tbuckley/cabot-search huggingface dataset:
Cumulative Blood Pressure in Early Adulthood and Cardiac Dysfunction in Middle Age
Authors: Satoru Kishi, Gisela Teixido-Tura, Hongyan Ning, Bharath Ambale Venkatesh, Colin Wu, Andre Almeida, Eui-Young Choi, Ola Gjesdal, David R. Jacobs, Pamela J. Schreiner, Samuel S. Gidding, Kiang Liu, João A.C. Lima
Journal: Journal of the American College of Cardiology (2015)
Abstract 14681: Heart Failure with Preserved Ejection Fraction (hfpef): What are the Predictors of Poor Outcome?
Authors: Rajender Singh, J J Murphy, D Wilson, G Brennan, A Fuat, A P S Hungin
Journal: Circulation (2012)

Introduction Heart failure (HF) is a complex clinical syndrome with high morbidity and mortality. For those with left ventricular systolic dysfunction (LVSD) there are models to predict long term outcome. HF with preserved ejection fraction (HFPEF) is increasingly recognised in clinic practice, but factors that predict poor outcome are not known. Predictors of poor outcome cannot be extrapolated from patients with LVSD, as the natural history of LVSD and HFPEF is not comparable. In this nested cohort study we report the predictors of long-term outcome of patients with HFPEF. Method Patients were referred from primary or secondary care to a diagnostic HF clinic. Based on the initial clinical assessment and echo, patients were allocated to one of 3 groups: HF due to LVSD, HFPEF & non-HF. HFPEF was diagnosed using the following criteria: ongoing NYHA class II-IV symptoms, preserved systolic function (EF > 45%) plus any two abnormal investigations 1) Chest X-ray showing pulmonary oedema or cardiomegaly, 2) ec...
Multi-institutional quality care initiative (QCI) to improve the care of patients with invasive bladder cancer (BlCa).
Authors: Bernard H. Bochner, Andrew Feifer, Dahlia Sperling, Joseph W Mashni, Dean F. Bajorin, Jay Bakul Shah, Ashish M. Kamat, Gary D. Steinberg, Walter Michael Stadler, Robert L. Grubb, Adam S. Kibel, Mark Schoenberg, Peter C. Black, Alexandre Zlotta, Wassim Kassouf, Seth P. Lerner, Yair Lotan
Journal: Journal of Clinical Oncology (2014)

298 Background: Level 1 evidence supports a survival benefit for BlCa pts that receive periop cisplatin chemotherapy in addition to radical cystectomy (RC). Underutilization of multimodal therapy has been reported nationally. We instituted a multicenter QCI to improve the use of periop chemotherapy. Methods: A two phase effort was initiated at 16 academic institutions. Phase 1 was initiated in 2010 and designed to evaluate baseline patterns of periop chemotherapy use for T2-4N0M0 BlCa pts that underwent RC between 2003-2008. Phase 2 was a prospective QCI. The quality indicators included (1) referral to medical oncology for consideration of multimodality therapy, (2) neoadjuvant, if recommended, be cisplatin based and at least 3 cycles, (3) adjuvant, if recommended, be cisplatin based and at least 3 cycles, (4) all treatment be completed within 6 months. Data on all eligible pts were collected prospectively for 12 months on a web-based survey system. Results: All 16 centers participated in phase 1. Of 4,344 pts on whom data was available, 34% received periop chemotherapy. Neoadjuvant and adjuvant therapy use was 14% and 20%, respectively. 65% of pts receiving periop chemotherapy were treated with a cisplatin-based regimen. Of those treated neoadjuvantly, cisplatin was received in 70% of cases. Nine of the 16 institutions completed phase 2 data collection. Over 700 pts that underwent RC were evaluated. 395 pts with T2-4N0M0 disease were deemed eligible for data entry. Fifty-six percent of eligible pts received periop systemic chemotherapy. Of this 56%, 47% received neoadjuvant cisplatin chemotherapy and 9% received adjuvant cisplatin chemotherapy. This represented a 64.7% increase in the use of any periop chemotherapy and a 3.4 fold increase in neoadjuvant chemotherapy compared to baseline data. Conclusions: We have successfully completed a multi-institutional QCI to improve the use of periop chemotherapy in pts undergoing RC for resectable, non-metastatic bladder cancer. Our data demonstrates that significant improvements can be achieved in not only overall use of periop chemotherapy but most notably in the use of neoadjuvant chemotherapy.
Should hepatic dysplastic nodules and regenerative nodules be regarded as premalignant lesions and treated?
Authors: Lei Zhao, Linda L. Wong, Xuetao Shi, Junfang Ji
Journal: Hepatology (2016)

