tbuckley/cabot-search huggingface dataset:
Inhibition of Graft-Versus-Host-Disease (GVHD) by Treatment with the Cyclopentenone Prostaglandin 15d-PGJ2 Involves Modulation of the NF-κB Signaling Pathway.
Authors: Huihui Ma, Judith Ziegler, Suzanne Lentzsch, Markus Mapara
Journal: Blood (2007)
TCT-619 Returning To The Gold Standard Measurement Of Cardiac Output: Comparison Of Measured And Assumed Oxygen Consumption And Thermodilution Techniques
Authors: Zaher Fanari, Mathew Groove, Anitha Rajamanickan, Sumaya Hammami, Paul Kolm, William Weintraub, Andrew Doorey
Journal: Journal of the American College of Cardiology (2015)
Tumour Burden Influence on Individual Rituximab Exposure and Response: Pharmacokinetic - Pharmacodynamic Approach by Using a Syngenic Bioluminescent Murine Model.
Authors: David Daydé, David Ternant, Stéphanie Lerondel, Hervé Watier, Alain Le Pape, Pierre Bardos, Gilles Paintaud, Guillaume Cartron
Journal: Blood (2007)
Structural Analysis Reveals that Toll-like Receptor 7 Is a Dual Receptor for Guanosine and Single-Stranded RNA
Authors: Zhikuan Zhang, Umeharu Ohto, Takuma Shibata, Elena Krayukhina, Masato Taoka, Yoshio Yamauchi, Hiromi Tanji, Toshiaki Isobe, Susumu Uchiyama, Kensuke Miyake, Toshiyuki Shimizu
Journal: Immunity (2016)
Impact of lactate dehydrogenase (LDH) and absolute lymphocyte count (ALC) on outcome of previously treated patients with malignant pleural mesothelioma (MPM) receiving chemotherapy (CT) with or without NGR-hTNF in the phase 3 trial NGR015.
Authors: Vanesa Gregorc, Maria G Viganò, Alessandra Bulotta, Giovanni Citterio, Giovanna Petrella, Elena Brioschi, Monika Ducceschi, Luca Gianni, Scialini Colombi, Gloria Rossoni, Giulia Salini, Emma Redaelli, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2016)

e20075 Background: NGR-hTNF selectively binds to CD13-expressing blood vessels and improves intratumor T-lymphocyte infiltration and CT uptake. CD13 expression is upregulated by tumor hypoxia/angiogenesis. High serum LDH has been associated with augmented tumor hypoxia, poor prognosis and sensitivity to antiangiogenic agents, while a high ALC may facilitate NGR-hTNF effects Methods: The impact of baseline LDH and ALC on outcome was tested in 400 patients (pts) receiving single-agent gemcitabine, vinorelbine or doxorubicin ± NGR-hTNF as second-line treatment. In NGR015 trial, there was interaction for OS only between treatment and treatment-free interval (TFI) after end of first-line therapy (p = 0.008). In pts with short TFI ( < median 4.8 months; n = 198), NGR-hTNF improved OS (HR = 0.69 p = 0.02) and PFS (HR = 0.69 p = 0.01). The prognostic impact of baseline LDH (median 274 U/L; interquartile range 196 to 388) and ALC (1.3/mL; 1.0 to 1.8) treated as continuous variable or categorized at the 25th, 50th or 75th percentile was tested by regression models controlled for risk factors Results: There were no prognostic effects of LDH on OS or treatment-by-LDH interaction. ALC was associated with OS (HR = 1.31 p = 0.006), without treatment-by-LDH interaction. Both LDH (p < 0.0001) and ALC (p = 0.02) were higher in short than long TFI subsets. In pts with short TFI, those with high LDH (n = 157) were more sensitive to NGR-hTNF effects (PFS HR = 0.56 p = 0.001 using 1st quartile as cutoff), which increased with increasing LDH (PFS HR = 0.36 p = 0.001 using 3rd quartile as cutpoint). Similar results were reported for OS: median 9.7 vs 6.0 months (25th percentile) and 12.8 vs 5.8 months (75th percentile). Likewise, pts with high ALC (n = 151) were more sensitive to NGR-hTNF effects (PFS HR = 0.69 p = 0.03; OS HR = 0.65 p = 0.02 using 1st quartile as cutpoint), which increased in those with stable or improved ALC after first treatment cycle (PFS HR = 0.41 p < 0.0001; OS HR = 0.55 p = 0.01) Conclusions: Increasing LDH and ALC levels are associated with increased NGR-hTNF benefit in MPM patients rapidly progressing after initial therapy Clinical trial information: NCT01098266.
Reconciliation of Type 2 Diabetes Remission Rates in Studies of Roux-en-Y Gastric Bypass
Authors: Deanna J.M. Isaman, Amy E. Rothberg, William H. Herman
Journal: Diabetes Care (2016)

