tbuckley/cabot-search huggingface dataset:
Prognostic value of different B symptoms in upper aerodigestive tract NK/T-cell lymphoma
Authors: J. Xiao, C. Guo, L. Zhai, H. Li, X. Fu, Y. Huang, Y. Huang, J. Huang, X. Pu, T. Lin, S. Ye
Journal: Journal of Clinical Oncology (2009)

e19544 Background: Extranodal NK/T-cell lymphoma (ENKL) is a rare disease originated from NK or toxic T cells. ENKL arising from the upper aerodigestive tract (UNKTL) is a newly recognized subtype and commonly presents with B symptoms. This study is to investigate the prognostic value of different B symptoms in UNKTL. Methods: UNKTL cases with detailed clinical, pathological and prognostic data in our center since 2001 to 2007 were retrospectively analyzed with the major study endpoint of overall survival (OS). Central pathological review was performed. Survival curves were estimated by Kaplan-Meier method and tested by Log Rank method. Statistically significant factors in univariate analysis were then included in multivariate analysis. B symptoms were defined as fever, night sweat and weight loss according to the Ann Arbor Cotswolds meeting. The predictive values of survival for each type of B symptoms were studied independently. Results: 172 cases of UNKTL with a median follow-up duration of 27.4 months were included. 45 ladies and 127 gentlemen had a median age of 43 years. 98 cases were Ann Arbor stage I, 54 were stage II and the remaining 20 cases were stage III or IV. About half of the patients present B symptoms: 82 had fever, 5 had night sweat and 6 present weight loss. Totally 18 patients had ECOG PS larger than 1. The 5-year OS rate of the whole group is 41.8%. Patients with persistent fever before treatment indicated a poor outcome in the univariate analysis (p=.033) and its prognostic value was also confirmed by the Cox regression (p=.030) whereas those of night sweat and weight loss were not (p= .960 and .824 respectively). Conclusions: B symptoms were common in UNKTL patients. Our data suggested that only fever among the three types of B symptoms was independent prognostic factor for UNKTL but it still needs further confirmation. No significant financial relationships to disclose.
Abstract 11930: Association of Inter- and Intra-Ventricular Dyssynchrony With Right Ventricular Performance in Patients With Pulmonary Hypertension
Authors: Yoshiki Motoji, Hidekazu Tanaka, Yuko Fukuda, Takuma Sawa, Yoshiki Yamadori, Junichi Imanishi, Tatsuya Miyoshi, Yasuhide Mochizuki, Kazuhiro Tatsumi, Kensuke Matsumoto, Noriaki Emoto, Hiroya Kawai, Ken-ichi Hirata
Journal: Circulation (2013)

Background: In pulmonary hypertension (PH) patients, increasing of right ventricular (RV) wall tension due to elevation of pulmonary artery pressure (PAP) leads to prolongation of RV systole, resul...
Heparan sulfate proteoglycans mediate Aβ-induced oxidative stress and hypercontractility in cultured vascular smooth muscle cells
Authors: Matthew R. Reynolds, Itender Singh, Tej D. Azad, Brandon B. Holmes, Phillip B. Verghese, Hans H. Dietrich, Marc Diamond, Guojun Bu, Byung Hee Han, Gregory J. Zipfel
Journal: Molecular Neurodegeneration (2016)

Substantial evidence suggests that amyloid-β (Aβ) species induce oxidative stress and cerebrovascular (CV) dysfunction in Alzheimer's disease (AD), potentially contributing to the progressive dementia of this disease. The upstream molecular pathways governing this process, however, are poorly understood. In this report, we examine the role of heparan sulfate proteoglycans (HSPG) in Aβ-induced vascular smooth muscle cell (VSMC) dysfunction in vitro. Our results demonstrate that pharmacological depletion of HSPG (by enzymatic degradation with active, but not heat-inactivated, heparinase) in primary human cerebral and transformed rat VSMC mitigates Aβ1-40- and Aβ1-42-induced oxidative stress. This inhibitory effect is specific for HSPG depletion and does not occur with pharmacological depletion of other glycosaminoglycan (GAG) family members. We also found that Aβ1-40 (but not Aβ1-42) causes a hypercontractile phenotype in transformed rat cerebral VSMC that likely results from a HSPG-mediated augmentation in intracellular Ca2+ activity, as both Aβ1-40-induced VSMC hypercontractility and increased Ca2+ influx are inhibited by pharmacological HSPG depletion. Moreover, chelation of extracellular Ca2+ with ethylene glycol tetraacetic acid (EGTA) does not prevent the production of Aβ1-40- or Aβ1-42-mediated reactive oxygen species (ROS), suggesting that Aβ-induced ROS and VSMC hypercontractility occur through different molecular pathways. Taken together, our data indicate that HSPG are critical mediators of Aβ-induced oxidative stress and Aβ1-40-induced VSMC dysfunction.
ERCC1 expression as a predictor for chemosensitivity in recurrent colorectal cancer patients receiving cisplatinum (CDDP) plus S-1 chemotherapy
Authors: K. Uchida, K. Hayashi, H. Kuramochi, K. Kudo, S. Miyakura, I. Fujita, M. Yamamoto, K. D. Danenberg, P. V. Danenberg, K. Takasaki
Journal: Journal of Clinical Oncology (2006)

