tbuckley/cabot-search huggingface dataset:
Reply to H.A. Azim Jr et al
Authors: Frédéric Amant, Patrick Neven, Kristel Van Calsteren
Journal: Journal of Clinical Oncology (2010)

We thank you for giving us the opportunity to respond to comments 1 on data from our multicentric and international study on cancer during pregnancy. 2 We reflect on the delay of chemotherapy during pregnancy, the typically aggressive biology of gestational breast cancer, the increased risk for preterm labor in patients with breast cancer, and the suggestion to standardize weekly epirubicin in pregnant patients with breast cancer.We agree that similar to treatment for nonpregnant women, delay of treatment should be avoided.We also state that continuation of chemotherapy during pregnancy is a good option to delay delivery and attain fetal maturity and thus prevent prematurity.Regarding the impact of delay of chemotherapy on the prognosis of patients with early breast cancer, the literature is indeed inconsistent. [3]4][5] Azim and Peccatori 1 quote the largest previous study that addressed this question in a retrospective analysis combining data from three International Breast Cancer Study Group trials of adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy given to premenopausal, node-positive patients. 3 The 10-year disease-free survival (DFS) for initiating chemotherapy within 21 days of surgery was 60% in 84 patients and 34% in 142 patients initiating chemotherapy beyond 21 days of surgery (hazard ratio, 0.48; 95% CI, 0.33 to 0.72; P Ͻ .001).This finding was not confirmed by Shannon et al, 4 who compared DFS and OS in a retrospective analysis between 368 patients starting chemotherapy within 21 days of surgery (group A) and 793 patients commencing chemotherapy Ն 21 days after surgery (group B).No significant difference in 5-year DFS was found between the two groups overall (70% for group A v 72% for group B; P ϭ .4).Likewise, there was no difference in 5-year OS (82% for group A v 84% for group B; P ϭ .2) or when the interval to the start of chemotherapy was considered as a continuous variable (P ϭ .4). 4 Also Cold et al 5 report on the safety of delay of chemotherapy up to 2 to 3 months.With this background, we would accept waiting a few weeks to avoid chemotherapy during the first trimester of pregnancy for patients with early breast cancer.Similarly, we would accept a waiting policy during the third trimester when only one cycle of chemotherapy is needed to attain fetal maturity. 6 Why do Azim and Peccatori believe that it is oncologically safe to delay chemotherapy during the first trimester but not during the third trimester?Pregnancy itself is not associated with aggressive tumor biology.The steroid receptor content, HER-2/neu status, proliferation rate, and the presence of the p53 mutation do not differ from those of age-matched, nonpregnant women. 7Age rather than the pregnancy determines the biologic features of the tumor. 8 In addition, population-based data suggest that the maternal outcome is not worse for breast cancer during pregnancy. 9 From the eight patients exposed to chemotherapy during pregnancy with preterm labor in our series, only three were treated for
Expression of the transcription factor cKrox in peripheral CD8 T cells reveals substantial postthymic plasticity in CD4-CD8 lineage differentiation
Authors: S. Rhiannon Jenkinson, Andrew M. Intlekofer, Guangping Sun, Lionel Feigenbaum, Steven L. Reiner, Rémy Bosselut
Journal: The Journal of Experimental Medicine (2007)

Most T cells belong to either of two lineages defined by the mutually exclusive expression of CD4 and CD8 coreceptors: CD4 T cells are major histocompatibility complex (MHC) II restricted and have helper function, whereas CD8 T cells are MHC I restricted and have cytotoxic function. The divergence between these two lineages occurs during intrathymic selection and is thought to be irreversible in mature T cells. It is, however, unclear whether the CD4-CD8 differentiation of postthymic T cells retains some level of plasticity or is stably maintained by mechanisms distinct from those that set lineage choice in the thymus. To address this issue, we examined if coreceptor or effector gene expression in mature CD8 T cells remains sensitive to the zinc finger transcription factor cKrox, which promotes CD4 and inhibits CD8 differentiation when expressed in thymocytes. We show that cKrox transduction into CD8 T cells inhibits their expression of CD8 and cytotoxic effector genes and impairs their cytotoxic activity, and that it promotes expression of helper-specific genes, although not of CD4 itself. These observations reveal a persistent degree of plasticity in CD4-CD8 differentiation in mature T cells.
Highly selective vagotomy plus dilatation of the stenosis compared with truncal vagotomy and drainage in the treatment of pyloric stenosis secondary to duodenal ulceration.
Authors: M J McMahon, M J Greenall, D Johnston, J C Goligher
Journal: Gut (1976)

