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Sample records for local fibrinolytic therapy

  1. Fibrinolytic therapy for mechanical pulmonary valve thrombosis.

    Science.gov (United States)

    Khajali, Zahra; Mohammadzadeh, Shabnam; Maleki, Majid; Peighambari, Mohammad Mehdi; Sadeghpoor, Anita; Ghavidel, Alireza; Elahi, Behrad; Mirzaaghayan, Mohammadreza

    2015-01-01

    Treatment of prosthetic heart valve thrombosis using intravenous thrombolytics, although an acceptable alternative to surgery, is not complication free, and the literature has a dearth of data on the subject. This study analyzed the results of fibrinolytic treatment (FT) among a single-center group of patients with mechanical pulmonary valve thrombosis. Between 2000 and 2013, 23 consecutive patients with 25 episodes of pulmonary valve thrombosis received FT. The diagnosis of mechanical pulmonary valve thrombosis was established by fluoroscopy and echocardiography. Streptokinase (SK) was used in 24 cases and alteplase in 1 case. The FT was continued a second day for 14 patients (58.3%), a third day for 1 patient, and a fourth day for 1 patient. Echocardiography and fluoroscopy were performed every day until improvement of malfunction was achieved. Of the 23 patients, 19 had complete resolution of hemodynamic abnormalities after FT, 1 had partial resolution, and 2 showed no change. No patient had major complications. Five minor complications were detected, namely, fever, nausea, thrombophlebitis, epistaxi, and pain. Seven patients (30%) experienced recurrence of thrombosis, whereas four patients had surgery (biological pulmonary valve replacement) without re-thrombolytic therapy, one patient was treated with Alteplase, one patient received SK, and one patient received intense anticoagulation using heparin and warfarin. Overall, FT had a success rate of 84%. The results indicate that regardless of the time to pulmonary valve replacement and echocardiographic and fluoroscopic findings, FT was effective in most cases of mechanical pulmonary valve thrombosis. The efficacy increased with second-day thrombolytic therapy. Major complications were not common after lytic therapy for mechanical pulmonary valve thrombosis.

  2. Spontaneous hemarthrosis following fibrinolytic therapy for acute myocardial infarction: a case report and literature review.

    Science.gov (United States)

    Ramadan, Mahmoud M; Khan, Iqbal S; Mahdi, Ousama

    2014-11-23

    Background Despite the widespread use of fibrinolytic therapy and the numerous reports on its bleeding complications, spontaneous hemarthrosis following fibrinolytic therapy is quite rare. Case Report We describe in this report a patient with no previous history of articular disease who developed a spontaneous right knee bloody effusion following fibrinolytic therapy using rt-PA for acute ST-elevation myocardial infarction. Furthermore, we provide a review of all cases of spontaneous hemarthrosis documented so far in the literature. Conclusions Several pre-existing joint diseases may predispose to hemarthrosis following fibrinolytic therapy, even in patients who deny previous or current articular disorders. Therefore, hemorrhage should be considered in the differential diagnosis of mono-arthritis following fibrinolytic therapy for STEMI.

  3. Fibrinolytic changes in pregnant women on highly active antiretroviral therapy.

    Science.gov (United States)

    Osime, Odaburhine E; Ese-Onakewhor, Joseph U; Kolade, Samson O

    2015-02-01

    To report on the changes in fibrinolytic activity in human immunodeficiency virus (HIV) infected pregnant women who are undergoing highly active antiretroviral therapy (HAART). Blood was collected from 50 HIV positive women on HAART (test subjects), and 50 HIV positive women not on HAART (controls). These women were attending the prevention of mother to child clinic (PMTCT) of the University of Benin Teaching Hospital, Benin City, Nigeria from January to June 2014. Standard manual techniques were used to estimate plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT), packed cell volume (PCV), and plasma viscosity (PV). The mean ± standard error of mean (SEM) of PFC was 4.02±0.13 g/l and ELT from the test subjects was 378±15 mins was significantly higher (p0.05). There were differences in the various parameters investigated when the various trimesters were compared. These differences did not, however, follow a particular pattern. Highly active antiretroviral therapy can cause changes in fibrinolytic activity that may predispose pregnant women to hyperfibrinogenemia and anemia.

  4. Spontaneous Hemarthrosis Following Fibrinolytic Therapy for Acute Myocardial Infarction: A Case Report and Literature Review

    OpenAIRE

    Mahmoud M. Ramadan; Khan, Iqbal S.; Mahdi, Ousama

    2014-01-01

    Patient: Male, 48 Final Diagnosis: Spontaneous hemarthrosis of right knee Symptoms: A rapidly growing knee swelling was “witnessed” associated with severe tenderness, hotness and profound agony but without color change Medication: — Clinical Procedure: Suprapatellar arthrocentesis of the right knee joint Specialty: Cardiology Objective: Unusual clinical course Background: Despite the widespread use of fibrinolytic therapy and the numerous reports on its bleeding complications, spontaneous hem...

  5. Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models.

    Science.gov (United States)

    Komissarov, Andrey A; Florova, Galina; Azghani, Ali O; Buchanan, Ann; Boren, Jake; Allen, Timothy; Rahman, Najib M; Koenig, Kathleen; Chamiso, Mignote; Karandashova, Sophia; Henry, James; Idell, Steven

    2016-08-01

    The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP.

  6. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction.

    Science.gov (United States)

    Tanswell, Paul; Modi, Nishit; Combs, Dan; Danays, Thierry

    2002-01-01

    Tenecteplase is a novel fibrinolytic protein bioengineered from human tissue plasminogen activator (alteplase) for the therapy of acute ST-segment elevation myocardial infarction. Specific mutations at three sites in the alteplase molecule result in 15-fold higher fibrin specificity, 80-fold reduced binding affinity to the physiological plasminogen activator inhibitor PAI-1 and 6-fold prolonged plasma half-life (22 vs 3.5 minutes). Consequently, tenecteplase can be administered as a single intravenous bolus of 30-50mg (0.53 mg/kg bodyweight) over 5-10 seconds, in contrast to the 90-minute accelerated infusion regimen of alteplase. Tenecteplase plasma concentration-time profiles have been obtained from a total of 179 patients with acute myocardial infarction. Tenecteplase exhibited biphasic disposition; the initial disposition phase was predominant with a mean half-life of 17-24 minutes, and the mean terminal half-life was 65-132 min. Over the clinically relevant dose range of 30-50mg, mean clearance (CL) was 105 ml/min. The mean initial volume of distribution V(1) was 4.2-6.3L, approximating plasma volume, and volume of distribution at steady state was 6.1-9.9L, suggesting limited extravascular distribution or binding. Bodyweight and age were found to influence significantly both CL and V(1). Total bodyweight explained 19% of the variability in CL and 11% of the variability in V(1), and a 10kg increase in total bodyweight resulted in a 9.6 ml/min increase in CL. This relationship aided the development of a rationale for the weight-adjusted dose regimen for tenecteplase. Age explained only a further 11% of the variability in CL. The percentage of patients who achieved normal coronary blood flow was clearly related to AUC. More than 75% of patients achieved normal flow at 90 minutes after administration when their partial AUC(2-90) exceeded 320 microg.min/ml, corresponding to an average plasma concentration of 3.6 microg/ml. Systemic exposure to tenecteplase at all

  7. Lessons learned from the TIMI trials in rescue interventions for elderly patients after failed fibrinolytic therapy: look beyond the TIMI flow

    Institute of Scientific and Technical Information of China (English)

    Dayi HU; Yifang GUO; Thach Nguyen

    2005-01-01

    @@ In ST-segment elevation myocardial infarction (STEMI), acute reperfusion of the infarct-related artery (IRA)is the main goal in the early minutes after the patient seeks medical attention. Fibrinolytic therapy (FT) and/or primary coronary intervention (PCI) were proven to be effective in opening the IRA.

  8. Fibrinolytic therapy for thrombosis in cardiac valvular prosthesis short and long term results

    Directory of Open Access Journals (Sweden)

    Auristela I. O. Ramos

    2003-10-01

    Full Text Available OBJECTIVE: To assess the short- and long-term results of the use of streptokinase (SK for the treatment of thromboses in cardiac valvular prostheses. METHODS: Seventeen patients with cardiac prosthetic thrombosis diagnosed by clinical, echocardiographic, and radioscopic findings underwent fibrinolytic treatment with a streptokinase bolus of 250,000 U followed by 100.000 U/hour. Short- and long-term results were assessed by radioscopy and echocardiography. RESULTS: Of the 17 patients, 12 had mechanical double-disk prostheses (4 aortic, 6 mitral, 2 tricuspid, 4 had single-disk prostheses (2 aortic, 1 mitral, and 1 tricuspid, and 1 had a tricuspid bioprosthesis. The success rate was 64.8%, the partial success rate was 17.6%, and the nonsuccess rate was 17.6%. All patients with a double-disk prosthesis responded, completely or partially, to the treatment. None of the patients with a single-disk prosthesis had complete resolution of the thrombosis. The time of streptokinase infusion ranged from 6 to 80 hours (mean of 56 h. The mortality rate due to the use of streptokinase was 5.8% and was secondary to cerebral bleeding. During streptokinase infusion, 3 (17.6% embolic episodes occurred as follows: 1 cerebral, 1 peripheral, and 1 coronary. The rethrombosis index was 33% in a mean follow-up of 42 months. CONCLUSION: The use of fibrinolytic agents was effective and relatively safe in patients with primary thrombosis of a double-disk prosthesis. A fatal hemorrhagic complication occurred in 1 (5.8% patient, and embolic complications occurred in 3 (17.6% patients. In a mean 42-month follow-up, 67% of the patients were free from rethrombosis.

  9. Effect of Atorvastatin intensive therapy on the serum inflammatory factors, platelet activity and fibrinolytic activity in patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    Xiao-Li Zhu; Yun Zhou; Fang Liu

    2016-01-01

    Objective:To observe the effect of Atorvastatin intensive therapy on the serum inflammatory factors, platelet activity and fibrinolytic activity in patients with acute coronary syndrome (ACS).Methods:A total of 92 patients with ACS were randomly divided into observation group (47 cases) and control group (45 cases). The control group was given Atorvastatin (10 mg/d) based on the conventional therapy, while the observation group was given Atorvastatin at an intensive dose (40 mg/d) based on the conventional therapy. Half a month later, the changes of IL-6, IL-8, hs-CRP, TNF-α, TXB2, GMP-140, PAI-1 and t-PA were observed and compared between the two groups.Results:After treatment, the inflammatory factors (IL-6, IL-8, hs-CRP and TNF-α) and the indicators of platelet activity (TXB2, GMP-140 and PAI-1) were obviously decreased, while the indicator of fibrinolytic activity (t-PA) was apparently increased in the two groups. Besides, the amplitudes of change referring to these indicators in the observation group were bigger than those in the control group after treatment, and the differences were statistically significant.Conclusion: The intensive therapy with the administration of Atorvastatin at a dose of 40 mg/d was better than the conventional therapy (Atorvastatin: 10 mg/d) in aspects of reducing inflammatory factors, inhibiting platelet activity and correcting the high coagulation state of fibrinolytic system.

  10. Positive impact of hormone replacement therapy on the fibrinolytic system: a long-term randomized controlled study in healthy postmenopausal women

    DEFF Research Database (Denmark)

    Madsen, J S; Kristensen, S R; Bladbjerg, E M;

    2003-01-01

    be of importance. OBJECTIVES: To investigate the prolonged effect of HRT on the fibrinolytic system and to determine whether two common polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) genes modulate this effect. Methods: Healthy postmenopausal women (n......BACKGROUND: The mechanisms by which postmenopausal hormone replacement therapy (HRT) may influence risk of cardiovascular disease are still unclear. Impaired fibrinolytic function is associated with an enhanced risk of cardiovascular disease and therefore the effect of HRT on fibrinolysis may...... of smoking and without influence from the two common polymorphisms PAI-1 -675(4G/5G) and t-PA intron8ins311. Furthermore, no difference between opposed estrogen (with norethisterone acetate as the gestagen component) and unopposed estrogen therapy was found. Both an intention-to-treat and a per...

  11. Activity assessment of microbial fibrinolytic enzymes.

    Science.gov (United States)

    Kotb, Essam

    2013-08-01

    Conversion of fibrinogen to fibrin inside blood vessels results in thrombosis, leading to myocardial infarction and other cardiovascular diseases. In general, there are four therapy options: surgical operation, intake of antiplatelets, anticoagulants, or fibrinolytic enzymes. Microbial fibrinolytic enzymes have attracted much more attention than typical thrombolytic agents because of the expensive prices and the side effects of the latter. The fibrinolytic enzymes were successively discovered from different microorganisms, the most important among which is the genus Bacillus. Microbial fibrinolytic enzymes, especially those from food-grade microorganisms, have the potential to be developed as functional food additives and drugs to prevent or cure thrombosis and other related diseases. There are several assay methods for these enzymes; this may due to the insolubility of substrate, fibrin. Existing assay methods can be divided into three major groups. The first group consists of assay of fibrinolytic activity with natural proteins as substrates, e.g., fibrin plate methods. The second and third groups of assays are suitable for kinetic studies and are based on the determination of hydrolysis of synthetic peptide esters. This review will deal primarily with the microorganisms that have been reported in literature to produce fibrinolytic enzymes and the first review discussing the methods used to assay the fibrinolytic activity.

  12. Fibrinolytic Therapy Versus Primary Percutaneous Coronary Interventions for ST-Segment Elevation Myocardial Infarction in Kentucky: Time to Establish Systems of Care?

    Science.gov (United States)

    Wallace, Eric L.; Kotter, John R.; Charnigo, Richard; Kuvlieva, Liliana B.; Smyth, Susan S.; Ziada, Khaled M.; Campbell, Charles L.

    2013-01-01

    Background Fibrinolytic therapy is recommended for ST-segment myocardial infarctions (STEMI) when primary percutaneous coronary intervention (PPCI) is not available or cannot be performed in a timely manner. Despite this recommendation, patients often are transferred to PPCI centers with prolonged transfer times, leading to delayed reperfusion. Regional approaches have been developed with success and we sought to increase guideline compliance in Kentucky. Methods A total of 191 consecutive STEMI patients presented to the University of Kentucky (UK) Chandler Medical Center between July 1, 2009 and June 30, 2011. The primary outcome was in-hospital mortality and the secondary outcomes were major adverse cardiovascular events, extent of myocardial injury, bleeding, and 4) length of stay. Patients were analyzed by presenting facility—the UK hospital versus an outside hospital (OSH)—and treatment strategy (PPCI vs fibrinolytic therapy). Further analyses assessed primary and secondary outcomes by treatment strategy within transfer distance and compliance with American Heart Association guidelines. Results Patients presenting directly to the UK hospital had significantly shorter door-to-balloon times than those presenting to an OSH (83 vs 170 minutes; P P = 0.45). Overall, only 20% of OSH patients received timely reperfusion, 13% PPCI, and 42% fibrinolytics. In a multivariable model, delayed reperfusion significantly predicted major adverse cardiovascular events (odds ratio 3.87, 95% confidence interval 1.15–13.0; P = 0.02), whereas the presenting institution did not. Conclusions In contemporary treatment of STEMI in Kentucky, ongoing delays to reperfusion therapy remain regardless of treatment strategy. For further improvement in care, acceptance of transfer delays is necessary and institutions should adopt standardized protocols in association with a regional system of care. PMID:23820318

  13. Microvascular obstruction after successful fibrinolytic therapy in acute myocardial infarction. Comparison of reteplase vs reteplase+abciximab: A cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Tiziano Gherli

    2010-05-01

    Full Text Available Background. About one third of patients with TIMI 3 after reperfusion have evidence of microvascular obstruction (MO which represents an independent predictor of myocardial wall rupture. This explains all efforts made to prevent MO. Magnetic resonance imaging (MRI has proved to be particularly useful in detecting MO. The aim of this study was to evaluate with MRI if different fibrinolytic regimens in acute myocardial infarction display different effects on left ventricle (LV volumes and ejection fraction (EF, as well as on myocardial infarct size (MIsz and MO. Methods. Twenty male patients, mean age 58 years, affected by acute myocardial infarction, ten anterior and ten inferior, were treated with: full dose reteplase in ten, and half dose reteplase plus full dose abciximab (R+Abcx in the other ten patients. In the fourth day after hospital admission, MRI STIR T2 images were used to quantify MIsz, while 2dflash cineloops were used after the injection of gadolinium, to quantify LV volumes, EF and to detect MO. Results. LV EF was higher in R+Abcx 51±10 than in reteplase 41±8. MIsz was similar in both treatment groups: however a close relationship was present between MIsz and EF in the reteplase group indicating that the greater the MIsz the lower the EF. In R+Abcx this relationship was no longer present, suggesting a protective effect of the drug on microcirculation. In fact extensive MO was present in 25% of all cases, 80% of which in the reteplase group while only 20% in R+Abcx. Conclusion. R+Abcx prevents MO: compared to traditional fibrinolytic therapy it allows better LV function and most likely improved long term survival.

  14. Fibrinolytic activity in Nigerian diabetics

    OpenAIRE

    Adediran, I; Ikem, R; Borisade, M

    2004-01-01

    Fibrinolytic activity, using euglobulin lysis time (ELT), was assessed in 46 Nigerians with type 2 diabetes mellitus to study the effect of the disease on fibrinolytic component of haemostasis. There were 20 females and 26 males. Fifty age matched non-diabetics and apparently healthy Nigerians were similarly studied as controls; there were 24 females and 26 males. In the patients, the mean (SD) age of the females was 56.7 (12.0) years and mean (SD) ELT was 276.4 (62.2) min; the mean age of th...

  15. Fibrinolytic agents in the treatment of intraventricular hemorrhage in adults

    Science.gov (United States)

    Haines; Lapointe

    1998-05-13

    This paper aims to review current literature on the treatment of acute intraventricular hemorrhage in adults with intraventricular infusion of fibrinolytic agents. A literature search on the topics of "intraventricular hemorrhage" or "intracerebral hemorrhage" with "thrombolytic therapy", "fibrinolytic therapy", "urokinase", "streptokinase", "tissue plasminogen activator" or "tPA" covering the years 1966-1997 was carried out electronically. This was supplemented by searching the reference lists of the identified articles. Articles regarding exclusively intracerebral hemorrhage or hematoma, neonatal intraventricular hemorrhage, non-therapeutic issues, and laboratory research were excluded. The included articles are summarized in evidence and evaluation tables. Six articles evaluating the treatment of intraventricular hemorrhage in adults with intraventricular fibrinolytic agents were identified. One reports a small randomized clinical trial including 16 patients and appears to show a statistically insignificant preference for urokinase treatment. Five other reports present case series for which a total of 58 patients were exposed to either streptokinase, urokinase, or recombinant tissue plasminogen activator (rt-PA) and suggest good outcome. Two of them were with non-randomized retrospective or prospective controls, and three have no controls. Despite important limitations, all reports suggest that blood is more rapidly cleared from the ventricles and outcome is better when administering a fibrinolytic agent intraventricularly. While the experience presented in these papers suggests that intraventricular administration of fibrinolytic agents may be associated with fewer complications, more rapid clearing of blood from the ventricles, less late hydrocephalus, and better long-term outcome than is seen in patients treated with ventricular drainage alone, it is insufficient to recommend such treatment as a matter of policy. Substantial methodologic flaws render these

  16. 纤维溶解疗法治疗放射性臂丛损伤16例初步报告%Fibrinolytic therapy in radiation-induced brachial plexopathy:16 cases report and review

    Institute of Scientific and Technical Information of China (English)

    高庆国; 张连波; 高琛茂; 李树义; 刘军; 吴世峰

    2011-01-01

    Objective To explore the feasibility and curative effect of extracellular matrix (ECM) fibrinolytic therapy in order to cure radiation-induced brachial plexopathy (RIBP) and to discuss the principle, indication and precautions. Methods The treatment was taken on 16 cases that had a definite clinical diagnosis and we took a systematic examination to make sure that there was no recurrence or metastasis of the tumor.Brachial plexus and tender area block was taken once a week by injection of mixture of hyaluronidase, hexadecadrol, Vitamine B12 and lidocaine. The therapy was applied for 6 to 12 weeks. Results All the patients were followed up for a period of 0.5 to 10 years. Four cases had an evident alleviation of the symptoms and got a function resumption of hands; 5 cases had an alleviation of pain and improvement of sensation and the progress of illness were terminated, but motor function didn't have improvement; 7 cases had a continued aggravation of the symptoms. All the cases found improvement in electromyography. Concluslon The aim of fibrinolytic therapy is to dissolve the extra ECM such as hyaluronic acid around nerves in order to achieve a new homeostasis. It can relieve the conglutination and entrapment at nerve inside and outside, reduce the pressure of neuraxon and create an availing condition for the regenesis of nerve and the regain of function.%目的 探讨纤维溶解疗法治疗放射性臂丛损伤的可行性与疗效,讨论其原理、适应证及注意事项.方法对临床诊断明确、排除肿瘤复发、转移的16例放射性臂丛损伤患者采用纤维溶解疗法进行治疗,具体方法为使用透明质酸酶、地塞米松、维生素B12、2%利多卡因进行臂丛阻滞和局部压痛点阻滞,每周1次,连续6~12次.结果 随访0.5~10.0年,手运动和感觉功能明显改善、疼痛明显减轻4例,占25.00%;感觉改善、疼痛缓解、运动功能无改善、病情不再进一步发展5例,占31.25%;感觉、运动及

  17. Development of local radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Hoon; Lim, Sang Moo; Choi, Chang Woon; Chai, Jong Su; Kim, Eun Hee; Kim, Mi Sook; Yoo, Seong Yul; Cho, Chul Koo; Lee, Yong Sik; Lee, Hyun Moo

    1999-04-01

    The major limitations of radiation therapy for cancer are the low effectiveness of low LET and inevitable normal tissue damage. Boron Neutron Capture Therapy (BNCT) is a form of potent radiation therapy using Boron-10 having a high propensityof capturing theraml neutrons from nuclear reactor and reacting with a prompt nuclear reaction. Photodynamic therapy is a similiar treatment of modality to BNCT using tumor-seeking photosenistizer and LASER beam. If Boron-10 and photosensitizers are introduced selectively into tumor cells, it is theoretically possible to destroy the tumor and to spare the surrounding normal tissue. Therefore, BNCT and PDT will be new potent treatment modalities in the next century. In this project, we performed PDT in the patients with bladder cancers, oropharyngeal cancer, and skin cancers. Also we developed I-BPA, new porphyrin compounds, methods for estimation of radiobiological effect of neutron beam, and superficial animal brain tumor model. Furthermore, we prepared preclinical procedures for clinical application of BNCT, such as the macro- and microscopic dosimetry, obtaining thermal neutron flux from device used for fast neutron production in KCCH have been performed.

  18. The fibrinolytic response in injured animal tissues normally low in fibrinolytic activity

    NARCIS (Netherlands)

    Smokovitis, A.; Astrup, T.

    1980-01-01

    Rabbit skin, normally of low fibrinolytic activity, and guinea-pig skin, of medium activity, after crush injury or after the intradermal or subcutaneous injection of aluminum hydroxide, show a remarkable increase in fibrinolytic activity. The activity is caused by a plasminogen activator and is

  19. The effect of chemical anti-inhibitors on fibrinolytic enzymes and inhibitors

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Jespersen, J; Kluft, C;

    1997-01-01

    Fibrinolytic enzyme inhibitors hamper the determination of the specific fibrinolytic serine protease activity. Reportedly, chemical anti-inhibitors eliminate the influence of fibrinolytic inhibitors, but it remains unclear to what extent they change the specific activity of fibrinolytic serine pr...

  20. Minimally invasive local therapies for liver cancer

    Institute of Scientific and Technical Information of China (English)

    David Li; Josephine Kang; Benjamin J Golas; Vincent W Yeung; David C Madoff

    2014-01-01

    Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have iflled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed.

  1. PAI-1 4G/5G polymorphism is associated with brain vessel reocclusion after successful fibrinolytic therapy in ischemic stroke patients.

    Science.gov (United States)

    Fernandez-Cadenas, I; Del Rio-Espinola, A; Rubiera, M; Mendioroz, M; Domingues-Montanari, S; Cuadrado, E; Hernandez-Guillamon, M; Rosell, A; Ribo, M; Alvarez-Sabin, J; Molina, C A; Montaner, J

    2010-04-01

    Despite t-PA proven benefits related to vessel reopening, up to 13% of stroke patients suffer reocclusions after t-PA. We aimed to analyze whether a functional polymorphism in a fibrinolysis inhibitor gene [plasminogen activator inhibitor-1 (PAI-1)] might be associated with reocclusion rates after stroke thrombolytic therapy. 165 patients with ischemic stroke who received t-PA 4G/5G polymorphism determination was performed by sequencing. PAI-1 mRNA was studied by real-time PCR analysis. National institutes of health stroke scale (NIHSS) was serially measured since patients arrival to assess the neurological outcome, and modified ranking scale (mRS) at 3rd month was used to evaluate functional outcome following stroke. PAI-1 4G/4G patients had higher reocclusion rates (4G/4G = 12.5% versus other genotypes = 2.7%, p = 0.025). . In a logistic regression, the 4G/4G genotype was the only factor associated with reocclusion (OR = 15.16 95%, CI = 1.4-163.4, p = 0.025). 4G/4G genotype was also associated with poor functional outcome at 3rd month (4G/4G = 4 versus others genotypes = 3, p = 0.017) and with mRNA levels at 12 h post stroke symptoms onset (4G/4G patients = 2.01% versus other genotypes = 0.68%, p = 0.034). PAI-1 4G/4G genotype is associated with reocclusion rates and poor functional outcome among stroke patients treated with t-PA.

  2. Impaired fibrinolytic activity is present in children with dyslipidemias

    NARCIS (Netherlands)

    Albisetti, M; Chan, AKC; McCrindle, BW; Wong, D; Monagle, P; Andrew, M

    2004-01-01

    Dyslipidemias are major risk factors for atherosclerosis and cardiovascular disease. Abnormalities of fibrinolytic and coagulation components are considered useful predictors of cardiovascular morbidity and mortality in adults. This study examined whether fibrinolytic and coagulation components are

  3. Cow dung is a novel feedstock for fibrinolytic enzyme production from newly isolated Bacillus sp. IND7 and its application in in vitro clot lysis

    Directory of Open Access Journals (Sweden)

    Ponnuswamy eVijayaraghavan

    2016-03-01

    Full Text Available Bacterial fibrinolytic enzymes find great applications to treat and prevent cardiovascular diseases. The novel fibrinolytic enzymes from food grade organisms are useful for thrombolytic therapy. This study reports fibrinolytic enzyme production by Bacillus sp. IND7 in solid-state fermentation (SSF. In this study, cow dung was used as the cheap substrate for the production of fibrinolytic enzyme. Enzyme production was primarily improved by optimizing the nutrient and physical factors by one-variable-at-a-time approach. A statistical method (two-level full factorial design was applied to investigate the significant variables. Of the different variables, pH, starch, and beef extract significantly influenced on the production of fibrinolytic enzyme (p < 0.05. The optimum levels of these significant factors were further investigated using response surface methodology. The optimum conditions for enhanced fibrinolytic enzyme production were 1.23% (w/w starch and 0.3 % (w/w beef extract with initial medium pH 9.0. Under the optimized conditions, cow dung substrate yielded 8,345 U/g substrate, and an overall 2.5-fold improvement in fibrinolytic enzyme production was achieved due to its optimization. This is the first report of fibrinolytic enzyme production using cow dung substrate from Bacillus sp. in SSF. The crude enzyme displayed potent activity on zymography and digested goat blood clot completely in in vitro condition.

  4. Characterization of Fibrinolytic Proteases from Gloydius blomhoffii siniticus Venom

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    Suk Ho Choi

    2011-09-01

    Full Text Available Objectives : This study was undertaken to identify fibrinolytic proteases from Gloydius blomhoffii siniticus venom and to characterize a major fibrinolytic protease purified from the venom. Methods: The venom was subjected to chromatography using columns of Q-Sepharose and Sephadex G-75. The molecular weights of fibrinolytic proteases showing fibrinolytic zone in fibrin plate assay were determined in SDS-PAGE (Sodium dodecyl sulfate-polyacrylamide gel electrophoresis The effects of inhibitors and metal ions on fibrinolytic protease and the proteolysis patterns of fibrinogen, gelatin, and bovine serum albumin were investigated. Results : 1 The fibrinolytic fractions of the three peaks isolated from Gloydius blomhoffii siniticus venom contained two polypeptides of 46 and 59 kDa and three polypeptides of 32, 18, and 15 kDa and a major polypeptide of 54 kDa, respectively. 2 The fibrinolytic activity of the purified protease of 54 kDA was inhibited by metal chelators, such as EDTA, EGTA, and 1,10-phenanthroline, and disulfhydryl-reducing compounds, such as dithiothreitol and cysteine. 3 Calcium chloride promoted the fibrinolytic activity of the protease, but mercuric chloride and cobalt(II chloride inhibited it. 4 The fibrinolytic protease cleaved preferentially A-chain and slowly B-chain of fibrinogen. It also hydrolyzed gelatin but not bovine serum albumin. Conclusions: The Gloydius blomhoffii siniticus venom contained more than three fibrinolytic proteases. The major fibrinolytic protease was a metalloprotease which hydrolyzed both fibrinogen and gelatin, but not bovine serum albumin.

  5. Multimodality Local Therapy for Retroperitoneal Sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Paryani, Nitesh N.; Zlotecki, Robert A.; Swanson, Erika L.; Morris, Christopher G. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Grobmyer, Stephen R.; Hochwald, Steven N. [Department of General Surgery, University of Florida College of Medicine, Gainesville, FL (United States); Marcus, Robert B. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    2012-03-01

    Purpose: Soft-tissue sarcomas of the retroperitoneum are rare tumors comprising less than 1% of all malignancies. Although surgery continues as the mainstay of treatment, the large size of these tumors coupled with their proximity to critical structures make resection with wide margins difficult to achieve. The role and timing of radiotherapy are controversial. This study updates our institutional experience using multimodality local therapy for resectable retroperitoneal sarcoma and identifies prognostic factors impacting disease control and survival. Methods and Materials: Between 1974 and 2007, 58 patients with nonmetastatic retroperitoneal sarcoma were treated with surgery and radiation at University of Florida. The median age at radiotherapy was 57 years old (range, 18-80 years). Forty-two patients received preoperative radiotherapy and 16 received postoperative radiotherapy. Nineteen patients received 1.8 Gy once daily and 39 patients received 1.2 Gy twice daily. Variables analyzed for prognostic value included age, grade, kidney involvement, histology, de novo versus recurrent presentation, tumor diameter, margin status, radiotherapy sequencing (preoperative vs. postoperative), total radiation dose, fractionation scheme, and treatment era. Results: The 5-year overall survival, cause-specific survival, and local control rates were 49%, 58%, and 62%, respectively. Nearly two-thirds of disease failures involved a component of local progression. On multivariate analysis, only margin status was significantly associated with improved 5-year local control (85%, negative margins; 63%, microscopic positive margins; 0%, gross positive margins; p < 0.0001) and 5-year overall survival (64%, negative margins; 56%, microscopic positive margins; 13%, gross positive margins; p = 0.0012). Thirty-one Grade 3 or greater toxicities were observed in 22 patients, including two treatment-related deaths (3%). Conclusion: For retroperitoneal sarcoma, local control remains a

  6. Screening for fibrinolytic activity in eight Viperid venoms.

    Science.gov (United States)

    Ramírez, M S; Sánchez, E E; García-Prieto, C; Pérez, J C; Chapa, G R; McKeller, M R; Ramírez, R; De Anda, Y

    1999-09-01

    Snake venoms contain direct-acting fibrinolytic metalloproteinases (MMP) that could have important applications in medicine. Fibrinolytic enzymes isolated from venom can induce in vitro clot lysis by directly acting on a fibrin clot. The most ideal fibrinolytic enzyme would have high affinity for clots, dissolve clots directly without causing hemorrhage, and would not be neutralized in vivo by endogenous metalloproteinase inhibitors. The purpose of this study was to compare DEAE/HPLC venom profiles from Viperid snakes and identify fractions that contain fibrinolytic activity with no hemorrhagic activity and are not neutralized by animal sera. The sera selected were from four (Virginia opossum, Gray woodrat, Mexican ground squirrel, and Hispid cottonrat) animals known to neutralize hemorrhagic activity in snake venoms. Nineteen fractions from the Viperid venoms had fibrinolytic activity. Agkistrodon venom fractions contained the highest specific fibrinolytic activities. A. piscivorus leucostoma fraction 4 contained a high specific fibrinolytic activity, no hemorrhagic activity, and the fibrinolytic activity was not neutralized by the proteinase inhibitors of the four animal sera. A. contortrix laticinctus fraction 1 also had a high specific fibrinolytic activity and no hemorrhagic activity. However, the fibrinolytic activity was neutralized by Didelphis virginiana (Virginia opossum) serum.

  7. Purification and Characterization of Fibrinolytic Proteases from Mushroom Volvariela volvaceae Extract.

    Directory of Open Access Journals (Sweden)

    Willy Praira

    2010-11-01

    Full Text Available Purification and Characterization of Fibrinolytic Proteases from Mushroom Volvariela volvaceae Extract. Ediblestraw mushroom (V. volvaceae has been known used for improvement of blood circulation due to its fibrinolyticcontent. The objective of the study is to purify and characterize fibrinolytic protease from straw mushroom extract.Purification were performed through several steps, i.e. precipitation using ammonium sulphate 75%, dialyzed membran(cut-off 10 kDa, and ion-exchange chromatography using DEAE Sepharose. The active fraction of DEAE-Sepharosecontains two purified protein bands with molecular weight of 12.9 and 15.8 kDa. The active fraction has specificactivity of 0.383 U/mg with 2.7 fold higher purification compared to its crude extract. Both crude and purified enzymeshad optimum activity at temperature of 50 ºC and pH 7 in 10 minutes of incubation. Fibrin zymographic profiledemonstrated that the enzyme hydrolyzed fibrin, as well as casein, indicating their potent fibrinolytic activity. Theenzyme was strongly inhibited by phenilmethylsulphonyl fluoride and N-p-tosil-L-lysinchloromethyl keton. Thissuggested that it was a serine protease. In summary, these results showed that crude and purified protease of strawmushroom (V. volvaceae has fibrinolytic activities that can be applied for alternative thrombolytic therapy.

  8. Functional characterization of fibrinolytic metalloproteinases (colombienases) isolated from Bothrops colombiensis venom.

    Science.gov (United States)

    Girón, María E; Guerrero, Belsy; Salazar, Ana María; Sánchez, Elda E; Alvarez, Marco; Rodríguez-Acosta, Alexis

    2013-11-01

    Researchers trying to improve the safety and efficacy of fibrinolytic therapy have been isolating fibrinolytic enzymes from snake venoms. Two fibrinolytic enzymes, colombienases 1 and 2, with significant activity have been isolated from the venom of Bothrops colombiensis. The colombienases were characterized for various biological activities which include hemorrhagic, fibrinogenolytic, proteolytic, hemolytic, edematogenic and cytotoxic. Colombienases directly acted on fibrin by degrading fibrinogen Aα and Bβ chains without activating the fibrinolytic system (plasminogen/plasmin), additionally colombienase-2 degraded fibrinogen γ chains as well as the fibronectin molecule. Laminin and type IV collagen were colombienases resistant. Gelatin-zymogram activity was present in B. colombiensis venom (BcV) bands between 64 and 148 kDa. All activities were abolished by metalloproteinases inhibitors. Both enzymes lacked hemorrhagic, hemolytic, cytotoxic, plasminogen activator and coagulant activities. Both colombienases had direct fibrino(geno)lytic activity without other toxic side effects including in vivo hemorrhaging, which could be promising in terms of therapeutic potential as thrombolytic agents. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. 血浆纤维蛋白原水平对溶栓治疗突发性聋疗效评价%Plasma fibrinogen level on fibrinolytic therapy effect assessment sudden deafness

    Institute of Scientific and Technical Information of China (English)

    潘芳名

    2012-01-01

    Objective To observe the level of plasma fibrinogen (FIB) for thrombolytic treatment of sudden deafness treatment of patients with sudden deafness evaluate the effect of its importance, and thus promote the clinical treatment of sudden deafness progress. Methods 108 patients in our hospital from March 2007 to March 2010 were treated with sudden deafness, and were divided into normal plasma fibrinogen group (fibrinogen ≤3.5 g/L, 54 ears) and elevated plasma fibrinogen group (fibrinogen>3.5 g/L, 54 ears) respectively according to plasma fibrinogen levels. Of the 54 cases, two groups of patients were also given Batroxobin thrombolytic infusion therapy. Before treatment and 7 days after treatment, the pure tone audiometry of patients was detected. The results of two groups before and after treatment were analyzed and compared. During the course of close observation of the patient's skin or mucous membranes at whether there was bleeding. Results After the end of treatment, plasma fibrinogen levels in patients with normal group, by thrombolytic therapy were cured in 1case, excellent in 3 cases, effective in 9 cases, invalid in 41 cases, the total efficiency of 24.1%, plasma fibrinogen elevated levels of the original group of patients cured in 6 cases, excellent in 15 cases, effective in 23 cases, invalid in 10 cases, the total efficiency of 81.5%. Elevated level of plasma fibrinogen treated group was significantly higher than normal plasma fibrinogen group, and the difference was statistically significant. Conclusion For the plasma fibrinogen level in patients with sudden deafness, the use of fibrinolytic thrombolytic treatment is more effective, efficient. And for normal levels of plasma fibrinogen in patients with sudden deafness, they should be adopted in other therapy, so as not to delay the disease.%目的 观察血浆纤维蛋白原水平(FIB)对溶栓治疗突发性聋患者的疗效影响,评价其重要性,进而推进临床上对突

  10. Fibrinolytic agents in the management of posthemorrhagic hydrocephalus in preterm infants: the evidence.

    Science.gov (United States)

    Haines, S J; Lapointe, M

    1999-05-01

    The objective of this study was to review current literature on the management of posthemorrhagic hydrocephalus in preterm infants with intraventricular administration of fibrinolytic agents; to this end a literature search was carried out electronically. The keywords used were "intraventricular hemorrhage" or "posthemorrhagic hydrocephalus" in combination with "fibrinolytic agent," "urokinase," "streptokinase," or "recombinant tissue plasminogen activator" and "intraventricular administration"; the search covered the years 1966-1998 and was restricted to English language papers and human subjects. It was supplemented by a search through the reference lists of the articles identified. Articles dealing with intracerebral hemorrhage or hematoma, intraventricular hemorrhage in adults, nontherapeutic issues and laboratory research were excluded. The articles included are summarized in evidence and evaluation tables. Five scientific publications evaluating the use of a fibrinolytic agent to manage posthemorrhagic hydrocephalus were retrieved. In the studies described in these reports, a total of 62 neonates received streptokinase, urokinase or r-tPA intraventricularly. No two of the regimens were identical in the drug used, method of administration and duration of therapy. The time before therapy was started ranged from 2 to 35 days after the ictus. Among the case series reported, three were small series with a total of 38 neonates. One other case series of 18 neonates compared the treatment group with an historical control group. All case series showed that endoventricular fibrinolytic therapy was practical. The proportion of cases in which shunt placement was performed ranged from 11% to 100%. Only one small prospective, randomized, controlled study was identified. That study was too small to allow useful conclusions. Overall, 3 cases of secondary intraventricular hemorrhage were reported. However, it was not possible to determine with certainty whether these episodes

  11. Local lysis in acute basilar artery occlusions: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Karnik, R.; Perneczky, G.; Ammerer, H.P.; Brenner, H.; Slany, J. (Krankenanstalt der Stadt Wien Rudolfstiftung (Austria))

    1984-01-01

    Thrombosis of the basilar artery is not a rare disease, and the mortality is reported to be 60 to 80%. Present standard therapy with heparin infusions yields poor results. The high risk of intracerebral haemorrhage prohibits systemic fibrinolytic therapy. Due to these facts and good experience in our department with the use of local intracoronary lysis in acute myocardial infarction, the method of local thrombolysis was applied in a case of acute basiliar artery thrombosis. Fibrinolytic therapy was started via an angiography catheter placed in the vertebral artery in a 28 year-old woman with hemiplegia and severe brain stem symptoms. The patient received 200,000 IU streptokinase within 2 hours and subsequently 300,000 IU urokinase within 10 hours. The vessel re-opened completely. The neurological symptoms decreased during the following weeks. Based on this experience and according to rare reports in the literature we believe local low-dose thrombolysis to be a causal therapy promising success for acute thrombosis of the basilar artery. This therapy can be carried out in every medical centre able to perform selective angiography and experienced in the administration of fibrinolytic drugs.

  12. The influence of lipoprotein(a) on fibrinolytic activity

    OpenAIRE

    Rahajuningsih D. Setiabudy; Marzuki Suryaatmadja; Fifi Henrika

    2004-01-01

    Lipoprotein(a) is a plasma lipoprotein whose structure and composition are similar with low density lipoprotein (LDL) with an addition of apo(a) that is bound to apo B100. The structure of apo(a) is similar with plasminogen, a proenzym in fibrinolytic system. Due to this similarity, it is assumed that Lp(a) can inhibit plasminogen activity and decreases fibrinolytic activity. The purpose of this study is to prove that addition of Lp(a) to normal plasma can inhibit fibrinolytic activity. Four ...

  13. Semi-automatic method for routine evaluation of fibrinolytic components.

    Science.gov (United States)

    Collen, D; Tytgat, G; Verstraete, M

    1968-11-01

    A semi-automatic method for the routine evaluation of fibrinolytic activity is described. The principle is based upon graphic recording by a multichannel voltmeter of tension drops over a potentiometer, caused by variations in the influence of light upon a light-dependent resistance, resulting from modifications in the composition of the fibrin fibres by lysis. The method is applied to the assessment of certain fibrinolytic factors with widespread fibrinolytic endpoints, and the results are compared with simultaneously obtained visual data on the plasmin assay, the plasminogen assay, and on the euglobulin clot lysis time.

  14. Heart rate turbulence in patients after primary percutaneous coronary intervention and fibrinolytic treatment for acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Isman Firdaus

    2007-03-01

    Full Text Available Heart rate turbulence (HRT as novel predictor of sudden cardiac death were superior to all other presently available indicators. HRT significantly was improves after successful reperfusion reflecting rapid restoration of baroreceptor response. We investigated turbulence onset (TO and turbulence slope (TS values among patients with acute ST-elevation myocardial infarction (STEMI underwent revascularization by means of primary PCI or fibrinolytic. We hypothesized that the values of TO and TS were different in two kinds of revascularization treatment. The subjects underwent 24 hours ECG recording after revascularization therapy. TO was quantified by the relative change of the first two sinus RR intervals following a ventricular premature beat (VPB and the last two sinus RR intervals before the VPB. TS was quantified by the maximum positive slope of a regression line assessed over any sequence of five subsequent sinus rhythm RR intervals within the first two sinus rhythm intervals after a VPB. Thirteen patients (mean of age 56 ± 9 years old who underwent revascularization treatment of acute STEMI were eligible as subject of this study.Ten patients underwent fibrinolytic therapy and three patients underwent primary PCI. TO value was significantly different between PCI group and fibrinolytic group (-3.3 ± 1.7 % vs -0.2 ± 0.9 % ; P=0.03. The Primary PCI group has better outcome on turbulence slope value (TS than fibrinolytic group but not significance (7.7 ± 4.4 msec/RR interval vs 3.4 ± 2.6 msec/RR interval; P = 0.056. In conclusion, TO was better in acute STEMI patient undergone PCI compare to that undergone fibrinolytic therapy. (Med J Indones 2007; 16:19-24 Keywords: heart rate turbulence, revascularization, myocardial infarction

  15. Risk-Based Therapy for Localized Osteosarcoma.

    Science.gov (United States)

    Venkatramani, Rajkumar; Murray, Jeffrey; Helman, Lee; Meyer, William; Hicks, M John; Krance, Robert; Lau, Ching; Jo, Eunji; Chintagumpala, Murali

    2016-03-01

    The outcome of localized osteosarcoma has remained constant over the past 30 years. Histological response to preoperative chemotherapy is the best predictor of outcome. Strategies to alter treatment based on histological response have not resulted in increased survival. Patients with localized osteosarcoma received preoperative chemotherapy with cisplatin, doxorubicin, and methotrexate. Patients whose tumors had a good histological response (≥90% necrosis) continued with the same treatment postoperatively. Patients with poor histological response (treatment-related deaths. Postoperative alkylator intensification with high-dose cyclophosphamide and melphalan in patients with localized osteosarcoma with poor histological response failed to improve survival. © 2015 Wiley Periodicals, Inc.

  16. Percutaneous local therapies for hepatocellular carcinoma impair gastric function

    Institute of Scientific and Technical Information of China (English)

    Fumihiko Kinekawa; Shigeki Kuriyama; Kazuya Matsuda; Tsutomu Masaki; Kazutaka Kurokohchi; Hirohito Yoneyama; Hideyuki Inoue; Hirohide Kurata; Yoshihito Uchida; Seishiro Watanabe

    2006-01-01

    @@ TO THE EDITOR Percutaneous local therapies, such as percutaneous ethanol injection (PEI), microwave coagulation and radiofrequency ablation (RFA), are frequently used worldwide for the treatment of hepatocellular carcinoma (HCC) because of their high effectiveness.

  17. In vitro decreases of the fibrinolytic potential of cultured human fibrosarcoma cell line, HT1080, by Nigella sativa oil.

    Science.gov (United States)

    Awad, E M

    2005-01-01

    It is generally accepted that the fibrinolytic potential of tumor cells is related to their malignant phenotype. In the present study, Nigella sativa oil (NSO) was studied to evaluate its effect on the fibrinolytic potential of the fibosarcoma cell line HT1080 to elucidate whether this oil might have an antitumor activity through its modulation of the fibrinolytic potential of such cells. NSO produced a concentration-dependent inhibition of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1). When subconfluent HT1080 cells were conditioned with oil, a concentration (0.0-200 microg oil/ml)-dependent decrease in t-PA, u-PA and PAI-1 antigen was observed. There was also a concentration-dependent decrease (from 0.0 to 112.5 microg oil/ml) in the confluent cultures. The results showed that blackseed oil decreases the fibrinolytic potential of the human fibrosarcoma cell line (HT1080) in vitro, implying that inhibition of local tumor invasion and metastasis may be one such mechanism.

  18. Asbestos exposure increases human bronchial epithelial cell fibrinolytic activity.

    Science.gov (United States)

    Gross, T J; Cobb, S M; Gruenert, D C; Peterson, M W

    1993-03-01

    Chronic exposure to asbestos fibers results in fibrotic lung disease. The distal pulmonary epithelium is an early target of asbestos-mediated injury. Local plasmin activity may be important in modulating endoluminal inflammatory responses in the lung. We studied the effects of asbestos exposure on cell-mediated plasma clot lysis as a marker of pericellular plasminogen activation. Exposing human bronchial epithelial (HBE) cells to 100 micrograms/ml of asbestos fibers for 24 h resulted in increased plasma clot lysis. Fibrinolytic activity was augmented in a dose-dependent fashion, was not due to secreted protease, and occurred only when there was direct contact between the plasma clot and the epithelial monolayer. Further analysis showed that asbestos exposure increased HBE cell-associated urokinase-type plasminogen activator (uPA) activity in a time-dependent manner. The increased cell-associated PA activity could be removed by acid washing. The increase in PA activity following asbestos exposure required new protein synthesis because it was abrogated by treatment with either cycloheximide or actinomycin D. Therefore, asbestos exposure increases epithelial-mediated fibrinolysis by augmenting expression of uPA activity at the cell surface by mechanisms that require new RNA and protein synthesis. These observations suggest a novel mechanism whereby exposure of the distal epithelium to inhaled particulates may result in a chronic inflammatory response that culminates in the development of fibrotic lung disease.

  19. [Localized lipohypertrophy during growth hormone therapy].

    Science.gov (United States)

    Mersebach, Henriette; Feldt-Rasmussen, Ulla F

    2002-04-01

    Accumulation of subcutaneous fat is described in a 51-year-old woman with panhypopituitarism treated on all insufficient pituitary axes, including growth hormone (GH). Malnutrition and alcoholic liver disease caused reduced synthesis of hepatic insulin-like growth factor I (IGF-I), and the function of IGF-I as biochemical marker of the GH effect was compromised. Peripheral levels of GH and IGF-I in tissues may have reached supra physiological levels and induced localised lipohypertrophy. Adjustment of GH treatment should not rest in all cases on IGF-I alone, but also depend on the clinical effect. Adjustment should follow suspected adverse events, such as lipohypertrophy, which is, however, an unusual complication of GH therapy.

  20. Mesoglycan treatment restores defective fibrinolytic potential in cutaneous necrotizing venulitis.

    Science.gov (United States)

    Lotti, T; Celasco, G; Tsampau, D; Teofoli, P; Benci, M; Dahm, M; Comacchi, C; Ghersetich, I; Matucci-Cerinic, M

    1993-05-01

    Cutaneous necrotizing venulitis (CNV) is a clinical disorder associated with segmental inflammation and fibrinoid necrosis of the dermal venules. It usually presents clinically as palpable purpura, even sometimes as nodules, bullae, ulcers, and urticarial lesions. This form, when showing as leukocytoclastic vasculitis is apparently characterized by the tissue deposition of circulating immune complexes and by reduced cutaneous (CFA) and plasma (PFA) fibrinolytic activity due to reduced release of plasminogen activator (PA) from the venular endotheliocytes. Reduced CFA and PFA cause large amounts of fibrin deposits in both intra- and perivascular areas, which are able to magnify and self perpetuate the inflammatory processes following immune complex deposition. We have studied both the PFA and CFA potential (the maximum amount of PA released in the skin after certain stimuli) and the deposits of immunoglobulins, C3, and fibrin related antigen, before and after intradermal injection of histamine (a substance able to provoke endothelial release of PA), in three subjects affected by CNV before and 20 days after 10 mg/kg/day I.M. treatment with the fibrinolytic agent mesoglycan. Cutaneous fibrinolytic activity and CFA potential, reduced prior to treatment, was normal after treatment, while the deposits of immunoglobulins (IgA, IgG and IgM), C3, and fibrin related antigen, detected with direct immune fluorescence (DIF) showed similar findings before and after treatment. These data suggest that reduced CFA may play a major role in the pathogenesis of the immunologically mediated injury in CNV. The intraperivascular deposition of fibrin is favored. The fibrinolytic agent mesoglycan seems effective in restoring defective fibrinolysis in patients affected by cutaneous necrotizing venulitis, suggesting that in cases with reduced cutaneous fibrinolytic activity (or potential) the use of a fibrinolytic agent should be considered.

  1. Combined modality therapy for locally advanced penile squamous cell carcinoma.

    Science.gov (United States)

    Pedrick, T J; Wheeler, W; Riemenschneider, H

    1993-12-01

    We report here a patient who presented with locally advanced Jackson Stage IV penile squamous cell carcinoma who was managed with preoperative 5-fluorouracil, mitomycin C chemotherapy, and concurrent radiation therapy. He experienced an excellent partial response which allowed more limited surgery than would otherwise be indicated. He is still alive and well 5 years after completion of his treatment without side effects, local recurrence, or distant metastatic disease.

  2. Local join therapy of vaginal infections by nifuratel-nistatin

    Directory of Open Access Journals (Sweden)

    Amra Habibović,

    2010-02-01

    Full Text Available A test included 40 women in the reproductive age with clinical symptoms of vaginitis and microbiologycal examination. They were treated by combined therapy of vaginal tablets of nifuratel, 500mg and nistatin 200 000 i. u. during six days, after which they underwent gynaecological reexamination and repeated microbiologycal examination of vaginal and cervical smears. An analiysis of vaginalsecretion found bacterial flora in 34 smears (65%, fungus (Candida albicans in 15 (24%and Trichomonas vaginalis in 7 (11%. Local vaginal therapy in vaginitis caused by Trichomonas vaginalis was successfull in all 7 patients,vaginitis caused by Candida albicans was successly treated in 14 (93% patients. Bacterial vaginitis was cured in 29 (71% patients during this tharapy. Local vaginal combined therapy of nifuratel and nistatin is eficient in patients with vaginitis caused by fungi and Trichomonas vaginalis too.

  3. Haemarthrosis stimulates the synovial fibrinolytic system in haemophilic mice

    NARCIS (Netherlands)

    Nieuwenhuizen, Laurens; Roosendaal, Goris; Coeleveld, Katja; Lubberts, Erik; Biesma, Douwe H.; Lafeber, Floris P. J. G.; Schutgens, Roger E. G.

    2013-01-01

    Recurrent joint bleeding is the most common manifestation of haemophilia resulting in haemophilic arthropathy (HA). The exact pathophysiology is unknown, but it is suggested that arthropathy is stimulated by liberation of fibrinolytic activators from the synovium during haemarthrosis. The aim of thi

  4. [The fibrinolytic treatment with urokinase of acute arterial thrombosis].