OBJECTIVE Bariatric surgery may induce remission of type 2 diabetes in obese patients. However, estimates of remission rates reported in the literature range from 25 to 81%, contributing to the uncertainty patients and physicians both face as they assess treatment options. This analysis attempts to reconcile the seemingly disparate rates of diabetes remission reported in studies of Roux-en-Y gastric bypass (RYGB) surgery. It examines variation in the methodologies used to derive the estimates and proposes outcomes that should be reported by all studies. RESEARCH DESIGN AND METHODS A literature review yielded 10 large (n &amp;gt; 100), recent (index surgery since 2000) studies of diabetes remission after RYGB. These studies differed in definitions of remission (partial vs. complete), lengths of follow-up (1 year vs. ≥3 years), reported outcomes (cumulative vs. prevalent remission), and risks of attrition bias. RESULTS Reported rates of partial remission were 10–30 percentage points higher than rates of complete remission. Study duration explained 69% of the variability in cumulative remission rates, plateauing at 3 years. Adjustment for attrition increased the explained variability to 87%. Attrition-adjusted, 3-year cumulative, complete remission rates ranged from 63 to 65%; however, this does not account for relapse. Attrition-adjusted, 3-year prevalent complete remission rates that accounted for relapse were 23%. CONCLUSIONS Variations in reported rates of diabetes remission after RYGB are primarily related to definitions and study duration. Future studies should report both cumulative and prevalent remission to aid decision making and more easily compare studies.
Inhibition of IRAK1 As a Novel Therapeutic Strategy in Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Garrett Rhyasen, Lyndsey Bolanos, Jing Fang, Carmen Rigolino, Agostino Cortelezzi, Esther Natalie Oliva, Mariella Cuzzola, Daniel T Starczynowski
Journal: Blood (2011)
Decrease in Microvascular Blood Flow in Sickle Cell Anemia Is Triggered by Autonomic Signals and Not Directly by Hypoxia: A New Hypothesis for Sickle Crisis.
Authors: Suvimol Sangkatumvong, Roberta Kato, Jon A Detterich, Herbert J Meiselman, John C Wood, Michael Khoo, Thomas D Coates
Journal: Blood (2009)
A phase II study of gemcitabine in combination with radiation therapy in patients with localized, unresectable, pancreatic cancer: a Hoosier Oncology Group Trial
Authors: A. M. Moore, H. Cardenes, C. S. Johnson, P. Helft, D. Seitz, A. Stephens, D. Fritz Tai, P. J. Loehrer
Journal: Journal of Clinical Oncology (2004)