Twenty-three consecutive patients with duodenal ulceration complicated by pyloric stenosis who came under the care of one surgeon were treated by highly selective vagotomy (HSV) combined with digital dilatation of the stenosis through a gastrotomy. No form of drainage procedure was used. Thus the antral "mill" and the pyloric sphineter were left intact. Since the stenosis is usually distal to the pylorus rather than truly pyloric such dilatation does not damage the pyloric ring, although it may on occasion lead to perforation of the first part of the duodenum. The subsequent progress of these patients was compared with that of a similar, consecutive series of 23 patients with pyloric stenosis who were treated by truncal vagotomy with a drainage procedure by other surgeons on the same surgical unit. Patients were followed up for between four months and five years. The clinical assessment was carried out in "blind" fashion at a special gastric follow-up clinic. No evidence of recurrent ulceration was found in either group of patients. Two patients from each group subsequently came to reoperation for the relief of gastric stasis. Twenty-two of the 23 patients (96%) who had undergone HSV plus dilatation eventually achieved a good-to-excellent clinical result (Visick grades 1+2), wheras only 17 of the 23 patients (74%) who had undergone truncal vagotomy with drainage achieved such a result. The main clinical difference between the two groups was that side effects such as diarrhoea and abdominal pain or discomfort were more common after vagotomy with drainage than after HSV. These results bear witness to the remarkable propulsive powers of the gastric antrum after HSV, which were evidently sufficient to overcome any tendency to re-stenosis in more than 90% of patients. The 9% incidence of failure due to re-stenosis could perhaps be avoided if a small duodenoplasty were performed instead of simple digital dilatation. The results support the hypothesis that damage to the antral mill and pyloric sphincter can be avoided in the course of operations for "pyloric" stenosis secondary to duodenal ulceration. Avoidance of the drainage procedure is of benefit to the patient, just as it is in patients who have duodenal ulceration without stenosis.
Reply: Does the adenosine A2A receptor stimulate the ryanodine receptor?
Authors: L HOVEMADSEN, C PRATVIDAL, A LLACH, F CIRUELA, V CASADO, C LLUIS, A BAYESGENIS, J CINCA, R FRANCO
Journal: Cardiovascular Research (2006)

In our paper on the expression and function of the adenosine A2A receptor (A2AR) in human atrial myocytes [1], we show that agonist stimulation of this receptor induces a protein kinase A (PKA)-dependent increase in the frequency of calcium sparks and spontaneous calcium waves. We therefore investigated whether A2AR stimulation affected the L-type calcium current, sarcoplasmic reticulum (SR) calcium uptake, or SR calcium release, as these mechanisms are known to be modulated by PKA-dependent phosphorylation [2–4]. Since only the fast (SR calcium release-dependent) time constant for I Ca inactivation was affected by A2AR stimulation, we proposed that a PKA-mediated increase in ryanodine receptor (RyR) opening may account for our results.

