tbuckley/cabot-search huggingface dataset:
Hedgehog signaling in capillary formation
Authors: Autumn M. Villarreal, Nelson R. Alexander, Carol E. Summers, Jessica Cantrell, Ronald L. Heimark
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1151 

Angiogenesis, the growth of new blood vessels from pre-existing vessels, is an essential step in solid tumor progression and the formation of metastases. The development of a new vasculature requires an integration of multiple signals from secreted factors such as Vascular Endothelial Growth Factor (VEGF) and angiopoietins as well as cell-matrix adhesions. Recent evidence suggests that the Hedgehog family of secreted growth factors may function in the regulation of vasculogenesis and angiogenesis during embryonic development. Hedgehog signaling has also been shown to be aberrantly reactivated leading to enhanced tumor growth in several cancers including basal cell carcinoma, medulloblastoma, and cancers of the prostate, colon, and pancreas. Therefore, we chose to investigate how Hedgehog signaling may be involved in regulating angiogenesis. Analysis of human and murine endothelial cells in vitro and in vivo by RT-PCR and in situ hybridization demonstrated the expression of Patched-1 , the Hedgehog transmembrane receptor, as well as the serpentine receptor Smoothened . Investigation of two murine endothelial cell lines, bEND3 and EOMA, indicated that bEND3 cells predominantly express Gli3 while EOMA cells predominantly express Gli1 . Addition of Shh-N to monolayers of bEND3 cells induced the cells to assemble into capillary-like structures, suggesting that Hedgehog signaling may mediate this morphogenic process. Using a three-dimensional collagen gel matrix, we found that inhibition of the Hedgehog signaling pathway with cyclopamine, a specific inhibitor of Hedgehog signaling, prevented endothelial cell capillary formation in a dose-dependent manner between 1 and 10 μM. Additionally, inhibition of Hedgehog signaling by 10 μM cyclopamine treatment blocked HUVEC formation of capillary structures on Matrigel. Treatment of endothelial cell monolayers with cyclopamine resulted in an increase in actin stress fiber formation, suggesting that Hedgehog signaling may play a role in the organization of the actin cytoskeleton. The Rho family of small GTPases are the primary regulators of the actin cytoskeleton, and levels of active RhoA and Rac1 are significantly increased following cyclopamine treatment. Furthermore, GLI3 nuclear localization is increased in cyclopamine treated endothelial cells. Our results suggest that by inhibiting the Hedgehog signaling pathway, endothelial cells undergo a reorganization of the actin cytoskeleton, thereby preventing angiogenesis from occurring. In conclusion, the evidence we present suggests that the Hedgehog signaling pathway plays a critical role in angiogenesis and may be a potential therapeutic target in the prevention of tumor angiogenesis.
Runx1 repression by histone deacetylation is critical for Setbp1-induced mouse myeloid leukemia development
Authors: B A Vishwakarma, N Nguyen, H Makishima, N Hosono, K O Gudmundsson, V Negi, K Oakley, Y Han, B Przychodzen, J P Maciejewski, Y Du
Journal: Leukemia (2015)
Obliterative bronchitis verified by bronchoscopic visualisation
Authors: Petr Pohunek, Karolina Vávrová, Tamara Svobodová, Magdalena Havlišová, Ludmila Hornofová
Journal: European Respiratory Journal (2011)

Background:  Chronic bronchial obstruction in children is mostly associated with bronchial asthma. In those with irreversible obstruction the most documented reason is a post-infectious obliterative bronchiolitis.   Case history:  We report a 13 years old patient with Tetralogy of Fallot corrected at the age of 3 years. She suffered from respiratory infections since early childhood, in addition four pneumonias at the age of 10, 11 and 12 years. Since age of 10 on anti-asthma medication for frequent wheezing. She was referred to us for poor response to anti-asthma therapy.   Summary of findings:  No dyspnoea, bilateral variable quiet wheezing. FVC 53%,FEV 1  34%,MEF 25/75 12%. TLC normal, severe hyperinflation. No immune deffect, no atopy. GOR excluded. On HRCT diffuse bilateral non-homogeneous air-trapping. On bronchoscopy normal anatomy, non-inflammatory mucosa. Bronchial biopsy with no inflammation, no remodelling.  Using 2.9 mm flexible bronchoscope and aiming for the areas with prominent air-trapping, we found at the level of 7th to 9th bronchial branching circular narrow stenoses and obliterative lesions completely closing the lumen. Biopsy revealed normal bronchial epithelium, mild thickening of the basement membrane and mild hypertrophy of smooth muscle.   Conclusion:  We confirmed existence of obliterative lesions causing irreversible obstruction in the bronchi of about 2 to 3 mm in diameter. This fits into the diagnosis of obliterative bronchitis, different from obliterative bronchiolitis. This should be suspected in children with irreversible bronchial obstruction and appropriate investigations initiated. Confirmation of this diagnosis can prevent patients from unnecessary burden of anti-asthma therapy.  Supported by MZ0FNM2005.
The Regression of Atherosclerosis: The Journey From the Liver to the Plaque and Back
Authors: Edward Fisher
Journal: Circulation (2013)