13065 Background: To test the hypotheses of whether the relative mRNA expression of excision cross complement-1 (ERCCI) are associated with response to CDDP+S-1 chemotherapy in recurrent colorectal cancer (CRC). We assessed the relationship between ERCC1 mRNA expression levels and the response. Methods: Thirty four patients with relapsed CRC were treated with cisplatin 30 mg/m 2 on Day 1 and Day 8, and S-1 twice daily (BSA = 1.5 m 2 , 60 mg/day) for 21 days, followed by a 2-week period of no treatment. cDNA was derived from paraffin-embeded tumor specimens to determine ERCC1 mRNA expression relative to the internal reference gene beta-actin using fluorescence-based, real-time reverse transcriptase polymerase chain reaction (Taqman) system. Results: Among 34 CRC patients, 4 patients were evaluated as CR, 13 as PR, and 17 as NC/PD. Relative ERCC1 mRNA gene expression level showed significant difference by the response with median expression levels of 0.70/1.33/1.80 in CR/PR/NC+PD patients respectively (P = 0.04). Conclusions: These data suggest that intratumoral ERCC1 mRNA expression levels are independent predictive markers of response to CDDP+S-1 chemotherapy in colorectal cancer. No significant financial relationships to disclose.
Case-Control Study Suggests a Favorable Impact of TEL Rearrangement in Patients With B-Lineage Acute Lymphoblastic Leukemia Treated With Antimetabolite-Based Therapy: A Pediatric Oncology Group Study
Authors: Jeffrey E. Rubnitz, Jonathan J. Shuster, Vita J. Land, Michael P. Link, D. Jeanette Pullen, Bruce M. Camitta, Ching-Hon Pui, James R. Downing, Frederick G. Behm
Journal: Blood (1997)
Do clinical practice guidelines (CPGs) change clinical practice? An analysis of CPG impact on referral and treatment patterns for neoadjuvant chemotherapy in bladder cancer
Authors: B. J. Miles, B. J. Eigl
Journal: Journal of Clinical Oncology (2008)

5077 Background: Neoadjuvant chemotherapy (CT) for muscle invasive urothelial BC improves survival and is considered standard of care. In Alberta, Canada, CPGs recommending CT were developed with input from the wider urologic community and disseminated in May 2005. To evaluate the effect of CPG on practice patterns, a review of referral and treatment patterns before and after CPG implementation was undertaken. Methods: All patients in the Calgary Health Region who underwent radical cystectomy for BC from a 5 year period encompassing the CPG release date were identified. Two cohorts (A: 2.5 to 0.5 years prior to CPG, B: 0.5 to 2.5 years post CPG) were defined. Charts were reviewed to identify patients who were eligible for CT based upon the diagnosis of clinical stage 2 or 3 urothelial BC. Rates of referral to medical oncology and actual treatment with CT were ascertained for each cohort. Logistic regression analysis was undertaken to identify variables impacting referral and treatment decisions. Results: 141 patients were identified. Of these, 67 (Cohort A: 32; Cohort B: 35) were eligible for CT by CPG criteria. The referral rates for cohorts A and B were 2 (6.3%) and 11 (31%) respectively (OR 6.88, p=0.018, 95% CI 1.34, 34.04) In cohort A no referred patients were offered CT. In cohort B, 9 patients (25%) were offered treatment and 6 (17%) received CT. In subgroup analysis there was a significant correlation between referral rate, female sex and pathologic stage 3 or 4 disease. Conclusions: Referral and treatment rates for CT have improved significantly after release of CPGs in Alberta, but are still low. Of patients who are referred to medical oncology in this jurisdiction the majority (82%) are offered treatment, indicating that the most significant limitation to provision of standard of care treatment is at the level of referral. While CPGs have positively impacted referral rates, it remains clear that the majority of BC patients are ultimately not accessing comprehensive cancer care. Further work should focus on both improving methods of effectively disseminating CPGs and on novel tools for increasing the uptake of evidence based practice. No significant financial relationships to disclose.
Clinical Outcomes of Recurrent Ovarian Granulosa Cell Tumours Treated with Letrozole: a 10-Year Retrospective Case-Series of the Royal Marsden Hospital
Authors: R. Canario, J.P. Lima, C. Migali, N. Tunariu, A. George, S.B. Kaye, M.E. Gore, S. Banerjee
Journal: Annals of Oncology (2014)
Abstract 180: Myocardial Triacylglycerole Accumulation Is Related To BNP And Myocardial Redox State In Advanced Systolic Heart Failure
Authors: Jan Benes, Ludmila Kazdova, Hana Malinska, Jan Pirk, Jaroslav Spatenka, Josef Kautzner, Vojtech Melenovsky
Journal: Circulation Research (2013)