LZ is funded by 2015 Innovation and Creation Fund of Shandong Academy of Medical Science. Potential conflict of interest: Dr. Wong is on the speakers' bureau for Bayer. To the Editor: The American Association for the Study of Liver Diseases (AASLD) practice guidelines on management of hepatocellular carcinoma (HCC) was last updated in 20111; another update is anticipated soon. For high‐grade dysplastic nodules (HGDNs), low‐grade dysplastic nodules (LGDNs), or large regenerative nodules (LRNs), it suggests "enhanced follow‐up." No treatment would be provided until the diagnosis of HCC established during the follow‐up. However, is follow‐up always the best choice? Perhaps we can attempt to compare this to colorectal adenoma by focusing on their clinical behavior and malignant potential. In the National Comprehensive Cancer Network (NCCN) guideline, adenomatous polyps are accepted precursors to colorectal cancer (CRC) and removed to prevent cancer.2 A recent cohort study estimated that the average annual transition rate from advanced adenoma to CRC in men was 3.1%,3 so the 5‐year‐transition rate was around 15%. In HCC, several studies have revealed a relatively high transition rate of hepatic nodular lesions to HCC. In 154 patients with chronic hepatitis and cirrhosis, Kobayashi et al. reported the annual transition rate of 20% for patients with HGDN and 10% for patients with LGDN. The 5‐year cumulative transition rate from HGDN and LGDN was 80.8% and 30.2%, respectively. Even regenerative nodules without dysplasia evolved into HCC in 12.4%.4 More recently, Sato et al. studied 68 LRNs and 20 dysplastic nodules (DNs) from 1,500 consecutive nodular lesions; the 50‐month transition rate was 13.6% in LRNs and 40% in DNs.5 Earlier studies support these findings. Thus, DNs, especially HGDNs, have the high potential of malignant transition, and LRNs in patients with chronic hepatitis and cirrhosis can be considered as pre‐HCC lesion. In AASLD guidelines, the continuum between HGDN and early HCC obscures the diagnosis, whereas the smaller lesions would be more likely to receive curative treatment. Thus, we further raise the enquiry of whether LRNs and DNs should undergo active treatment, perhaps with minimally invasive ablation therapies. Preventing the transition to HCC by actively treating DNs and LRNs, such as removing colonic adenomas, may not only improve overall outcome, but also potentially decrease the need for liver transplantation in patients who can live with well‐compensated cirrhosis. Certainly, this provocative concept would need to be studied in a prospective, randomized controlled trial with long‐term follow‐up.
Controlled Cell Growth and Cell Migration in Periodic Mesoporous Organosilica/Alginate Nanocomposite Hydrogels
Authors: Nermin Seda Kehr, Kristina Riehemann
Journal: Advanced Healthcare Materials (2015)

Nanocomposite (NC) hydrogels with different periodic mesoporous organosilica (PMO) concentrations and a NC hydrogel bilayer with various PMO concentrations inside the layers of the hydrogel matrix are prepared. The effect of the PMO concentration on cell growth and migration of cells is reported. The cells migrate in the bilayer NC hydrogel towards higher PMO concentrations and from cell culture plates to NC hydrogel scaffolds.
Chemo-selection as a strategy for organ preservation in patients with T4 laryngeal squamous cell carcinoma
Authors: F. P. Worden, G. Wolf, A. Eisbruch, J. Lee, C. R. Bradford, D. Chepeha, T. Teknos, M. Prince, N. Hogikyan, C. Tsien, S. G. Urba
Journal: Journal of Clinical Oncology (2007)