    Science.gov (United States)

    Ballester, A; Donato di Paola, M; Saccà, A; Cappello, I; D'Addato, M

    1993-01-01

    We present our experiences on 86 patients with acute arterial thrombosis of the legs, undergoing a fibrinolytic treatment with urokinase. Results from the treatment are analyzed according to: the administration way (systemic, locoregional, intrathrombotic), the level of thrombosis (upper or lower legs), the associated morbidity and mortality.

  5. The influence of lipoprotein(a on fibrinolytic activity

    Directory of Open Access Journals (Sweden)

    Rahajuningsih D. Setiabudy

    2004-09-01

    Full Text Available Lipoprotein(a is a plasma lipoprotein whose structure and composition are similar with low density lipoprotein (LDL with an addition of apo(a that is bound to apo B100. The structure of apo(a is similar with plasminogen, a proenzym in fibrinolytic system. Due to this similarity, it is assumed that Lp(a can inhibit plasminogen activity and decreases fibrinolytic activity. The purpose of this study is to prove that addition of Lp(a to normal plasma can inhibit fibrinolytic activity. Four healthy people whose fibrinogen levels, plasminogen activities and euglobulin clot lysis time were within normal range were enrolled in this study. Fibrinolytic activity were assessed by euglobulin clot lysis time (ECLT. In the first experiment, the addition of Lp(a was done before centrifugation to obtain euglobulin precipitates, while in the second experiment, Lp(a was added to the euglobulin precipitates. As a control, ECLT was performed in the plasma with the addition of NaCl 0.9% in the same volume with Lp(a. The results of the study showed that in the first experiment, there was no clot formation. It is assumed that Lp(a can bind fibrinogen and both of them floated in the supernatant, so there was no fibrinogen in the euglobulin precipitate that can be clotted by thrombin. In the second experiment, the clot did not dissolve until the fourth day. In conclusion, the addition of Lp(a to normal plasma can inhibit the activity of fibrinolytic system. (Med J Indones 2004; 13: 135-9 Keywords: plasminogen, fibrinogen, apo(a, euglobulin clot lysis time (ECLT

  6. Purification and characterization of a novel fibrinolytic enzyme from culture supernatant of Pleurotus ostreatus.

    Science.gov (United States)

    Liu, Xiao-Lan; Zheng, Xi-Qun; Qian, Peng-Zhi; Kopparapu, Narasimha-Kumar; Deng, Yong-Ping; Nonaka, Masanori; Harada, Naoki

    2014-02-28

    A fibrinolytic enzyme was produced by an edible mushroom of Pleurotus ostreatus using submerged culture fermentation. The enzyme was purified from the culture supernatant by applying a combination of freeze-thaw treatment, ammonium sulfate precipitation, hydrophobic interaction, and gel filtration chromatographies. The enzyme was purified by a 147-fold, with a yield of 7.54%. The molecular masses of the enzyme an determined by gel filtration and SDSPAGE were 13.6 and 18.2 kDa, respectively. The isoelectric point of the enzyme was 8.52. It hydrolyzed fibrinogen by cleaving the α and β chains of fibrinogen followed by the γ chains, and also activated plasminogen into plasmin. The enzyme was optimally active at 45°C and pH 7.4. The enzyme activity was completely inhibited by EDTA, whereas protease inhibitors of TPCK, SBTI, PMSF, aprotinin and pepstatin showed no inhibition on its activity. The partial amino acid sequences of the enzyme as determined by Q-TOF2 were ATFVGCSATR, GGTLIHESSHFTR, and YTTWFGTFVTSR. These sequences showed a high degree of homology with those of metallo-endopeptidases from P. ostreatus and Armillaria mellea. The purified enzyme can also be applied as a natural agent for oral fibrinolytic therapy or prevention of thrombosis.

  7. Fibrinolytic enzyme production by newly isolated Bacillus cereus SRM-001 with enhanced in-vitro blood clot lysis potential.

    Science.gov (United States)

    Narasimhan, Manoj Kumar; Chandrasekaran, Muthukumaran; Rajesh, Mathur

    2015-01-01

    The discovery of plasmin-like microbial fibrinolytic enzymes having high specificity and negligible side effects is crucial for thrombolytic therapy. Herein, we report one such extra-cellular fibrinolytic enzyme producing Bacillus cereus SRM-001 isolated from the blood-laden soil of a chicken dump yard. The potency of the enzyme was established with fibrin plate assay and in-vitro blood clot lysis assay. The shake-flask operating parameters and media composition were optimized for maximizing the productivity of the enzyme. The operating parameters, pH 7, 37°C, 1% inoculum volume and 24 h inoculum age, were found to be the optimum. The levels of media components, corn flour (0.3% w/v), soyabean powder (1.9% w/v) and MnSO4 (11.5 mM) were optimized by statistical analysis using Box-Behnken design derived RSM. This resulted in an almost 1.8 fold increase in fibrinolytic enzyme productivity. The 3D response surface plots showed soyabean powder and MnSO4 to be the key ingredients for enhancing the enzyme productivity, whereas corn flour had a marginal effect. The in-vitro blood clot lysis assay conducted at near physiological pH 7 at 37°C showed the enzyme to be a potential therapeutic thrombolytic agent.

  8. A fibrinolytic protease AfeE from Streptomyces sp. CC5, with potent thrombolytic activity in a mouse model.

    Science.gov (United States)

    Sun, Zhibin; Liu, Pingping; Cheng, Guangyan; Zhang, Biying; Dong, Weiliang; Su, Xingli; Huang, Yan; Cui, Zhongli; Kong, Yi

    2016-04-01

    Fibrinolytic proteases have potential applications in cardiovascular disease therapy. A novel fibrinolytic protease, AfeE, with strong thrombolytic activity was purified from Streptomyces sp. CC5. AfeE displayed maximum activity at 40°C in the pH range of 7.0-12.0. It was strongly inhibited by serine protease inhibitor phenylmethanesulfonylfluoride, soybean trypsin inhibitor, tosyl-l-lysine chloromethyl ketone and tosyl-l-phenylalanine chloromethyl ketone. The activity of the enzyme was partially inhibited by Cu(2+), Co(2+) and Zn(2+). AfeE exhibited higher substrate specificity for fibrin than fibrinogen, which has rarely been reported in fibrinolytic enzymes. AfeE also showed high thrombolytic activity in a carrageenan-induced mouse tail thrombosis model. AfeE prolonged prothrombin time, activated partial thromboplastin time, and thrombin time in rat blood. A bleeding time assay revealed that AfeE did not prolong bleeding time in mice at a dose of 1mg/kg. No acute cytotoxicity was observed for AfeE at 320μg/well in human umbilical vein endothelial cells. The afeE gene was cloned from the genome of Streptomyces sp. CC5. Full-length AFE-CC5E contained 434 amino acids and was processed into a mature form consisting 284 amino acids by posttranslational modification, as revealed by high-resolution mass spectrometry analysis. These results indicate that AfeE is a prospective candidate for antithrombotic drug development.

  9. Chemothermal Therapy for Localized Heating and Ablation of Tumor

    Directory of Open Access Journals (Sweden)

    Zhong-Shan Deng

    2013-01-01

    Full Text Available Chemothermal therapy is a new hyperthermia treatment on tumor using heat released from exothermic chemical reaction between the injected reactants and the diseased tissues. With the highly minimally invasive feature and localized heating performance, this method is expected to overcome the ubiquitous shortcomings encountered by many existing hyperthermia approaches in ablating irregular tumor. This review provides a relatively comprehensive review on the latest advancements and state of the art in chemothermal therapy. The basic principles and features of two typical chemothermal ablation strategies (acid-base neutralization-reaction-enabled thermal ablation and alkali-metal-enabled thermal/chemical ablation are illustrated. The prospects and possible challenges facing chemothermal ablation are analyzed. The chemothermal therapy is expected to open many clinical possibilities for precise tumor treatment in a minimally invasive way.

  10. [Systemic therapy and hyperthermia for locally advanced soft tissue sarcoma].

    Science.gov (United States)

    Lindner, L H; Angele, M; Dürr, H R; Rauch, J; Bruns, C

    2014-05-01

    Patients with high-risk soft tissue sarcomas (FNCLCC grades 2-3, > 5 cm and deep lying) are at a high risk of local recurrence or distant metastases despite optimal surgical tumor resection. Therefore, multimodal treatment should be considered for this difficult to treat patient group. Besides surgery, radiation therapy and chemotherapy, hyperthermia has become a valid, complementary treatment option within multimodal treatment concepts. Hyperthermia in this context means the selective heating of the tumor region to temperatures of 40-43 °C for 60 min by microwave radiation in addition to simultaneous chemotherapy or radiation therapy. A randomized phase III study demonstrated that the addition of hyperthermia to neoadjuvant chemotherapy improved tumor response and was associated with a minimal risk of early disease progression as compared to chemotherapy alone. The addition of hyperthermia to a multimodal treatment regimen for high-risk soft tissue sarcoma consisting of surgery, radiation therapy and chemotherapy, either in the neoadjuvant or adjuvant setting after incomplete or marginal tumor resection, significantly improved local progression-free and disease-free survival. Based on these results and due to the generally good tolerability of hyperthermia, this treatment method in combination with chemotherapy should be considered as a standard treatment option within multimodal treatment approaches for locally advanced high-risk soft tissue sarcoma.

  11. 54. Fibrinolytic therapy and polyvalvular heart disease in pediatric patient

    Directory of Open Access Journals (Sweden)

    Aiman Ayesh Alshamaley

    2015-10-01

    Conclusion: As growing surgical skills we are facing many pediatric cases with prosthetic valves with stuck valves. Which tPA dose should be used? Is streptokinase better? How long do you wait before considering surgery?

  12. Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

    Science.gov (United States)

    Andersen, Toril; Bleher, Stefan; Flaten, Gøril Eide; Tho, Ingunn; Mattsson, Sofia; Škalko-Basnet, Nataša

    2015-01-01

    Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances. PMID:25574737

  13. Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy

    Directory of Open Access Journals (Sweden)

    Toril Andersen

    2015-01-01

    Full Text Available Mucoadhesive drug therapy destined for localized drug treatment is gaining increasing importance in today’s drug development. Chitosan, due to its known biodegradability, bioadhesiveness and excellent safety profile offers means to improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to develop liposomes able to ensure prolonged residence time at vaginal site. Two types of mucoadhesive liposomes, namely the chitosan-coated liposomes and chitosan-containing liposomes, where chitosan is both embedded and surface-available, were made of soy phosphatidylcholine with entrapped fluorescence markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively. Both liposomal types were characterized for their size distribution, zeta potential, entrapment efficiency and the in vitro release profile, and compared to plain liposomes. The proof of chitosan being both surface-available as well as embedded into the liposomes in the chitosan-containing liposomes was found. The capability of the surface-available chitosan to interact with the model porcine mucin was confirmed for both chitosan-containing and chitosan-coated liposomes implying potential mucoadhesive behavior. Chitosan-containing liposomes were shown to be superior in respect to the simplicity of preparation, FITC-dextran load, mucoadhesiveness and in vitro release and are expected to ensure prolonged residence time on the vaginal mucosa providing localized sustained release of entrapped model substances.

  14. Hyperbaric oxygen therapy improves local microenvironment after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Yang Wang; Shuquan Zhang; Min Luo; Yajun Li

    2014-01-01

    Clinical studies have shown that hyperbaric oxygen therapy improves motor function in patients with spinal cord injury. In the present study, we explored the mechanisms associated with the recovery of neurological function after hyperbaric oxygen therapy in a rat model of spinal cord injury. We established an acute spinal cord injury model using a modiifcation of the free-falling object method, and treated the animals with oxygen at 0.2 MPa for 45 minutes, 4 hours after injury. The treatment was administered four times per day, for 3 days. Compared with model rats that did not receive the treatment, rats exposed to hyperbaric oxygen had fewer apoptotic cells in spinal cord tissue, lower expression levels of aquaporin 4/9 mRNA and protein, and more NF-200 positive nerve ifbers. Furthermore, they had smaller spinal cord cavities, rapid recovery of somatosensory and motor evoked potentials, and notably better recovery of hindlimb motor function than model rats. Our ifndings indicate that hyperbaric oxygen therapy reduces apop-tosis, downregulates aquaporin 4/9 mRNA and protein expression in injured spinal cord tissue, improves the local microenvironment for nerve regeneration, and protects and repairs the spinal cord after injury.

  15. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    Science.gov (United States)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  16. Evaluating localized prostate cancer and identifying candidates for focal therapy.

    Science.gov (United States)

    Sartor, A Oliver; Hricak, Hedvig; Wheeler, Thomas M; Coleman, Jonathan; Penson, David F; Carroll, Peter R; Rubin, Mark A; Scardino, Peter T

    2008-12-01

    accurate staging, grading, and tumor localization needed for a focal therapy program. Nevertheless, for men with minimal cancer who are amenable to active surveillance or focal therapy, consensus about the most accurate biopsy strategy has not yet been reached. Imaging, particularly magnetic resonance imaging and magnetic resonance spectroscopic imaging, has been used to assess men with early-stage prostate cancer. Large-volume cancers can be seen reasonably well, but small lesions have been difficult to detect reliably or measure accurately. Factors such as voxel resolution, organ movement, biopsy artifact, and benign changes have limited the consistent estimation of the quantitative tumor volume. Nevertheless, magnetic resonance imaging and magnetic resonance spectroscopic imaging can aid in evaluating patients with prostate cancer being considered for focal therapy by providing additional evidence that the patient does not harbor an otherwise undetected high-risk, aggressive cancer. In some cases, imaging can usefully identify the location of even a limited-sized index cancer. When imaging findings are substantiated by mapping biopsy results, confidence in the accurate characterization of the cancer is enhanced. Correlating the imaging results with tissue changes during and after treatment can be of use in monitoring the ablative effects in the prostate and in assessing for tumor recurrence. More work is necessary before staging studies can uniformly characterize a prostate cancer before therapy, much less reliably identify and locate small-volume cancer within the prostate. However, exploring the role of focal ablation as a therapeutic option for selected men with low-risk, clinically localized, prostate cancer need not await the emergence of perfectly accurate staging studies, any more than the application of radical surgery or radiotherapy have. Modern biopsy strategies, combined with optimal imaging and nomograms to estimate the pathologic stage and risk, taken

  17. Effect of supine exercise on platelet aggregation and fibrinolytic activity

    DEFF Research Database (Denmark)

    Dag, B; Fornitz, Gitte Gleerup; Bak, A M

    1994-01-01

    In 12 healthy young men, strenuous cycling exercise in the supine position, caused platelet aggregability to decrease and the ADP threshold to rise from 7.0 microM resting, to 9.5 exercising (P ... from 178 to 68 min, PAI-1 fell from 8.91 to 5.16 IU ml-1, and t-PA rose from 0.56 to 3.95 IU ml-1, all three values were significant to P exercise, it did not increase platelet activity as expected, but caused a modest increase...... of fibrinolytic activity. These results suggest that supine exercise will not affect the haemostatic system adversely....

  18. Fibrinolytic efficacy of Amediplase, Tenecteplase and scu-PA in different external plasma clot lysis models: sensitivity to the inhibitory action of thrombin activatable fibrinolysis inhibitor (TAFI).

    Science.gov (United States)

    Guimarães, Ana H C; Barrett-Bergshoeff, Marrie M; Criscuoli, Marco; Evangelista, Stefano; Rijken, Dingeman C

    2006-09-01

    In this study, the in-vitro fibrinolytic efficacy of Tenecteplase, Amediplase and scu-PA was investigated in different external lysis models by measuring the lysis of human plasma clots after the addition of the plasminogen activators (PAs) to the surrounding plasma. The effect of TAFI was examined for each PA by neutralising TAFIa with potato carboxypeptidase inhibitor (PCI). The lytic efficacy of Amediplase was lower than that of Tenecteplase at low PA concentrations but slightly higher at therapeutic concentrations. The activity of scu-PA was clearly lower than that of either Tenecteplase or Amediplase. The TAFI system inhibited external clot lysis mediated by all the PAs when thrombomodulin was present in the model. In the therapeutic range (5-10 mug/ml) however, the TAFIa effect was negligible for both Amediplase and Tenecteplase. At lower PA concentrations the effect of TAFI on Amediplase was slightly stronger than that on Tenecteplase. Under static conditions the lysis rates were lower than with stirring. The role of TAFI was similar under both conditions. In conclusion, at therapeutic concentrations Amediplase was slightly more active than Tenecteplase and scu-PA under all conditions used. Therefore, Amediplase might possibly be a more potent thrombolytic agent at these concentrations and increase the efficacy of thrombolysis. The potential of TAFI for inhibiting thrombolytic therapy is probably low. However in conditions where the local PA concentrations are sub-optimal TAFI might affect the lysis rate.

  19. Fibrinolytic markers and neurologic outcome in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Bayir Aysegul

    2006-01-01

    Full Text Available Aims: To determine the usefulness of fibrinolytic markers as early prognostic indicators in patients with isolated head trauma. Materials and Methods: Sixty-two consecutive patients (26 women and 36 men; mean age 61 years, range 2-76 years with isolated head trauma seen within the first three hours of the trauma were included in the study. The Glasgow Coma score (GCS, platelet counts (Plt, prothrombin time (PT, partial thromboplastin time (PTT, fibrinogen, fibrin degradation products (FDP and D-dimer levels were measured. Head computerized tomography (CT findings were categorized as brain edema, linear fracture, depressed fracture, contusion and bleeding. Plt counts, PT, PTT, fibrinogen, FDP, D-dimer levels and CT findings were compared with both GCS and mortality in the first week. Statistical significance was accepted at P£0.05. Results: A marked negative relationship was found between GCS and PT, PTT, FDP and D-dimer levels ( P < 0.001. Plt levels did not correlate with GCS. Mortality was most strongly related to GCS, PT, FDP and D-dimer levels ( P < 0.001, P < 0.001, P < 0.001 and P < 0.001, respectively. We found no relationship between mortality and CT findings, nor was there any significant relationship between Plt, PTT and fibrinogen levels. Conclusion: GCS and fibrinolytic markers measured within the first three hours were useful in determining the prognosis of patients with isolated head trauma.

  20. Fibrinolytic activity of kaempferol isolated from the fruits of Lagenaria siceraria (Molina) Standley.

    Science.gov (United States)

    Rajput, M S; Mathur, Vineet; Agrawal, Purti; Chandrawanshi, H K; Pilaniya, Urmila

    2011-11-01

    This study was undertaken to isolate a flavonol, kaempferol, from the fruits of Lagenaria siceraria (bottle gourd) as a sole compound and to explore the fibrinolytic potential of the methanolic extract of the fruits of L. siceraria and the isolated compound using their in vitro activity. The fibrinolytic activity in terms of percentage of plasma clot liquefaction was determined by plasma clot lysis at 37°C in 24 h. The fibrinolytic activity of both substances was compared to the well-known thrombolytic agent streptokinase (30,000 IU). The percentage of fibrinolytic activity of the extract and isolated compound were found to be 54.72 ± 0.7210 and 77.37 ± 1.3010, respectively. Streptokinase was considered as the standard fibrinolytic enzyme for comparative purposes and had 91.46 ± 0.7625% fibrinolytic activity. The conclusion drawn in our study after testing the hypothesis by experimental procedures is that in vitro fibrinolytic activity on plasma clots is an inherent property of kaempferol isolated from the fruits of L. siceraria, and its comparison with streptokinase is a new aspect for further study.

  1. Fibrinolytic enzyme from newly isolated marine bacterium Bacillus subtilis ICTF-1: media optimization, purification and characterization.

    Science.gov (United States)

    Mahajan, Prafulla M; Nayak, Shubhada; Lele, Smita S

    2012-03-01

    Fibrinolytic enzymes are important in treatment of cardiovascular diseases. The present work reports isolation, screening and identification of marine cultures for production of fibrinolytic enzymes. A potent fibrinolytic enzyme-producing bacterium was isolated from marine niches and identified as Bacillus subtilis ICTF-1 on the basis of the 16S rRNA gene sequencing and biochemical properties. Further, media optimization using L(18)-orthogonal array method resulted in enhanced production of fibrinolytic enzyme (8814 U/mL) which was 2.6 fold higher than in unoptimized medium (3420 U/mL). In vitro assays revealed that the enzyme could catalyze blood clot lysis effectively, indicating that this enzyme could be a useful thrombolytic agent. A fibrinolytic enzyme was purified from the culture supernatant to homogeneity by three step procedures with a 34.42-fold increase in specific activity and 7.5% recovery. This purified fibrinolytic enzyme had molecular mass of 28 kDa, optimal temperature and pH at 50 °C and 9, respectively. It was stable at pH 5.0-11.0 and temperature of 25-37 °C. The enzyme activity was activated by Ca(2+) and obviously inhibited by Zn(2+), Fe(3)(+), Hg(2+) and PMSF. The purified fibrinolytic enzyme showed high stability towards various surfactants and was relatively stable towards oxidizing agent. Considering these properties purified fibrinolytic enzyme also finds potential application in laundry detergents in addition to thrombolytic agent. The gene encoding fibrinolytic enzyme was isolated and its DNA sequence was determined. Compared the full DNA sequence with those in NCBI, it was considered to be a subtilisin like serine-protease.

  2. Platelet function and fibrinolytic activity following distance running.

    Science.gov (United States)

    Knudsen, J B; Brodthagen, U; Gormsen, J; Jordal, R; Nørregaard-Hansen, K; Paulev, P E

    1982-11-01

    6 long distance runners from the Danish marathon elite and 6 non-runners completed test runs of 28 and 12 km, respectively. Distance runners and non-runners showed the same responses in platelet function. We found a significant decrease in ADP induced platelet aggregability, a decreased serotonin release induced by ADP and collagen and an increase in platelet factor 4 immediately following the run. The antithrombin III levels remained constant. Euglobulin lysis time was shortened (by approximately 50%) and the plasminogen levels significantly increased. The last 2 findings indicate an equal increase in fibrinolytic activity during distance running in both groups. While short term, strenuous exercise induces platelet hyperaggregation, long term distance running induces a state of exhaustion of platelet aggregation capacity.

  3. FDG PET for monitoring response to local and locoregional therapy in HCC and liver metastases

    NARCIS (Netherlands)

    Dierckx, R.; Maes, A.; Peeters, M.; Van de Wiele, C.

    2009-01-01

    Local ablative therapies and loco-regional therapies are being increasingly used for the purpose of providing local control of primary liver tumors and liver metastases while sparing normal liver tissue. in this manuscript, literature on the use of fluorodeoxyglucose positron emission tomography (FD

  4. Neoadjuvant therapy for locally advanced melanoma: new strategies with targeted therapies

    Directory of Open Access Journals (Sweden)

    La Greca M

    2014-06-01

    Full Text Available Michele La Greca,1 Giuseppe Grasso,2 Giovanna Antonelli,1 Alessia Erika Russo,1 Salvatore Bartolotta,3 Alessandro D’Angelo,1 Felice Vito Vitale,1 Francesco Ferraù1 1Medical Oncology Department, San Vincenzo Hospital, Taormina, Messina, Italy; 2Pathology Department, San Vincenzo Hospital, Taormina, Messina, Italy; 3Surgical Unit, Casa di Cura Gretter-Lucina, Catania, Catania, Italy Abstract: Neoadjuvant chemotherapy has been successfully tested in several bulky solid tumors, but it has not been utilized in advanced cutaneous melanoma, primarily because effective medical treatments for this disease have been lacking. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1] and small molecules interfering with intracellular pathways (anti-BRAF and mitogen-activated protein kinase kinase [anti- MEK] the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. The neoadjuvant setting provides a double opportunity for a better knowledge of these drugs: a short-term evaluation of their intrinsic activity, and a deeper analysis of their action and resistance-induction mechanisms. BRAF inhibitors seem to be ideal candidates for the neoadjuvant setting, because of their prompt, repeatedly confirmed response in V600E BRAF-mutant metastatic melanoma. In this report we summarize studies focused on the neoadjuvant use of traditional medical treatments in advanced melanoma and anecdotal cases of this approach with the use of biologic therapies. Moreover, we discuss our experience with neoadjuvant targeted therapy as a priming for radical surgery in a patient with BRAF V600E mutation-positive advanced melanoma. Keywords: neoadjuvant setting, biologic, targeted therapy, vemurafenib, advanced melanoma

  5. Neoadjuvant therapy for locally advanced melanoma: new strategies with targeted therapies.

    Science.gov (United States)

    La Greca, Michele; Grasso, Giuseppe; Antonelli, Giovanna; Russo, Alessia Erika; Bartolotta, Salvatore; D'Angelo, Alessandro; Vitale, Felice Vito; Ferraù, Francesco

    2014-01-01

    Neoadjuvant chemotherapy has been successfully tested in several bulky solid tumors, but it has not been utilized in advanced cutaneous melanoma, primarily because effective medical treatments for this disease have been lacking. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1]) and small molecules interfering with intracellular pathways (anti-BRAF and mitogen-activated protein kinase kinase [anti- MEK]) the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. The neoadjuvant setting provides a double opportunity for a better knowledge of these drugs: a short-term evaluation of their intrinsic activity, and a deeper analysis of their action and resistance-induction mechanisms. BRAF inhibitors seem to be ideal candidates for the neoadjuvant setting, because of their prompt, repeatedly confirmed response in V600E BRAF-mutant metastatic melanoma. In this report we summarize studies focused on the neoadjuvant use of traditional medical treatments in advanced melanoma and anecdotal cases of this approach with the use of biologic therapies. Moreover, we discuss our experience with neoadjuvant targeted therapy as a priming for radical surgery in a patient with BRAF V600E mutation-positive advanced melanoma.

  6. Cloning and Expression of One Fibrinolytic Enzyme from Bacillus sp.zlw-2

    Institute of Scientific and Technical Information of China (English)

    NAN Xin-mian; GUO Run-fang; YU Hong-wei; JIA Ying-min

    2009-01-01

    The gene encoding fibrinolytic enzyme from Bacillus sp.zlw-2 was cloned and sequenced (accession no.EU734749),which was 1146 bp,encoded 381 amino acids and had 99% homology with Nattokinase YF308 and NAT.The genes encoding pre-pro-fibrinolytic enzyme (including signal peptide,propeptide,and mature peptide) and fibrinolytic enzyme (including mature peptide) were cloned into pET28a vector respectively and then transformed into Escherichia coil BL21 (DE3).The recombinant of pre-pro-fibrinolytic enzyme showed enzyme activity of 183 U mL-1,while no detectable enzyme activity could be found from the recombinant of the mature peptide.

  7. FIBRINOLYTIC-ACTIVITY IN THE ABDOMINAL-CAVITY OF RATS WITH FECAL PERITONITIS

    NARCIS (Netherlands)

    van Goor, Harry; de Graaf, JS; Sluiter, WJ; van der Meer, J; Bom, VJJ; Bleichrodt, RP

    1994-01-01

    Generalized peritonitis causes a reduction in abdominal fibrinolytic activity, resulting in persistence of intraabdominal fibrin with subsequent adhesion and abscess formation. The activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI) were measured in the periton

  8. Impact of fibrinolytics on the outcome of empyema in South African ...

    African Journals Online (AJOL)

    introduction of 7-valent pneumococcal conjugate vaccine (PCV7), the incidence of ... after the child received fibrinolytics were included in the treatment analysis. ... pleural effusion causing symptoms (pain ... Persistent fever >38°C more than.

  9. Production, optimization and characterization of fibrinolytic enzyme by Bacillus subtilis RJAS19.

    Science.gov (United States)

    Kumar, D J Mukesh; Rakshitha, R; Vidhya, M Annu; Jennifer, P Sharon; Prasad, Sandip; Kumar, M Ravi; Kalaichelvan, P T

    2014-04-01

    The present study aimed at the production, purification and characterization of fibrinolytic nattokinase enzyme from the bacteria isolated from natto food. For the purpose, a fibrinolytic bacterium was isolated and identified as Bacillus subtilis based on 16S rDNA sequence analysis. The strain was employed for the production and optimization of fibrinolytic enzyme. The strain showed better enzyme production during 72nd h of incubation time with 50 degrees C at the pH 9. The lactose and peptone were found to be increasing the enzyme production rate. The enzyme produced was purified and also characterized with the help of SDS-PAGE analysis. The activity and stability profile of the purified enzyme was tested against different temperature and pH. The observations suggesting that the potential of fibrinolytic enzyme produced by Bacillus subtilis RJAS 19 for its applications in preventive medicines.

  10. FIBRINOLYTIC-ACTIVITY IN THE ABDOMINAL-CAVITY OF RATS WITH FECAL PERITONITIS

    NARCIS (Netherlands)

    van Goor, Harry; de Graaf, JS; Sluiter, WJ; van der Meer, J; Bom, VJJ; Bleichrodt, RP

    1994-01-01

    Generalized peritonitis causes a reduction in abdominal fibrinolytic activity, resulting in persistence of intraabdominal fibrin with subsequent adhesion and abscess formation. The activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI) were measured in the periton

  11. Ultrasound-enhanced Fibrinolysis Pro-fibrinolytic and Non-beneficial Effects Of Ultrasound Exposure

    OpenAIRE

    Madsen-Härdig, Bjarne

    2005-01-01

    The aim of this study was to further clarify the pro-fibrinolytic effects, and to explore the possible non-beneficial effects in ischemic organs, during exposure to pulsed ultrasound. This was accomplished by studies of the effects of different intensities of pulsed ultrasound exposure on the fibrinolytic properties of streptokinase and reteplase. Measurements were performed both following pre-exposure of the drugs and clots to pulsed ultrasound, and following concomitant exposure of clots an...

  12. Fibrinolytic Activity of Blood and its Determinants in Healthy Medical Students

    Science.gov (United States)

    Shoeb, M.; Bose, S.

    2015-01-01

    Background Decreased fibrinolytic activity results in longer fibrinolysis time of blood and an increased propensity for hypercoagulable states of blood. Subjects with less fibrinolytic activity are prone to coronary artery disease, stroke and thromboembolic phenomena. Aim The study aims to identify the impact of gender, dietary habits, body mass index, physical activity level and menstrual cycle on fibrinolytic activity in healthy subjects. Settings and Design Cross-sectional study on randomly selected 206 healthy medical students aged 17 to 23 years. Materials and Methods Anthropometric measurements, dietary habits, physical activity level and menstrual history were obtained. Fibrinolysis time of fasting venous blood sample was determined by Euglobulin Lysis Time (ELT) method. Results Highly significant gender difference was noted in mean fibrinolytic activity (p=0.002). Mean fibrinolytic activity also showed a significant relationship with BMI (p=0.001) and with different phases of menstrual cycle in females (p=0.004). However, such relationship was not observed with diet and physical activity (p>0.05) in boys and girls. Conclusion Gender difference, body mass index and menstrual cycle phases have influences on the fibrinolytic activity of blood. This might be due to cyclical changes in the sex hormones levels, endometrium-derived plasmin and plasminogen activators and excess production of plasminogen activator inhibitor type-1 (PAI-I) in visceral adipocytes. PMID:26266114

  13. Local control of piriform sinus cancer treated by radiation therapy alone

    Energy Technology Data Exchange (ETDEWEB)

    Itami, Jun [Department of Radiation Therapy and Oncology, International Medical Center of Japan, Tokyo (Japan); Uno, Takashi [Department of Radiation Therapy and Oncology, International Medical Center of Japan, Tokyo (Japan); Aruga, Moriyo [Department of Radiation Therapy and Oncology, International Medical Center of Japan, Tokyo (Japan); Ode, Shigeomi [Department of Radiation Therapy and Oncology, International Medical Center of Japan, Tokyo (Japan)

    1997-09-01

    Local control rate by radical radiation therapy was analyzed in 33 patients with a piriform sinus cancer. Twenty-five patients (76%) were in stage T3+T4. Local recurrence-free survival at 3 years was 49% in T1+T2 and 25% in T3+T4 (p=0.01). In T1+T2 lesions, a biologically effective dose for an acute reaction over 80 Gy and total treatment time less than 70 days appeared to improve local control. In T3+T4 lesions, good radiation response assessed by the regaining of laryngeal mobility affected local control favorably. An esophageal involvement and destruction of the laryngeal cartilage as well as soft tissue extension precluded the possibility of local control by radiation therapy alone. In addition to the T-stage, other tumor factors should also be considered for predicting local control with radiation therapy. (orig.).

  14. Enzymatic properties of UFE,a novel marine fibrinolytic enzyme

    Institute of Scientific and Technical Information of China (English)

    WANG Dianliang; LIU Wanshun; HAN Baoqin

    2007-01-01

    A novel potent protease, Urechis unicinctus fibrinolytic enzyme (UFE), was firstly discovered. The enzymatic properties of UFE were further investigated.As a low molecular mass protein,UFE appeared to be very stable to heat and pH.When temperature was below 50 °C ,the remnant enzyme activity remained almost unchanged, but when temperature was raised to 60 °C ,the remnant enzyme activity began to decrease rapidly. UFE was quite stable in the range of pH value from 3 to 12,especially in slightly alkaline pH value.Mn2+ ,Cu2+ and Fe2+ ions were activators of UFE, while Fe3+ and Ag+ ions were inhibitors of UFE.Fe2+ ion along with Fe3+ ion might regulate UFE activity in vivo. The optimum pH and temperature of UFE were about 8 and 50 °C ,respectively. Other characteristics of this enzyme were also studied. Systematic research results are significant when UFE is applied for medical and industrial purposes.

  15. The binding interactions of imidacloprid with earthworm fibrinolytic enzyme

    Science.gov (United States)

    Wang, Yan-Qing; Zhang, Hong-Mei; Chen, Tao

    2014-08-01

    In this paper, several studies were conducted to elucidate the binding mechanism of earthworm fibrinolytic enzyme (EFE) with imidocloprid (IMI) by using theoretical calculation, fluorescence, UV-vis, circular dichroism spectroscopy and an enzymatic inhibition assay. The spectral data showed that the binding interactions existed between IMI and EFE. The binding constants, binding site, thermodynamic parameters and binding forces were analyzed in detail. The results indicate a single class of binding sites for IMI in EFE and that this binding interaction is a spontaneous process with the estimated enthalpy and entropy changes being 2.195 kJ mol-1 and 94.480 J mol-1 K-1, respectively. A single class of binding site existed for IMI in EFE. The tertiary or secondary structure of EFE was partly destroyed by IMI. The visualized binding details were also exhibited by the theoretical calculation and the results indicated that the interaction between IMI and Phe (Tyr, or Trp) or EFE occurred. Combining the experimental data with the theoretical calculation data, we showed that the binding forces between IMI and EFE were mainly hydrophobic force accompanied by hydrogen binding, and π-π stacking. In addition, IMI did not obviously influence the activity of EFE. In a word, the above analysis offered insights into the binding mechanism of IMI with EFE and could provide some important information for the molecular toxicity of IMI for earthworms.

  16. Purification and characterization of fibrinolytic metalloprotease from Perenniporia fraxinea mycelia.

    Science.gov (United States)

    Kim, Jae-Sung; Kim, Ji-Eun; Choi, Bong-Suk; Park, Se-Eun; Sapkota, Kumar; Kim, Seung; Lee, Hyun-Hwa; Kim, Chun-Sung; Park, Yeal; Kim, Myung-Kon; Kim, Yoon-Sik; Kim, Sung-Jun

    2008-08-01

    In this study we purified and characterized a fibrinolytic protease from the mycelia of Perenniporia fraxinea. The apparent molecular mass of the purified enzyme was estimated to be 42kDa by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), fibrin zymography and size exclusion using fast protein liquid chromatography (FPLC). The first 20 amino acid residues of the N-terminal sequence were ASYRVLPITKELLPPEFFVA, which shows a high degree of similarity with a fungalysin metallopeptidase from Coprinopsis cinerea. The optimal reaction pH value and temperature were pH 6.0 and 35-40 degrees C, respectively. Results for the fibrinolysis pattern showed that the protease rapidly hydrolyzed the fibrin alpha-chain followed by the beta-chain. The gamma-gamma chains were also hydrolyzed, but more slowly. The purified protease effectively hydrolyzed fibrinogen, preferentially digesting the Aalpha-chains of fibrinogen, followed by Bbeta- and gamma-chains. We found that protease activity was inhibited by Cu(2+), Fe(3+), and Zn(2+), but enhanced by the additions of Mn(2+), Mg(2+) and Ca(2+) metal ions. Furthermore, the protease activity was inhibited by EDTA, and it was found to exhibit a higher specificity for the chromogenic substrate S-2586 for chymotrypsin, indicating that the enzyme is a chymotrypsin-like metalloprotease. The mycelia of P. fraxinea may thus represent a source of new therapeutic agents to treat thrombosis.

  17. POSSIBILITIES OF LOCAL THERAPY FOR LOW BACK PAIN

    Directory of Open Access Journals (Sweden)

    A. V. Chugunov

    2014-11-01

    Full Text Available Low back pain (LBP is one of the most common pain syndromes caused by musculoarticular pathology. Analgesics, nonsteroidal antiinflammatory drugs (NSAIDs, myorelaxants, and non-drug therapies are used to treat patients with LBP. The sufficient efficiency of this type of therapy is strongly supported by the results of clinical trials; its fundamentals have been embodied in a number of regional and international guidelines for the management of patients with LBP. Alongside the sufficient efficacy of NSAIDs, their use, their long-term use in particular, is associated with a wide range of adverse reactions. The increased efficiency of treatment in patients with LBP is frequently achieved by the application of topical dosage forms. Whether the new Russian drug Nanoplast forte may be used to treat patients with LBP is considered.

  18. Local treatment failure after globe-conserving therapy for choroidal melanoma.

    Science.gov (United States)

    Chang, Melinda Y; McCannel, Tara A

    2013-07-01

    Local treatment failure after globe-conserving therapy for choroidal melanoma is a surgical complication with significant morbidity to the vision and eye. Few reports in the literature have addressed this complication exclusively. A review of the published literature with reference to local treatment failure in the management of choroidal melanoma was performed to make known the potential differences in failure rates between treatment modalities and methods. A search of the literature regarding local treatment failure was performed to identify relevant studies using combinations of the following keywords on PubMed: uveal melanoma, choroidal melanoma, local recurrence, local failure, endoresection, gamma knife, radiotherapy, helium, iodine, proton, palladium, ruthenium, trans-scleral resection, transpupillary thermotherapy. Further studies were found by searching the text and references of previously identified studies for articles reporting local treatment failure rates in choroidal melanoma. Among the 49 studies identified, the local treatment failure rate ranged from 0% to 55.6%, with follow-up ranging from 10 to 150 months. The two most widely used forms of radiation therapy, iodine-125 and ruthenium-106 brachytherapy, were both associated with a local recurrence rate of 9.6%. The weighted-average of treatment failure in all radiation therapies was 6.15% compared with 18.6% in surgical and 20.8% in laser therapies. Rates of local treatment failure for globe-conserving therapy of choroidal melanoma varied widely between modalities and between centres using similar modalities. Radiation therapy overall resulted in lower local treatment failures compared with surgical or transpupillary thermotherapy.

  19. Laryngeal amyloidosis : Localized versus systemic disease and update on diagnosis and therapy

    NARCIS (Netherlands)

    Bartels, H.; Dikkers, FG; Van der Wal, JE; Lokhorst, HM; Hazenberg, BPC

    2004-01-01

    The clinical and pathological characteristics, possibility of systemic disease, and effect of local therapy were studied in laryngeal amyloidosis. Records of all patients with localized laryngeal amyloidosis in a single tertiary referral center were examined retrospectively at diagnosis and after lo

  20. Intervention of CT Localization plus TCM Therapy on Prolapse of Lumbar Intervertebral Disc

    Institute of Scientific and Technical Information of China (English)

    LUO Zhi-hong; SHEN Wei-na

    2003-01-01

    Purpose To observe the curative effect of interventional therapy by CT localization combined traditional Chinese medicine on prolapse of lumbar intervertebral disc. Method The inpatients of lumbar intervertebral disc prolapse were randomly divided into treatmentgroup and control group. Interventional therapy by CT localization combined TCM was used in the treatment group while in the control group TCM therapy was taken only. The treatment lasted for 10 days in both groups. Results The curative effect was 94.3% in the treatment group while 76.8% in the control one (P < 0.05), which had statistical meaning. Conclusion Interventional therapy by CT localization combined TCM on prolapse of lumbar intervertebral disc had better effect and shorter treatment course.

  1. Biochemical characterization of a novel fibrinolytic enzyme from Cordyceps militaris.

    Science.gov (United States)

    Liu, Xiaolan; Kopparapu, Narasimha-Kumar; Li, Yao; Deng, Yongping; Zheng, Xiqun

    2017-01-01

    A fibrinolytic enzyme was produced by the medicinal mushroom, Cordyceps militaris using submerged fermentation. The enzyme was purified from culture supernatant by hydrophobic interaction, ion exchange and gel filtration chromatographies. It was purified by 36 fold, with a specific activity of 1,467.4U/mg protein and the final yield was 5.8%. The molecular weight of the enzyme as determined by SDS-PAGE and gel filtration was 28kDa and 24.5kDa, respectively, and its isoelectric point (pI) was 9.0±0.2. It was found to be a glycoprotein with carbohydrate content of 1.67% (w/v). The enzyme was optimally active at 37°C and pH 7.2. The enzyme activity was strongly inhibited by soybean trypsin inhibitor (SBTI) and aprotinin which indicated it to be a serine protease, while other inhibitors like N-α-tosyl-l-phenylalanine chloromethyl ketone (TPCK), phenyl methane sulfonyl fluoride (PMSF), pepstatin and metal chelator EDTA did not inhibit its activity. Amino acid sequences of the purified enzyme were determined partially by Q-TOF2 and they were IEDFPYQVDLR; ANCGGTVISEK; YVLTAGHCAEGYTGLNIR; TNYASVTPITADMICAGFPEGK; KDSCSGDSGGPLVTGGK; VVGIVSFGTGCAR; ANKPGVYSSVASAEIR. Sequences of the seven peptides completely matched with those of a trypsin-like serine protease from Cordyceps militaris CM01 (accession no. EGX95217.1). The purified enzyme degraded α chains of fibrinogen first and then β and γ chains and also activated plasminogen into plasmin. It can act as an anticoagulant and prevent clot formation by degrading fibrinogen. Based on these studies, the purified enzyme has great potential to be developed as a natural agent for prevention and treatment of thrombolytic diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. "Cell therapy for stroke: use of local astrocytes"

    Directory of Open Access Journals (Sweden)

    Melek eChouchane

    2012-10-01

    Full Text Available Stroke refers to a variety of conditions caused by the occlusion or hemorrhage of blood vessels supplying the brain, which is one of the main causes of death and the leading cause of disability worldwide. In the last years, cell-based therapies have been proposed as a new approach to ameliorate post stroke deficits. However, the most appropriate type of cell to be used in such therapies, as well as their sources, remains a matter of intense research. A good candidate cell should, in principle, display high plasticity to generate diverse types of neurons and, at the same type, low risk to cause undesired outcomes, such as malignant transformation. Recently, a new approach grounded on the reprogramming of endogenous astrocytes towards neuronal fates emerged as an alternative to restore neurological functions in several central nervous system diseases. In this perspective, we review data about the potential of astrocytes to become functional neurons following expression of neurogenic genes and discuss the potential benefits and risks of reprogramming astrocytes in the glial scar to replace neurons lost after stroke.

  3. Local Therapy of Gonarthrosis Using Autologous Platelet-Enriched Plasma

    OpenAIRE

    2012-01-01

    The aim of the investigation is to assess clinical effect of local (intra-articular) application of autologous platelet-enriched plasma (PEP) in treating gonarthrosis. Materials and Methods. Clinical observation of 83 women with gonarthrosis was performed within 3 months. Within 3 weeks the patients were receiving PEP intra-articular injections of 5 ml twice a week. Results. In intra-articular PEP administration in patients with gonarthrosis, the change of knee joint functional state ...

  4. Change in fibrinolytic activity under the influence of a constant magnetic field. [blood coagulation normilization in heart patients

    Science.gov (United States)

    Yepishina, S. G.

    1974-01-01

    The fibrinolytic activity of plasma changes under the influence of a constant magnetic field (CMF) with a strength of 250 or 2500 oersteds. CMF shows a tendency toward normalization of fibrinolytic processes in the presence of pathological disturbances in fibrinolysis activation.

  5. PROTEOLYTIC AND FIBRINOLYTIC ACTIVITIES OF HALOPHILIC LACTIC ACID BACTERIA FROM TWO INDONESIAN FERMENTED FOODS

    Directory of Open Access Journals (Sweden)

    Asep A. Prihanto

    2013-04-01

    Full Text Available Exploration of fermented foods as sources of fibrinolytic enzymes is increased in the last decades. Terasi and Jambal roti is Indonesian traditional fermented fish products, which were famous in Java Island. Both are important products in Indonesian dishes, especially in Java. Investigation on halophilic lactic acid bacteria using MRS and M-17 agar obtained seventy four isolated strains. Their proteolytic and fibrinolytic activities were determined using skim milk agar and plasminogen-free fibrin plate. Twenty five isolates showed protease activities, while only four of them secreted fibrinolitic enzyme. The highest proteolytic and fibrinolytic activity was shown by TB1 strain, which is identified as Bacillus coagulans. The 16s rDNA is still in investigating to confirm the TB1 strain identity.

  6. Role of Local Radiation Therapy in Cancer Immunotherapy.

    Science.gov (United States)

    Demaria, Sandra; Golden, Encouse B; Formenti, Silvia C

    2015-12-01

    The recent success of cancer immunotherapy has demonstrated the power of the immune system to clear tumors, generating renewed enthusiasm for identifying ways to induce antitumor immune responses in patients. Natural antitumor immune responses are detectable in a fraction of patients across multiple malignant neoplasms and can be reactivated by targeting rate-limiting immunosuppressive mechanisms. In most patients, however, interventions to induce a de novo antitumor immune response are necessary. We review growing evidence that radiation therapy targeted to the tumor can convert it into an in situ tumor vaccine by inducing release of antigens during cancer cell death in association with proinflammatory signals that trigger the innate immune system to activate tumor-specific T cells. In addition, radiation's effects on the tumor microenvironment enhance infiltration of activated T cells and can overcome some of the barriers to tumor rejection. Thus, the complementary effects of radiation on priming and effector phases of antitumor immunity make it an appealing strategy to generate immunity against a patient's own individual tumor, that through immunological memory, can result in long-lasting systemic responses. Several anecdotal cases have demonstrated the efficacy of combining radiation with available immunotherapies, and results of prospective trials are forthcoming.

  7. Reactivation of pulmonary tuberculosis following local radiation therapy of prostate cancer.

    Science.gov (United States)

    Thomas, Persis; Foley, Raymond; Kosowicz, Lynn

    2014-02-01

    In this report, we describe the case of an 81-year-old male with reactivation tuberculosis following local radiation therapy for prostate cancer. The patient was asymptomatic except for an unintentional 20-pound weight loss and was incidentally found to have a pulmonary infiltrate in the right upper lobe on imaging for shoulder pain. The medical history was not able for recently treated prostate cancer. After further investigation, the patient was determined to have Mycobacterium tuberculosis infection. It is important to have a high level of suspicion for reactivation tuberculosis in patients with a pulmonary infiltrate following radiation therapy due to the impact of radiation on the host's immune system. We will review the literature on reactivation tuberculosis following radiation therapy and explore the mechanism of immunosuppression in this process. To our knowledge, this is the first reported case of tuberculosis reactivation following local radiation therapy for prostate cancer.

  8. Low Incidence of Fatigue after Hypofractionated Stereotactic Body Radiation Therapy for Localized Prostate Cancer

    OpenAIRE

    Dash, Chiranjeev; Demas, Kristina; Uhm, Sunghae; Hanscom, Heather N; Kim, Joy S; Suy, Simeng; Davis, Kimberly M.; Sween, Jennifer; Collins, Sean; Lucile L Adams-Campbell

    2012-01-01

    Background: Fatigue is a common side effect of conventional prostate cancer radiation therapy. The increased delivery precision necessitated by the high dose per fraction of stereotactic body radiation therapy (SBRT) offers the potential of reduce target volumes and hence the exposure of normal tissues to high radiation doses. Herein, we examine the level of fatigue associated with SBRT treatment. Methods: Forty patients with localized prostate cancer treated with hypofractionated SBRT, and a...

  9. Low Incidence of Fatigue after Hypofractionated Stereotactic Body Radiation Therapy (SBRT) for Localized Prostate Cancer

    OpenAIRE

    Chiranjeev eDash; Kristina eDemas; Sunghae eUhm; Hanscom, Heather N; Kim, Joy S; Simeng eSuy; Davis, Kimberly M.; Jennifer eSween; Sean eCollins; Lucile L Adams-Campbell

    2012-01-01

    Background: Fatigue is a common side-effect of conventional prostate cancer radiation therapy. The increased delivery precision necessitated by the high dose per fraction of stereotactic body radiation therapy (SBRT) offers the potential of reduce target volumes and hence the exposure of normal tissues to high radiation doses. Herein, we examine the level of fatigue associated with SBRT treatment.Methods: Forty patients with localized prostate cancer treated with hypofractionated SBRT, an...

  10. Local hypothermia and optimal temperature for stroke therapy in rats

    Institute of Scientific and Technical Information of China (English)

    WU Hao; JIANG Li-dan; Karsten H.Wrede; JI Xun-ming; ZHAO Xi-qing; TIAN Xin; GAO Yu-fei; LING Feng

    2009-01-01

    Background Local hypothermia induced by intravascular infusion of cold saline solution effectively reduces brain damage in stroke. We further determined the optimal temperature of local hypothermia in our study. Methods Seventy-eight adult male Sprague Dawley rats (260-300 g) were randomly divided into 3 groups: group A, ischemia/reperfusion without cold saline infusion (n=-26) (control group); group B, infusion with 20℃ saline before reperfusion (n=26); group C: infusion with 10~C saline before reperfusion (n=26). In each group, we chose 15 rats for monitoring physical indexes and the temperature of the brain (cortex and striatum) and body (anus), measurement of brain infarction volume, assessment of neurological deficits and the survival rate of reperfusion at 48 hours. Another 8 rats from each group was chosen for examining brain edema, another 3 from each group for histological observation by electron microscopy (EM) and light microscopy (LM) at 48 hours after reperfusion. Results There was no significant difference among the 3 groups for physical indexes during the examination (F(2,45)=0.577, P=0.568; F(2, 45)= 0.42, P=0.78 for blood pressure and blood gas analysis, respectively). The brain temperature was significantly reduced in the group C compared to the other groups (F(2, 45)=37.074, P=0.000; F(2, 45)=32.983, P=0.000, for cortex and striatum temperature respectively), while the difference in rectal temperature between group A and B or C after reperfusion was not significant (F(2, 45)= 0.17115, P=0.637). And the brain infarct volume was significantly reduced in group C (from 40%±10% in group A, 26%±8% in group B, to 12%±6% in group C, F<(2,45)=43.465, P=0.000) with the neurological deficits improving in group C (X2=27.626, P=0.000). The survival rate at 48 hours after 10℃ and 20℃ saline reperfusion was increased by 132.5% and 150%, respectively, as compared to the control group (X2=10.489, P=0.005). The extent of the brain edema showed no

  11. Combined oral and local therapy for the dissolution of urinary calculi.

    Science.gov (United States)

    Götz, F; Frang, D; Hübler, J; Nagy, Z

    1982-01-01

    The factors underlying the formation of Ca-phosphate and struvite calculi, as well as the present possibilities for oral and local therapy, their advantages and drawbacks are discussed in the light of published evidence. In this context a clinical case of multiple injuries is reported in which practically complete chemolitholysis has been achieved by combined oral and local therapy. The rapid growth of the calculi and their alarming tendency to recurrence in case of inadequate treatment is emphasized. The therapeutic method used in this case is regarded as suitable for practical purposes.

  12. STOMATOLOGIC ASPECTS IN THERAPY OF LOCALLY DISTRIBUTED CANCER OF ORAL CAVITY MUCUS

    Directory of Open Access Journals (Sweden)

    G. G. Matyakin

    2013-01-01

    Full Text Available Aim of the investigation: to improve prophylaxis of dental complications during the therapy in the patients with locally distributed cancer of oral cavity mucus.Materials. Results of sanation of oral cavity in 305 patients with cancer of oral and pharyngeal area are analyzed.Results. The best results are noted in the patients given surgical sanation before chemo-radial therapy. The most number of complications is observed when teeth were extracted after chemical therapy in the period of radial therapy at summary focal dose above 20 Gy as well as in the late periods after radial therapy.Conclusion. A complex of preventive measures with using haemostatic sponge with canamycin in such patients decreases the number of complications and the terms of healing of alveoli of extracted teeth.

