tbuckley/cabot-search huggingface dataset:
Practice patterns for prophylaxis and treatment of cancer related venous thromboembolism (VTE) in Germany: Comparison hematologists/oncologists (HOs) vs. angiologists/phlebologists (APs).
Authors: Axel Matzdorff, Bettina Ledig, Markus Stuecker, Hanno Riess
Journal: Journal of Clinical Oncology (2015)

e20663 Background: VTE is a serious threat for cancer patients (pts). Guidelines recommend prophylactic education for all cancer patients about symptoms of VTE. Established VTE should be treated with low molecular weight heparin (LMWH) rather than vitamin K antagonists (VKAs) or any of the new direct oral anticoagulants (DOACs). We present a survey on the current approach to cancer related VTE in Germany by specialists and their adherence to guideline recommendations. Methods: A questionnaire on prophylaxis and treatment of cancer related VTE was sent to members of DGHO (German Society for Hematology and Oncology), BNHO (Professional Association of Hematologists and Oncologists in Private Practice) and DGP (German Society for Phlebology). Results: 214 HOs and 34 APs responded. 38% HOs and 70% APs routinely provide prophylactic education (p = 0.004) to pts. 33% HOs and 11% APs treat established VTE for max. 3 months (p = 0.024). For initial treatment (first 3-4 weeks) 79% HOs and 70% APs prescribe only LMWHs while 20% HOs and 30% APs (1% no answer) switch to VKAs or DOACs during this early phase (p = 0.421). For secondary prophylaxis (until 3 to 6 months after VTE) 56% HOs and 41% APs continue LMWH, 13% and 22% switch to VKAs, 18% and 19% to DOACs, 14% and 19% to VKAs or DOACs, respectively (p = 0.422). Among those who continue LMWH beyond 3 months 21% HOs and 50% APs reduce LMWH dose to 75% and 44% HOs and 12% APs to 50% (p = 0.001). For both HOs and APs important factors guiding treatment decision pro LMWHs were the availability of a partner/spouse, contra VKAs the necessity for frequent lab controls, and contra DOACs the total number of oral medications. Conclusions: This survey reveals that practice patterns often do not follow guidelines and that type, dose, and duration of anticoagulation vary substantially. Implementation of guideline recommendations on cancer related VTEs should become a priority in oncology training of all medical subspecialties. Further subgroup analyses (hospital- vs. practice-based oncologists, younger vs. older physicians, and specialists in hemostasis vs. non-specialists) will be presented at the meeting.
The potential of natural products for targeting PPAR α
Authors: Daniela Rigano, Carmina Sirignano, Orazio Taglialatela-Scafati
Journal: Acta Pharmaceutica Sinica B (2017)

Peroxisome proliferator activated receptors (PPARs) α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, e.g. rosiglitazone and pioglitazone) are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPARγ, while PPARα is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating the PPARα system with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this "hot" target.
Abstract 094: Antithrombin Exerts a Cardioprotective Effect against Myocardial Ischemic/reperfusion Injury through Induction of Prostacyclin and Inhibition of NF-kB Signaling
Authors: Ji Li, Jingying Wang, Yanqing Wang, Jinli Wang, Junjie Gao, Emmanuel Yawson, Chandrashekhara Manithody, Alireza R Rezaie
Journal: Circulation Research (2013)

Antithrombin (AT) is a plasma serpin inhibitor that regulates the proteolytic activity of procoagulant proteases of the clotting cascade. In addition to its anticoagulant activity, AT also possesses potent antiinflammatory and antiangiogenic properties. In this study, we investigated the antiinflammatory activity of wild-type AT (AT-WT) and a reactive center loop mutant of AT (AT-RCL) not capable of inhibiting thrombin in a mouse model of ischemia/reperfusion injury in which the left anterior descending coronary artery (LAD) was occluded and released then. The results demonstrate that AT markedly reduces the myocardial infarct size (p&lt;0.05 vs. vehicle) by a mechanism that is independent of its anticoagulant activity. Thus, the AT-RCL mutant, lacking any detectable reactivity with thrombin, attenuated myocardial infarct size to the same extent as the AT-WT in the acute injury model. Further studies revealed that AT binds to vascular heparan sulfate proteoglycans via its heparin-binding domain to exert its protective activity as evidenced by the therapeutic AT-binding pentasaccharide fragment of heparin (fondaparinux) abrogating the cardioprotective activity of AT. We further demonstrate that AT up-regulates the production of prostacyclin in myocardial tissues (p&lt;0.05 vs. vehicle) and inhibits the production of proinflammatory cytokines TNF-α and IL-6 (p&lt;0.05 vs. vehicle) in vivo by attenuating the ischemia/reperfusion-induced JNK and NF-κB signaling pathways. These results suggest that AT, through its antiinflammatory signaling effect, may have therapeutic potential for reducing cardiac ischemia/reperfusion injury and that a normal cardioprotective activity for the AT-RCL variant renders it a superior drug candidate if bleeding becomes a concern in the treatment.
Correlation of dynamic infrared imaging with radiologic and pathologic response for patients treated with primary systemic therapy for locally advanced breast cancer
Authors: S. R. Fanning, S. Short, K. Coleman, S. Andresen, G. T. Budd, H. Moore, A. Rim, J. Crowe, D. E. Weng
Journal: Journal of Clinical Oncology (2006)

