tbuckley/cabot-search huggingface dataset:
Apicularen A Induces Cell Death through Fas Ligand Up-Regulation and Microtubule Disruption by Tubulin Down-Regulation in HM7 Human Colon Cancer Cells
Authors: Jong-Seok Kim, Young-Chul Lee, Ho-Tak Nam, Ge Li, Eun-Jin Yun, Kyoung-Sub Song, Kang-Sik Seo, Ji-Hoon Park, Jong-Woong Ahn, OkPyo Zee, Jong-Il Park, Wan-Hee Yoon, Kyu Lim, Byung-Doo Hwang
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Apicularen A has been shown to cause growth inhibition and apoptosis in several cancer cell lines. However, the mechanisms of apicularen A–induced cell death and in vivo effects remain unclear. In this study, we investigated the molecular mechanisms of apicularen A–induced cell death in HM7 human colon cancer cells in vitro and anticancer activity in vivo. Experimental Design: We tested cytotoxicity with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, apoptosis with DNA fragmentation assay, mitochondrial membrane potential, and cell cycle with fluorescence-activated cell sorting. Caspase activation was done by fluorometry. Alterations of microtubule structure, tubulin protein, and mRNA level were assessed by immunofluorescence, Western blot, and reverse transcription-PCR. In vivo studies were assessed using nude mice tumor cell growth in xenograft model and liver colonization assay. Results: Apicularen A treatment of HM7 cells inhibited cell growth and this inhibition was partially rescued by z-VAD-fmk. Apicularen A caused accumulation of sub-G1-G0, DNA fragmentation, Fas ligand induction, and activation of caspase-8 and caspase-3, but mitochondrial membrane potential was not changed. Furthermore, β-tubulin protein and mRNA were decreased by apicularen A, but in vitro polymerization of tubulin was not affected. Concurrently, apicularen A–treated cell showed disruption of microtubule architecture. In in vivo studies, apicularen A reduced tumor volume by ∼72% at the end of a 15-day treatment. Moreover, apicularen A reduced liver colonization as much as 95.6% (50 μg/kg/d). Conclusion: Apicularen A induces cell death of HM7 cells through up-regulating Fas ligand and disruption of microtubule architecture with down-regulation of tubulin level. These findings indicate that apicularen A is a promising new microtubule-targeting compound.
The role of ICAM-1 on T-cells in the pathogenesis of asthma
Authors: LA Stanciu, R Djukanovic
Journal: European Respiratory Journal (1998)

The capacity of inflammatory cells to adhere is critical to inflammatory responses and involves an array of adhesion molecules grouped into distinct families. Intercellular adhesion molecule (ICAM)-1 has recently attracted much interest in view of increasing evidence that it plays a prominent role in allergic diseases such as asthma and rhinitis. Apart from its role in adhesion of inflammatory cells to vascular endothelium, the extracellular matrix and epithelium, ICAM-1 mediates T-cell/T-cell, T-cell/target cell and T-cell/B-cell interactions. ICAM-1 on the surface of T-cells is thought to participate in signal transduction and may thus modulate several functions including activation, proliferation, cytotoxicity and cytokine production. Because ICAM-1 is the receptor for the major group of rhinoviruses, the most important cause of acute asthma attacks, binding of rhinovirus (RV) to ICAM-1 on T-cells may, at least theoretically, modulate their function. We review here the role of ICAM-1 in asthma and focus more specifically on its expression on T-cells. We present evidence for a general increase in ICAM-1 expression in this disease including recent observations of enhanced expression on the surface of T-cells in the airways lumen. Whilst the implications of intercellular adhesion molecule- upregulation in asthma remain to be fully elucidated, its participation in cell trafficking and activation are being considered as a target for treatment. We present here early attempts to interfere with intercellular adhesion molecule-1 as an adhesion molecule involved in cell influx and studies aimed preventing virus-induced exacerbations of asthma in children based on the knowledge that intercellular adhesion molecule-1 is the receptor for rhinoviruses.
Nuclear Factor-κB in Development, Prevention, and Therapy of Cancer
Authors: Carter Van Waes
Journal: Clinical Cancer Research (2007)