4105 Background: Survival of patients (pts) with locally advanced pancreas cancer is poor. Gemcitabine (GEM) is a known potent radiosensitizer with single agent activity in advanced disease. A phase I study conducted at IUCC, University of Michigan, and Fox Chase Cancer Center determined the MTD for GEM to be 600 mg/m2/week IV when administered with 5040 cGy external beam radiation (personal communication Dr. Steve Nicol). We conducted a phase II study to confirm safety and efficacy of GEM-radiation. Methods: Eligible pts had localized, biopsy-proven adenocarcinoma of the pancreas, deemed unresectable by CT scans and/or endoscopic ultrasound and confirmed by surgical evaluation. Pts received GEM 600 mg/m2 IV weekly, with concurrent radiotherapy, 180 cGy/day, 5 days/week, for a total of 5040 cGy, (part A ). Approx. 4 weeks after completion of combination therapy, pts without disease progression received GEM 1000mg/m2on days 1 & 8, of a 21-day cycle for 6 cycles (part B). Results: From April 2001-June 2003, 32 pts were enrolled on trial; 28 pts were evaluable (4 never received treatment). Pt characteristics: mean age 65 (36–78); PS 0/1= 18/10; and M:F= 15:13. Median follow-up is 7.8 mos. Twenty four (85.7%) pts completed part A of treatment. Grade 3 toxicities were principally hematologic and gastrointestinal, occurring in 12 pts (42.8%) and 10 pts (35.7%), respectively. Three (10.7%) pts had grade 4 toxicities (1 each for hyperbilirubinemia, infection and dyspnea). Six pts (21%) had a partial response, 16 pts (57%) had stable disease and 4 pts (14%) had progressive disease. Although not part of the study, 4 pts (14%) went on to surgical resection (findings: microscopic adenocarcinoma-1; extensive fibrosis-1; unresectable-2). The median time to progression was 6.3 mos (95% C.I. 4.5–7.4 mos). The one-year survival time is 31.1% (95% C.I.: 7.4%–54.8%). Median survival time was 7.9 mos (95% C.I. 6.6–17.1 mos). Conclusion: GEM/radiation has moderate toxicities and can be safely administered in the community setting. An Intergroup Phase III study comparing GEM alone versus GEM/radiation is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly
Primary angiosarcoma of the breast: Pattern of presentation, surgery, radiation, and survival
Authors: J. C. Yap, S. Kulkarni, S. Fernando, M. K. Wong
Journal: Journal of Clinical Oncology (2008)

21509 Background: Angiosarcoma of the female breast is most often associated with history of irradiation and/or lymphedema. Primary angiosarcoma of the breast is rare. The benefit of adjuvant radiation treatment (RT) is not known in this disease entity. Methods: A search of the SEER database (1973 to 2003) revealed 162 records of pathologically confirmed angiosarcoma. After exclusion of patients with multiple cancers, 99 patients with primary angiosarcoma were identified. Cox regression model was used in multivariate analysis. Kaplan-Meier estimates and Mantel-Cox modeling were used to calculate and compare survival rates. Results: Median age was 47 years (range 18–92). 66 patients presented with localized disease, 20 had regional involvement, 8 presented with metastatic disease, and 5 were unstaged. 58 patients had overlapping or extensive involvement, and 41 patients had disease in an isolated quadrant or was centrally located. Surgery comprised of partial mastectomy in 6 patients, total or subcutaneous mastectomy in 29 patients, modified radical mastectomy in 19 patients, radical mastectomy in 5 patients, unknown procedures in 37 patients, and 3 patients might not have surgery. Postoperative external beam RT was given to 31 patients. 64 patients did not receive RT, and 4 patients had no clear use of RT. On multivariate analysis, RT was not a predictor of survival (p=0.19). The actuarial survival rates at 10 years were 46% vs. 37% respectively (No RT vs. RT, p=0.15). Among the 6 patients who had partial mastectomy, 5 patients had no RT and were surviving at last follow up with 9 or more years of crude overall survival. Conclusions: Primary angiosarcoma of the breast presents as advanced disease. Surgical extirpation is the primary treatment. The database lacks information on use of chemotherapy and local disease control. When RT was used, it was given postoperatively. Adjuvant RT did not appear to yield survival benefit. No significant financial relationships to disclose.
Impact of Ischemic Heart Failure Etiology on Cardiac Recovery During Mechanical Unloading
Authors: James Wever-Pinzon, Craig H. Selzman, Greg Stoddard, Omar Wever-Pinzon, Anna Catino, Abdallah G. Kfoury, Nikolaos A. Diakos, Bruce B. Reid, Stephen McKellar, Michael Bonios, Antigone Koliopoulou, Deborah Budge, Aaron Kelkhoff, Josef Stehlik, James C. Fang, Stavros G. Drakos
Journal: Journal of the American College of Cardiology (2016)
Myeloperoxidase-Derived Halogenative Stress, a Possible Cause of Benzene Leukemogenesis
Authors: Takuro Nishikawa, Emiko Miyahara, Masahisa Horiuchi, Kimiko Izumo, Yasuhiro Okamoto, Yoshichika Kawai, Yoshifumi Kawano, Toru Takeuchi
Journal: Blood (2011)
Real-World “myelodysplastic Syndrome-unclassifiable” and Its Comparison With “refractory Cytopenia With Multi-Lineage dysplasia” and “refractory anemia”
Authors: Kebede Begna, Mrinal M. Patnaik, Naseema Gangat, Biruk Mengistu, Curtis A. Hanson, Ayalew Tefferi
Journal: Blood (2013)
The intensity of CEACAM-1 expression in melanoma patients and the timing of treatment with recombinant human interferon &amp; 2b showed correlation with survival
Authors: C. L. Mihalcioiu, P. Watson, S. Alowami
Journal: Journal of Clinical Oncology (2004)

