tbuckley/cabot-search huggingface dataset:
Insulin-Like Growth Factor-1 Receptor Identifies a Pool of Human Cardiac Stem Cells With Superior Therapeutic Potential for Myocardial Regeneration
Authors: Domenico D'Amario, Mauricio C. Cabral-Da-Silva, Hanqiao Zheng, Claudia Fiorini, Polina Goichberg, Elisabeth Steadman, João Ferreira-Martins, Fumihiro Sanada, Marco Piccoli, Donato Cappetta, David A. D'Alessandro, Robert E. Michler, Toru Hosoda, Luigi Anastasia, Marcello Rota, Annarosa Leri, Piero Anversa, Jan Kajstura
Journal: Circulation Research (2011)

Age and coronary artery disease may negatively affect the function of human cardiac stem cells (hCSCs) and their potential therapeutic efficacy for autologous cell transplantation in the failing heart.
Evidence for functional alpha 2-adrenoceptors on vascular sympathetic nerve endings in the human forearm.
Authors: E Grossman, P C Chang, A Hoffman, M Tamrat, D S Goldstein
Journal: Circulation Research (1991)

The role of alpha 2-adrenoceptors on vascular sympathetic nerve endings in modulating release of the sympathetic neurotransmitter norepinephrine (NE) in humans was examined by measuring the regional rate of appearance of NE in forearm venous plasma (forearm NE spillover [FSO]) in 32 healthy volunteers during intra-arterial infusion of drugs acting at adrenoceptors or directly on vascular smooth muscle. Simultaneous intra-arterial infusions of tracer amounts of [3H]NE were used to calculate the extraction rate of NE in the forearm. Methoxamine or propranolol with epinephrine (PRO + EPI) was used to stimulate alpha-adrenoceptors, yohimbine was used to inhibit alpha-adrenoceptors, and sodium nitroprusside (NIP) was used to produce increases in forearm blood flow directly. Sympathetic efferent activity was manipulated by systemic intravenous infusions of NIP or trimethaphan. Yohimbine and NIP increased and PRO + EPI and methoxamine decreased NE FSO, without effects on systemic blood pressure, heart rate, or arterial levels of catechols. Changes in FSO were flow dependent; therefore, the slope of the relation between the changes in FSO and forearm blood flow was used to evaluate the effects of each drug on regional sympathoneural activity. During administration of yohimbine, the mean slope of the relation between the change in estimated FSO and the change in forearm blood flow was about four times that of the mean slope during administration of NIP (F = 6.35, p less than 0.05). The slopes of the relations between changes in FSO and forearm blood flow were unaffected by systemic trimethaphan or NIP infusion, indicating that the activity of alpha 2-adrenoceptors was not altered during inhibition or reflexive stimulation of sympathetic outflow. The results suggest that alpha 2-adrenoceptors modulate release of NE from vascular sympathetic nerve endings in humans and that the function of these receptors is unchanged during acute changes in junctional NE concentrations.
X-gp70: a third molecular species of the envelope protein gp70 of murine leukemia virus, expressed on mouse lymphoid cells.
Authors: J S Tung, F W Shen, E Fleissner, E A Boyse
Journal: The Journal of Experimental Medicine (1976)

Three variants of the gp70 envelope component of MuLV are now recognizable serologically: GIX-gp70, 0-gp70, and X-gp70. The last of these, X-gp70, has so far been found only in mice or cells producing abundant C-type virus. This distinguishes X-gp70, provisionally, from the GIX-gp70 and 0-gp70 variants, each of which can be expressed on normal thymocytes without accompanying virus production, as exemplified by mouse strains 129 and B6, respectively. The X-gp70 genotype, however, is not limited to strains of mice-producing abundant virus, because X-gp70+ leukemias occur in strains of mice which do not produce a great deal of virus and whose thymocytes and other tissues are X-gp70-; this is analogous to the appearance of GIX+ leukemias in GIX- mouse strains.
Requirement for Etoposide in the Treatment of Epstein-Barr Virus–Associated Hemophagocytic Lymphohistiocytosis
Authors: Shinsaku Imashuku, Kikuko Kuriyama, Tomoko Teramura, Eiichi Ishii, Naoko Kinugawa, Masahiko Kato, Masahiro Sako, Shigeyoshi Hibi
Journal: Journal of Clinical Oncology (2001)