The Duff Memorial Award Lecture will consist of 3 short stories. In the first, new developments will be presented on how the production of very low density lipoproteins (VLDL, which become LDL) by the liver is controlled by the degradation of their apolipoprotein B (apoB) component. In particular, our recent results have shown that insulin and niacin, two medically relevant regulators of the plasma levels of VLDL, utilize a process called autophagy to accomplish this. In the second, recent studies on the regression of atherosclerosis in novel mouse models will be presented. Specifically, I will show that to get rid of the cholesterol-filled disease-causing cells from the arterial plaques, new, healthy, monocytes need to be recruited from the circulation. In the third story, the use of natural and synthetic nanoparticles to carry imaging and therapeutic agents directly to atherosclerotic plaques will be presented.
Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group.
Authors: J J Rusthoven, I C Quirt, N A Iscoe, P B McCulloch, K W James, R C Lohmann, J Jensen, S Burdette-Radoux, A J Bodurtha, H K Silver, S Verma, G R Armitage, B Zee, K Bennett
Journal: Journal of Clinical Oncology (1996)

PURPOSE We designed and conducted a randomized, double-blind, placebo-controlled trial to compare the response rates and survival of patients with metastatic melanoma who received carmustine (BCNU), dacarbazine (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo. PATIENTS AND METHODS Eligible patients with metastatic melanoma received either BCNU 150 mg/m2 intravenously (i.v.) on day 1, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24 with placebo every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughout the remainder of the treatment cycle. Patients were treated on protocol for up to three cycles depending on the type of response. Assuming that a minimum increase in response rate of 20% would be necessary to conclude that tamoxifen conferred a clinically important benefit, we designed the study with an 80% chance of detecting that difference at the 5% level (two-sided). RESULTS Between February 1992 and January 1995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity. The overall response rate was 21% in the placebo group and 30% in the tamoxifen group (P = .187). Complete and partial responses were 3% and 27%, respectively, for the tamoxifen group and 6% and 14%, respectively, for the placebo group. Poor performance status and liver involvement were associated with a reduced likelihood to respond to treatment. Major toxicities were similar in both groups with no statistically significant difference in the rates of deep vein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grade 4 thrombocytopenia. CONCLUSION These results demonstrate that the addition of high doses of tamoxifen to this chemotherapy regimen does not increase the response rate compared with chemotherapy alone in unselected patients with metastatic melanoma.
Failure of low-dose, total-body irradiation to augment combination chemotherapy in extensive-stage small cell carcinoma of the lung.
Authors: R O Dillman, S L Seagren, R Taetle
Journal: Journal of Clinical Oncology (1983)

In a pilot study, 21 consecutive eligible patients with extensive-stage small cell carcinoma of the lung were scheduled for treatment with combination chemotherapy followed by total-body irradiation (TBI), prophylactic cranial irradiation, and consolidative chemotherapy. Induction chemotherapy consisted of VP16-213, vincristine, cyclophosphamide, and doxorubicin (VOCA). TBI was given as 100 rads in 10 fractions over 2 wk. Consolidation chemotherapy consisted of cyclophosphamide, methotrexate, and hexamethylmelamine (CMH). VOCA chemotherapy was well tolerated, with a 79% response rate in 19 evaluable patients. TBI was successfully given after four cycles of VOCA without excessive morbidity in 11 patients, although subsequent CMH chemotherapy in 8 patients has required dose reductions and some delays in therapy. Unfortunately, TBI did not increase the degree of response, and 2 patients relapsed during this therapy. Median survival in this study was 40-44 wk. One patient has survived 78 wk and remains in remission. TBI can be safely given following induction chemotherapy in extensive-stage small cell carcinoma of the lung, but it does not appear to add to the therapeutic benefit of combination chemotherapy alone.
The effects of inspiratory muscle training on the interleukin-6 response to intense volitional hyperpnoea
Authors: Dean Mills, Michael Johnson, Martin McPhillimey, Neil Williams, Javier Ganzalez, Barnett Yvonne, Sharpe Graham
Journal: European Respiratory Journal (2012)

