tbuckley/cabot-search huggingface dataset:
Differential regulation of cellular proliferation between transformed and non-transformed immortal cells.
Authors: Keiko Hiyama, Momomi Tsugane, Keiji Tanimoto, Youhei Nishimura, Eiso Hiyama, Masahiko Nishiyama
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5006 

Acquiring indefinite proliferation almost always requires telomerase expression in human cells regardless of whether they are transformed or not. However, we have found that additional molecules involeved in cellular immortalization in normal cells are differnet according to their origin and quite different from those in cancer (Int J Oncol 27: 87-95, 2005). We then explored the candidate genes regulating the immortalization of cancer or transformed cells, but not normal cells, in cooporation with telomerase. We carried out microarray analysis on 70 cancer derived cell lines, 8 non-cancerous cell strains, 9 in-vitro transformed and/or immortalized cell strains, and 24 cancerous or adjacent noncancerous tissues using CodeLink UniSet Human 20K I Bioarray system. Among the 19,881 human probes spotted on the array, 3 genes were detected as commonly down-regulated in the cancer cell lines of any origin: lung, esophageal, gastrointestinal, breast, ovarian, and pancreas cancers. One of the 3 genes revealed to be downregulated also in in-vitro transformed immortal cells but not in transformed mortal cells, telomerase negative cancer tissues, or in immortal non-transformed cells. Moreover, overexpression of this gene using expression vectors in immortal transformed cells: an esophageal cancer cell line and in-vitro transfomed immortal fibrobalsts transfected with SV40 early antigens and hTERT , but not in normal immortal cells: in-vitro immortalized fibrobalsts transfected with hTERT , caused their growth inhibition. Downregulation of this gene in immortal cells did not recover by the treatment with DNA demethylating reagent 5-azacytidine or histone deacetylase inhibitor trichostatin A (TSA). These findings indicate that down-egulation of this gene with undetermined mechanism is required in immortalization of transformed cells but not in that of normal human cells. This gene might be the cancer-specific regulator of cellular immortalization, and elucidation of its mechanism and function may provide a cancer-specific antiproliferative strategy in future.
Abstract #5532: Pathologic response to neoadjuvant chemotherapy for breast cancer: Linked to enzymes that metabolize ceramide?
Authors: Partha Ray, Valerie Gouaze-Andersson, Armando Giuliano, Myles Cabot
Journal: Cancer Research (2009)

Background:   While the role of glucosylceramide synthase (GCS) in drug resistance is well documented, other enzymes of ceramide metabolism may affect the pathologic response to chemotherapy. We hypothesized that upregulation or downregulation of key enzymes responsible for ceramide metabolism would be associated with poor pathologic response to neoadjuvant chemotherapy in breast cancer.   Methods:  Our cohort comprised 133 previously reported ( J Clin Oncol 24:4236-4244; 2006 ) patients who underwent neoadjuvant chemotherapy for biopsy-proven invasive breast cancer. Diagnostic biopsy specimens (fine-needle aspiration) were retrieved and analyzed by microarray (Affymetrix U133A platform) for expression of 16 enzymes involved in ceramide metabolism. Each patient\#8217;s pathologic response to chemotherapy (sequential paclitaxel and fluorouracil-doxorubicin-cyclophosphamide) was determined by the presence or absence of primary and/or regional node tumor in the specimen from definitive resection. Two-way unequal variance Students9 T-test was used to assess statistical significance of pretreatment enzyme expression levels (normalized signal intensity) with respect to pathologic response or nonresponse.   Results:   Of the 16 enzymes, 4 were significantly upregulated in nonresponders compared to responders: acid ceramidase [2207±143 (SEM) vs. 1327±134 (SEM), p= 1.74 X 10 -5 ] and dihydroceramide synthases 2, 4 and 6. Although GCS was upregulated [1076±104 (SEM) vs. 719±171 (SEM)], it was not significant because of two outlier values. Interestingly, sphingosine kinase 1 was significantly downregulated in non-responders compared to responders [262±6.5 (SEM) vs. 388±36 (SEM), p=0.001].   Conclusion:   This is the first clinical study to implicate acid ceramidase as a mediator of multidrug resistance in breast cancer. Our findings suggest that a multimarker panel based on the enzymes of ceramide metabolism might be able to predict failure of response to neoadjuvant chemotherapy in breast cancer; a validation study is underway.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5532.
Competing for Spring Beauties
Authors: Frederick Butzen
Journal: JAMA (1980)

