tbuckley/cabot-search huggingface dataset:
Epidermal Growth Factor Receptor Inhibition Augments the Expression of MHC Class I and II Genes
Authors: Brian P. Pollack, Bishu Sapkota, Todd V. Cartee
Journal: Clinical Cancer Research (2011)

Diverse immune-related effects occur with the use of epidermal growth factor receptor inhibitors (EGFRI). In addition to the cutaneous inflammation induced by EGFRIs, these agents have been associated with the exacerbation of autoimmune skin disease and contact hypersensitivity, antiviral effects, and fatal alveolar damage in the setting of lung transplantation. Because EGFR ligands can modulate MHC class I (MHCI) and II (MHCII) molecule expression, we hypothesized that some of the immune-related effects of EGFRIs are due to direct effects on the expression of MHCI and/or MHCII molecules.Primary human keratinocytes and a malignant keratinocyte cell line (A431) were treated with EGFRIs alone or prior to IFN-γ, a potent inducer of MHCI and MHCII molecule expression. CIITA, MHCI, and MHCII RNA expression was measured using quantitative real-time reverse transcriptase PCR, and cell surface MHCI and MHCII protein expression was measured using flow cytometry. Skin biopsies from patients were analyzed for MHCI and MHCII protein expression before and during therapy with an EGFRI using immunohistochemistry.Both EGFR tyrosine kinase inhibitors and ligand-blocking antibodies (cetuximab) augmented the induction of MHCI and MHCII molecules by IFN-γ in primary and malignant human keratinocytes. Unexpectedly, the increase in MHCI protein expression did not require the presence of IFN-γ. Consistent with these in vitro findings, skin biopsies from cancer patients exhibited increased epidermal MHCI protein expression during therapy with an EGFRI as well as increases in MHCI and MHCII molecule RNA.These studies suggest that EGFRIs may influence immune/inflammatory responses by directly modulating MHC expression. Clin Cancer Res; 17(13); 4400-13. ©2011 AACR.
Breastfeeding, PAM50 Tumor Subtype, and Breast Cancer Prognosis and Survival
Authors: Marilyn L. Kwan, Philip S. Bernard, Candyce H. Kroenke, Rachel E. Factor, Laurel A. Habel, Erin K. Weltzien, Adrienne Castillo, Erica P. Gunderson, Kaylynn S. Maxfield, Inge J. Stijleman, Bryan M. Langholz, Charles P. Quesenberry, Lawrence H. Kushi, Carol Sweeney, Bette J. Caan
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Breastfeeding is associated with decreased breast cancer risk, yet associations with prognosis and survival by tumor subtype are largely unknown.
Store-Operated Ca <sup>2+</sup> Influx and Expression of TRPC Genes in Mouse Sinoatrial Node
Authors: Yue-Kun Ju, Yi Chu, Herve Chaulet, Donna Lai, Othon L. Gervasio, Robert M. Graham, Mark B. Cannell, David G. Allen
Journal: Circulation Research (2007)

Store-operated Ca(2+) entry was investigated in isolated mouse sinoatrial nodes (SAN) dissected from right atria and loaded with Ca(2+) indicators. Incubation of the SAN in Ca(2+)-free solution caused a substantial decrease in resting intracellular Ca(2+) concentration ([Ca(2+)](i)) and stopped pacemaker activity. Reintroduction of Ca(2+) in the presence of cyclopiazonic acid (CPA), a sarcoplasmic reticulum Ca(2+) pump inhibitor, led to sustained elevation of [Ca(2+)](i), a characteristic of store-operated Ca(2+) channel (SOCC) activity. Two SOCC antagonists, Gd(3+) and SKF-96365, inhibited 72+/-8% and 65+/-8% of this Ca(2+) influx, respectively. SKF-96365 also reduced the spontaneous pacemaker rate to 27+/-4% of control in the presence of CPA. Because members of the transient receptor potential canonical (TRPC) gene family may encode SOCCs, we used RT-PCR to examine mRNA expression of the 7 known mammalian TRPC isoforms. Transcripts for TRPC1, 2, 3, 4, 6, and 7, but not TRPC5, were detected. Immunohistochemistry using anti-TRPC1, 3, 4, and 6 antibodies revealed positive labeling in the SAN region and single pacemaker cells. These results indicate that mouse SAN exhibits store-operated Ca(2+) activity which may be attributable to TRPC expression, and suggest that SOCCs may be involved in regulating pacemaker firing rate.
Prognostic Significance of [<sup>18</sup>F]-Misonidazole Positron Emission Tomography–Detected Tumor Hypoxia in Patients With Advanced Head and Neck Cancer Randomly Assigned to Chemoradiation With or Without Tirapazamine: A Substudy of Trans-Tasman Radiation Oncology Group Study 98.02
Authors: Danny Rischin, Rodney J. Hicks, Richard Fisher, David Binns, June Corry, Sandro Porceddu, Lester J. Peters
Journal: Journal of Clinical Oncology (2006)