7561 Background: In this retrospective analysis, we tested if the timing of interferon (iFN) as adjuvant or as treatment of the relapse, when correlated with CEACAM-1 intensity, affects survival. Methods: After ethics approval was obtained, paraffin blocks from 27 patients previously diagnosed with malignant melanoma were analyzed using immunohistochemical staining with monoclonal CEACAM-1 antibody. The patients were grouped based on intensity; weakly positive (intensity 0–1) and strongly positive (intensity 2–3). Each group was analyzed based on survival status, pathological stage, and the time iFN was started. Results: Grade 3 intensity was identified in 10 patients, 6 of whom died (60%) and 4 patients are alive (2 relapsed but are disease-free). None of these patients had T4 or N1–2 disease at presentation. Adjuvant low-dose iFN was given in 4/10 patients, and 3/4 patients (75%) were alive at 3–5 years follow-up. High-dose iFN was given at the time of relapse in 6/10 patients and 5/6 patients died (83%) from disease progression. Grade 2 intensity was identified in 7 patients and 4 of them died (57%) and 3 patients are alive (2 relapsed but are disease-free). Adjuvant iFN was given in 4/7 patients and 3/4 remained alive (75%). iFN was started at the time of the first relapse in 3/7 patients; all 3/3 died (100%). Grade 1 intensity was observed in 10 patients and 3/10 died (30%). Out of 7 patients alive, 5 relapsed, but remained disease-free after local treatment at 4–7 years follow-up. Adjuvant iFN was given in 6/10 patients with 50% success rate (3/6 died). In 4/10 patients, iFN was given at first relapse and 4/4 (100%) are alive and disease-free at 4–7 years follow-up. Conclusions: Grade 2 and 3 intensity for CEACAM-1 correlates with poor prognosis despite early stage at diagnosis, but adjuvant iFN seems to correlate with survival benefit. Grade 1 intensity patients have a high survival rate and the timing of iFN was associated with good survival in both settings. No significant financial relationships to disclose.
La couverture vaccinale des enfants d’âge préscolaire en France en 2000
Authors: D Antona, E Bussière, N. Guignon, G Badeyan, D Lévy-Bruhl
Journal: Eurosurveillance (2003)