PURPOSE: We sought to identify the clinical variables most critical to successful treatment of Epstein-Barr virus (EBV)–associated hemophagocytic lymphohistiocytosis (HLH). PATIENTS AND METHODS: Among the factors tested were age at diagnosis (&lt; 2 years or ≥ 2 years), time from diagnosis to initiation of treatment with or without etoposide-containing regimens, timing of cyclosporin A (CSA) administration during induction therapy, and the presence or absence of etoposide. RESULTS: By Kaplan-Meier analysis, the overall survival rate for the entire cohort of 47 patients, most of whom had moderately severe to severe disease, was 78.3% ± 6.7% (SE) at 4 years. The probability of long-term survival was significantly higher when etoposide treatment was begun less than 4 weeks from diagnosis (90.2% ± 6.9% v 56.5% ± 12.6% for patients receiving this agent later or not at all; P &lt; .01, log-rank test). Multivariate analysis with the Cox proportional hazards model demonstrated the independent prognostic significance of a short interval from EBV-HLH diagnosis to etoposide administration (relative risk of death for patients lacking this feature, 14.1; 95% confidence interval, 1.16 to 166.7; P = .04). None of the competing variables analyzed had significant predictive strength in the Cox model. However, concomitant use of CSA with etoposide in a subset of patients appears to have prevented serious complications from neutropenia during the first year of treatment. CONCLUSION: We conclude that early administration of etoposide, preferably with CSA, is the treatment of choice for patients with EBV-HLH.
Noninvasive Measurements of Capecitabine Metabolism in Bladder Tumors Overexpressing Thymidine Phosphorylase by Fluorine-19 Magnetic Resonance Spectroscopy
Authors: Yuen-Li Chung, Helen Troy, Ian R. Judson, Russell Leek, Martin O. Leach, Marion Stubbs, Adrian L. Harris, John R. Griffiths
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Previous studies have shown that tumor response to capecitabine strongly correlates with tumor thymidine phosphorylase (TP). The aims of our study were to (a) investigate the pharmacological role of TP by measuring the pharmacokinetics (PK) of capecitabine in a human bladder tumor model that was characterized by the overexpression of TP and (b) develop the use of PK measurements for capecitabine by fluorine-19 magnetic resonance spectroscopy as a noninvasive surrogate marker for determining TP levels in tumors and for predicting tumor response to capecitabine in patients. Experimental Design: TP overexpressing (2T10) and control tumors were grown s.c. in nude mice. Mice were given a dose of capecitabine or 5′-deoxy-5-fluorouridine (5′DFUR). 19F tumor spectra were acquired for determination of rate constants of capecitabine breakdown and buildup and subsequent breakdown of intermediates, 5′-deoxy-5-fluorocytidine (5′DFCR) and 5′DFUR. The rate constant of 5′DFUR breakdown was also evaluated. Results: The rate constant of breakdown of intermediates was significantly faster in 2T10 tumors than controls (P &amp;lt; 0.003). No significant differences in the rate of capecitabine breakdown or intermediate buildup were observed. The rate constant of 5′DFUR breakdown in the 2T10 tumors was doubled compared with controls (P &amp;lt; 0.001). Conclusions: This study confirmed the expected pathway of capecitabine metabolism and showed that the level of TP was related to the rate of 5′DFUR conversion. Using in vivo fluorine-19 magnetic resonance spectroscopy to mea-sure the PK of capecitabine and its intermediate metabolites in tumors may provide a noninvasive surrogate method for determining TP levels in tumors and for predicting tumor response to capecitabine in patients.
Comparison of salbutamol given by intermittent positive-pressure breathing and pressure-packed aerosol in chronic asthma.
Authors: P B Anderson, A Goude, M D Peake
Journal: Thorax (1982)