Purpose To determine the association between tumor hypoxia, treatment regimen, and locoregional failure (LRF) in patients with stage III or IV squamous cell carcinoma of the head and neck randomly assigned to radiotherapy (70 Gy in 35 fractions over 7 weeks) plus either tirapazamine and cisplatin in weeks 1, 4, and 7 and tirapazamine alone in weeks 2 and 3 (TPZ/CIS) or cisplatin and infusional fluorouracil during weeks 6 and 7 (chemoboost). Patients and Methods Forty-five patients were enrolled onto a hypoxic imaging substudy of a larger randomized trial. Pretreatment and midtreatment [ 18 F]-fluoromisonidazole positron emission tomography scans (FMISO-PET) were performed 2 hours after tracer administration, with qualitative scoring of uptake in both primary tumors and nodes. Results Thirty-two patients (71%) had detectable hypoxia in either or both primary and nodal disease. In patients who received chemoboost, one of 10 patients without hypoxia had LRF compared with eight of 13 patients with hypoxia; the risk of LRF was significantly higher in hypoxic patients (exact log-rank, P = .038; hazard ratio [HR] = 7.1). By contrast, in patients who received the TPZ/CIS regimen, only one of 19 patients with hypoxic tumors had LRF; risk of LRF was significantly higher in chemoboost patients (P = .001; HR = 15). Similarly, looking at the primary site alone, in patients with hypoxic primaries, zero of eight patients treated with TPZ/CIS experienced failure locally compared with six of nine patients treated with chemoboost (P = .011; HR = 0). Conclusion Hypoxia on FMISO-PET imaging, in patients receiving a nontirapazamine-containing chemoradiotherapy regimen, is associated with a high risk of LRF. Our data provide the first clinical evidence to support the experimental observation that tirapazamine acts by specifically targeting hypoxic tumor cells.
Polycystin
Authors: PATRICIA D. WILSON
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Polycystin-1 is a modular membrane protein with a long extracellular N-terminal portion that bears several ligand-binding domains, 11 transmembrane domains, and a ≥200 amino acid intracellular C-terminal portion with several phosphorylation signaling sites. Polycystin-1 is highly expressed in the basal membranes of ureteric bud epithelia during early development of the metanephric kidney, and disruption of the PKD1 gene in mice leads to cystic kidneys and embryonic or perinatal death. It is proposed that polycystin-1 functions as a matrix receptor to link the extracellular matrix to the actin cytoskeleton via focal adhesion proteins. Co-localization, co-sedimentation, and co-immunoprecipitation studies show that polycystin-1 forms multiprotein complexes with α2β1-integrin, talin, vinculin, paxillin, p130cas, focal adhesion kinase, and c-src in normal human fetal collecting tubules and sub-confluent epithelial cultures. In normal adult kidneys and confluent epithelial cultures, polycystin-1 is downregulated and forms complexes with the cell-cell adherens junction proteins E-cadherin and β-, γ-, and α-catenin. Polycystin-1 activation at the cell membrane leads to intracellular signaling via phosphorylation through the c-Jun terminal kinase and wnt pathways leading to activation of AP-1 and TCF/LEF-dependent genes, respectively. The C-terminal of polcystin-1 has been shown to be phosphorylated by c-src at Y4237, by protein kinase A at S4252, and by focal adhesion kinase and protein kinase X at yet-to-be identified residues. Inhibition of tyrosine phosphorylation or increased cellular calcium increases polycystin-1 focal adhesion complexes versus polycystin-1 adherens junction complexes, whereas disruption of the actin cytoskeleton dissociates all polycystin-1 complexes. Genetic evidence suggests that PKD1, PKD2, NPHP1 , and tensin are in the same pathway.
Renal endothelin system in polycystic kidney disease.
Authors: B Hocher, R Zart, A Schwarz, V Vogt, C Braun, C Thöne-Reineke, N Braun, H H Neumayer, K Koppenhagen, C Bauer, P Rohmeiss
Journal: Journal of the American Society of Nephrology (1998)