PURPOSE: Experimental studies suggest that accumulation of triacylglyceroles (TAG) in myocardium and ensuing lipotoxicity may contribute to the progression of heart failure (HF), but relevance to human HF remains uncertain. We strived to quantify myocardial TAG in HF patients and controls and to identify their determinants. Methods: 49 myocardial samples from patients with terminal HF (52 yrs, 86% male, 45% CAD, 49% DCM, 6% other dg.) that underwent heart transplantation or LVAD implantation and 20 control samples from cadaverous organ donors without HF (42 years, 45% males) were analyzed. Myocardial TAG (determined chemically), reduced (GSH) and oxidized glutathione (GSSG) were determined. Results: Patients with HF had higher amount of myocardial TAG (8.07± 3.95 vs. 5.60±3.36 μmol/g wet tissue, p= 0.017) and lower levels of both GSH and GSSG (p&lt; 0.05) with similar GSH/GSSG ratio. The amount of myocardial TAG was independent of age, gender, HF etiology, diabetes mellitus, BMI, mitral regurgitation grade and plasma lipids (total-, HDL-, LDL-cholesterol, TAG) but it correlated with plasmatic BNP level (p=0.049, r=0.28). In controls, a positive correlation between myocardial TAG and the myocardial redox state (GSH/GSSG ratio) was found (r=0.53, p=0.015). On the contrary, this correlation was negative (r= -0.31, p=0.02) in HF patients. Conclusion: Myocardial TAG in HF and controls have opposite relationship to redox state, indicating disparate mechanisms involved. Failing hearts display higher TAG accumulation, that is independent of comorbidities, but proportional to circulating BNP, supporting the role of natriuretic peptides in abnormal lipid homeostasis in HF.
Abstract 253: Modeling of Pathologic Hypertophy with Cardiac Microtissues
Authors: Rosa M Alvarez, Kenneth B Margulies
Journal: Circulation Research (2013)

Introduction: Pathological myocyte hypertrophy and fibroblast activation are key features of myocardial remodeling in hypertension and heart failure. Crosstalk between myocytes and fibroblasts contributes to the structural, mechanical, and electrical remodeling involved in various forms of heart failure. Replicating these responses in traditional 2D cell culture conditions has proven difficult. In this study, we utilized a novel platform to examine the cellular crosstalk and biological processes that underlie functional and structural changes in the 3D engineered tissues when exposed to pathological factors. We hypothesized that engineered cardiac tissues can report structural and functional responses to pathologic biochemical stimuli. Methods: These studies employ microfabricated polydimethylsiloxane (PDMS) templates to engineer arrays of 3D cardiac microtissues (CMT). Cantilevers within templates provide physiologically-relevant biomechanical loading to the CMTs, promote the appropriate organization of neonatal rat cardiac myocytes and fibroblasts, and report active and passive force generation in real time. Data was collected using fluorescent and confocal microscopy. Results: CMTs in a controlled mechanical environment demonstrate mechanical and structural changes within 24 hours of exposure to a cocktail of factors involved in maladaptive remodeling, including Transforming Growth Factor-β, Endothelin-1, and Angiotensin II. Analysis of 40 microtissues revealed that the percent change in passive tension was 45% higher (16.4 ± 10.3% vs. 61.1 ± 11.8%, p&lt;0.01) and in active tension 170% higher (24.9 ± 9.5% vs.196.1 ± 76.0%, p&lt;0.001) in treated CMTs compared to untreated CMTs. The percentage change in cross-sectional area of CMTs treated with pathological factors was 35% higher (-24.5 ± 15.6% vs.11.6 ± 7.9%, p&lt;0.001) than untreated samples. Conclusions: These findings demonstrate that the CMT model can be used to study and dissect the dynamics of pathological hypertrophy. Ongoing experiments are examining the distinct contributions of the pathologic growth factors, the relative contributions of fibroblasts and cardiomyocytes to the pathologic growth response, and the interactions between biomechanical and humoral inputs.
Women with sleeping problems may be more likely to develop diabetes
Authors: Jacqui Wise
Journal: BMJ (2016)

Difficulty in sleeping is associated with an increased risk of developing type 2 diabetes, a study published in Diabetologia has found.1

The US researchers found that the positive association was explained only partly by hypertension, body mass index, and depression. The association was particularly strong when combined with other sleep disorders such as frequent snoring or sleep apnoea.