Abstract Nuclear factor-κB (NF-κB) is a signal transcription factor that has emerged as an important modulator of altered gene programs and malignant phenotype in development of cancer. Major carcinogens and oncogenic viruses induce NF-κB activation, and a variety of subsequent oncogenic events contribute to a progressive increase in constitutive NF-κB activation as an important common pathway in most forms of cancer. NF-κB target genes promote tumor cell proliferation, survival, migration, inflammation, and angiogenesis. Inhibition of NF-κB has been found to be an important mechanism of action of steroids, nonsteroidal anti-inflammatory drugs, and natural and synthetic compounds that show therapeutic and preventive activity. Newer agents targeting the proteasome, inhibitor-κB kinase, and other upstream kinases involved in NF-κB activation have shown anticancer activity in clinical or preclinical studies.
Breast Cancer Surveillance Practices Among Women Previously Treated With Chest Radiation for a Childhood Cancer
Authors: Kevin C. Oeffinger
Journal: JAMA (2009)

<h3>Context</h3>Women treated with chest radiation for a pediatric malignancy have a significantly increased risk of breast cancer at a young age and are recommended to have an annual screening mammogram starting at age 25 years or 8 years after radiation, whichever occurs last.<h3>Objective</h3>To characterize the breast cancer surveillance practices among female pediatric cancer survivors who were treated with chest radiation and identify correlates of screening.<h3>Design, Setting, and Participants</h3>Between June 2005 and August 2006, a 114-item questionnaire was administered to a random sample of 625 women aged 25 through 50 years who had survived pediatric cancer, who had been treated with chest radiation, and who were participating in the Childhood Cancer Survivor Study (CCSS), a North American cohort of long-term survivors diagnosed from 1970-1986. Comparisons were made with similarly aged pediatric cancer survivors not treated with chest radiation (n = 639) and the CCSS siblings cohort (n = 712).<h3>Main Outcome Measure</h3>Screening mammogram within the previous 2 years.<h3>Results</h3>Of 1976 cancer survivors and siblings who were contacted, 87.9% participated. Among the 551 women with a history of chest radiation, 55% reported a screening mammogram in the past 2 years (ages 25-39 years, 36.5%; 95% confidence interval [CI], 31.0%-42.0%; ages 40-50 years, 76.5%; 95% CI, 71.3%-81.7%). In comparison, 40.5% of survivors without chest radiation and 37.0% of CCSS siblings reported a screening mammogram in the same time interval. Notably, among women with a history of chest radiation, 47.3% (95% CI; 41.6%-53.0%) of those younger than 40 years had never had a mammogram and only 52.6% (95% CI; 46.4%-58.8%) of women aged 40 through 50 years were being regularly screened (2 mammograms within 4 years). Screening rates were higher among women who reported a physician recommendation than those who did not (ages 25-39 years, 76.0% vs 17.6%; ages 40-50 years, 87.3% vs 58.3%). In multivariate models, the association was particularly strong for younger women (ages 25-39 years, prevalence ratio [PR], 3.0; 95% CI, 2.0-4.0; ages 40-50 years, PR, 1.3; 95% CI, 1.1-1.6).<h3>Conclusions</h3>In this cohort of women who had childhood cancer treated with chest radiation, 63.5% of those aged 25 through 39 years and 23.5% of those aged 40 through 50 years had not had mammography screening for breast cancer within the previous 2 years despite a guideline recommendation that survivors of childhood cancer who were treated with chest radiation should undergo annual screening mammography.
Effects of leg massage on recovery from high intensity cycling exercise
Authors: A Robertson, J M Watt, S D R Galloway
Journal: British Journal of Sports Medicine (2004)

Background: The effect of massage on recovery from high intensity exercise is debatable. Many studies on massage suffer from methodological flaws such as poor standardisation of previous exercise, lack of dietary control, and inappropriate massage duration. Objective: To examine the effects of leg massage compared with passive recovery on lactate clearance, muscular power output, and fatigue characteristics after repeated high intensity cycling exercise, with the conditions before the intervention controlled and standardised. Methods: Nine male games players participated. They attended the laboratory on two occasions one week apart and at the same time of day. Dietary intake and activity were replicated for the two preceding days on each occasion. After baseline measurement of heart rate and blood lactate concentration, subjects performed a standardised warm up on the cycle ergometer. This was followed by six standardised 30 second high intensity exercise bouts, interspersed with 30 seconds of active recovery. After five minutes of active recovery and either 20 minutes of leg massage or supine passive rest, subjects performed a second standardised warm up and a 30 second Wingate test. Capillary blood samples were drawn at intervals, and heart rate, peak power, mean power, and fatigue index were recorded. Results: There were no significant differences in mean power during the initial high intensity exercise bouts (p = 0.92). No main effect of massage was observed on blood lactate concentration between trials (p = 0.82) or heart rate (p = 0.81). There was no difference in the maximum power (p = 0.75) or mean power (p = 0.66) in the subsequent Wingate test, but a significantly lower fatigue index was observed in the massage trial (p = 0.04; mean (SD) fatigue index 30.2 (4.1)% v 34.2 (3.3)%). Conclusions: No measurable physiological effects of leg massage compared with passive recovery were observed on recovery from high intensity exercise, but the subsequent effect on fatigue index warrants further investigation.
Inhibition of neointima formation by local delivery of estrogen receptor alpha and beta specific agonists
Authors: Y KROM, N PIRES, J JUKEMA, M DEVRIES, R FRANTS, L HAVEKES, K VANDIJK, P QUAX
Journal: Cardiovascular Research (2006)