Vassilakopoulos et al. (Am. J. Physiol 1999; 277:R1013–R1019) demonstrated a breathing-induced interleukin-6 (IL-6) response. Whether inspiratory muscle training (IMT) can attenuate this response is unknown. Therefore, we tested the hypothesis that the IL-6 response to volitional hyperpnoea (VH) could be reduced with IMT and investigated whether this response was related to diaphragm fatigue (assessed by phrenic nerve stimulation) and/or changes in blood lactate concentration ([Lac-]B).

Twelve male participants performed either 6 weeks of pressure-threshold IMT (n=6) or placebo (PLA) training (n=6). Prior to training, a maximal incremental cycling test (max) was performed. Before and after training, participants undertook two 1 h experimental trials on separate days: passive rest or VH. In VH, they voluntarily mimicked at rest the breathing and respiratory muscle recruitment pattern equal to 70-80% of the maximum minute ventilation achieved during max.

IL-6 increased (P<0.01) following the pre-training VH and was (mean ± SD) 5.02 ± 0.63 and 4.87 ± 0.86 pg·mL-1 at 2 h post for IMT and PLA groups, respectively. [Lac-]B remained (P<0.01) elevated above baseline values for the duration of VH at 1.36 ± 0.24 and 1.29 ± 0.18 mmol⋅L-1. The IL-6 (-29%) and [Lac-]B (-11%) responses were reduced (P<0.05) for the IMT, but not for the PLA group. There were no increases in IL-6 or [Lac-]B over time for either group during passive rest and no evidence of diaphragm fatigue during any trial.

In conclusion, 6 weeks of IMT reduces the magnitude of the IL-6 response to VH with no evidence of diaphragm fatigue. The reduction in IL-6 may be related to the post-IMT reduction in [Lac-]B.
In vivo metabolism of complement
Authors: Lawrence D. Petz, Diane J. Fink, Elizabeth A. Letsky, H. Hugh Fudenberg, Hans J. Müller-Eberhard
Journal: Journal of Clinical Investigation (1968)

The in vivo metabolism of purified third component of complement labeled with (125)-iodine (C'3-(125)I) was studied in normal subjects and in patients with acquired hemolytic anemias. 27 such studies were performed; in addition, three studies were performed using C'3i, the biologically inactive reaction product of C'3. In normal subjects the mean fractional catabolic rate of C'3 was 2.12%/hr and the normal range (defined throughout as the mean +/- 2 SD) was from 1.56 to 2.68. The mean percentage of C'3 that was intravascular was 66.6% and the normal range was from 51 to 83. The C'3 synthesis rate averaged 1.16 mg/kg per hr with a normal range of from 0.90 to 1.42. The mean serum concentration of C'3 was 1.43 mg/ml with a normal range of from 1.00 to 1.87. The fractional catabolic rate and synthesis rate of C'3 were at the upper limit of normal or were increased above normal in patients who had warm antibody autoimmune hemolytic anemia with complement on their erythrocytes and in patients with paroxysmal nocturnal hemoglobinuria studied during periods of active hemolysis. An increased C'3 synthesis rate was also found in one patient who was hematologically normal but had an active peptic ulcer and elevated serum concentration of C'3.A normal fractional catabolic rate and C'3 synthesis rate were found in patients with autoimmune hemolytic anemia associated with alpha-methyldopa administration, atypical cold antibody autoimmune hemolytic anemia, and in paroxysmal nocturnal hemoglobinuria during an asymptomatic interval. The three studies with C'3i-(125)I revealed a very rapid removal of the labeled protein from the plasma with less than 10% remaining after 2 hr and with a corresponding increase in urinary excretion rate of the label. The fractional catabolic rate of C'3i averaged 37%/hr. The findings are consistent with the previously elucidated in vitro reaction mechanism of C'3 and strengthen the concept that serum complement participates in immune reactions in vivo.
Treatment of Autoimmune Disease by Intense Immunosuppressive Conditioning and Autologous Hematopoietic Stem Cell Transplantation
Authors: Richard K. Burt, Ann E. Traynor, Richard Pope, James Schroeder, Bruce Cohen, Karyn H. Karlin, Lorri Lobeck, Charles Goolsby, Philip Rowlings, Floyd A. Davis, Dusan Stefoski, Cass Terry, Carolyn Keever-Taylor, Steve Rosen, David Vesole, Maryanne Fishman, Mary Brush, Salim Mujias, Marcelo Villa, William H. Burns
Journal: Blood (1998)
Abstract 5425: Human CD34+ Cell Differentiation toward the Endothelial Lineage in the Zebrafish Embryo
Authors: Ombretta Pozzoli, Pietro Vella, Grazia Iaffaldano, Marta Lacovich, Paolo Devanna, Carla Lora Lamia, Franco Cotelli, Umberto Fascio, Andrea Biondi, Maurizio C Capogrossi, Maurizio Pesce
Journal: Circulation (2009)