However, according to the letter …
Approval Summary for Erlotinib for Treatment of Patients with Locally Advanced or Metastatic Non–Small Cell Lung Cancer after Failure of at Least One Prior Chemotherapy Regimen
Authors: John R. Johnson, Martin Cohen, Rajeshwari Sridhara, Yeh-Fong Chen, Gene M. Williams, John Duan, Jogarao Gobburu, Brian Booth, Kimberly Benson, John Leighton, Li Shan Hsieh, Nallalerumal Chidambaram, Paul Zimmerman, Richard Pazdur
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To describe the Food and Drug Administration (FDA) review and approval of erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY) for treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Experimental Design: The FDA reviewed raw data in electronic format from a randomized controlled clinical trial comparing erlotinib with placebo in patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. Results: Patients were randomized in a 2:1 ratio (erlotinib, n = 488 and placebo, n = 243). Erlotinib was superior to placebo for survival, progression-free survival, and tumor response rate. Exploratory analyses indicate that epidermal growth factor receptor status may be an important predictor of the erlotinib survival effect. Rash (75% versus 17%) and diarrhea (54% versus 18%) in the erlotnib and placebo group respectively were the most common adverse events. Severe rash occurred in 9% and severe diarrhea in 6% of erlotinib-treated patients and each resulted in study discontinuation in 1% of patients. Dose reductions were required for 10% of patients with rash and 4% of patients with diarrhea. Conclusions: On November 18, 2004, the FDA granted erlotinib regular approval for treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. The applicant has committed to conduct post-marketing clinical trials to assess further the effect of epidermal growth factor receptor expression, measured with immunohistochemical staining, on erlotinib treatment effect.
TCT-80 In-Vivo Long Term Evaluation of a Novel Mitral Valve Regurgitation Therapy: Experience in a Preclinical Large Animal Model
Authors: Athanasios Peppas, Adrienne Dardenne, Yanping Cheng, Masahiko Shibuya, Christopher Seguin, Olaf Wendler, Serge D. Rousselle, Greg L. Kaluza, Juan Granada
Journal: Journal of the American College of Cardiology (2014)
The Complement Inhibitor CD59 Regulates Insulin Secretion by Modulating Exocytotic Events
Authors: Ulrika Krus, Ben C. King, Vini Nagaraj, Nikhil R. Gandasi, Jonatan Sjölander, Pawel Buda, Eliana Garcia-Vaz, Maria F. Gomez, Emilia Ottosson-Laakso, Petter Storm, Malin Fex, Petter Vikman, Enming Zhang, Sebastian Barg, Anna M. Blom, Erik Renström
Journal: Cell Metabolism (2014)
Consensus Statement on Natural Orifice Transluminal Endoscopic Surgery and Single-Incision Laparoscopic Surgery: Heralding a New Era in Urology?
Authors: Matthew T. Gettman, Geoffrey Box, Timothy Averch, Jeffrey A. Cadeddu, Edward Cherullo, Ralph V. Clayman, Mihr Desai, Igor Frank, Indebir Gill, Mantu Gupta, Georges-Pascal Haber, Mitchell Humphreys, Jihad Kaouk, Jaime Landman, Estevao Lima, Lee Ponsky
Journal: European Urology (2008)
Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-tumour necrosis factor α therapy: results from the British Society for Rheumatology Biologics Register
Authors: M J Harrison, W G Dixon, K D Watson, Y King, R Groves, K L Hyrich, D P M Symmons
Journal: Annals of the Rheumatic Diseases (2008)

Anti-tumour necrosis factor (TNF)alpha treatments improve outcome in severe rheumatoid arthritis (RA) and are efficacious in psoriasis and psoriatic arthritis. However recent case reports describe psoriasis occurring as an adverse event in patients with RA receiving anti-TNFalpha therapy.We aimed to determine whether the incidence rate of psoriasis was higher in patients with RA treated with anti-TNFalpha therapy compared to those treated with traditional disease-modifying antirheumatic drugs (DMARDs). We also compared the incidence rates of psoriasis between the three anti-TNFalpha drugs licensed for RA.We studied 9826 anti-TNF-treated and 2880 DMARD-treated patients with severe RA from The British Society for Rheumatology Biologics Register (BSRBR). All patients reported with new onset psoriasis as an adverse event were included in the analysis. Incidence rates of psoriasis were calculated as events/1000 person years and compared using incidence rate ratios (IRR).In all, 25 incident cases of psoriasis in patients receiving anti-TNFalpha therapy and none in the comparison cohort were reported between January 2001 and July 2007. The absence of any cases in the comparison cohort precluded a direct comparison; however the crude incidence rate of psoriasis in those treated with anti-TNFalpha therapy was elevated at 1.04 (95% CI 0.67 to 1.54) per 1000 person years compared to the rate of 0 (upper 97.5% CI 0.71) per 1000 person years in the patients treated with DMARDs. Patients treated with adalimumab had a significantly higher rate of incident psoriasis compared to patients treated with etanercept (IRR 4.6, 95% CI 1.7 to 12.1) and infliximab (IRR 3.5, 95% CI 1.3 to 9.3).Results from this study suggest that the incidence of psoriasis is increased in patients treated with anti-TNFalpha therapy. Our findings also suggest that the incidence may be higher in patients treated with adalimumab.
Injuries in the Victorian thoroughbred racing industry
Authors: S Cowley, B Bowman, M Lawrance
Journal: British Journal of Sports Medicine (2007)

