tbuckley/cabot-search huggingface dataset:
Evaluating Overall Survival and Competing Risks of Death in Patients With Localized Renal Cell Carcinoma Using a Comprehensive Nomogram
Authors: Alexander Kutikov, Brian L. Egleston, Yu-Ning Wong, Robert G. Uzzo
Journal: Journal of Clinical Oncology (2009)

Many patients with localized node-negative renal cell carcinoma (RCC) are elderly with competing comorbidities. Their overall survival benefit after surgical treatment is unknown. We reviewed cases in the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the impact of kidney cancer versus competing causes of death in patients with localized RCC and develop a comprehensive nomogram to quantitate survival differences.We identified individuals with localized, surgically treated clear-cell, papillary, or chromophobe RCC in SEER (1988 through 2003). We used Fine and Gray competing risks proportional hazards regressions to predict 5-year probabilities of three competing mortality outcomes: kidney cancer death, other cancer death, and noncancer death.We identified 30,801 cases of localized RCC (median age, 62 years; median tumor size, 4.5 cm). Five-year probabilities of kidney cancer death, other cancer death, and noncancer death were 4%, 7%, and 11%, respectively. Age was strongly predictive of mortality and most predictive of nonkidney cancer deaths (P < .001). Increasing tumor size was related to death from RCC and inversely related to noncancer deaths (P < .001). Racial differences in outcomes were most pronounced for nonkidney cancer deaths (P < .001). Men were more likely to die than women from all causes (P < .002). This nomogram integrates commonly available factors into a useful tool for comparing competing risks of death.Management of localized RCC must consider competing causes of mortality, particularly in elderly populations. Effective decision making requires treatment trade-off calculations. We present a tool to quantitate competing causes of mortality in patients with localized RCC.
Fibulin-2 is present in murine vascular lesions and is important for smooth muscle cell migration
Authors: A STROM, A OLIN, A ASPBERG, A HULTGARDHNILSSON
Journal: Cardiovascular Research (2006)

Objective: The vascular extracellular matrix (ECM) can affect smooth muscle cell (SMC) adhesion, migration and proliferation–events that are important during the atherosclerotic process. Fibulin-2 is a member of the ECM protein family of fibulins and has been found to cross-link versican/hyaluronan complexes, an ECM network that has been suggested to be important during tissue repair. In this study we have analysed the presence of fibulin-2 in two different models of murine vascular lesions. We have also examined how the fibulin-2/versican network influences SMC migration.
Prostate Stem Cell Antigen: A Jekyll and Hyde Molecule?
Authors: Norihisa Saeki, Jian Gu, Teruhiko Yoshida, Xifeng Wu
Journal: Clinical Cancer Research (2010)

Abstract Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. Although PSCA is thought to be involved in intracellular signaling, much remains unknown about its physiological function and regulatory mechanism in normal and cancer cells. It is up-regulated in several major cancers including prostate, bladder, and pancreatic cancers. The expression of PSCA is positively correlated with advanced clinical stage and metastasis in prostate cancers and is also associated with malignant progression of premalignant prostate lesions. Therefore, PSCA has been proposed as a biomarker of diagnosis and prognosis, as well as a target of therapy for these cancers. In addition, PSCA has also shown clinical potential in immunotherapy as a prostate-specific antigen, which, when presented by dendritic cells, may elicit strong tumor-specific immunity. In contrast, PSCA is down-regulated in esophageal and gastric cancer and may have a tumor-suppressing function in the gastric epithelium. Recent exciting findings that genetic variations of PSCA conferred increased risks of gastric cancer and bladder cancer have opened up a new avenue of research about the pathological function of PSCA. PSCA seems to be a Jekyll and Hyde molecule that plays differential roles, tumor promoting or suppressing, depending on the cellular context. Clin Cancer Res; 16(14); 3533–8. ©2010 AACR.
Accuracy of Contrast-Enhanced Magnetic Resonance Imaging in Predicting Improvement of Regional Myocardial Function in Patients After Acute Myocardial Infarction
Authors: Bernhard L. Gerber, Jérôme Garot, David A. Bluemke, Kathérine C. Wu, João A.C. Lima
Journal: Circulation (2002)