Researchers analysed data from 133 353 women without diabetes, cardiovascular disease, or cancer at baseline from two …
Indoxyl sulfate suppresses endothelial progenitor cell–mediated neovascularization
Authors: Szu-Chun Hung, Ko-Lin Kuo, Hsin-Lei Huang, Chia-Chun Lin, Tung-Hu Tsai, Chao-Hung Wang, Jaw-Wen Chen, Shing-Jong Lin, Po-Hsun Huang, Der-Cherng Tarng
Journal: Kidney International (2016)
P2X1‐regulated IL‐22 secretion by innate lymphoid cells is required for efficient liver regeneration
Authors: Ramesh Kudira, Thomas Malinka, Andreas Kohler, Michel Dosch, Mercedes Gomez de Agüero, Nicolas Melin, Stefanie Haegele, Patrick Starlinger, Niran Maharjan, Smita Saxena, Adrian Keogh, Deborah Stroka, Daniel Candinas, Guido Beldi
Journal: Hepatology (2016)

Paracrine signalling mediated by cytokine secretion is essential for liver regeneration after hepatic resection, yet the mechanisms of cellular crosstalk between immune and parenchymal cells are still elusive. Interleukin‐22 (IL‐22) is released by immune cells and mediates strong hepatoprotective functions. However, it remains unclear whether IL‐22 is critical for the crosstalk between liver lymphocytes and parenchymal cells during liver regeneration after partial hepatectomy (PH). Here, we found that plasma levels of IL‐22 and its upstream cytokine, IL‐23, are highly elevated in patients after major liver resection. In a mouse model of PH, deletion of IL‐22 was associated with significantly delayed hepatocellular proliferation and an increase of hepatocellular injury and endoplasmic reticulum stress. Using Rag1 −/− and Rag2−/−γc−/ − mice, we show that the main producers of IL‐22 post‐PH are conventional natural killer cells and innate lymphoid cells type 1. Extracellular adenosine triphosphate (ATP), a potent danger molecule, is elevated in patients immediately after major liver resection. Antagonism of the P2‐type nucleotide receptors, P2X1 and P2Y6, significantly decreased IL‐22 secretion ex vivo . In vivo , specific inhibition of P2X1 was associated with decreased IL‐22 secretion, elevated liver injury, and impaired liver regeneration. Conclusion: This study shows that innate immune cell‐derived IL‐22 is required for efficient liver regeneration and that secretion of IL‐22 in the regenerating liver is modulated by the ATP receptor, P2X1. (H epatology 2016;63:2004‐2017)
Birth Weight and Childhood Cancer Deaths&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D E Eisenberg, T Sorahan
Journal: JNCI Journal of the National Cancer Institute (1987)

For investigation of the hypothesis that elevated birth weight characterizes children dying from cancer, birth weights of over 3,000 children who died of cancer were compared with those of matched controls alive at the time of the case's death. Analysis revealed no consistent pattern of association between birth weight and subsequent cancer death. Girls who died of solid tumors between ages 1 and 10 had a significantly higher mean birth weight and an excess of high birth weights separate from the influence of maternal age, birth order, and socioeconomic status. Boys who died of solid tumors between birth and 2 years had a significantly lower mean birth weight and exhibited a significant, progressive linear decrease in representation across the birth-weight distribution in the controlled analysis. However, this study, the largest to date, did not support previous claims that birth weight may be an important predictor of childhood cancer risk.
The billion dollar business of being smart
Authors: Krishna Chinthapalli
Journal: BMJ (2015)