There is increasing concern in Australia about safety in the thoroughbred racing industry, but there has been no reported analysis of injury data. This review analyses injury and workers' compensation data recorded in Victoria. On the basis of the results, it is recommended that the injury and incident data collection systems are improved such that they are not only more complete but also accumulate more detailed information about the location of an incident or injury event, the activity at the time of the incident or injury event, and factors that may have influenced the occurrence.
Increased <i>EGFR</i> Gene Copy Number Detected by Fluorescent In Situ Hybridization Predicts Outcome in Non–Small-Cell Lung Cancer Patients Treated With Cetuximab and Chemotherapy
Authors: Fred R. Hirsch, Roy S. Herbst, Christine Olsen, Kari Chansky, John Crowley, Karen Kelly, Wilbur A. Franklin, Paul A. Bunn, Marileila Varella-Garcia, David R. Gandara
Journal: Journal of Clinical Oncology (2008)

Purpose Epidermal growth factor receptor (EGFR) gene copy number detected by fluorescent in situ hybridization (FISH) has proven to be useful for selection of non–small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors. Here, we evaluate EGFR FISH as a predictive marker in NSCLC patients receiving the EGFR monoclonal antibody inhibitor cetuximab plus chemotherapy. Patients and Methods Two hundred twenty-nine chemotherapy-naive patients with advanced-stage NSCLC were enrolled onto a phase II selection trial evaluating sequential or concurrent chemotherapy (paclitaxel plus carboplatin) with cetuximab. Results EGFR FISH was assessable in 76 patients with available tumor tissue and classified as positive (four or more gene copies per cell in ≥ 40% of the cells or gene amplification) in 59.2%. Response (complete response/partial response) was numerically higher in FISH-positive (45%) versus FISH-negative (26%) patients (P = .14), whereas disease control rate (complete response/partial response plus stable disease) was statistically superior (81% v 55%, respectively; P = .02). Patients with FISH-positive tumors had a median progression-free survival time of 6 months compared with 3 months for FISH-negative patients (P = .0008). Median survival time was 15 months for the FISH-positive group compared with 7 months for patients who were FISH negative. (P = .04). Furthermore, survival favored FISH-positive patients receiving concurrent therapy. Conclusion These results are the first to suggest that EGFR FISH is a predictive factor for selection of NSCLC patients for cetuximab plus chemotherapy. Prospective validation of these findings is warranted.
Induction of Inflammatory Mediators in Human Airway Epithelial Cells by Lipid Ozonation Products
Authors: RAMZI M. KAFOURY, WILLIAM A. PRYOR, GIUSEPPE L. SQUADRITO, MARIA GIULIA SALGO, XIAOYAN ZOU, MITCHELL FRIEDMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We have proposed that exposure of epithelial cell membrane lipids in the lung (mainly phospholipids) to ozone will generate lipid ozonation products (LOP), which could be responsible for the proinflammatory effects of ozone. The ozonation of phosphocholine, the principal membrane phospholipid, produces a limited number of LOP, including hydroxyhydroperoxides and aldehydes. We now report that exposure of cultured human bronchial epithelial cells to the ozonized 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) product, 1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine (PC-ALD), a phospholipase A(2) (PLA(2))-stimulatory LOP, resulted in a 113 +/- 11% increase in the amounts of tritiated platelet-activating factor ((3)H-PAF) released apically. (3)H-PAF release was also induced by 1-hydroxy-1-hydroperoxynonane of ozonized POPC (HHP-C9), a phospholipase C (PLC)- stimulatory LOP (134 +/- 40% increase in (3)H-PAF). PC-ALD at 10 microM, but not HHP-C9, induced a 127 +/- 24% increase in prostaglandin E(2) (PGE(2)) release (n = 6, p < 0.05). In contrast, HHP-C9, but not PC-ALD, induced interleukin (IL)-6 release (178 +/- 23% increase, n = 6, p < 0.05) and IL-8 release (101 +/- 23% increase, n = 8, p < 0. 05). These results suggest that LOP-dependent release of proinflammatory mediators may play an important role in the early inflammatory response seen during exposure to ozone.
Hydroxamic Acid Analogue Histone Deacetylase Inhibitors Attenuate Estrogen Receptor-α Levels and Transcriptional Activity: A Result of Hyperacetylation and Inhibition of Chaperone Function of Heat Shock Protein 90
Authors: Warren Fiskus, Yuan Ren, Alex Mohapatra, Purva Bali, Aditya Mandawat, Rekha Rao, Bryan Herger, Yonghua Yang, Peter Atadja, Jie Wu, Kapil Bhalla
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The molecular chaperone heat shock protein (hsp)-90 maintains estrogen receptor (ER)-α in an active conformation, allowing it to bind 17β-estradiol (E2) and transactivate genes, including progesterone receptor (PR)-β and the class IIB histone deacetylase HDAC6. By inhibiting HDAC6, the hydroxamic acid analogue pan-HDAC inhibitors (HA-HDI; e.g., LAQ824, LBH589, and vorinostat) induce hyperacetylation of the HDAC6 substrates α-tubulin and hsp90. Hyperacetylation of hsp90 inhibits its chaperone function, thereby depleting hsp90 client proteins. Here, we determined the effect of HA-HDIs on the levels and activity of ERα, as well as on the survival of ERα-expressing, estrogen-responsive human breast cancer MCF-7 and BT-474 cells. Experimental Design: Following exposure to HA-HDIs, hsp90 binding, polyubiquitylation levels, and transcriptional activity of ERα, as well as apoptosis and loss of survival, were determined in MCF-7 and BT-474 cells. Results: Treatment with HA-HDI induced hsp90 hyperacetylation, decreased its binding to ERα, and increased polyubiquitylation and depletion of ERα levels. HA-HDI treatment abrogated E2-induced estrogen response element-luciferase expression and attenuated PRβ and HDAC6 levels. Exposure to HA-HDI also depleted p-Akt, Akt, c-Raf, and phospho-extracellular signal–regulated kinase-1/2 levels, inhibited growth, and sensitized ERα-positive breast cancer cells to tamoxifen. Conclusions: These findings show that treatment with HA-HDI abrogates ERα levels and activity and could sensitize ERα-positive breast cancers to E2 depletion or ERα antagonists.
The requirement of an adherent cell substratum for the growth of developing plasmacytoma cells in vivo.
Authors: M Cancro, M Potter
Journal: The Journal of Experimental Medicine (1976)

The intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) produces an environment conductive to primary plasmacytoma growth in as few as 3 days. After pristane injection, the total free peritoneal cell population increases from a normal value of 1.55 X 10(6) to 5.28 X 10(6) and remains at this elevated level for at least 50 days. The adherent peritoneal cell population, composed of both mononuclear cells and polymorphonuclear leukocytes, is the primary source of this increase. In the pristane-conditioned peritoneum, these cells rapidly form a chronic granuloma on the peritoneal connective tissues. Daily subcutaneous treatment of mice with 0.5 mg of hydrocortisone beginning simultaneously with pristane injection prevents the increase in the peritoneal cell population, granuloma formation, d the production of a conditoned environment. In mice treated with hydrocortisone beginning 3 days after pristane injection, however, neither the peritoneal cell increase nor the production of a conditioned environment is prevented. The intraperitoneal injection of thioglycolate medium at 4-day intervals produces an elevation of the free adherent peritoneal cell population similar to pristane, but does not produce a granuloma or a conditioned environment. The intraperitoneal transfer of thioglycolate-induced adherent peritonel cells to mice treated with pristane and hydrocortisone simultaneously restores the production of a conditioned environment. These findings indicate that the adherent peritoneal cell population is responsible for the conditioning effect, and that the establishment of a resident population of these cells is necessary to produce conditioning.
Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease.
Authors: S J Blander, M A Horwitz
Journal: Journal of Clinical Investigation (1993)

We have examined the capacity of the major cytoplasmic membrane protein (MCMP) of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, to induce protective immunity in a guinea pig model of Legionnaires' disease. We purified MCMP to homogeneity from L. pneumophila by buffer extraction, ion-exchange chromatography, and molecular sieve chromatography. Guinea pigs immunized with MCMP developed a strong cell-mediated immune response to the immunogen manifest by marked cutaneous delayed-type hypersensitivity. Guinea pigs immunized with MCMP and then challenged with a lethal aerosol dose of L. pneumophila exhibited a high level of protective immunity. Altogether, in four independent experiments, 55 of 64 (86%) animals immunized three times with 0.6-40 micrograms MCMP including 11 of 11 (100%) animals immunized three times with 40 micrograms MCMP survived aerosol challenge with L. pneumophila compared with 1 of 29 (3%) sham-immunized control animals (P < 0.0001, Cochran-Mantel-Haenszel X2 statistic for pooled data). To our knowledge, MCMP is the first member of the hsp 60 family of proteins shown to induce protective immunity to a microbial pathogen. MCMP has potential as a vaccine against Legionnaires' disease. Since MCMP is a genus common antigen, vaccination with a combination of MCMPs derived from different Legionella species has the potential of inducing protective immunity against all the major Legionella species causing human disease.