Cet article presente les taux de couverture vaccinale eva-lues en France chez les enfants jusqu’a l’âge de 6 ans. Les couvertures vaccinales sont tres elevees en ce qui concerne la diphterie, le tetanos, la coqueluche et la poliomyelite, et satisfaisante pour le vaccin contre les infection invasives a Haemophilus influenzae b. Par contre, pour la vaccination contre la rougeole, les oreillons et la rubeole, il est neces-saire d’augmenter la couverture des nourrissons et d’assu-rer un rattrapage efficace. En ce qui concerne l’hepatite B, la couverture vaccinale est tres insuffisante chez les nour-rissons et devrait pouvoir etre amelioree quand le vaccin sera disponible sous forme combinee.
MPTH-08ZEB1 IS UBIQUITOUSLY EXPRESSED ACROSS SUBTYPES IN HUMAN GLIOBLASTOMA AND A SURROGATE MARKER OF TUMOR PURITY
Authors: Philipp Euskirchen, Josefine Radke, Marc Sören Schmidt, Eva Schulze Heuling, Eric Kadikowski, Meron Maricos, Felix Knab, Jun Cheng, Ulrike Grittner, Norman Zerbe, Marcus Czabanka, Christoph Dieterich, Hrvoje Miletic, Sverre Mørk, Arend Koch, Matthias Endres, Christoph Harms
Journal: Neuro-Oncology (2015)

OBJECTIVE: The transcription factor ZEB1 has gained attention in tumor biology of epithelial cancers because of its suggested roles in epithelial-mesenchymal transition, DNA repair, mediation of stem cell properties and tumor-induced immunosuppression, but its role in CNS tumors, especially glioblastoma multiforme is not well understood. METHODS: We comprehensively characterized ZEB1 expression at single cell level by automated classification of 1.6 million nuclei in biopsy samples from 273 human astroglial tumors and correlated its expression with EGFR status, IDH1 mutation and Ki67, CD44, GFAP and CD68 immunohistochemistry. Interaction of ZEB1 and EGFR signalling was interrogated in vitro by realtime quantitative PCR and immunocytochemistry in glioma stem cell lines from subtype-stratified parental tumors based on RNAseq transcriptomic gene expression profiles. RESULTS: ZEB1 is expressed in nearly all examined tumors but in highly variable fraction of cells. Co-staining of reactive CNS cell types in non-tumor tissue show that besides bona fide tumor cells, only reactive astrocytes but not leucocytes, microglia and macrophages contribute to the ZEB1 positive population. In GBM, ZEB1 labelling index correlates with EGFR amplification and IDH1 mutation, but EGFR modulation by cetuximab treatment did not alter ZEB1 expression in vitro. CONCLUSION: ZEB1 is expressed ubiquitously and across molecularily defined subtypes in glioblastoma multiforme as well as in non-GBM astroglial tumors. ZEB1 labelling varies across GBM subtypes, but a causal link remains questionable. We speculate that ZEB1 is a pan-astroglial tumor marker that reflects tumor purity.
Adipose-Vascular Coupling and Potential Therapeutics
Authors: Maik Gollasch
Journal: The Annual Review of Pharmacology and Toxicology (2016)

Excess visceral adipose tissue is associated with increased risk of high blood pressure, lipid disorders, type 2 diabetes, and cardiovascular disease. Adipose tissue is an endocrine organ with multiple humoral and metabolic roles in regulating whole-body physiology. However, perivascular adipose tissue (PVAT) also plays a functional role in regulating the contractile state of the underlying smooth muscle cell layer. Work during the past decade has shown that this adipose-vascular coupling is achieved by production of numerous substances released from PVAT. Animal disease models have been instrumental in identifying biological and pathophysiological functions of this regulation. These studies have produced strong evidence that alterations in the paracrine control of PVAT in the regulation of arterial tone contribute to vascular dysfunction in obesity, hypertension, and cardiometabolic disease. Perivascular relaxing factors, or perhaps their putative targets, might represent exciting new targets for the prevention and treatment of cardiovascular and metabolic diseases.
Study on the Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma
Authors: Petter Gjersvik
Journal: JAMA Dermatology (2016)