Objective: Neointima formation is the underlying mechanism of (in-stent) restenosis. 17β-Estradiol (E2) is known to inhibit injury-induced neointima formation and post-angioplasty restenosis. Estrogen receptor alpha (ERα) has been demonstrated to mediate E2 anti-restenotic properties. However, the role of estrogen receptor beta (ERβ) is not fully elucidated. In the present study, the specific role of vascular ERα and ERβ in neointima formation is assessed. Methods and results: Neointima formation was induced by placement of a perivascular cuff around the femoral artery of male C57BL/6J mice. E2-eluting cuffs significantly inhibited cuff-induced neointima formation. To address the specific roles of ERα and ERβ on neointima formation, the ERα-selective agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol (PPT) and the ERβ-selective agonist 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN) were applied via a drug-eluting cuff. PPT inhibited neointima formation at low but not at high concentrations. Conversely, DPN inhibited neointima formation dose dependently. To demonstrate the specificity of these responses, an ERα-selective antagonist, MPP, was also used in combination with E2, PPT, or DPN. While the effect of PPT on neointima formation inhibition was blocked by co-delivery of MPP, E2 and DPN could still inhibit neointima formation. Conclusions: Our data suggest that, in addition to ERα, specific ERβ activation inhibits neointima formation in a mouse model of restenosis. These data reveal a yet unidentified protective role of ERβ on neointima formation.
Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques
Authors: William R. Wikoff, Gurudutt Pendyala, Gary Siuzdak, Howard S. Fox
Journal: Journal of Clinical Investigation (2008)

HIV infiltrates the CNS soon after an individual has become infected with the virus, and can cause dementia and encephalitis in late-stage disease. Here, a global metabolomics approach was used to find and identify metabolites differentially regulated in the cerebrospinal fluid (CSF) of rhesus macaques with SIV-induced CNS disease, as we hypothesized that this might provide biomarkers of virus-induced CNS damage. The screening platform used a non-targeted, mass-based metabolomics approach beginning with capillary reverse phase chromatography and electrospray ionization with accurate mass determination, followed by novel, nonlinear data alignment and online database screening to identify metabolites. CSF was compared before and after viral infection. Significant changes in the metabolome specific to SIV-induced encephalitis were observed. Metabolites that were increased during infection-induced encephalitis included carnitine, acyl-carnitines, fatty acids, and phospholipid molecules. The elevation in free fatty acids and lysophospholipids correlated with increased expression of specific phospholipases in the brains of animals with encephalitis. One of these, a phospholipase A2 isoenzyme, is capable of releasing a number of the fatty acids identified. It was expressed in different areas of the brain in conjunction with glial activation, rather than linked to regions of SIV infection and inflammation, indicating widespread alterations in infected brains. The identification of specific metabolites as well as mechanisms of their increase illustrates the potential of mass-based metabolomics to address problems in CNS biochemistry and neurovirology, as well as neurodegenerative diseases.
EVIDENCE FOR AN IMMUNE RESPONSE TO HLA CLASS I ANTIGENS IN THE VANISHING-BILEDUCT SYNDROME AFTER LIVER TRANSPLANTATION
Authors: P.T. Donaldson, J. O'Grady, B. Portmann, H. Davis, G.J.M. Alexander, J. Neuberger, M. Thick, R.Y. Calne, Roger Williams
Journal: The Lancet (1987)
Effect of thrombin inhibition on the dynamics of thrombolysis and on platelet function during thrombolytic therapy.
Authors: M A Rudd, D George, M T Johnstone, R T Moore, L Collins, L E Rabbani, J Loscalzo
Journal: Circulation Research (1992)