A double-blind crossover study was performed to compare 4 . 8 mg salbutamol given by pressure-packed aerosol and intermittent positive-pressure breathing nebulization in chronic asthmatic patients. The two delivery techniques produced similar changes in respiratory function and pulse rates. Given equal effect, a high-dose pressure-packed aerosol would have advantages in cost and convenience over nebulization techniques.
Reduction of persistent air leak with endoscopic valve implants
Authors: T. P Toma, O. M. Kon, W. Oldfield, R. Sanefuji, M. Griffiths, F. Wells, S. Sivasothy, M. Dusmet, D. M Geddes, M. I Polkey
Journal: Thorax (2007)

The standard management of air leaks due to persistent bronchopleural fistula involves chest drainage and occasionally pleurodesis, with intractable cases requiring surgical decortication or surgical repair. However, some of these patients may be at high risk for surgery, particularly if they have already had thoracic surgery or have other medical problems; for this group there is a need for less invasive methods of stopping or reducing air leaks. Emphasys endobronchial valves (EBV) are occlusive devices designed primarily for endoscopic lung volume reduction in emphysema. Because the device is a one-way inspiratory airway blocker, it is possible that it could be used in controlling persistent air leaks while maintaining the drainage of secretions. Two cases are reported of persistent air leaks that were managed by endoscopic occlusion with EBV. In one case complete stoppage of the air leak was achieved with immediate clinical benefits. The second patient died 5 days after treatment from additional complications apparently not related to the procedure. Endobronchial blockage may be a useful salvage procedure for patients with persistent air leak for whom there is no other treatment available.
Ion Movement in the Eye
Authors: V. EVERETT KINSEY
Journal: Circulation (1960)

The optical integrity and the metabolism of the eye depend on the exchange of substances between the blood vessels of the eye and the ocular chambers. The present paper considers the exchange of 3 ions in particular, i.e., sodium, chloride and bicarbonate, in the eye, with particular reference to the role of diffusion and active transport in determining the ionic composition of the various ocular fluids.
Eosinophil cationic protein and immunoglobulin levels in bronchoalveolar lavage fluid obtained from patients with chronic eosinophilic pneumonia
Authors: KA Boomars, H van Velzen-Blad, PG Mulder, L Koenderman, JW Lammers, JM van den Bosch
Journal: European Respiratory Journal (1996)

In chronic eosinophilic pneumonia (CEP), histopathological evidence exists for the degranulation of eosinophils and the release of various toxic proteins. In vitro studies have demonstrated the degranulation of eosinophils in response to aggregated and complexed immunoglobulins. The aims of this study were to investigate: 1) whether the eosinophil cationic protein (ECP) and immunoglobulin (Ig) levels in bronchoalveolar lavage (BAL) fluid from patients with CEP are increased compared to those of healthy controls; 2) and whether a relationship is present between immunoglobulin levels and ECP levels in BAL fluid from patients with CEP. The BAL from 12 patients with CEP was selected, retrospectively, from all BAL analyses performed in our centre between 1986 and 1992. ECP levels were measured using a radioimmunoassay in BAL fluid of patients with CEP and 10 healthy controls. ECP levels and immunoglobulin levels in BAL fluid from patients with CEP were found to be elevated compared to controls (p &lt; 0.001). A relationship was found between IgA levels and ECP levels in BAL fluid from patients with CEP (r = 0.72; p = 0.043). In conclusion, eosinophil cationic protein and immunoglobulin levels were found to be increased in bronchoalveolar lavage fluid from patients with chronic eosinophilic pneumonia. The relationship found between immunoglobulin A levels and eosinophil cationic protein levels may suggest that immunoglobulin A could be involved in the degranulation of eosinophils in chronic eosinophilic pneumonia.
REO-10: A Phase I Study of Intravenous Reovirus and Docetaxel in Patients with Advanced Cancer
Authors: Charles Comins, James Spicer, Andrew Protheroe, Victoria Roulstone, Katie Twigger, Christine M. White, Richard Vile, Alan Melcher, Matt C. Coffey, Karl L. Mettinger, Gerard Nuovo, David E. Cohn, Mitch Phelps, Kevin J. Harrington, Hardev S. Pandha
Journal: Clinical Cancer Research (2010)