6005 Background: We previously reported high rates of overall survival (OS) and laryngeal preservation in two sequential phase II trials with stage III/IV laryngeal squamous cell carcinoma patients (pts), who attained a &gt;50% response after 1 cycle of induction chemotherapy, and who were treated with chemoradiation. Since then, all pts were re-staged to correspond with the most recent American Joint Committee on Cancer staging guidelines. Here we report the outcomes of the T 4 pts from both studies. Methods: Pts received 1 cycle of cisplatin 100 mg/m 2 &amp; 5-FU 1,000 mg/m 2 /day × 5 days (P+5FU). Pts with &gt; 50% response received chemoradiation with 70 Gy &amp; P 100 mg/m 2 , days 1, 22, &amp; 43. Pts with ≤ 50% response underwent laryngectomy. Final planned tumor assessment by direct laryngoscopy with biopsy was performed 8 wks after chemoradiation. Pts who were histologic complete responders, received 2 cycles of P+5FU. Pts with residual disease had planned salvage surgery. Results: Thirty-two T 4 eligible (cartilage invasion 31, base of tongue involvement 1) pts were enrolled, 23 M; 9 F; median age 56; stage: IVA 31, IVB 1; site: 19 supraglottic, 13 glottic. After 1 cycle induction chemotherapy, 26 pts (81%) had &gt; 50% response &amp; received chemoradiation; 5 (16%) had surgery; &amp; 1 refused surgery. After chemoradiation, 22 pts had a complete histologic response, &amp; 4 pts required immediate salvage larngectomy for residual disease. Of those responding to chemoradiation, 2 pts eventually required salvage laryngectomy. Currently, 17/32 (53%) are alive (15 without disease), 10 are dead of disease, &amp; 5 are dead from other causes. Toxicity: grade 3/4 granulocytopenia 19%, grade 3/4 mucositis 49%. Median time to follow-up is 45 months. The 3 yr overall survival (OS) is 75% (95% CI=55%, 86%), &amp; the 4 yr OS is 70% (95% CI = 50%, 83%). The 3 yr disease-free survival (DFS) is 77% (CI=58%, 88%), &amp; the 4 yr DFS is 72% (CI=52%, 85%). Conclusions: Our results suggest that chemo-selection is an alternative, organ preservation strategy to total laryngectomy for pts with T 4 laryngeal squamous cell carcinoma. No significant financial relationships to disclose.
Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer
Authors: Johan F. Vansteenkiste, Jean-Luc Canon, Filippo De Braud, Francesco Grossi, Tommaso De Pas, Jhanelle E. Gray, Wu-Chou Su, Enriqueta Felip, Hiroshige Yoshioka, Cesare Gridelli, Grace K. Dy, Sumitra Thongprasert, Martin Reck, Paola Aimone, Gena Atalla Vidam, Pantelia Roussou, Ying A. Wang, Emmanuelle Di Tomaso, Jean-Charles Soria
Journal: Journal of Thoracic Oncology (2015)

The phosphatidylinositol 3-kinase (PI3K) pathway promotes tumor growth and treatment resistance in non-small cell lung cancer (NSCLC). The aim of the open-label, two-stage, Phase II study BASALT-1 (NCT01820325) was to investigate the pan-PI3K inhibitor buparlisib (BKM120) in patients with PI3K pathway-activated, relapsed NSCLC.After prescreening for PI3K pathway activation, patients with PI3K pathway-activated, metastatic, squamous or nonsquamous NSCLC, who had relapsed after prior systemic antineoplastic therapy, were enrolled. In Stage 1, patients received single-agent buparlisib (100 mg/day). A futility analysis was performed independently in each histology group, based on the 12-week progression-free survival rate for the first 30 patients treated in each group being less than 50%. Exploratory biomarker analyses were performed in archival tissue samples and circulating tumor DNA (ctDNA).Of 1242 prescreened patients, 13.5% exhibited PI3K pathway activation. As of June 5, 2014, 63 patients (30 squamous and 33 nonsquamous) were treated in Stage 1. The 12-week progression-free survival rates were 23.3% (95% confidence interval: 9.9-42.3) and 20.0% (95% confidence interval: 7.7-38.6) in the squamous and nonsquamous groups, respectively. Stage 2 was therefore not initiated in either group. PI3K pathway mutations in ctDNA were more concordant with metastatic tissue than with primary biopsies.Despite preselecting patients for targeted treatment, BASALT-1 did not meet its primary objective during Stage 1. PI3K pathway activation can be detected using ctDNA, but may not be the main oncogenic driver in NSCLC. Combinations of PI3K inhibitors with other agents may demonstrate greater efficacy than monotherapy.
<i>LOX</i> Mutations Predispose to Thoracic Aortic Aneurysms and Dissections
Authors: Dong-chuan Guo, Ellen S. Regalado, Limin Gong, Xueyan Duan, Regie Lyn P. Santos-Cortez, Pauline Arnaud, Zhao Ren, Bo Cai, Ellen M. Hostetler, Rocio Moran, David Liang, Anthony Estrera, Hazim J. Safi, Suzanne M. Leal, Michael J. Bamshad, Jay Shendure, Deborah A. Nickerson, Guillaume Jondeau, Catherine Boileau, Dianna M. Milewicz
Journal: Circulation Research (2016)