10696 Background: Assessment of response to therapy for locally advanced breast cancer includes serial assessments of physical exam, radiologic imaging, or repeated biopsies. Expense, subjective assessment, and patient risk make these methods impractical. Dynamic infrared imaging (DIRI) utilizes a quantum well infrared photon (QWIP) sensor with software to analyze the emission patterns over time. DIRI can detect biological temperature gradients with sensitivity of 0.009ºC. Tumor-induced local tissue nitric oxide production can increase local capillary blood flow. Anti-tumor therapies have been shown to result in decreased peri-tumoral capillary blood flow. These changes in temperature, detected by serial DIRI imaging, may provide a low cost, non-invasive, easily reproducible objective tool for real-time clinical assessment. Methods: In this prospective pilot study, we are evaluating patients with locally advanced breast cancer using serial DIRI. Primary endpoints include: sensitivity, specificity, PPV, and NPV of DIRI in comparison to pathologic response, concordance of DIRI to physical exam, and concordance of DIRI to standard radiographic evaluation at initial diagnosis and prior to surgery. DIRI results are reported as quantification of changes in the 0.2Hz modulation of temperature over the breast during the course of treatment and measurement of area of average temperature in a region of interest compared between breasts. One hundred patients will be enrolled in this trial. Results: Sixteen patients have been enrolled. Six have proceeded to surgery. All but one patient exhibited evidence of tumor response by physical exam. These findings correlated with response when comparing initial to pre-surgical MRI. In all responding patients, DIRI results revealed a decrease in the number of regions over the breast in which the 0.2Hz frequency dominated. Similarly, DIRI evaluation according to area of average temperature in the region of interest compared between breasts was concordant in patients with response to therapy. Conclusions: Assessment of response by physical exam, MRI, and DIRI were consistent. Preliminary data reveals that serial DIRI imaging can be an effective adjunctive tool. No significant financial relationships to disclose.
Identification and Functional Characterization of Hypoxia-Induced Endoplasmic Reticulum Stress Regulating lncRNA (HypERlnc) in Pericytes
Authors: Florian C. Bischoff, Astrid Werner, David John, Jes-Niels Boeckel, Maria-Theodora Melissari, Phillip Grote, Simone F. Glaser, Shemsi Demolli, Shizuka Uchida, Katharina M. Michalik, Benjamin Meder, Hugo A. Katus, Jan Haas, Wei Chen, Soni S. Pullamsetti, Werner Seeger, Andreas M. Zeiher, Stefanie Dimmeler, Christoph M. Zehendner
Journal: Circulation Research (2017)

Pericytes are essential for vessel maturation and endothelial barrier function. Long noncoding RNAs regulate many cellular functions, but their role in pericyte biology remains unexplored.Here, we investigate the effect of hypoxia-induced endoplasmic reticulum stress regulating long noncoding RNAs (HypERlnc, also known as ENSG00000262454) on pericyte function in vitro and its regulation in human heart failure and idiopathic pulmonary arterial hypertension.RNA sequencing in human primary pericytes identified hypoxia-regulated long noncoding RNAs, including HypERlnc. Silencing of HypERlnc decreased cell viability and proliferation and resulted in pericyte dedifferentiation, which went along with increased endothelial permeability in cocultures consisting of human primary pericyte and human coronary microvascular endothelial cells. Consistently, Cas9-based transcriptional activation of HypERlnc was associated with increased expression of pericyte marker genes. Moreover, HypERlnc knockdown reduced endothelial-pericyte recruitment in Matrigel assays (P<0.05). Mechanistically, transcription factor reporter arrays demonstrated that endoplasmic reticulum stress-related transcription factors were prominently activated by HypERlnc knockdown, which was confirmed via immunoblotting for the endoplasmic reticulum stress markers IRE1α (P<0.001), ATF6 (P<0.01), and soluble BiP (P<0.001). Kyoto encyclopedia of genes and gene ontology pathway analyses of RNA sequencing experiments after HypERlnc knockdown indicate a role in cardiovascular disease states. Indeed, HypERlnc expression was significantly reduced in human cardiac tissue from patients with heart failure (P<0.05; n=19) compared with controls. In addition, HypERlnc expression significantly correlated with pericyte markers in human lungs derived from patients diagnosed with idiopathic pulmonary arterial hypertension and from donor lungs (n=14).Here, we show that HypERlnc regulates human pericyte function and the endoplasmic reticulum stress response. In addition, RNA sequencing analyses in conjunction with reduced expression of HypERlnc in heart failure and correlation with pericyte markers in idiopathic pulmonary arterial hypertension indicate a role of HypERlnc in human cardiopulmonary disease.
Clinical and Pathological Staging Validation in the Eighth Edition of the TNM Classification for Lung Cancer: Correlation between Solid Size on Thin-Section Computed Tomography and Invasive Size in Pathological Findings in the New T Classification
Authors: Keiju Aokage, Tomohiro Miyoshi, Genichiro Ishii, Masahiro Kusumoto, Shogo Nomura, Shinya Katsumata, Keigo Sekihara, Tomoyuki Hishida, Masahiro Tsuboi
Journal: Journal of Thoracic Oncology (2017)
Sudden Cardiac Death in US Young Adults, 1989-1996
Authors: Zhi-Jie Zheng, Janet B. Croft, Wayne H. Giles, George A. Mensah
Journal: Circulation (2001)