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Pretreatment serum mitochondrial DNA (mtDNA) correlates with shorter progression-free and overall survival in patients with advanced ovarian cancer (OC).
Authors: Kassondra S. Grzankowski, Anm Nazmul H. Khan, Kevin H. Eng, Melissa Grimm, Kelly L. Singel, Nonna Kolomeyevskaya, Kirsten B. Moysich, Kunle Odunsi, Brahm H. Segal
Journal: Journal of Clinical Oncology (2014)

5545 Background: Mitochondrial damage-associated molecular patterns, comprised of mtDNA and formylated peptides, are released after cellular injury and activate innate immune responses. Extracellular mtDNA activates TLR-9 and other pathogen recognition receptors. While mitochondrial metabolism and DNA mutations have been widely studied in tumor cells, this study analyzes mtDNA at an extracellular level as a marker of injury. Since OC is associated with cellular necrosis, we reason that extracellular mtDNA may be a molecular prognostic marker. Methods: Serum collected in OC patients prior to primary surgery (n=41) and from age-matched cancer free women (n=3) was analyzed for mtDNA. Q-PCR with cytochrome B primers specific for mtDNA was done. The high group was pre-specified as patients with serum mtDNA > 5-fold above the mean control level, and the remainder was defined as the low group. Primary endpoint was PFS. Results: 41% had high levels of mtDNA. 76% in the high mtDNA and 74% in the low groups were Stage 3. Histology and grade were similar. The mean age at diagnosis was 69. Median PFS in the high and low groups was 228 vs. 489 days, respectively (p = 0.17). The high mtDNA group had quicker relapse (HR=2.7; p = 0.0278) and a reduced OS trend (HR=3.5; p = 0.0593) within the first year of surgery. Consistent with this effect, additional exploratory analysis showed that patients with serum mtDNA in the highest 15% had markedly reduced PFS (5 vs. 16 mo; p = 0.0015) and OS (8 vs. 50 mo; p = 0.00022) compared to the remaining patients. The relationship between pre-treatment serum mtDNA levels and PFS and OS involve a threshold effect rather than a direct linear relationship. Comparing pre-treatment serum mtDNA levels to published data on serum CA-125 levels from a Gynecology Oncology Group study that analyzed 1,299 patients with OC, we observed significantly greater effect sizes with serum mtDNA in predicting prognosis, with the greatest effect in the top 15% serum mtDNA group. Conclusions: Increased levels of circulating mtDNA correlated with significantly reduced PFS and OS. If validated in an independent cohort, pre-treatment serum mtDNA may be of value as a prognostic marker for OC.
mTOR has distinct functions in generating versus sustaining humoral immunity
Authors: Derek D. Jones, Brian T. Gaudette, Joel R. Wilmore, Irene Chernova, Alexandra Bortnick, Brendan M. Weiss, David Allman
Journal: Journal of Clinical Investigation (2016)

Little is known about the role of mTOR signaling in plasma cell differentiation and function. Furthermore, for reasons not understood, mTOR inhibition reverses antibody-associated disease in a murine model of systemic lupus erythematosus. Here, we have demonstrated that induced B lineage-specific deletion of the gene encoding RAPTOR, an essential signaling adaptor for rapamycin-sensitive mTOR complex 1 (mTORC1), abrogated the generation of antibody-secreting plasma cells in mice. Acute treatment with rapamycin recapitulated the effects of RAPTOR deficiency, and both strategies led to the ablation of newly formed plasma cells in the spleen and bone marrow while also obliterating preexisting germinal centers. Surprisingly, although perturbing mTOR activity caused a profound decline in serum antibodies that were specific for exogenous antigen or DNA, frequencies of long-lived bone marrow plasma cells were unaffected. Instead, mTORC1 inhibition led to decreased expression of immunoglobulin-binding protein (BiP) and other factors needed for robust protein synthesis. Consequently, blockade of antibody synthesis was rapidly reversed after termination of rapamycin treatment. We conclude that mTOR signaling plays critical but diverse roles in early and late phases of antibody responses and plasma cell differentiation.