REOLYSIN (Oncolytics Biotech) consists of a wild-type oncolytic reovirus, which has selective cytotoxicity for tumor cells while sparing normal cells. In a phase I study as a single agent, repeated infusions of reovirus were safe with evidence of antitumor activity. Preclinical studies indicate potential for synergy between reovirus and chemotherapeutic agents. A multicenter, phase I dose escalation study was designed to assess the safety of combining reovirus with docetaxel chemotherapy in patients with advanced cancer.Patients received 75 mg/m(2) docetaxel (day 1) and escalating doses of reovirus up to 3 × 10(10) TCID(50) (days 1-5) every 3 weeks.Twenty-five patients were enrolled, and 24 patients were exposed to treatment, with 23 completing at least one cycle and 16 suitable for response assessment. Dose-limiting toxicity of grade 4 neutropenia was seen in one patient, but the maximum tolerated dose was not reached. Antitumor activity was seen with one complete response and three partial responses. A disease control rate (combined complete response, partial response, and stable disease) of 88% was observed. Immunohistochemical analysis of reovirus protein expression was observed in posttreatment tumor biopsies from three patients.The combination of reovirus and docetaxel is safe, with evidence of objective disease response, and warrants further evaluation in a phase II study at a recommended schedule of docetaxel (75 mg/m(2), three times weekly) and reovirus (3 × 10(10) TCID(50), days 1-5, every 3 weeks).
A Placebo-Controlled Trial of Pioglitazone in Subjects with Nonalcoholic Steatohepatitis
Authors: Renata Belfort, Stephen A. Harrison, Kenneth Brown, Celia Darland, Joan Finch, Jean Hardies, Bogdan Balas, Amalia Gastaldelli, Fermin Tio, Joseph Pulcini, Rachele Berria, Jennie Z. Ma, Sunil Dwivedi, Russell Havranek, Chris Fincke, Ralph DeFronzo, George A. Bannayan, Steven Schenker, Kenneth Cusi
Journal: New England Journal of Medicine (2006)

No pharmacologic therapy has conclusively proved to be effective for the treatment of nonalcoholic steatohepatitis, which is characterized by insulin resistance, steatosis, and necroinflammation with or without centrilobular fibrosis. Pioglitazone is a thiazolidinedione that ameliorates insulin resistance and improves glucose and lipid metabolism in type 2 diabetes mellitus.
Immunoglobulin free light chains and solitary plasmacytoma of bone
Authors: David Dingli, Robert A. Kyle, S. Vincent Rajkumar, Grzegorz S. Nowakowski, Dirk R. Larson, John P. Bida, Morie A. Gertz, Terry M. Therneau, L. Joseph Melton, Angela Dispenzieri, Jerry A. Katzmann
Journal: Blood (2006)
The current state of breast cancer classification
Authors: G. Viale
Journal: Annals of Oncology (2012)

