tbuckley/cabot-search huggingface dataset:
Abstract LB-363: Intravesical delivery of lipid nanoparticle formulated p21(Waf1/Cip1) activating dsRNA induces tumor regression and enhances animal survival in a orthotopic bladder cancer model
Authors: MooRim Kang, Glen Yang, Klaus Charisse, Hila Epstein-Barash, Muthiah Manoharan, Long-Cheng Li
Journal: Cancer Research (2012)

Abstract Small RNA molecules are a promising new class of drugs by offering expanded targets not druggable by conventional therapies with high target specificity and low toxicity. However, their clinical use is significantly hindered by the lack of vehicles that deliver the molecules efficiently to target tissues and cells. The bladder is an easily accessible hollow organ and is ideal for local delivery of drugs or molecules such as small RNA. RNA activation (RNAa) is a newly discovered mechanism of gene induction triggered by promoter targeted double-stranded RNA, also known as small activating RNA (saRNA). In this study, we investigate, in an orthotopic bladder cancer model, antitumor effects of a saRNA (dsP21) targeting the promoter of the p21WAF1/CIP1 (p21) gene, a key negative regulator of the cell cycle rarely mutated or deleted in bladder cancer. Introducing dsP21 into bladder cancer cells activated p21 expression with subsequent inhibition of cell proliferation, arrest of the cell cycle and induction of apoptosis accompanied by the activation of caspase 3 and PARP. Chemical modification (2′-Fluoro) and subsequent formulation of dsP21 in lipid nanoparticles (LNPs) retained its RNAa activity with minimal immunostimulatory effect and extended its stability in urine, and when delivered intravesically it could well diffuse into the bladder wall. Delivery of LNP-formulated dsP21 (LNP-dsP21) into mouse bladder with established human bladder cancer significantly inhibited tumor growth and extended animal survival with demonstrated p21 activation in vivo. Of particular significance, LNP-dsP21 treatment caused the regression or disappearance of established tumors in 30% of the treated mice. Our results provide proof-of-principle that targeted activation of p21 can be applied to the treatment of bladder cancer and LNP-formulated small RNA can be successfully delivered to the bladder by intravesical instillation. Further clinical development of RNAa-based intravesical therapy is warranted for the treatment of residual and recurring bladder cancer in humans. Acknowledgement: financial support from the AACR Henry Shepard Bladder Cancer Research Grants (09-60-30-LI). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-363. doi:1538-7445.AM2012-LB-363
Coronary angioplasty versus left internal mammary artery grafting for isolated proximal left anterior descending artery stenosis
Authors: J-J Goy, E Eeckhout, P Vogt, J-C Stauffer, L Kappenberger, B Burnand, M Hurni, F Stumpe, P Ruchat, H Sadeghi
Journal: The Lancet (1994)
Detection of acute effects of cigarette smoking on airway dynamics: A critical and comparative study of pulmonary function tests.
Authors: B J Sobol, L Van Voorhies, C Emirgil
Journal: Thorax (1977)

In an effort to determine which measure of airway dynamics was the most sensitive to airway obstruction, comparisons were made between a variety of tests. Twenty cigarette smokers were studied both before and immediately after smoking a cigarette. The maximum midexpiratory flow (FEV25-75) and the FEV1/FVC per cent were abnormal in the largest number of cases. Closing volume was abnormal in only one case. Significant worsening in function after smoking a cigarette occurred in airway resistance and specific conductance. A lesser degree of impairment in airway dynamics was evident from FEV25-75 and first-second expired volume. The closing volume showed no change.
Regulation of the balance of cytokine production and the signal transducer and activator of transcription (STAT) transcription factor activity by cytokines and inflammatory synovial fluids.
Authors: F Wang, T K Sengupta, Z Zhong, L B Ivashkiv
Journal: The Journal of Experimental Medicine (1995)