Background— Contrast-enhanced (CE) MRI demonstrates a pattern of hypoenhancement early after contrast injection in acute myocardial infarction (MI) and a pattern of hyperenhancement late after contrast injection. Because the significance of these CE patterns for myocardial viability remains debated, we evaluated their diagnostic accuracy to quantitatively predict late functional improvement of regional contractility. Methods and Results— Twenty patients underwent CE and tagged MRI at 4 days and again at 7 months after acute MI. Resting circumferential shortening strain (Ecc) was analyzed in 24 segments per patient, and its improvement was correlated with the presence or absence of the CE patterns. Immediately after MI, 389 segments were considered dysfunctional because of having less than mean±2 SD Ecc of the remote region (−18±4%). At follow-up, significant improvement of Ecc occurred in 170 dysfunctional segments with normal CE (from −4±7% to −12±7%, P &lt;0.001) but not in 60 segments with early hypoenhancement (from −2±6% to −6±9% Ecc, P =NS). In 240 dysfunctional segments with delayed hyperenhancement, the improvement of Ecc (from −2±6% to −5±8%, P &lt;0.001) decreased with increasing transmural extent of hyperenhancement. Receiver operating characteristic analysis demonstrated that absence of delayed hyperenhancement, compared with absence of early hypoenhancement, had better sensitivity (82% versus 19%, respectively; P &lt;0.001) and accuracy (74% versus 49%, respectively; P &lt;0.001) in predicting recovery of Ecc to any given level. Conclusions— Compared with lack of early hypoenhancement, lack of delayed hyperenhancement has better diagnostic accuracy in predicting functional improvement in dysfunctional segments. The early hypoenhanced regions, which represent only the fraction of infarcted tissue with concomitant microvascular obstruction, greatly underestimate the amount of irreversibly injured myocardium present after acute MI.
Docetaxel and cisplatin: An active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck
Authors: P. Schöffski, G. Catimel, A.S.T. Planting, J.-P. Droz, J. Verweij, D. Schrijvers, L. Gras, A. Schrijvers, J. Wanders, A.R. Hanauske
Journal: Annals of Oncology (1999)
Harm Reduction Approaches to Reducing Tobacco-Related Mortality
Authors: Dorothy K. Hatsukami, Jack E. Henningfield, Michael Kotlyar
Journal: Annual Review of Public Health (2004)

Tobacco harm reduction approaches are gaining increased attention. Much of this attention is due to a growing concern that significant populations of smokers either do not want to quit or believe they are unable to quit smoking, and to a concern over tobacco-industry attempts to produce tobacco products that claim to result in less toxin exposure. Decreasing tobacco toxin exposure as a method for reducing mortality and morbidity may be a reasonable tobacco control strategy. However, the impact of this strategy must be explored both on individual and population levels. A significant amount of independent research is needed to inform policy decisions. Regulatory authority over potential reduced exposure products is also essential.
Updated consensus statement on biological agents for the treatment of rheumatoid arthritis and other immune mediated inflammatory diseases (May 2003)
Authors: D E Furst
Journal: Annals of the Rheumatic Diseases (2003)