Polycystic kidney disease (PKD) is characterized by interstitial fibrosis and formation of renal cysts. Interestingly, interstitial fibrosis and renal cyst formation were also seen in human endothelin-1 (ET-1) transgenic mice. This study, therefore, analyzes the tissue distribution of ET-1, the tissue concentrations of ET-1, as well as the expression of ET receptor subtypes in the kidneys of a rat model of PKD: Han:SPRD rats. Six-week-old heterozygous (cy/+) and homozygous (cy/cy), as well as 6-mo-old heterozygous (cy/+) Han:SPRD rats and the corresponding age-matched Sprague Dawley littermates (SD) (+/+) were analyzed. Furthermore, the acute effects of the mixed (A/B) endothelin receptor antagonist bosentan on hemodynamic and renal function were investigated in 6-mo-old, conscious, chronically instrumented (cy/+) rats. The kidneys of affected rats showed significantly elevated tissue levels of ET-1 compared with age-matched controls (3.5 +/- 0.3-fold in young cy/cy rats, P < 0.01; 1.4 +/- 0.2-fold in young cy/+ rats, P < 0.01; 6.2 +/- 0.4-fold in old cy/+ rats, P < 0.001) due to a highly increased ET-1 synthesis within the epithelial cells of the cysts. Analyzing tissue sections from patients with typical autosomal dominant PKD demonstrated a high ET-1 expression within the epithelial cells of the cysts as well. Scatchard analysis revealed a markedly decreased ETA and ETB receptor density in all groups of affected rats. The acute blockade of both endothelin receptor subtypes using bosentan in 6-mo-old heterozygous PKD rats led to a significant decrease in mean arterial BP (MAP) (-19.7 +/- 2.1 mmHg, P < 0.05) and GFR (-41 +/- 5%, P < 0.005). Renal blood flow (RBF) was significantly increased (+2.1 +/- 0.5 ml/min, P < 0.05) after bosentan, whereas bosentan had no effect on MAP, GFR, and RBF in age-matched controls. These data show that the paracrine renal endothelin system is activated in PKD and participates in the regulation of MAP, GFR, RBF, and possibly contributes to renal cyst formation and fibrosis.
Non-African Origin of a Local Beneficial Mutation in D. melanogaster
Authors: F. Catania, C. Schlötterer
Journal: Molecular Biology and Evolution (2004)

It is well understood that the out-of-Africa habitat expansion of D. melanogaster was associated with the fixation of many beneficial mutations. Nevertheless, it is not clear yet whether these beneficial mutations segregated already in Africa or originated outside of Africa. In this article, we describe an ongoing selective sweep specific to one European population. One microsatellite allele has increased in a population from The Netherlands to a frequency of 18%, whereas it is virtually absent in 12 other European populations. The selective sweep resulted in a genomic region of more than 600 kb that is identical by descent. This is probably the first evidence of a beneficial mutation that has arisen outside of Africa and has resulted in a selective sweep localized in a population from The Netherlands.
Continuous determination of beat to beat stroke volume from aortic pressure pulses in the dog.
Authors: M J Bourgeois, B K Gilbert, G Von Bernuth, E H Wood
Journal: Circulation Research (1976)