The balance between type 1 and 2 T helper cell cytokine production plays an important role in several animal models of autoimmunity, and skewed patterns of cytokine expression have been described in human inflammatory diseases. Many cytokines activate signal transducer and activation of transcription (STAT) transcription factors, which, in turn, activate transcription of inflammatory effector genes. We used mononuclear cell priming cultures and inflammatory synovial fluids (SFs) derived from arthritis patients to examine the regulation of cytokine production and STAT activity by an inflammatory synovial microenvironment. Exposure to SFs during priming resulted in an 81% inhibition of interferon (IFN)-gamma, but not interleukin (IL) 4, production by effector cells generated in priming cultures. SF suppression was mediated by IL-4 and IL-10 and inhibition of IL-12 expression, and it was reversed in a dominant fashion by exogenous IL-12. SFs blocked the sustained activity of transcription factor Stat1, but not Stat3, during the priming period, and Stat1 activity was differentially regulated by cytokines in parallel with their positive or negative regulation of IFN-gamma production. Active Stat3, but not Stat1, was detected in cells from inflamed joints. These results suggest a role for altered balance of Stat1 and Stat3 transcriptional activity in the regulation of T cell differentiation and in the pathogenesis of inflammatory synovitis.
Book Review Breast Cancer Management: Application of Evidence to Patient Care Edited by Jean-Marc Nabholtz, Katia Tonkin, Matti S. Aapro, and Aman U. Buzdar. 569 pp. London, Martin Dunitz, 2000. $135. 1-85317-915-9
Authors: Judith Salmon Kaur
Journal: New England Journal of Medicine (2001)
Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury.
Authors: J F Eidt, P Allison, S Noble, J Ashton, P Golino, J McNatt, L M Buja, J T Willerson
Journal: Journal of Clinical Investigation (1989)

Cyclic variations in coronary blood flow (CFVs) in dogs with experimental coronary artery stenosis and endothelial injury appear to result primarily from the aggregation of platelets at the site of stenosis followed by dislodgement and distal embolization. Using this canine model, we tested the hypotheses: (a) that thrombin is an important mediator of CFVs in dogs with coronary stenoses and endothelial injury; (b) that inhibition of thrombin with heparin, or MCI-9038, a selective thrombin inhibitor, abolishes CFVs in this model; and (c) that abolition of CFVs by thrombin inhibition is time dependent. CFVs, produced in open-chest dogs by placing a flow-reducing plastic constrictor around the left anterior coronary artery, were monitored for either 30 min (group I) or 3 h (group II) before treatment with either heparin or 4-methyl-1-(N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl (MCI-9038). In group I, cyclic flow variations were abolished by heparin in 12 of 18 dogs and by MCI-9038 in 5 of 7 dogs. In group II, cyclic flow variations were not abolished by heparin in any of seven dogs and were abolished by MCI-9038 in only one of seven dogs. Thus, (a) thrombin appears to be an important mediator of cyclic flow variations in dogs with coronary artery stenosis and endothelial injury and (b) inhibition of thrombin abolishes CFVs after short but not prolonged periods of CFVs.
THE TREATMENT OF FIBROID TUMORS OF THE UTERUS.
Authors: CHARLES P. NOBLE
Journal: JAMA (1904)

When I addressed the British Gynecological Society<sup>1</sup>in 1901 on the subject, "The Complications and Degenerations of Fibroid Tumors of the Uterus as Bearing on the Treatment of These Growths," reporting 218 cases, it was with the purpose of pointing out that, in my judgment, the profession had not had a proper estimate of the natural history, degenerations, complications and dangers of fibroid tumors. At that time no one had considered this subject from the standpoint in question. Martin, 1888, had written a paper<sup>2</sup>reporting the degenerations in the tumors themselves, but ignoring the complications which existed in the particular cases reported. But from 1888 until 1901 the literature shows that no special attention had been paid to this subject, and that the complications of fibroid tumors had attracted practically no attention whatever. It can not be otherwise than gratifying to me that following my own paper on the subject
Improved Endoscopic Stenting for Malignant Dysphagia Using Tygon Plastic Prostheses
Authors: S. Bohnacker, F. Thonke, M. Hinner, U. Seitz, K. F. Binmoeller, B. Brand, V.d. Rathod, N. Soehendra
Journal: Endoscopy (1998)