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 Journals 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 2024 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
Abstract 11804: The Blood Glucose Concentration at Hospitalization is a Significant Predictor of In-Hospital Death in the Patients With Non-Diabetic Acute Decompensated Heart Failure
Authors: Shin Kawasoe, Takuro Kubozono, Hiroyuki Torii, Tsuyoshi Yamaguchi, Masaaki Miyata, Mitsuru Ohishi
Journal: Circulation (2014)

Background: The blood glucose (BG) concentration (BG≧140 mg/dL) at hospitalization is reported to be the short-term prognostic predictor in patients with acute myocardial infarction. However, it’s significance in patients with acute decompensated heart failure (ADHF) has not been elucidated. Purpose: To evaluate the prognostic power of BG levels at hospitalization in the patients with ADHF. Methods: We analyzed consecutive 517 ADHF patients admitted from January 2007 to December 2013. They were divided into the high BG group (H-BG: BG≧140 mg/dL, n=215) and the low BG group (L-BG: BG&lt;140 mg/dL, n=302) by BG levels in an emergency room. Echocardiographic findings, laboratory data and in-hospital mortality were analyzed. Results: In 517 ADHF patients, the mean age, BG levels at hospitalization, left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) were 79.7±11.8 years, 153.0±75.2 mg/dL, 52.2±15.8% and 831.5±787.9 pg/mL, respectively. There were no significant differences in age, LVEF and BNP level between H-BG and L-BG groups. The mortality rate in H-BG group was significantly higher than that in L-BG group (17.0% vs 8.1%, p=0.0081). In diabetic ADHF patients (n=138), there was no significant difference in the in-hospital mortality rate between H-BG (n=100) and L-BG (n=38) groups (13.2% vs 24.4%, p=0.1116). However, in non-diabetic ADHF patients (n=379), the in-hospital mortality rate was significantly higher in H-BG (n=115) group compared to L-BG (n=264) group (21.2% vs 5.6%, p&lt;0.0001), and the logistic regression analysis revealed that the BG level at hospitalization could predict the in-hospital death (p=0.0381). The Kaplan-Meier survival curve demonstrated poorer prognosis in H-BG group compared to L-BG group in non-diabetic ADHF patients (Figure, p&lt;0.0001). Conclusion: The BG concentration at hospitalization is a significant predictor of in-hospital death in ADHF patients without diabetes, but not with diabetes.
Tocilizumab for Giant Cell Arteritis—A New Giant Step in an Old Disease
Authors: Hiromichi Tamaki, Rula A. Hajj-Ali
Journal: JAMA Neurology (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 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
Abstract 13992: The Clinical Significance of Diastolic Late Mitral Annular Velocity in Heart Failure With Preserved Left Ventricular Ejection Fraction
Authors: Fumi Oike, Eiichiro Yamamoto, Takanori Tokitsu, Yoshihiro Hirata, Satoru Yamamura, Yasuhiro Izumiya, Koichi Kaikita, Seiji Hokimoto
Journal: Circulation (2016)