As in previous years, the consensus group to consider the use of biological agents was constituted by rheumatologists from the Universities of Erlangen, Leiden, and Vienna in Europe in cooperation with universities in the United States, Canada, and Europe. Pharmaceutical industry support was obtained from a number of companies, but these institutions had no part in the decisions about the specific programme or about the academic participants at this conference. The 158 rheumatologists and bioscientists from 21 countries who attended the consensus conference were chosen from a worldwide group of doctors and other scientists interested in the use of biological agents for the treatment of immune mediated inflammatory diseases. The perspective of this consensus is from the treating doctor's point of view, rather than from the perspective of those paying for their use. The number of attendees and participants was limited so that not everyone who might have been appropriate could be invited. Additional information has come to light in the past year, both corroborating the major positive effect these drugs have had in rheumatoid arthritis (RA) and other immune mediated inflammatory diseases, as well as documenting possible new and unexpected adverse events. Therefore an update of the previous consensus statement seems both appropriate and necessary ( Ann Rheum Dis2002;61(suppl II):ii2–7 [OpenUrl][1][FREE Full Text][2] ). The consensus statement is annotated to document the credibility of the data supporting it as much as possible. This annotation is that of Shekelle et al and is described in appendix 3.99 All participants reviewed relevant clinical published articles relating to tumour necrosis factor (TNF) and interleukin 1 (IL1) blocking agents. They were given a draft consensus statement and were asked to revise the document in small discussion groups; open discussion of the revisions led to a final document, representing this updated consensus statement. Individual patients differ in the aggressiveness of … [1]: {openurl}?query=rft.jtitle%253DAnnals%2Bof%2Bthe%2BRheumatic%2BDiseases%26rft.stitle%253DAnn%2BRheum%2BDis%26rft.issn%253D0003-4967%26rft.aulast%253DFurst%26rft.auinit1%253DD%2BE%26rft.volume%253D61%26rft.issue%253D90002%26rft.spage%253Dii2%26rft.epage%253D7%26rft.atitle%253DUpdated%2Bconsensus%2Bstatement%2Bon%2Bbiological%2Bagents%2Bfor%2Bthe%2Btreatment%2Bof%2Brheumatoid%2Barthritis%2Band%2Bother%2Brheumatic%2Bdiseases%2B%2528May%2B2002%2529%26rft_id%253Dinfo%253Apmid%252F12379612%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=annrheumdis&resid=61/suppl_2/ii2&atom=%2Fannrheumdis%2F62%2Fsuppl_2%2Fii2.atom
Accuracy of Hysteroscopy in the Diagnosis of Endometrial Cancer and Hyperplasia
Authors: T. Justin Clark, Doris Voit, Janesh K. Gupta, Christopher Hyde, Fujian Song, Khalid S. Khan
Journal: JAMA (2002)

Hysteroscopy (direct endoscopic visualization of the endometrial cavity) is used extensively in the evaluation of common gynecologic problems, such as menorrhagia and postmenopausal bleeding. However, there is a continuing debate about the value of this technology in the diagnosis of serious endometrial disease.To determine the accuracy of hysteroscopy in diagnosing endometrial cancer and hyperplasia in women with abnormal uterine bleeding.Relevant articles were identified through searches of the Cochrane Library, MEDLINE, and EMBASE (1984-2001), manual searches of bibliographies of known primary and review articles, and contact with manufacturers.Studies were selected blindly, independently, and in duplicate if accuracy of hysteroscopy was estimated in women with abnormal uterine bleeding, using histopathologic findings as a reference standard. Our search identified 3486 articles; 208 of these were deemed to be potentially eligible and were retrieved for detailed data extraction. Sixty-five primary studies were analyzed, including 26 346 women.Data were abstracted on characteristics and quality from each study. Results for diagnostic accuracy were extracted to form 2 x 2 contingency tables separately for endometrial cancer and endometrial disease (cancer, hyperplasia, or both). Pooled likelihood ratios (LRs) were used as summary accuracy measures.The pretest probability of endometrial cancer was 3.9% (95% confidence interval [CI], 3.7%-4.2%). A positive hysteroscopy result (pooled LR, 60.9; 95% CI, 51.2-72.5) increased the probability of cancer to 71.8% (95% CI, 67.0%-76.6%), whereas a negative hysteroscopy result (pooled LR, 0.15; 95% CI, 0.13-0.18) reduced the probability of cancer to 0.6% (95% CI, 0.5%-0.8%). There was statistical heterogeneity in pooling of LRs, but an explanation for this could not be found in spectrum composition and study quality. The overall accuracy for the diagnosis of endometrial disease was modest compared with that of cancer, and the results were heterogeneous. The accuracy tended to be higher among postmenopausal women and in the outpatient setting.The diagnostic accuracy of hysteroscopy is high for endometrial cancer, but only moderate for endometrial disease (cancer or hyperplasia).
Predictors of Resistance to Preoperative Trastuzumab and Vinorelbine for HER2-Positive Early Breast Cancer
Authors: Lyndsay N. Harris, Fanglei You, Stuart J. Schnitt, Agnes Witkiewicz, Xin Lu, Dennis Sgroi, Paula D. Ryan, Steven E. Come, Harold J. Burstein, Beth-Ann Lesnikoski, Madhavi Kamma, Paula N. Friedman, Rebecca Gelman, J. Dirk Iglehart, Eric P. Winer
Journal: Clinical Cancer Research (2007)