Background. The zebrafish embryo provides a number of advantages for in vivo studies of vertebrate angiogenesis, including the possibility to observe in real-time the development of the embryonic vasculature. Furthermore, cell transplantation into the zebrafish embryo is an interesting model system for the study of stem cells differentiation. Objective. The objective of the present work is to determine whether human CD34 + progenitor (hCD34 + ) cells differentiate toward the endothelial lineage and contribute to new blood vessels development after transplantation into the zebrafish embryo. Methods and Results. hCD34 + cells were isolated from cord blood, labelled and injected into the zebrafish blastula (400 cells). Human CD14 − cells were used as controls. Flow cytometry analysis of injected embryos dissociated 24- and 44-hours after transplantation showed endothelial differentiation of hCD34 + cells, as demonstrated by increased expression levels of endothelial markers (KDR, CD105, CD146), whereas hematopoietic lineage markers were not affected. Further, we showed KDR + and Endothelin + human cells localized in the dorsal artery and in the cardinal vein. hCD34 + and hCD14 − cells (500–1000) were injected into the sinus venosus of developing Tg( fli1 :EGFP) transgenic embryos (48hpf), prior to immune system development. Time-lapse confocal analysis performed 2h after transplantation showed circulating hCD34 + cells in developing vessels. At 12h after injection, some hCD34 + cells had incorporated into the vessel wall. One day after transplantation, hCD34 + - injected embryos exhibited altered blood vessels sprouting in the growing tail vasculature as well as enhanced angiogenesis at the level of the subintestinal vein; these results raised the possibility that hCD34 + cells may synthesize angiogenic factors. In agreement with this hypothesis it was found that hCD34 + cell injection into the zebrafish blastula rescued the vascular phenotype caused by Vegfc knock-down. The above results were not observed in hCD14 − cell - injected zebrafish. Conclusions. The present study demonstrates the evolutionary conservation of hCD34 + cells differentiation mechanisms toward the endothelial lineage and their angiogenic properties in the zebrafish embryo.
Characterization of schizophrenic patients who commit suicide
Authors: Alan Breier, B. M. Astrachan
Journal: American Journal of Psychiatry (1984)

Twenty schizophrenic patients who committed suicide were compared with a randomly selected group and a sex-matched group of nonsuicidal schizophrenic patients and with a group of nonschizophrenic patients who committed suicide. The schizophrenic patients who committed suicide were more often men, and tended to be young, never married, non-Protestant, and white. They failed to communicate their suicidal intent directly, used highly lethal suicide methods, and tended not to have undergone stressful life events associated with their suicides. A thorough, case-by-case clinical assessment of potential suicidal ideation is essential with schizophrenic patients.
Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer.
Authors: E Chabner, A Nixon, R Gelman, S Hetelekidis, A Recht, B Bornstein, J Connolly, S Schnitt, B Silver, J Manola, J Harris, J Garber
Journal: Journal of Clinical Oncology (1998)

To evaluate the safety and efficacy of breast-conserving therapy for young women with a family history (FH) suggestive of inherited breast cancer susceptibility.A total of 201 patients aged 36 or younger at diagnosis treated with breast-conserving surgery and radiation therapy (> or = 60 Gy) for early-stage breast cancer were categorized by FH. FH was considered positive in 29 patients who, at the time of diagnosis, had a mother or sister previously diagnosed with breast cancer before age 50 or ovarian cancer at any age. Clinical, pathologic, and demographic variables; sites of first failure; disease-free survival; and overall survival (OS) were compared between FH-positive and -negative groups. Median follow-up time was 11 years.Patient and tumor features were similar between those with and without an FH. Regression analysis of sites of first failure at 5 years demonstrated a risk ratio (RR) of 5.7 for opposite breast cancer for FH-positive patients. Rates of local, regional, and distant failure and disease-free survival or OS did not differ between FH-positive and -negative patients. Age at diagnosis and Ashkenazi heritage were not significantly predictors of patterns of failure.Breast-conserving surgery combined with radiation therapy is not associated with a higher rate of local recurrence, distant failure, or second (non-breast) cancers in young women with an FH suggestive of inherited breast cancer susceptibility compared with young women without an FH. However, their increased risk of opposite breast cancer should be taken into account when considering breast conservation as a treatment option.
Swimming pool attendance and atopic asthma among 11-12 years old children
Authors: Martin Andersson, Linnea Hedman, Gunnar Nordberg, Bertil Forsberg, Kåre Eriksson, Eva Rönmark
Journal: European Respiratory Journal (2014)