Endoscopic palliative treatment of malignant esophageal stenosis using conventional plastic stents has been reported to be associated with a considerable risk of perforation. Stenoses with a distance of less than 2cm from the upper esophageal sphincter (UES) have generally been excluded from treatment. Using self-expandable metal stents, procedure-related complications are rare. However, the rates of late complications necessitating retreatment appear to be as high as those of plastic stents. This study describes our stent placement technique and our results using a modified Tygon plastic stent.Over a two-year period, 71 consecutive patients with incurable malignant esophageal stenosis were prospectively studied. Tygon plastic stents of diameter 9-14 mm were individually tailored according to length and location of the stenosis. Prior to stenting, stepwise bougienage was performed, if necessary over several sessions. After endoscopic placement of a guide wire, the stent was inserted over a bougie without fluoroscopic monitoring.A total of 71 patients (54 men and 17 women, median age 69, range 34-93), were treated with Tygon plastic stents (14 mm: 19 patients; 12 mm: 50 patients; 9 mm: 2 patients). Median length of the strictures and of the stents were 7 (range 2-18) and 10 (range 6-25) cm, respectively. Four patients had an associated esophago-respiratory fistula. After a median of 2 (range 1-5) bougienage sessions, stent insertion was technically successful in all patients. Forty-one stents were placed across the cardia, 13 were positioned 0.5-1 cm below the UES. Three patients had to undergo retreatment within 24 hours because of pain or stent migration and the stents were repositioned or exchanged. No procedure-related perforation, hemorrhage or respiratory problems were observed. During a median follow-up of 63 (range 2-388) days, 82% of the patients died. Improvement or stabilization of dysphagia allowing for oral nutrition could be achieved in 89%. Dislocation occurred in eight patients, bolus obstruction in five patients and tumor overgrowth in four patients. Three of the four fistulas could be covered by the stent. In one patient with a fistula located at the level of the UES, a stent was placed but migrated after 5 days. Overall, 27 patients (38%) required reinterventions, mainly for dysphagia or nutritional problems.In our experience, Tygon plastic stents with a diameter of 9-14 mm can be safely placed after stepwise, less extensive bougienage. Effective palliation is possible even for lesions located close to the UES. Perforation can be avoided. Reintervention rates seem to be comparable to those seen with self-expanding metal stents.
Flow velocity patterns in and distensibility of the carotid artery bulb in subjects of various ages.
Authors: R S Reneman, T van Merode, P Hick, A P Hoeks
Journal: Circulation (1985)

Velocity patterns in and distensibility of the carotid artery bulb were studied in younger (20 to 30 years; n = 11) and older (50 to 60 years; n = 9) volunteers without detectable lesions of the cervical carotid arteries by means of a high-resolution, multigate, pulsed Doppler system coupled to a B mode imager. In the bulb the axial velocities were highest on the side of the flow divider, while regions of flow separation and recirculation were observed on the side opposite to this divider. Flow separation and recirculation were less pronounced and less common in the older subjects. Flow separation was not continuously present throughout the cardiac cycle. The distensibility of the carotid arteries was significantly diminished in older subjects, especially in the bulb. The velocity patterns in the carotid artery bulb of younger subjects corroborate the patterns observed in models. The diminished flow separation and recirculation in the older subjects might result from alterations in distensibility at the transition from common to internal carotid artery with increasing age.
Nosocomial pneumonia. Risk factors
Authors: F. J. de Latorre, T. Pont, A. Ferré, M. Palomar, J. Rosselló, A. Pahissa, A. Sanz, R. Rivera, P. Navarrete, G. Vazquez Mata, J. Ibáñez, R. Jordá, P. Marsé, J. M. Raurich, J. M. Polo, J. Engler, T. Miorini, M. G. Schimek, K. Hiotakis, L. Holzapfel, S. Chevret, G. Mekdissi, T. Jacquet-Francillon, G. Demingeon, C. Clément, A. Coupry, S. Nouira, S. Elatrous, A. Bchlr, M. Jaafoura, F. Abroug, S. Bouchoucha
Journal: Intensive Care Medicine (1992)
Measurement of Bronchial Blood Flow in Tetralogy of Fallot
Authors: TAKASHI NAKAMURA, RYO KATORI, KOZUI MIYAZAWA, JUNSHI ODA, KINJI ISHIKAWA
Journal: Circulation (1967)

Bronchial blood flow was measured in nine patients with tetralogy of Fallot and in two of these cases after radical operation also. The study was made of simultaneous recording of dye-dilution curves from the left atrium and the ear following dye injection into the aortic root. A method of calculating the bronchial blood flow was devised by combining the dye-dilution method with the Fick principle. The bronchial blood flow was increased in all cases. The mean value was 0.46±0.31 L/min, with a range from 0.14 to 1.27 L/min; this is equivalent to 15.3% of the pulmonary artery flow on the average. This study showed no definite relationships among pulmonary artery blood flow, pulmonary artery pressure, arterial oxygen saturation, severity of disease, and patient's age. The postoperative measurement revealed no significant change in bronchial blood flow though its ratios to the pulmonary artery or aortic blood flows were considerably decreased.
Non-A, Non-B Hepatitis
Authors: Alfred M. Prince
Journal: JAMA (1982)