  13. Angiogenic and fibrinolytic factors in blood during the first half of pregnancy and adverse pregnancy outcomes.

    NARCIS (Netherlands)

    Coolman, M.; Timmermans, S.; Groot, C.J. de; Russcher, H.; Lindemans, J.; Hofman, A.; Geurts-Moespot, A.; Sweep, F.C.; Jaddoe, V.V.; Steegers, E.A.P.

    2012-01-01

    OBJECTIVE: To estimate whether the imbalance of angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and fibrinolytic factors (plasminogen activator inhibitor-2 [PAI-2]) might affect placentation in early pregnancy. METHODS: We studied the associations of maternal soluble

  14. Association among Fibrinolytic Proteins, Metabolic Syndrome Components, Insulin Secretion, and Resistance in Schoolchildren

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    Jin-Shuen Chen

    2015-01-01

    Full Text Available We investigated the role of urokinase plasminogen activator (uPA and its soluble receptors (suPAR and plasminogen activator inhibitor-1 (PAI-1 in metabolic syndrome (MetS components, insulin secretion, and resistance in schoolchildren. We enrolled 387 children, aged 10.3 ± 1.5 years, in Taipei. Anthropometry, fibrinolytic proteins, MetS components, insulin secretion, and resistance were measured. Subjects were divided into normal, overweight, and obese groups. Finally, the relationship between fibrinolytic proteins and metabolic syndrome in boys and girls was analyzed. In boys, PAI-1 was positively associated with body mass index (BMI percentile, hypertriglyceride, insulin secretion, and resistance. In girls, PAI-1 was positively associated with obesity, hypertriglyceridemia, and insulin secretion. In girls, uPA was positively associated with insulin secretion. suPAR was positively associated with high-sensitivity C-reactive protein in both boys and girls, and with BMI percentile and body fat in girls. The obese boys had higher suPAR and PAI-1 levels than the normal group. The obese girls had higher uPA, suPAR, and PAI-1 than the normal group. Boys and girls with MetS had higher PAI-1. Fibrinolytic proteins, especially PAI-1, are associated with MetS components and insulin secretion in children. Fibrinolytic proteins changes were more likely to occur in girls than in boys.

  15. A newly derived protein from Bacillus subtilis natto with both antithrombotic and fibrinolytic effects.

    Science.gov (United States)

    Omura, Kazunobu; Hitosugi, Masahito; Zhu, Xia; Ikeda, Masashi; Maeda, Hiroaki; Tokudome, Shogo

    2005-11-01

    Natto, steamed soybeans fermented by Bacillus subtilis natto, is a traditional Japanese food. We derived a purified protein layer, called NKCP as a trade mark, from B. subtilis natto fermentation. In the present study, we examined the fibrinolytic and antithrombotic effects of NKCP and identified its active component to clarify the fibrinolytic effect of NKCP observed in preliminary clinical trials previously. The active component of NKCP was identified as a 34-kilodalton protein designated bacillopeptidase F. NKCP showed direct degradation of artificial blood clot in saline. The protease activity, accounting for the fibrinolytic effect of NKCP, was examined with a chromogenic substrate for plasmin. Dose-dependent prolongations of both prothrombin time and active partial thromboplastin time were observed in rats with intra-duodenum administration of NKCP. Our in vitro and in vivo studies suggest that NKCP has both a fibrinolytic effect and an antithrombotic effect similar to heparin. Because NKCP is derived from food and has safety data demonstrated by previous animal experiments and preliminary clinical trials, NKCP is considered as safe for clinical use.

  16. cDNA cloning and expression of earthworm fibrinolytic enzyme component A

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Earthworm fibrinolytic enzyme component A (EFEa), a protein with dual fibrinolytic activity, is one of the major therapeutically important earthworm fibrinolytic enzyme components. The cDNA fragment encoded the mature protein was cloned from earthworm (Eisenia fetida) by the RT-PCR technique. The deduced amino acid sequence of the EFE component A shows high homology with some members of serine proteases trypsin family, and the amino acid residues constituting the active sites are conserved in the EFEa as compared with the other proteins of the trypsin family. The cDNA fragment was subcloned into the expression vector pQE31 and pMAL-c2X of E. coli. The resulting expression plasmids, pQE-efea and pMAL-efea, were used to transform the E. coli strain M15. Recombinant protein bands corresponding with calculated molecular weights were induced. The induced His6-EFEa fusion protein with pQE- efea was accumulated into inclusion body, while the induced MBP-EFEa fusion protein with pMAL-efea was soluble and showed fibrinolytic activities.

  17. The fibrinolytic system in the hemolytic uremic syndrome: In vivo and in vitro studies

    NARCIS (Netherlands)

    Kar, N.C.A.J. van de; Hinsbergh, V.W.M. van; Brommer, E.J.P.; Monnens, L.A.H.

    1994-01-01

    Fibrinolytic parameters and von Willebrand factor (vWF) antigen were measured in the plasma of 10 patients with hemolytic uremic syndrome (HUS). Samples were taken at presentation and again 2 wk later, before and after infusion of 1-desamino-8-arginine vasopressin. Compared with the plasma values of

  18. Evaluation of fibrinolytic and antioxidant effects of Allium elburzense bulb extracts

    Directory of Open Access Journals (Sweden)

    Leila Safaeian

    2017-04-01

    Full Text Available Objective: Allium elburzense is an endemic plant of the family Amaryllidaceae that grows wild in northern Iran with some nutritional and medicinal applications. The present study was aimed to investigate the fibrinolytic and antioxidant effects of A. elburzense bulb extracts. Materials and Methods: Hydroalcoholic, aqueous, chloroformic and butanolic extracts were evaluated in this research. In vitro antioxidant assays were performed using total phenolic, DPPH, and FRAP methods. In the in vivo analysis, animals receivedi.p. injection of A. elburzense hydroalcoholic extract for 21 days and hydroperoxides level, FRAP value, PT and aPTT were determined in serum samples. The fibrinolytic activity of different extracts was quantitatively evaluated by measurement of clot weight. Results: In vitro antioxidant assay showed that A. elburzense aqueous extract had the highest DPPH scavenging and the highest total antioxidant capacity. In the in vivo assay, A. elburzense hydroalcoholic extract reduced serum hydroperoxides level and increased serum total antioxidant capacity in rats.In vitro fibrinolytic assay revealed remarkable thrombolytic activity for this plant with the highest effect for the aqueous extract. However, coagulation parameters including PT and aPTT were not affected by administration of A. elburzense hydroalcoholic extract in rats. Conclusion: In conclusion, the results of this study revealed the potential antioxidant and fibrinolytic effects of A. elburzense bulbextracts. For developing novel thrombolytic agents, further investigations for isolation of bioactive constituents and finding the underlying mechanisms are suggested.

  19. Effect of low-dose aspirin during pregnancy on fibrinolytic variables before and after parturition

    NARCIS (Netherlands)

    H.A. Bremer (Henk); N. Rotmans (Nel); E.J.Ph. Brommer; H.C.S. Wallenburg (Henk)

    1995-01-01

    textabstractOBJECTIVE: We assessed the effects of a daily oral dose of 60 to 80 mg of aspirin from 12 weeks gestation until delivery on fibrinolytic variables before and after parturition. STUDY DESIGN: In a prospective controlled study labor was electively induced in 24 patients, eight receiving

  20. Resistance and barriers to local estrogen therapy in women with atrophic vaginitis.

    Science.gov (United States)

    Kingsberg, Sheryl A; Krychman, Michael L

    2013-06-01

    Vaginal atrophy results from a decrease in circulating estrogen and is experienced by approximately 50% of postmenopausal women. Its symptoms affect multiple dimensions of genitopelvic health, sexuality, and overall quality of life. Nonhormonal over-the-counter treatments may provide temporary symptom relief, but the condition is progressive, and hormonal treatment may be warranted. The study aims to review the literature and discuss the impact of atrophic vaginitis and various treatment options, including the resistance and barriers to the use of local estrogen therapy for atrophic vaginitis. This article also aims to provide a greater awareness of the condition and the difficulties in communicating effectively with patients, and to provide strategies to help healthcare professionals acquire effective communication skills to initiate a candid dialogue with patients who may be suffering in silence and may benefit from therapy. This review was based on peer-reviewed publications on the topic of atrophic vaginitis and local estrogen therapy identified from key word searches of PubMed, in addition to landmark studies/surveys and treatment guidelines/recommendations on menopause available in the literature and on the Internet. The main outcomes are the impact of atrophic vaginitis and the various treatment options, including the resistance and barriers to the use of local estrogen therapy. Minimally absorbed local vaginal estrogen therapy enables administration of estrogen doses much lower than systemic doses used for vasomotor symptoms. Local therapy is also the first-line pharmacologic treatment recommended by the North American Menopause and International Menopause Societies. Despite treatment options, the sensitive nature of the condition and embarrassment may prohibit or limit many women from openly discussing symptoms with healthcare professionals. Many are hesitant to initiate hormonal treatment because of safety concerns. Healthcare professionals should

  1. Role of mesenchymal stem cell-derived fibrinolytic factor in tissue regeneration and cancer progression.

    Science.gov (United States)

    Heissig, Beate; Dhahri, Douaa; Eiamboonsert, Salita; Salama, Yousef; Shimazu, Hiroshi; Munakata, Shinya; Hattori, Koichi

    2015-12-01

    Tissue regeneration during wound healing or cancer growth and progression depends on the establishment of a cellular microenvironment. Mesenchymal stem cells (MSC) are part of this cellular microenvironment, where they functionally modulate cell homing, angiogenesis, and immune modulation. MSC recruitment involves detachment of these cells from their niche, and finally MSC migration into their preferred niches; the wounded area, the tumor bed, and the BM, just to name a few. During this recruitment phase, focal proteolysis disrupts the extracellular matrix (ECM) architecture, breaks cell-matrix interactions with receptors, and integrins, and causes the release of bioactive fragments from ECM molecules. MSC produce a broad array of proteases, promoting remodeling of the surrounding ECM through proteolytic mechanisms. The fibrinolytic system, with its main player plasmin, plays a crucial role in cell migration, growth factor bioavailability, and the regulation of other protease systems during inflammation, tissue regeneration, and cancer. Key components of the fibrinolytic cascade, including the urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), are expressed in MSC. This review will introduce general functional properties of the fibrinolytic system, which go beyond its known function of fibrin clot dissolution (fibrinolysis). We will focus on the role of the fibrinolytic system for MSC biology, summarizing our current understanding of the role of the fibrinolytic system for MSC recruitment and the functional consequences for tissue regeneration and cancer. Aspects of MSC origin, maintenance, and the mechanisms by which these cells contribute to altered protease activity in the microenvironment under normal and pathological conditions will also be discussed.

  2. Production and Purification of Pharmaceutically Important Fibrinolytic Enzyme from Bacillus Species

    Directory of Open Access Journals (Sweden)

    Sharav A. Desai

    2015-11-01

    Full Text Available The medicinal and pharmaceutical importance of currently available thrombolytic agents like urokinase, t-PA, streptokinase, staphylokinase and others, demonstrated repeatedly since 1970s, however sometimes they cause undesirable side effects like bleeding and allergic responds. The present findings reports isolation, screening and identification of soil bacterium for production of fibrinolytic enzyme. Samples for the study were collected from different locations were first screened for proteolytic activity using skimmed milk agar plate and lastly fibrin plate method was used to evaluate fibrinolytic activity. The strain capable of producing fibrinolytic protein was identified as Bacillus Spp. Using both Bergery’s manual of systemic bacteriology and biochemical characterization simultaneously. Selected strain was than subjected to the process of fermentation using basal media for 5 days, 37°C and at 180rpm. Protein content and fibrinolytic activity were measured by Biuret method using bovine serum albumin as standard and fibrinolytic assay respectively. Three stage purification was done, that includes salting out with ammonium sulphate, followed by gel filtration chromatography and finally separated by RP-HPLC, proteins were eluted in peaks with a retention time of 2.092, 3.188, 5.178, 7.295, and 11.32 minutes. The fraction with retention time 7.295 minutes shows a maximum activity. The enzyme found to be having an optimum pH between 7.0 and 7.5. Enzyme is also stable at the optimum pH and found to lose its activity on higher side of acidity or alkalinity. It is more active at 40°C and is stable at 37°C to 43°C with slight modification in activity.

  3. Two Cases of Mastectomy after Paclitaxel + Bevacizumab Therapy for Locally Advanced Breast Cancer

    Directory of Open Access Journals (Sweden)

    Chika Shinoda

    2014-05-01

    Full Text Available Introduction: Locally advanced breast cancer (LABC deteriorates the quality of life (QOL of the affected patients. Combination chemotherapy or extended chemotherapy is considered to help to shrink local lesions. Case 1: A 71-year-old female with a history of tympanitis and cystitis with methicillin-resistant Staphylococcus aureus (MRSA visited our hospital. There was a tumor of 7 cm in diameter in her right breast with skin ulceration. Paclitaxel + bevacizumab therapy was started, and after five cycles of therapy, a mastectomy with axillary dissection was performed. Chemotherapy with anthracycline was avoided for fear of activating the MRSA. After the operation, the patient's wound opened. However, it naturally epithelialized. Case 2: A 41-year-old female visited our hospital due to a tumor of 8 cm in diameter in her right breast with skin ulceration. Four cycles of paclitaxel + bevacizumab therapy were started, and her tumor almost disappeared during the first cycle. Then, doxorubicin + cyclophosphamide therapy was performed for four cycles, and a mastectomy with axillary dissection was performed. Her postoperative course was good. Discussion: Chemotherapy with bevacizumab or extended chemotherapy is generally not considered to contribute to a survival improvement. However, such therapy contributes in increasing the response to chemotherapy, and should be considered for patients with LABC to shrink the local lesions and improve the QOL.

  4. Quality of local authority occupational therapy services: developing an instrument to measure the user's perspective.

    NARCIS (Netherlands)

    Calnan, S.; Sixma, H.J.; Calnan, M.W.; Groenewegen, P.P.

    2000-01-01

    The aims of this paper are threefold: (1) to describe the development of an instrument measuring quality of care from the specific perspective of the users of local authority occupational therapy services; (2) to present the results from a survey of users' views about the quality of services offered

  5. Quality of local authority occupational therapy services: developing an instrument to measure the user's perspective.

    NARCIS (Netherlands)

    Calnan, S.; Sixma, H.J.; Calnan, M.W.; Groenewegen, P.P.

    2000-01-01

    The aims of this paper are threefold: (1) to describe the development of an instrument measuring quality of care from the specific perspective of the users of local authority occupational therapy services; (2) to present the results from a survey of users' views about the quality of services offered

  6. User involvement in measuring service quality of local authority occupational therapy services: a new approach.

    NARCIS (Netherlands)

    Sixma, H.J.; Calnan, S.; Calnan, M.; Groenewegen, P.P.

    2001-01-01

    The aim of this paper is two-fold: (i) to describe the development of a new measuring instrument for quality of care from the perspective of the users of local authority Occupational Therapy (OT) services, and (ii) to evaluate the potential of the new instrument as a standardized approach for the

  7. [Hepon, promoter of local immunity in the complex therapy of dysfunctional microflora in bowel disorders].

    Science.gov (United States)

    Parfenov, A I; Ruchkina, I N

    2003-01-01

    The promoter of local immunity Heponum contributes to the restoration of eubiosis and normalization of showings of the immune status in patients with post-infection IBS. It is recommended to include Heponum in the complex therapy of chronic bowels diseases with the purpose of the restoration of normal microbiocenosis.

  8. Low-level laser therapy and vibration therapy for the treatment of localized adiposity and fibrous cellulite.

    Science.gov (United States)

    Savoia, Antonella; Landi, Simone; Vannini, Fulvio; Baldi, Alfonso

    2013-06-01

    In recent years, there has been an upsurge in the application of low-level laser therapy in various medical diseases. Additionally, vibration therapy is a new and effective measure to prevent muscular atrophy and osteoporosis, along with some general health-related beneficial effects of exercise on skeletal muscles such as improvement of endothelial function and an increased enzyme capacity of energy metabolism. The aim of this study was to evaluate the application of a 635 nm and 0.040 W exit power per multiple diode laser in combination with vibration therapy for the application of non-invasive reduction of circumference in patients with localized adiposity and cellulite. The study enrolled men and women (N = 33) aged 18-64 years with localized adiposity or fibrous cellulite. The evaluation parameters were: photographic evaluation, perimetric evaluation, blood tests, ecographic evaluation, histological evaluation, and subjective and objective tests. The results produced were statistically analyzed and resulted in a significant reduction of fat thickness when compared to the measurement prior to the treatment (P cellulite.

  9. Radiation therapy for breast cancer patients who undergo oncoplastic surgery: localization of the tumor bed for the local boost.

    Science.gov (United States)

    Pezner, Richard D; Tan, Mark C; Clancy, Sharon L; Chen, Yi-Jen; Joseph, Thomas; Vora, Nayana L

    2013-12-01

    Oncoplastic reconstructive surgery is performed in select patients with breast cancer to allow conservation treatment when the lumpectomy would be expected to have a poor cosmetic outcome. These techniques not only rearrange the breast tissue but may also shift the position of the tumor bed. The oncoplastic incision may have no relationship to the tumor bed. Although use of whole-breast radiation therapy (RT) is straightforward, difficulties in localization of the tumor bed for the local RT boost have not been investigated. A retrospective review was performed of 25 patients with 26 cancers who received RT after breast conservation surgery with oncoplastic reconstruction. Among 11 patients with a minimum of 4 surgical clips placed at tumor resection, 8 (73%) had the final tumor bed extend beyond the original breast quadrant or be completely relocated into a different region. In 3 (27%) cases, the clinical treatment volume was 2 to 3 separated regions within the breast. For breast cancer patients who have had oncoplastic surgery, the tumor bed is frequently more extensive and possibly relocated compared with original presentation. Placement of surgical clips after tumor resection and before oncoplastic reconstruction may be the most accurate method to localize the RT local boost field.

  10. Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sabolch, Aaron [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Else, Tobias [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Griffith, Kent A. [Center for Cancer Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Mchigan (United States); Ben-Josef, Edgar [Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Williams, Andrew [University of Michigan Medical School, Ann Arbor, Mchigan (United States); Miller, Barbra S. [Division of Endocrine Surgery, Department of General Surgery, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Worden, Francis [Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Hammer, Gary D. [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Jolly, Shruti, E-mail: shrutij@med.umich.edu [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States)

    2015-06-01

    Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

  11. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    DEFF Research Database (Denmark)

    Appelt, A. L.; Ploen, J.; Vogelius, I. R.

    2013-01-01

    of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect......Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we...... estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...

  12. Optimal management of prostate cancer with lethal biology--state-of-the-art local therapy.

    Science.gov (United States)

    Chapin, Brian F

    2015-01-01

    Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy. However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient's death. Patients with clinical features of "high-risk" prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy) are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT). Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes while others showing an advantage of surgery over RT. Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT) alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes. Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice. While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals. [

  13. Neoadjuvant therapy for localized prostate cancer: Examining mechanism of action and efficacy within the tumor

    Science.gov (United States)

    Lou, David Y.; Fong, Lawrence

    2015-01-01

    Objectives Efforts to improve the clinical outcome for patients with localized high-risk prostate cancer have led to the development of neoadjuvant systemic therapies. We review the different modalities of neoadjuvant therapies for localized prostate cancer and highlight emerging treatment approaches including immunotherapy and targeted therapy. Methods We performed a PubMed search of clinical trials evaluating preoperative systemic therapies for treating high-risk prostate cancer published after 2000, and those studies with the highest clinical relevance to current treatment approaches were selected for review. The database at clinicaltrials.gov was queried for neoadjuvant studies in high-risk prostate cancer, and those evaluating novel targeted therapies and immunotherapies are spotlighted here. Results Neoadjuvant chemotherapy has become standard of care for treating some malignancies, including breast and bladder cancers. In prostate cancer, preoperative hormonal therapy or chemotherapy has failed to demonstrate improvements in overall survival. Nevertheless, the emergence of novel treatment modalities such as targeted small molecules and immunotherapy has spawned neoadjuvant clinical trials that provide a unique vantage from which to study mechanism of action and biological potency. Tissue-based biomarkers are being developed to elucidate the biological efficacy of these treatments. With targeted therapy, these can include phospho-proteomic signatures of target pathway activation and deactivation. With immunotherapies, including sipuleucel-T and ipilimumab, recruitment of immune cells to the tumor microenvironment can also be used as robust markers of a biological effect. Such studies can provide insight not only into mechanism of action for these therapies but can also provide paths forward to improving clinical efficacy like with rationally designed combinations and dose selection. Conclusions The use of neoadjuvant androgen-deprivation therapy and

  14. Rectal cancer - local staging and imaging under neoadjuvant therapy; Rektumkarzinom - Lokales Staging und Bildgebung unter neoadjuvanter Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Karpitschka, M. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2012-06-15

    Rectal cancer restaging after neoadjuvant therapy is based on two principles: an anatomic definition of the tumor allowing surgical planning and prognostic stage grouping. Emerging data suggest that reassessment using a combination of different imaging modalities may help to provide valuable prognostic information before definitive surgery. Perfusion computed tomography (CT) may provide special information regarding tumor vascularity. Evaluation of therapy response, especially of the circumferential resection margin (CRM) is necessary for surgical planning. For local staging high-resolution and diffusion-weighted magnetic resonance imaging has proven to be of high diagnostic accuracy. The M status should be assessed using multidetector computed tomography (MDCT) according to response evaluation criteria in solid tumors (RECIST) while lymph node evaluation requires either magnetic resonance imaging or positron emission tomography/computed tomography scanning. (orig.) [German] Beim Rektumkarzinom ist das Restaging nach neoadjuvanter Therapie von zentraler Bedeutung. Einerseits kann anhand der aktuellen Tumorausdehnung das weitere chirurgische Vorgehen geplant, andererseits durch die radiologische Evaluation des Therapieansprechens eine prognostische Einschaetzung getroffen werden. Als bildgebende Modalitaeten stehen die Endosonographie, die CT bzw. PET/CT und die MRT zur Verfuegung. Die Perfusions-CT koennte in Zukunft wertvolle Informationen bzgl. des Therapieansprechens liefern, da hierdurch die Tumorvaskularitaet und ihre Veraenderungen unter Therapie dargestellt werden koennen. Die Evaluation des Therapieansprechens, insbesondere die Beurteilung des zirkumferenziellen Resektionsrandes (CRM) ist zur operativen Planung erforderlich. Die Bildgebung nach neoadjuvanter Therapie ist praeoperativer Standard in der Rektumchirurgie. Fuer die Beurteilung des lokalen Therapieansprechens (T-Status) hat sich die hochaufloesende Duennschicht-MRT bewaehrt, wohingegen der M

  15. Photodynamic therapy trials with lutetium texaphyrin (Lu-Tex) in patients with locally recurrent breast cancer

    Science.gov (United States)

    Renschler, Markus F.; Yuen, Alan R.; Panella, Timothy J.; Wieman, Thomas J.; Dougherty, Shona; Esserman, Laura; Panjehpour, Masoud; Taber, Scott W.; Fingar, Victor H.; Lowe, Elizabeth; Engel, Julie S.; Lum, Bert; Woodburn, Kathryn W.; Cheong, Wai-Fung; Miller, Richard A.

    1998-05-01

    Photodynamic therapy (PDT) of locally recurrent breast cancer has been limited to treatment of small lesions because of non- selective necrosis of adjacent normal tissues in the treatment field. Lutetium Texaphyrin (PCI-0123, Lu-Tex) is a photosensitizer with improved tumor localization that is activated by 732 nm light, which can penetrate through larger tumors. We have evaluated Lu-Tex in a Phase I trial and in an ongoing Phase II trial in women with locally recurrent breast cancer with large tumors who have failed radiation therapy. Patients received Lu-Tex intravenously by rapid infusion 3 hours before illumination of cutaneous or subcutaneous lesions. In Phase I, Lu-Tex doses were escalated from 0.6 to 7.2 mg/kg in 7 cohorts. Sixteen patients with locally recurrent breast cancer lesions were treated. Dose limiting toxicities above 5.5 mg/kg were pain in the treatment field during therapy, and dysesthesias in light exposed areas. No necrosis of normal tissues in the treated field was noticed. Responses were observed in 60% of evaluable patients [n equals 15, 27% complete remission (CR), 33% partial remission (PR)], with 63% of lesions responding (n equals 73: 45% CR, 18% PR). In Phase II, 25 patients have been studied to date, receiving two treatments ranging from 1.0 to 3.0 mg/kg at a 21 day interval. Treatment fields up to 480 cm2 in size were treated successfully and activity has been observed. Patients have experienced pain at the treatment site but no tissue necrosis. These studies demonstrate the feasibility of Lu-Tex PDT to large chest wall areas in women who have failed radiation therapy for the treatment of locally recurrent breast cancer. Treatment conditions are currently being optimized in the ongoing Phase II trials.

  16. Current and Emerging Systemic Therapy in Gastro-Esophageal Cancer "The Old and New Therapy for Metastatic Disease, The Role of Adjuvant and Neoadjuvant Therapy for Localized Disease".

    Science.gov (United States)

    Lim, Bora; Jiang, Yixing

    2015-01-01

    Cancers of esophagus and stomach are common malignant diseases worldwide, and they are associated with serious morbidity and high mortality rates. When diagnosed at an early stage, gastro-esophageal cancers are potentially curable. Neo-adjuvant or adjuvant therapies using both chemotherapy and radiation therapy have been shown to reduce the risk of local recurrence and distant metastasis. For advanced or metastatic tumors, systemic chemotherapy offers symptomatic palliation and moderate benefits in survival. With recent advances in anti-cancer therapeutics, progress has been made to improve treatment response and life expectancy in patients with advanced gastro-esophageal cancers. Furthermore, the clinical use of molecularly targeted agents in combination with cytotoxic chemotherapeutics is being evaluated in a number of ongoing clinical trials. In this article, we review currently used standard systemic therapies including recently evolving targeted therapies for metastatic gastro-esophageal cancers, as well as the proven role and the regimens that are used as neoadjuvant and adjuvant treatment in localized gastro-esophageal cancers.

  17. Progesterone - new therapy in mild carpal tunnel syndrome? Study design of a randomized clinical trial for local therapy

    Directory of Open Access Journals (Sweden)

    Ginanneschi Federica

    2010-04-01

    Full Text Available Abstract Background Local corticosteroid injection for carpal tunnel syndrome (CTS provides greater clinical improvement in symptoms one month after injection compared to placebo but significant symptom relief beyond one month has not been demonstrated and the relapse of symptoms is possible. Neuroprotection and myelin repair actions of the progesterone was demonstrated in vivo and in vitro study. We report the design of a randomized controlled trial for the local injection of cortisone versus progesterone in "mild" idiopathic CTS. Methods Sixty women with age between 18 and 60 years affected by "mild" idiopathic CTS, diagnosed on the basis of clinical and electrodiagnostic tests, will be enrolled in one centre. The clinical, electrophysiological and ultasonographic findings of the patients will be evaluate at baseline, 1, 6 and 12 months after injection. The major outcome of this study is to determine whether locally-injected progesterone may be more beneficial than cortisone in CTS at clinical levels, tested with symptoms severity self-administered Boston Questionnaire and with visual analogue pain scale. Secondary outcome measures are: duration of experimental therapy; improvement of electrodiagnostic and ultrasonographic anomalies at various follow-up; comparison of the beneficial and harmful effects of the cortisone versus progesterone. Conclusion We have designed a randomized controlled study to show the clinical effectiveness of local progesterone in the most frequent human focal peripheral mononeuropathy and to demonstrate the neuroprotective effects of the progesterone at the level of the peripheral nervous system in humans.

  18. Angiographic and clinical outcomes in elderly subjects treated with percutaneous coronary intervention following fibrinolytic administration for ST-elevation myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Ajay J. Kirtane; C. Michael Gibson; Adam H. Skolnick; Hilary Oman; Christopher Ruisi; Leida Perez; Nicole Kraimer; Dimitrios Karmpaliotis; Duane S. Pinto; Eugene Braunwald

    2005-01-01

    Background Prior studies have demonstrated that the achievement of faster coronary artery flow following reperfusion therapies is associated with improved outcomes among ST-elevation myocardial infarction (STEMI) patients. The association of patient age with angiographic characteristics of flow and perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) following the administration of fibrinolytic therapy has not been previously investigated. Objectives and Methods We examined the association between age (≥ 70 years or < 70years)and clinical and angiographic outcomes in 1472 STEMI patients who underwent rescue/adjunctive PCI following fibrinolytic therapy in 7 TIMI trials. We hypothesized that elderly patients would have slower post-PCI epicardial flow and worsened outcomes compared to younger patients. Results The 218 patients aged ≥ 70 years (14.8%) had more comorbidities than younger patients. Although these patients had significant angiographic improvement in TIMI frame counts and rates of TIMI Grade 3 flow following rescue/adjunctive PCI, elderly patients had higher (slower)post-PCI TIMI frame counts compared to the younger cohort (25 vs 22 frames, P = 0.039), and less often achieved post-PCI TIMI Grade 3 flow (80.1 vs 86.4%, P = 0.017). The association between age ( ≥70 years) and slower post-PCI flow was independent of gender, time to treatment, left anterior descending (LAD) lesion location, and pulse and blood pressure on admission. Elderly patients also had 4-fold higher mortality at 30 days (12.0 vs 2.7%,P = 0. 001 ). Conclusions This study suggests one possible mechanism underlying worsened outcomes among elderly STEMI patients insofar as advanced chronological age was associated with higher TIMI frame counts and less frequent TIMI Grade 3 flow after rescue/adjunctive PCI.

  19. Prehospital versus hospital fibrinolytic therapy using automated versus cardiologist electrocardiographic diagnosis of myocardial infarction: abortion of myocardial infarction and unjustified fibrinolytic therapy.

    NARCIS (Netherlands)

    Lamfers, E.J.P.; Schut, A.; Hertzberger, D.P.; Hooghoudt, T.E.H.; Stolwijk, P.W.J.; Boersma, E.; Simoons, M.L.; Verheugt, F.W.A.

    2004-01-01

    BACKGROUND: This study investigated the incidence of abortion of myocardial infarction and of unjustified fibrinolysis by using automated versus cardiologist-assisted diagnosis of acute ST-elevation myocardial infarction. The results of prehospital diagnosis and treatment (2 cities in the Netherland

  20. High dose level radiation therapy for local tumour control in esthesioneuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Guedea, F. [Universidad Autonoma de Barcelona (Spain); Limbergen, E. Van; Bogaert, W. Van Den [University Hospital, Leuven (Belgium). Dept. of Radiotherapy

    1994-12-31

    Esthesioneuroblastoma is an uncommon tumour of neural crest origin arising in the nasal cavity. This paper is a retrospective review of 7 patients with esthesioneuroblastoma treated at a single institution from May 1974 to July 1990. 5 patients were treated with radiation therapy alone and 2 patients were irradiated after surgical resection. No local or regional occurrence was observed in any patient at 6 months, or at 1, 3, 6, 11.5 and 12 years following treatment. One patient died of intercurrent disease 6 years after radiation therapy, 2 patients died of disease, 1 of distant metastasis at 6 months and the other patient of meningeal carcinomatosis and distant metastases 1 year after treatment. One patient is alive with distant metastases 1 year after treatment. None of the patients experienced significant complications of irradiation. High-dose irradiation (60 Gy or more) alone or in combination with resection is an effective local treatment modality for esthesioneuroblastoma. (author).

  1. The role of local estrogen therapy in the management of pelvic floor disorders.

    Science.gov (United States)

    Tzur, T; Yohai, D; Weintraub, A Y

    2016-04-01

    Pelvic floor disorders are common and bothersome problems that include a variety of conditions. These conditions greatly affect the performance of daily activities and social function such as work, traveling, physical exercise, sleep and sexual function. Aging is a well-known factor affecting the pelvic floor and lower urinary tract anatomy and function. It is clear that the pelvic organs and their surrounding muscular and connective tissue support are estrogen-responsive. Treatment of pelvic floor disorders requires significant health-care resources and their impact is likely to increase in the near future. This literature review aims to provide an overview of both research and clinical aspects of the pathophysiology of urogenital estrogen deficiency and the role of local estrogen therapy as part of the management strategy of different pelvic floor disorders. The safety and risk concerns regarding the use of local estrogen therapy are addressed as well.

  2. Molecular Cloning and Characterization of cDNA Encoding Fibrinolytic Enzyme-3 from Earthworm Eisenia foetida

    Institute of Scientific and Technical Information of China (English)

    Guo-Qing DONG; Xiao-Ling YUAN; Ya-Jun SHAN; Zhen-Hu ZHAO; Jia-Pei CHEN; Yu-Wen CONG

    2004-01-01

    The earthworm fibrinolytic enzyme-3 (EFE-3, GenBank accession No: AY438622), from the earthworm Eiseniafoetida, is a component of earthworm fibrinolytic enzymes. In this study, cDNA encoding the EFE-3 was cloned by RT-PCR. The eDNA contained an open reading frame of 741 nucleotides, which encoded a deduced protein of 247 amino acid residues, including signal sequences. EFE-3 showed a high degree of homology to earthworm (Lumbricus rebullus) proteases F-III-1, F-III-2, and bovine trypsin. The recombinant EFE-3 was expressed in E. coli as inclusion bodies, and the gene encoding the native form of EFE-3 was expressed in COS-7 cells in the medium. Both the refolding product of inclusion bodies and the secreted protease could dissolve the artificial fibrin plate.

  3. Polymorphic variation of genes in the fibrinolytic system and the risk of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Yaakov Bentov

    Full Text Available INTRODUCTION: The etiology of ovarian cancer is largely unknown. One hypothesis is that the inefficient removal of the blood clots and fibrin products which are deposited in the vicinity of the ovary by retrograde menstruation might be associated with an increased risk of ovarian cancer. Several single nucleotide polymorphisms within genes which comprise the fibrinolytic system have been shown to have functional effects on the rate of blood clot degradation. These were considered to be candidate genes in the present study. AIM: We studied the genotype distributions of 12 functional SNPs of four genes (tPA, uPA PAI1 and TAFI among 775 ovarian cancer cases and 889 controls. RESULTS: No significant associations were seen between any of the ten SNPs and the risk of ovarian cancer as a whole, or in any histologic subgroup. DISCUSSION: Germline known functional variants of genes in the fibrinolytic system are not associated with risk of ovarian cancer.

  4. Low Temperature Plasma: A Novel Focal Therapy for Localized Prostate Cancer?

    Directory of Open Access Journals (Sweden)

    Adam M. Hirst

    2014-01-01

    Full Text Available Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially novel approach for the treatment of early onset prostate cancer: low temperature plasma. The rapidly evolving plasma technology has the potential to deliver a wide range of promising medical applications via the delivery of plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect of low temperature plasma on cell lines and xenografts have demonstrated DNA damage leading to apoptosis and reduction in cell viability. However, there have been no studies on prostate cancer, which is an obvious candidate for this novel therapy. We present here the potential of low temperature plasma as a focal therapy for prostate cancer.

  5. Targeted therapy for localized non-small-cell lung cancer: a review

    Directory of Open Access Journals (Sweden)

    Paleiron N

    2016-07-01

    Full Text Available Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC, but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations is a major challenge. Keywords: targeted therapy, non-small-cell lung cancer, adjuvant, neo-adjuvant, surgery 

  6. Stereotactic body radiation therapy for the primary treatment of localized prostate cancer

    OpenAIRE

    Oliai, Caspian; Lanciano, Rachelle; Sprandio, Brian; Yang, Jun; Lamond, John; Arrigo, Steven; Good, Michael; Mooreville, Michael; Garber, Bruce; Brady, Luther W.

    2012-01-01

    Objective The low alpha/beta ratio of prostate cancer suggests that hypofractionated schemes of dose-escalated radiotherapy should be advantageous. We report our experience using stereotactic body radiation therapy (SBRT) for the primary treatment of prostate cancer to assess efficacy and toxicity. Methods From 2007 to 2010, 70 patients (51 % low risk, 31 % intermediate risk, and 17 % high risk) with localized prostate cancer were treated with SBRT using the CyberKnife system. One-third of pa...

  7. Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer

    OpenAIRE

    Cleary, James M.; Mamon, Harvey J.; Szymonifka, Jackie; Bueno, Raphael; Choi, Noah; Donahue, Dean M.; Fidias, Panos M.; Gaissert, Henning A.; Jaklitsch, Michael T.; Kulke, Matthew H.; Lynch, Thomas P.; Mentzer, Steven J.; Meyerhardt, Jeffrey A.; Swanson, Richard S.; Wain, John

    2016-01-01

    Background: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. Methods...

  8. Global fibrinolytic capacity in pediatric patients with sepsis and disseminated intravascular coagulation.

    Science.gov (United States)

    Bay, Ali; Oner, Ahmet Faik; Kose, Dogan; Dogan, Murat

    2006-10-01

    There are many complex pathophysiologic changes of the coagulation system in sepsis. The fibrinolytic system was evaluated in septic children using the global fibrinolytic capacity (GFC), a new technique reflecting the overall fibrinolytic activity. The study consisted of 24 children with sepsis, 36 children with sepsis plus disseminated intravascular coagulation (DIC), and 20 healthy age-matched control individuals. Compared with controls, 86% of sepsis patients and 87% of sepsis plus DIC patients had decreased GFC levels. Between the sepsis plus DIC and sepsis groups there was no significant difference in terms of GFC levels. While 19 patients (52.7%) died in the sepsis plus DIC group, only three patients (12.5%) died in the sepsis group. When survivors and nonsurvivors were compared in terms of coagulation tests, there were significant differences for protein C, antithrombin, platelet, fibrinogen, aspartate aminotransferase, alanine aminotransferase, prothrombin time, and white blood cell values. In conclusion, the level of GFC reduced in most of the pediatric sepsis patients but no difference was observed between patients with sepsis and patients with sepsis plus DIC. While inhibition of fibrinolysis is an important finding in sepsis, the mortality is mainly associated with the presence of end-organ damage and the status of coagulation parameters.

  9. A Fibrinolytic Enzyme Produced by Bacillus subtilis Using Chickpea (Cicer arietinum L. as Substrate

    Directory of Open Access Journals (Sweden)

    Ping Xiao

    2014-12-01

    Full Text Available A Fibrinolytic Enzyme (BSFE was isolated from fermented chickpeas using Bacillus subtilis. BSFE was purified with ammonium sulfate precipitation, ion exchange and gel filtration chromatography. The fibrin (ogen olytic activity of BSFE was investigated by means of fibrinolysis plate and hydrolysis of fibrinogen. Through these steps, the purity of the enzyme increased with 74.60-fold with 6.88% recovery activity. The molecular weight of the BSFE was estimated to be 30 kDa by SDS-PAGE. The optimum pH, optimum temperature, pH stability and thermal stability of BSFE were measured, respectively as 8.0, 55°C, 6.0-8.0 and less than 45°C. The activity was inhibited by serine protease inhibitor PMSF as well as metalloprotease inhibitor EDTA, indicating that the BSFE is a serine metalloprotease. In fibrin plate assay, BSFE showed more stronger fibrinolytic activity than that of nattokinase and it specifically hydrolyzed Aα and Bβ chains followed by γ chain of fibrinogen. Therefore, this study provided a method and it for the preparation of multifunctional food of chickpeas which has strong fibrinolytic activity.

  10. Purification and Characterisation of a Fibrinolytic Enzyme from Rhizopus micro sporus var. tuberosus

    Directory of Open Access Journals (Sweden)

    Shuli Zhang

    2015-01-01

    Full Text Available Extracellular fibrinolytic enzyme from Rhizopus microsporus var. tuberosus was purified and characterised. The microorganism was isolated in a distillery from daqu, a fermentative agent used in the production of Chinese liquor and vinegar at diff erent temperatures. The fibrinolytic enzyme was partially purifi ed by ammonium sulphate precipitation, dialysis, DEAE Sepharose® Fast Flow ion exchange chromatography and Sephadex G-75 gel filtration chromatography. The molecular mass of the fi brinolytic enzyme was estimated to be 24.5 kDa by SDS-PAGE. The purified enzyme showed optimal activity at pH=7.0 and 37 °C by fibrin plate method. It showed stronger resistance to the inhibition by trypsin and was stable at 37 °C retaining 96.1 % residual activity aft er 4 h of incubation. The fibrinolytic activity of the enzyme was enhanced by Na+, Ca2+, Mg2+ and Mn2+. Conversely, Zn2+ and Cu2+ partly inhibited enzymatic activity. Using fibrin plate method, we found that the enzyme not only degrades fibrin directly, but also activates plasminogen into plasmin to degrade fibrin. The results indicate that the pure enzyme has a potential in dissolving blood clot, and the possibility for application in the treatment of thrombosis.

  11. The fibrinolytic system: A new target for treatment of depression with psychedelics.

    Science.gov (United States)

    Idell, R D; Florova, G; Komissarov, A A; Shetty, S; Girard, R B S; Idell, S

    2017-03-01

    Current understanding of the neurobiology of depression has grown over the past few years beyond the traditional monoamine theory of depression to include chronic stress, inflammation and disrupted synaptic plasticity. Tissue plasminogen activator (tPA) is a key factor that not only promotes fibrinolysis via the activation of plasminogen, but also contributes to regulation of synaptic plasticity and neurogenesis through plasmin-mediated activation of a probrain derived neurotrophic factor (BDNF) to mature BDNF. ProBDNF activation could potentially be supressed by competition with fibrin for plasmin and tPA. High affinity binding of plasmin and tPA to fibrin could result in a decrease of proBDNF activation during brain inflammation leading to fibrosis further perpetuating depressed mood. There is a paucity of data explaining the possible role of the fibrinolytic system or aberrant extravascular fibrin deposition in depression. We propose that within the brain, an imbalance between tPA and urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) and neuroserpin favors the inhibitors, resulting in changes in neurogenesis, synaptic plasticity, and neuroinflammation that result in depressive behavior. Our hypothesis is that peripheral inflammation mediates neuroinflammation, and that cytokines such as tumor necrosis factor alpha (TNF-α) can inhibit the fibrinolytic system by up- regulating PAI-1 and potentially neuroserpin. We propose that the decrement of the activity of tPA and uPA occurs with downregulation of uPA in part involving the binding and clearance from the surface of neural cells of uPA/PAI-1 complexes by the urokinase receptor uPAR. We infer that current antidepressants and ketamine mitigate depressive symptoms by restoring the balance of the fibrinolytic system with increased activity of tPA and uPA with down-regulated intracerebral expression of their inhibitors. We lastly hypothesize that psychedelic 5-ht2a receptor agonists

  12. Stereotactic Ablative Radiation Therapy as First Local Therapy for Lung Oligometastases From Colorectal Cancer: A Single-Institution Cohort Study

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Badellino, Serena [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Ceccarelli, Manuela [Cancer Epidemiology and CPO Piemonte, Città della Salute e della Scienza, Torino (Italy); Guarneri, Alessia [Radiation Oncology, Città della Salute e della Scienza, Torino (Italy); Franco, Pierfrancesco [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Monagheddu, Chiara [Cancer Epidemiology and CPO Piemonte, Città della Salute e della Scienza, Torino (Italy); Spadi, Rosella [Medical Oncology, Colorectal Cancer Unit, Città della Salute e della Scienza, Torino (Italy); Ragona, Riccardo [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Racca, Patrizia [Medical Oncology, Colorectal Cancer Unit, Città della Salute e della Scienza, Torino (Italy); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy)

    2015-03-01

    Purpose: To estimate stereotactic ablative radiation therapy (SABR) efficacy and its potential role as an alternative to surgery for the treatment of lung metastases from colorectal cancer. Methods and Materials: Forty consecutive patients who received SABR as first local therapy at the time of lung progression were included, from 2004 to 2014. The primary study endpoint was overall survival. Secondary endpoints were progression-free survival and safety. Results: A single nodule was treated in 26 patients (65%), 2 nodules in 10 patients (25%), 3 in 3 patients (7.5%), and 4 in 1 patient (2.5%), for a total of 59 lesions. The median delivered biological effective dose was 96 Gy, in 1 to 8 daily fractions. Median follow-up time was 20 months (range, 3-72 months). Overall survival rates at 1, 2, and 5 years were, respectively, 84%, 73%, and 39%, with 14 patients (35%) dead. Median overall survival was 46 months. Progression occurred in 25 patients (62.5%), at a median interval of 8 months; failure at SABR site was observed in 3 patients (7.5%). Progression-free survival rates were 49% and 27% at 1 and 2 years, respectively. Discussion: The results of this retrospective exploratory analysis suggest safety and efficacy of SABR in patients affected with colorectal cancer lung oligometastases and urge inclusion of SABR in prospective clinical trials.

  13. DEGRO practical guidelines for radiotherapy of breast cancer V. Therapy for locally advanced and inflammatory breast cancer, as well as local therapy in cases with synchronous distant metastases

    Energy Technology Data Exchange (ETDEWEB)

    Budach, Wilfried; Matuschek, Christiane; Boelke, Edwin [University Hospital, Heinrich-Heine-University Duesseldorf, Klinik fuer Strahlentherapie und Radioonkologie, Duesseldorf (Germany); Dunst, Juergen [University Hospital Schleswig-Holstein, Luebeck (Germany); Feyer, Petra [Vivantes Hospital Neukoelln, Berlin (Germany); Fietkau, Rainer; Sauer, Rolf [University Hospital Erlangen, Erlangen (Germany); Harms, Wolfgang [St. Clara Hospital, Basel (Switzerland); Piroth, Marc D. [Helios Hospital, Wuppertal (Germany); Sautter-Bihl, Marie-Luise [Municipal Hospital, Karlsruhe (Germany); Sedlmayer, Felix [Paracelsus Medical University Hospital, Salzburg (Austria); Wenz, Frederick [Universitaetsmedizin Mannheim, Mannheim (Germany); Haase, Wulf; Souchon, Rainer; Collaboration: Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)

    2015-08-15

    The purpose of this work is to give practical guidelines for radiotherapy of locally advanced, inflammatory and metastatic breast cancer at first presentation. A comprehensive survey of the literature using the search phrases ''locally advanced breast cancer'', ''inflammatory breast cancer'', ''breast cancer and synchronous metastases'', ''de novo stage IV and breast cancer'', and ''metastatic breast cancer'' and ''at first presentation'' restricted to ''clinical trials'', ''randomized trials'', ''meta-analysis'', ''systematic review'', and ''guideline'' was performed and supplemented by using references of the respective publications. Based on the German interdisciplinary S3 guidelines, updated in 2012, this publication addresses indications, sequence to other therapies, target volumes, dose, and fractionation of radiotherapy. International and national guidelines are in agreement that locally advanced, at least if regarded primarily unresectable and inflammatory breast cancer should receive neoadjuvant systemic therapy first, followed by surgery and radiotherapy. If surgery is not amenable after systemic therapy, radiotherapy is the treatment of choice followed by surgery, if possible. Surgery and radiotherapy should be administered independent of response to neoadjuvant systemic treatment. In patients with a de novo diagnosis of breast cancer with synchronous distant metastases, surgery and radiotherapy result in considerably better locoregional tumor control. An improvement in survival has not been consistently proven, but may exist in subgroups of patients. Radiotherapy is an important part in the treatment of locally advanced and inflammatory breast cancer that should be given to all patients regardless to the intensity and effect of

  14. Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

    Science.gov (United States)

    Distler, Oliver; Cozzio, Antonio

    2016-01-01

    Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

  15. Delayed postoperative radiation therapy in local control of squamous cell carcinoma of the tongue and floor of the mouth

    Energy Technology Data Exchange (ETDEWEB)

    Amar, Ali; Chedid, Helma Maria; Curioni, Otavio Alberto; Rapoport, Abrao, E-mail: arapoport@uol.com.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil); Dedivitis, Rogerio Aparecido; Cernea, Claudio Roberto; Brandao, Lenine Garcia [Hospital Heliopolis, Sao aulo, SP (Brazil)

    2014-10-15

    Objective: to evaluate the effect of time between surgery and postoperative radiation therapy on local recurrence of squamous cell carcinoma of the tongue and floor of the mouth. Methods: a total of 154 patients treated between 1996 and 2007 were selected considering local recurrence rate and time of the adjuvant radiotherapy. Results: local recurrence was diagnosed in 54 (35%) patients. Radiation therapy reduced the rate of local recurrences, although with no statistical significance. The time between surgery and initiation of postoperative radiotherapy did not significantly influence the risk of local recurrence in patients referred to adjuvant treatment (p=0.49). Conclusion: in the presence of risk factors for local recurrence, a short delay in starting the adjuvant radiation therapy does not contraindicate its performance. (author)

  16. Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

    Directory of Open Access Journals (Sweden)

    Lima Carmen SP

    2011-03-01

    Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

  17. Can the combination of localized "proliferative therapy" with "minor ozonated autohemotherapy" restore the natural healing process?

    Science.gov (United States)

    Gracer, R I; Bocci, V

    2005-01-01

    Regenerative injection therapy (RIT), also known as proliferative therapy, has been used for over 30 years in the USA in patients with spinal and peripheral joint and ligamentous pathologies. It involves the injection of mildly irritating medications onto ligaments and tendons, most commonly at origins and insertions. These injections cause a mild inflammatory response which "turns on" the normal healing process and results in the regeneration of these structures. At the same time they strengthen and become less sensitive to pain through a combination of neurolysis of small nerve fibers (C-fibers) and increased stability of the underlying structures. Oxygen/ozone therapy is a well established complementary therapy practiced in many European countries. The ozone dissolves in body fluids and immediately reacts with biomolecules generating messengers responsible for biological and therapeutic activities. This results in an anti inflammatory response, which also results in a similar trophic reaction to that of RIT. It is logical to expect that combining these two modalities would result in enhanced healing and therefore improved clinical outcomes. Oxygen/ozone therapy, accomplished by autohemotherapy (AHT), is performed by either administering ozonated blood intravenously (Major AHT) or via intramuscular route (Minor AHT). These procedures result in stimulation of the immune and healing systems. Our concept is that the local injection of this activated blood injected directly to the ligamentous areas that are also being treated with RIT will act as a direct stimulation to the healing process. In addition, combining this with intravenous major AHT should stimulate the immune system to augment and support this process. RIT and oxygen/ozone therapy have been extensively studied separately. We propose a study of lumbosacral ligamentous pain to explore this therapeutic combination. We hope that this paper will stimulate general interest in this area of medicine and result

  18. Localized therapy for male breast cancer: functional advantages with comparable outcomes using breast conservation.

    Science.gov (United States)

    Fogh, Shannon; Kachnic, Lisa A; Goldberg, Saveli I; Taghian, Alphonse G; Powell, Simon N; Hirsch, Ariel E

    2013-10-01

    Male breast cancer (MBC) accounts for approximately 1% of all breast cancers. Given the rarity of this disease, treatment of MBC generally follows the same principles as treatment of female breast cancer. However, the traditional surgical approach for MBC is modified radical mastectomy (MRM) or total simple mastectomy (TSM) instead of breast conservation surgery (BCS). The purpose of this study was to examine the feasibility of BCS as an alternative to mastectomy for MBC with respect to musculoskeletal functionality and treatment outcome. A retrospective analysis was undertaken of all male patients with breast cancer who presented to Massachusetts General Hospital or Boston Medical Center for localized therapy from 1990 to 2003. Musculoskeletal functionality (tissue fibrosis, arm edema, and range of motion) and treatment outcome (local-regional control, disease-free survival, and overall survival) were evaluated. Functional/cosmetic outcomes were assessed by multidisciplinary review of patient follow-up visits and were scored as either "good-excellent" or "fair-poor" to account for subjectivity between different clinicians. Forty-two patients in total were identified to undergo localized treatment. Thirty patients (71%) received MRM, 4 (10%) had TSM, and 8 (19%) underwent BCS. Actuarial overall 1-year fair-poor documented tissue fibrosis, arm edema, and decreased range of motion rates were 13%, 23%, and 27% for patients receiving MRM; 25%, 0%, and 50% for patients who underwent TSM; and 13%, 0%, and 0% for those undergoing BCS, respectively. Overall survival and disease-free survival were not statistically different between the groups. These data suggest that breast conservation therapy may be considered a reasonable local treatment option for male patients presenting with breast cancer because it may offer functional advantages over mastectomy with comparable rates of local control and disease-free survival and overall survival. Copyright © 2013 Elsevier Inc. All

  19. Current trends in local antibacterial therapy of periprosthetic infection and osteomyelitis

    Directory of Open Access Journals (Sweden)

    S. A. Bozhkova

    2015-01-01

    Full Text Available The rational use of antibiotics in the treatment of orthopedic infection still presents a significant problem. Local antibiotic delivery systems enable to achieve effective concentrations of drugs in the focus of bone infection without the development of toxicity. It is the important accompaniment to systemic antibiotics in the treatment of periprosthetic infection and osteomyelitis. The data collected through the PubMed and eLIBRARY databases (http://www.ncbi.nlm. nih.gov/pubmed, 1995-2015; http://elibrary.ru, 2005-2015 years present the information about bone substitutes used for local antibiotic therapy in scientific investigations and in clinical practice. The information is submitted in accordance with the groups of materials: cements based on polymethylmethacrylate, bone grafts, demineralized bone matrix, bioceramics, natural and synthetic polymers, combined antibiotic delivery systems. The majority of these materials have only been studied experimentally and only a limited range of them is registered for use in clinical practice. Informing orthopedic surgeons about current methods of local antibiotic use is the key to the development of a modern integrated approach to the therapy of infectious complications after orthopedic surgery.