Background By-products of water disinfectants have been suggested to cause asthma, especially in atopic children. However, studies on indoor swimming pool attendance and asthma in children have presented conflicting results.  Aims The present study examined the relation between indoor swimming pool attendance and asthma among sensitized and non-sensitized children aged 11-12 years.  Methods An extended ISAAC questionnaire was sent to the families of all children attending fifth or sixth grade (age 11-12y) in two municipalities in Northern Sweden in 2010, and 1866 (96% of invited) participated. Skin prick testing to ten standard airborne allergens was performed in 1657(85%). Asthma was defined as physician-diagnosed asthma in combination with wheeze or use of asthma medication in the last 12 months. Reported physician-diagnosed asthma has previously been validated. Swimming pool attendance was reported as >1/week or   Results The prevalence of asthma was 8.8% (boys 10.0%, girls 7.9%) and 13% had attended indoor pools >1/week. Children attending pools >1/week had an increased risk of having asthma. A stratified analysis adjusted for sex, parental smoking, parental asthma and ever dampness, showed an association only among sensitized subjects (OR 1.9 95%CI 1.1-3.3). No association between wheeze and pool attendance was found.  Conclusion  Our study supports an association between asthma in sensitized children and swimming pool attendance.
Intraoperative photodinamic therapy as a part of combined radical treatment for stage III NSCLC
Authors: Andrey Akopov, Anatoly Rusanov, Garry Papayan, Valentina Molodtcova, Margarita Urtenova, Ivan Chistiakov, Nikita Kazakov
Journal: European Respiratory Journal (2011)

Background: Incomplete resections for lung cancer remain an important problem. To increase the radicalism we proposed an intraoperative photodynamic therapy (PDT) of resection margins.

Methods: 16 patients with central NSCLC (12 men, 4 women) were prospectively included in the study (10 – IIIb, 6 – IIIa). Hystological types were: squamous cell – 10, adeno – 4, large cell – 2. At the time of diagnosis all patients were considered as unresectable or inoperable, reasons were tracheal involvement (7), functional intolerance to pneumonectomy (7) and N3 disease (2). Preoperative treatment included three cycles of chemotherapy and two courses of endobronchial PDT. During operation, after lung resection (pneumonectomy – 11, lobectomy – 5) intraoperative PDT of resection margins (bronchial and vascular stumps, mediastinum) was done. Chlorine e6 complex was used as a photosensitizer in dose of 2 mg/kg. The interval between the injection and illumination was 2 hours. Red light at 662±1 nm wavelength was used to achieve a total illumination dose of 250 j/cm2.

Results: After preoperative treatment partial response of tumor was achieved in all cases and patients underwent surgery with radical intent. There was no post PDT complication. 14 operations were R0, 2 – R1. No major postoperative complications noted except cardiac arrhythmia in 3 patients (19%). Average period of follow-up was 16 months (4 to 30 months), all patients are alive without any signs of recurrence.

Conclusion: The first experience of the combined treatment including intraoperative PDT for locally advanced NSCLC demonstrates safety and effectiveness. Additional studies are needed to proof the value of intraoperative PDT.
Analysis of Regional Left Ventricular Function by Cineventriculography, Cardiac Magnetic Resonance Imaging, and Unenhanced and Contrast-Enhanced Echocardiography
Authors: Rainer Hoffmann, Stephan von Bardeleben, Jaroslaw D. Kasprzak, Adrian C. Borges, Folkert ten Cate, Christian Firschke, Stephane Lafitte, Nidal Al-Saadi, Stefanie Kuntz-Hehner, Georg Horstick, Christian Greis, Marc Engelhardt, Jean Louis Vanoverschelde, Harald Becher
Journal: Journal of the American College of Cardiology (2005)