0007     Anecdotal evidence and case reports indicate that sudden  cardiac death (SCD) occurs in adolescents and young adults. To  investigate the epidemiologic pattern and secular trend of SCD among  ages 15-34 years, we analyzed US Multiple Causes of Death data from  1989 to 1996. SCD is defined as death due to cardiac disease (ICD-9  codes: 390-398, 402 and 404-429)that occurred out of hospital or in  emergency room. This definition has been used in prior studies with  reasonable accuracy. Mortality rates were calculated using mid-year  population estimates as the denominators, and standardized to 1970. In  1996, 3,000 sudden cardiac deaths occurred for this specific age group,  which reflects a 10% increase from 1989 (n=2,719). The leading  underlying causes of SCD were ischemic heart disease (ICD codes  410-414, and 429.2), and arrhythmias or cardiomyopathies (ICD codes  425-427), each accounting for 35% of all SCDs. SCD mortality rates  were twice as high in men as in women, and increased with age. From  1989 to 1996, age-standardized SCD mortality rates increased in both  men (+10%) and women (+31%) (Figure). Although SCD is relatively rare  in US adolescents and young adults, the increased trend of SCD  mortality warrants further investigation. This is the first national  surveillance report on SCD in young adults.
Comparison of mRNA and protein expression profiles in the NCI-60 cancer cell panel
Authors: Uma Shankavaram, Satoshi Nishizuka, William C. Reinhold, Sylvia Major, Mark Reimers, Uwe Scherf, Douglas Dolginow, Eric Kaldjian, Jeffrey Cossman, Krishna Chary, Emanuel Petricoin, Lance Liotta, John Weinstein
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1563 

To evaluate the relationship between transcript and protein expression levels in cancer cells, we compared mRNA and protein levels in the NCI-60 human cancer cell line panel, which represents nine different tissues of origin. We and others have previously reported that mRNA expression patterns differ considerably among measurement platforms and that they also differ considerably from patterns of protein expression. To sharpen the present analysis, we analyzed the transcript expression data for concordance across multiple platforms (cDNA arrays and Affymetrix Hu68, U95, and U133 chips). The resulting consensus data (with largest contribution from U133set) were then compared with protein expression levels obtained from our NCI-60 reverse-phase protein microarray database (Nishizuka, et al., PNAS 100:14229, 2003 and Shankavaram, et al., in preparation). Among 89 genes for which we were matched transcript and protein names using our MatchMiner program (Bussey, et al., Genome Research 4:R27, 2003), the transcript-protein correlations ranged from -0.08 to 0.848. Fifty-eight of the 89 transcript/protein pairs were statistically significantly correlated (r > ∼0.258). The distribution of significant correlations showed a bimodal pattern, indicating two distinct groups. Functional characterization of the significant genes by Gene Ontology classification using GoMiner (Zeeberg, et al., Genome Research 4:R28, 2003) showed that cytoskeleton-related processes are associated with high correlations (mean r = 0.71), whereas processes involved in signaling mechanisms are associated with lower correlation (mean r =0.39). When the transcript data were stratified by intensity of signal, the difference remained. Although, in general, mRNA expression levels do not predict all protein levels across these disparate cell types, our analysis suggests that transcriptional profiling can be a good indicator of protein expression for some functional categories. The MatchMiner and GoMiner program are publicly available at our web site,  .
Histiocytoid Sweet Syndrome and Myelodysplastic Syndrome—Reply
Authors: Victoria Alegría-Landa, Lorenzo Cerroni, Luis Requena
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Improving pre-clinical screening of drug candidates for pancreatic cancer by applying a systems genomics approach to pinpoint ideal cell line models.
Authors: Benjamin Zeskind, Yoonjeong Cha, Andrew Lysaght, Rain Cui, Brian Weiner, Sarah Kolitz, Fadi Towfic, Jason Funt, Kevin Fowler, Badri Vardarajan, Maxim Artyomov, Rebecca Kusko
Journal: Journal of Clinical Oncology (2015)