Background: Left atrial (LA) structure are altered in the majority of HF with preserved LVEF (HFpEF) patients. Because diastolic late mitral annular velocity (a’) measured by transthoracic echocardiography (TTE) is reported to represent the severity of LA remodeling, we investigated clinical significance of a’ in HFpEF. Methods: We enrolled 422 consecutive HFpEF patients (sinus rhythm [SR]: n=337 [79.9%], atrial fibrillation [AF] rhythm: n=85 [20.1%]), admitted to Kumamoto University Hospital from 2006 to 2013, and performed TTE at stable condition after optimal therapy for HF. In patients with SR at the time of TTE, a’ values as an average of tissue Doppler velocities measured at septal and lateral mitral annuli. All HFpEF patients were followed until occurrence of cardiovascular events. Results: In HFpEF patients with SR, a’ had a weak but significant negative correlations with B-type natriuretic peptide (BNP) (r=0.22, p&lt;0.001), LA volume (r=0.28, p&lt;0.001), the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (E/e’) (r=0.24, p&lt;0.001) and LV mass index (LVMI) (r=0.35, p&lt;0.001). In multivariate logistic-regression analysis, E/e’ and LVMI were significantly and independently associated with decreased a’ (both, p&lt;0.05). HFpEF patients with low-a’ (&lt;8; median value of a’) had significantly higher BNP (p=0.01) and prevalence of hypertension (p&lt;0.01), and lower prevalence of coronary artery disease (p=0.01) than those with high-a’ (≧8). In Kaplan-Meier analysis, HFpEF patients with AF had a significant higher risk of all cardiovascular and HF-related events than those with SR (both, log-lank test, p&lt;0.01). Furthermore, HFpEF patients with low-a’ had a significant higher risk of cardiovascular events and HF-related events (both, log-lank test, p&lt;0.01) than those with high-a’, and was prognostically equivalent to those with AF. Multivariate-Cox-hazard analysis identified that low-a’ as an independent predictor of both cardiovascular (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.76-0.99, p=0.04) and HF-related events (HR: 0.71, 95%CI: 0.57-0.88, p=0.002). Conclusion: Estimation of a’ value is a non-invasive and useful method for risk stratification in patients with HFpEF.
Prognostic accuracy of age-adapted SOFA, SIRS, PELOD-2, and qSOFA for in-hospital mortality among children with suspected infection admitted to the intensive care unit
Authors: Luregn J. Schlapbach, Lahn Straney, Rinaldo Bellomo, Graeme MacLaren, David Pilcher
Journal: Intensive Care Medicine (2017)

The Sepsis-3 consensus task force defined sepsis as life-threatening organ dysfunction caused by dysregulated host response to infection. However, the clinical criteria for this definition were neither designed for nor validated in children. We validated the performance of SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores as predictors of outcome in children. We performed a multicentre binational cohort study of patients < 18 years admitted with infection to ICUs in Australia and New Zealand. The primary outcome was ICU mortality. SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores were compared using crude and adjusted area under the receiver operating characteristic curve (AUROC) analysis. Of 2594 paediatric ICU admissions due to infection, 151 (5.8%) children died, and 949/2594 (36.6%) patients died or experienced an ICU length of stay ≥ 3 days. A ≥ 2-point increase in the individual score was associated with a crude mortality increase from 3.1 to 6.8% for SIRS, from 1.9 to 7.6% for age-adapted SOFA, from 1.7 to 7.3% for PELOD-2, and from 3.9 to 8.1% for qSOFA (p < 0.001). The discrimination of outcomes was significantly higher for SOFA (adjusted AUROC 0.829; 0.791–0.868) and PELOD-2 (0.816; 0.777–0.854) than for qSOFA (0.739; 0.695–0.784) and SIRS (0.710; 0.664–0.756). SIRS criteria lack specificity to identify children with infection at substantially higher risk of mortality. We demonstrate that adapting Sepsis-3 to age-specific criteria performs better than Sepsis-2-based criteria. Our findings support the translation of Sepsis-3 into paediatric-specific sepsis definitions and highlight the importance of robust paediatric organ dysfunction characterization.
Treatment of a bilaterally nephrectomized patient with recombinant IFNα-2b (IFN): Pharmacokinetic evaluation suggests that approximately 50% of serum IFN is eliminated by hemodialysis.
Authors: Wendy G. Brick, Walter D. Y. Quan, Radhika Shah, Nawazish A. Khan, George Sigounas, Russell E. Burgess
Journal: Cancer Research (2004)

3818   The purpose of this study was to evaluate the pharmacokinetics of IFN in a bilaterally nephrectomized patient with metastatic renal cell carcinoma. It is well known that greater than 80% of administered interferon is cleared by the kidneys via filtration through the glomerulus, reabsorption in the proximal tubules and, ultimately lysosomal degradation without urinary excretion. It was previously thought that dose modification of IFN in dialysis patients was unnecessary because the pharmacokinetics of IFN in these patients was similar to that of patients with normal renal function. However, more recent reports suggest that there is a difference between the two and thus dose modification is necessary. Published reports evaluating IFN in dialysis patients are few and all either use natural IFN (vs recombinant) or are in Hepatitis C patients, neither of which is consistent with the usual metastatic renal cell carcinoma patient. We compared the serum levels of IFN, at specified times pre- and post-dialysis, with serum levels of IFN in a control patient with normally functioning kidneys. Our analysis revealed that with each dialysis approximately 50% of the serum IFN is removed. In addition, if TIW(three times per week) IFN is given, there is a steady state accumulation of IFN that ultimately can lead to relatively high serum levels (157 pg/ml in our patient after just 7 TIW doses of IFN) even with TIW hemodialysis. To our knowledge, this is the only report evaluating pre and post-dialysis IFN levels in a patient who is status post bilateral nephrectomy.
Abstract 18879: Nicotinamide Phosphoribosyltransferase as a Potential New Genetic Biomarker for Stroke
Authors: Sean M Riordan, Dilyara Cherenova, Suman Chaudhary, Inna Sokolovsky, Dan Heruth, Dmitry Grigoryev, Li Q Zhang, Shui Q Ye
Journal: Circulation (2014)

