Authors: Michal Kunz
Journal: JAMA (2004)

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
The Whole Price of Vancomycin: Toxicities, Troughs, and Time
Authors: Meghan N. Jeffres
Journal: Drugs (2017)

Vancomycin is a glycopeptide antibiotic that is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Nephrotoxicity, which is usually reversible, is the most serious common adverse effect of vancomycin. Vancomycin-associated nephrotoxicity prolongs hospital stays, imposes a need for additional antibiotics and, in rare circumstances, dialysis treatment, and increases medical costs and mortality. Risk factors for nephrotoxicity include the dose and duration of vancomycin treatment, serum trough concentration, patient characteristics, and concomitant receipt of nephrotoxins. Contemporary guidelines recommend targeting vancomycin trough concentrations of ≥10 mg/L to prevent resistance and trough concentrations of 15–20 mg/L to optimize outcomes. There is significant correlation between vancomycin trough serum concentrations and the incidence of vancomycin-associated nephrotoxicity; however, evidence of an association between trough concentrations and efficacy is less convincing. Routine monitoring of serum vancomycin concentrations consumes time and limited healthcare resources and may not be cost effective. The use of alternative antibacterial agents that do not require monitoring would free up pharmacy resources. This time could then be devoted to initiatives such as pharmacist-led antibiotic stewardship programs that are known to reduce antibiotic use and promote improved patient outcomes.
Preclinical study of a Bcl-2 inhibitor in neuroblastoma.
Authors: Assila Belounis, Anissa Addioui, Anne-Hélène Conan, Dominic- Vidaroun Thanvilay, Sonia Cournoyer, Carine Nyalendo, Pierre Teira, Mona Beaunoyer, Rose- Marie Brito, Hervé Sartelet
Journal: Journal of Clinical Oncology (2012)

9563 Background: Neurblastoma (NB) is the most common and deadly extracranial solid tumor of childhood. This malignant tumor exhibits a broad spectrum of clinical features, including spontaneous regression or maturation without any treatment or progression to metastisis leading to death. However, in spite of many therapeutic improvements, only 60% survive long term. In fact, 40% of patients with high-risk NB still relapse and eventually die of the disease despite aggressive combinations of multi-agent chemotherapy. In those cases, new therapeutic strategies must be developed. Studies have shown that BCl-2, a central anti-apoptotic protein, is over-expressed in NB. Although Bcl-2 is not a significant prognostic factor in NB, its increased expression would contribute to chemotherapy resistance. BCl-2 is also shown to be involved in the modulation of autophagy by inhibiting Beclin-1. Therefore, BCl-2 protein represents an attractive target for new therapeutic strategies in NB.The objective of this study is to determine the efficacy in vitro of Obatoclax (OB), a BCl-2 inhibitor, used in monotherapy or in combination to cisplatine (CP), a classical chemotherapeutic agent used in NB treatment, on NB cell survival. Methods: Six NB cell lines (SK-N-DZ, SK-N-FI, SK-N-SH, N91, NB8 and NB10) were treated with OB alone or in association to CP. Cell survival was measured by MTT test. Autophagy was measured by MDC test. Western Blots (WB) were done to evaluate the modulation of apoptotic and autophagic pathways in treated cells. Results: OB used in monotherapy shows promising results on NB cell lines with an average IC50 of 0.12µM. Also, OB demonstrates synergistic effects when associated to CP. The IC50 of CP treated cells varied from 3.183µM to 6.837µM but dropped from 0.003µM to 0.008µM when combined with 0.5µM of OB. Moreover, our WB show an increase in cleaved Caspase-3 and PARP-1 expression, suggesting an upregulation of apoptosis in treated cells. Autophagy is also upregulated confirmed by an increase in autophagic vacuoles and cleaved LC3 II protein. Conclusions: OB used in monotherapy or in combination at potentially therapeutic doses shows promising results in NB. These results will allow for the improvement of NB treatments by introducing a new therapeutic strategy.
Tregs restrain dendritic cell autophagy to ameliorate autoimmunity
Authors: Themis Alissafi, Aggelos Banos, Louis Boon, Tim Sparwasser, Alessandra Ghigo, Kajsa Wing, Dimitrios Vassilopoulos, Dimitrios Boumpas, Triantafyllos Chavakis, Ken Cadwell, Panayotis Verginis
Journal: Journal of Clinical Investigation (2017)

Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte–associated protein 4–dependent (CTLA4-dependent) manner. Autophagy-deficient DCs exhibited reduced immunogenic potential and failed to prime autoantigen-specific CD4+ T cells to mediate autoimmunity. Mechanistically, CTLA4 binding promoted activation of the PI3K/Akt/mTOR axis and FoxO1 nuclear exclusion in DCs, leading to decreased transcription of the autophagy component microtubule-associated protein 1 light chain 3β (Lc3b). Human DCs treated with CTLA4-Ig, a fusion protein composed of the Fc region of IgG1 and the extracellular domain of CTLA4 (also known as abatacept, marketed as Orencia), demonstrated reduced levels of autophagosome formation, while DCs from CTLA4-Ig–treated rheumatoid arthritis patients displayed diminished LC3B transcripts. Collectively, our data identify the canonical autophagy pathway in DCs as a molecular target of Foxp3+ Treg–mediated suppression that leads to amelioration of autoimmune responses. These findings may pave the way for the development of therapeutic protocols that exploit Tregs for the treatment of autoimmunity as well as diseases in which disturbed tolerance is a common denominator.