"Non-A, non-B (NANB) hepatitis" is a term that has been given to the viruses that cause hepatitis in man other than the well-characterized hepatitis viruses type A and B. Since these agents are of great clinical and public health importance, a volume summarizing current knowledge, most of which is of recent origin, was much needed. R. J. Gerety has admirably fulfilled this need by bringing together in one volume a collection of excellent reviews by active workers in this field. These authors have reviewed the history, diagnosis, clinical course, and epidemiology of the disease and have described in detail the results of studies in experimentally infected chimpanzees, including a description of the light and electron microscope findings. The controversial and confusing area of putative NANB-specific antigens and particles is also carefully reviewed, although Gerety seems to be more optimistic regarding the specificity of immunofluorescent methods of NANB antigen detection than
AT-10 * SURGERY (S) AND PERMANENT INTRAOPERATIVE BRACHYTHERAPY (BT) IMPROVES TIME TO PROGRESSION OF RECURRENT INTRACRANIAL NEOPLASMS: A REPORT OF 27 CASES USING A MODULAR, BIOCOMPATIBLE CARRIER AND REAL-TIME DOSIMETRIC PLANNING
Authors: D. Brachman, P. Nakaji, C. Dardis, S. Sorensen, T. Thomas, K. Smith, N. Sanai, E. Youssef, H. McBride
Journal: Neuro-Oncology (2014)

BACKGROUND: We report our experience using surgery (S) and permanent brachytherapy (BT) implants in the treatment of 27 separate recurrent/progressive intracranial neoplasms in 20 adult patients, all of whom had progressed despite prior standard of care treatment. Tumors treated: Grade II meningioma (9), Grade III meningioma (5), metastases (7), high grade glioma (4), craniopharyngioma (1) and dural sarcoma (1). Prior same site surgeries: mean 2, range 0-4. Prior same site RT courses: mean 2, range 1-3. Prior cumulative radiation dose: mean 70.5 Gy, range 50-89 Gy. METHODS: All patients underwent resection and intraoperative BT utilizing a modular-design biocompatible radiation-source carrier and Cs-131 in seed form. The modular geometry of the carrier, with placement under direct visualization, enabled real-time dosimetry with 60 Gy at 5 mm depth utilized for all cases. Cox's proportional-hazards model was used to model the effect of BT, with each tumor serving as its own control. RESULTS: Median progression-free survival (PFS) for prior treatment was 5.8 months (range 1-27 months). Following S + BT, only one patient, with chondrosarcoma, has progressed in the treated area (after 5 months). Thus, median PFS has not been reached for S + BT (follow-up range 0.13-21.5 months; hazard ratio 0.05, p < 0.0001, log-rank test). Time added to surgery averaged 20 min. Mean number of seed sources used was 21 (range 4-41); mean implanted mCi 101 (range 9-228). One tumor bed had clinically silent, biopsy proven radiation necrosis. No other patient has had symptomatic or asymptomatic necrosis. 8 patients have died: 5 of intracranial progression away from the treated area(s), 2 from extracranial causes, and 1 post-op death unrelated to the implant. CONCLUSION: Resection and precise intraoperative BT made possible by the carrier design demonstrate excellent early results in this ongoing, IRB approved trial for patients with recurrent intracranial neoplasms.
Effect of chronic dihydropyridine (isradipine) on the large arterial walls of spontaneously hypertensive rats.
Authors: B I Levy, M Duriez, M Phillipe, P Poitevin, J B Michel
Journal: Circulation (1994)