Breast cancer is a highly heterogeneous disease due to its diverse morphological features, the variable clinical outcome and the response to different therapeutic options. It is therefore necessary to devise a clinically meaningful classification of the disease, which has to be scientifically sound, clinically useful and widely reproducible. The established histopathological classification has a limited clinical utility, due to insufficient prognostic and predictive power. More recent classification schemes, based on the immunohistochemical characterization of breast cancer for the assessment of hormone receptor status, HER2 gene over-expression or amplification and the proliferative fraction or on gene expression profiles, correlate much better with the clinical outcome and may be used to inform the choice of the systemic therapy.
Predictive Potential of Angiogenic Growth Factors and Circulating Endothelial Cells in Breast Cancer Patients Receiving Metronomic Chemotherapy Plus Bevacizumab
Authors: Angelica Calleri, Anna Bono, Vincenzo Bagnardi, Jessica Quarna, Patrizia Mancuso, Cristina Rabascio, Silvia Dellapasqua, Elisabetta Campagnoli, Yuval Shaked, Aron Goldhirsch, Marco Colleoni, Francesco Bertolini
Journal: Clinical Cancer Research (2009)

PURPOSE: The association of chemotherapy and antiangiogenic drugs has shown efficacy in clinical oncology. However, there is a need for biomarkers that allow selection of patients who are likely to benefit from such treatment and are useful for indicating best drug combination and schedule. EXPERIMENTAL DESIGN: We investigated the predictive potential of six angiogenic molecules/transcripts and nine subpopulations of circulating endothelial cells (CEC) and progenitors (CEP) in 46 patients with advanced breast cancer treated with metronomic cyclophosphamide and capecitabine plus bevacizumab. RESULTS: Median time to progression was 281 days. Baseline CECs higher than the first quartile were associated with an increased time to progression (P = 0.021). At progression, CECs were markedly reduced (P = 0.0002). In the cohort of 15 long-term responders, who progressed later than 1 year after beginning of therapy, circulating vascular endothelial growth factor (VEGF)-A levels measured after 2 months of therapy were significantly reduced, and there were significant trends toward lower levels of PDGF-BB, CEPs, and CECs. At the time of progression, angiogenic growth factors VEGF-A and basic fibroblast growth factor were significantly increased. CONCLUSIONS: Baseline CECs (likely reflecting an active vascular turnover) predicted a prolonged clinical benefit. At the time of relapse, a pattern of decreased CECs and increased angiogenic growth factors suggested a switch toward a different type of cancer vascularization. VEGF-A and basic fibroblast growth factor levels after 2 months of therapy were also useful to identify patients whose disease was likely to progress. These biomarkers are likely to be useful for treatment selection and might be incorporated in design of future studies. (Clin Cancer Res 2009;15(24):7652-7).
O6.10 * GLIOMA CELL VEGFR-2 EXPRESSION IMPAIRS CHEMOTHERAPEUTIC AND ANTIANGIOGENIC TREATMENTS IN PTEN-DEFICIENT GLIOBLASTOMA
Authors: M. Weiler, T. Kessler, F. Sahm, J. Blaes, M. Osswald, D. Milford, S. Urban, C. Ruiz de Almodovar, S. Heiland, W. Wick
Journal: Neuro-Oncology (2014)

BACKGROUND: Given the recent failure of bevacizumab (BEV) in extending overall survival of patients with newly diagnosed glioblastoma, tissue biomarkers predicting response to antiangiogenic treatments are urgently needed. Here, we hypothesized that loss of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a prerequisite for glioma cell expression of vascular endothelial growth factor receptor (VEGFR)-2 in glioblastoma defining a more aggressive glioblastoma subgroup prone to develop evasive resistance towards antiangiogenic treatments including BEV. METHODS AND RESULTS: Besides its ubiquitous expression on endothelial cells, immunohistochemical analysis of 59 glioblastoma tissues showed glioma cell-bound VEGFR-2 expression was restricted to PTEN-deficient tumor specimens and detectable in 20% of all specimens examined, most pronounced in infiltration zones. In glioma cells, pharmacological and RNAi-mediated inhibition of VEGFR-2 signaling revealed proproliferative, antiinvasive and chemoprotective functions for VEGFR-2 in several experimental paradigms comprising flow cytometry-based cell cycle analyses, in vitro proliferation and invasion assays, organotypic brain slice culture assays, and an MRI-monitored orthotopic mouse model. VEGFR-2-dependent cellular effects were concomitant with activation of three potent resistance factors: 'kappa-light-chain-enhancer' of activated B-cells (NF-κB), protein kinase B (AKT/PKB), and N-myc downstream regulated gene (NDRG)1. Two-photon in vivo microscopy demonstrated that glioma cell expression of VEGFR-2 hampers antiangiogenesis and favors a proinvasive response to treatment with BEV. CONCLUSIONS: Glioma cell expression of VEGFR-2, next to its expression on vessels, indicates a particularly aggressive glioblastoma subgroup prone to develop early resistance to chemotherapy with temozolomide or antiangiogenic treatment with BEV. Loss of PTEN can serve as a readily available surrogate marker to identify those tumors upfront by routine neuropathological methods.
Cytological sampling at fibreoptic bronchoscopy: comparison of catheter aspirates and brush biopsies.
Authors: M F Muers, M M Boddington, M Cole, D Murphy, A I Spriggs
Journal: Thorax (1982)