Mutations in several genes have been identified that are responsible for 25% of families with familial thoracic aortic aneurysms and dissections. However, the causative gene remains unknown in 75% of families.To identify the causative mutation in families with autosomal dominant inheritance of thoracic aortic aneurysms and dissections.Exome sequencing was used to identify the mutation responsible for a large family with thoracic aortic aneurysms and dissections. A heterozygous rare variant, c.839G>T (p.Ser280Arg), was identified in LOX, encoding a lysyl oxidase, that segregated with disease in the family. Sanger and exome sequencing was used to investigate mutations in LOX in an additional 410 probands from unrelated families. Additional LOX rare variants that segregated with disease in families were identified, including c.125G>A (p.Trp42*), c.604G>T (p.Gly202*), c.743C>T (p.Thr248Ile), c.800A>C (p.Gln267Pro), and c.1044T>A (p.Ser348Arg). The altered amino acids cause haploinsufficiency for LOX or are located at a highly conserved LOX catalytic domain, which is relatively invariant in the population. Expression of the LOX variants p.Ser280Arg and p.Ser348Arg resulted in significantly lower lysyl oxidase activity when compared with the wild-type protein. Individuals with LOX variants had fusiform enlargement of the root and ascending thoracic aorta, leading to ascending aortic dissections.These data, along with previous studies showing that the deficiency of LOX in mice or inhibition of lysyl oxidases in turkeys and rats causes aortic dissections, support the conclusion that rare genetic variants in LOX predispose to thoracic aortic disease.
Human Bone Marrow Myeloma Cells Express RANKL
Authors: Orhan Sezer, Ulrike Heider, Christian Jakob, Jan Eucker, Kurt Possinger, G. David Roodman
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.1.353 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11773196 Human Bone Marrow Myeloma Cells Express RANKL Orhan SezerxOrhan SezerSearch for articles by this author , Ulrike HeiderxUlrike HeiderSearch for articles by this author , Christian JakobxChristian JakobSearch for articles by this author , Jan EuckerxJan EuckerSearch for articles by this author , Kurt PossingerxKurt PossingerSearch for articles by this author G. David RoodmanxG. David RoodmanSearch for articles by this author Show More Universitätsklinikum Charité, Berlin, GermanyUniversity of Texas Science Center at San Antonio, San Antonio, TX https://doi.org/10.1200/JCO.2002.20.1.353 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01012002In Reply:Thank you for your letter. Several groups, including the data you have provided, have found that myeloma cells themselves express receptor activator of NF-kappaB ligand (RANKL), although the levels of RANKL expression have been variable. In contrast to the results that you report, others, such as Pearse et al,1 have not detected RANKL expression by myeloma cells in bone marrow biopsy specimens from patients with myeloma. These researchers found that RANKL was not expressed by myeloma cells in the 14 bone marrow biopsy specimens from myeloma patients they examined either by immunocytochemistry, in situ hybridization, or polymerase chain reaction. They found that RANKL expression was increased in multiple myeloma–infiltrated marrow but that RANKL was expressed by activated T cells and stromal cells and not by myeloma cells. Furthermore, they could not find RANKL expression by myeloma cell lines ARP-1, U266, RPM18226, H929, and ARH-77, as assessed by receptor activator of NF-kappaB (RANK)-Fc binding or by reverse transcriptase polymerase chain reaction. Although expression of RANKL by myeloma cells is shown very nicely by your results and those of others, it has not been a consistent finding by all investigators. The most consistent finding by most investigators is that RANKL expression is increased in marrow stromal cells from myeloma patients.REFERENCE1. Pearse RN, Sordillo EM, Yaccoby S, et al: Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci U S A 98:: 11581,2001-11586, Crossref, Medline, Google Scholar
Lymph node ratio and survival for gastric cancer: A retrospective analysis of the SEER database
Authors: R. Shridhar, G. W. Dombi
Journal: Journal of Clinical Oncology (2009)