To evaluate the effect of thrombin on the dynamics of thrombolysis, we infused rabbits with heparin or hirudin alone or in conjunction with tissue-type plasminogen activator (t-PA) and monitored the kinetics of fibrinolysis and changes in ex vivo platelet aggregation responses over time. Both heparin and hirudin enhanced total fibrinolysis in an ex vivo arteriovenous shunt preparation: 82 +/- 2% and 79 +/- 2%, respectively, compared with 51 +/- 8% for t-PA alone (P less than 0.05) and 50 +/- 4% for t-PA plus aspirin (p less than 0.05). Heparin coadministered with t-PA significantly reduced the half-time for clot lysis compared with t-PA alone (p less than 0.05), whereas hirudin coadministered with t-PA significantly reduced the half-time for clot lysis compared with that for t-PA alone, t-PA plus aspirin, and t-PA plus heparin (5.5 +/- 0.6 versus 12.1 +/- 2.0 versus 12.6 +/- 2.2 versus 10.0 +/- 0.8 minutes, respectively; p less than 0.05). Both heparin and hirudin prevented the increase in ADP-induced platelet aggregation normally seen with t-PA alone (p less than 0.01 by t test; p less than 0.05 by two-way analysis of variance). These data demonstrate that selective, antithrombin III-independent thrombin inhibitors can enhance the efficacy of thrombolysis by modulating the dynamics of the process and preventing platelet activation associated with plasminogen activator therapy.
Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone
Authors: Aya Kobayashi, Hiroshi Okuda, Fei Xing, Puspa R. Pandey, Misako Watabe, Shigeru Hirota, Sudha K. Pai, Wen Liu, Koji Fukuda, Christopher Chambers, Andrew Wilber, Kounosuke Watabe
Journal: The Journal of Experimental Medicine (2011)

Metastatic disease is the major cause of cancer deaths, and recurrent tumors at distant organs are a critical issue. However, how metastatic tumor cells become dormant and how and why tumors recur in target organs are not well understood. In this study, we demonstrate that BMP7 (bone morphogenetic protein 7) secreted from bone stromal cells induces senescence in prostate cancer stem-like cells (CSCs) by activating p38 mitogen-activated protein kinase and increasing expression of the cell cycle inhibitor, p21, and the metastasis suppressor gene, NDRG1 (N-myc downstream-regulated gene 1). This effect of BMP7 depended on BMPR2 (BMP receptor 2), and BMPR2 expression inversely correlated with recurrence and bone metastasis in prostate cancer patients. Importantly, this BMP7-induced senescence in CSCs was reversible upon withdrawal of BMP7. Furthermore, treatment of mice with BMP7 significantly suppressed the growth of CSCs in bone, whereas the withdrawal of BMP7 restarted growth of these cells. These results suggest that the BMP7–BMPR2–p38–NDRG1 axis plays a critical role in dormancy and recurrence of prostate CSCs in bone and suggest a potential therapeutic utility of BMP7 for recurrent metastatic disease.
Oncogenic <i>K-RAS</i> Is Required to Maintain Changes in Cytoskeletal Organization, Adhesion, and Motility in Colon Cancer Cells
Authors: Claire B. Pollock, Senji Shirasawa, Takehiko Sasazuki, Walter Kolch, Amardeep S. Dhillon
Journal: Cancer Research (2005)

Abstract RAS oncogenes are thought to play a role at multiple stages of tumorigenesis. The role and mechanisms by which RAS oncogenes maintain the transformed state of human cancer cells are poorly understood. Here, we have studied the role of oncogenic K-RAS in maintaining cytoskeletal disruption, cell adhesion and motility in metastatic colon carcinoma cells. Targeted deletion of K-RASG13D from HCT116 colon carcinoma cells restored their ability to assemble stress fibers and focal adhesions/complexes, accompanied by increased cell-matrix adhesion and reduced motility. We further show that oncogenic K-Ras induces high Rho activity, but uncouples Rho from stress fiber formation. This uncoupling required the maintenance of high levels of the activator protein-1 family member, Fra-1, via a mitogen-activated protein/extracellular signal-regulated kinase–dependent pathway. We also show that PI3-kinase signaling is required for the motility of HCT116 cells downstream of oncogenic K-Ras. Our findings suggest that mutated K-RAS oncogenes are essential for maintenance of the transformed and invasive phenotype of human colon cancer cells.
A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle
Authors: Moritz F Kircher, Adam de la Zerda, Jesse V Jokerst, Cristina L Zavaleta, Paul J Kempen, Erik Mittra, Ken Pitter, Ruimin Huang, Carl Campos, Frezghi Habte, Robert Sinclair, Cameron W Brennan, Ingo K Mellinghoff, Eric C Holland, Sanjiv S Gambhir
Journal: Nature Medicine (2012)
The Cell Biology of Vertebrate Taste Receptors
Authors: S D Roper
Journal: Annual Review of Neuroscience (1989)