  20. Local antibiotic therapy strategies in orthopaedic trauma: Practical tips and tricks and review of the literature.

    Science.gov (United States)

    Hake, Mark E; Young, Heather; Hak, David J; Stahel, Philip F; Hammerberg, E Mark; Mauffrey, Cyril

    2015-08-01

    The use of local antibiotics for the prevention of infection in the setting of open fractures and as part of the treatment of osteomyelitis is well established. Antibiotics are most commonly incorporated into polymethylmethacrylate (PMMA) cement, which can then be formed into beads, moulded to fit a bone defect or used to coat a guide wire or IM nail. Newer delivery vehicles and techniques are being evaluated to improve upon these methods. Many factors influence how local antibiotics are applied. Treatment strategies are challenging to standardise due to the variability of clinical presentations. The presence of hardware, upper versus lower extremity, healed versus non-healed fracture and quality of soft tissues overlying the affected bone, as well as patients' comorbidities all need to be considered. Despite the accepted use of local antibiotic therapy in orthopaedic trauma, high-quality evidence regarding the use of local antibiotics is lacking. Indications, techniques, dosages, types of antibiotics, elution properties and pharmacokinetics are poorly defined in the clinical setting. The purpose of our manuscript is to review current strategies and provide practical tips for local application of antibiotics in orthopaedic trauma. We focus on delivery vehicles, types of antibiotics, dosage recommendations when mixed with PMMA and indications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The use of magnetic nanoparticles in thermal therapy monitoring and screening: Localization and imaging (invited).

    Science.gov (United States)

    Weaver, John B

    2012-04-01

    Magnetic nanoparticles have many diagnostic and therapeutic applications. A method termed magnetic spectroscopy of nanoparticle Brownian motion (MSB) was developed to interrogate in vivo the microscopic environment surrounding magnetic nanoparticles. We can monitor several effects that are important in thermal therapy and screening including temperature measurement and the bound state distribution. Here we report on simulations of nanoparticle localization. Measuring the spatial distribution of nanoparticles would allow us to identify ovarian cancer much earlier when it is still curable or monitor thermal therapies more accurately. We demonstrate that with well-designed equipment superior signal to noise ratio (SNR) can be achieved using only two harmonics rather than using all the harmonics containing signal. Alternatively, smaller magnetic field amplitudes can be used to achieve the same SNR. The SNR is improved using fewer harmonics because the noise is limited.

  2. Evolving lessons on nanomaterial-coated viral vectors for local and systemic gene therapy.

    Science.gov (United States)

    Kasala, Dayananda; Yoon, A-Rum; Hong, Jinwoo; Kim, Sung Wan; Yun, Chae-Ok

    2016-07-01

    Viral vectors are promising gene carriers for cancer therapy. However, virus-mediated gene therapies have demonstrated insufficient therapeutic efficacy in clinical trials due to rapid dissemination to nontarget tissues and to the immunogenicity of viral vectors, resulting in poor retention at the disease locus and induction of adverse inflammatory responses in patients. Further, the limited tropism of viral vectors prevents efficient gene delivery to target tissues. In this regard, modification of the viral surface with nanomaterials is a promising strategy to augment vector accumulation at the target tissue, circumvent the host immune response, and avoid nonspecific interactions with the reticuloendothelial system or serum complement. In the present review, we discuss various chemical modification strategies to enhance the therapeutic efficacy of viral vectors delivered either locally or systemically. We conclude by highlighting the salient features of various nanomaterial-coated viral vectors and their prospects and directions for future research.

  3. Focal therapy as primary treatment for localized prostate cancer: definition, needs and future.

    Science.gov (United States)

    Ouzzane, Adil; Betrouni, Nacim; Valerio, Massimo; Rastinehad, Ardeshir; Colin, Pierre; Ploussard, Guillaume

    2017-04-01

    Focal therapy (FT) may offer a promising treatment option in the field of low to intermediate risk localized prostate cancer. The aim of this concept is to combine minimal morbidity with cancer control as well as maintain the possibility of retreatment. Recent advances in MRI and targeted biopsy has improved the diagnostic pathway of prostate cancer and increased the interest in FT. However, before implementation of FT in routine clinical practice, several challenges are still to overcome including patient selection, treatment planning, post-therapy monitoring and definition of oncologic outcome surrogates. In this article, relevant questions regarding the key steps of FT are critically discussed and the main available energy modalities are analyzed taking into account their advantages and unmet needs.

  4. Outcomes for Spine Stereotactic Body Radiation Therapy and an Analysis of Predictors of Local Recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Bishop, Andrew J.; Tao, Randa [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rebueno, Neal C. [Department of Radiation Dosimetry, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Christensen, Eva N.; Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Xin A. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Amini, Behrang [Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tannir, Nizar M. [Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tatsui, Claudio E.; Rhines, Laurence D. [Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Li, Jing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Eric L. [Department of Radiation Oncology, USC Norris Cancer Hospital, Keck School of Medicine of USC, Los Angeles, California (United States); Brown, Paul D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ghia, Amol J., E-mail: ajghia@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-08-01

    Purpose: To investigate local control, survival outcomes, and predictors of local relapse for patients treated with spine stereotactic body radiation therapy. Methods and Materials: We reviewed the records of 332 spinal metastases consecutively treated with stereotactic body radiation therapy between 2002 and 2012. The median follow-up for all living patients was 33 months (range, 0-111 months). Endpoints were overall survival and local control (LC); recurrences were classified as either in-field or marginal. Results: The 1-year actuarial LC and overall survival rates were 88% and 64%, respectively. Patients with local relapses had poorer dosimetric coverage of the gross tumor volume (GTV) compared with patients without recurrence (minimum dose [Dmin] biologically equivalent dose [BED] 23.9 vs 35.1 Gy, P<.001; D98 BED 41.8 vs 48.1 Gy, P=.001; D95 BED 47.2 vs 50.5 Gy, P=.004). Furthermore, patients with marginal recurrences had poorer prescription coverage of the GTV (86% vs 93%, P=.01) compared with those with in-field recurrences, potentially because of more upfront spinal canal disease (78% vs 24%, P=.001). Using a Cox regression univariate analysis, patients with a GTV BED Dmin ≥33.4 Gy (median dose) (equivalent to 14 Gy in 1 fraction) had a significantly higher 1-year LC rate (94% vs 80%, P=.001) compared with patients with a lower GTV BED Dmin; this factor was the only significant variable on multivariate Cox analysis associated with LC (P=.001, hazard ratio 0.29, 95% confidence interval 0.14-0.60) and also was the only variable significant in a separate competing risk multivariate model (P=.001, hazard ratio 0.30, 95% confidence interval 0.15-0.62). Conclusions: Stereotactic body radiation therapy offers durable control for spinal metastases, but there is a subset of patients that recur locally. Patients with local relapse had significantly poorer tumor coverage, which was likely attributable to treatment planning directives that prioritized the

  5. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarty, Twisha; Crane, Christopher H. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mansfield, Paul F. [Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Briere, Tina M.; Beddar, A. Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  6. Isolation and identification of a novel fibrinolytic Bacillus tequilensis CWD-67 from dumping soils enriched with poultry wastes.

    Science.gov (United States)

    Velusamy, Palaniyandi; Pachaiappan, Raman; Christopher, Meera; Vaseeharan, Baskaralingam; Anbu, Periasamy; So, Jae-Seong

    2015-01-01

    A newly isolated strain, CWD-67, which exhibited high fibrinolytic activity, was screened from dumping soils enriched with poultry wastes. The strain was identified as Bacillus tequilensis (KF897935) by 16Sr RNA gene sequence analysis and biochemical characterization. A fibrinolytic enzyme was purified to homogeneity from the culture supernatant using ammonium sulfate precipitation, membrane concentration, dialysis, ion-exchange, and gel filtration chromatography. SDS-PAGE analysis showed that the purified enzyme was a monomeric protein with an apparent molecular weight of 22 kDa, which is the lowest among Bacillus fibrinolytic enzymes reported to date. The purified enzyme was confirmed to have fibrinolytic activity by a fibrin zymogram. The optimal pH and temperature values of the enzyme were 8.0 and 45 °C, respectively. The enzyme was completely inhibited by PMSF and significantly inhibited by EDTA, TPCK, Co(2+), Zn(2+), and Cu(2+), suggesting a chymotrypsin-like serine metalloprotease. In vitro assays revealed that the purified enzyme could catalyze fibrin lysis effectively, indicating that this enzyme could be a useful fibrinolytic agent.

  7. Radiation or chemoradiation: initial utility study of selected therapy for local advanced stadium cervical cancer

    Science.gov (United States)

    Pramitasari, D. A.; Gondhowiardjo, S.; Nuranna, L.

    2017-08-01

    This study aimed to compare radiation only or chemo radiation treatment of local advanced cervical cancers by examining the initial response of tumors and acute side effects. An initial assessment employed value based medicine (VBM) by obtaining utility values for both types of therapy. The incidences of acute lower gastrointestinal, genitourinary, and hematology side effects in patients undergoing chemoradiation did not differ significantly from those undergoing radiation alone. Utility values for patients who underwent radiation alone were higher compared to those who underwent chemoradiation. It was concluded that the complete response of patients who underwent chemoradiation did not differ significantly from those who underwent radiation alone.

  8. 77 FR 24717 - Scientific Information Request on Local Therapies for the Treatment of Stage I Non-Small Cell...

    Science.gov (United States)

    2012-04-25

    ... Therapies for the Treatment of Stage I Non-Small Cell Lung Cancer and Endobronchial Obstruction Due to... for the Treatment of Stage I Non-Small Cell Lung Cancer and Endobronchial Obstruction Due to Advanced... effectiveness review of the evidence for local therapies for the treatment of stage I non-small cell lung...

  9. Doing It Collaboratively! Addressing the Dilemmas of Designing Quantitative Effect Studies on Narrative Family Therapy in a Local Clinical Context

    DEFF Research Database (Denmark)

    Ejbye-Ernst, Ditte; Jørring, Nina Tejs

    2017-01-01

    in a local clinical context. The article offers a detailed case description of implementing psychometric effect measurements on narrative family therapy and of creating a shared collaborative stance for researchers using quantitative effect measurements and clinicians using narrative therapy. Our findings...

  10. Intersections between Music Education and Music Therapy: Education Reform, Arts Education, Exceptionality, and Policy at the Local Level

    Science.gov (United States)

    Salvador, Karen; Pasiali, Varvara

    2017-01-01

    In this article, a music teacher educator and a music therapy clinician and educator discuss special education policy and arts instruction at the district level. To illustrate the gulf between federal and local policies with regard to exceptional learners and arts instruction, we examine the intersections of music therapy and music education with…

  11. Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program

    DEFF Research Database (Denmark)

    See, William A; Wirth, Manfred P; McLeod, David G;

    2002-01-01

    We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer.......We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer....

  12. Modelling combined chemotherapy and particle therapy for locally advanced pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Marco eDurante

    2015-07-01

    Full Text Available Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond. Combined radiochemotherapy protocols using gemcitabine and hypofractionated X-rays are ongoing in several clinical trials. Recent results indicate that charged particle therapy substantially increases local control of resectable and unresectable pancreas cancer, as predicted from previous radiobiology studies considering the high tumour hypoxia. Combination with chemotherapy improves the overall survival. We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose. We show that chemoradiotherapy with protons or carbon ions results in 1-year overall survival significantly higher than those obtained with other treatment schedules. Further hypofractionation using charged particles may result in improved local control and survival. A comparative clinical trial using the standard X-ray scheme vs. the best current standard with carbon ions is crucial and may open new opportunities for this deadly disease.

  13. Intensity-Modulated Radiation Therapy in the Salvage of Locally Recurrent Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Qiu Sufang [Department of Radiation Oncology, Cancer Hospital of Fujian Medical University, Fuzhou, Fujian (China); Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore (Singapore); Lin Shaojun [Department of Radiation Oncology, Cancer Hospital of Fujian Medical University, Fuzhou, Fujian (China); Tham, Ivan W.K. [Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore (Singapore); Pan Jianji; Lu Jun [Department of Radiation Oncology, Cancer Hospital of Fujian Medical University, Fuzhou, Fujian (China); Lu, Jiade J., E-mail: mdcljj@nus.edu.sg [Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore (Singapore)

    2012-06-01

    Purpose: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. Methods and Materials: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. Results: The median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. Conclusion: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

  14. Late results of catheter-directed recombinant tissue plasminogen activator fibrinolytic therapy of iliofemoral deep venous thrombosis Resultados de longo prazo do tratamento fibrinolítico da trombose venosa iliacofemoral por infusão seletiva do ativador de plasminogênio tissular recombinante em baixas doses

    Directory of Open Access Journals (Sweden)

    Ivan Benaduce Casella

    2007-02-01

    Full Text Available PURPOSE: To evaluate the efficacy of catheter-directed low-dose recombinant tissue-type plasminogen activator infusion in the treatment of iliofemoral deep venous thrombosis and prevention of post-thrombotic syndrome. METHOD: Eighteen patients (out of 260 evaluated with acute iliofemoral deep venous thrombosis and no previous evidence of venous insufficiency were prospectively selected for thrombolytic therapy. Catheter-directed low-dose recombinant tissue-type plasminogen activator (1 mg/h was infused into the thrombotic segments. RESULTS: Effective fibrinolysis was achieved in 14 of 18 cases, with correlation between effective fibrinolysis and major/complete resolution of acute signs and symptoms (P OBJETIVOS: Avaliar a eficácia da infusão seletiva por cateter do ativador de plasminogênio tecidual recombinante em baixas doses no tratamento da trombose venosa iliacofemoral e na prevenção da síndrome pós-trombótica. MÉTODO: Dezoito pacientes (de 260 avaliados portadores de trombose venosa profunda iliacofemoral sem evidência prévia de insuficiência venosa foram selecionados para terapia fibrinolítica e submetidos a infusão seletiva por cateter do ativador de plasminogênio tecidual recombinante na dose de 1mg/dl nos segmentos venosos trombóticos. RESULTADOS: Quatorze pacientes apresentaram fibrinólise efetiva; observamos correlação entre o grau de melhora clínica observado e a redução percentual do volume trombótico (P<.01. Não houve episódios de complicações graves. Quatro pacientes apresentaram retrombose precoce (1 a 8 semanas. Os pacientes foram seguidos por um período de até 131 semanas (média 85.2. A incidência de sinais e sintomas clínicos de insuficiência venosa e os achados ecográficos de refluxo valvular foram significativamente menores nos pacientes em que a terapia fibrinolítica foi efetiva e a perviedade mantida ao longo do período de seguimento, na comparação com os casos de falha aguda ou de

  15. Long-term stability of fibrinolytic factors stored at -80 degrees C.

    Science.gov (United States)

    Hernestål-Boman, Jenny; Jansson, Jan-Håkan; Nilsson, Torbjörn K; Eliasson, Mats; Johansson, Lars

    2010-05-01

    Blood samples in epidemiological studies are often stored for several years and analysed at different occasions. The reagent kits are continually modified for better precision and accuracy. Our hypothesis was that epidemiological studies are affected by long-term storage and/or modifications of reagent kits. Plasma samples stored at -80( degrees )C from two populations were used: A case-referent study with samples collected from 1985 to 2000 and analysed 2005 (n=1598) were used to study influence of long-term storage. A cross-sectional study analysed 1990 (n=1558) and re-analysed 2001 (n=78) and 2005 (n=828) was used to study influence of reagent kit modifications. Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex and chromogenic substrate assays of the activities of tPA and PAI-1. Long-term storage for a median time of 11.6 years (range 5 to 20) showed an effect of time on tPA antigen R(2)=0.01, PAI-1 antigen R(2)=0.01 and tPA-PAI-1 complex R(2) = 0.02. Modifications in reagent kits affected the levels of fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72 and 0.95 (R(2) 0.47 - 0.75), whereas tPA activity showed an agreement with slope coefficients 1.06 to 1.09 (R(2) 0.67 - 0.93). This study showed that long-term storage affects fibrinolytic variables to a negligible extent, but modifications in reagent kits introduced an element of bias. We conclude that analysis of samples on a single occasion is preferable to multiple occasions, as storage has negligible effect. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  16. Exploring Value From the Patient's Perspective Between Modern Radiation Therapy Modalities for Localized Prostate Cancer.

    Science.gov (United States)

    Shaverdian, Narek; Verruttipong, Darlene; Wang, Pin-Chieh; Kishan, Amar U; Demanes, D Jeffrey; McCloskey, Susan; Kupelian, Patrick; Steinberg, Michael L; King, Christopher R

    2017-03-01

    Patients' perspectives on their treatment experiences have not been compared between modern radiation modalities for localized prostate cancer. We evaluated treatment regret and patients' perceptions of their treatment experiences to better inform our understanding of a treatment's value. Patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT), intensity modulated radiation therapy (IMRT), or high-dose-rate (HDR) brachytherapy between 2008 and 2014 with at least 1 year of follow-up were surveyed. The questionnaire explored the decision-making experience, expectations of toxicities versus the reality, and treatment regret by means of a validated tool. Three hundred twenty-nine consecutive patients were surveyed, with an 86% response rate (IMRT, n=74; SBRT, n=108; HDR, n=94). The median patient age and posttreatment follow-up time were 68 years and 47 months, respectively. Eighty-two percent of patients had T1c disease with either Gleason 6 (42%) or Gleason 7 (58%) pathologic features and a median initial prostate-specific antigen of 5.8 ng/mL. Thirteen percent expressed regret with their treatment. Among patients with regret, 71% now wish they had elected for active surveillance. The incidence of regret was significantly different between treatment modalities: 5% of patients treated with SBRT expressed regret versus 18% with HDR and 19% with IMRT (Pcounseling is essential. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Medium Optimization for the Production of Fibrinolytic Enzyme by Paenibacillus sp. IND8 Using Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Ponnuswamy Vijayaraghavan

    2014-01-01

    Full Text Available Production of fibrinolytic enzyme by a newly isolated Paenibacillus sp. IND8 was optimized using wheat bran in solid state fermentation. A 25 full factorial design (first-order model was applied to elucidate the key factors as moisture, pH, sucrose, yeast extract, and sodium dihydrogen phosphate. Statistical analysis of the results has shown that moisture, sucrose, and sodium dihydrogen phosphate have the most significant effects on fibrinolytic enzymes production (P<0.05. Central composite design (CCD was used to determine the optimal concentrations of these three components and the experimental results were fitted with a second-order polynomial model at 95% level (P<0.05. Overall, 4.5-fold increase in fibrinolytic enzyme production was achieved in the optimized medium as compared with the unoptimized medium.

  18. Effect of a single dose of mesoglycan on the human fibrinolytic system, and the profibrinolytic action of nine daily doses.

    Science.gov (United States)

    Vittoria, A; Messa, G L; Frigerio, C; Celasco, G; Auteri, A

    1988-01-01

    The profibrinolytic activity of orally administered Mesoglycan was evaluated in 18 patients affected by impaired plasma fibrinolytic activity. Mesoglycan was administered by a single oral dose of 24, 48 or 72 mg on 1 day, and by repeated doses of 48 mg twice a day for 9 consecutive days. After the single administration all the fibrinolytic parameters were significantly and positively influenced with an order of magnitude and a duration of effects proportional to the dose employed. After the repeated administration, a constant and reproducible activation of the fibrinolytic system was observed without any interference with haemocoagulative parameters. These results confirm that Mesoglycan is endowed with a relevant profibrinolytic activity in man after oral administration. The pharmacological activity of Mesoglycan could possibly involve the liberation of a certain amount of plasminogen tissue activator.

  19. Procoagulant changes induced by oral contraceptives are balanced by an increased fibrinolytic tendency.

    Science.gov (United States)

    Mackie, I J; Campbell, S; Gallimore, M; Robinson, G; Machin, S J

    1992-01-01

    Oral contraceptives caused increased fibrinogen, FVII, FX, and fibrinolysis. The latter was associated with elevated FXII and PKK, while C1-INH was decreased, ATIII and alpha 2M were unchanged; it could not be accounted for by changes in t-PA, u-PA, PAI, plasminogen, alpha 2-AP, proteins C or S. HCII and alpha 1-PI were increased and may regulate the availability of thrombin and FXIa. The increased FXII/PKK dependent fibrinolytic potential and HCII may offset any increase in thrombin generation, while alpha 1-PI limits intrinsic coagulation.

  20. Local transdermal therapy to the breast for breast cancer prevention and DCIS therapy: preclinical and clinical evaluation.

    Science.gov (United States)

    Lee, Oukseub; Ivancic, David; Allu, Subhashini; Shidfar, Ali; Kenney, Kara; Helenowski, Irene; Sullivan, Megan E; Muzzio, Miguel; Scholtens, Denise; Chatterton, Robert T; Bethke, Kevin P; Hansen, Nora M; Khan, Seema A

    2015-12-01

    Women at high risk of breast cancer and those with carcinoma in situ need non-toxic, well-tolerated preventive interventions. One promising approach is drug delivery through the breast skin (local transdermal therapy, LTT). Our goal was to test novel drugs for LTT, to establish that LTT is applicable to non-steroidal drugs. Athymic nude rats were treated with oral tamoxifen, transdermal 4-hydroxytamoxifen (4-OHT) or endoxifen gel applied daily to the axillary mammary gland for 6 weeks (Study 1). Study 2 was identical to Study 1, testing transdermal telapristone acetate (telapristone) gel versus subcutaneous implant. At euthanasia, mammary glands and blood were collected. In Study 3, consenting women requiring mastectomy were randomized to diclofenac patch applied to the abdomen or the breast for 3 days preoperatively. At surgery, eight tissue samples per breast were collected from predetermined locations, along with venous blood. Drug concentrations were measured using liquid chromatography-tandem mass spectroscopy. Mammary tissue concentrations of 4-OHT, endoxifen, and telapristone were significantly higher in the axillary glands of the gel-treated animals, compared to inguinal glands or to systemically treated animals. Plasma concentrations were similar in gel and systemically treated animals. The clinical trial showed significantly higher mammary concentrations when diclofenac was applied to the breast skin versus the abdominal skin, but concentrations were variable. These results demonstrate that lipophilic drugs can be developed for LTT; although the nude rat is suitable for testing drug permeability, delivery is systemic. In human, however, transdermal application to the breast skin provides local delivery.

  1. Local tumor irradiation augments the response to IL-2 therapy in a murine renal adenocarcinoma.

    Science.gov (United States)

    Younes, E; Haas, G P; Dezso, B; Ali, E; Maughan, R L; Kukuruga, M A; Montecillo, E; Pontes, J E; Hillman, G G

    1995-10-15

    We have previously demonstrated that local tumor irradiation effectively enhanced the therapeutic effect of IL-2 therapy on pulmonary metastases from a murine renal adenocarcinoma, Renca. Irradiation with 300 rad to the left lung only, followed by systemic IL-2 therapy, results in increased tumor reduction in both lungs, suggesting that radiation enhances the systemic effect of immunotherapy. In this study, we show that irradiation of the tumor-bearing organ is essential for the combined effect of both modalities. This effect is radiation dose-dependent as increases in the radiation dosage result in greater tumor reduction in the irradiated field as well as systemically in nonirradiated fields when combined with immunotherapy. We find that irradiation has a direct inhibitory effect on Renca cell growth in vitro. Irradiation of Renca cells also causes an upregulation in H-2Kd class I MHC antigen detectable at 300 rad and more pronounced with 800 rad. By in vivo selective depletion of lymphocyte subsets, we demonstrate the involvement of Lyt-2+ and L3T4+ T cell subsets and AsGM1+ cells, including NK cells, in the antitumor effect mediated by tumor irradiation and IL-2 therapy. Immunohistochemistry studies, performed on lung sections, showed a significant infiltration of CD3+ T cells and macrophages in the tumor nodules following treatment with tumor irradiation and IL-2 therapy. Our studies indicate that the mechanism of interaction between tumor irradiation and immunotherapy may include radiation-induced alterations in the tumor growth and antigenicity which may enhance or trigger an anti-tumor response elicited by IL-2 and mediated by T cells, AsGM1+ cells, and macrophages.

  2. Retrospective analysis of multidisciplinary therapy for locally advanced squamous cell carcinoma of the maxillary sinus

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Hiroshi; Seo, Yuji; Nakajima, Kaori; Miyano, Takashi [Asahikawa Medical Univ., Hokkaido (Japan); Kikuchi, Yuzou [Kanazawa Univ. (Japan). School of Medicine

    2002-06-01

    The purpose of this study was to retrospectively investigate the efficacy of multidisciplinary therapy (concomitant radiotherapy and intra-arterial infusion of 5-fluorouracil (5-FU) followed by maxillectomy) in the treatment of squamous cell carcinoma of the maxillary sinus. We reviewed 71 patient records with locally advanced but respectable carcinoma of the maxillary sinus treated by means of multidisciplinary therapy between 1978 through 1997. The clinical T factor for these patients, according to the UICC definitions (1997), was 12 for T2, 46 for T3, and 13 for T4. Twelve patients were diagnosed as node-positive at initial presentation. Intra-arterial 5-FU was delivered via a superficial temporal artery in accordance with radiotherapy, and the cumulative 5-FU dose ranged from 2,900 mg to 5,250 mg (median 5,000 mg). The total radiotherapy dose ranged from 29 Gy to 48 Gy (median 48 Gy) with conventional fractionation. Patients underwent radical maxillectomy thereafter. The 5-year overall survival rate and disease-specific survival rate of all the patients were 58% and 68%, respectively. There was no significant correlation of clinical T factor or N factor with disease-specific survival on univariate and multivariate analysis. The overall treatment-related mortality rate was 3.7%. Radiation cataract later developed in all evaluable patients whose lenses were within the treatment volume. About a half of the operable T4 patients survived over 5 years by means of the above-mentioned multidisciplinary therapy. This multidisciplinary therapy should be compared to treatment with a combination of surgery and postoperative chemoradiotherapy. (author)

  3. Dosimetric evaluation of neutron capture therapy for local advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yanagie, H. [Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)], E-mail: yanagie@n.t.u-tokyo.ac.jp; Kumada, H. [Japan Atomic Research Institute, Ibaraki (Japan); Sakurai, Y. [Research Reactor Institute, Kyoto University, Osaka (Japan); Nakamura, T. [Japan Atomic Research Institute, Ibaraki (Japan); Department of Nuclear Physics, Ibaraki University, Ibaraki (Japan); Furuya, Y. [Department of Surgery, Satukidai Hospital, Chiba (Japan); Sugiyama, H. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Ono, K. [Research Reactor Institute, Kyoto University, Osaka (Japan); Takamoto, S. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Cardiac Surgery, University of Tokyo Hospital, Tokyo (Japan); Eriguchi, M. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Microbiology, Syowa University School of Pharmaceutical Sciences, Tokyo (Japan); Takahashi, H. [Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)

    2009-07-15

    Local recurrence breast cancer is one of the most difficult conditions to cure and there is a need for new therapy. If sufficient boron compound can be targeted to the tumor, boron neutron capture therapy (BNCT) can be applied to local recurrent breast cancer. In this study, we performed a preliminary dosimetry with a phantom model of the mammary gland at Kyoto University Research Reactor (KUR), and a feasibility dosimetry with JAERI Computational Dosimetry System (JCDS) at JRR4 reactor of Japan Atomic Research Institute. We performed preliminary dosimetry of a phantom model of the mammary gland with thermal neutron irradiation (OO-0011 mode) on LiF collimation at KUR. The thermal neutron flux was 5.16 E+08 cm{sup -2} s{sup -1} at the surface of phantom. The blood boron concentration is estimated to be 30 ppm; tumor boron concentration is also estimated to be 90 ppm according to tumor/blood ratio 3 and skin/blood ratio 1.2. Tumor RBE dose is estimated to be 47 Gy/h, and skin RBE dose is 12.4 Gy/h. In case of advanced breast cancer, we performed the feasibility estimation of 3D construction of tumor according to the MRI imaging of a patient with epithermal neutron mode at JRR4. The blood boron concentration (ppm) and tumor/normal tissue ratio are estimated to be 24 and 3.5, respectively. Skin RBE dose is restricted to 10 Gy/h, the maximum tumor RBE dose, minimum tumor RBE dose, and mean tumor RBE dose are 42.2, 11.3, and 28.9 Gy-Eq, respectively, in half hour irradiation. In this study, we showed the possibility to apply BNCT to local recurrent breast cancer. We can irradiate tumors selectively and as safely as possible, reducing the effects on neighboring healthy tissues.

  4. Statistical optimization of fibrinolytic enzyme production using agroresidues by Bacillus cereus IND1 and its thrombolytic activity in vitro.

    Science.gov (United States)

    Vijayaraghavan, Ponnuswamy; Vincent, Samuel Gnana Prakash

    2014-01-01

    A potent fibrinolytic enzyme-producing Bacillus cereus IND1 was isolated from the Indian food, rice. Solid-state fermentation was carried out using agroresidues for the production of fibrinolytic enzyme. Among the substrates, wheat bran supported more enzyme production and has been used for the optimized enzyme production by statistical approach. Two-level full-factorial design demonstrated that moisture, supplementation of beef extract, and sodium dihydrogen phosphate have significantly influenced enzyme production (P blood clot, which suggests its potential as an effective thrombolytic agent.

  5. Evaluation of the local dose enhancement in the combination of proton therapy and nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Rovira, I., E-mail: immamartinez@gmail.com; Prezado, Y. [Laboratoire d’Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC), Centre National de la Recherche Scientifique (CNRS), Université Paris 7 and 11, Campus Universitaire, Bât. 440, 1er étage, 15 rue Georges Clemenceau, Orsay Cedex 91406 (France)

    2015-11-15

    Purpose: The outcome of radiotherapy can be further improved by combining irradiation with dose enhancers such as high-Z nanoparticles. Since 2004, spectacular results have been obtained when low-energy x-ray irradiations have been combined with nanoparticles. Recently, the same combination has been explored in hadron therapy. In vitro studies have shown a significant amplification of the biological damage in tumor cells charged with nanoparticles and irradiated with fast ions. This has been attributed to the increase in the ionizations and electron emissions induced by the incident ions or the electrons in the secondary tracks on the high-Z atoms, resulting in a local energy deposition enhancement. However, this subject is still a matter of controversy. Within this context, the main goal of the authors’ work was to provide new insights into the dose enhancement effects of nanoparticles in proton therapy. Methods: For this purpose, Monte Carlo calculations (GATE/GEANT4 code) were performed. In particular, the GEANT4-DNA toolkit, which allows the modeling of early biological damages induced by ionizing radiation at the DNA scale, was used. The nanometric radial energy distributions around the nanoparticle were studied, and the processes (such as Auger deexcitation or dissociative electron attachment) participating in the dose deposition of proton therapy treatments in the presence of nanoparticles were evaluated. It has been reported that the architecture of Monte Carlo calculations plays a crucial role in the assessment of nanoparticle dose enhancement and that it may introduce a bias in the results or amplify the possible final dose enhancement. Thus, a dosimetric study of different cases was performed, considering Au and Gd nanoparticles, several nanoparticle sizes (from 4 to 50 nm), and several beam configurations (source-nanoparticle distances and source sizes). Results: This Monte Carlo study shows the influence of the simulations’ parameters on the local

  6. Cloning, Expression and Activity Analysis of a Novel Fibrinolytic Serine Protease fromArenicola cristata

    Institute of Scientific and Technical Information of China (English)

    ZHAO Chunling; JU Jiyu

    2015-01-01

    The full-length cDNA of a protease gene from a marine annelid Arenicola cristata was amplified through rapid amplifi-cation of cDNA ends technique and sequenced. The size of the cDNA was 936 bp in length, including an open reading frame encod-ing a polypeptide of 270 amino acid residues. The deduced amino acid sequnce consisted of pro- and mature sequences. The protease belonged to the serine protease family because it contained the highly conserved sequence GDSGGP. This protease was novel as it showed a low amino acid sequence similarity (<40%) to other serine proteases. The gene encoding the active form ofA. cristata serine protease was cloned and expressed inE. coli. Purified recombinant protease in a supernatant could dissolve an artificial fibrin plate with plasminogen-rich fibrin, whereas the plasminogen-free fibrin showed no clear zone caused by hydrolysis. This result sug-gested that the recombinant protease showed an indirect fibrinolytic activity of dissolving fibrin, and was probably a plasminogen activator. A rat model with venous thrombosis was established to demonstrate that the recombinant protease could also hydrolyze blood clotin vivo. Therefore, this recombinant protease may be used as a thrombolytic agent for thrombosis treatment. To our knowledge, this study is the first of reporting the fibrinolytic serine protease gene inA. cristata.

  7. Multi-isomorphous replacement phasing of the earthworm fibrinolytic enzyme component A from Eisenia fetida

    Institute of Scientific and Technical Information of China (English)

    汤涌; 江涛; 张季平; 樊蓉; 吴骋; 梁栋材; 常文瑞

    2003-01-01

    Earthworm fibrinolytic enzyme component A (EFEa) from Eisenia fetida, a protein functioning not only as a direct fibrinolytic enzyme, but also as a plasminogen activator, has been crystallized in P212121 space group with 3 proteinmolecules per asymmetric unit. Four heavy atom derivatives were prepared using a mother liquor containing 1.4 mol@L-1 Li2SO4 and 0.1 mol@L-1 MOPS buffer (pH7.2) and used to solve the protein's diffraction phase. The heavy atom binding sites in the derivative crystals were determined using difference Patterson and difference Fourier methods and were refined in combination to yield the initial protein's structure phase at 0.25 nm resolution. The non-crystallographic symmetryrelationship of the three independent protein molecules in the asymmetric unit was determined using the correlative heavy atom sites and used for the averagingof the initial electron density. As a result, the electron density was significantly improved, providing a solid foundation for subsequent structure determination.

  8. [Effects of cholesterol rich diet on blood coagulative and fibrinolytic activities in male rabbits].

    Science.gov (United States)

    Si, Quan-jin; Li, Xiao-ying

    2005-05-01

    To explore the effects of cholesterol rich diet on the activities of blood coagulative and fibrinolytic systems in male rabbits. 14 male New Zealand white rabbits were randomized to cholesterol rich diet(CRD) group and common diet (control) group. Rabbits in CRD group were fed with 1% cholesterol embedded diet and those in the control group were fed with common diet. Levels of blood TG, TC, LDL, HDL, Lp(a), apoA1, apoB, FIB, D-dimers and FDP, PT and APTT, activity of ADP, AT-III, PLG and alpha2-PI were tested in all rabbits before given cholesterol rich diet and after 12 weeks' feeding with different kinds of diet. Levels of blood TG, TC, LDL, HDL, Lp(a), apoA1, apoB, FIB, D-dimers in CRD group were all elevated significantly compared with those in the control group and the baseline levels. PT and APTT were shortened, ADP, PLG and alpha2-PI activity were increased in CRD group. Cholesterol rich diet not only is the direct cause of hyperlipidemia but also can increase the coagulative activity and inhibit the fibrinolytic activity and promoting the evolution of arteriosclerosis.

  9. Cloning, expression and activity analysis of a novel fibrinolytic serine protease from Arenicola cristata

    Science.gov (United States)

    Zhao, Chunling; Ju, Jiyu

    2015-06-01

    The full-length cDNA of a protease gene from a marine annelid Arenicola cristata was amplified through rapid amplification of cDNA ends technique and sequenced. The size of the cDNA was 936 bp in length, including an open reading frame encoding a polypeptide of 270 amino acid residues. The deduced amino acid sequnce consisted of pro- and mature sequences. The protease belonged to the serine protease family because it contained the highly conserved sequence GDSGGP. This protease was novel as it showed a low amino acid sequence similarity (< 40%) to other serine proteases. The gene encoding the active form of A. cristata serine protease was cloned and expressed in E. coli. Purified recombinant protease in a supernatant could dissolve an artificial fibrin plate with plasminogen-rich fibrin, whereas the plasminogen-free fibrin showed no clear zone caused by hydrolysis. This result suggested that the recombinant protease showed an indirect fibrinolytic activity of dissolving fibrin, and was probably a plasminogen activator. A rat model with venous thrombosis was established to demonstrate that the recombinant protease could also hydrolyze blood clot in vivo. Therefore, this recombinant protease may be used as a thrombolytic agent for thrombosis treatment. To our knowledge, this study is the first of reporting the fibrinolytic serine protease gene in A. cristata.

  10. Effects of whole-body vibration training on fibrinolytic and coagulative factors in healthy young men

    Directory of Open Access Journals (Sweden)

    Farshad Ghazalian

    2014-01-01

    Full Text Available Background: The aim was to evaluate effects of 5-week whole body vibration (WBV training with different amplitudes and progressive frequencies on fibrinolytic/coagulative factors. Materials and Methods: 25 subjects were divided randomly in high or low-amplitude vibration, and control groups. Training consisted of 5-week WBV with amplitudes 4 or 2 mm. Plasma samples were analyzed before and after training. Statistical analysis was done using one-way analysis of variance and Wilcoxon signed ranked test. P <0.05 was considered significant. Results: High-amplitude vibration caused an increase in tissue plasminogen activator (tPA (P = 0.028 (pretest: 1744.61 ± 707.95; posttest: 2313.63 ± 997.19 pg/ml, and decrease in plasminogen activator inhibitor-1 (PAI-1 (P = 0.033 (pretest: 97.94 ± 34.37; posttest: 85.12 ± 36.92 ng/ml. Fibrinogen and plasminogen were not changed significantly. Low-amplitude vibration caused an increase in tPA (P = 0.006 (pretest: 2208.18 ± 1280.37; posttest: 3492.72 ± 3549.22 pg/ml. PAI-1, fibrinogen and plasminogen were not changed significantly. There were no significant differences between groups. Conclusion: Amplitude of vibrations in WBV training may affect fibrinolytic factors.

  11. Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: A dosimetric analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rachit; Wild, Aaron T.; Ziegler, Mark A.; Hooker, Ted K.; Dah, Samson D.; Tran, Phuoc T.; Kang, Jun; Smith, Koren; Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231 (United States); Pawlik, Timothy M. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231 (United States); Ford, Eric [Department of Radiation Oncology, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA (United States); Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231 (United States)

    2013-10-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal D{sub max} of<30 Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal D{sub mean}, D{sub max}, D{sub 1cc}, D{sub 4%}, and V{sub 20} {sub Gy} compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V{sub 95%} (p = 0.01) and D{sub mean} (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at

  12. Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment.

    Science.gov (United States)

    Niwińska, Anna

    2016-10-01

    The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.

  13. Capsaicin-loaded vesicular systems designed for enhancing localized delivery for psoriasis therapy.

    Science.gov (United States)

    Gupta, Ruchi; Gupta, Madhu; Mangal, Sharad; Agrawal, Udita; Vyas, Suresh Prasad

    2016-05-01

    The aim of the current investigation is to evaluate the potential of capsaicin (CAP)-containing liposomes, niosomes and emulsomes in providing localized and controlled delivery, to improve the topical delivery of drug. CAP-bearing systems were prepared by the film hydration method and compared through various in vitro and in vivo parameters. The TEM photographs suggested that the carrier systems were spherical in shape and nanometric in size range. Skin retention studies of CAP from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of the emul-gel formulation. Based on the results, we concluded that the emul-gel may be a potential approach for the topical delivery of CAP, for an effective therapy for psoriasis.

  14. Improved highly accurate localized motion imaging for monitoring high-intensity focused ultrasound therapy

    Science.gov (United States)

    Qu, Xiaolei; Azuma, Takashi; Sugiyama, Ryusuke; Kanazawa, Kengo; Seki, Mika; Sasaki, Akira; Takeuchi, Hideki; Fujiwara, Keisuke; Itani, Kazunori; Tamano, Satoshi; Takagi, Shu; Sakuma, Ichiro; Matsumoto, Yoichiro

    2016-07-01

    Visualizing an area subjected to high-intensity focused ultrasound (HIFU) therapy is necessary for controlling the amount of HIFU exposure. One of the promising monitoring methods is localized motion imaging (LMI), which estimates coagulation length by detecting the change in stiffness. In this study, we improved the accuracy of our previous LMI by dynamic cross-correlation window (DCCW) and maximum vibration amount (MVA) methods. The DCCW method was used to increase the accuracy of estimating vibration amplitude, and the MVA method was employed to increase signal-noise ratio of the decrease ratio at the coagulated area. The qualitative comparison of results indicated that the two proposed methods could suppress the effect of noise. Regarding the results of the quantitative comparison, coagulation length was estimated with higher accuracy by the improved LMI method, and the root-mean-square error (RMSE) was reduced from 2.51 to 1.69 mm.

  15. Liquid fiducial marker applicability in proton therapy of locally advanced lung cancer

    DEFF Research Database (Denmark)

    Scherman Rydhög, Jonas; Perrin, Rosalind; Jølck, Rasmus Irming

    2017-01-01

    .164 for the LFM. Phantom measurements revealed a maximum relative deviation in dose of 4.8% for the LFM in the spread-out Bragg Peak, compared to 12-67% for the solid markers. Using the experimentally determined RSP, the maximum proton range error introduced by the LFM is about 1. mm. If the marker was displaced......Background and purpose: We investigated the clinical applicability of a novel liquid fiducial marker (LFM) for image-guided pencil beam scanned (PBS) proton therapy (PBSPT) of locally advanced lung cancer (LALC). Materials and methods: The relative proton stopping power (RSP) of the LFM...... was calculated and measured. Dose perturbations of the LFM and three solid markers, in a phantom, were measured. PBSPT treatment planning on computer tomography scans of five patients with LALC with the LFM implanted was performed with 1-3 fields. Results: The RSP was experimentally determined to be 1...

  16. Barriers to effective treatment of vaginal atrophy with local estrogen therapy

    Directory of Open Access Journals (Sweden)

    Reiter S

    2013-03-01

    Full Text Available Suzanne ReiterMid-County Health Center, Largo, FL, USAAbstract: Vaginal atrophy is a common condition among postmenopausal women, among whom many exhibit both vulvovaginal symptoms (eg, dryness, irritation, itching, and pain with intercourse and urinary symptoms (eg, increased frequency, urgency, incontinence, urinary tract infections, and dysuria. Unfortunately, few women with symptoms of vaginal atrophy report seeking treatment from a health care provider. The goal of this article is to examine reasons why patients and health care providers do not engage in discourse regarding this important topic. It is important to initiate conversations with postmenopausal women and counsel them on both why the changes occur and potential treatment options.Keywords: local estrogen therapy, vaginal atrophy, barriers, postmenopausal women

  17. Low Incidence of Fatigue after Hypofractionated Stereotactic Body Radiation Therapy (SBRT for Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Chiranjeev eDash

    2012-10-01

    Full Text Available Background: Fatigue is a common side-effect of conventional prostate cancer radiation therapy. The increased delivery precision necessitated by the high dose per fraction of stereotactic body radiation therapy (SBRT offers the potential of reduce target volumes and hence the exposure of normal tissues to high radiation doses. Herein, we examine the level of fatigue associated with SBRT treatment.Methods: Forty patients with localized prostate cancer treated with hypofractionated SBRT, and a minimum of 12 months follow-up were included in this analysis. Self-reported fatigue and other quality of life measures were assessed at baseline and at 1, 3, 6, 9, and 12 months post-SBRT.Results: Mean levels of fatigue were elevated at 1 month post-SBRT compared to baseline values (p=0.02. Fatigue at the 3-month follow-up and later were higher but not statistically significantly different compared to baseline. African-American patients reported higher fatigue post-SBRT than Caucasian patients. Fatigue was correlated with hormonal symptoms as measured by the Expanded Prostate Cancer Index Composite (EPIC quality of life questionnaire, but not with urinary, bowel, or sexual symptoms. Age, co-morbidities, smoking, prostate specific antigen (PSA levels, testosterone levels, and tumor stage were not associated with fatigue. Conclusion: This is the first study to investigate fatigue as a side-effect of SBRT. In contrast to standard radiation therapy, results suggest SBRT-related fatigue is short-term rather than a long-term side effect of SBRT. These results also suggest post-SBRT fatigue to be a more frequent complication in African-Americans than Caucasians.

  18. Salvage Stereotactic Body Radiation Therapy (SBRT) for Local Failure After Primary Lung SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Hearn, Jason W.D., E-mail: hearnj@ccf.org; Videtic, Gregory M.M.; Djemil, Toufik; Stephans, Kevin L.

    2014-10-01

    Purpose: Local failure after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) is uncommon. We report the safety and efficacy of SBRT for salvage of local failure after previous SBRT with a biologically effective dose (BED) of ≥100 Gy{sub 10}. Methods and Materials: Using an institutional review board–approved lung SBRT registry, we identified all patients initially treated for early-stage NSCLC between August 2004 and January 2012 who received salvage SBRT for isolated local failure. Failure was defined radiographically and confirmed histologically unless contraindicated. All patients were treated on a Novalis/BrainLAB system using ExacTrac for image guidance, and received a BED of ≥100 Gy{sub 10} for each SBRT course. Tumor motion control involved a Bodyfix vacuum system for immobilization along with abdominal compression. Results: Of 436 patients treated from August 2004 through January 2012, we identified 22 patients with isolated local failure, 10 of whom received SBRT for salvage. The median length of follow-up was 13.8 months from salvage SBRT (range 5.3-43.5 months). Median tumor size was 3.4 cm (range 1.7-4.8 cm). Two of the 10 lesions were “central” by proximity to the mediastinum, but were outside the zone of the proximal bronchial tree. Since completing salvage, 3 patients are alive and without evidence of disease. A fourth patient died of medical comorbidities without recurrence 13.0 months after salvage SBRT. Two patients developed distant disease only. Four patients had local failure. Toxicity included grade 1-2 fatigue (3 patients) and grade 1-2 chest wall pain (5 patients). There was no grade 3-5 toxicity. Conclusions: Repeat SBRT with a BED of ≥100 Gy{sub 10} after local failure in patients with early-stage medically inoperable NSCLC was well tolerated in this series and may represent a viable salvage strategy in select patients with peripheral tumors ≤5 cm.

  19. Cell Based Autologous Immune Enhancement Therapy (AIET after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

    Directory of Open Access Journals (Sweden)

    Sumana Premkumar

    2013-01-01

    Full Text Available Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life.

  20. Purification and characterization of a fibrinolytic enzyme of Bacillus subtilis DC33, isolated from Chinese traditional Douchi

    NARCIS (Netherlands)

    Wang, C.T.; Ji, B.P.; Li, B.; Nout, M.J.R.; Li, P.L.; Ji, H.; Chen, L.F.

    2006-01-01

    Bacillus subtilis DC33 producing a novel fibrinolytic enzyme was isolated from Ba-bao Douchi, a traditional soybean-fermented food in China. The strong fibrin-specific enzyme subtilisin FS33 was purified to electrophoretic homogeneity using the combination of various chromatographic steps. The

  1. Enhancement of protease production by Pseudomonas aeruginosa isolated from dairy effluent sludge and determination of its fibrinolytic potential

    Institute of Scientific and Technical Information of China (English)

    Amrita Raj; Nancy Khess; Namrata Pujari; Sourav Bhattacharya; Arijit Das; Subbaramiah Sundara Rajan

    2012-01-01

    Objective: The present study aimed at isolating proteolytic bacteria from dairy effluent sludge, designing the process parameters for the enhanced production of protease and determination of its fibrinolytic potential. Methods: The dairy sludge was processed according to the microbiological criteria for the isolation of proteolytic bacteria. All the isolates were screened for their protease production ability and the isolate showing highest proteolysis was selected for further studies. Effects of various media components and process parameters like carbon and nitrogen supplementation, temperature, pH and incubation period were investigated. Partial purification of the protease was done using ammonium sulphate fractionation, following which its molecular weight and fibrinolytic activity were determined. Results: Based on the biochemical studies, the selected isolate was identified as Pseudomonas aeruginosa. The highest protease yield was obtained with maltose and yeast extract as supplements. The optimum pH, temperature and incubation period for protease production by the isolate was found to be 7.0, 37℃ and 48 h respectively. The partially purified enzyme preparation showed a single protein band in sodium dodecyl sulphate polyacrylamide gel electrophoresis, revealing the apparent molecular weight of the enzyme to be 35 kDa. The efficient removal of the blood stain emphasized its fibrinolytic potential. Conclusions: From the present study it is envisaged that cultural parameters significantly affect the protease production. Based upon the fibrinolytic activity, this protease may find broad applications in detergent and pharmaceutical industries.

  2. Fibrinolytic Activity and Dose-Dependent Effect of Incubating Human Blood Clots in Caffeic Acid Phenethyl Ester: In Vitro Assays

    Directory of Open Access Journals (Sweden)

    Abuzar Elnager

    2015-01-01

    Full Text Available Background. Caffeic acid phenethyl ester (CAPE has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM. After 3 hours, D-dimer (DD levels and WB clot weights were measured for each concentration. Thromboelastography (TEG parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM. The 50% effective dose (ED50 of CAPE (based on DD was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.

  3. Localized and systemic scleroderma show different histological responses to methotrexate therapy.

    Science.gov (United States)

    Seyger, M M; van den Hoogen, F H; van Vlijmen-Willems, I M; van de Kerkhof, P C; de Jong, E M

    2001-04-01

    Although morphoea (localized scleroderma) and systemic sclerosis are distinct disease entities, the skin lesions show identical histological characteristics and both diseases respond favourably to low-dose treatment with methotrexate (MTX). The aim of this study was to find out whether MTX treatment induces different histological response patterns in these two diseases. In seven patients with morphoea and eight with systemic sclerosis, skin biopsies were taken before and after 24 weeks of treatment with low-dose MTX. In the centre and active margin of morphoea lesions, a significant reduction in tenascin staining was seen after 24 weeks of treatment, in contrast to systemic sclerosis. The numbers of mast cells decreased in the active margin of morphoea lesions, whereas in systemic sclerosis no significant change was seen after MTX therapy. Epidermal proliferation and staining of heparan sulphate proteoglycans showed no changes. Although skin lesions from both diseases respond clinically to treatment with MTX, systemic sclerosis shows no change in the immunohistochemical parameters investigated, whereas morphoea does. This difference in dynamic pattern suggests that the apparently similar lesions in localized and systemic sclerosis are not identical.

  4. Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rajiv, E-mail: r.kumar@neu.edu [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Belz, Jodi [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Markovic, Stacey [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Jadhav, Tej; Fowle, William [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Niedre, Mark [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Cormack, Robert; Makrigiorgos, Mike G. [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Sridhar, Srinivas [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States)

    2015-02-01

    Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when

  5. Urokinase plasminogen receptor and the fibrinolytic complex play a role in nerve repair after nerve crush in mice, and in human neuropathies.

    Directory of Open Access Journals (Sweden)

    Cristina Rivellini

    Full Text Available Remodeling of extracellular matrix (ECM is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies.

  6. Urokinase Plasminogen Receptor and the Fibrinolytic Complex Play a Role in Nerve Repair after Nerve Crush in Mice, and in Human Neuropathies

    Science.gov (United States)

    Rivellini, Cristina; Dina, Giorgia; Porrello, Emanuela; Cerri, Federica; Scarlato, Marina; Domi, Teuta; Ungaro, Daniela; Carro, Ubaldo Del; Bolino, Alessandra; Quattrini, Angelo; Comi, Giancarlo; Previtali, Stefano C.

    2012-01-01

    Remodeling of extracellular matrix (ECM) is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR) is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA) promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies. PMID:22363796

  7. Hypofractionated Radiotherapy for Small-sized Hepatocellular Carcinoma as Salvage Therapy: Sustained Local Control and Safety

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sun Hyun; Park, Hee Chul; Lim, Do Hoon; Lee, Jung Ae; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2010-11-15

    To evaluate the rate of tumor response, local control, and treatment-related complications after hypofractionated radiotherapy for recurrent hepatocelluar carcinoma (HCC) less than 5 cm in size. Among the HCC patients who were treated by radiotherapy (RT) between 2006 and 2007 after the failure of previous treatment, a total of 12 patients were treated with hypofractionated RT. The criteria for hypofractionated RT was as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to a critical organ, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that irradiated 50% of the prescribed dose. Hypofractionated RT was performed with 50 Gy delivered in 10 fractions, at a rate of 5 fractions per week. The evaluation of tumor response was determined by CT scans performed at 3 months after the cessation of RT, followed by the evaluation of toxicity by Common Terminology Criteria for Adverse Events version 3.0. The median follow-up period after radiotherapy was 18 months. A complete response (CR) was achieved in 5 of 12 lesions (41.7%) at CT performed at 3 months after the cessation, whereas the overall complete response was observed in 7 of 12 cases (58.3%). In-field local control rate was sustained in 83.3% of patients. All patients developed intra-hepatic metastases except for 2 patients. The overall survival rate was 90.0% at 1 year and 67.5% at 2 years, respectively. Three patients developed Grade 1 nausea during RT and 1 patient showed a progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Hypofractionated RT for small-sized HCC as a salvage therapy showed a 58.3% CR rate and 83.3% of local control. Fifty Gy administered in 10 fractions of partial liver irradiation is considered as a tolerable dose that does not cause severe complications.