Present methods for measurement of stroke volume from the aortic pressure pulse are not suitable for beat-to-beat determinations during non-steady state conditions because these methods assume that each systolic ejection is equal to the peripheral runoff during the same beat. We have tested a new method which allows determination of an aortic pressure-volume conversion factor over a wide range of pressures during transient changes in stroke volume and infusions of vasoactive drugs in 6 dogs with chronically implanted aortic electromagnetic flowmeters. Each aortic diastolic pressure decay is approximated by an exponential the time constant of which is used to calculate the pressure loss during systole due to blood flow into the periphery. The total increment in aortic pressure due to systolic ejection, if there were no flow from the aorta during systole, then is calculated. The total systolic increment (delta PSV) is assumed to describe the pressure-volume characteristics during systole and is related to stroke volume by a constant multiplier that is derived from the indicator-dilution measurements of cardiac output. The values for beat-to-beat variations that were determined by use of the aortic electromagnetic flowmeter and by this aortic pressure pulse method were found to be within the range of measurement errors of stroke volume determined from individual aortic electromagnetic flow pulses.
Inflammatory bowel disease and tobacco smoke--a case-control study.
Authors: P G Persson, A Ahlbom, G Hellers
Journal: Gut (1990)

A case-control study was carried out in Stockholm, Sweden between 1984 and 1987 to evaluate the association of cigarette smoking and exposure to environmental tobacco smoke during childhood and the subsequent development of inflammatory bowel disease. Information on smoking was obtained by a postal questionnaire. The relative risk of Crohn9s disease in current smokers compared with those who had never smoked was 1.33 (95% confidence limits 0.7; 2.6) in men and 4.99 (2.7; 9.2) in women; the corresponding results for ulcerative colitis were 0.96 (0.5; 1.8) and 0.72 (0.4; 1.4). The relative risk of ulcerative colitis in recent exsmokers compared with those who had never smoked was 2.18 (0.9; 5.0). Furthermore, an increase in the risk of Crohn9s disease was found in those who were exposed to environmental tobacco smoke during childhood, the relative risk being 1.50 (1.0; 2.3). The corresponding relative risk of ulcerative colitis was 0.98 (0.6; 1.5).
Dose and Dose Intensity as Determinants of Outcome in the Adjuvant Treatment of Breast Cancer
Authors: Daniel R. Budman, Donald A. Berry, Constance T. Cirrincione, I. Craig Henderson,, William C. Wood, Raymond B. Weiss, Carolyn R. Ferree, Hyman B. Muss, Mark R. Green, Larry Norton, Emil Frei
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. Methods: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5- fluorouracil on day 1 of each chemotherapy cycle, with 5- fluorouracil administration repeated on day 8. The highdose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. Results: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average ± standard error) is 79% ± 2% for patients on the high-dose arm, 77% ± 2% for the patients on the moderate-dose arm, and 72% ± 2% for patients on the low-dose arm; disease-free survival is 66% ± 2%, 61% ± 2%, and 56% ± 2%, respectively. Conclusion: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival. [J Natl Cancer Inst 1998;90: 1205–11]
Molecular Pathways Mediating Liver Metastasis in Patients with Uveal Melanoma
Authors: Silvin Bakalian, Jean-Claude Marshall, Patrick Logan, Dana Faingold, Shawn Maloney, Sebastian Di Cesare, Claudia Martins, Bruno F. Fernandes, Miguel N. Burnier
Journal: Clinical Cancer Research (2008)

Abstract Uveal melanoma arises from melanocytes located in the uveal tract of the eye and is the most common primary intraocular tumor in adults. Metastatic liver disease is the overwhelming cause of death in uveal melanoma patients, with almost 50% of patients developing liver metastases up to 15 years after diagnosis. Most of these patients do not present with any evidence of overt metastasis at the time of initial diagnosis although it is assumed that they have undetectable micrometastases. Currently, there are no therapeutic modalities to prevent or efficiently treat the metastatic disease in uveal melanoma patients. Recent discoveries have shed light on the molecular pathways that may contribute to the progression of liver metastasis. The aim of this review is to describe new insights into the genetic and molecular pathways that may play a role in the development of liver metastases in uveal melanoma patients.
On the influence of the natriuretic factor from patients with chronic uremia on the bioelectric properties and sodium transport of the isolated mammalian collecting tubule.
Authors: L G Fine, J J Bourgoignie, K H Hwang, N S Bricker
Journal: Journal of Clinical Investigation (1976)