BACKGROUND The effect of genetic hypertension and of chronic therapy by calcium entry blocker (CEB, isradipine) on the function and structure of large arteries has been studied in adult spontaneously hypertensive rats (SHR, n = 30) and in their normotensive control Wistar-Kyoto (WKY) rats (n = 30). METHODS AND RESULTS Fifteen-week-old rats were randomly allocated to treatment with isradipine (3 mg/kg subcutaneously once a day) or to placebo and followed for 12 weeks. Hemodynamic parameters, including instantaneous pressure and aortic velocity, were recorded under anesthesia at the end of the treatment period. Passive mechanical properties of carotid arteries were measured in situ in the presence or the absence of smooth muscle cell activity (potassium cyanide poisoning). Histomorphometric parameters of the carotid and aortic media, including cross-sectional area, medial thickness, nucleus density and size, and medial contents of proteins of interstitial matrix, were measured by an automated morphometric system. Untreated SHRs had greater peripheral resistance, stiffer and thicker arterial walls because of smooth muscle cell hyperplasia (thoracic aorta and carotid artery) and/or hypertrophy (thoracic aorta), and increased collagen content than did normotensive control rats. SHRs showed a significant left ventricular hypertrophy. For the whole duration of treatment, treatment with CEB normalized the arterial pressure in SHRs. We observed a significant decrease in peripheral resistance, increased cardiac output, and left ventricular contractility without significant reduction in left ventricular hypertrophy. Increases in diuresis and natriuresis were associated during the last week of treatment in both treated strains with marked increase in plasma renin activity; in contrast, urinary aldosterone was increased by treatment in WKY rats but not in SHRs. Arterial compliance was significantly increased by CEB under control and passive conditions. CEB induced a significant reduction in the medial hypertrophy of the aortic walls of SHRs and WKY rats associated with a reduction in medial hyperplasia. In the carotid artery, CEB reduced smooth muscle cell hypertrophy but did not affect the smooth muscle cell hyperplasia. Isradipine significantly reduced the arterial wall collagen contents in both strains, with marked increases in the elastin content in the carotid but not in the aortic wall. CONCLUSIONS These results suggest that (1) despite normalization of arterial pressure, chronic treatment with CEB in SHRs does not significantly reduce left ventricular hypertrophy, probably because of increase in myocardial contractility and/or increase in plasma renin activity; (2) mechanical properties of the arterial wall are normalized by treatment; and (3) remodeling of the arterial wall by CEB is not uniform according to the studied vessel.
Adjuvant Chemotherapy for Adenocarcinoma of the Lung — Is the Standard of Care Ready for Change?
Authors: Robert B. Diasio
Journal: New England Journal of Medicine (2004)

The treatment for stage I non–small-cell lung cancer, regardless of cell type, is wide surgical resection (lobectomy or pneumonectomy) of the involved area.1 Although the propensity of non–small-cell lung cancer to metastasize early is well recognized, there is no convincing evidence that postoperative radiotherapy or adjuvant chemotherapy improves survival in stage I disease. As a result, guidelines in the United States do not recommend any adjuvant treatment outside of the clinical-trial setting.1 Many of the relatively small studies that have suggested that chemotherapy can improve survival in non–small-cell lung cancer2,3 used the same agents that have proved useful in . . .
Selective Destruction of Gliomas in Immunocompetent Rats by Thymidine Kinase-Defective Herpes Simplex Virus Type 1
Authors: W. W.-G. Jia, M. McDermott, J. Goldie, M. Cynader, J. Tan, F. Tufaro
Journal: JNCI Journal of the National Cancer Institute (1994)

Thymidine kinase-deficient herpes simplex virus type 1 [tk(-) HSV-1] replicates well in dividing cells but not in nondividing cells such as neurons, suggesting a potential use in the treatment of brain tumors.We attempted to examine the efficacy of using tk(-) HSV-1 for treating brain tumors in immunocompetent animals.9L glioma cells were cultured and subsequently implanted intracerebrally in immunocompetent, adult male Long-Evans rats. A thymidine kinase-defective HSV-1 virus, KOS-SB, was used to infect 9L cells in culture, and the viability of the infected cells was compared with that of mock-infected (i.e., uninfected) cells. We also injected the virus intratumorally and determined the mortality of the tumor-bearing animals. Tumor regression and viral spread following virus injection were examined by histologic and immunocytochemical assays.In vitro, the tk(-) virus destroyed cultured 9L cell monolayers at multiplicities of infection of 0.1 and 1.0 within 48 hours. With the same quantity of virus, no remarkable difference in survival of neural cells was found. Foscarnet, an antiviral drug that acts independently of tk activity, blocked viral replication by greater than 99% at a concentration of 100 micrograms/mL. The mortality of animals bearing tumors declined with an increase in the amount of virus injected. Histologic examination showed that the HSV-1 treatment caused severe tumor regression. Immunocytochemistry using an anti-HSV-1 antibody revealed only a weak staining within the regressing tumors, and few immunopositive neurons were evident in the surrounding brain tissue.The results indicate that tk(-) HSV-1 mutants can selectively and effectively destroy glioma cells both in vitro and in vivo in normal, immunocompetent animals.Our failure to detect viral spread associated with regressing tumors suggests that some other cytopathic factors might be involved in the tumor regression. Regardless of the precise mode of tumor cell killing, HSV-1 may be useful for treating brain tumors.