Introduction:   We reported that Nicotinamide Phosphoribosyltransferase (NAMPT, also called PBEF) displays a protective role in acute ischemic stroke in both mouse and neuronal cell models. We had also identified that NAMPT SNPs in the human NAMPT gene promoter were associated with acute respiratory distress syndrome. This study aimed to determine whether NAMPT SNPs are associated with stroke by genetic association and reporter gene assays.   Methods:  Four NAMPT SNPs (G-1535A,A-1001C, C-948A, T-423C) were genotyped using the Taqman Assay on stroke patient population from the Coriell biorepository (n = 376), consisting of Caucasian and African American patients, and compared to healthy controls (n = 625) from the 1000 Human Genomes Project. Their haplotypes and diplotypes were analyzed using HPlus software (FHCRC, Seattle, WA). Stratified analyses included: race, gender, hypertension, diabetes, family history of cerebrovascular disease, atrial fibrillation, and history of smoking. Significant NAMPT promoter SNP haplotypes and diplotypes were identified and are being tested in luciferase reporter gene assays in SH-SY5Y neuroblastoma cells.   Results:  In this study, within the African American population carriers of the ‘protective haplotype’ of GACT had a significantly lower risk of stroke (OR= 0.59, 95% CI, 0.35-0.996, p   Conclusions:  These results suggest that NAMPT is a potential new predictive genetic biomarker for human stroke though the replication of this observation in larger patient populations and the further exploration of underpinning mechanisms are warranted.
Discordant Findings on 18F-NaF and 99mTc-HDP Bone Scans in a Patient With ATTR Cardiac Amyloidosis
Authors: Quinn K.T. Ng, Pooja Sethi, Tara A. Saunders, Miguel Hernandez Pampaloni, Robert R. Flavell
Journal: Clinical Nuclear Medicine (2017)

Abstract Cardiac amyloidosis is an important cause of restrictive cardiomyopathy and congestive heart failure. Bone scintigraphy with [ 99m Tc]hydroxymethylene diphosphonate ( 99m Tc-HDP) and [ 18 F]sodium fluoride ( 18 F-NaF) have been investigated in the noninvasive diagnosis of transthyretin (ATTR)–related cardiac amyloidosis. We present a case of a 76-year-old man with metastatic prostate cancer who underwent 99m Tc-HDP bone scintigraphy with an incidental finding of diffuse left ventricular abnormal uptake suggesting ATTR cardiac amyloidosis. Review of previous imaging showed a negative 18 F-NaF PET/CT study. This example suggests that the mechanism of uptake of 99m Tc-HDP and 18 F-NaF may differ in patients with ATTR cardiac amyloidosis.
Mapping genetic variations to three-dimensional protein structures to enhance variant interpretation: a proposed framework
Authors: Gustavo Glusman, Peter W. Rose, Andreas Prlić, Jennifer Dougherty, José M. Duarte, Andrew S. Hoffman, Geoffrey J. Barton, Emøke Bendixen, Timothy Bergquist, Christian Bock, Elizabeth Brunk, Marija Buljan, Stephen K. Burley, Binghuang Cai, Hannah Carter, JianJiong Gao, Adam Godzik, Michael Heuer, Michael Hicks, Thomas Hrabe, Rachel Karchin, Julia Koehler Leman, Lydie Lane, David L. Masica, Sean D. Mooney, John Moult, Gilbert S. Omenn, Frances Pearl, Vikas Pejaver, Sheila M. Reynolds, Ariel Rokem, Torsten Schwede, Sicheng Song, Hagen Tilgner, Yana Valasatava, Yang Zhang, Eric W. Deutsch
Journal: Genome Medicine (2017)

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods.
Intensive Lifestyle Intervention for Type 2 Diabetes
Authors: Dario Giugliano, Maria Ida Maiorino, Katherine Esposito
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