A gel filtration fraction of urine from patients with chronic renal disease (natriuretic factor) has been shown previously to cause natriuresis in rats and to inhibit sodium transport in the isolated toad bladder. The effect of this fraction on transtubular potential difference and sodium transport was examined on the isolated perfused cortical collecting tubule of the rabbit. A rapid inhibition of potential difference from -22.5 mV to -12 mV (P less than 0.001) was observed when the fraction was applied to the peritubular surface. This effect was accompanied by a decrease in net sodium flux from 6.29 to 3.21 pmol/cm per s (P less than 0.001). Unidirectional fluxes using isotopic sodium revealed that the inhibition of net sodium transport was due to a decrease in flux from the lumen to the peritubular surface, i.e., an inhibition of active sodium transport. There was no change in sodium flux in the reverse direction. These changes were all rapidly reversed by removal of the fraction from the peritubular surface. The addition of the fraction to the lumen had no effect on potential difference or net sodium flux. Control studies using the same fraction from the urine of normal subjects had no effect on any of the parameters studies. Where both a uremic and a normal fraction were sequentially applied to the peritubular surface of the same tubule, inhibition of potential difference was obtained only with the former. In the light of evidence implicating the collecting duct fraction from normal animals, the data are consistent with the view that the natriuretic factor may be biologically important in the regulation of sodium balance via it's regulatory role in active sodium transport in the collecting tubule.
POSSIBILITY OF HEREDITARY TRANSMISSION OF YELLOW FEVER VIRUS BY AEDES AEGYPTI (LINN.)
Authors: Cornelius B. Philip
Journal: The Journal of Experimental Medicine (1929)

Attempts to obtain passage of yellow fever virus from one generation to the next in A. aegypti were unsuccessful. Subcutaneous injections at varying intervals of a saline emulsion of 200 eggs laid by an infective lot of mosquitoes produced no reaction in six normal M. rhesus monkeys. Negative results were also obtained in five biting and two injection experiments with progeny of the same infective lot of mosquitoes in which seven normal monkeys were used. The eggs consisted of batches laid after the first, second and fourth blood-meals of the original lot; the latter feeding occurred 41 days after the initial infecting meal. The imaginal offspring represented rearings following the first, second and fifth blood-meals of the parent lot. The last feeding occurred 54 days after the first. It is concluded that under the conditions of the experiments here reported hereditary transmission of yellow fever by A. aegypti is improbable. Variations in age and in number of blood-meals of parent and offspring mosquitoes had no effect in achieving passage of the virus from one stage of the insect to another.
Expression of tenascin, biglycan and decorin in disorders of keratinization
Authors: P.M. STEIJLEN, E. MAESSEN, H. KRESSH, I.M.J.J. VLIJMEN, A.A. VERSTRAETEN, H. TRAUPER, J. SCHALKWIJK
Journal: British Journal of Dermatology (1994)

Journal Article Expression of tenascin, biglycan and decorin in disorders of keratinization Get access P.M. STEIJLEN, P.M. STEIJLEN Department of Dermatology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E. MAESSEN, E. MAESSEN Department of Dermatology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar H. KRESSH, H. KRESSH Institute of Psysiological Chemistry and Pathobiochemistry Search for other works by this author on: Oxford Academic Google Scholar I.M.J.J. VAN VLIJMEN, I.M.J.J. VAN VLIJMEN Department of Dermatology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar A.A. VERSTRAETEN, A.A. VERSTRAETEN Department of Obstetrics and Gynaecology, Free University Hospital Amsterdam, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar H. TRAUPER, H. TRAUPER Department of Dermatology, University of Münster, Search for other works by this author on: Oxford Academic Google Scholar J. SCHALKWIJK J. SCHALKWIJK Department of Dermatology, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 5, 1 May 1994, Pages 564–568, https://doi.org/10.1111/j.1365-2133.1994.tb13100.x Published: 01 May 1994 Article history Accepted: 27 September 1993 Published: 01 May 1994
Abstract 13813: High Levels of Cardiometabolic Risk, Knowledge, and Risk Perception Co-Occur with Low Self-Efficacy to Prevent Cardiometabolic Disease in American Indian Women with Previous Gestational Diabetes
Authors: Emily J Jones, Susan J Appel
Journal: Circulation (2011)

Background: Knowledge of risk factors, risk perception, and self-efficacy are central to preventing cardiometabolic disease (CMD) among women with previous gestational diabetes mellitus (GDM). Alth...