  8. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis.

    Science.gov (United States)

    Jepsen, Karin; Jepsen, Søren

    2016-06-01

    This review gives an update of the current scientific evidence on the efficacy of the adjunctive use of systemic and local antibiotics/antimicrobials in the treatment of periodontitis. In particular, it addresses whether their use can improve the results of nonsurgical mechanical therapy in mild-to-moderate forms of the disease. Large numbers of randomized clinical trials and systematic reviews with meta-analyses have clearly established that adjunctive systemic antibiotics, combined with mechanical debridement, offer clinical improvements additional to those obtained with scaling and root planing alone. These effects are more pronounced in aggressive periodontitis and in initially deep pockets, whereas more limited additional improvements, of 0.3 mm for additional pocket reduction and 0.2 mm for additional clinical attachment gain, have been documented for moderately deep sites (4-6 mm) in patients with chronic periodontitis. The marginal clinical benefit in patients with moderate disease has to be balanced against possible side effects. Notably, it has to be realized that an increasing number of warnings have been articulated against the unrestricted use of antibiotics in treating periodontal diseases because of the emerging global public health issue of bacterial resistance. The effects of the adjunctive local administration of antimicrobials have also been very well documented in several systematic reviews. Overall, in persistent or recurrent localized deep sites, the application of antimicrobials by sustained-delivery devices may offer a benefit of an additional 0.4 mm in pocket depth reduction and 0.3 mm in clinical attachment level gain. In conclusion, the slight additional benefits of adjunctive antimicrobials, which were shown for moderate forms of periodontitis, have to be balanced against their side effects and therefore their prescription should be limited as much as possible. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Comparison of whole brain radiation therapy and locally limited radiation therapy in the treatment of solitary brain metastases from non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ueki, Keisuke; Matsutani, Masao; Nakamura, Osamu; Tanaka, Yoshiaki [Tokyo Metropolitan Komagome Hospital (Japan)

    1996-06-01

    The benefit and risk of whole brain radiation therapy (WBRT) compared to locally limited radiation therapy was assessed in 61 patients with solitary brain metastases from non-small cell lung cancer without an unresectable active primary lesion or systemic dissemination in the other organs. Twenty-three patients received local irradiation (Group A), and 38 patients received whole brain irradiation with or without local irradiation (Group B). The survival was significantly better in Group A than in Group B (p<0.05), with median survivals of 83.1 and 30.7 weeks, respectively. One-year local recurrence rates were 7% in Group A and 21% in Group B, but the difference was not statistically significant. The 1-year distant recurrence rate was similar at 18%. Radiation-induced dementia occurred in two patients in Group A (8.7%) and seven in Group B (18.4%), but was not statistically significant (p=0.30). There is no obvious benefit and possible disadvantages of WBRT compared to local irradiation for the population of patients investigated in this study. Intraoperative radiation therapy or stereotactic radiosurgery without WBRT should be considered in the patients with solitary brain metastases. (author)

  10. The mechanism of local tumor irradiation combined with interleukin 2 therapy in murine renal carcinoma: histological evaluation of pulmonary metastases.

    Science.gov (United States)

    Dezso, B; Haas, G P; Hamzavi, F; Kim, S; Montecillo, E J; Benson, P D; Pontes, J E; Maughan, R L; Hillman, G G

    1996-09-01

    We have demonstrated that tumor irradiation enhanced the therapeutic effect of interleukin 2 (IL-2) on pulmonary metastases from a murine renal adenocarcinoma, Renca. To investigate the mechanism of interaction between tumor irradiation and IL-2 therapy, we have histologically evaluated the effects of each therapy alone or in combination on Renca pulmonary metastases. Following treatment of established lung metastases with irradiation and IL-2 therapy, lung sections were processed for H&E or immunohistochemical staining. We found that tumor irradiation or IL-2 therapy locally induced vascular damage, resulting in multifocal hemorrhages and mononuclear cell mobilization in the lung tissue. This effect was amplified in lungs treated with the combined therapy. Immunohistochemistry showed that irradiation produced a macrophage influx into irradiated tumor nodules, and systemic IL-2 therapy induced T-cell infiltration in tumor nodules. Lungs treated with the combined therapy exhibited massive macrophage, T-cell, and natural killer cell mobilization in disintegrating tumor nodules and in the lung tissue. This combined therapy caused a decrease in the number of proliferating tumor cells and an increase in the number of apoptotic cells, which were more marked than with either therapy alone. We suggest that the macrophages mobilized by radiation-induced tissue injury could play a role in phagocytosis of apoptotic tumor cells, processing and presenting of tumor antigens for a systemic immune response activated by IL-2. Tumor destruction may result from the concomitant action of activated T cells, natural killer cells, and macrophages infiltrating the tumor nodules.

  11. Prostate-specific antigen kinetics after primary stereotactic body radiation therapy using CyberKnife for localized prostate cancer

    OpenAIRE

    Park, Yong Hyun; Choi, In Young; Yoon, Sei Chul; Jang, Hong Seok; Moon, Hyong Woo; Hong, Sung-Hoo; Kim, Sae Woong; Hwang, Tae-Kon; Lee, Ji Youl

    2015-01-01

    Purpose To assess prostate-specific antigen (PSA) kinetics and report on the oncologic outcomes for patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT) using CyberKnife. Methods We extracted the list and data of 39 patients with clinically localized prostate cancer who had undergone primary SBRT using CyberKnife between January 2008 and December 2012 from the Smart Prostate Cancer database system of Seoul St. Mary's Hospital. Changes in PSA over tim...

  12. The Impact of Definitive Local Therapy for Lymph Node-Positive Prostate Cancer: A Population-Based Study

    Energy Technology Data Exchange (ETDEWEB)

    Rusthoven, Chad G., E-mail: chad.rusthoven@ucdenver.edu [Department of Radiation Oncology, University of Colorado-Denver, Aurora, Colorado (United States); Carlson, Julie A.; Waxweiler, Timothy V.; Raben, David [Department of Radiation Oncology, University of Colorado-Denver, Aurora, Colorado (United States); Dewitt, Peter E. [Department of Biostatistics, University of Colorado-Denver, Aurora, Colorado (United States); Crawford, E. David [Department of Radiation Oncology, University of Colorado-Denver, Aurora, Colorado (United States); Department of Urology, University of Colorado-Denver, Aurora, Colorado (United States); Maroni, Paul D. [Department of Urology, University of Colorado-Denver, Aurora, Colorado (United States); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado-Denver, Aurora, Colorado (United States)

    2014-04-01

    Purpose: To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. Methods and Materials: The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated, with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. Results: A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. Conclusions: In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.

  13. NEW DIRECTION IN LOCAL THERAPY OF OSTEOARTHRITIS OF THE KNEE JOINT

    Directory of Open Access Journals (Sweden)

    Ye. S. Tsvetkova,

    2014-01-01

    decreased only with the use of the active Nanoplast forte patch (p = 0.05; ANOVA two-factor analysis, and evident decreasing of pain was marked as quickly as on the 4th day of application. Due to the therapy, morning stiffness was evidently decreased and functional activity was increased in the main group. The general state of patients in accordance with their subjective assessment (p = 0.05 and with the doctor’s opinion (p = 0.01 was improved with statistic significance. Elimination and decreasing of the dose of NSAIDs took place evidently more frequently (p = 0.007; Fisher exact criterion in the group of patients that applied active Nanoplast forte patch than in the placebo group. All patients completed the study in the active therapy group. No side effects associated with application of the Nanoplast forte patch were revealed. Due to application of the Nanoplast forte patch, 50 percent of patients eliminated or decreased the dose of previously prescribed NSAIDs, while only 25 % of patients did the same in the placebo group.Conclusion. Nanoplast forte may be recommended as an efficient and safe method of local therapy of OA of the KJ.

  14. NEW DIRECTION IN LOCAL THERAPY OF OSTEOARTHRITIS OF THE KNEE JOINT

    Directory of Open Access Journals (Sweden)

    Ye. S. Tsvetkova,

    2015-01-01

    decreased only with the use of the active Nanoplast forte patch (p = 0.05; ANOVA two-factor analysis, and evident decreasing of pain was marked as quickly as on the 4th day of application. Due to the therapy, morning stiffness was evidently decreased and functional activity was increased in the main group. The general state of patients in accordance with their subjective assessment (p = 0.05 and with the doctor’s opinion (p = 0.01 was improved with statistic significance. Elimination and decreasing of the dose of NSAIDs took place evidently more frequently (p = 0.007; Fisher exact criterion in the group of patients that applied active Nanoplast forte patch than in the placebo group. All patients completed the study in the active therapy group. No side effects associated with application of the Nanoplast forte patch were revealed. Due to application of the Nanoplast forte patch, 50 percent of patients eliminated or decreased the dose of previously prescribed NSAIDs, while only 25 % of patients did the same in the placebo group.Conclusion. Nanoplast forte may be recommended as an efficient and safe method of local therapy of OA of the KJ.

  15. Blood Fibrinolytic Activity in Patients with Type 2 Diabetes Mellitus Associated with Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Т.Yu. Yuzvenko

    2015-06-01

    Full Text Available The objective of the research was to study the level of plasminogen activator inhibitor type 1 (PAI-1 in the blood serum of patients with type 2 diabetes mellitus (DM in combination with hypothyroidism. We have observed 62 patients with type 2 DM, 32 of them had primary hypothyroidism. Control group consisted of 20 persons without carbohydrate metabolism disorders and thyroid pathology. In patients with type 2 DM, we have detected violations in the fibrinolytic system as an increase of PAI-1, whose level depends on the body mass index, waist circumference, level of glycated haemoglobin, indexes of insulin resistance, blood lipid spectrum, as well as on the presence of microalbuminuria. The presence of hypothyroidism has an additional negative impact on the parameters of carbohydrate, lipid metabolism and PAI-1 level in patients with type 2 DM.

  16. Fluorescent studies on the binding-Ca 2+ in fibrinolytic principle separated from snake venom

    Science.gov (United States)

    Wang, Shouye; Liu, Qingliang; Chen, Zhenlong; Zhang, Yuhui

    2000-08-01

    By using equilibrium dialysis, atomic absorption spectrometry, fluorescence titration and determination of fluorescence lifetime, it can be determined that each fibrinolytic principle (FP) molecule contains one Ca 2+-binding site and one Ca 2+ ion, which can be substituted by a Tb 3+ ion completely. The intramolecular energy transfer between Tb 3+ and the tryptophan (Trp) residue in FP has been investigated through fluorescence spectroscopy. In the FP molecule, the excited energy can transfer from the Trp residue as an energy donor to the Tb 3+ ion substituted as an acceptor. The distance between Tb 3+ and the Trp residue, ˜0.38 nm, has been calculated with the experimental data and Forster theory.

  17. Influence of dietary saturated fat intake on endothelial fibrinolytic capacity in adults.

    Science.gov (United States)

    Dow, Caitlin A; Stauffer, Brian L; Greiner, Jared J; DeSouza, Christopher A

    2014-09-01

    Approximately 50% of middle-aged and older adults in the United States regularly consume a diet high in saturated fat. High dietary saturated fat intake has been linked to promote atherothrombotic vascular disease. We tested the hypothesis that endothelial fibrinolytic function is diminished in middle-aged and older adults who habitually consume a diet high in saturated fat. Twenty-four healthy, sedentary middle-aged, and older adults (54 to 71 years) were studied: 10 (8 men and 2 women) with a dietary saturated fat intake saturated fat) of total calories and 14 (9 men and 5 women) with a dietary saturated fat intake ≥10% of total calories (high saturated fat). Net endothelial release of tissue-type plasminogen activator (t-PA), the primary activator of fibrinolysis, was determined, in vivo, in response to intrabrachial infusions of bradykinin (12.5 to 50.0 ng/100 ml tissue/min) and sodium nitroprusside (1.0 to 4.0 μg/100 ml tissue/min). Capacity of the endothelium to release t-PA in response to bradykinin was ∼30% less (p saturated fat group. Moreover, total amount of t-PA released was significantly less (∼30%) (201 ± 22 vs 274 ± 29 ng/100 ml tissue) in the adults who reported consuming a diet high in saturated fat. These results indicate that the capacity of the endothelium to release t-PA is lower in middle-aged and older adults who habitually consume a diet high in saturated fat. In conclusion, endothelial fibrinolytic dysfunction may underlie the increased atherothrombotic disease risk with a diet high in saturated fat.

  18. Intensity modulated radiation therapy and chemotherapy for locally advanced pancreatic cancer: Results of feasibility study

    Institute of Scientific and Technical Information of China (English)

    Yong-Rui Bai; Guo-Hua Wu; Wei-Jian Guo; Xu-Dong Wu; Yuan Yao; Yin Chen; Ren-Hua Zhou; Dong-Qin Lu

    2003-01-01

    AIM: To explore whether intensity modulated radiation therapy (IMRT) in combination with chemotherapy could increase radiation dose to gross tumor volume without severe acute radiation related toxicity by decreasing the dose to the surrounding normal tissue in patients with locally advanced pancreatic cancer.METHODS: Twenty-one patients with locally advanced pancreatic cancer were evaluated in this clinical trial,Patients would receive the dose of IMRT from 21Gy to 30Gy in 7 to 10 fractions within two weeks after conventional radiotherapy of 30Gy in 15 fractions over 3 weeks. The total escalation tumor dose would be 51, 54,57, 60Gy, respectively. 5-fluororacil (5-FU) or gemcitabine was given concurrently with radiotherapy during the treatment course.RESULTS: Sixteen patients who had completed the radiotherapy plan with doses of 51Gy (3 cases), 54Gy (3 cases), 57Gy (3 cases) and 60Gy (7 cases) were included for evaluation. The median levels of CA19-9 prior to and after radiotherapy were 716 U/ml and 255 U/ml respectively (P<0.001) in 13 patients who demonstrated high levels of CA19-9 before radiotherapy. Fourteen patients who suffered from pain could reduce at least 1/3-1/2 amount of analgesic intake and 5 among these patients got complete relief of pain. Ten patients improved in Kamofsky performance status (KPS). The median follow-up period was 8 months and one-year survival rate was 35 %. No patient suffered more than grade Ⅲ acute toxicities induced by radiotherapy.CONCLUSION: Sixty Gy in 25 fractions over 5 weeks with late course IMRT technique combined with concurrent 5-FU chemotherapy can provide a definitely palliative benefit with tolerable acute radiation related toxicity for patients with advanced pancreatic cancer.

  19. The efficacy of stereotactic body radiation therapy on huge hepatocellular carcinoma unsuitable for other local modalities.

    Science.gov (United States)

    Que, Jenny Y; Lin, Li-Ching; Lin, Kuei-Li; Lin, Chia-Hui; Lin, Yu-Wei; Yang, Ching-Chieh

    2014-05-28

    To evaluate the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients with unresectable huge hepatocellular carcinoma (HCC) unsuitable of other standard treatment option. Between 2009 and 2011, 22 patients with unresectable huge HCC (≧10 cm) were treated with SBRT. dose ranged from 26 Gy to 40 Gy in five fractions. Overall survival (OS) and disease-progression free survival (DPFS) were determined by Kaplan-Meier analysis. Tumor response and toxicities were also assessed. After a median follow-up of 11.5 month (range 2-46 months). The objective response rate was achieved in 86.3% (complete response (CR): 22.7% and partial response (PR): 63.6%). The 1-yr. local control rate was 55.56%. The 1-year OS was 50% and median survival was 11 months (range 2-46 months). In univariate analysis, Child-Pugh stage (p = 0.0056) and SBRT dose (p = 0.0017) were significant factors for survival. However, in multivariate analysis, SBRT dose (p = 0.0072) was the most significant factor, while Child-Pugh stage of borderline significance. (p = 0.0514). Acute toxicities were mild and well tolerated. This study showed that SBRT can be delivered safely to huge HCC and achieved a substantial tumor regression and survival. The results suggest this technique should be considered a salvage treatment. However, local and regional recurrence remain the major cause of failure. Further studies of combination of SBRT and other treatment modalities may be reasonable.

  20. Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy.

    Science.gov (United States)

    Planas, J; Celma, A; Placer, J; Maldonado, X; Trilla, E; Salvador, C; Lorente, D; Regis, L; Cuadras, M; Carles, J; Morote, J

    2016-11-01

    To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY FOR LOCALLY RECURRENT NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    ZHENG; Xiao-kang

    2001-01-01

    nasopharyngeal carcinomas [J]. Laryngoscope 1999; 109:805.[12]Zheng XK, Chen LH, Xu ZX, et al. The advantages of stereotactic conformal radiotherapy for locally recurrent nasopharyngeal carcinoma [J]. Chin J Cancer 1999; 18:596.[13]International Commission on Radiation Units and Measurements. Prescribing Recording and Reporting Photons Beam Therapy [R]. ICRU Report No. 50, 1992;[14]Gong QY, Zheng GL, Zhu HY. MRI differentiation of recurrent nasopharyngeal carcinoma from postradiation fibrosis [J]. Comput Med Imaging Graph 1991; 15:422.[15]Zhang XK, Chen LH, Xu YL, et al. Quality assure of thermoplastic immobilization for 3-\\d CTR [J]. Chin J Cancer 2001; 20:553.

  2. Engaged Scholarship in Partnership with a Local Hospice: A Qualitative Case Study in a Radiation Therapy Classroom

    Science.gov (United States)

    Trad, Megan

    2012-01-01

    This qualitative case study focuses on providing answers to the following research questions. How do radiation therapy students respond to the implementation of an engaged scholarship partnership with the local hospice in relation to educational gains, experiential learning, transformational learning, and professional growth? This question is…

  3. A Randomized Controlled Trial of Local Heat Therapy Versus Intravenous Sodium Stibogluconate for the Treatment of Cutaneous Leishmania Major Infection

    Science.gov (United States)

    2010-01-01

    Dermatotrophic Leishmania species such as L. major, L. tropica , and L. mexicana are thermosensitive with higher temperatures limiting amastigote replication...Wahid M, Bismullah M, Quinnell RJ, et al. (2005) Efficacy of thermotherapy to treat cutaneous leishmaniasis caused by Leishmania tropica in Kabul...A Randomized Controlled Trial of Local Heat Therapy Versus Intravenous Sodium Stibogluconate for the Treatment of Cutaneous Leishmania major

  4. Three-dimensional conformal hypofractionated simultaneous integrated boost in breast conserving therapy : Results on local control and survival

    NARCIS (Netherlands)

    Bantema-Joppe, Enja J.; van der Laan, Hans Paul; de Bock, Geertruida H.; Wijsman, Robin; Dolsma, Wil V.; Busz, Dianne M.; Langendijk, Johannes A.; Maduro, John H.

    2011-01-01

    PURPOSE: To report on local control and survival after breast conserving therapy (BCT) including three-dimensional conformal simultaneous integrated boost irradiation (3D-CRT-SIB) and on the influence of age on outcome. PATIENT AND METHODS: For this study, 752 consecutive female breast cancer patien

  5. Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors.

    Science.gov (United States)

    Yu, Helena A; Sima, Camelia S; Huang, James; Solomon, Stephen B; Rimner, Andreas; Paik, Paul; Pietanza, M Catherine; Azzoli, Christopher G; Rizvi, Naiyer A; Krug, Lee M; Miller, Vincent A; Kris, Mark G; Riely, Gregory J

    2013-03-01

    Development of acquired resistance limits the utility of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for the treatment of EGFR-mutant lung cancers. There are no accepted targeted therapies for use after acquired resistance develops. Metastasectomy is used in other cancers to manage oligometastatic disease. We hypothesized that local therapy is associated with improved outcomes in patients with EGFR-mutant lung cancers with acquired resistance to EGFR TKI. Patients who received non-central nervous system local therapy were identified by a review of data from a prospective biopsy protocol for patients with EGFR-mutant lung cancers with acquired resistance to EGFR TKI therapy and other institutional biospecimen registry protocols. Eighteen patients were identified, who received elective local therapy (surgical resection, radiofrequency ablation, or radiation). Local therapy was well tolerated, with 85% of patients restarting TKI therapy within 1 month of local therapy. The median time to progression after local therapy was 10 months (95% confidence interval [CI]: 2-27 months). The median time until a subsequent change in systemic therapy was 22 months (95% CI: 6-30 months). The median overall survival from local therapy was 41 months (95% CI: 26-not reached). EGFR-mutant lung cancers with acquired resistance to EGFR TKI therapy are amenable to local therapy to treat oligometastatic disease when used in conjunction with continued EGFR inhibition. Local therapy followed by continued treatment with an EGFR TKI is well tolerated and associated with long PFS and OS. Further study in selected individuals in the context of other systemic options is required.

  6. Anesthetic strategy during endovascular therapy: General anesthesia or conscious sedation? (GOLIATH - General or Local Anesthesia in Intra Arterial Therapy) A single-center randomized trial.

    Science.gov (United States)

    Simonsen, Claus Z; Sørensen, Leif H; Juul, Niels; Johnsen, Søren P; Yoo, Albert J; Andersen, Grethe; Rasmussen, Mads

    2016-12-01

    Endovascular therapy after acute ischemic stroke due to large vessel occlusion is now standard of care. There is equipoise as to what kind of anesthesia patients should receive during the procedure. Observational studies suggest that general anesthesia is associated with worse outcomes compared to conscious sedation. However, the findings may have been biased. Randomized clinical trials are needed to determine whether the choice of anesthesia may influence outcome. The objective of GOLIATH (General or Local Anestesia in Intra Arterial Therapy) is to examine whether the choice of anesthetic regime during endovascular therapy for acute ischemic stroke influence patient outcome. Our hypothesis is that that conscious sedation is associated with less infarct growth and better functional outcome. GOLIATH is an investigator-initiated, single-center, randomized study. Patients with acute ischemic stroke, scheduled for endovascular therapy, are randomized to receive either general anesthesia or conscious sedation. The primary outcome measure is infarct growth after 48-72 h (determined by serial diffusion-weighted magnetic resonance imaging). Secondary outcomes include 90-day modified Rankin Scale score, time parameters, blood pressure variables, use of vasopressors, procedural and anesthetic complications, success of revascularization, radiation dose, and amount of contrast media. Choice of anesthesia may influence outcome in acute ischemic stroke patients undergoing endovascular therapy. The results from this study may guide future decisions regarding the optimal anesthetic regime for endovascular therapy. In addition, this study may provide preliminary data for a multicenter randomized trial. © 2016 World Stroke Organization.

  7. Radiation therapy for localized prostate cancer. For high-dose rate conformal brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kinugawa, Keigo; Jo, Yoshimasa; Morioka, Masaaki; Tanaka, Hiroyoshi; Hiratsuka, Junichi; Imajo, Yoshinari [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    1999-05-01

    Sixteen patients with localized prostate cancer were referred to our clinic for radiation therapy in combination with HDR brachytherapy using Ir-192 pellets between October 1997 and August 1998. The patients were given external beam radiation of 45 Gy to the whole pelvis in combination with an interstitial HDR brachytherapy implant of 3 fractions each delivering 5.5 Gy during two days. Using an implanting device especially designed for HDR, 10-18 applicator needles (17 gauge) were implanted into the prostate using transrectal ultrasound (TRUS) with perineal template guidance under spinal anesthesia. Pathological evaluation was performed at 6 months after treatment. This technique of external beam radiation combined with HDR brachytherapy was well tolerated. Serum prostatic antigen (PSA) levels became normalized in 87.5% of the patients (14 out of 16) within 1-14 months (median 2 months) after the irradiation. No significant intraoperative or perioperative complications occurred, however one patient (6.25%) experienced Grade 3 hematuria. Most of the early complications were otherwise Grade 1 or 2. From prospectively planned prostatic rebiopsies performed at 6 months, we can observe the radiation effects in the pathological findings such as fibrosis, basal cell hyperplasia, bizarre cells and intraductal calcifications. (K.H.)

  8. Stereotactic body radiation therapy for local control of inoperable glomangiomatosis pedis: a case report

    Directory of Open Access Journals (Sweden)

    Zachary D Horne

    2013-03-01

    Full Text Available The vast majority of glomangiomas are small, benign neoplasms that can occur anywhere in the body but typically arise in the subcutaneous tissues of the extremities and are capable of causing extreme pain. Typically, these lesions are managed surgically with excellent rates of tumor control. On occasion, patients present with a variant of the glomangioma tumor consisting of numerous or recurrent nodules, a condition classified as glomangiomatosis. The authors present a case report of a young patient with multiply recurrent painful glomangiomas of the left foot, who was ultimately diagnosed with glomangiomatosis pedis. After multiple surgeries and surgical consultations, no surgery other than amputation was recommended. Therefore, the patient sought consultation with regard to stereotactic body radiation therapy (SBRT. In the absence of other options, and based on its effectiveness in treating glomus tumors of the head and neck which display similar natural history and histologic features, SBRT was offered. The patient underwent SBRT to the largest of his remaining tumors with excellent local control and significant reduction in pain at two and a half years follow-up.

  9. A Comparison of Dose Metrics to Predict Local Tumor Control for Photofrin-mediated Photodynamic Therapy.

    Science.gov (United States)

    Qiu, Haixia; Kim, Michele M; Penjweini, Rozhin; Finlay, Jarod C; Busch, Theresa M; Wang, Tianhao; Guo, Wensheng; Cengel, Keith A; Simone, Charles B; Glatstein, Eli; Zhu, Timothy C

    2017-07-01

    This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [(1) O2 ]rx , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm(-2) ) and in-air fluence rates (50-150 mW cm(-2) ) at Photofrin dosages of 5 and 15 mg kg(-1) and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [(1) O2 ]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [(1) O2 ]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [(1) O2 ]rx ≥ 1.1 mm or PDT dose ≥1200 μm J cm(-2) but cannot be predicted with fluence alone. LCR increases with increasing [(1) O2 ]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [(1) O2 ]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR. © 2017 The American Society of Photobiology.

  10. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Alan eDal Pra

    2016-02-01

    Full Text Available Radiation therapy (RT is one of the mainstay treatments for prostate cancer (PCa. The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: I. androgen signaling pathway; II. hypoxic tumor cells and regions; III. DNA damage response (DDR pathway; and IV. abnormal extra/intra-cell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa.

  11. SU-E-J-259: Quantification of Rotational Localization Offset in Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Y; Nguyen, N; Lee, S; Liu, F [Rhode Island Hospital / Warren Alpert Medical, Providence, RI (United States)

    2014-06-01

    Purpose: To verify the necessity of 6D localization detection and correction in radiation therapy. Methods: An anthropomorphic head and neck phantom was used to test the BrainLab ExacTrac x-ray imaging system. After initial positioning, both ExacTrac and the on-board kV CBCT were used to detect the offset at the same position, using both manual and automatic registration algorithms. Then 6D offset including rotational errors up to 5 degree were introduced. Both ExacTrac and CBCT were used to correct the offsets and the residual errors were evaluated. Finally, 6D offset detected by ExacTrac for a C-Spine patient was reported. Results: The differences in 3D offset detected by ExacTrac and CBCT were 1.5 ± 1.2(Lateral), 2.7 ± 2.7(Vertical), and 4.0 ± 6.3(longitudinal) mm with manual registration while the corresponding differences decreased to 0.6 ± 0.3, 1.0 ± 0.3, and 0.3 ± 0.3 when automatic registration were used. CBCT corrected the translational offset to within 0.5 mm but the rotational errors remained and detected by the ExacTrac system (Yaw=2.1, Roll=1.1, Pitch=1.4 degree). When similar offset was introduced and corrected using ExacTrac, the residual error detected by both CBCT and ExacTrac were within 0.5 mm / 0.5 degree. The average offset from the 112 ExacTrac x-ray corrections for the C-Spine patient was 0.6 ± 1.6 (lateral), 5.4 ± 8(vertical), 1.6±1.1(longitudinal) mm, and 0.7 ± 0.6 (pitch), 0.7 ± 0.4(roll), 1.2 ± 0.7 (yaw) degree. Larger rotational errors, with a maximum of 2.7 degree (corresponds to about 1.5 to 4.5 mm offset for a POI 10 to 30 cm away from the isocenter), were observed when couch rotational were involved. Conclusion: Rotational errors are common in patient localization, especially when couch rotation is involved. Both appropriate imaging system and 6D robotic couch are necessary to detect and correct the rotational localization errors.

  12. Localized Orbital Mucosa-Associated Lymphoma Tissue Lymphoma Managed With Primary Radiation Therapy: Efficacy and Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Goda, Jayant Sastri [Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Le, Lisa W. [Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Lapperriere, Normand J.; Millar, Barbara-Ann; Payne, David; Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander [Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Simpson, Rand [Ocular Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Tsang, Richard W., E-mail: richard.tsang@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)

    2011-11-15

    Purpose: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). Methods and Materials: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. Results: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade {>=}2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). Conclusions: POML responds favorably to moderate doses

  13. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Valentini, Anna Lia, E-mail: alvalentini@rm.unicatt.it [Department of Bioimaging and Radiological Sciences, Section of Radiology, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy); Gui, Benedetta [Department of Bioimaging and Radiological Sciences, Section of Radiology, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy); D' Agostino, Giuseppe Roberto; Mattiucci, Giancarlo [Department of Bioimaging and Radiological Sciences, Section of Radiotherapy, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy); Clementi, Valeria [Clinical Science Development Group, GE Healthcare, Milan (Italy); Di Molfetta, Ippolita Valentina [Department of Bioimaging and Radiological Sciences, Section of Radiology, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy); Bonomo, Pierluigi [OU Clinic Radiobiology, I.F.C.A. Florence (Italy); Mantini, Giovanna [Department of Bioimaging and Radiological Sciences, Section of Radiotherapy, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy)

    2012-11-01

    Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

  14. Novel Sequential Screening and Enhanced Production of Fibrinolytic Enzyme by Bacillus sp. IND12 Using Response Surface Methodology in Solid-State Fermentation

    Science.gov (United States)

    Rajendran, P.; Young Kwon, Oh; Kim, Young Ock

    2017-01-01

    Fibrinolytic enzymes have wide applications in clinical and waste treatment. Bacterial isolates were screened for fibrinolytic enzyme producing ability by skimmed milk agar plate using bromocresol green dye, fibrin plate method, zymography analysis, and goat blood clot lysis. After these sequential screenings, Bacillus sp. IND12 was selected for fibrinolytic enzyme production. Bacillus sp. IND12 effectively used cow dung for its growth and enzyme production (687 ± 6.5 U/g substrate). Further, the optimum bioprocess parameters were found out for maximum fibrinolytic enzyme production using cow dung as a low cost substrate under solid-state fermentation. Two-level full-factorial experiments revealed that moisture, pH, sucrose, peptone, and MgSO4 were the vital parameters with statistical significance (p white (100%), and bovine serum albumin (29 ± 4.9%). PMID:28321408

  15. 78 FR 24750 - Scientific Information Request Therapies for Clinically Localized Prostate Cancer

    Science.gov (United States)

    2013-04-26

    ... Systems, Linear Accelerator ; Radiotherapy Systems, and Proton Beam . Scientific information is being...: Scientific Information Packet Coordinator, 3710 SW US Veterans Hospital Road, Mail Code: R&D 71, Portland, OR... conformal radiation therapy, intensity-modulated radiation therapy, proton beam therapy, and...

  16. Anesthetic strategy during endovascular therapy: General anesthesia or conscious sedation? (GOLIATH - General or Local Anesthesia in Intra Arterial Therapy) A single-center randomized trial

    DEFF Research Database (Denmark)

    Simonsen, Claus Z; Sørensen, Leif H; Juul, Niels

    2016-01-01

    RATIONALE: Endovascular therapy after acute ischemic stroke due to large vessel occlusion is now standard of care. There is equipoise as to what kind of anesthesia patients should receive during the procedure. Observational studies suggest that general anesthesia is associated with worse outcomes...... compared to conscious sedation. However, the findings may have been biased. Randomized clinical trials are needed to determine whether the choice of anesthesia may influence outcome. AIM AND HYPOTHESIS: The objective of GOLIATH (General or Local Anestesia in Intra Arterial Therapy) is to examine whether....... Patients with acute ischemic stroke, scheduled for endovascular therapy, are randomized to receive either general anesthesia or conscious sedation. STUDY OUTCOMES: The primary outcome measure is infarct growth after 48-72 h (determined by serial diffusion-weighted magnetic resonance imaging). Secondary...

  17. Local and systemic inflammatory and immunologic reactions to cyathostomin larvicidal therapy in horses.

    Science.gov (United States)

    Nielsen, M K; Loynachan, A T; Jacobsen, S; Stewart, J C; Reinemeyer, C R; Horohov, D W

    2015-12-15

    Encysted cyathostomin larvae are ubiquitous in grazing horses. Arrested development occurs in this population and can lead to an accumulation of encysted larvae. Large numbers of tissue larvae place the horse at risk for developing larval cyathostominosis. This disease complex is caused by mass emergence of these larvae and is characterized by a generalized acute typhlocolitis and manifests itself as a profuse protein-losing watery diarrhea with a reported case-fatality rate of about 50%. Two anthelmintic formulations have a label claim for larvicidal therapy of these encysted stages; moxidectin and a five-day regimen of fenbendazole. There is limited knowledge about inflammatory and immunologic reactions to larvicidal therapy. This study was designed to evaluate blood acute phase reactants as well as gene expression of pro-inflammatory cytokines, both locally in the large intestinal walls and systemically. Further, mucosal tissue samples were evaluated histopathologically as well as analyzed for gene expression of pro- and anti-inflammatory cytokines, cluster of differentiation (CD) cell surface proteins, and select transcription factors. Eighteen juvenile horses with naturally acquired cyathostomin infections were randomly assigned to three treatment groups; one group served as untreated controls (Group 1), one received a five-day regimen of fenbendazole (10mg/kg) (Group 2), and one group received moxidectin (0.4mg/kg) (Group 3). Horses were treated on day 0 and euthanatized on days 18-20. Serum and whole blood samples were collected on days 0, 5, and 18. All horses underwent necropsy with collection of tissue samples from the ventral colon and cecum. Acute phase reactants measured included serum amyloid A, iron and fibrinogen, and the cytokines evaluated included interferon γ, tumor necrosis factor α, transforming growth factor (TGF)-β, and interleukins 1β, 4, 5, 6, and 10. Transcription factors evaluated were FoxP3, GATA3 and tBet, and CD markers included

  18. local

    Directory of Open Access Journals (Sweden)

    Abílio Amiguinho

    2005-01-01

    Full Text Available The process of socio-educational territorialisation in rural contexts is the topic of this text. The theme corresponds to a challenge to address it having as main axis of discussion either the problem of social exclusion or that of local development. The reasons to locate the discussion in this last field of analysis are discussed in the first part of the text. Theoretical and political reasons are there articulated because the question is about projects whose intentions and practices call for the political both in the theoretical debate and in the choices that anticipate intervention. From research conducted for several years, I use contributions that aim at discuss and enlighten how school can be a potential locus of local development. Its identification and recognition as local institution (either because of those that work and live in it or because of those that act in the surrounding context are crucial steps to progressively constitute school as a partner for development. The promotion of the local values and roots, the reconstruction of socio-personal and local identities, the production of sociabilities and the equation and solution of shared problems were the dimensions of a socio-educative intervention, markedly globalising. This scenario, as it is argued, was also, intentionally, one of transformation and of deliberate change of school and of the administration of the educative territoires.

  19. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp [Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba (Japan); Ioka, Tatsuya [Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Yonemoto, Naohiro [Department of Epidemiology and Biostatistics, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (Japan); Nagase, Michitaka [Department of Clinical Oncology, Jichi Medical University, Tochigi (Japan); Yamao, Kenji [Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya (Japan); Miyakawa, Hiroyuki [Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo (Japan); Ishii, Hiroshi [Hepatobiliary and Pancreatic Division, Cancer Institute Hospital, Tokyo (Japan); Furuse, Junji [Department of Internal Medicine, Medical Oncology School of Medicine, Kyorin University, Tokyo (Japan); Sato, Keiko [Kyoto Unit Center, Japan Environment and Children' s Study, Kyoto University Graduate School of Medicine, Kyoto (Japan); Sato, Tosiya [Department of Biostatistics, Kyoto University School of Public Health, Kyoto (Japan); Okusaka, Takuji [Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo (Japan)

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  20. Locally Targeted Delivery of a Micron-Size Radiation Therapy Source Using Temperature-Sensitive Hydrogel

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yusung, E-mail: yusung-kim@uiowa.edu [Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa (United States); Seol, Dong Rim [Department of Orthopaedic Surgery, The University of Iowa, Iowa City, Iowa (United States); Mohapatra, Sucheta [Department of Biomedical Engineering, The University of Iowa, Iowa City, Iowa (United States); Sunderland, John J. [Department of Radiology, The University of Iowa, Iowa City, Iowa (United States); Schultz, Michael K. [Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa (United States); Department of Radiology, The University of Iowa, Iowa City, Iowa (United States); Domann, Frederick E. [Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa (United States); Department of Surgery, The University of Iowa, Iowa City, Iowa (United States); Lim, Tae-Hong [Department of Biomedical Engineering, The University of Iowa, Iowa City, Iowa (United States)

    2014-04-01

    Purpose: To propose a novel radiation therapy (RT) delivery modality: locally targeted delivery of micron-size RT sources by using temperature-sensitive hydrogel (RT-GEL) as an injectable vehicle. Methods and Materials: Hydrogel is a water-like liquid at room temperature but gels at body temperature. Two US Food and Drug Administration-approved polymers were synthesized. Indium-111 (In-111) was used as the radioactive RT-GEL source. The release characteristics of In-111 from polymerized RT-GEL were evaluated. The injectability and efficacy of RT-GEL delivery to human breast tumor were tested using animal models with control datasets of RT-saline injection. As proof-of-concept studies, a total of 6 nude mice were tested by injecting 4 million tumor cells into their upper backs after a week of acclimatization. Three mice were injected with RT-GEL and 3 with RT-saline. Single-photon emission computed tomography (SPECT) and CT scans were performed on each mouse at 0, 24, and 48 h after injection. The efficacy of RT-GEL was determined by comparison with that of the control datasets by measuring kidney In-111 accumulation (mean nCi/cc), representing the distant diffusion of In-111. Results: RT-GEL was successfully injected into the tumor by using a 30-gauge needle. No difficulties due to polymerization of hydrogel during injection and intratumoral pressure were observed during RT-GEL injection. No back flow occurred for either RT-GEL or RT-saline. The residual tumor activities of In-111 were 49% at 24 h (44% at 48 h, respectively) for RT-GEL and 29% (22%, respectively) for RT-saline. Fused SPECT-CT images of RT-saline showed considerable kidney accumulation of In-111 (2886%, 261%, and 262% of RT-GEL at 0, 24, and 48 h, respectively). Conclusions: RT-GEL was successfully injected and showed much higher residual tumor activity: 170% (200%, respectively), than that of RT-saline at 24 h (48 h, respectively) after injection with a minimal accumulation of In-111 to the

  1. Planned preoperative cisplatin and radiation therapy for locally advanced bladder cancer.

    Science.gov (United States)

    Herr, H W; Yagoda, A; Batata, M; Sogani, P C; Whitmore, W F

    1983-12-15

    Cisplatin (DDP) is an active agent in the treatment of disseminated bladder cancer. In addition to its direct tumor cytotoxicity, recent animal and clinical data suggest synergism with radiation therapy (RT). Since improved survival with preoperative RT is largely restricted to bladder cancer patients in whom radiation-induced downstaging (P less than T) may be recognized, the authors administered DDP + RT preoperatively to patients with locally advanced (T3, T4) bladder tumors selected for cystectomy. The aim was to evaluate the feasibility of such a combination in relation to surgical and hematologic complications, the immediate effect on tumor downstaging, disease progression, and survival. Two thousand rad (400 rad X 5 days) was delivered to the whole pelvis, followed by cystectomy in 2 days. DDP (70 mg/m2) was given intravenously on day 2 of the RT. Twenty-four patients received preoperative DDP + RT and underwent attempted cystectomy; however, six patients were nonresectable owing to extensive pelvic disease, and an additional five patients had resectable pelvic lymph node metastases. Pelvic complications developed in 3 of 24 (12%) patients, but none required reoperation. No patient had a wound dehiscence. Transient myelosuppression was similar to that induced by 2000 rad preoperative RT alone. Tumor downstaging (P less than T) was seen in 9 of 24 (38%) patients, and in 5 (21%) patients, no tumor was found in the surgical specimen (P0). Distant metastases alone have been detected in 4 of 18 (22%) patients who had a cystectomy (all 4 had nodal metastases). Disease-free survival at a median follow-up of 22 months (range, 12-34 months) is 60% (14/24) for all patients (89% for P less than T and 40% for P greater than or equal to T patients) and 78% (14/18) for the resected patients. Combined preoperative DDP + RT proved to be a safe and feasible regimen which resulted in a possibly greater recognition of radioresponsive bladder tumors, and after cystectomy, an

  2. Long-term outcomes of ethanol injection therapy for locally recurrent papillary thyroid cancer.

    Science.gov (United States)

    Kim, Soo Young; Kim, Seok-Mo; Chang, Hojin; Kim, Bup-Woo; Lim, Chi Young; Lee, Yong Sang; Chang, Hang-Seok; Park, Cheong Soo

    2017-06-29

    The standard treatment regimen for locally recurrent lesions is total thyroidectomy, or complete removal of the recurrent thyroid lesion within the thyroid bed. However, reoperation increases the risk of complications and patients have to undergo general anesthesia. Percutaneous ethanol injection therapy represents a far less invasive procedure without general anesthesia and with lower risk of complications. Thirty-four patients who received PEIT at Yonsei University Medical Center between October 2002 and August 2009 for recurrent cervical nodal metastases of differentiated papillary thyroid cancer were included in this retrospective study. During a minimum follow-up of 60 months, treatment outcomes were determined by measuring the lesion size prior to the first injection and 3 months after the last injection. A total of 46 recurrent lesions were detected in 34 patients. Five patients underwent surgery and PEIT was administered to the remaining 19 and 22 lesions in the central compartment and lateral neck lymph nodes, respectively. Size increases were observed in seven (17.1%) lesions, whereas no changes in size and decreases were detected in 10 (24.4%) and 24 (58.5%) lesions. Patients with increased lymph nodes were significantly older (65.3 ± 14.4 vs. 48.2 ± 16.3 years; p = 0.02) and had smaller sizes (9.3 ± 1.0 vs. 12.3 ± 6.4 mm; p = 0.012). Although reoperation remains the first-line treatment for recurrent thyroid cancer, PEIT may be considered as a treatment option in selected patients with lesions larger than 1 cm who are ineligible for surgery or have refused reoperation.

  3. Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

    Science.gov (United States)

    Chen, Yingtai; Che, Xu; Zhang, Jianwei; Huang, Huang; Zhao, Dongbing; Tian, Yantao; Li, Yexiong; Feng, Qinfu; Zhang, Zhihui; Jiang, Qinglong; Zhang, Shuisheng; Tang, Xiaolong; Huang, Xianghui; Chu, Yunmian; Zhang, Jianghu; Sun, Yuemin; Zhang, Yawei; Wang, Chengfeng

    2016-01-01

    Abstract To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT. A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter < 6 cm (hazards ratio [HR], 0.67; 95% confidence interval [CI], 0.47–0.97), no intraoperative interstitial sustained-release 5-fluorouracil chemotherapy (HR, 0.46; 95% CI, 0.32–0.66), and receipt of postoperative chemoradiotherapy followed by chemotherapy (HR, 0.11; 95% CI, 0.04–0.25) were significantly associated with improved OS. Pain relief after IOERT was achieved in 111 of the 117 patients, with complete remission in 74 and partial remission in 37. Postoperative complications rate and mortality were 14.0% and 0.4%, respectively. Nonmetastatic LAPC patients with smaller size tumors could achieve positive long-term survival outcomes with a treatment strategy incorporating IOERT and postoperative adjuvant treatment. Chemoradiotherapy followed by chemotherapy might be a recommended adjuvant treatment strategy for well-selected cases. Intraoperative interstitial sustained-release 5-fluorouracil chemotherapy should not be recommended for patients with nonmetastatic LAPC. PMID:27661028

  4. Targeted local simultaneous iontophoresis of chemotherapeutics for topical therapy of head and neck cancers.

    Science.gov (United States)

    Gratieri, Taís; Kalia, Yogeshvar N

    2014-01-02

    The objective was to investigate the feasibility of using buccal iontophoresis for the simultaneous delivery of chemotherapeutic agents with a view to developing a new approach to treat head and neck cancers. Short duration cathodal iontophoresis of 5-fluorouracil (5-FU; 20mM) and leucovorin (LV; 10 mM) at 1 mA/cm(2) for 10 or 20 min from aqueous solution and a 2% hydroxyethyl cellulose gel at pH 7.6 was evaluated using bovine mucosa in vitro. Iontophoresis resulted in a statistically significant increase in the mucosal deposition of both drugs as compared to passive diffusion (Student's t-test, α=0.05); in each case, drug delivery was selective for deposition with no permeation being observed. After 20 min of iontophoresis, there was an ~ 8-fold enhancement for 5-FU (1.46 ± 0.86 and 11.93 ± 3.81 μg/cm(2), respectively) and a 3-fold increase for LV (8.31 ± 2.44 and 25.08 ± 6.89 μg/cm(2), respectively) when using aqueous solutions. The same trend was observed when the gel was applied for 10 min; passive delivery of 5-FU from the gel resulted in non-detectable levels in the mucosa, while 4.62 ± 1.76 μg/cm(2) were deposited in the mucosa following iontophoresis. Similarly, iontophoretic delivery of LV from the gel resulted in ~ 3-fold higher deposition as compared to passive diffusion (6.71 ± 1.36 and 21.12 ± 9.94 μg/cm(2), respectively). No drug permeation was observed in either case. In conclusion, iontophoresis can be used for targeted topical delivery of chemotherapeutics to the buccal mucosa and may enable less invasive local therapy of head and neck cancers.

  5. COMPLEX INTRAVENOUS OR LOCAL OZONE AND LOW-INTENSE LASER THERAPY IN CORRECTION OF MALIGNANT TUMORS MULTIMODAL TREATMENT COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    V. A. Titova

    2009-01-01

    Full Text Available Multmodal programs are the perspective trend in different malignant tumors treatment but increasing risk of combined complications may influence negatively on the results. Ozone therapy and low-intense laser therapy are perspective methods for complication treatment and prevention as they show their own antibacterial, analgesia and detoxing activity in experiment.To form the algorhythm and to evaluate the results of intravenous and local ozone applications plus low-intense laser (LILT therapeutic complex used in treatment and prevention of malignant tumors multimodal treatment complications.

  6. Localization accuracy from automatic and semi-automatic rigid registration of locally-advanced lung cancer targets during image-guided radiation therapy

    Science.gov (United States)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2012-01-01

    Purpose: To evaluate localization accuracy resulting from rigid registration of locally-advanced lung cancer targets using fully automatic and semi-automatic protocols for image-guided radiation therapy. Methods: Seventeen lung cancer patients, fourteen also presenting with involved lymph nodes, received computed tomography (CT) scans once per week throughout treatment under active breathing control. A physician contoured both lung and lymph node targets for all weekly scans. Various automatic and semi-automatic rigid registration techniques were then performed for both individual and simultaneous alignments of the primary gross tumor volume (GTVP) and involved lymph nodes (GTVLN) to simulate the localization process in image-guided radiation therapy. Techniques included “standard” (direct registration of weekly images to a planning CT), “seeded” (manual prealignment of targets to guide standard registration), “transitive-based” (alignment of pretreatment and planning CTs through one or more intermediate images), and “rereferenced” (designation of a new reference image for registration). Localization error (LE) was assessed as the residual centroid and border distances between targets from planning and weekly CTs after registration. Results: Initial bony alignment resulted in centroid LE of 7.3 ± 5.4 mm and 5.4 ± 3.4 mm for the GTVP and GTVLN, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTVP centroid LE to 4.7 ± 3.7 mm (p = 0.011) and 4.3 ± 2.5 mm (p < 1 × 10−3), respectively, but the smallest GTVP LE of 2.4 ± 2.1 mm was provided by rereferenced registration (p < 1 × 10−6). Standard registration significantly reduced GTVLN centroid LE to 3.2 ± 2.5 mm (p < 1 × 10−3) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low as 3

  7. [Besides fibrinogen, are haemostatic, coagulation and/or fibrinolytic parameters predictors or markers of the risk of cardiovascular events?].

    Science.gov (United States)

    Drouet, Ludovic; Bal dit Sollier, Claire

    2005-01-01

    Most cardiovascular events result from a thrombotic complication of atherosclerotic lesions. In arterial vessels such as the coronary bed, an interrelationship of haemostatic, coagulation and fibrinolytic factors is implicated. While it can be demonstrated that fibrinogen is a risk factor/marker, the role of other factors is not well established. Under arterial flow conditions, platelets are predominantly involved in the thrombotic reaction. Yet, apart from a large increase in the platelet count, the involvement of platelet parameters in cardiovascular risk is not clearly evident. The lack of definitive platelet markers is at least partly due to the difficulty of studying platelet function ex vivo. Several polymorphisms of platelet glycoproteins carrying a moderate increase in risk have been reported, but only in younger patients. One potentially important factor for coagulation is the fibrin structure, which is dependent on fibrinogen, the rate of thrombin generation, the activity of factor XIII and the interrelationship of the cells concerned, all of which act on its sensitivity to thrombosis. Coagulation factors largely affect the rate of thrombin generation. The activity of the fibrinolytic system (and principally any deficiency) has a role in the cardiovascular risk. General markers of cardiovascular risk such as D-dimers are potentially useful, but they increase with thrombin generation and are decreased by a deficiency in fibrinolysis. Furthermore, possibly because they are not indicative of the fibrin structure, they are poorly correlated with clinical events. The poor significance of the available haemostatic, coagulation and/or fibrinolytic parameters is probably due to their lack of representativeness, since haemostatic, coagulation and fibrinolytic systems are all involved in the thrombotic response (and some in atherogenesis itself). Atherogenesis is a multifactorial process and numerous moderate risk factors act in association. Better predictability

  8. Anti-inflammatory and anti-fibrinolytic effects of thrombomodulin alfa through carboxypeptidase B2 in the presence of thrombin.

    Science.gov (United States)

    Tawara, Shunsuke; Sakai, Takumi; Matsuzaki, Osamu

    2016-11-01

    Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities. Therefore, TM alfa may also have anti-inflammatory and anti-fibrinolytic effects through CPB2. However, these effects of TM alfa have not been elucidated. In the present study, we investigated the effects of TM alfa on inactivation of complement component C5a as an anti-inflammatory effect and prolongation of clot lysis time as an anti-fibrinolytic effect via CPB2 in vitro. CPB2 activity and tissue factor-induced thrombin generation was examined by a chromogenic assay. C5a inactivation was evaluated by C-terminal cleavage of C5a and inhibition of C5a-induced human neutrophil migration. Clot lysis time prolongation was examined by a tissue-type plasminogen activator-induced clot lysis assay. CPB2 activity in human plasma was increased by TM alfa and thrombin in a concentration-dependent manner. TM alfa inhibited tissue factor-induced thrombin generation and enhanced pro-CPB2 activation in human plasma simultaneously. The mass spectrum of C5a treated with TM alfa, thrombin, and pro-CPB2 was decreased at 156m/z, indicating that TM alfa enhanced the processing of C5a to C-terminal-cleaved C5a, an inactive form of C5a. C5a-induced human neutrophil migration was decreased after C5a treatment with TM alfa, thrombin, and pro-CPB2. TM alfa prolonged the clot lysis time in human plasma, and this effect was completely abolished by addition of a CPB2 inhibitor. TM alfa exerts anti-inflammatory and anti-fibrinolytic effects through CPB2 in the presence of thrombin in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Comparison of the effectiveness of local corticosteroid injection and extracorporeal shock wave therapy in patients with lateral epicondylitis.