To assess pathologic complete response (pCR), clinical response, feasibility, safety, and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer.Forty-eight patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks. Single and multigene biomarker studies were done in an attempt to identify predictors of response.Eight of 40 (20%) patients achieved pCR (95% confidence interval, 9-36%). Of 9 additional patients recruited for protocol-defined toxicity analysis, 8 were evaluable; 42 of 48 (88%) patients had clinical response (16 patients, clinical complete response; 26 patients, clinical partial response). T(1) tumors more frequently exhibited clinical complete response (P = 0.05) and showed a trend to exhibit pCR (P = 0.07). Five (13%) patients experienced grade 1 cardiac dysfunction during preoperative treatment. Neither HER2 nor estrogen receptor status changed significantly after exposure to trastuzumab and vinorelbine. RNA profiling identified three top-level clusters by unsupervised analysis. Tumors with extremes of response [pCR (n = 3) versus nonresponse (n = 3)] fell into separate groups by hierarchical clustering. No predictive genes were identified in pCR tumors. Nonresponding tumors were more likely to be T(4) stage (P = 0.02) and express basal markers (P < 0.00001), growth factors, and growth factor receptors. Insulin-like growth factor-I receptor membrane expression was associated with a lower response rate (50% versus 97%; P = 0.001).Preoperative trastuzumab plus vinorelbine is active and well tolerated in patients with HER2-positive, operable, stage II/III breast cancer. HER2-overexpressing tumors with a basal-like phenotype, or with expression of insulin-like growth factor-I receptor and other proteins involved in growth factor pathways, are more likely to be resistant to this regimen.
Subfornical organ. Does it protect against angiotensin II-induced hypertension in the rat?
Authors: C A Bruner, M L Mangiapane, G D Fink
Journal: Circulation Research (1985)

The purpose of this study was to examine the contribution of the subfornical organ to the chronic hypertension produced by intravenous angiotensin II infusion in rats. Male rats were instrumented with permanent arterial and venous catheters and housed in metabolism cages for daily measurement of arterial pressure, heart rate, water intake, water balance, and urinary electrolyte excretion. Angiotensin II was infused intravenously at a rate of 10 ng/minute for 5 consecutive days, preceded by 2 control days, and followed by 2 recovery days. Normal rats with an intact subfornical organ (n = 7), and rats with an electrolytic lesion placed such that greater than 80% of the subfornical organ was destroyed (n = 9), were studied using this infusion protocol. An additional group of eight rats did not receive angiotensin II, and, thus, served as a time control. Both groups of rats receiving angiotensin II exhibited significant elevations in arterial pressure during the 5-day hormone infusion period, but pressure in rats with subfornical organ lesions (delta 23-29 mm Hg) was increased significantly more than that of intact rats (delta 14-20 mm Hg). Water intake was significantly increased on the 3rd, 4th, and 5th days of angiotensin II infusion only in rats with lesions in the subfornical organ. In contrast to previous studies showing that an intact subfornical organ is required for normal pressor and drinking responses to acute elevations in circulating angiotensin II in the rat, the current experiments indicate that the presence of the subfornical organ actually inhibits these same responses during more chronic increases in plasma angiotensin II levels.
p38 Mitogen-Activated Protein Kinase Downregulates Endothelial Progenitor Cells
Authors: Florian H. Seeger, Judith Haendeler, Dirk H. Walter, Ulrich Rochwalsky, Johannes Reinhold, Carmen Urbich, Lothar Rössig, Anne Corbaz, Yolande Chvatchko, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation (2005)

Background— Transplantation of endothelial progenitor cells (EPCs) improves neovascularization after ischemia, but patients with coronary artery disease (CAD) or diabetes mellitus show a reduced number of EPCs and impaired functional activity. Therefore, we investigated the effects of risk factors, such as glucose and TNF-α, on the number of EPCs in vitro to elucidate the underlying mechanisms. Methods and Results— EPCs of patients or healthy subjects were isolated from peripheral blood. Incubation with glucose or TNF-α dose-dependently reduced the number of EPCs (79.9±1.3% and 74.3±8.1% of control; P &lt;0.05, respectively). This reduction was not caused by apoptosis. TNF-α and glucose induced a dose- and time-dependent activation of the p38 MAP kinase, the downstream kinase mitogen- and stress-activated kinase 1, and the transcription factor cAMP-responsive element–binding protein (CREB), in EPCs. Moreover, EPCs from CAD patients had significantly higher basal p38-phosphorylation levels (1.83±0.2-fold increase; P &lt;0.05) compared with healthy subjects. The inhibition of the p38-kinase by SB203580 or infection with a dominant negative p38 kinase adenovirus significantly increased basal number of EPCs (136.7±6.3% and 142.9±18% versus control, respectively). Likewise, ex vivo cultivation of EPCs from patients with CAD with SB203580 significantly increased the number of EPCs and partially reversed the impaired capacity for neovascularization of EPCs in vivo (relative blood flow: 0.40±0.03 versus 0.64±0.08, P &lt;0.05). The increased numbers of EPCs by SB203580 were associated with an augmentation of EPC proliferation and a reduction of cells expressing the monocytic marker proteins CD14 and CD64, suggesting that p38 regulates proliferation and differentiation events. Conclusions— These results demonstrate that p38 MAP kinase plays a pivotal role in the signal transduction pathways regulating the number of EPCs ex vivo. SB203580 can prevent the negative effects of TNF-α and glucose on the number of EPCs and may be useful to improve the number of EPCs for potential cell therapy.
Give me A5 for lipoprotein hydrolysis!
Authors: Martin Merkel, Joerg Heeren
Journal: Journal of Clinical Investigation (2005)