<h3>Background and Objectives:</h3> The presence of post-interventional subarachnoid hyperdensities (SA-HD) is a relatively common finding after mechanical thrombectomy (MT). We aimed to assess the incidence, characteristics, clinical relevance and predictors of SA-HD after MT as categorized through the use of post-interventional Dual Energy-CT (DE-CT). <h3>Methods:</h3> A single-center consecutive series of acute stroke patients treated with MT were retrospectively reviewed. Post-treatment SA-HD were defined as incident extra-axial hyperdensities in a follow-up DE-CT performed within a median of 8 hours after MT. SA-HD were further classified according to their content (isolated contrast extravasation versus blood extravasation) and extension [diffuse (hyperdensities in more than one extraparenchymal compartments) versus non-diffuse]. Adjusted logistic regression models assessed the association of SA-HD with pretreatment and procedural variables and with bad clinical outcome (shift towards worse categories in the ordinal Rankin Scale at 90 days). <h3>Results:</h3> SA-HD were observed in 120 (28%) of the 424 included patients (isolated contrast extravasation n=22, blood extravasation n=98). In this group, SA-HD were diffuse in 72 (60%) patients (isolated contrast extravasation n=7, blood extravasation n=65) and non-diffuse in 48 (40%) patients (isolated contrast extravasation n=15, blood extravasation n=33). Diffuse SA-HD were significantly associated with worse clinical outcome in adjusted models (cOR=2.3, 95%CI=1.36-4.00, p=0.002), unlike the specific SA-HD content alone. In contrast with the absence of SA-HD, only the diffuse pattern with blood extravasation was significantly associated with worse clinical outcome (cOR=2.4, 95%CI=1.36-4.15, p=0.002). Diffuse SA-HD patterns were predicted by M2 occlusions, more thrombectomy passes and concurrent parenchymal hematomas. <h3>Discussion:</h3> In our cohort of patients imaged within a median of 8 hours after MT, post-interventional SA-HD showed a diffuse pattern in 17% of thrombectomies and were associated with more arduous procedures. Diffuse SA-HD but not local collections of blood or contrast extravasations were associated with an increased risk of poor outcome and death. These findings reinforce the need for improvement in reperfusion strategies. <h3>Classification of Evidence:</h3> This study provides Class II evidence that in individuals with proximal carotid artery territory occlusions treated with mechanical thrombectomy, diffuse post-interventional subarachnoid hyperdensities on imaging 8 hours post-procedure are associated with worse clinical outcomes at 90 days.
Marginal Zone B-Cell Lymphoma: A Clinical Comparison of Nodal and Mucosa-Associated Lymphoid Tissue Types
Authors: Bharat N. Nathwani, James R. Anderson, James O. Armitage, Franco Cavalli, Jacques Diebold, Milton R. Drachenberg, Nancy L. Harris, Kenneth A. MacLennan, H. Konrad Müller-Hermelink, Fred A. Ullrich, Dennis D. Weisenburger
Journal: Journal of Clinical Oncology (1999)

PURPOSE: In the International Lymphoma Study Group classification of lymphoma, extranodal marginal zone B-cell lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) type is listed as a distinctive entity. However, nodal MZL is listed as a provisional entity because of questions as to whether it is truly a disease or just an advanced stage of MALT-type MZL. To resolve the issue of whether primary nodal MZL without involvement of mucosal sites exists and whether it is clinically different from extranodal MALT-type lymphoma, we compared the clinical features of these two lymphomas. PATIENTS AND METHODS: Five expert hematopathologists reached a consensus diagnosis of MZL in 93 patients. Seventy-three were classified as having MALT-type MZL because of involvement of a mucosal site at the time of diagnosis, and 20 were classified as having nodal MZL because of involvement of lymph nodes without involvement of a mucosal site. RESULTS: A comparison of the clinical features of nodal MZL and MALT-type MZL showed that more patients with nodal MZL presented with advanced-stage disease (71% v 34%; P = .02), peripheral lymphadenopathy (100% v 8%; P &lt; .001), and para-aortic lymphadenopathy (56% v 14%; P &lt; .001) than those with MALT-type MZL. However, fewer patients with nodal MZL had a large mass (≥ 5 cm) than those with MALT-type MZL (31% v 68%; P = .03). The 5-year overall survival of patients with nodal MZL was lower than that for patients with MALT-type MZL (56% v 81%; P = .09), with a similar result for failure-free survival (28% v 65%; P = .01). Comparisons of patients with International Prognostic Index scores of 0 to 3 showed that those with nodal MZL had lower 5-year overall survival (52% v 88%; P = .025) and failure-free survival (30% v 75%; P = .007) rates than those with MALT-type MZL. CONCLUSION: Nodal MZL seems to be a distinctive disease entity rather than an advanced stage of MALT-type MZL because the clinical presentations and survival outcomes are different in these two types of MZL. Clinically, nodal MZL is similar to other low-grade, node-based B-cell lymphomas, such as follicular and small lymphocytic lymphomas.