e15268 Background: Despite substantial research efforts in pancreatic cancer the estimated 5-year survival rate remains 5-6%. The lack of early detection methods compounded by a startlingly low clinical trial success rate precipitates the need for innovative approaches to pancreatic cancer drug development. Choice of cell lines used for pre-clinical compound screening is usually based on ease of culture, popularity, and availability. However, we have observed that the constellation of pathway derangements in commonly used pancreatic cancer cell lines may not optimally model pancreatic cancer tumors. Methods: With this motivation, we leveraged gene expression (GE), copy number variation (CNV) and targeted sequencing data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) to predict cell lines that best model pancreatic tumor genomic architecture. Inspired by the hypothesis that a disease relevant CNV should impact GE, we used an eQTL-like approach independently in pancreatic cancer cell lines and in tumors to select only genes which have a significant relationship between CNV and GE. Next, we used published methods to score mutations and guided the significance cutoff using our positive (KRAS and TP53) and negative (TTN) controls. To unite these two arms of analysis we merged genes with CNVs or mutations passing our cutoffs together into a scaled KEGG pathway level event matrix. Pancreatic cancer cell line and tumor event matrices were clustered together in an unsupervised manner. Results: Cluster analysis strikingly revealed that popular cell lines such as PK1 and PANC1 occupy a discrete cell line only branch of the dendrogram indicating dissimilarity with patient tumors from TCGA. In contrast, less popular cell lines such as SNU410 and L33 clustered intermixed amongst tumor predominant branches, indicating that they may better model TCGA patient tumors. Conclusions: In summary, our work highlights the emerging role of systems genomics in improving R&D productivity, and raises the possibility that screening drug candidates against certain less commonly utilized cell lines could improve clinical trial success rates.
Inferences from differing temporal incidence patterns of skin cancer induced by ionizing radiation, ultraviolet radiation and arsenite or chromate.
Authors: Fredric J. Burns, Ahmed N. Uddin, Max Costa, Feng Wu, Toby G. Rossman
Journal: Cancer Research (2004)

2498  Ionizing radiation (IR), carcinogenic metals (arsenite and chromate) and ultraviolet radiation (UVR) are known to elevate the level of reactive oxygen species (ROS) in cells, and yet substantial differences are apparent in their carcinogenic actions in rat or mouse skin. For example, (1) IR is carcinogenic after single, acute exposures (a rarity among carcinogens), while UVR is carcinogenic via chronic exposure and (2) metals given chronically in drinking water are not carcinogenic but exhibit strong co-carcinogenic activity when combined with chronic UVR, whereas IR is additive with chronic UVR. Animal protocols were performed with the following carcinogens in paired combinations (and singly) in mouse skin: UVR & sodium arsenite, UVR & potassium chromate and in rat skin: IR & UVR, IR & 7,12 dimethylbenz(a)anthracene (DMBA). Analysis of the temporal patterns of cancer onset reveals differences related to the type of carcinogen and the mode of administration. For example, the temporal incidence of human skin cancers closely conforms to a power function with an exponent on the order of 6, which means cancers are rare in the young but rise rapidly with age. A similar exponent is applicable to skin cancer induction in rats and mice exposed topically and chronically to UVR or polycyclic hydrocarbons, such as benzo(a)pyrene or DMBA, except the time frame is contracted approximately by the ratio of comparative life-spans. By contrast the exponent for acute IR-induced skin cancer in rats is lower (generally about 2 or less) in comparison to chronically administered carcinogens, meaning that cancer onset is slower with time. Combining acute IR with chronic UVR or chronic polycyclic carcinogens produced separate, additive cancer incidence patterns with exponents typical of each agent. However when rats were exposed chronically to IR, the exponent increased from 2 to about 6, implying that the exponent is probably more a reflection of the exposure pattern than of the carcinogen. To the extent that the exponent reflects progression of carcinogenic stages, the increase can be interpreted as IR acting to increase progression-type events in early neoplastic cells. Chronic arsenite in drinking water coupled to topical UVR caused little change in the UVR-induced exponent (average about 6.5), whereas chromate caused the UVR exponent to increase from about 6.5 to about 10. One implication of these findings is that early neoplastic cells are being altered in separate and individual ways typical of each type of carcinogen and/or its exposure pattern. This work was supported by NIEHS grant ES09252 and is part of Center programs supported by Grants ES00260 from NIEHS and CA16087 from NCI and NASA Grant NAG9-1528.