    Science.gov (United States)

    Beyazal, Münevver Serdaroğlu; Devrimsel, Gül

    2015-12-01

    [Purpose] This study aimed to determine and compare the effectiveness of extracorporeal shock wave therapy and local corticosteroid injection in patients with lateral epicondylitis. [Subjects and Methods] Sixty-four patients with lateral epicondylitis were randomly divided into extracorporeal shock wave therapy and steroid injection groups. Patients were evaluated using hand grip strength, visual analog scale, and short-form McGill pain questionnaire at baseline and at 4 and 12 weeks post-treatment. [Results] Both groups showed statistically significant increase in hand grip strength and decreases on the visual analog scale and short form McGill pain questionnaire overtime. There was no statistically significant difference in the percentage of improvement in hand grip strength and on the short-form McGill pain questionnaire between groups at 4 weeks post-treatment, whereas the extracorporeal shock wave therapy group showed better results on the visual analog scale. The percentages of improvements in all 3 parameters were higher in the extracorporeal shock wave therapy group than in the injection group at 12 weeks post-treatment. [Conclusion] Both the extracorporeal shock wave therapy and steroid injection were safe and effective in the treatment of lateral epicondylitis. However, extracorporeal shock wave therapy demonstrated better outcomes than steroid injection at the long-term follow-up.

  10. BRACHYTHERAPY ALONE OR WITH NEOADJUVANT PHOTODYNAMIC THERAPY FOR AMELANOTIC CHOROIDAL MELANOMA: Functional Outcomes and Local Tumor Control.

    Science.gov (United States)

    Blasi, Maria A; Laguardia, Michela; Tagliaferri, Luca; Scupola, Andrea; Villano, Antonio; Caputo, Carmela G; Pagliara, Monica M

    2016-11-01

    To compare visual outcomes and local tumor control between two groups of patients with amelanotic choroidal melanoma treated with brachytherapy alone, or neoadjuvant photodynamic therapy before brachytherapy. Patients diagnosed with amelanotic choroidal melanoma were recruited for the study and divided into two groups: brachytherapy alone (Group A) and photodynamic therapy preceding brachytherapy (Group B). Patients of both groups were selected to be comparable. Twenty-six patients with amelanotic choroidal melanoma were enrolled in the study. Within Group B, 1 month after photodynamic therapy, ultrasonography showed reduction of tumor height in 11 patients (73.4%). The mean doses of irradiation to macula and optic nerve, at baseline were 74.37 and 52.07 Gy, whereas after photodynamic therapy there was a decrease of 17.26% (P = 0.008) and 21.22% (P = 0.025), respectively. In terms of visual acuity, a mean decrease of 14 ETDRS letters and 5 ETDRS letters was observed at 24 months follow-up, in Groups A and B, respectively (P = 0.001). Photodynamic therapy as neoadjuvant therapy before brachytherapy reduces tumor thickness in 73.4% of cases. As a result, a decrease of radiation toxic effects on visual function could be obtained, without compromising disease control.

  11. Production, Purification and Characterisation of a Potential Fibrinolytic Protease from Endophytic Xylaria curta by Solid Substrate Fermentation.

    Science.gov (United States)

    Meshram, Vineet; Saxena, Sanjai; Paul, Karan; Gupta, Mahiti; Kapoor, Neha

    2017-04-01

    The present investigation highlights the optimal conditions for production of a non-toxic, bi-functional fibrinolytic enzyme xylarinase produced by endophytic fungus Xylaria curta by solid substrate fermentation using rice chaff medium. The purified enzyme is a monomeric protein with a molecular mass of ∼33 kDa. The enzyme exhibits cleavage of Aα and Bβ chains of fibrin(ogen) and has no effect on γ chain. The optimal fibrinolytic activity of the enzyme was observed at 35 °C and pH 8. The fibrinolytic activity was enhanced in the presence of Ca(2+), whereas it was completely inhibited in the presence of Fe(2+) and Zn(2+) ions and inhibitors like EDTA and EGTA suggesting it to be a metalloprotease. The K m and V max of the enzyme for azocasein were 326 μM and 0.13 μM min(-1). The N-terminal sequence of the enzyme (SNGPLPGGVVWAG) was same when compared to xylarinase isolated from culture broth of X. curta. Thus, xylarinase could be exploited as a potent clot busting enzyme which could be produced on large scale using solid substrate fermentation.

  12. Verticase:a Fibrinolytic Enzyme Produced by Verticillium sp.Tj33,an Endophyte of Trachelospermum jasminoides

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Plant endophytes are among the most important resources of biologically active metabolites.Twenty-three endophyte strains residing in Trachelospermum jasminoides were cultivated In with the cultures assayed for the fibrinolytic substance production.As a result,the culture of Verticillium sp.Tj33 was shown to be the most active.A fibrinolytic enzyme designated as verticase was subsequently purified from the supernatant of Verticillium sp.culture broth by a combination of DEAE-52,Sephadex G-75 and hydrophobic column chromatographies.Verticase,with its molecular mass of 31 kDa and pl of 8.5,was demonstrated to be homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing electrophoresis.Verticase is an enzyme that hydrolyzes fibrin directly without activation of plaminogen.It was stable in a broad pH range from 4 through to 11 with the optimal reaction pH value and temperature shown to be around 9-10 and 50-60℃,respectively.The fibrinolytic activity of verticase was severely inhibited by phenylmethylsulfony fluoride,Indicating that verticase was a serine protease.

  13. Local dose enhancement in radiation therapy: Monte Carlo simulation study; Reforco local de dose em radioterapia utilizando nanoparticulas: estudo por simulacao Monte Carlo

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Laura E. da; Nicolucci, Patricia, E-mail: laura.emilia.fm@gmail.com [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras

    2014-04-15

    The development of nanotechnology has boosted the use of nanoparticles in radiation therapy in order to achieve greater therapeutic ratio between tumor and healthy tissues. Gold has been shown to be most suitable to this task due to the high biocompatibility and high atomic number, which contributes to a better in vivo distribution and for the local energy deposition. As a result, this study proposes to study, nanoparticle in the tumor cell. At a range of 11 nm from the nanoparticle surface, results have shown an absorbed dose 141 times higher for the medium with the gold nanoparticle compared to the water for an incident energy spectrum with maximum photon energy of 50 keV. It was also noted that when only scattered radiation is interacting with the gold nanoparticles, the dose was 134 times higher compared to enhanced local dose that remained significant even for scattered radiation. (author)

  14. Very Late Local Relapse of Ewing's Sarcoma of the Head and Neck treated with Aggressive Multimodal Therapy

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    J. Thariat

    2008-01-01

    Full Text Available Ewing's sarcoma's relapse rarely occurs more than two years after the initial diagnosis. We report the case of a 26-year-old man with a history of Ewing's sarcoma of the left maxillary sinus at the age of 10 who presented with a very late local relapse, 16 years after the first occurrence of disease. Ultimate control was achieved after multimodal therapy including surgery, high-dose chemotherapy, and radiotherapy. This report indicates that local relapses of Ewing's sarcoma can be treated with curative intent in selected cases.

  15. Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model

    Science.gov (United States)

    Conde, João; Oliva, Nuria; Zhang, Yi; Artzi, Natalie

    2016-10-01

    Conventional cancer therapies involve the systemic delivery of anticancer agents that neither discriminate between cancer and normal cells nor eliminate the risk of cancer recurrence. Here, we demonstrate that the combination of gene, drug and phototherapy delivered through a prophylactic hydrogel patch leads, in a colon cancer mouse model, to complete tumour remission when applied to non-resected tumours and to the absence of tumour recurrence when applied following tumour resection. The adhesive hydrogel patch enhanced the stability and provided local delivery of embedded nanoparticles. Spherical gold nanoparticles were used as a first wave of treatment to deliver siRNAs against Kras, a key oncogene driver, and rod-shaped gold nanoparticles mediated the conversion of near-infrared radiation into heat, causing the release of a chemotherapeutic as well as thermally induced cell damage. This local, triple-combination therapy can be adapted to other cancer cell types and to molecular targets associated with disease progression.

  16. Thoracoscopic monitoring for pericardial application of local drug or gene therapy

    NARCIS (Netherlands)

    Tio, RA; Grandjean, JG; Suurmeijer, AJH; van Gilst, WH; van Veldhuisen, DJ; van Boven, AJ

    Cardiovascular gene therapy is a promising new approach for a variety of diseases. As far as gene therapy aimed at the myocardium is concerned a new transcutaneous delivery method may be into the pericardial sac. Objective: To evaluate the safety and applicability of the percutaneous pericardial

  17. Thoracoscopic monitoring for pericardial application of local drug or gene therapy

    NARCIS (Netherlands)

    Tio, RA; Grandjean, JG; Suurmeijer, AJH; van Gilst, WH; van Veldhuisen, DJ; van Boven, AJ

    2002-01-01

    Cardiovascular gene therapy is a promising new approach for a variety of diseases. As far as gene therapy aimed at the myocardium is concerned a new transcutaneous delivery method may be into the pericardial sac. Objective: To evaluate the safety and applicability of the percutaneous pericardial del

  18. Outcome and Toxicity of an Ifosfamide-Based Soft Tissue Sarcoma Treatment Protocol in Children. The Importance of Local Therapy

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    S. Murray Yule

    1998-01-01

    Full Text Available Background. Although the survival of children with soft tissue sarcoma (STS has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide-based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.

  19. Prospective Randomized Comparison of the Effectiveness of Radiation Therapy and Local Steroid Injection for the Treatment of Plantar Fasciitis

    Energy Technology Data Exchange (ETDEWEB)

    Canyilmaz, Emine, E-mail: dremocan@ktu.edu.tr [Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon (Turkey); Canyilmaz, Fatih [Department of Orthopaedics and Traumatology, Yavuz Selim Bone Disease and Rehabilitation Hospital, Trabzon (Turkey); Aynaci, Ozlem; Colak, Fatma; Serdar, Lasif [Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon (Turkey); Uslu, Gonca Hanedan [Department of Radiation Oncology, Kanuni Research and Education Hospital, Trabzon (Turkey); Aynaci, Osman [Department of Orthopaedics and Traumatology, Faculty of Medicine, Karadeniz Technical University, Trabzon (Turkey); Yoney, Adnan [Department of Radiation Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon (Turkey)

    2015-07-01

    Purpose: The purpose of this study was to conduct a randomized trial of radiation therapy for plantar fasciitis and to compare radiation therapy with local steroid injections. Methods and Materials: Between March 2013 and April 2014, 128 patients with plantar fasciitis were randomized to receive radiation therapy (total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy three times a week) or local corticosteroid injections a 1 ml injection of 40 mg methylprednisolone and 0.5 ml 1% lidocaine under the guidance of palpation. The results were measured using a visual analog scale, a modified von Pannewitz scale, and a 5-level function score. The fundamental phase of the study was 3 months, with a follow-up period of up to 6 months. Results: The median follow-up period for all patients was 12.5 months (range, 6.5-18.6 months). For the radiation therapy patients, the median follow-up period was 13 months (range, 6.5-18.5 months), whereas in the palpation-guided (PG) steroid injection arm, it was 12.1 months (range, 6.5-18.6 months). After 3 months, results in the radiation therapy arm were significantly superior to those in the PG steroid injection arm (visual analog scale, P<.001; modified von Pannewitz scale, P<.001; 5-level function score, P<.001). Requirements for a second treatment did not significantly differ between the 2 groups, but the time interval for the second treatment was significantly shorter in the PG steroid injection group (P=.045). Conclusion: This study confirms the superior analgesic effect of radiation therapy compared to mean PG steroid injection on plantar fasciitis for at least 6 months after treatment.

  20. Local steroid therapy as the first-line treatment for boys with symptomatic phimosis - a long-term prospective study.

    Science.gov (United States)

    Reddy, Srinath; Jain, Viral; Dubey, Manish; Deshpande, Pankaj; Singal, Arbinder K

    2012-03-01

    Phimosis is a common paediatric urological disorder and often necessitates circumcision. We prospectively evaluated local steroid therapy (LST) as the first choice therapy for such children. Two hundred and sixty symptomatic boys up to 15 years of age (mean 34 months) with phimosis were started on betamethasone dipropionate (0.05%) application on gently stretched prepuce twice a day. Follow-up visits were arranged at the end of weeks 1, 2 and 4 and 6 months. Grade of phimosis was objectively graded. Ninety one percent of the boys showed a successful outcome at the end of 4 weeks; 72% responded in first week, further 16% responded in week 2, and only 2.6% achieved alleviation of phimosis on further application of LST beyond 2 weeks. Fourty two (17.8%) boys had a recurrence of phimosis on a long-term follow-up (mean - 25.4 months, range 6-48 months); thus, the long-term success rate was 77%, while 60 (23%) boys underwent surgery. Local steroid therapy is safe and successful in alleviating symptomatic tight foreskin in a large majority of children. The response can be seen as early as 1 week; most of the children respond by week 2 and continuing therapy further may not be very effective. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

  1. Treatment response evaluation with three-dimensional contrast-enhanced ultrasound for liver cancer after local therapies

    Energy Technology Data Exchange (ETDEWEB)

    Xu Huixiong, E-mail: xuhuixiong@hotmail.co [Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China); Lu Mingde, E-mail: lumd@21cn.co [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China); Xie Xiaohua; Xie Xiaoyan [Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China); Kuang Ming [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China); Xu Zuofeng; Liu Guangjian; Wang Zhu; Chen Lida; Lin Manxia [Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, First Affiliated Hospital, Sun Yat-Sen University, 58th Zhongshan Road 2, Guangzhou 510080 (China)

    2010-10-15

    Objective: To investigate the potential usefulness of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in evaluating the treatment response for liver cancer after local therapies. Methods: A total of 107 lesions in 95 consecutive patients with liver cancer underwent local therapies and thereafter received low acoustic power 3D-CEUS examination. The LOGIQ 9 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The image quality of 3D-CEUS images was evaluated and the influence of 3D-CEUS to clinical outcome was investigated. Results: The image quality of 3D-CEUS was defined as high in 102 (102/107, 95.3%) lesions and common in 5 (5/107, 4.7%) lesions. 3D-CEUS did not change the diagnosis in any patient compared with 2D-CEUS. However, 3D-CEUS changed the management in 3 (2.8%) of 107 lesions, increased confidence but made no change in diagnosis in 85 (79.5%) lesions, added some information but did not change management or diagnosis in 15 (14.0%), and made no change in 4 (3.7%), respectively, in comparison with 2D-CEUS. Conclusion: 3D-CEUS enhances the diagnostic confidence in the majority of the patients and even changes the management in some patients. 3D-CEUS has potential usefulness in evaluating treatment response for liver cancer after local therapies.

  2. Impact of reperfusion therapy and infarct localization on frequency of premature ventricular beats in acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Davor Horvat

    2015-08-01

    Full Text Available Aim To determine the impact of infarct localization and types of reperfusion therapy on the frequency of ventricular premature beats (VPBs in patients with acute myocardial infarction (AMI and reduced left ventricular ejection fraction (LVEF. Methods A total of 705 patients with acute ST elevation myocardial infarction (STEMI were divided according to the infarct localization (anteroseptal, anterolateral, inferior and posterior and reperfusion therapy (fibrinolysis or percutaneous coronary intervention with stenting into two groups: LVEF45% was a control group. The occurrence of VPBs10 per hour defined as a significant. Results In patients with fibrinolysis therapy and LVEF<45% significant number of VPBs were in anteroseptal (p=0.017, anterolateral (p<0.001 and posterior AMI (p<0.001, but in patients with percutaneous coronary intervention (PCI and LVEF<45% significant number of VPBs were only in anteroseptal AMI (p=0.001 localization. Conclusion In patients with reduced ejection fraction in AMI, treatment with PCI method has a better antiarrhythmic effect compared to fibrinolysis treatment.

  3. Geometric validation of MV topograms for patient localization on TomoTherapy

    Science.gov (United States)

    Blanco Kiely, Janid P.; White, Benjamin M.; Low, Daniel A.; Qi, Sharon X.

    2016-01-01

    Our goal was to geometrically validate the use of mega-voltage orthogonal scout images (MV topograms) as a fast and low-dose alternative to mega-voltage computed tomography (MVCT) for daily patient localization on the TomoTherapy system. To achieve this, anthropomorphic head and pelvis phantoms were imaged on a 16-slice kilo-voltage computed tomography (kVCT) scanner to synthesize kilo-voltage digitally reconstructed topograms (kV-DRT) in the Tomotherapy detector geometry. MV topograms were generated for couch speeds of 1-4 cm s-1 in 1 cm s-1 increments with static gantry angles in the anterior-posterior and left-lateral directions. Phantoms were rigidly translated in the anterior-posterior (AP), superior-inferior (SI), and lateral (LAT) directions to simulate potential setup errors. Image quality improvement was demonstrated by estimating the noise level in the unenhanced and enhanced MV topograms using a principle component analysis-based noise level estimation algorithm. Average noise levels for the head phantom were reduced by 2.53 HU (AP) and 0.18 HU (LAT). The pelvis phantom exhibited average noise level reduction of 1.98 HU (AP) and 0.48 HU (LAT). Mattes Mutual Information rigid registration was used to register enhanced MV topograms with corresponding kV-DRT. Registration results were compared to the known rigid displacements, which assessed the MV topogram localization’s sensitivity to daily positioning errors. Reduced noise levels in the MV topograms enhanced the registration results so that registration errors were  <1 mm. The unenhanced head MV topograms had discrepancies  <2.1 mm and the pelvis topograms had discrepancies  <2.7 mm. Result were found to be consistent regardless of couch speed. In total, 64.7% of the head phantom MV topograms and 60.0% of the pelvis phantom MV topograms exactly measured the phantom offsets. These consistencies demonstrated the potential for daily patient positioning using MV topogram pairs in the

  4. Monotherapy of androgen deprivation therapy versus radical prostatectomy among veterans with localized prostate cancer: comparative effectiveness analysis of retrospective cohorts

    Directory of Open Access Journals (Sweden)

    Liu J

    2012-05-01

    Full Text Available Jinan Liu1,2, Lizheng Shi1,2,3, Oliver Sartor31Tulane University, School of Public Health and Tropical Medicine, 2Southeast Louisiana Veterans Health Care System, Tulane University, 3School of Medicine and Tulane Cancer Center, New Orleans, LA, USABackground: This retrospective cohort study aimed to examine the comparative effectiveness of monotherapy of primary androgen deprivation therapy or radical prostatectomy.Methods: Male patients with localized prostate cancer (T1-T2, N0, M0 were identified in the Veterans Affairs Veterans Integrated Service Network 16 data warehouse (January 2003 to June 2006, with one-year baseline and at least three-year follow-up data (until June 2009. Patients were required to be 18–75 years old and without other recorded cancer history. The initiation of primary androgen deprivation therapy or monotherapy of radical prostatectomy within six months after the first diagnosis of prostate cancer was used as the index date. Primary androgen deprivation therapy patients were matched to the radical prostatectomy patients via propensity score, which was predicted from a logistic regression of treatment selection (primary androgen deprivation therapy versus radical prostatectomy on age, race, marital status, insurance type, cancer stage, Charlson comorbidity index, and alcohol and tobacco use. The overall survival from initiation of index treatment was then analyzed using the Kaplan–Meier and Cox proportional hazards model.Results: The two cohorts were well matched at baseline (all P > 0.05. During a median follow-up of 4.3 years, the cumulative incidence of death was 13 (10.57% among 123 primary androgen deprivation therapy patients and four (3.25% among 123 radical prostatectomy patients (P < 0.05. The overall three-year survival rate was 92.68% for primary androgen deprivation therapy and 98.37% for radical prostatectomy (P < 0.05. Patients who received primary androgen deprivation therapy had almost three times as

  5. Detection of Local Cancer Recurrence After Stereotactic Ablative Radiation Therapy for Lung Cancer: Physician Performance Versus Radiomic Assessment.

    Science.gov (United States)

    Mattonen, Sarah A; Palma, David A; Johnson, Carol; Louie, Alexander V; Landis, Mark; Rodrigues, George; Chan, Ian; Etemad-Rezai, Roya; Yeung, Timothy P C; Senan, Suresh; Ward, Aaron D

    2016-04-01

    Stereotactic ablative radiation therapy (SABR) is a guideline-specified treatment option for early-stage lung cancer. However, significant posttreatment fibrosis can occur and obfuscate the detection of local recurrence. The goal of this study was to assess physician ability to detect timely local recurrence and to compare physician performance with a radiomics tool. Posttreatment computed tomography (CT) scans (n=182) from 45 patients treated with SABR (15 with local recurrence matched to 30 with no local recurrence) were used to measure physician and radiomic performance in assessing response. Scans were individually scored by 3 thoracic radiation oncologists and 3 thoracic radiologists, all of whom were blinded to clinical outcomes. Radiomic features were extracted from the same images. Performances of the physician assessors and the radiomics signature were compared. When taking into account all CT scans during the whole follow-up period, median sensitivity for physician assessment of local recurrence was 83% (range, 67%-100%), and specificity was 75% (range, 67%-87%), with only moderate interobserver agreement (κ = 0.54) and a median time to detection of recurrence of 15.5 months. When determining the early prediction of recurrence within recurrence, with a mean error of 35%, false positive rate (FPR) of 1%, and false negative rate (FNR) of 99%. At the same time point, a radiomic signature consisting of 5 image-appearance features demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.85, classification error of 24%, FPR of 24%, and FNR of 23%. These results suggest that radiomics can detect early changes associated with local recurrence that are not typically considered by physicians. This decision support system could potentially allow for early salvage therapy of patients with local recurrence after SABR. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Multimodal Therapy including Yttrium-90 Radioembolization as a Bridging Therapy to Liver Transplantation for a Huge and Locally Advanced Intrahepatic Cholangiocarcinoma.

    Science.gov (United States)

    Rayar, Michel; Levi Sandri, Giovanni Battista; Houssel-Debry, Pauline; Camus, Christophe; Sulpice, Laurent; Boudjema, Karim

    2016-09-01

    Treatment of intrahepatic cholangiocarcinoma remains a major challenge. For an unresectable lesion without extrahepatic spread, liver transplantation could be a potential solution but it is still associated with poor oncologic results owing to the absence of effective neoadjuvant treatment. We report the case of a young man with locally advanced intrahepatic cholangiocarcinoma presenting with multiple intrahepatic metastases and vascular structure involvement. The lesion was significantly downstaged by a multimodal therapy including intra-arterial Yttrium-90 radioembolization, systemic chemotherapy and external radiotherapy, allowing liver transplantation. Three years after the procedure, oncologic outcome is excellent with no sign of recurrence. Multimodal therapy including Yttrium-90 radioembolization could be relevant as neoadjuvant treatment before liver transplantation for unresectable intrahepatic cholangiocarcinoma.

  7. Definitive radiation therapy for treatment of laryngeal carcinoma. Impact of local relapse on outcome and implications for treatment strategies

    Energy Technology Data Exchange (ETDEWEB)

    Hoebers, F.; Rios, E.; Troost, E.; Ende, P. van den; Jong, J. de [Maastricht Univ. Medical Centre, Maastricht (Netherlands). Dept. of Radiation Oncology (MAASTRO Clinic); Kross, K.; Lacko, M.; Kremer, B. [Maastricht Univ. Medical Centre, Maastricht (Netherlands). Dept. of Otorhinolaryngology - Head and Neck Surgery; Lalisang, R. [Maastricht Univ. Medical Centre, Maastricht (Netherlands). Div. of Medical Oncology

    2013-10-15

    Purpose: The purpose of this work was to evaluate outcome after radiotherapy (RT) for laryngeal carcinoma and investigate effects of local relapse on ultimate disease control, including surgical salvage procedures. Methods and materials: In all, 435 patients with laryngeal carcinoma (cT1-cT4a) treated with primary RT were retrospectively analyzed. Uni- and multivariate analyses were performed to identify prognostic factors for local relapse-free survival and overall survival. Results: Median follow-up was 38 months (range 1-144 months). The cumulative frequency of local recurrence was dependent on T stage: cT1 tumors 10 %, cT2 18 %, cT3 23 %, and cT4 36 % (p < 0.001). Salvage surgery for local persistent/recurrent disease was performed in 59 of 78 patients (76 %). The ultimate local control rates at 5 years (including salvage therapy) were 98, 98, 87, and 68 % for cT1, cT2, cT3, and cT4 tumors (p < 0.001), respectively. For the patients who developed local recurrence, the 5-year ultimate local control rates were 80, 88, 55, and 26 % (p < 0.001), respectively. Overall survival at 5 years was 68 % for patients without local relapse and 50 % for patients experiencing local failure (p < 0.001). In univariate analysis, cT stage, cN stage, and tumor volume were statistically significant associated with local relapse-free survival. In multivariate analysis for the cT3-4 tumors, only tumor volume remained statistically significant (HR 1.017, p = 0.001) for local relapse-free survival. Conclusion: Local control rates for cT1-2 laryngeal carcinomas are favorable and in concordance with previous reports and most recurrences are salvaged. For cT3-4 tumors treated with RT alone, initial local control rates are moderate, and in 60 % of recurring cases salvage surgery is attempted, with ultimate local control being achieved in only a subset. For voluminous, locally advanced laryngeal tumors, more aggressive treatment modalities should be considered, including upfront laryngectomy

  8. Changes in Coagulation and Fibrinolytic Indices in Women with Polycystic Ovarian Syndrome Undergoing Controlled Ovarian Hyperstimulation

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    Ying Huang

    2014-01-01

    Full Text Available Background. Polycystic ovarian syndrome (PCOS women undergoing in vitro fertilization and embryo transfer (IVF-ET treatment always attain a low cumulative pregnancy rate disaccording with the satisfactory number of oocytes. Objective. We aim to evaluate the status of coagulation and fibrinolytic system in PCOS patients undergoing controlled ovarian hyperstimulation (COH process. Method. Of the 97 women, 30 patients with PCOS composed the study group; 67 women of child-bearing age with normal endocrine function composed the control group. All participants underwent GnRH agonist standard long protocol, and plasma HCY, FVIII, FX, and D-dimer levels as well as hormone parameters were measured at day of full downregulation, hCG priming, and embryos transfer. Results. On day of full downregulation, FX levels were significantly higher in PCOS group (P<0.01. On hCG priming day, FX and estrogen levels in PCOS group were higher than in the control group and FVIII levels were significantly lower on day of embryos transfer whereas FX and E2 levels were significantly higher in PCOS group. Conclusion. Hypercoagulable state during peri-implantation phase would probably lead to poor microcirculation of endometrium and be one of the most important disadvantages of successful implantation and subsequent clinical pregnancy.

  9. Enzymological characterization of Flla, a fibrinolytic enzyme from Agkistrodon acutus venom

    Institute of Scientific and Technical Information of China (English)

    Xiu-xia LIANG; Ying-na ZHOU; Jia-shu CHEN; Peng-xin QIU; Hui-zhen CHEN; Huan-huan SUN; Yu-ping WU; Guang-mei YAN

    2005-01-01

    Aim: To study the enzymological characterization of a fibrinolytic enzyme (FⅡa)from Agkistrodon acutus venom. Methods: The fibrinogenolytic effect and the influences of several protease inhibitors, chelating agents, and metal ions on fibrinogenolytic activity were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The metal content of FⅡa was determined by atomic absorption spectroscopy. Results: After incubation with EⅡa (0.25 g/L), Aα-, Bβ-and γ-chains of fibrinogen disappeared within 5 min, 30 min, and 8 h, respectively.The molecular weights of major degradation products were 45 000 and 41 000,which were different from those bands produced by plasmin. The fibrinogenolytic activity of FⅡa was strongly inhibited by ethylenediamine tetraacetic acid (EDTA),ethyleneglycol tetraacetic acid (EGTA), dithiothreitol and cysteine, but not by phenylmethyl-sulfonyl fluoride and soybean trypsin inhibitor. Zinc (3171±25mg/kg), potassium (489± 17 mg/kg) and calcium (319± 13 mg/kg) were found in FⅡa.Zn2+, Ca2+ and Mg2+ could recover the fibrinogenolytic activity of FⅡa, which was inhibited by EDTA. Only Ca2+ could recover the fibrinogenolytic activity inhibited by EGTA. Conclusion: FⅡa can degrade the Aα-, Bβ- and γ-chains of fibrinogen.EⅡa is a metalloproteinase, and Zn2+, Ca2+, and disulfide bonds are necessary for its fibrinogenolytic activity.

  10. Effect of ascorbate on fibrinolytic factors in septic mouse skeletal muscle.

    Science.gov (United States)

    Swarbreck, Scott; Secor, Dan; Li, Fuyan; Gross, Peter L; Ellis, Christopher G; Sharpe, Michael D; Wilson, John X; Tyml, Karel

    2014-10-01

    Plugging of the capillary bed in tissues correlates with organ failure during sepsis. In septic mouse skeletal muscle, we showed that blood in capillaries becomes hypercoagulable and that ascorbate injection inhibits capillary plugging. In the present study, we hypothesized that ascorbate promotes fibrinolysis, reversing this plugging. Sepsis in mice was induced by fecal injection into peritoneum. Mice were injected intravenously with a bolus of streptokinase (fibrinolytic agent) or ascorbate at 5-6 h. Both agents reversed capillary plugging in muscle at 7 h. Sepsis increased mRNA expression of urokinase plasminogen activator (u-PA) (profibrinolytic) and plasminogen activator inhibitor 1 (PAI-1) (antifibrinolytic) in muscle and liver homogenates at 7 h. Ascorbate did not affect u-PA mRNA in either tissue, but it inhibited PAI-1 mRNA in muscle, suggesting enhanced fibrinolysis in this tissue. However, ascorbate did not affect increased PAI-1 mRNA in the liver (dominant source of soluble PAI-1 in systemic blood). Consistently, ascorbate affected neither elevated PAI-1 protein/enzymatic activity in septic liver nor lowered plasmin antiplasmin level in septic blood. Furthermore, hypocoagulability of septic blood revealed by thrombelastography and thrombin-induced PAI-1 release from isolated platelets (ex-vivo model of sepsis) were not affected by ascorbate. Based on the PAI-1 protein data, the present study does not support the hypothesis that ascorbate promotes fibrinolysis in sepsis.

  11. Purification and characterization of a serine protease (CPM-2) with fibrinolytic activity from the dung beetles.

    Science.gov (United States)

    Ahn, Mi Young; Hahn, Bum-Soo; Ryu, Kang Sun; Hwang, Jae Sam; Kim, Yeong Shik

    2005-07-01

    Catharsius protease-2 (CPM-2) was isolated from the body of dung beetles, Catharsius molossus, using a three step purification process (ammonium sulfate fractionation, gel filtration on Bio-Gel P-60, and affinity chromatography on DEAE Affi-Gel blue). The purified CPM-2, having a molecular weight of 24 kDa, was assessed homogeneously by SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of CPM-2 was composed of X Val Gln Asp Phe Val Glu Glu Ile Leu. CPM-2 was inactivated by Cu2+ and Zn2+ and strongly inhibited by typical serine proteinase inhibitors such as TLCK, soybean trypsin inhibitor, aprotinin, benzamidine, and alpha1-antitrypsin. However, EDTA, EGTA, cysteine, beta-mercaptoethanol, E64, and elastatinal had little effect on enzyme activity. In addition, antiplasmin and antithrombin III were not sensitive to CPM-2. Based on the results of a fibrinolytic activity test, CPM-2 readily cleaved Aalpha- and Bbeta-chains of fibrinogen and fibrin, and gamma-chain of fibrinogen more slowly. The nonspecific action of the enzyme resulted in extensive hydrolysis, releasing a variety of fibrinopeptides of fibrinogen and fibrin. Polyclonal antibodies of CPM-2 were reactive to the native form of antigen. The ELISA was applied to detect quantities, in nanograms, of the antigen in CPM-2 protein.

  12. Improved compliance and patient satisfaction with estradiol vaginal tablets in postmenopausal women previously treated with another local estrogen therapy

    Directory of Open Access Journals (Sweden)

    Minkin MJ

    2013-03-01

    Full Text Available Mary Jane Minkin,1 Ricardo Maamari,2 Suzanne Reiter31Obstetrics, Gynecology, and Menopause, Temple Medical Center, New Haven, CT, 2Hormone Therapy, Novo Nordisk Inc, Princeton, NJ, 3Mid-County Health Center, Largo, FL, USAAbstract: Up to half of all postmenopausal women will experience changes in the genitourinary tract induced by the hypoestrogenic state, collectively known as vaginal atrophy. Vaginally administered local estrogen therapy (LET is the standard of care for symptoms of vaginal atrophy that do not respond to nonhormonal interventions. Several LET formulations are available, and choice of therapy is based largely on patient needs and preferences. This online survey of postmenopausal LET users was conducted to investigate reasons for switching to vaginal estradiol tablets from other formulations and to evaluate factors associated with patient preference for and compliance with use of LET. Data was analyzed from 73 respondents currently using estradiol vaginal tablets who have previously used the estradiol vaginal ring, estradiol vaginal cream, and/or conjugated estrogen vaginal cream. Patients in this survey rated vaginal symptoms of vaginal atrophy as being more bothersome than urinary symptoms. Respondents preferred their current treatment with the vaginal tablet to their previous treatment with a cream or ring. The preference for tablets over creams was mainly related to formulation and application rather than to any perceived safety issues. Tablets were perceived as efficacious, convenient, and neat to apply. The study participants also reported a longer duration of tablet use compared with creams or rings, and greater compliance with vaginal tablets than with vaginal cream. This study provides new insights into reasons for patient noncompliance with estrogen cream or ring therapy that can be used to maximize patient adherence with LET.Keywords: vaginal atrophy, local estrogen therapy, estradiol, vaginal ring, vaginal tablet

  13. PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Kristiansen, C.; Loft, A.; Berthelsen, Anne Kiil;

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locall...

  14. Characterization of a Novel Fibrinolytic Enzyme, BsfA, from Bacillus subtilis ZA400 in Kimchi Reveals Its Pertinence to Thrombosis Treatment.

    Science.gov (United States)

    Ahn, Min-Ju; Ku, Hye-Jin; Lee, Se-Hui; Lee, Ju-Hoon

    2015-12-28

    Recently, the cardiovascular disease has been widely problematic in humans probably due to fibrin formation via the unbalanced Western style diet. Although direct (human plasmin) and indirect methods (plasminogen activators) have been available, bacterial enzyme methods have been studied because of their cheap and mass production. To detect a novel bacterial fibrinolytic enzyme, 111 bacterial strains with fibrinolytic activity were selected from kimchi. Among them, 14 strains were selected because of their stronger activity than 0.02 U of plasmin. Their 16S rRNA sequence analysis revealed that they belong to Bacillus, Leuconostoc, Propionibacterium, Weissella, Staphylococcus, and Bifidobacterium. The strain B. subtilis ZA400, with the highest fibrinolytic activity, was selected and the gene encoding fibrinolytic enzyme (bsfA) was cloned and expressed in the E. coli overexpression system. The purified enzyme was analyzed with SDS-PAGE, western blot, and MALDI-TOF analyses, showing to be 28.4 kDa. Subsequently, the BsfA was characterized to be stable under various stress conditions such as temperature (4-40°C), metal ions (Mn(2+), Ca(2+), K(2+), and Mg(2+)), and inhibitors (EDTA and SDS), suggesting that BsfA could be a good candidate for development of a novel fibrinolytic enzyme for thrombosis treatment and may even be useful as a new bacterial starter for manufacturing functional fermented foods.

  15. Neoadjuvant therapy and surgical resection for locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Meko, J; Rusch, V W

    2000-10-01

    During the past 15 years, treatment of stage IIIA (N2) non-small cell lung cancer has evolved considerably because of improvements in patients selection, staging, and combined modality therapy. Results of several clinical trials suggest that induction chemotherapy or chemoradiation and surgical resection is superior to surgery alone. However, the optimal induction regimen has not been defined. An intergroup trial is also underway to determine whether chemoradiation and surgical resection leads to better survival than chemotherapy and radiation alone. Future studies will assess ways to combine radiation and novel chemotherapeutic agents, and will identify molecular abnormalities that predict response to induction therapy.

  16. Comparative cost-effectiveness of stereotactic body radiation therapy versus intensity-modulated and proton radiation therapy for localized prostate cancer.

    Directory of Open Access Journals (Sweden)

    Anju eParthan

    2012-08-01

    Full Text Available Objective. To determine the cost-effectiveness of several external beam radiation treatment modalities for the treatment of patients with localized prostate cancer.Methods. A lifetime Markov model incorporated the probabilities of experiencing treatment-related long-term toxicity or death. Toxicity probabilities were derived from published sources using meta-analytical techniques. Utilities and costs in the model were obtained from publically available secondary sources. The model calculated quality-adjusted life expectancy and expected lifetime cost per patient, and derived ratios of incremental cost per quality-adjusted life year (QALY gained between treatments. Analyses were conducted from both a payer and societal perspectives. One-way and probabilistic sensitivity analyses were performed.Results. Compared to intensity modulated radiation therapy (IMRT and proton beam therapy (PT, stereotactic body radiation therapy (SBRT was less costly and resulted in more QALYs. Sensitivity analyses showed that the conclusions in the base-case scenario were robust with respect to variations in toxicity and cost parameters consistent with available evidence. At a threshold of $50,000/QALY, SBRT was cost effective in 75%, and 94% of probabilistic simulations compared to IMRT and PT, respectively, from a payer perspective. From a societal perspective, SBRT was cost-effective in 75%, and 96% of simulations compared to IMRT and PT, respectively, at a threshold of $50,000/QALY. In threshold analyses, SBRT was less expensive with better outcomes compared to IMRT at toxicity rates 23% greater than the SBRT base-case rates. Conclusions. Based on the assumption that each treatment modality results in equivalent long-term efficacy, SBRT is a cost-effective strategy resulting in improved quality-adjusted survival compared to IMRT and PT for the treatment of localized prostate cancer.

  17. Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy.

    Science.gov (United States)

    Tumati, Vasu; Mathur, Sanjeev; Song, Kwang; Hsieh, Jer-Tsong; Zhao, Dawen; Takahashi, Masaya; Dobin, Timothy; Gandee, Leah; Solberg, Timothy D; Habib, Amyn A; Saha, Debabrata

    2013-05-01

    The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.

  18. Computed tomographic features predictive of local recurrence in patients with early stage lung cancer treated with stereotactic body radiation therapy.

    Science.gov (United States)

    Halpenny, Darragh; Ridge, Carole A; Hayes, Sara; Zheng, Junting; Moskowitz, Chaya S; Rimner, Andreas; Ginsberg, Michelle S

    2015-01-01

    The objective of this study is to identify computed tomography (CT) features of local recurrence (LR) after stereotactic body radiation therapy (SBRT) for lung cancer. Two hundred eighteen patients underwent SBRT for lung cancer from January 1st, 2006 to March 1st, 2011. Signs of LR recorded: opacity with new bulging margin, opacification of air bronchograms, enlarging pleural effusion, new or enlarging mass, and increased lung density at the treatment site. A new bulging margin at the treatment site was the only feature significantly associated with LR (P<.005). Most CT features classically associated with LR following conventional radiation therapy are unreliable for predicting LR following SBRT. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Few-view and limited-angle cone-beam megavoltage CT for breast localization in radiation therapy

    Science.gov (United States)

    Yu, Lifeng; Pan, Xiaochuan; Pelizzari, Charles A.; Martel, Mary

    2004-05-01

    In radiation therapy for breast cancer treatment, information about the external (skin) and internal (lung) boundaries is highly useful for determining the relative locations of the target and lung. In this work, we investigate the feasibility of tomographic reconstruction from few-view and limited-angle cone-beam projections acquired in radiation therapy unit for obtaining critical boundary information. From the few-view and limited-angle projections acquired directly in the treatment machine with an amorphous silicon electronic portal imaging device (EPID), We compared and evaluated the performance of the conventional cone-beam FDK algorithm and an iterative algorithm based upon the maximum-likelihood method for transmission tomography (ML-TR). Preliminary results demonstrated that the ML-TR algorithm is more promising than is the cone-beam FDK algorithm. Useful boundary information for breast localization can be obtained with very few projections in a limited angle range from the reconstruction of ML-TR algorithm.

  20. Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming Zeng; Fernando N Aguila; Taral Patel; Mark Knapp; XueQiang Zhu; XiLin Chen; Phillip D Price

    2016-01-01

    AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR) rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%) and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n = 16),the p CR rate was 47%(n = 8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n = 7) and 53%(n = 9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.

  1. 77 FR 11123 - Scientific Information Request on Local Therapies for Unresectable Colorectal Cancer Metastases...

    Science.gov (United States)

    2012-02-24

    ... Therapies for Unresectable Colorectal Cancer Metastases to the Liver AGENCY: Agency for Healthcare Research... unresectable colorectal cancer metastases to the liver. The EHC Program is dedicated to identifying as many... manufacturers of unresectable colorectal cancer medical devices. Scientific information is being solicited...

  2. The Effect of Levonorgestrel on Fibrinolytic Factors in Human Endometrial Endothelial Cells.

    Science.gov (United States)

    Pakrashi, Tarita; Taylor, Joelle E; Nelson, Ashley; Archer, David F; Jacot, Terry

    2016-11-01

    The levonorgestrel-releasing intrauterine system is considered a highly effective treatment of heavy menstrual bleeding (HMB). While LNG has established effects on the stromal and glandular compartments of the endometrial tissue, its effect on the endometrial endothelial cells has not been investigated. We examined whether LNG regulates fibrinolytic factors, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) secreted by human endometrial endothelial cells (HEECs) and determined the steroid receptor through which LNG exerts its effect on the endothelium. The HEECs were treated with LNG or progesterone and levels of tPA and plasminogen activator inhibitor 1 (PAI-1) measured. The HEECs were specifically examined for the presence of androgen receptors through Western blot. Levonorgestrel ± flutamide were added to HEECs and the levels of tPA and uPA were examined. An enzyme-linked immunosorbent assay performed on culture media confirmed a statistically significant decrease in tPA levels in cells treated with LNG (77.80% ± 8.0% of control; n = 5, P < .05 vs control) but not progesterone. The androgen receptor (110 kDa) was detected in HEEC lysates. The decrease in tPA was blocked by the addition of flutamide (101.3% ± 16% of control), a classic nonsteroidal androgen receptor blocker. There was no change in uPA or PAI-1 levels in cells treated with LNG. Levonorgestrel decreases tPA levels through the androgen receptor in HEECs. Thus, LNG inhibits tPA secretion by the endometrial endothelial cell. This response suggests reduction in HMB with LNG-IUS could reflect an LNG-mediated promotion of hemostasis. © The Author(s) 2016.

  3. Lipids, lipoproteins, fibrinogen and fibrinolytic activity in angiographically assessed coronary heart disease.

    Science.gov (United States)

    Lipinska, I; Gurewich, V; Meriam, C M; Kosowsky, B D; Ramaswamy, K; Philbin, E; Losordo, D

    1987-01-01

    Plasma lipids, lipoproteins, fibrinogen and fibrinolytic activity (FA) were measured in 202 consecutive patients undergoing coronary angiography. Twenty-one patients, 13 men and 8 women with a mean age of 52.8 years and 56.7 years respectively, were found to be angiographically free of coronary artery disease (CAD) and served as the principal control group. Since this group contained a disproportionate number of subjects with risk factors such as family history, hypertension and smoking, a second control group of clinically healthy subjects selected for age was also tested. Their laboratory results were not used in the statistical calculations. The group with angiographic CAD consisted of 130 men (mean age 57.6 years) and 51 women (mean age 61.5 years). Abnormal angiograms were graded according to the number of major vessels with more than 50% stenosis involved. The laboratory variables which were significantly (p less than .01-.001) associated with the presence of CAD were: High density lipoprotein (HDL) when determined by polyacrylamide gel electrophoresis (PAGE) and expressed as a percentage of total lipoproteins rather than concentration, presence of Intermediate Density Lipoprotein (IDL), percent of Very Low Density Lipoprotein (VLDL), fibrinogen concentration and FA. The HDL2 subfraction was significantly inversely correlated only in women. The total plasma cholesterol was normal and virtually identical in both groups. Within the CAD group, only two of the laboratory results were significantly correlated with the extent of disease. By univariate analysis, the FA showed the closest association with the score for severity of CAD (p less than .001) followed by the presence of IDL (p less than .01). In conclusion, lipoprotein analysis by a method which measures not only HDL, but also LDL, VLDL and IDL, together with the determination of fibrinogen and FA provides information useful in the identification of individuals at risk for CAD.

  4. Comparative fibrinolytic properties of staphylokinase and streptokinase in animal models of venous thrombosis.

    Science.gov (United States)

    Lijnen, H R; Stassen, J M; Vanlinthout, I; Fukao, H; Okada, K; Matsuo, O; Collen, D

    1991-10-01

    The thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function (formula: see text) and the maximal percent clot lysis (c), the maximal rate of lysis (z = 1/4 ac.eb) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 +/- 1,100% lysis per mg/kg streptokinase administered versus 1,100 +/- 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than streptokinase (z = 1,600 +/- 440 versus 1,200 +/- 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than streptokinase in rabbits,as revealed by a higher z-value (950 +/- 350% lysis per mg/kg staphylokinase administered versus 330 +/- 39% lysis per mg/kg for streptokinase) and a lower b-value (0.035 +/- 0.010 mg/kg staphylokinase versus 0.091 +/- 0.008 mg/kg for streptokinase.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Ammodytase, a metalloprotease from Vipera ammodytes ammodytes venom, possesses strong fibrinolytic activity.

    Science.gov (United States)

    Leonardi, Adrijana; Fox, Jay W; Trampus-Bakija, Alenka; Krizaj, Igor

    2007-05-01

    Ammodytase, a high molecular mass metalloproteinase with fibrinogenolytic and fibrinolytic activities, was purified from long-nosed viper (Vipera ammodytes ammodytes) venom by gel filtration, affinity and ion-exchange chromatographies. The enzyme is a single-chain glycoprotein with apparent molecular mass of 70 kDa and isoelectric point of 6.6. Ammodytase shows very weak hemorrhagic activity, and only at doses higher than 20 microg. Consistent with this, it partially degrades some components of the extracellular matrix in vitro. It cleaves the Aalpha-chain of fibrinogen preferentially at peptide bonds Glu(441)-Leu(442) and Glu(539)-Phe(540). Its preference for bulky and hydrophobic amino acids at the P1' position in substrates is demonstrated by its hydrolysis of only the Gln(4)-His(5) and Tyr(16)-Leu(17) bonds in the B-chain of insulin. Ammodytase is able to dissolve fibrin clots. It neither activates nor degrades plasminogen and prothrombin, and has no effect on collagen- or ADP-induced platelet aggregation in vitro. LC/MS and MS/MS analyses of its tryptic fragments demonstrated that ammodytase is a P-III class snake venom metalloproteinase composed of metalloproteinase, disintegrin-like and cysteine-rich domains. Its similarity to hemorrhagins from V. a. ammodytes venom, accompanied by very low toxicity, makes ammodytase a promising candidate as an antigen to prepare antisera against these most dangerous components of the viper's venom. Moreover, its ability to degrade fibrin clots suggests its clinical use as an antithrombotic agent.

  6. 77 FR 24959 - Scientific Information Request on Local Therapies for Unresectable Primary Hepatocellular Carcinoma

    Science.gov (United States)

    2012-04-26

    ... HUMAN SERVICES Agency for Healthcare Research and Quality Scientific Information Request on Local... Quality (AHRQ), HHS. ACTION: Request for scientific information submissions. SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is seeking scientific information submissions from manufacturers...

  7. The Effects of Scraping Therapy on Local Temperature and Blood Perfusion Volume in Healthy Subjects

    OpenAIRE

    Qin-Yan Xu; Jin-Sheng Yang; Bing Zhu; Li Yang; Ying-Ying Wang; Xin-Yan Gao

    2012-01-01

    Objective. We aim to study the therapeutic effects of scraping by investigating the changes of temperature and local blood perfusion volume in healthy subjects after scraping stimulation, and to explore the mechanism of scraping stimulation from the points of microcirculation and energy metabolism. Methods. Twenty-three health subjects were included in this study. Local blood perfusion volume and body surface temperature was detected at 5 min before scraping stimulation, 0, 15, 30, 60 and 90 ...

  8. External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Eunpi [University of Washington School of Medicine, Seattle, Washington (United States); Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Mostaghel, Elahe A. [Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A. [University of Washington School of Medicine, Seattle, Washington (United States); Kurland, Brenda F. [University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Marck, Brett T. [Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Matsumoto, Alvin M. [University of Washington School of Medicine, Seattle, Washington (United States); Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Dalkin, Bruce L. [University of Washington School of Medicine, Seattle, Washington (United States); Montgomery, R. Bruce, E-mail: rbmontgo@uw.edu [University of Washington School of Medicine, Seattle, Washington (United States)

    2015-06-01

    Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

  9. Statistical Optimization of Fibrinolytic Enzyme Production Using Agroresidues by Bacillus cereus IND1 and Its Thrombolytic Activity In Vitro

    Directory of Open Access Journals (Sweden)

    Ponnuswamy Vijayaraghavan

    2014-01-01

    Full Text Available A potent fibrinolytic enzyme-producing Bacillus cereus IND1 was isolated from the Indian food, rice. Solid-state fermentation was carried out using agroresidues for the production of fibrinolytic enzyme. Among the substrates, wheat bran supported more enzyme production and has been used for the optimized enzyme production by statistical approach. Two-level full-factorial design demonstrated that moisture, supplementation of beef extract, and sodium dihydrogen phosphate have significantly influenced enzyme production (P<0.05. A central composite design resulted in the production of 3699 U/mL of enzyme in the presence of 0.3% (w/w beef extract and 0.05% (w/w sodium dihydrogen phosphate, at 100% (v/w moisture after 72 h of fermentation. The enzyme production increased fourfold compared to the original medium. This enzyme was purified to homogeneity by ammonium sulfate precipitation, diethylaminoethyl-cellulose ion-exchange chromatography, Sephadex G-75 gel filtration chromatography, and casein-agarose affinity chromatography and had an apparent molecular mass of 29.5 kDa. The optimum pH and temperature for the activity of fibrinolytic enzyme were found to be 8.0 and 60°C, respectively. This enzyme was highly stable at wide pH range (7.0–9.0 and showed 27% ± 6% enzyme activity after initial denaturation at 60°C for 1 h. In vitro assays revealed that the enzyme could activate plasminogen and significantly degraded the fibrin net of blood clot, which suggests its potential as an effective thrombolytic agent.

  10. Purification and biochemical characterization of a novel fibrinolytic enzyme, PSLTro01, from a medicinal animal Porcellio scaber Latreille.

    Science.gov (United States)

    Tian, Zhou; Li, Bo; Guo, Liwei; Wu, Mianhua; Fu, Tingming; Cheng, Haibo; Zhu, Huaxu

    2015-09-01

    A novel protease, named PSLTro01, with fibrinolytic and anticoagulant activity was isolated from Porcellio scaber Latreille and was purified by a combination of hollow fibre membrane molecular weight cut-off (MWCO), ammonium sulfate fractionation, gel filtration and ion-exchange chromatography. PSLTro01 is a single-chain protein with a molecular mass of 38,497 Da as estimated by non-reduced SDS-PAGE and MALDI-TOF MS spectrometry, and its N-terminal 15 amino acid sequence was determined as DINGGGATLPQPLYQ. PSLTro01 is stable in the range of 20-40 °C and pH 6.0-10.0, with a maximum fibrinolytic activity at 40 °C and pH 7.0. The PSLTro01-induced fibrinolytic activity was not influenced by K(+) or Na(+) but was slightly increased by Mg(2+) and completely inhibited by aprotinin and pepstatin A. Fibrin plate assays revealed that PSLTro01 could not directly degrade fibrin but was a plasminogen activator. PSLTro01 exhibited high specificity for the substrate S-2251 for plasmin, followed by S-2238 for thrombin and S-2444 for urokinase. Moreover, the fibrinogenolysis pattern of PSLTro01 was Aα-chains>Bβ-chains>γ-chain. Tail-thrombus of the enzyme treated group was significantly shorter than the physiological saline treated group and the thrombus decrement was correlated with the enzyme dose. PSLTro01 prolongs both thrombin time (TT) and activated partial thromboplastin time (APTT). These results indicate that PSLTro01 may have potential applications in the prevention and treatment of thrombosis.

  11. Is photodynamic therapy a selective treatment? Analysis of local complications after endoscopic photodynamic therapy of early stage tumors of gastrointestinal, tracheobronchial, and urinary tracts

    Science.gov (United States)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea

    1995-03-01

    Selectivity is the most emphasized advantage of photodynamic therapy (PDT). However, at drug and light doses used for clinical applications, response from normal tissue surrounding the tumor reduces the real selectivity of the drug-light system and increases the surface of the area responding to the treatment. It is now evident that light irradiation of a sensitized patient produces damage at a various degree not only in the tumor but also in non-neoplastic tissues included in the field of irradiation. We report our experience in endoscopic PDT of early stage tumors in tracheobronchial, gastrointestinal and urinary tracts, describing early and late local complications caused by the damage of normal tissues adjacent to the tumors and included in the field of light irradiation. Among 44 patients treated, local complications, attributable to a poor selectivity of the modality, occurred in 6 patients (14%). In particular, the rate of local complications was 9% in patients treated for esophageal tumors, 14% in patients with gastric tumors, 9% in patients with tracheobronchial tumors, and 67% in bladder cancer patients. Clinical pictures as well as endoscopic findings at various intervals from treatment showed that mucositis is a common event following endoscopic PDT. It causes exudation and significant tissue inflammatory response, whose consequences are different in the various organs treated. Photoradiation must be, as much as possible, limited to the malignant area.