4561 Purpose: To determine the prognostic significance of the lymph node ratio (ratio of number of positive lymph nodes to number of dissected lymph nodes) in gastric cancer patients. Methods: We retrospectively analyzed 10,176 gastric patients from 1990–2003 who underwent curative gastrectomy from the SEER database. Survival curves were calculated according to the Kaplan-Meier method and analyzed with log-rank test. Multivariate analysis of prognostic factors related to survival was performed by the Cox proportional hazard model. Results: The lymph node ratio (LNR) was a strong predictor of survival. LNR was equally predictive of survival whether the analysis was restricted to patients with &lt;15 lymph nodes dissected or &gt;15 lymph nodes dissected. Survival of patients with a LNR of 0.1–5% was not significantly different than node negative patients; however, survival of patients with a LNR of 5–10% was significantly different than node negative patients. Multivariate analysis showed that LNR, T-stage, tumor size, and number of lymph nodes positive were independent prognostic predictors of death and that LNR was the strongest predictor for death. Multivariate analysis showed that the number of lymph nodes dissected was an independent prognostic factor for survival. Moreover, LNR was an independent prognostic factor for N1 and N2 patients by AJCC staging. LNR trended toward significance in AJCC N3 patients. Conclusions: LNR was the strongest predictor of death in gastric cancer patients when compared to T-stage, number of lymph nodes positive, and tumor size. LNR is equally predictive regardless of the adequacy of the lymph node dissection. No significant financial relationships to disclose.
Abstract 15386: Reduction in Striated Preferentially Expressed Gene leads to Decompensated Heart Failure after Transverse Aortic Constriction in Mice
Authors: Xiaoli Liu, Mark A Perrella
Journal: Circulation (2014)

Introduction:  Striated preferentially expressed gene (Speg) is a member of the myosin light chain kinase family of proteins. Disruption of the Speg gene locus in mice leads to a dilated cardiomyopathy and pervasive death shortly after birth on a C57BL/6 background, and occasional survival on a C57/BL/6 x 129 SvJ background.   Hypothesis:  Beyond the neonatal period, Speg also plays an important role in adult heart function.   Methods:  1) To characterize adult mice, we bred Speg heterozygous (+/-) mice (C57BL/6 x 129SvJ), and performed echocardiograms (echos) on surviving Speg homozygous (-/-) mice at 10 weeks of age. 2) 8 week old wild-type (Speg+/+) and Speg+/- mice (C57BL/6) underwent transverse aortic constriction (TAC), and echos were performed at 2 and 4 weeks post-TAC.   Results:  1) Adult Speg-/- mice (C57BL/6 x 129SvJ) showed a significant increase in ratio of heart to body weight when compared with Speg+/+ and Speg+/- hearts (7.57±0.34 mg/gm versus 4.42±0.25 and 4.12±0.08 mg/gm, respectively). Both ejection fraction (EF) and fractional shortening (FS) were significantly decreased in Speg-/- hearts (46.7±10.9% and 24.3±6.2%, respectively), compared with Speg+/+ (84.4±7.2% and 52.3±2.6%) and Speg+/- (77.2±1.6% and 44.9±1.7%) hearts. 2) There was no significant difference between heart weight and function of Speg+/+ and Speg+/- mice (C57BL/6) at baseline, and both groups showed a significant increase in heart weight at 2 and 4 weeks after TAC. LV internal diameter (LVID) decreased in both groups at 2 weeks after TAC. However, by 4 weeks post-TAC, LVID increased significantly in Speg+/- mice compared with sham mice, and Speg+/+ mice receiving TAC of the same duration. Cardiac function was initially preserved in both groups after 2 weeks of TAC, however at 4 weeks the EF and FS more dramatically decreased in the Speg+/- (39.8±3.5% and 19.6±2.0%, respectively) compared with Speg+/+ (56.3±4.3% and 30.5±3.4%) mice.   Conclusions:  1) Speg-/- mice (C57BL/6 x 129SvJ) that survive to adulthood develop severe cardiac dysfunction. 2) After 4 weeks of pressure overload, the Speg+/- hearts decompensated, with a greater increase in LV chamber size and a more marked decrease in function, compared with Speg+/+ hearts. Thus, Speg expression is important for adult heart function.