A prospective study was undertaken to compare bronchial brushings with dry catheter aspiration for the cytological diagnosis of lung cancer at fibreoptic bronchoscopy. Duplicate samples taken by aspirate and brush were obtained at 103 consecutive routine bronchoscopies. Aspirate and brush samples were reported on separately by two cytologists. At the end of the study a 30% sample, including the 19 cases with different findings by the two methods, were subjected to a blind crossover review, and then an open review. Forceps biopsy specimens for routine histological assessment were taken in 94 cases (92%). Ninety-eight of 103 (95%) aspirates and 99 of 103 (96%) brush specimens were technically satisfactory. Carcinoma was diagnosed at bronchoscopy on cytological or histological evidence or both in 57 cases. Fifty-five of these tumours (96%) were recognised by either the aspirate or the brush method, 52 (91%) by brush, and 50 (88%) by aspirate. Thirty-four cases (60%) could be diagnosed from histological specimens. The order of cytological sampling did not systematically affect yield. It is concluded that fine-catheter aspirates, permitting smears to be prepared in the laboratory, are a satisfactory alternative to brush smears for the cytological diagnosis of lung cancer at bronchoscopy. The routine use of both techniques at bronchoscopy will increase diagnostic yield by about 5%. Duplicate sampling may be especially useful in obtaining diagnostic material from upper-lobe or apical-segment tumours.
Cyclosporin A treatment of systemic sclerosis
Authors: H. ZACHARIAE, L. HALKIER-SORENSEN, L. HEICKENDORFF, E. ZACHARIAE, H.E. HANSEN
Journal: British Journal of Dermatology (1990)

Journal Article Cyclosporin A treatment of systemic sclerosis Get access H. ZACHARIAE, H. ZACHARIAE Department of Dermatology, University of Aarhus, DK‐8000 Aarhus, Denmark Search for other works by this author on: Oxford Academic Google Scholar L. HALKIER‐SØRENSEN, L. HALKIER‐SØRENSEN Department of Dermatology, University of Aarhus, DK‐8000 Aarhus, Denmark Search for other works by this author on: Oxford Academic Google Scholar L. HEICKENDORFF, L. HEICKENDORFF Department of Clinical Chemistry, University of Aarhus, DK‐8000 Aarhus, Denmark Search for other works by this author on: Oxford Academic Google Scholar E. ZACHARIAE, E. ZACHARIAE Department of Rheumatology, University of Aarhus, DK‐8000 Aarhus, Denmark Search for other works by this author on: Oxford Academic Google Scholar H.E. HANSEN H.E. HANSEN Department of Nephrology, Marselisborg Hospital, Aarhus Kommunehospital, University of Aarhus, DK‐8000 Aarhus, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 122, Issue 5, 1 May 1990, Pages 677–681, https://doi.org/10.1111/j.1365-2133.1990.tb07290.x Published: 01 May 1990