  12. Locally advanced prostate cancer: combination of high-dose high-precision radiotherapy and androgen deprivation therapy%Locally advanced prostate cancer:combination of high-dose high-precision radiotherapy and androgen deprivation therapy

    Institute of Scientific and Technical Information of China (English)

    Michel Bolla; René-Olivier Mirimanoff

    2014-01-01

    Locally advanced prostate cancer entails a risk of local,regional and systemic relapse requiring the combination of a Ioco-regional treatment,namely external beam radiotherapy(EBRT) to control the pelvic-confined disease,combined with a systemic therapy,namely androgen-deprivation therapy(ADT),to potentiate irradiation and to destroy the infra-clinical androgen-dependant disease outside the irradiated volume.Many phases Ⅲ randomized trials have paved the way in establishing the indications of this combined approach,which requires a long term ADT(≥2 years) with LHRH agonists.The duration of ADT may be reduced to 6 months should there be a significant comorbidity,a reluctance from the patient or a poor tolerance.A multidisciplinary approach will enable physicians to tailor the treatment strategy and a close cooperation between the specialists and the general practitioners will be set up to prevent as much as possible the side-effects of ADT.

  13. Endobronchial ultrasound—guidance for interstitial photodynamic therapy of locally advanced lung cancer—a new interventional concept

    Science.gov (United States)

    Oakley, Emily; Bellnier, David; Shafirstein, Gal

    2017-01-01

    Recent advances in interventional pulmonology led to a significant expansion of the diagnostic and therapeutic role of endobronchial ultrasound. In this paper, we describe a new concept for using endobronchial ultrasound to guide interstitial photodynamic therapy (PDT). For this purpose, we conducted in vitro and in vivo experiments using a phantom and animal models, respectively. A new 0.5 mm optical fiber, with cylindrical diffuser end, was used to deliver the therapeutic light through the 21-gauge endobronchial ultrasound needle. The animal experiments were performed under real-time ultrasonography guidance in mice and rabbits’ tumor models. Safe and effective fiber placements and tumor illumination was accomplished. In addition, computer simulation of light propagation suggests that locally advanced lung cancer tumor can be illuminated. This study demonstrates the potential feasibility of this new therapeutic modality approach, justifying further investigation in the treatment of locally advanced lung cancers. PMID:28932569

  14. Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Brasso, Klaus; Christensen, Ib J

    2015-01-01

    -metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). FINDINGS: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised......BACKGROUND: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. METHODS: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non...... disease (HR=1.19 (95% CI: 1.00-1.43), p=0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting...

  15. The acute effects of local vibration therapy on ankle sprain and hamstring strain injuries.

    Science.gov (United States)

    Peer, Kimberly S; Barkley, Jacob E; Knapp, Danielle M

    2009-12-01

    The purpose of this study was to determine if biomechanical muscle stimulation (BMS) applied directly to different segments of the body using the Swisswing device results in acute improvements in range of motion and perceived stiffness in physically active adults with acute or subacute ankle sprain and hamstring strain injuries. Two separate groups of individuals with grade I or II ankle sprain (n = 5; 21.2 +/- 1.9 years) or hamstring strain (Nn= 5; 20.6 +/- 1.8 year) underwent 20 minutes of a controlled therapy consisting of ice, compression, and elevation, and 10 minutes of segmental BMS using the Swisswing at 20 Hz. Ankle (dorsiflexion, plantar flexion, inversion, eversion), hamstring flexibility, and subjective ratings of stiffness were assessed prior to control treatment (baseline), post-control treatment, and post-Swisswing treatment. Relative to the post-control condition, Swisswing treatment significantly (P < 0.03 for all) increased ankle dorsiflexion and eversion and hamstring flexibility, and significantly (P therapy using the Swisswing device appears to have significant acute benefits for improving flexibility and reducing perceived stiffness in healthy adults with ankle or hamstring injury. Future research is needed to determine the duration of these effects and if repeated periods of segmental BMS therapy aid in long-term injury recovery.

  16. Accurate tumor localization and tracking in radiation therapy using wireless body sensor networks.

    Science.gov (United States)

    Pourhomayoun, Mohammad; Jin, Zhanpeng; Fowler, Mark

    2014-07-01

    Radiation therapy is an effective method to combat cancerous tumors by killing the malignant cells or controlling their growth. Knowing the exact position of the tumor is a very critical prerequisite in radiation therapy. Since the position of the tumor changes during the process of radiation therapy due to the patient׳s movements and respiration, a real-time tumor tracking method is highly desirable in order to deliver a sufficient dose of radiation to the tumor region without damaging the surrounding healthy tissues. In this paper, we develop a novel tumor positioning method based on spatial sparsity. We estimate the position by processing the received signals from only one implantable RF transmitter. The proposed method uses less number of sensors compared to common magnetic transponder based approaches. The performance of the proposed method is evaluated in two different cases: (1) when the tissue configuration is perfectly determined (acquired beforehand by MRI or CT) and (2) when there are some uncertainties about the tissue boundaries. The results demonstrate the high accuracy and performance of the proposed method, even when the tissue boundaries are imperfectly known.

  17. The effects of scraping therapy on local temperature and blood perfusion volume in healthy subjects.

    Science.gov (United States)

    Xu, Qin-Yan; Yang, Jin-Sheng; Zhu, Bing; Yang, Li; Wang, Ying-Ying; Gao, Xin-Yan

    2012-01-01

    Objective. We aim to study the therapeutic effects of scraping by investigating the changes of temperature and local blood perfusion volume in healthy subjects after scraping stimulation, and to explore the mechanism of scraping stimulation from the points of microcirculation and energy metabolism. Methods. Twenty-three health subjects were included in this study. Local blood perfusion volume and body surface temperature was detected at 5 min before scraping stimulation, 0, 15, 30, 60 and 90 min after scraping using Laser Doppler imager and infrared thermograph. Results. Significant increase was noted in the blood perfusion volume in the scraping area within 90 minutes compared to the baseline level and non-scraping area (P scraping area, an increase of body temperature with an average of 1°C was observed after scraping stimulation (P Scraping can significantly improve the blood perfusion volume and increase the temperature in the scraping area, promoting the local blood circulation and energy metabolism.

  18. PET/CT and Histopathologic Response to Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer

    DEFF Research Database (Denmark)

    Kristiansen, Charlotte; Loft, Annika; Berthelsen, Anne K

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral(R) (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared...... of chemoradiation is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography....

  19. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cuaron, John J. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David [Procure Proton Therapy Center, Somerset, New Jersey (United States); Ho, Alice; Powell, Simon [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Hug, Eugen [Procure Proton Therapy Center, Somerset, New Jersey (United States); Cahlon, Oren, E-mail: cahlono@mskcc.org [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Procure Proton Therapy Center, Somerset, New Jersey (United States)

    2015-06-01

    Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  20. Focal salvage therapy for local prostate cancer recurrences after primary radiotherapy : a comprehensive review

    NARCIS (Netherlands)

    Duijzentkunst, D A Smit; Peters, M; van der Voort van Zyp, J R N; Moerland, M A; van Vulpen, M

    2016-01-01

    BACKGROUND/AIM: Patients with locally recurrent prostate cancer after primary radiotherapy can be eligible for salvage treatment. Whole-gland salvage techniques carry a high risk of toxicity. A focal salvage approach might reduce the risk of adverse events while maintaining cancer control in careful

  1. Localized and systemic scleroderma show different histological responses to methotrexate therapy.

    NARCIS (Netherlands)

    Seijger, M.M.B.; Hoogen, F.H.J. van den; Vlijmen-Willems, I.M.J.J. van; Kerkhof, P.C.M. van de; Jong, E.M.G.J. de

    2001-01-01

    Although morphoea (localized scleroderma) and systemic sclerosis are distinct disease entities, the skin lesions show identical histological characteristics and both diseases respond favourably to low-dose treatment with methotrexate (MTX). The aim of this study was to find out whether MTX treatment

  2. COMPARATIVE STUDY OF EFFICACY OF LOCAL STEROID INJECTION AND EXTRACORPOREAL SHOCKWAVE THERAPY IN THE TREATMENT OF PLANTAR FASCITIS

    Directory of Open Access Journals (Sweden)

    Rajan

    2014-04-01

    Full Text Available INTRODUCTION: Plantar fasciitis is a common condition causing misery to lot of patients. The etiology and treatment of plantar fasciitis are poorly understood. The results from such treatments vary considerably, and there is no consensus of opinion on the best method. MATERIAL AND METHODS: We conducted a controlled trial in our institute to compare the results of local steroid injections & the use of Extra-corporeal shock wave therapy (ESWT for managing plantar fasciitis. 200 patients with 240 painful heels were evaluated. All patients with moderate to severe heel pain who had already taken ten days of unsatisfactory treatment with oral NSAIDS were divided in two main groups. Group A of 100 patients received 1000 impulses of shock waves in three sessions at weekly interval. In Group B of 100 patients up to three local injections of 40 mg methyl prednisone mixed with 1 ml. of 2% lignocaine were given at biweekly interval. Pain assessment was done using VAS scale and the results were evaluated at six weeks, three months and six months after the completion of the therapy. CONCLUSIONS: There was a significant difference between two groups of patients being treated. The group B patients had significantly greater improvement in pain scale and early return to daily activities

  3. 3D-printed hierarchical scaffold for localized isoniazid/rifampin drug delivery and osteoarticular tuberculosis therapy.

    Science.gov (United States)

    Zhu, Min; Li, Kun; Zhu, Yufang; Zhang, Jianhua; Ye, Xiaojian

    2015-04-01

    After surgical treatment of osteoarticular tuberculosis (TB), it is necessary to fill the surgical defect with an implant, which combines the merits of osseous regeneration and local multi-drug therapy so as to avoid drug resistance and side effects. In this study, a 3D-printed macro/meso-porous composite scaffold is fabricated. High dosages of isoniazid (INH)/rifampin (RFP) anti-TB drugs are loaded into chemically modified mesoporous bioactive ceramics in advance, which are then bound with poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) through a 3D printing procedure. The composite scaffolds show greatly prolonged drug release time compared to commercial calcium phosphate scaffolds either in vitro or in vivo. In addition, the drug concentrations on the periphery tissues of defect are maintained above INH/RFP minimal inhibitory concentrations even up to 12 weeks post-surgery, while they are extremely low in blood. Examinations of certain serum enzymes suggest no harm to hepatic or renal functions. Micro-CT evaluations and histology results also indicate partly degradation of the composite scaffolds and new bone growth in the cavity. These results suggest promising applications of our hierarchical composite scaffold in bone regeneration and local anti-TB therapy after osteoarticular TB debridement surgery.

  4. Intensity-modulated radiation therapy use for the localized treatment of thyroid cancer: Nationwide practice patterns and outcomes.

    Science.gov (United States)

    Goffredo, Paolo; Robinson, Timothy J; Youngwirth, Linda M; Roman, Sanziana A; Sosa, Julie A

    2016-09-01

    In the absence of randomized data, the optimal approach to adjuvant radiation therapy in locally advanced thyroid cancer remains unclear. We employed a large retrospective analysis to assess the best available evidence of a potential beneficial impact of intensity-modulated versus 3D-conformal radiotherapy (IMRT vs. 3D-CT). Retrospective analysis of adult thyroid cancer diagnosed between 2004 and 2011 within the National Cancer Database. Among patients treated with radiation therapy (N = 855), the use of IMRT (N = 437) increased among both comprehensive and academic centers (both p HR, 0.67; 95 % CI, 0.40-1.10; p = 0.115). This study presents the largest cohort to date examining receipt of IMRT in patients with locally advanced thyroid cancer and demonstrates an association between IMRT, treatment at a tertiary care center, higher total dose, and comparable or superior outcomes compared to patients treated with 3D conformal techniques despite more adverse disease features. In the absence of adequately powered prospective randomized trials, our retrospective analysis provides empirical evidence to support the use in these patients of dose escalation and IMRT, particularly at tertiary care centers.

  5. Seizure-freedom with combination therapy in localization-related epilepsy.

    Science.gov (United States)

    Peltola, Jukka; Peltola, Maria; Raitanen, Jani; Keränen, Tapani; Kharazmi, Elham; Auvinen, Anssi

    2008-04-01

    We analyzed the effect of combination therapy on seizure frequency in all adult patients (N=193) with focal epilepsy followed at a single institution in a cross-sectional study. One hundred and thirty-five patients were on two AEDs, of them, 37 (27%) were seizure-free, 50 patients were on three AEDs including 5 (10%) seizure-free patients (pseizure-freedom with two AEDs versus three AEDs). Thirty-five different combinations were used in patients on two AEDs and 40 combinations on patients on three drugs emphasizing the difficulties involved in evaluation of the efficacy and tolerability of specific combinations. The significant proportion of seizure-free cases (27%) on duotherapy is suggesting the usefulness of combination therapy in achieving seizure-freedom in epilepsies refractory to single drug treatment. The material in the study was not from a randomized trial and therefore the comparability of patients on different AEDs is uncertain, but on the other hand the clinical practice followed provides a natural experiment suitable for comparative, non-randomized assessment of treatment outcomes.

  6. A 5-year investigation of children's adaptive functioning following conformal radiation therapy for localized ependymoma.

    Science.gov (United States)

    Netson, Kelli L; Conklin, Heather M; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E

    2012-09-01

    Conformal and intensity modulated radiation therapies have the potential to preserve cognitive outcomes in children with ependymoma; however, functional behavior remains uninvestigated. This longitudinal investigation prospectively examined intelligence quotient (IQ) and adaptive functioning during the first 5 years after irradiation in children diagnosed with ependymoma. The study cohort consisted of 123 children with intracranial ependymoma. Mean age at irradiation was 4.60 years (95% confidence interval [CI], 3.85-5.35). Serial neurocognitive evaluations, including an age-appropriate IQ measure and the Vineland Adaptive Behavior Scales (VABS), were completed before irradiation, 6 months after treatment, and annually for 5 years. A total of 579 neurocognitive evaluations were included in these analyses. Baseline IQ and VABS were below normative means (PVABS across the follow-up period, except for the VABS Communication Index, which declined significantly (P=.015). Annual change in IQ (-.04 points) did not correlate with annual change in VABS (-.90 to +.44 points). Clinical factors associated with poorer baseline performance (P<.05) included preirradiation chemotherapy, cerebrospinal fluid shunt placement, number and extent of surgical resections, and younger age at treatment. No clinical factors significantly affected the rate of change in scores. Conformal and intensity modulated radiation therapies provided relative sparing of functional outcomes including IQ and adaptive behaviors, even in very young children. Communication skills remained vulnerable and should be the target of preventive and rehabilitative interventions. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy

    Directory of Open Access Journals (Sweden)

    Hou Wei

    2008-05-01

    Full Text Available Abstract Background- Data exist that demonstrate isoflavones' potent antiproliferative effects on prostate cancer cells. We evaluated the efficacy of isoflavone in patients with PSA recurrent prostate cancer after prior therapy. We postulated that isoflavone therapy would slow the rate of rise of serum PSA. Methods- Twenty patients with rising PSA after prior local therapy were enrolled in this open-labeled, Phase II, nonrandomized trial (Trial registration # NCT00596895. Patients were treated with soy milk containing 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months. Serum PSA, testosterone, lipids, isoflavone levels (genistein, daidzein, and equol, and quality of life (QOL were measured at various time points from 0 to 12 months. PSA outcome was evaluated. Results- Within the mixed regression model, it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period (p = 0.05. Specifically, the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy. Conclusion- Dietary intervention with isoflavone supplementation may have biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA. This study may lend support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore, further studies with these agents in randomized clinical trials should be encouraged.

  8. Systemic and localized infection by Candida species in patients with rheumatic diseases receiving anti-TNF therapy

    Directory of Open Access Journals (Sweden)

    Nadia E. Aikawa

    Full Text Available ABSTRACT Objective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA, 47 with ankylosing spondylitis (AS, 36 with juvenile idiopathic arthritis (JIA, 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 ± 16 years, with 68 (35% male and mean disease duration of 15 ± 10 years. Sixty-four (33% patients were receiving adalimumab, 59 (30% etanercept and 71 (36% infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5% patient had localized fungal infection (vaginal candidiasis. None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.

  9. Efficacy of intraarterial chemoinfusion therapy for locally advanced breast cancer patients: a retrospective analysis of 28 cases

    Directory of Open Access Journals (Sweden)

    Zhang W

    2013-06-01

    Full Text Available Wei Zhang,1,* Rong Liu,1,* Yingying Wang,1 Sheng Qian,1 Jianhua Wang,1 Zhiping Yan,1 Hongwei Zhang21Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China; 2Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China*These authors contributed equally to this workObjective: The objective of this study was to evaluate the outcome of image-guided delivery of intraarterially infused chemotherapeutic drugs for patients with locally advanced breast cancer.Methods: Twenty-eight patients with pathologically proven, locally advanced breast cancer received intraarterial chemoinfusion therapy (chemoinfusion with docetaxel 75 mg/m2 and epirubicin 50 mg/m2. Digital subtraction angiography was performed to determine tumor arterial blood supply and to guide chemotherapy infusion. Patients were evaluated for complete remission (CR and partial remission (PR.Results: Twenty-eight patients received a total of 64 intraarterial chemoinfusions, 20 patients (71.4% received two infusions, and eight patients (28.6% received three infusions. One patient (3.6% had CR and 23 (82.1% had PR. The total effectiveness rate (CR and PR was 85.7% (24/28. All stage 3 patients underwent Phase II surgical resection after chemoinfusion, and the surgical resection participation rate was 100% (26/26. The mean time from the first chemoinfusion to surgery was 2 ± 1.2 months. Two patients with stage 4 cancer died of distant metastasis and cachexia, and the remaining 26 patients were still alive.Conclusion: Intraarterial chemoinfusion is a safe and effective therapy, achieving down-staging in a relatively short period for locally advanced breast cancer.Keywords: advanced breast cancer, intraarterial infusion, chemotherapy, therapeutic effect

  10. Novel strategies in glioblastoma surgery aim at safe, supra-maximum resection in conjunction with local therapies

    Institute of Scientific and Technical Information of China (English)

    John G. Wolbers

    2014-01-01

    The biggest challenge in neuro-oncology is the treatment of glioblastoma, which exhibits poor prognosis and is increasing in incidence in an increasing aging population. Diverse treatment strategies aim at maximum cytoreduction and ensuring good quality of life. We discuss multimodal neuronavigation, supra-maximum tumor resection, and the postoperative treatment gap. Multimodal neuronavigation al ows the integration of preoperative anatomic and functional data with intraoperative information. This approach includes functional magnetic resonance imaging (MRI) and diffusion tensor imaging in preplanning and ultrasound, computed tomography (CT), MRI and direct (sub)cortical stimulation during surgery. The practice of awake craniotomy decreases postoperative neurologic deficits, and an extensive supra-maximum resection appears to be feasible, even in eloquent areas of the brain. Intraoperative MRI- and fluorescence-guided surgery assist in achieving this goal of supra-maximum resection and have been the subject of an increasing number of reports. Photodynamic therapy and local chemotherapy are properly positioned to bridge the gap between surgery and chemoradiotherapy. The photosensitizer used in fluorescence-guided surgery persists in the remaining peripheral tumor extensions. Additionally, blinded randomized clinical trials showed firm evidence of extra cytoreduction by local chemotherapy in the tumor cavity. The cutting-edge promise is gene therapy although both the delivery and efficacy of the numerous transgenes remain under investigation. Issues such as the choice of (cell) vector, the choice of therapeutic transgene, the optimal route of administration, and biosafety need to be addressed in a systematic way. In this selective review, we present various evidence and promises to improve survival of glioblastoma patients by supra-maximum cytoreduction via local procedures while minimizing the risk of new neurologic deficit.

  11. Phase I study of photodynamic therapy using talaporfin sodium and diode laser for local failure after chemoradiotherapy for esophageal cancer

    Directory of Open Access Journals (Sweden)

    Yano Tomonori

    2012-07-01

    Full Text Available Abstract Background Photodynamic therapy (PDT is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT for esophageal cancer, however it causes a high rate of skin phototoxicity and requires a long sun shade period. Talaporfin sodium is a rapidly cleared photosensitizer that is expected to have less phototoxicity. This study was undertaken to clarify the optimum laser fluence rate of PDT using talaporfin sodium and a diode laser for patients with local failure after CRT or radiotherapy (RT for esophageal cancer. Methods This phase I, laser dose escalation study used a fixed dose (40 mg/m2 of intravenous talaporfin sodium administered 4 to 6 hours before irradiation in patients with local failure limited to T2 after CRT or RT (≥ 50 Gy. The primary endpoint was to assess the dose limiting toxicity (DLT of PDT, and the secondary endpoints were to evaluate the adverse events and toxicity related to PDT. The starting fluence of the 664 nm diode laser was 50 J/cm2, with an escalation plan to 75 J/cm2 and 100 J/cm2. Results 9 patients with local failure after CRT or RT for ESCC were enrolled and treated in groups of 3 individuals to the third fluence level. No DLT was observed at any fluence level. Phototoxicity was not observed, but one subject had grade 1 fever, three had grade 1 esophageal pain, and 1 had grade 1 dysphagia. Five of 9 patients (55.6% achieved a complete response after PDT. Conclusions PDT using talaporfin sodium and a diode laser was safe for local failure after RT in patients with esophageal cancer. The recommended fluence for the following phase II study is 100 J/cm2.

  12. Systematic study of target localization for bioluminescence tomography guided radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jingjing [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231 and School of Physics and Information Technology, Shaanxi Normal University, Shaanxi 710119 (China); Zhang, Bin; Reyes, Juvenal; Wong, John W.; Wang, Ken Kang-Hsin, E-mail: kwang27@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231 (United States); Iordachita, Iulian I. [Laboratory for Computational Sensing and Robotics, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Lu, Zhihao [Department of Oncology and Department of Surgery, Johns Hopkins University, Baltimore, Maryland 21231 and Key laboratory of Carcinogenesis and Translational Research, Department of GI Oncology, Peking University, Beijing Cancer Hospital and Institute, Beijing 100142 (China); Brock, Malcolm V. [Department of Oncology and Department of Surgery, Johns Hopkins University, Baltimore, Maryland 21231 (United States); Patterson, Michael S. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario L8S 4L8 (Canada)

    2016-05-15

    Purpose: To overcome the limitation of CT/cone-beam CT (CBCT) in guiding radiation for soft tissue targets, the authors developed a spectrally resolved bioluminescence tomography (BLT) system for the small animal radiation research platform. The authors systematically assessed the performance of the BLT system in terms of target localization and the ability to resolve two neighboring sources in simulations, tissue-mimicking phantom, and in vivo environments. Methods: Multispectral measurements acquired in a single projection were used for the BLT reconstruction. The incomplete variables truncated conjugate gradient algorithm with an iterative permissible region shrinking strategy was employed as the optimization scheme to reconstruct source distributions. Simulation studies were conducted for single spherical sources with sizes from 0.5 to 3 mm radius at depth of 3–12 mm. The same configuration was also applied for the double source simulation with source separations varying from 3 to 9 mm. Experiments were performed in a standalone BLT/CBCT system. Two self-illuminated sources with 3 and 4.7 mm separations placed inside a tissue-mimicking phantom were chosen as the test cases. Live mice implanted with single-source at 6 and 9 mm depth, two sources at 3 and 5 mm separation at depth of 5 mm, or three sources in the abdomen were also used to illustrate the localization capability of the BLT system for multiple targets in vivo. Results: For simulation study, approximate 1 mm accuracy can be achieved at localizing center of mass (CoM) for single-source and grouped CoM for double source cases. For the case of 1.5 mm radius source, a common tumor size used in preclinical study, their simulation shows that for all the source separations considered, except for the 3 mm separation at 9 and 12 mm depth, the two neighboring sources can be resolved at depths from 3 to 12 mm. Phantom experiments illustrated that 2D bioluminescence imaging failed to distinguish two sources

  13. Hematuria following stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer.

    Science.gov (United States)

    Gurka, Marie K; Chen, Leonard N; Bhagat, Aditi; Moures, Rudy; Kim, Joy S; Yung, Thomas; Lei, Siyuan; Collins, Brian T; Krishnan, Pranay; Suy, Simeng; Dritschilo, Anatoly; Lynch, John H; Collins, Sean P

    2015-02-19

    Hematuria following prostate radiotherapy is a known toxicity that may adversely affect a patient's quality of life. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT hematuria would be more common than with alternative radiation therapy approaches. Herein, we describe the incidence and severity of hematuria following stereotactic body radiation therapy (SBRT) for prostate cancer at our institution. Two hundred and eight consecutive patients with prostate cancer treated with SBRT monotherapy with at least three years of follow-up were included in this retrospective analysis. Treatment was delivered using the CyberKnife® (Accuray) to doses of 35-36.25 Gy in 5 fractions. Toxicities were scored using the CTCAE v.4. Hematuria was counted at the highest grade it occurred in the acute and late setting for each patient. Cystoscopy findings were retrospectively reviewed. Univariate and multivariate analyses were performed. Hematuria-associated bother was assessed via the Expanded Prostate Index Composite (EPIC)-26. The median age was 69 years with a median prostate volume of 39 cc. With a median follow-up of 48 months, 38 patients (18.3%) experienced at least one episode of hematuria. Median time to hematuria was 13.5 months. In the late period, there were three grade 3 events and five grade 2 events. There were no grade 4 or 5 events. The 3-year actuarial incidence of late hematuria ≥ grade 2 was 2.4%. On univariate analysis, prostate volume (p = 0.022) and history of prior procedure(s) for benign prostatic hypertrophy (BPH) (p = 0.002) were significantly associated with hematuria. On multivariate analysis, history of prior procedure(s) for BPH (p prostate cancer was well tolerated with hematuria rates comparable to other radiation modalities. Patients factors associated with BPH, such as larger prostate volume, alpha antagonist usage, and prior history of procedures for BPH

  14. The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy.

    Directory of Open Access Journals (Sweden)

    Ines Lakhal-Naouar

    Full Text Available The effectiveness of systemic antimonial (sodium stibogluconate, Pentostam, SSG treatment versus local heat therapy (Thermomed for cutaneous leishmaniasis was studied previously and showed similar healing rates. We hypothesized that different curative immune responses might develop with systemic and local treatment modalities.We studied the peripheral blood immune cells in a cohort of 54 cutaneous Leishmania major subjects treated with SSG or TM. Multiparameter flow cytometry, lymphoproliferative assays and cytokine production were analyzed in order to investigate the differences in the immune responses of subjects before, on and after treatment.Healing cutaneous leishmaniasis lead to a significant decline in circulating T cells and NKT-like cells, accompanied by an expansion in NK cells, regardless of treatment modality. Functional changes involved decreased antigen specific CD4+ T cell proliferation (hyporesponsiveness seen with CD8+ T cell depletion. Moreover, the healing (or healed state was characterized by fewer circulating regulatory T cells, reduced IFN-γ production and an overall contraction in polyfunctional CD4+ T cells.Healing from cutaneous Leishmaniasis is a dynamic process that alters circulating lymphocyte populations and subsets of T, NK and NKT-like cells. Immunology of healing, through local or systemic treatments, culminated in similar changes in frequency, quality, and antigen specific responsiveness with immunomodulation possibly via a CD8+ T cell dependent mechanism. Understanding the evolving immunologic changes during healing of human leishmaniasis informs protective immune mechanisms.

  15. A case of a gastric submucosal tumor treated with combined therapy using superselective TAE and endoscopic local resection.

    Science.gov (United States)

    Chikamori, Fumio; Kuniyoshi, Nobutoshi; Okamoto, Hiroshi; Kuniyoshi, Kazushige

    2012-10-01

    The case was a 76-year-old female, who was noted to have a gastric submucosal tumor 25 mm in size located at the lesser curvature of the gastric body. Computed tomography revealed that the tumor was located near the coronary loop between the left and right gastric arteries. On the day before endoscopic local resection, abdominal angiography was performed and it revealed that the tumor was supplied by the left and right gastric arteries. Superselective transarterial embolization of the left and right gastric arteries around the tumor was performed to prevent accidental bleeding during the endoscopic procedure. Endoscopic local resection using full-thickness resection and submucosal dissection techniques was performed under general anesthesia. The tumor was completely resected without accidental bleeding. A gastric wall defect was closed using metallic clips and loop snares. Histologic examination revealed that the tumor was a low-risk gastrointestinal stromal tumor. We suggest that the combined therapy using superselective transarterial embolization and endoscopic local resection is an optional safe method for the treatment of gastric submucosal tumors.

  16. Adjunctive Systemic and Local Antimicrobial Therapy in the Surgical Treatment of Peri-implantitis: A Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Carcuac, O; Derks, J; Charalampakis, G; Abrahamsson, I; Wennström, J; Berglundh, T

    2016-01-01

    The aim of the present randomized controlled clinical trial was to investigate the adjunctive effect of systemic antibiotics and the local use of chlorhexidine for implant surface decontamination in the surgical treatment of peri-implantitis. One hundred patients with severe peri-implantitis were recruited. Surgical therapy was performed with or without adjunctive systemic antibiotics or the local use of chlorhexidine for implant surface decontamination. Treatment outcomes were evaluated at 1 y. A binary logistic regression analysis was used to identify factors influencing the probability of treatment success, that is, probing pocket depth ≤5 mm, absence of bleeding/suppuration on probing, and no additional bone loss. Treatment success was obtained in 45% of all implants but was higher in implants with a nonmodified surface (79%) than those with a modified surface (34%). The local use of chlorhexidine had no overall effect on treatment outcomes. While adjunctive systemic antibiotics had no impact on treatment success at implants with a nonmodified surface, a positive effect on treatment success was observed at implants with a modified surface. The likelihood for treatment success using adjunctive systemic antibiotics in patients with implants with a modified surface, however, was low. As the effect of adjunctive systemic antibiotics depended on implant surface characteristics, recommendations for their use in the surgical treatment of peri-implantitis should be based on careful assessments of the targeted implant (ClinicalTrials.gov NCT01857804).

  17. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    Science.gov (United States)

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  18. Validation of the 2nd Generation Proteasome Inhibitor Oprozomib for Local Therapy of Pulmonary Fibrosis.

    Directory of Open Access Journals (Sweden)

    Nora Semren

    Full Text Available Proteasome inhibition has been shown to prevent development of fibrosis in several organs including the lung. However, effects of proteasome inhibitors on lung fibrosis are controversial and cytotoxic side effects of the overall inhibition of proteasomal protein degradation cannot be excluded. Therefore, we hypothesized that local lung-specific application of a novel, selective proteasome inhibitor, oprozomib (OZ, provides antifibrotic effects without systemic toxicity in a mouse model of lung fibrosis. Oprozomib was first tested on the human alveolar epithelial cancer cell line A549 and in primary mouse alveolar epithelial type II cells regarding its cytotoxic effects on alveolar epithelial cells and compared to the FDA approved proteasome inhibitor bortezomib (BZ. OZ was less toxic than BZ and provided high selectivity for the chymotrypsin-like active site of the proteasome. In primary mouse lung fibroblasts, OZ showed significant anti-fibrotic effects, i.e. reduction of collagen I and α smooth muscle actin expression, in the absence of cytotoxicity. When applied locally into the lungs of healthy mice via instillation, OZ was well tolerated and effectively reduced proteasome activity in the lungs. In bleomycin challenged mice, however, locally applied OZ resulted in accelerated weight loss and increased mortality of treated mice. Further, OZ failed to reduce fibrosis in these mice. While upon systemic application OZ was well tolerated in healthy mice, it rather augmented instead of attenuated fibrotic remodelling of the lung in bleomycin challenged mice. To conclude, low toxicity and antifibrotic effects of OZ in pulmonary fibroblasts could not be confirmed for pulmonary fibrosis of bleomycin-treated mice. In light of these data, the use of proteasome inhibitors as therapeutic agents for the treatment of fibrotic lung diseases should thus be considered with caution.

  19. Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity

    DEFF Research Database (Denmark)

    Høgberg, Lotte Christine Groth; Bania, Theodore C; Lavergne, Valéry

    2016-01-01

    BACKGROUND: Following national and regional recommendations, intravenous lipid emulsion (ILE) has become established in clinical practice as a treatment for acute local anesthetic (LA) toxicity, although evidence of efficacy is limited to animal studies and human case reports. A collaborative lipid...... emulsion workgroup was therefore established by the American Academy of Clinical Toxicology to review the evidence on the effect of ILE for LA toxicity. METHODS: We performed a systematic review of the literature published through 15 December 2014. Relevant articles were determined based on pre...

  20. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Francois, E-mail: francois.meyer@chuq.qc.ca [Laval University Cancer Research Center, Centre hospitalier universitaire de Quebec - L' Hotel-Dieu de Quebec, Quebec (Canada); Fortin, Andre; Wang, Chang Shu [Radiation Therapy Department, Centre hospitalier universitaire de Quebec - L' Hotel-Dieu de Quebec, Quebec (Canada); Liu, Geoffrey [Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto (Canada); Bairati, Isabelle [Laval University Cancer Research Center, Centre hospitalier universitaire de Quebec - L' Hotel-Dieu de Quebec, Quebec (Canada)

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  1. Cobalt nanoparticles coated with graphitic shells as localized radio frequency absorbers for cancer therapy

    Science.gov (United States)

    Xu, Yang; Mahmood, Meena; Li, Zhongrui; Dervishi, Enkeleda; Trigwell, Steve; Zharov, Vladimir P.; Ali, Nawab; Saini, Viney; Biris, Alexandru R.; Lupu, Dan; Boldor, Dorin; Biris, Alexandru S.

    2008-10-01

    Graphitic carbon-coated ferromagnetic cobalt nanoparticles (C-Co-NPs) with diameters of around 7 nm and cubic crystalline structures were synthesized by catalytic chemical vapor deposition. X-ray diffraction and x-ray photoelectron spectroscopy analysis indicated that the cobalt nanoparticles inside the carbon shells were preserved in the metallic state. Fluorescence microscopy images and Raman spectroscopy revealed effective penetrations of the C-Co-NPs through the cellular plasma membrane of the cultured HeLa cells, both inside the cytoplasm and in the nucleus. Low radio frequency (RF) radiation of 350 kHz induced localized heat into the metallic nanoparticles, which triggered the killing of the cells, a process that was found to be dependent on the RF application time and nanoparticle concentration. When compared to carbon nanostructures such as single-wall carbon nanotubes, these coated magnetic cobalt nanoparticles demonstrated higher specificity for RF absorption and heating. DNA gel electrophoresis assays of the HeLa cells after the RF treatment showed a strong broadening of the DNA fragmentation spectrum, which further proved the intense localized thermally induced damages such as DNA and nucleus membrane disintegration, under RF exposure in the presence of C-Co-NPs. The data presented in this report indicate a great potential of this new process for in vivo tumor thermal ablation, bacteria killing, and various other biomedical applications.

  2. Local injection of botulinum toxin A: an alternative therapy for axillary osmidrosis.

    Science.gov (United States)

    Xie, Aiguo; Nie, Lanjun; Tan, Qian

    2014-02-01

    The objective of this study was to investigate the efficacy of local injection of botulinum toxin A for treating axillary osmidrosis. One hundred and fifty patients with axillary osmidrosis were randomly divided to receive botulinum toxin A injection treatment (50 U of botulinum toxin A was injected intracutaneously into 6-20 different sites within each axilla, n = 74) or surgical excision of the apocrine glands (n = 76). The patients were followed up for 1-3 months to analyze the therapeutic effect and complications of the two methods. The curative effect in patients with mild and moderate axillary osmidrosis was not significantly different between the botulinum toxin A injection group and operation group. However, for patients with severe axillary osmidrosis, surgery treatment seemed to be superior to botulinum toxin A treatment (P = 0.005). There was also no significant difference in the modified Dermatology Life Quality Index between the two treatments. Two cases showed complications related to hemorrhage and incision infection in the operation group. In conclusion, local injection of botulinum toxin A is a safe, fast and effective treatment for mild and moderate axillary osmidrosis, but the long-term effect remains to be further investigated.

  3. Cerebral venous thrombosis: treatment with local fibrinolysis plus alteplase; Trombosis venosa cerebral. Tratamiento mediante fibrinolisis local con alteplasa

    Energy Technology Data Exchange (ETDEWEB)

    Asis Bravo, F. de; Delgado, F.; Cano, A.; Bautista, D.

    2002-07-01

    Cerebral venous thrombosis is a rare entity with widely variable clinical signs: thus, a high degree of suspicion is required for diagnosis. It affects the dural sinuses and may or may not invade cerebral veins. The diagnosis has usually been based on an angiographic study although, at the present time, new noninvasive imaging techniques, such as computed tomography, magnetic resonance and magnetic resonance angiography are being employed in a growing number of cases. Treatment should involve symptomatic and etiologic therapy. Although anti coagulation would appear to be a reasonable option in these patients, it remains controversial. As in other processes such as pulmonary embolism and coronary thrombosis, the introduction of novel and increasingly safe fibrinolytic drugs, together with technical innovations in the field of interventional neuroradiology, is changing the perspectives for the management of these patients. We present the case of a 43-year-old woman with right sinus thrombosis who was treated with local thrombolysis plus alteplase (tissue plasminogen activator). The authors describe the technique employed and review the literature. (Author) 16 refs.

  4. Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure

    Energy Technology Data Exchange (ETDEWEB)

    Kukielka, A.M.; Hetnal, M.; Dabrowski, T.; Walasek, T.; Brandys, P.; Reinfuss, M. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Radiotherapy, Krakow (Poland); Nahajowski, D.; Kudzia, R.; Dybek, D. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Medical Physics, Department of Radiotherapy, Krakow (Poland)

    2014-02-15

    The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy. Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83 %). The aim of the hyperthermia treatment was to heat the prostate to 41-43 C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir + 2 ng/ml). The median age was 71 years (range 62-83 years), the median initial PSA level was 16.3 ng/ml (range 6.37-64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044-25.346 ng/ml). The median follow-up was 13 months (range 4-48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan-Meier estimate of biochemical control after salvage treatment was 74 %. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir < 0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients. IHT in combination

  5. Thrombin inhibitory and clot-specific fibrinolytic activities of the urokinase variant, M23 (rscu-PA-40 kDa/Hir)

    NARCIS (Netherlands)

    Schneider, J; Wnendt, S; Saunders, D; HeinzelWieland, R; Wilffert, B; Steffens, G

    1996-01-01

    The recombinant bifunctional urokinase variant, M23 (rscu-PA-40 kDA/Hir), comprising the kringle and protease domain of single-chain urokinase-type plasminogen activator and a C-terminal fragment of hirudin in one single-chain molecule, was evaluated for its thrombin-inhibitory and fibrinolytic

  6. Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis.

    Science.gov (United States)

    Vuckovic, Biljana A; Djeric, Mirjana J; Tomic, Branko V; Djordjevic, Valentina J; Bajkin, Branislav V; Mitic, Gorana P

    2017-08-01

    : Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis.Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs).Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20).Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.

  7. Optimization of fibrinolytic enzyme production by Bacillus subtilis DC-2 in aqueous two-phase system (poly-ethylene glycol 4000 and sodium sulfate).

    Science.gov (United States)

    Ashipala, Onesmus K; He, Qian

    2008-07-01

    The central composite rotable design (CCRD) was used to determine optimal conditions for fibrinolytic enzyme production by Bacillus subtilis DC-2 in poly-ethylene glycol 4000 (PEG 4000) and sodium sulfate (Na(2)SO(4)) aqueous two-phase system (ATPS). PEG 4000 and Na(2)SO(4) concentration, fermentation time and temperature, and pH were selected as variables to evaluate the fibrinolytic activity in PEG phase. Using response surface methodology (RSM), a second-order polynomial equation was obtained by multiple regression analysis. The predicted maximal fibrinolytic activity in PEG phase was 1241.02 IU/ml with 9.05% PEG 4000 concentration, 5.06% Na(2)SO(4) concentration, 118.77 h fermentation time, 37.57 degrees C fermentation temperature and pH 6.52. The validity of the response model was verified by a good agreement between predicted and experimental results. The fibrinolytic activity obtained from experimental results in PEG phase (1223.61 IU/ml) was higher than that produced in homogeneous fermentation (1165.58 IU/ml).

  8. Production of fibrinolytic enzyme from Bacillus amyloliquefaciens by fermentation of chickpeas, with the evaluation of the anticoagulant and antioxidant properties of chickpeas.

    Science.gov (United States)

    Wei, Xuetuan; Luo, Mingfang; Xu, Lin; Zhang, Yewei; Lin, Xing; Kong, Peng; Liu, Huizhou

    2011-04-27

    To develop safe and cheap thrombolytic agents, a fibrinolytic enzyme productive strain of LSSE-62 was isolated from Chinese soybean paste. This strain was identified as Bacillus amyloliquefaciens by 16S rDNA sequence analysis. Nucleotide and amino acid sequence analysis showed that this fibrinolytic enzyme was identical to subtilisin DJ-4. Chickpeas were used as the substrate for fibrinolytic enzyme production from B. amyloliquefaciens in solid-state fermentation. Under the optimized conditions (34 °C and 50% initial moisture content), the fibrinolytic activity of fermented chickpeas reached 39.28 fibrin degradation units (FU)/g. Additionally, the fermented chickpeas showed anticoagulant activity, and the purified anticoagulant component showed higher anticoagulant activity than heparin sodium. After fermentation, the total phenolic and total flavonoid contents increased by 222 and 71%, respectively, and then the antioxidant activities were improved significantly. This study provided a novel method for the preparation of multifunctional food of chickpeas or raw materials for the preparation of functional food additives and potential drugs.

  9. Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Shu-Lian Wang; Zhongxing Liao; Helen Liu; Jaffer Ajani; Stephen Swisher; James D Cox; Ritsuko Komaki

    2006-01-01

    AIM: To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer.METHODS: A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed.RESULTS: Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%).tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%)of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula.CONCLUSION: Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

  10. [Extrapulmonary tuberculosis in Denmark. A review of the incidence, localization and therapy].

    Science.gov (United States)

    Kok-Jensen, A; Viskum, K

    1994-09-12

    In Denmark, just under 20% of tuberculosis (TB) cases amongst Danes and 25-30% of cases amongst people of foreign nationalities are made up of isolated extrapulmonary (EP) TB. The incidence among Danes is falling, whereas an increasing amount of EP TB cases are found among foreigners due to continued immigration, and these now constitute 50% of all cases of EP TB. EP TB is found among older Danes and younger foreigners. The HIV/AIDS epidemic has not had any effect on the incidence of TB and EP TB in Denmark. EP TB is most frequently found in lymph nodes and the urogenital system. Since the disease is rare, it may be overlooked; it should be considered as a differential diagnosis in unresolved cases, particularly in immigrants from countries with a high prevalence of TB. Treatment is as for pulmonary TB, namely "four drug" therapy for six months. Surgical intervention is rarely required. Supplementation with oral steroids may be useful in very special cases.

  11. Lysostaphin: immunogenicity of locally administered recombinant protein used in mastitis therapy.

    Science.gov (United States)

    Daley, M J; Oldham, E R

    1992-03-01

    A recombinant bactericidal protein, recombinant lysostaphin (r-lysostaphin), that may be useful as an intramammary therapeutic for Staphylococcus aureus mastitis in dairy cattle, was evaluated for immunogenicity to various hosts. Although immunogenicity could be demonstrated in a variety of other species when administered parenterally, oral administration failed to elicit a significant immunological response. Similarly, intramammary infusion of r-lysostaphin failed to elicit significant serum titers in the bovine until 18-21 infusions were administered (total administered dose of 2-3 g of protein). Antibody titers from dairy cattle which did develop an immune response were predominantly of the IgG1 subclass. Dairy cattle with significant anti-lysostaphin titers showed no deleterious symptoms (anaphylaxis, etc.) upon subsequent infusion, and these titers did not effect the in vitro bacteriostatic activity of r-lysostaphin. Intramammary infusion of r-lysostaphin does not elicit any observable effects on the host animal or on the potential efficacy of the recombinant molecule. Intramammary recombinant proteins may be suitable effective and safe infusion products that provide an alternative to classical antibiotic therapy.

  12. The importance of combined radiation and endocrine therapy in locally advanced prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Phillip J Gray; William U Shipley

    2012-01-01

    The management of all stages of prostate cancer has become an increasingly complex task as new treatment paradigms are tested and the results of large randomized studies become available.Despite these advances,prostate cancer remains the second leading cause of eancer death and the seventh overall cause of death in men in the United States.1 The advent of prostate-specific antigen (PSA) testing in the 1980s resulted in a significant downward stage migration such that many men now present with the earliest and most curable form of the disease.2,3 Despite this fact,high-risk locally advanced prostate cancer remains a common and complex problem facing clinicians across the world.

  13. Comparing complementary alternative treatment for chronic shoulder pain of myofascial origin: Collateral meridian therapy versus local tender area-related meridians therapy.

    Science.gov (United States)

    Pan, Ru-Yu; Hsu, Yung-Chi; Wong, Chih-Shung; Lin, Shinn-Long; Li, Tsung-Ying; Cherng, Chen-Hwan; Ko, Shan-Chi; Yeh, Chun-Chang

    2016-08-01

    The aim of this study was to compare the short-term outcomes between 2 different treatments for unilateral chronic shoulder pain of myofascial origin, that is, local tender area related meridians (LTARMs) treatment and collateral meridian therapy (CMT), which were performed 6 times over a period of 4 weeks.Seventy patients with unilateral shoulder pain of chronic myofascial origin were enrolled. The patients were randomly assigned to 2 different treatment groups: 1 group received CMT (n = 35) and the other received LTARM (n = 35). Before and after the 2 treatment processes, all patients rated their overall pain intensity on a visual analogue scale (VAS) and a validated 13-question shoulder pain and disability index (SPADI) questionnaire was used to measure shoulder pain and functional impairment after therapy for 4 weeks.After CMT, the pain intensity was reduced after CMT. VAS score is reduced from 5.90 ± 2.07 (a mean of 5.90 and standard deviation of 2.07) to 3.39 ± 1.2. This was verified by the SPADI pain subscale scores (from 0.58 ± 0.193 to 0.33 ± 0.14). The pain-relief effect of CMT was significantly better than that of LTARM (VAS score from 5.78 ± 1.64 to 4.58 ± 1.40; P myofascial origin than the LTARM treatment, where treatment with the former resulted in better functional recovery after 4 weeks than the latter.

  14. Transcatheter arterial chemoembolization and radiation therapy for treatment-naive patients with locally advanced hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won [Dept. of Radiation Oncology, Yeungnam University Medical Center, Daegu (Korea, Republic of); Oh, Dong Ryul; Park, Hee Chul; Lim, Do Hoon; Shin, Sung Wook; Cho, Sung Ki; Gwak, Geum Youn; Choi, Moon Seok; Paik, Yong Han; Paik, Seung Woon [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-naive patients with locally advanced hepatocellular carcinoma (HCC). Eligibility criteria were as follows: newly diagnosed with HCC, the Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59 patients were retrospectively enrolled. All patients were treated with TACE followed by RT. The time interval between TACE and RT was 2 weeks as per protocol. A median RT dose was 47.25 Gy10 as the biologically effective dose using the α/β = 10 (range, 39 to 65.25 Gy10). At 1 month, complete response was obtained in 3 patients (5%), partial response in 27 patients (46%), stable disease in 13 patients (22%), and progressive disease in 16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%, respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4 months). The median time to progression was 4 months (range, 1 to 35 months). Grade 3 or greater liver enzyme elevation occurred in only two patients (3%) after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%). The combination treatment of TACE followed by RT with two-week interval was safe and it showed favorable outcomes in treatment-naive patients with locally advanced HCC. A prospective randomized trial is needed to validate these results.

  15. Treatment of two postoperative endophthalmitis cases due to Aspergillus flavus and Scopulariopsis spp. with local and systemic antifungal therapy

    Directory of Open Access Journals (Sweden)

    Uyar Guliz

    2007-07-01

    Full Text Available Abstract Background Endophthalmitis is the inflammatory response to invasion of the eye with bacteria or fungi. The incidence of endophthalmitis after cataract surgery varies between 0.072–0.13 percent. Treatment of endophthalmitis with fungal etiology is difficult. Case Presentation Case 1: A 71-year old male diabetic patient developed postoperative endophthalmitis due to Aspergillus flavus. The patient was treated with topical amphotericin B ophthalmic solution, intravenous (IV liposomal amphotericin-B and caspofungin following vitrectomy. Case 2: A 72-year old male cachectic patient developed postoperative endophthalmitis due to Scopulariopsis spp. The patient was treated with topical and IV voriconazole and caspofungin. Conclusion Aspergillus spp. are responsible of postoperative fungal endophthalmitis. Endophthalmitis caused by Scopulariopsis spp. is a very rare condition. The two cases were successfully treated with local and systemic antifungal therapy.

  16. Preoperative Induction Therapy for Locally Advanced Thymic Tumors: A Retrospective Analysis Using the ChART Database

    Directory of Open Access Journals (Sweden)

    Yucheng WEI

    2016-07-01

    Full Text Available Background and objective To evaluate the role of preoperative induction therapy on prognosis of locally advanced thymic malignancies. Methods Between 1994 and 2012, patients received preoperative induction therapies (IT group in the Chinese Alliance for Research in Thymomas (ChART database, were compared with those having surgery directly after preoperative evaluation (DS group. All tumors receiving induction therapies were locally advanced (clinically stage III-IV before treatment and those turned out to be in pathological stage I and II were considered downstaged by induction. Clinical pathological characteristics were retrospectively analyzed. To more accurately study the effect of induction therapies, stage IV patients were then excluded. Only stage I-III tumors in the IT group and stage III cases in the DS group were selected for further comparison in a subgroup analysis. Results Only 68 (4% out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS of 49.7% and 19.9%. Seventeen patients (25% were downstaged after induction. Significantly more thymomas were downstaged than thymic carcinomas (38.7% vs 13.9%, P=0.02. Tumors downstaged after induction had significantly higher 5-year OS than those not downstaged (93.8% vs 35.6%, P=0.013. For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P<0.001, although R0 resection were similar (76.4% vs 73.3%, P=0.63. However, 5-year OS in tumors downstaged after induction (93.8% was similar to those in the DS group (85.2%, P=0.438, both significantly higher than those not downstaged after induction (35.6%, P<0.001. Conclusion Only 68 (4% out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS of 49.7% and 19.9%. Seventeen patients (25% were downstaged after

  17. Preoperative Intensity Modulated Radiation Therapy and Chemotherapy for Locally Advanced Vulvar Carcinoma: Analysis of Pattern of Relapse

    Energy Technology Data Exchange (ETDEWEB)

    Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Shukla, Gaurav; Shinde, Ashwin; Heron, Dwight E. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Kelley, Joseph L.; Edwards, Robert P.; Sukumvanich, Paniti; Richards, Scott; Olawaiye, Alexander B.; Krivak, Thomas C. [Division of Gynecologic Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States)

    2013-04-01

    Purpose: To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-two patients with stage I-IV{sub A} (stage I, n=3; stage II, n=13; stage III, n=23; stage IV{sub A}, n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results: Thirty-three patients (78.6%) had surgery for resection of vulva; 13 of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions: Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes.

  18. The Hippocampus Sparing Volume Modulated Arc Therapy does not Influence Plan Quality on Locally Advanced Nasopharyngeal Carcinoma Patients.

    Science.gov (United States)

    Gu, Wendong; Li, Qilin; Xi, Dan; Tian, Ye; Mo, Juncong; Pei, Honglei

    2017-06-13

    Irradiation on hippocampus would lead to neuro-cognitive dysfunction in locally advanced nasopharyneal carcinoma (LA-NPC) patients accepting radiotherapy. Our study here aimed to investigate if undergoing hippocampus sparing (HS) volume modulated arc therapy (VMAT) would influence the plan quality in LA NPC patients. We designed three kinds of radiotherapeutic plans for 11 LA NPC patients: conventional VMAT (C-VMAT), HS-VMAT and HS intensity modulated radiation therapy with dynamic multileaf collimator (HS-dMLC). And the dose distribution on targets and surrounding organs at risk (OAR) were carefully evaluated. We found out that the expected doses on hippocampus were significantly lowered in HS-VMAT (899 ± 378 cGy) and HS-dMLC (896 ± 321 cGy) as compared to C-VMAT (1518 ± 337 cGy, p plan quality of targets (p > 0.05). Moreover, lower radiation doses on brain stem were observed in HS-VMAT plan in comparison with C-VMAT plan (p plans. Here we concluded that HS-VMAT presented promising advantages on protecting hipppcampus and brain stem as compared to C-VMAT and HS-dMLC, but enthusiastically had no effects on plan quality in LA-NPC patients.