New technologies in neurophysiology and ultrastructural research are bringing about rapid advances in our understanding of taste, particularly at the cellular level. The model of chemosensory processing in the taste bud presented here can now be explored in great detail. The synaptic organization of the taste bud indicates a potential for intriguing peripheral integrative mechanisms, including cross-talk between taste cells, summation of chemoreceptor responses by interneurons (basal cells) in the taste bud, and centrifugal control of taste buds via efferent input from the CNS. Figure 2 summarizes these findings. The existence of voltage-gated ionic channels on taste cells and their unequal distribution in apical and basolateral membrane suggests mechanisms for chemosensory transduction: A primary event in the transduction process for many taste stimuli is likely to be the closure of apical potassium channels, thus leading to a depolarizing receptor potential. The closure of these apical potassium channels is probably mediated via cyclic nucleotides or intracellular Ca2+.
Keratinocyte growth factor and coeliac disease
Authors: V M Salvati, M Bajaj-Elliott, R Poulsom, G Mazzarella, K E A Lundin, E M Nilsen, R Troncone, T T MacDonald
Journal: Gut (2001)

BACKGROUND Coeliac disease is characterised by increased epithelial renewal associated with a mucosal T cell response to gliadin. Keratinocyte growth factor (KGF) is produced by cytokine activated gut stromal cells and may be a link between mucosal T cell activation in untreated coeliac disease and epithelial hyperplasia. AIMS To characterise expression of KGF in coeliac disease. METHODS KGF transcripts in coeliac disease were measured by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR) and localised using in situ hybridisation. KGF production by gluten reactive CD4+ T cell clones was examined. In addition, KGF transcripts were measured following ex vivo challenge of coeliac biopsies with a peptic-tryptic digest of gliadin. RESULTS KGF transcripts were elevated in coeliac biopsies compared with normal controls but were not different from non-coeliac disease controls. By in situ hybridisation, KGF mRNA containing cells were present in the upper half of the lamina propria, most abundantly just under the epithelium. There was no signal from cells within the epithelium. Gluten reactive T cell clones did not make KGF. In vitro challenge of coeliac biopsies generated a strong interferon γ response but a specific KGF response could not be detected because of an extremely high number of KGF transcripts in all cultured biopsies. CONCLUSIONS KGF is overexpressed in coeliac biopsies and in tissues with non-coeliac enteropathy. No evidence was found for KGF production by intraepithelial lymphocytes or lamina propria T cells.
Comparison of shuttle walk with measured peak oxygen consumption in patients with operable lung cancer
Authors: T Win
Journal: Thorax (2005)

The relationship between the shuttle walk test and peak oxygen consumption in patients with lung cancer has not previously been reported. A study was undertaken to examine this relationship in patients referred for lung cancer surgery to test the hypothesis that the shuttle walk test would be useful in this clinical setting.125 consecutive patients with potentially operable lung cancer were prospectively recruited. Each performed same day shuttle walking and treadmill walking tests.Shuttle walk distances ranged from 104 m to 1020 m and peak oxygen consumption ranged from 9 to 35 ml/kg/min. The shuttle walk distance significantly correlated with peak oxygen consumption (r = 0.67, p<0.001). All 55 patients who achieved more than 400 m on the shuttle test had a peak oxygen consumption of at least 15 ml/kg/min. Seventy of 125 patients failed to achieve 400 m on the shuttle walk test; in 22 of these the peak oxygen consumption was less than 15 ml/kg/min. Nine of 17 patients who achieved less than 250 m had a peak oxygen consumption of more than 15 ml/kg/min.The shuttle walk is a useful exercise test to assess potentially operable lung cancer patients with borderline lung function. However, it tends to underestimate exercise capacity at the lower range compared with peak oxygen consumption. Our data suggest that patients achieving 400 m on the shuttle walk test do not require formal measurement of oxygen consumption. In patients failing to achieve this distance we recommend assessment of peak oxygen consumption, particularly in those unable to walk 250 m, because a considerable proportion would still qualify for surgery as they had an acceptable peak oxygen consumption.