APOA5 is a newly identified apolipoprotein that plays a crucial role in the regulation of plasma triglyceride levels. In several human studies, common APOA5 single nucleotide polymorphisms have been strongly associated with elevated plasma triglyceride levels. In this issue of the JCI, Marçais et al. report that the rare Q139X mutation in APOA5 leads to severe hypertriglyceridemia by exerting a dominant-negative effect on the plasma lipolytic system for triglyceride-rich lipoproteins. The presented data support the idea that the molecular mechanism of APOA5 function may include the enhancement of binding between lipoproteins and proteoglycans at the vascular wall and activation of proteoglycan-bound lipoprotein lipase.
Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study
Authors: Yoo-Joung Ko, Christine M Canil, Som D Mukherjee, Eric Winquist, Christine Elser, Andrea Eisen, M Neil Reaume, Liying Zhang, Srikala S Sridhar
Journal: The Lancet Oncology (2013)
The legacy of Homer W. Smith: mechanistic insights into renal physiology
Authors: L. Gabriel Navar
Journal: Journal of Clinical Investigation (2004)

In 1945, Homer W. Smith published an article in the JCI that clearly demonstrated that para-aminohippuric acid is the most suitable agent for the evaluation of renal plasma flow in both humans and dogs; in addition, the paper provided detailed methodology that is still in use today. This paper is but one of many outstanding works performed by Smith and his colleagues that clearly established the clearance technique as a powerful noninvasive approach to gain mechanistic insights into intrarenal function.
Magnetic Resonance Imaging Visualization of Hyaluronidase in Ovarian Carcinoma
Authors: Liora Shiftan, Tomer Israely, Miriam Cohen, Veronica Frydman, Hagit Dafni, Robert Stern, Michal Neeman
Journal: Cancer Research (2005)

Abstract Hyaluronan, a high molecular weight, negatively charged polysaccharide, is a major constituent of the extracellular matrix. High molecular weight hyaluronan is antiangiogenic, but its degradation by hyaluronidase generates proangiogenic breakdown products. Thus, by expression of hyaluronidase, cancer cells can tilt the angiogenic balance of their microenvironment. Indeed, hyaluronidase-mediated breakdown of hyaluronan correlates with aggressiveness and invasiveness of ovarian cancer metastasis and with tumor angiogenesis. The goal of this work was to develop a novel smart contrast material for detection of hyaluronidase activity by magnetic resonance imaging (MRI). Gadolinium-diethylenetriaminepentaacetic acid (GdDTPA) covalently linked to hyaluronan on the surface of agarose beads showed attenuated relaxivity. Hyaluronidase, either purified from bovine testes or secreted by ES-2 and OVCAR-3 human epithelial ovarian carcinoma cells, activated the hyaluronan-GdDTPA-beads by rapidly altering the R1 and R2 relaxation rates. The change in relaxation rates was consistent with the different levels of biologically active hyaluronidase secreted by those cells. Hyaluronan-GdDTPA-beads were further used for demonstration of MRI detection of hyaluronidase activity in the proximity of s.c. ES-2 ovarian carcinoma tumors in nude mice. Thus, hyaluronan-GdDTPA-beads could allow noninvasive molecular imaging of hyaluronidase-mediated tilt of the peritumor angiogenic balance.