  19. The FLUKA Monte Carlo code coupled with the local effect model for biological calculations in carbon ion therapy

    CERN Document Server

    Mairani, A; Kraemer, M; Sommerer, F; Parodi, K; Scholz, M; Cerutti, F; Ferrari, A; Fasso, A

    2010-01-01

    Clinical Monte Carlo (MC) calculations for carbon ion therapy have to provide absorbed and RBE-weighted dose. The latter is defined as the product of the dose and the relative biological effectiveness (RBE). At the GSI Helmholtzzentrum fur Schwerionenforschung as well as at the Heidelberg Ion Therapy Center (HIT), the RBE values are calculated according to the local effect model (LEM). In this paper, we describe the approach followed for coupling the FLUKA MC code with the LEM and its application to dose and RBE-weighted dose calculations for a superimposition of two opposed C-12 ion fields as applied in therapeutic irradiations. The obtained results are compared with the available experimental data of CHO (Chinese hamster ovary) cell survival and the outcomes of the GSI analytical treatment planning code TRiP98. Some discrepancies have been observed between the analytical and MC calculations of absorbed physical dose profiles, which can be explained by the differences between the laterally integrated depth-d...

  20. Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schreiber, David; Weiss, Jeffrey P.; Safdieh, Joseph; Weiner, Joseph; Rotman, Marvin; Schwartz, David [Veterans Affairs, New York Harbor Healthcare System, Brooklyn (United States); Rineer, Justin [University of Florida Health Cancer Center at Orlando Health, Orlando (United States)

    2015-03-15

    We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation. From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (> or =7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

  1. Personalized therapy in locally advanced head and neck squamous-cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sánchez-Escribano R

    2013-11-01

    Full Text Available Introduction: Locally advanced head and neck squamous cell carcinoma patients (LAHNSCC represents a truly heterogeneous population with differences in comorbidities, primary tumor location and etiology. These are key factors in optimal treatment selection. Material and methods: An extensive literature review was made in order to identify the most relevant factor in the therapeutic decision, with special interest in induction chemotherapy as the latest and most debatable option. Results: In the therapeutic decision we have to take into account factors related to the patient, age and performance status are the most important, and others related to the tumor as stage, site of origin and etiology, between this ones l, viral subtypes (EBV and HPV are becoming relevant in the later decades. Chemoradiotherapy is considered the gold standard treatment, supported by several randomized trials and metaanalysis. Induction chemotherapy is one of the later options appeared in the therapeutic arena, improving results in organ preservation and survival. Although a substantial increase in toxicities and lack of prospective comparisons with the standard concurrent chemoradioterapy, warrants a cautious use. Conclusions: Therapeutic choice in the LAHNSCC patient is a complex and multidimensional process, that should be carried in a specialized and multidisciplinary team that can assure the highest efficiency and security for the patient

  2. A Dosimetric Comparison between Conventional Fractionated and Hypofractionated Image-guided Radiation Therapies for Localized Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    Ming Li; Gao-Feng Li; Xiu-Yu Hou; Hong Gao; Yong-Gang Xu; Ting Zhao

    2016-01-01

    Background:Image-guided radiation therapy (IGRT) is the preferred method for curative treatment of localized prostate cancer,which could improve disease outcome and reduce normal tissue toxicity reaction.IGRT using cone-beam computed tomography (CBCT) in combination with volumetric-modulated arc therapy (VMAT) potentially allows smaller treatment margins and dose escalation to the prostate.The aim of this study was to compare the difference of dosimetric diffusion in conventional IGRT using 7-field,step-and-shoot intensity-modulated radiation therapy (IMRT) and hypofractionated IGRT using VMAT for patients with localized prostate cancer.Methods:We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT (n =12) or VMAT (n =12) for prostate cancer between November 2013 and October 2015.Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator.Offline planning was performed using the daily treatment images registered with simulation computed tomography (CT) images.A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study.Dose distributions were recalculated on CBCT images registered with the planning CT scanner.Results:Compared with 7-field,step-and-shoot IMRT,VMAT plans resulted in improved planning target volume (PTV) D95% (7663.17 ± 69.57 cGy vs.7789.17 ± 131.76 cGy,P < 0.001).VMAT reduced the rectal D25 (P < 0.001),D35 (P < 0.001),and D50 (P < 0.001),bladder V50 (P < 0.001),D25 (P =0.002),D35 (P =0.028),and D50 (P =0.029).However,VMAT did not statistically significantly reduce the rectal V50,compared with 7-field,step-and-shoot IMRT (25.02 ± 5.54% vs.27.43 ± 8.79%,P =0.087).Conclusions:To deliver the hypofractionated radiotherapy in prostate cancer,VMAT significantly increased PTV D95% dose and decreased the dose of radiation delivered to adjacent

  3. A Dosimetric Comparison between Conventional Fractionated and Hypofractionated Image-guided Radiation Therapies for Localized Prostate Cancer

    Science.gov (United States)

    Li, Ming; Li, Gao-Feng; Hou, Xiu-Yu; Gao, Hong; Xu, Yong-Gang; Zhao, Ting

    2016-01-01

    Background: Image-guided radiation therapy (IGRT) is the preferred method for curative treatment of localized prostate cancer, which could improve disease outcome and reduce normal tissue toxicity reaction. IGRT using cone-beam computed tomography (CBCT) in combination with volumetric-modulated arc therapy (VMAT) potentially allows smaller treatment margins and dose escalation to the prostate. The aim of this study was to compare the difference of dosimetric diffusion in conventional IGRT using 7-field, step-and-shoot intensity-modulated radiation therapy (IMRT) and hypofractionated IGRT using VMAT for patients with localized prostate cancer. Methods: We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT (n = 12) or VMAT (n = 12) for prostate cancer between November 2013 and October 2015. Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator. Offline planning was performed using the daily treatment images registered with simulation computed tomography (CT) images. A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study. Dose distributions were recalculated on CBCT images registered with the planning CT scanner. Results: Compared with 7-field, step-and-shoot IMRT, VMAT plans resulted in improved planning target volume (PTV) D95% (7663.17 ± 69.57 cGy vs. 7789.17 ± 131.76 cGy, P V50 (P statistically significantly reduce the rectal V50, compared with 7-field, step-and-shoot IMRT (25.02 ± 5.54% vs. 27.43 ± 8.79%, P = 0.087). Conclusions: To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation delivered to adjacent normal tissues comparing to 7-field, step-and-shoot IMRT. Daily online image-guidance and better management of bladder and rectum could make a more precise

  4. Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999-2012).

    Science.gov (United States)

    Lejeune, A; Skorupski, K; Frazier, S; Vanhaezebrouck, I; Rebhun, R B; Reilly, C M; Rodriguez, C O

    2015-09-01

    This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188-2340). Median disease-free interval was 2120 days (149-2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188-2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300-2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco-regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local-regional therapy can provide a median survival in excess of 40 months.

  5. Radio(chemo)therapy for locally advanced squamous cell carcinoma of the esophagus. Long-term outcome

    Energy Technology Data Exchange (ETDEWEB)

    Ordu, Arif Deniz; Deymann, Lisa Felicia; Scherer, Vera; Combs, Stephanie E. [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Muenchen (Germany); Nieder, Carsten [University of Tromsoe, Department of Oncology and Palliative Medicine, Nordland Hospital Trust, Bodoe (Norway); Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Geinitz, Hans [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Muenchen (Germany); Krankenhaus der Barmherzigen Schwestern Linz, Department of Radiation Oncology, Linz (Austria); Kup, Philipp Guenther [Marien Hospital Herne, Universitaetsklinikum der Ruhr-Universitaet Bochum, Department of Radiation Oncology, Herne (Germany); Fakhrian, Khashayar [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Muenchen (Germany); Marien Hospital Herne, Universitaetsklinikum der Ruhr-Universitaet Bochum, Department of Radiation Oncology, Herne (Germany); Universitaetsklinikum der Ruhr-Universitaet Bochum, Department of Radiation Oncology, Sankt Josef Hospital Bochum, Bochum (Germany)

    2014-11-18

    The purpose of this work is to report the long-term outcomes of three-dimensional conformal radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC). A retrospective analysis of patients treated with radio(chemo)therapy between 1988 and 2011 at Klinikum rechts der Isar, Technische Universitaet Muenchen was performed. In all, 168 patients received radio(chemo)therapy for ESCC in curative intention. The median follow-up time was 91 months (range 1-212 months). There were 128 men and 40 women with a median age of 63 years. Selection criteria for radio(chemo)therapy were unfit for surgery and/or unresectable primary tumor (n = 146, 87 %) or patients' choice (n = 22, 13 %). The majority of the patients received a combination of cisplatin and 5-fluorouracil chemotherapy with 54 Gy in 30 fractions of radiotherapy. The median overall survival (OS) was 20 months (95 % confidence interval 17-23 months). The OS at 2 and 5 years for the whole cohort was 41 ± 4 % and 22 ± 3 %, respectively. Forty patients (24 %) suffered an in-field recurrence. The most common acute nonhematologic toxicity >grade 2 was dysphagia in 35 % of the patients. Acute hematologic toxicity > grade 2 was recorded in 14 % of the patients. There was no grade 5 toxicity observed during the study. Poor ECOG performance status (0-1 vs. 2-3, HR = 1.70, p = 0.002) and weight loss ≥ 10 % before the start of therapy (HR = 1.99, p = 0.001) were among the factors significantly associated with poor OS in multivariate analysis. Three-dimensional conformal definitive radio(chemo)therapy is well tolerated and leads to long-term survival in more than 20 % of patients with advanced disease and/or contraindication to surgery. However, 24 % in-field recurrence remains a major concern. Prospective trials are warranted to assess if a well-tailored conformal radiochemotherapy can improve the local control and obviate the need for surgical resection in patients with good general

  6. Long-term results of preoperative 5-fluorouracil-oxaliplatin chemoradiation therapy in locally advanced rectal cancer.

    Science.gov (United States)

    Fontana, Elisa; Pucci, Francesca; Camisa, Roberta; Bui, Simona; Galdy, Salvatore; Leonardi, Francesco; Negri, Francesca Virginia; Anselmi, Elisa; Losardo, Pier Luigi; Roncoroni, Luigi; Dell'abate, Paolo; Crafa, Pellegrino; Cascinu, Stefano; Ardizzoni, Andrea

    2013-02-01

    To evaluate the activity, safety and long-term survival of patients after preoperative oxaliplatin and 5-fluorouracil chemoradiation therapy in locally advanced rectal cancer (LARC). Patients with resectable, T3-4 and/or nodal involvement rectal adenocarcinoma were treated with oxaliplatin 60 mg/m(2) weekly and 5-fluorouracil 200 mg/m(2)/d infused continuously for five days, over a period of five weeks, and radiotherapy (45 Gy/25 fractions). The primary end-point was pathological complete response (ypCR). Safety, overall survival (OS) and relapse-free survival (RFS) were secondary end-points. Sixty-six patients were treated. Grade 1-2 diarrhea was the most common adverse event. The ypCR rate was 16.7% (95% confidence interval=7.7-25.7%). After a median follow-up of 73.5 months, 23 patients (34.8%) had experienced relapse. Five-year actuarial RFS and OS rates were 64% and 73%, respectively. Five-year actuarial RFS was 91.7% in the ypCR group versus 57.8% in non-ypCR cases. Long-term local control and survival after this very well-tolerated regimen appear encouraging.

  7. The Prevalence of Cardiac Risk Factors in Men with Localized Prostate Cancer Undergoing Androgen Deprivation Therapy in British Columbia, Canada

    Directory of Open Access Journals (Sweden)

    Margot K. Davis

    2015-01-01

    Full Text Available Background. While androgen deprivation therapy (ADT reduces the risk of prostate cancer-specific mortality in high-risk localized prostate cancer, it adversely affects cardiovascular (CV risk factor profiles in treated men. Methods. We retrospectively reviewed the charts of 100 consecutive men with intermediate- or high-risk localized prostate cancer referred to the British Columbia Cancer Agency for ADT. Data on CV risk factors and disease were collected and Framingham risk scores were calculated. Results. The median age of the study cohort was 73 years. Established cardiovascular disease was present in 25% of patients. Among patients without established CV disease, calculated Framingham risk was high in 65%, intermediate in 33%, and low in 1%. Baseline hypertension was present in 58% of patients, dyslipidemia in 51%, and diabetes or impaired glucose tolerance in 24%. Hypertension was more prevalent in the study cohort than in an age- and sex-matched population sample (OR 1.74, P=0.006; diabetes had a similar prevalence (OR 0.93, P=0.8. Conclusions. Patients receiving ADT have a high prevalence of cardiovascular disease and risk factors and are more likely to be hypertensive than population controls. Low rates of CV risk screening suggest opportunities for improved primary and secondary prevention of CV disease in this population.

  8. Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer.

    Science.gov (United States)

    Cho, Eun Jung; Sun, Bo; Doh, Kyung-Oh; Wilson, Erin M; Torregrosa-Allen, Sandra; Elzey, Bennett D; Yeo, Yoon

    2015-01-01

    Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks: conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers.

  9. Addition of gemcitabine to standard therapy in locally advanced cervical cancer: A randomized comparative study

    Directory of Open Access Journals (Sweden)

    Sanjoy Roy

    2011-01-01

    Full Text Available Background: The concurrent chemoradiotherapy for cervical cancer treatment is well accepted since 1999. This randomized, phase III trial aimed to observe if any improved outcome could be obtained capitalizing on the synergistic activity of gemcitabine, cisplatin, XRT. Materials and Methods: Stage IIB-IIIB, 18-70 years of age, KPS score ≥70, were randomized to control group and study group. Control group received cisplatin 40 mg/m 2 weekly with concurrent XRT, followed by brachytherapy and study group received gemcitabine 125 mg/m 2 weekly top of the same control group treatment. The primary end point was pathological response and toxicities along with patient compliance to treatment, late reactions, DFS and OS. Fifty patients were randomized between two arms. Results: The complete response in study and control arm was 96% and 88% respectively. Toxicities was significantly high in the study group compared to control group [leucopenia (P=0.015, skin reaction (P=0.03 and bleeding (P=0.019]. Local recurrence rate: 8% in study arm, none in control arm. The distant failure prevailed in control arm (20% vs. 8%. On a median follow up of 21 months in control arm, the DFS was 73% whereas 83% in study arm in 16 months (P=0.69. OS in the study arm was 100% and 84.5% in the control arm (P=0.14. Conclusions: If the toxicity can be managed adequately in the combination chemo radiation group, it may produce an improvement in response. Survival benefit can also be obtained by introducing gemcitabine to cisplatin as radio sensitizer.

  10. Snake venom induced local toxicities: plant secondary metabolites as an auxiliary therapy.

    Science.gov (United States)

    Santhosh, M Sebastin; Hemshekhar, M; Sunitha, K; Thushara, R M; Jnaneshwari, S; Kemparaju, K; Girish, K S

    2013-01-01

    Snakebite is a serious medical and socio-economic problem affecting the rural and agricultural laborers of tropical and sub-tropical region across the world leading to high morbidity and mortality. In most of the snakebite incidences, victims usually end up with permanent tissue damage and sequelae with high socioeconomic and psychological impacts. Although, mortality has been reduced markedly due to anti-venom regimen, it is associated with several limitations. Snake venom metalloprotease, hyaluronidase and myotoxic phospholipase A2 are the kingpins of tissue necrosis and extracellular matrix degradation. Thus, inhibition of these enzymes is considered to be the rate limiting step in the management of snakebite. Unfortunately, tissue necrosis and extracellular matrix degradation persists even after the administration of anti-venom. At present, inhibitors from snake serum and plasma, several synthetic compounds and their analogs have been demonstrated to possess anti-snake venom activities, but the use of plant metabolites for this purpose has an added advantage of traditional knowledge and will make the treatment cheaper and more accessible to the affected population. Therefore, the clinical and research forums are highly oriented towards plant metabolites and interestingly, certain phytochemicals are implicated as the antibody elicitors against venom toxicity that can be exploited in designing effective anti-venoms. Based on these facts, we have made an effort to enlist plant based secondary metabolites with antiophidian abilities and their mechanism of action against locally acting enzymes/toxins in particular. The review also describes their functional groups responsible for therapeutic beneficial and certainly oblige in designing potent inhibitors against venom toxins.

  11. Amide-type local anesthetics and human mesenchymal stem cells: clinical implications for stem cell therapy.

    Science.gov (United States)

    Dregalla, Ryan C; Lyons, Nicolette F; Reischling, Patrick D; Centeno, Christopher J

    2014-03-01

    In the realm of regenerative medicine, human mesenchymal stem cells (hMSCs) are gaining attention as a cell source for the repair and regeneration of tissues spanning an array of medical disciplines. In orthopedics, hMSCs are often delivered in a site-specific manner at the area of interest and may require the concurrent application of local anesthetics (LAs). To address the implications of using hMSCs in combination with anesthetics for intra-articular applications, we investigated the effect that clinically relevant doses of amide-type LAs have on the viability of bone marrow-derived hMSCs and began to characterize the mechanism of LA-induced hMSC death. In our study, culture-expanded hMSCs from three donors were exposed to the amide-type LAs ropivacaine, lidocaine, bupivacaine, and mepivacaine. To replicate the physiological dilution of LAs once injected into the synovial capsule, each anesthetic was reduced to 12.5%, 25%, and 50% of the stock solution and incubated with each hMSC line for 40 minutes, 120 minutes, 360 minutes, and 24 hours. At each time point, cell viability assays were performed. We found that extended treatment with LAs for 24 hours had a significant impact on both hMSC viability and adhesion. In addition, hMSC treatment with three of the four anesthetics resulted in cell death via apoptosis following brief exposures. Ultimately, we concluded that amide-type LAs induce hMSC apoptosis in a time- and dose-dependent manner that may threaten clinical outcomes, following a similar trend that has been established between these particular anesthetics and articular chondrocytes both in vitro and in vivo.

  12. Amide-Type Local Anesthetics and Human Mesenchymal Stem Cells: Clinical Implications for Stem Cell Therapy

    Science.gov (United States)

    Lyons, Nicolette F.; Reischling, Patrick D.; Centeno, Christopher J.

    2014-01-01

    In the realm of regenerative medicine, human mesenchymal stem cells (hMSCs) are gaining attention as a cell source for the repair and regeneration of tissues spanning an array of medical disciplines. In orthopedics, hMSCs are often delivered in a site-specific manner at the area of interest and may require the concurrent application of local anesthetics (LAs). To address the implications of using hMSCs in combination with anesthetics for intra-articular applications, we investigated the effect that clinically relevant doses of amide-type LAs have on the viability of bone marrow-derived hMSCs and began to characterize the mechanism of LA-induced hMSC death. In our study, culture-expanded hMSCs from three donors were exposed to the amide-type LAs ropivacaine, lidocaine, bupivacaine, and mepivacaine. To replicate the physiological dilution of LAs once injected into the synovial capsule, each anesthetic was reduced to 12.5%, 25%, and 50% of the stock solution and incubated with each hMSC line for 40 minutes, 120 minutes, 360 minutes, and 24 hours. At each time point, cell viability assays were performed. We found that extended treatment with LAs for 24 hours had a significant impact on both hMSC viability and adhesion. In addition, hMSC treatment with three of the four anesthetics resulted in cell death via apoptosis following brief exposures. Ultimately, we concluded that amide-type LAs induce hMSC apoptosis in a time- and dose-dependent manner that may threaten clinical outcomes, following a similar trend that has been established between these particular anesthetics and articular chondrocytes both in vitro and in vivo. PMID:24436443

  13. CMV-specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies

    Directory of Open Access Journals (Sweden)

    Corinne J Smith

    2016-09-01

    Full Text Available Human cytomegalovirus (HCMV is a ubiquitous virus that causes chronic infection, and thus is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8+ T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8+ T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8+ T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8+ T cell response. Finally mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease.

  14. Local Control and Toxicity in a Large Cohort of Central Lung Tumors Treated With Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Modh, Ankit; Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Williams, Eric [Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York (United States); Foster, Amanda; Shah, Mihir [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Shi, Weiji; Zhang, Zhigang [Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Gelblum, Daphna Y. [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Rosenzweig, Kenneth E. [Department of Radiation Oncology, Mount Sinai Medical Center, New York, New York (United States); Yorke, Ellen D.; Jackson, Andrew [Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York (United States); Wu, Abraham J., E-mail: wua@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

    2014-12-01

    Purpose: Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters. Methods and Materials: We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity. Results: One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT (“no-fly-zone” [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum. Conclusions: Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and

  15. Local recurrence following hepatic radiofrequency ablation: diagnosis and treatment; Diagnostik und Therapie von Lokalrezidiven nach Radiofrequenzablation an der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Eisele, R.M.; Schumacher, G.; Neuhaus, P. [Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie, Charite Campus Virchow-Klinikum, Berlin (Germany)

    2008-11-15

    Background: radiofrequency ablation (RFA) is an established treatment in irresectable malignant liver disease. The most severe constraint is re-occurrence at site of ablation. Whereas factors influencing local recurrence rates have been determined, little is known about the timespan within local recurrence (LR) is to be expected, and further treatment options. Patients and methods: in the presented trial, RFA was performed using two different types of monopolar devices. All procedures were conducted under general anesthesia. Follow-up examinations took part after 3, 6, 12 months and annually. Results: 149 RFAs in 125 patients were enrolled. Percutaneous access was chosen in 74 cases (50%), laparoscopic in 15 (10%) and open surgical in 60 cases (40%). Indications were primary liver tumors in 99 (67%) and metastases in 50 cases (33%). Overall LR rate was 29.5% on a per-patient- and 19.7% on a per-tumor-basis. The majority of LRs (71%) occurred within 9 months after the RFA despite observations beyond 2 years following the treatment (Figure 1). 75% of LR could be treated by targeted interventions (RFA, n = 18, 53%, laser-induced thermo therapy (LITT), n = 2.6%, brachytherapy, n = 2.6% or transarterial chemoembolisation (TACE), n = 2.6%) or resection (n = 6.18%); 4 patients underwent liver transplantation (12%) (Figure 2). Conclusion: local recurrence can be considered rather common after RFA. It is observed during the first 3 years of the follow-up period, and schedules have to be designed according to this finding. Follow-on treatment is feasible in approximately 75% of LR. Factors influencing the secondary success of repeated procedures have yet to be determined. (orig.)

  16. Boron-Containing Compounds for Liposome-Mediated Tumor Localization and Application to Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hawthorne, M. Frederick [Univ. of California, Los Angeles, CA (United States)

    2005-04-07

    Medical application of boron neutron capture therapy (BNCT) has been significantly hindered by the slow development of boron drug-targeting methodologies for the selective delivery of high boron concentration sto malignant cells. We have successfully sought to fill this need by creating liposomes suitable as in vivo boron delivery vehicles for BNCT. Delivery of therapeutic quantities of boron to tumors in murine models has been achieved with small unilamellar boron-rich liposomes. Subsequently, attempts have been made to improve delivery efficiency of liposomes encapsulating boron-containing water-soluble species into their hollow core by incorporating lipophilic boron compounds as addenda to the liposome bilayer, incorporating boron compounds as structural components of the bilayer (which however, poses the risk of sacrificing some stability), and combinations thereof. Regardless of the method, approximately 90% of the total liposome mass remains therapeutically inactive and comprised of the vehicle's construction materials, while less than 5% is boron for neutron targeting. Following this laboratory's intensive study, the observed tumor specificity of certain liposomes has been attributed to their diminutive size of these liposomes (30-150 nm), which enables these small vesicles to pass through the porous, immature vasculature of rapidly growing tumor tissue. We surmised that any amphiphilic nanoparticle of suitable size could possess some tumor selectivity. Consequently, the discovery of a very boron-rich nanoparticle delivery agent with biodistribution performance similar to unilamellar liposomes became one of our goals. Closomers, a new class of polyhedral borane derivatives, attracted us as an alternative BNCT drug-delivery system. We specifically envisioned dodeca (nido-carboranyl)-substituted closomers as possibly having a great potential role in BNCT drug delivery. They could function as extraordinarily boron-rich BNCT drugs since they are

  17. Boron-Containing Compounds for Liposome-Mediated Tumor Localization and Application to Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hawthorne, M. Frederick [Univ. of California, Los Angeles, CA (United States)

    2005-04-07

    Medical application of boron neutron capture therapy (BNCT) has been significantly hindered by the slow development of boron drug-targeting methodologies for the selective delivery of high boron concentration sto malignant cells. We have successfully sought to fill this need by creating liposomes suitable as in vivo boron delivery vehicles for BNCT. Delivery of therapeutic quantities of boron to tumors in murine models has been achieved with small unilamellar boron-rich liposomes. Subsequently, attempts have been made to improve delivery efficiency of liposomes encapsulating boron-containing water-soluble species into their hollow core by incorporating lipophilic boron compounds as addenda to the liposome bilayer, incorporating boron compounds as structural components of the bilayer (which however, poses the risk of sacrificing some stability), and combinations thereof. Regardless of the method, approximately 90% of the total liposome mass remains therapeutically inactive and comprised of the vehicle's construction materials, while less than 5% is boron for neutron targeting. Following this laboratory's intensive study, the observed tumor specificity of certain liposomes has been attributed to their diminutive size of these liposomes (30-150 nm), which enables these small vesicles to pass through the porous, immature vasculature of rapidly growing tumor tissue. We surmised that any amphiphilic nanoparticle of suitable size could possess some tumor selectivity. Consequently, the discovery of a very boron-rich nanoparticle delivery agent with biodistribution performance similar to unilamellar liposomes became one of our goals. Closomers, a new class of polyhedral borane derivatives, attracted us as an alternative BNCT drug-delivery system. We specifically envisioned dodeca (nido-carboranyl)-substituted closomers as possibly having a great potential role in BNCT drug delivery. They could function as extraordinarily boron-rich BNCT drugs since they are

  18. [Effect of combined and local cytokine- and ozone therapy on the indices of lipid peroxidation, endogenous intoxication and ferroproteins in diffuse peritonitis].

    Science.gov (United States)

    Gadzhiev, N Dzh; Nasirov, M Ia; Sushkov, S V; Klimova, E M

    2014-01-01

    The article analyzes the results of effect of combined and local cytokine- and ozone therapy on the indices of lipid peroxidation, endogenous intoxication and ferroproteins in 111 patients with diffuse peritonitis. It was shown, that combined sequential local and systemic cytokine and ozone therapy allows correcting the expression of endogenous intoxication and lipid peroxidation in diffuse peritonitis. This method suppresses an inflammation in the abdominal cavity. At the same time, it accelerates the elimination of intestine atony and thereby potentiates the possibilities of traditional methods of treatment.

  19. Surgical Margins and the Risk of Local-Regional Recurrence After Mastectomy Without Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Childs, Stephanie K. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Chen Yuhui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Duggan, Margaret M. [Department of Surgery, Faulkner Hospital, Boston, Massachusetts (United States); Department of Surgery, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Golshan, Mehra [Department of Surgery, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Pochebit, Stephen [Department of Pathology, Faulkner Hospital, Boston, Massachusetts (United States); Wong, Julia S. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Bellon, Jennifer R., E-mail: jbellon@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2012-12-01

    Purpose: Although positive surgical margins are generally associated with a higher risk of local-regional recurrence (LRR) for most solid tumors, their significance after mastectomy remains unclear. We sought to clarify the influence of the mastectomy margin on the risk of LRR. Methods and Materials: The retrospective cohort consisted of 397 women who underwent mastectomy and no radiation for newly diagnosed invasive breast cancer from 1998-2005. Time to isolated LRR and time to distant metastasis (DM) were evaluated by use of cumulative-incidence analysis and competing-risks regression analysis. DM was considered a competing event for analysis of isolated LRR. Results: The median follow-up was 6.7 years (range, 0.5-12.8 years). The superficial margin was positive in 41 patients (10%) and close ({<=}2 mm) in 56 (14%). The deep margin was positive in 23 patients (6%) and close in 34 (9%). The 5-year LRR and DM rates for all patients were 2.4% (95% confidence interval, 0.9-4.0) and 3.5% (95% confidence interval, 1.6-5.3) respectively. Fourteen patients had an LRR. Margin status was significantly associated with time to isolated LRR (P=.04); patients with positive margins had a 5-year LRR of 6.2%, whereas patients with close margins and negative margins had 5-year LRRs of 1.5% and 1.9%, respectively. On univariate analysis, positive margins, positive nodes, lymphovascular invasion, grade 3 histology, and triple-negative subtype were associated with significantly higher rates of LRR. When these factors were included in a multivariate analysis, only positive margins and triple-negative subtype were associated with the risk of LRR. Conclusions: Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable

  20. Combined high-intensity local treatment and systemic therapy in metastatic head and neck squamous cell carcinoma: An analysis of the National Cancer Data Base.

    Science.gov (United States)

    Zumsteg, Zachary S; Luu, Michael; Yoshida, Emi J; Kim, Sungjin; Tighiouart, Mourad; David, John M; Shiao, Stephen L; Mita, Alain C; Scher, Kevin S; Sherman, Eric J; Lee, Nancy Y; Ho, Allen S

    2017-08-17

    There is increasing evidence that primary tumor ablation can improve survival for some cancer patients with distant metastases. This may be particularly applicable to head and neck squamous cell carcinoma (HNSCC) because of its tropism for locoregional progression. This study included patients with metastatic HNSCC undergoing systemic therapy identified in the National Cancer Data Base. High-intensity local treatment was defined as radiation doses ≥ 60 Gy or oncologic resection of the primary tumor. Multivariate Cox regression, propensity score matching, landmark analysis, and subgroup analysis were performed to account for imbalances in covariates, including adjustments for the number and location of metastatic sites in the subset of patients with this information available. In all, 3269 patients were included (median follow-up, 51.5 months). Patients undergoing systemic therapy with local treatment had improved survival in comparison with patients receiving systemic therapy alone in propensity score-matched cohorts (2-year overall survival, 34.2% vs 20.6%; P < .001). Improved survival was associated only with patients receiving high-intensity local treatment, whereas those receiving lower-intensity local treatment had survival similar to that of patients receiving systemic therapy without local treatment. The impact of high-intensity local therapy was time-dependent, with a stronger impact within the first 6 months after the diagnosis (adjusted hazard ratio [AHR], 0.255; 95% confidence interval [CI], 0.210-0.309; P < .001) in comparison with more than 6 months after the diagnosis (AHR, 0.622; 95% CI, 0.561-0.689; P < .001) in the multivariate analysis. A benefit was seen in all subgroups, in landmark analyses of 1-, 2-, and 3-year survivors, and when adjusting for the number and location of metastatic sites. Aggressive local treatment warrants prospective evaluation for select patients with metastatic HNSCC. Cancer 2017. © 2017 American Cancer Society. © 2017

  1. Co-operation between interleukin-1 and the fibrinolytic system in the degradation of collagen by articular chondrocytes.

    Science.gov (United States)

    Cruwys, S C; Davies, D E; Pettipher, E R

    1990-07-01

    1. The interaction between interleukin 1 (IL-1) and the fibrinolytic system in the control of collagen degradation by rabbit chondrocytes has been investigated in a tissue-culture system where cells are grown on a 14C-labelled collagen matrix. 2. Culture of rabbit chondrocytes in the presence of human recombinant IL-1 beta at a concentration of 57pM for 48 h led to the presence of procollagenase but not active collagenase in the medium. The latent collagenase could be activated by incubation with an organomercurial, aminophenylmercuric acetate (APMA). 3. Addition of IL-1 beta to chondrocytes grown on a 14C-labelled collagen matrix did not increase the degradation of the matrix compared to control over a 48 h period. However, in the presence of plasmin (200 micrograms ml-1) or plasminogen (100 micrograms ml-1), IL-1 beta (57 pM) caused almost complete degradation of the collagen matrix. Plasmin or plasminogen alone caused only slight degradation of the collagen matrix. 4. Tissue inhibitor of metalloproteinases (TIMP) or the selective metalloproteinase inhibitor, SC44463, inhibited the degradation induced by IL-1 beta and plasminogen in a concentration-related manner and at concentrations that were correlated with inhibition of collagenase. 5. When concentrations of IL-1 beta which caused only minimal degradation of the matrix in the presence of plasminogen were combined with fibrin (1 microgram ml-1), there was almost total degradation of the matrix by 48 h. 6. These results indicate there is a synergistic interaction between IL-1 and the fibrinolytic system in the degradation of collagen by rabbit chondrocytes in culture.

  2. Effect of bloodletting therapy at local myofascial trigger points and acupuncture at Jiaji (EX-B 2) points on upper back myofascial pain syndrome: a randomized controlled trial.

    Science.gov (United States)

    Jiang, Guimei; Jia, Chao; Lin, Mode

    2016-02-01

    To observe the clinical efficacy of bloodletting therapy and acupuncture at Jiaji points for treating upper back myofascial pain syndrome (MPS), and compare this with lidocaine block therapy. A total of 66 upper back MPS patients were randomly assigned to either the treatment group or the control group in a 1: 1 ratio. The treatment group (n = 33) were treated with bloodletting therapy at local myofascial trigger points and acupuncture at Jiaji (EX-B 2) points; one treatment course consisted of five, single 20-min-treatments with a 2-day break between each treatment. The control group (n = 33) were treated with a lidocaine block at trigger points; one treatment course consisted of five sessions of lidocaine block therapy with a 2-day break between each session. The simplified McGill Scale (SF-MPQ) and tenderness threshold determination were used to assess pain before and after a course of treatment. After the third and fifth treatment, the SF-MPQ values were significantly decreased (P 0.05). There were five cases with minor adverse reactions reported in the control patients, while no adverse reactions were reported in the treatment group. Bloodletting therapy at local myofascial trigger points and acupuncture at Jiaji points was effective in treating upper back MPS. Clinically, bloodletting and acupuncture therapy had the same efficacy as the lidocaine block therapy, with fewer adverse reactions.

  3. Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V.; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Dong, Lei; Zhu, X. Ronald [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Likhacheva, Anna; Liao, Zhongxing [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Cox, James D. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

    2011-12-01

    Purpose: We have previously found that {<=} 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Patients and Methods: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Results: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p < .0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p {<=} .0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p < .001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p {<=} .02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p < .0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p {<=} .005), heart (p {<=} .003), and liver (p {<=} .04). Conclusions: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for

  4. Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using {sup 11}C-choline Positron Emission Tomography Scans

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Joe H. [Radiation Oncology Centre, Austin Health, Victoria (Australia); University of Melbourne, Victoria (Australia); Lim Joon, Daryl [Radiation Oncology Centre, Austin Health, Victoria (Australia); Lee, Sze Ting [University of Melbourne, Victoria (Australia); Centre for PET, Austin Health, Victoria (Australia); Ludwig Institute for Cancer Research, Victoria (Australia); Gong, Sylvia J. [Centre for PET, Austin Health, Victoria (Australia); Anderson, Nigel J. [Radiation Oncology Centre, Austin Health, Victoria (Australia); Scott, Andrew M. [University of Melbourne, Victoria (Australia); Centre for PET, Austin Health, Victoria (Australia); Ludwig Institute for Cancer Research, Victoria (Australia); Davis, Ian D. [University of Melbourne, Victoria (Australia); Ludwig Institute for Cancer Research, Victoria (Australia); Clouston, David [Focus Pathology, Victoria (Australia); Bolton, Damien [University of Melbourne, Victoria (Australia); Department of Urology, Austin Health, Victoria (Australia); Hamilton, Christopher S. [Radiation Oncology Centre, Austin Health, Victoria (Australia); Khoo, Vincent, E-mail: vincent.khoo@rmh.nhs.uk [Radiation Oncology Centre, Austin Health, Victoria (Australia); University of Melbourne, Victoria (Australia); Department of Clinical Oncology, Royal Marsden Hospital and Institute of Cancer Research, London (United Kingdom)

    2012-08-01

    Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using {sup 11}C-choline positron emission tomography PET scans in patients with localized prostate cancer. Methods and Materials: This was an RT planning study of 8 patients with prostate cancer who had {sup 11}C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV{sub 60%} and SUV{sub 70%}). Three IMRT plans were generated for each patient: PLAN{sub 78}, which consisted of whole-prostate radiation therapy to 78 Gy; PLAN{sub 78-90}, which consisted of whole-prostate RT to 78 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy; and PLAN{sub 72-90}, which consisted of whole-prostate RT to 72 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP{sub PET}) and on prostatectomy-defined volumes (TCP{sub path}), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. Results: All plans for all patients reached prescription doses while adhering to dose constraints. TCP{sub PET} values for PLAN{sub 78}, PLAN{sub 78-90}, and PLAN{sub 72-90} were 65%, 97%, and 96%, respectively. TCP{sub path} values were 71%, 97%, and 89%, respectively. Both PLAN{sub 78-90} and PLAN{sub 72-90} had significantly higher TCP{sub PET} (P=.002 and .001) and TCP{sub path} (P<.001 and .014) values than PLAN{sub 78}. PLAN{sub 78-90} and PLAN{sub 72-90} were not significantly different in terms of TCP{sub PET} or TCP{sub path}. There were no significant differences in rectal NTCPs between the 3 plans. Conclusions: IMRT dose painting for

  5. Re: Final Report of the Intergroup Randomized Study of Combined AndrogenDeprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Malcolm D. Mason

    2015-06-01

    Full Text Available No certain treatment recommendations were given for locally advanced or high-risk prostate cancer in the European Association of Urology (EAU guidelines (1. In the guidelines, studies supporting surgery or radiotherapy (RT were listed, and the readers were left alone to make their own decisions. In the present study, Mason et al. reported the impact of adding RT to androgen deprivation therapy (ADT. One thousand two hundred and five patients with T3- 4, N0/Nx, M0 prostate cancer or T1-2 disease with either PSA more than 40 μg/L or PSA 20 to 40 μg/L plus Gleason score of 8 to 10 were randomized to ADT alone (n=602 or to ADT+RT (n=603. A lower dose radiation 64 to 69 Gy was used for RT. Overall survival (OS risk reduction was 30% for ADT+RT group (P<0.001 at a median follow-up of 8 years. Cancer-specific survival (CSS was significantly improved by the addition of RT to ADT (HR: 0.46, 95% CI: 0.34 to 0.61; p<0.001. Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity. However, reported frequency of ADT-related toxicities (impotence, hot flushes, urinary frequency, ischemia, and hypertension were similar for both arms. The present study provided results of high-risk patients in a longer median follow-up time than SPCG-7 study (2. Because the study took place between 1995 and 2005, less than 70 Gy was used for RT. Even at lower radiation doses, the authors confirmed that adding RT to ADT improved both OS and cancer-specific survival (CSS with minimal general toxicity. In the modern era, improved RT techniques may help achieve better outcomes with much higher radiation doses without increased morbidity in this group of patients

  6. Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control

    Directory of Open Access Journals (Sweden)

    Robinson William

    2011-04-01

    Full Text Available Abstract Background Melanoma and renal cell carcinoma (RCC are traditionally considered less radioresponsive than other histologies. Whereas stereotactic body radiation therapy (SBRT involves radiation dose intensification via escalation, we hypothesize SBRT might result in similar high local control rates as previously published on metastases of varying histologies. Methods The records of patients with metastatic melanoma (n = 17 patients, 28 lesions or RCC (n = 13 patients, 25 lesions treated with SBRT were reviewed. Local control (LC was defined pathologically by negative biopsy or radiographically by lack of tumor enlargement on CT or stable/declining standardized uptake value (SUV on PET scan. The SBRT dose regimen was converted to the single fraction equivalent dose (SFED to characterize the dose-control relationship using a logistic tumor control probability (TCP model. Additionally, the kinetics of decline in maximum SUV (SUVmax were analyzed. Results The SBRT regimen was 40-50 Gy/5 fractions (n = 23 or 42-60 Gy/3 fractions (n = 30 delivered to lung (n = 39, liver (n = 11 and bone (n = 3 metastases. Median follow-up for patients alive at the time of analysis was 28.0 months (range, 4-68. The actuarial LC was 88% at 18 months. On univariate analysis, higher dose per fraction (p max was 7.9 and declined with an estimated half-life of 3.8 months to a post-treatment plateau of approximately 3. Conclusions An aggressive SBRT regimen with SFED ≥ 45 Gy is effective for controlling metastatic melanoma and RCC. The SFED metric appeared to be as robust as the BED in characterizing dose-response, though additional studies are needed. The LC rates achieved are comparable to those obtained with SBRT for other histologies, suggesting a dominant mechanism of in vivo tumor ablation that overrides intrinsic differences in cellular radiosensitivity between histologic subtypes.

  7. Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Binkley, Michael S. [Department of Radiation Oncology and Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Trakul, Nicholas [Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California (United States); Jacobs, Lisa Rose; Eyben, Rie von; Le, Quynh-Thu; Maxim, Peter G.; Loo, Billy W. [Department of Radiation Oncology and Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Shultz, David Benjamin, E-mail: DavidS4@Stanford.edu [Department of Radiation Oncology and Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: Diehn@Stanford.edu [Department of Radiation Oncology and Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States)

    2015-08-01

    Purpose: Stereotactic ablative radiation therapy (SABR) is increasingly used to treat lung oligometastases. We set out to determine the safety and efficacy of this approach and to identify factors associated with outcomes. Methods and Materials: We conducted a retrospective study of patients treated with SABR for metastatic lung tumors at our institution from 2003 to 2014. We assessed the association between various patient and treatment factors with local failure (LF), progression, subsequent treatment, systemic treatment, and overall survival (OS), using univariate and multivariate analyses. Results: We identified 122 tumors in 77 patients meeting inclusion criteria for this study. Median follow-up was 22 months. The 12- and 24-month cumulative incidence rates of LF were 8.7% and 16.2%, respectively; the 24-month cumulative incidence rates of progression, subsequent treatment, and subsequent systemic treatment were 75.2%, 64.5%, and 35.1%, respectively. Twenty-four-month OS was 74.6%, and median OS was 36 months. Colorectal metastases had a significantly higher cumulative incidence of LF at 12 and 24 months (25.5% and 42.2%, respectively), than all other histologies (4.4% and 9.9%, respectively; P<.0004). The 24-month cumulative incidences of LF for colorectal metastases treated with a biologically effective dose at α/β = 10 (BED{sub 10}) of <100 Gy versus BED{sub 10} of ≥100 Gy were 62.5% and 16.7%, respectively (P=.08). Toxicity was minimal, with only a single grade 3 or higher event observed. Conclusions: SABR for metastatic lung tumors appears to be safe and effective with excellent local control, treatment-free intervals, and OS. An exception is metastases from colorectal cancer, which have a high LF rate consistent with a radioresistant phenotype, suggesting a potential role for dose escalation.

  8. Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study

    DEFF Research Database (Denmark)

    Kirchheiner, Kathrin; Pötter, Richard; Tanderup, Kari

    2016-01-01

    Purpose This study analyzed functioning and symptom scores for longitudinal quality of life (QoL) from patients with locally advanced cervical cancer who underwent definitive chemoradiation therapy with image guided adaptive brachytherapy in the EMBRACE study. Methods and Materials In total, 744 ...

  9. Low-level laser therapy decreases local effects induced by myotoxins isolated from Bothrops jararacussu snake venom

    Directory of Open Access Journals (Sweden)

    AM Barbosa

    2010-01-01

    Full Text Available The prominent myotoxic effects induced by Bothrops jararacussu crude venom are due, in part, to its polycationic myotoxins, BthTX-I and BthTX-II. Both myotoxins have a phospholipase A2 structure: BthTX-II is an active enzyme Asp-49 PLA2, while BthTX-I is a Lys-49 PLA2 devoid of enzymatic activity. In this study, the effect of low-level laser therapy (LLLT, 685 nm laser at a dose of 4.2 J/cm2 on edema formation, leukocyte influx and myonecrosis caused by BthTX-I and BthTX-II, isolated from Bothrops jararacussu snake venom, was analyzed. BthTX-I and BthTX-II caused a significant edema formation, a prominent leukocyte infiltrate composed predominantly by neutrophils and myonecrosis in envenomed gastrocnemius muscle. LLLT significantly reduced the edema formation, neutrophil accumulation and myonecrosis induced by both myotoxins 24 hours after the injection. LLLT reduced the myonecrosis caused by BthTX-I and BthTX-II, respectively, by 60 and 43%; the edema formation, by 41 and 60.7%; and the leukocyte influx, by 57.5 and 51.6%. In conclusion, LLLT significantly reduced the effect of these snake toxins on the inflammatory response and myonecrosis. These results suggest that LLLT should be considered a potential therapeutic approach for treatment of local effects of Bothrops species venom.

  10. Vascular targeted photodynamic therapy with TOOKAD® Soluble (WST11) in localized prostate cancer: efficiency of automatic pre-treatment planning.

    Science.gov (United States)

    Betrouni, N; Boukris, S; Benzaghou, F

    2017-08-01

    Vascular targeted photodynamic therapy (VTP) with WST11 is a novel non-thermal focal treatment for localized prostate cancer that has shown favorable and early efficacy results in previously published studies. In this work, we investigate the efficiency of automatic dosimetric treatment planning. An action model established in a previous study was used in an image-guided optimization scheme to define the personalized optimal light dose for each patient. The calculated light dose is expressed as the number of optical cylindrical fibers to be used, their positions according to an external insertion grid, and the lengths of their diffuser parts. Evaluation of the method was carried out on data collected from 17 patients enrolled in two multi-centric clinical trials. The protocol consisted of comparing the method-simulated necrosis to the result observed on day 7 MR enhanced images. The method performances showed that the final result can be estimated with an accuracy of 10%, corresponding to a margin of 3 mm. In addition, this process was compatible with clinical conditions in terms of calculation times. The overall process took less than 10 min. Different aspects of the VTP procedure were already defined and optimized. Personalized treatment planning definition remained as an issue needing further investigation. The method proposed herein completes the standardization of VTP and opens new pathways for the clinical development of the technique.

  11. Enhanced tumor localization and retention of chlorin e6 in cationic nanolipoplexes potentiate the tumor ablation effects of photodynamic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Gayong; Lee, Sangbin; Kim, Chan-Wha [School of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Kim, Young Bong [Department of Animal Biotechnology, Konkuk University, Seoul (Korea, Republic of); Oh, Yu-Kyoung, E-mail: ohyk@snu.ac.kr [College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul (Korea, Republic of)

    2011-09-07

    Here we report the tumor ablation effects of the negatively charged photosensitizer chlorin e6 (Ce6) in nanocomplexes. Ce6 was complexed to cationic 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine-based liposomes, forming cationic nanolipoplexes. The loading efficiency of Ce6 to cationic nanolipoplexes was greater than 90%. The degree of enhancement of cellular uptake of Ce6 by treatment in cationic nanolipoplexes increased with the concentration of Ce6, showing 18.3-fold higher uptake than free Ce6 at 15 {mu}M. Molecular imaging revealed the preferential distribution and retention of Ce6 in SCC7 tumor tissues after intravenous administration of Ce6 in cationic nanolipoplexes. Moreover, localized illumination of mice receiving Ce6 in cationic nanolipoplexes resulted in the formation of thick scabs over tumor regions, and complete ablation of tumors after scab detachment. In contrast, continuous growth of tumors was observed in the group treated with free Ce6. Our results suggest that the cationic nanolipoplexes of Ce6 improve the therapeutic effects of photodynamic cancer therapy as compared to free Ce6.

  12. A novel polymer gel for the delivery of local therapies to intracranial tumors: In vivo safety evaluation.

    Science.gov (United States)

    Gerber, David E; Gallia, Gary L; Tyler, Betty M; Eberhart, Charles G; Royer, Gar; Grossman, Stuart A

    2011-12-01

    The treatment of intracranial malignancies is limited by the ability of systemically administered therapies to cross the blood-brain barrier. Royer resorbable matrix, or R-Gel, is a dextran polymer administered in liquid form via needle injection. Within minutes of preparation, the polymer forms a gel and subsequently solidifies, thereby conforming to the dimensions of the injection cavity. R-Gel can accommodate a wide variety of therapeutic agents that may provide new options for local treatment delivery. This preclinical study evaluates the neurotoxicity of R-Gel implanted in the rat brain. Fifteen rats underwent intracranial administration of R-Gel (N = 9) or saline (N = 6) were monitored for systemic and neurotoxicity, and sacrificed at pre-determined time points. Animals that received the R-Gel injection demonstrated no behavioral changes or weight loss. Histopathologic analysis revealed an inflammatory response in both groups on day 3 and day 7 after implantation, which resolved by day 42. These results suggest that intracranial R-Gel is well tolerated. Therapeutic studies of chemotherapy-complexed R-Gel are underway. Copyright © 2011 Wiley Periodicals, Inc.

  13. [Ozone therapy and phototherapy with polarized polychromatic light in treatment of patients suffering from lower limb critical ischaemia].

    Science.gov (United States)

    Drozhzhin, E V; Sidorkina, O N

    2012-01-01

    The authors generalized their experience in treating a total of 77 patients presenting with atherosclerosis of the arteries of lower limbs with degree III-IV ischaemia according to the A.V. Pokrovsky-Fontain classification. The patients were subjected to comprehensive treatment including the impact of piler-light (apparatus Bioptron 2) and ozone therapy. The control group was composed of 66 people receiving conventional therapy. The two groups were comparable by the nosological entity of the disease, gender, age, and the nature of accompanying pathology. Despite carried out classical anticoagulation therapy there was a tendency towards hypercoagulation in phase I (formation of prothrombinase) and phase III (formation of fibrin) of plasma haemostasis, as well as insufficiency of the fibrinolytic system. The obtained results showed direct influence of ozone therapy and piler light on phase I and III plasmatic haemostasis, as well as enhanced fibrinolytic activity of blood on the background of their administration thereof.

  14. Isolation and Characterization of a 32-kDa Fibrinolytic Enzyme (FE-32kDa from Gloydius blomhoffii siniticus Venom

    Directory of Open Access Journals (Sweden)

    Kim Joung-Yoon

    2014-03-01

    Full Text Available Objectives: This study was undertaken to isolate a fibrinolytic enzyme from the snake venom of Gloydius blomhoffii siniticus and to investigate its enzymatic characteristics and hemorrhagic activity as a potential pharmacopuncture agent. Methods: The fibrinolytic enzyme was isolated by using chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fibrin plate assay. The characteristics of the enzyme were investigated using fibrin plate assay, protein hydrolysis analysis, and hemorrhage assay. Its amino acid composition was determined. Results: The fibrinolytic enzyme with the molecular weight of 32kDa (FE-32kDa from Gloydius blomhoffii siniticus showed a fibrin hydrolysis zone at the concentration of 0.2 mg/mL in the fibrin plate assay. The fibrin hydrolysis activity of the enzyme was inhibited completely by ethylenediaminetetraacetic acid (EDTA, ethyleneglycoltetraacetic acid (EGTA, and 1, 10-phenanthroline, thiothreitol and cysteine, and partially by phenylmethanesulfonylfluoride (PMSF. Metal ions such as Fe2+ and Hg2+ inhibited the fibrin hydrolysis completely, but Zn2+ enhanced it. FE-32kDa hydrolyzed α-chain but did not hydrolyze β-chain and γ-chain of fibrinogen. High-molecular-weight polypeptides of gelatin were hydrolyzed partially into low-molecular-weight polypeptides, but the extent of hydrolysis was limited. FE-32kDa induced hemorrhage beneath back skin of mice at the dose of 2 μg. Conclusions: FE-32kDa is a α-fibrin(ogenolytic metalloprotease that requires Zn2+ for fibrinolytic activity and causes hemorrhage, suggesting that the enzyme is not appropriate for use as a clinical pharmacopuncture.

  15. A comparative analysis of the clotting and fibrinolytic activities of the snake venom (Bothrops atrox) from different geographical areas in Venezuela.

    Science.gov (United States)

    Salazar, Ana Maria; Rodriguez-Acosta, Alexis; Girón, Maria E; Aguilar, Irma; Guerrero, Belsy

    2007-01-01

    Venom constitution within the same snake species can present considerable geographical variations. Bothrops atrox venoms were obtained from adult snakes captured at different geographical locations: Parguasa (Bolívar state); Puerto Ayacucho 1, Serranía del Cuao and Puerto Ayacucho 2 (Amazon state). The coagulant and fibrinolytic activities of these venoms were compared. Amidolytic activity of crude snake venom was measured by a micromethod designed in our laboratory. Coagulant activity on plasma and fibrinogen due to thrombin-like activity in venoms was also determined. Crude snake venom fibrinolytic activity by the fibrin plate method was assayed. Chromatographic studies were developed on Protein-Pack 300 column. Polyacrylamide gel electrophoresis was carried out under reduced conditions. After SDS-PAGE of samples, the fibrin-zymography was tested on agarose-fibrin plates. The results demonstrated several differences among B. atrox venoms from different geographical areas. Chromatograms and SDS-PAGE profiles indicated that venoms from the same species presented differences in the molecular mass of their components. The procoagulant activity depended on the utilized method (amidolytic versus clotting). Parguasa and Puerto Ayacucho 2 venoms presented procoagulant activity for both methods. Furthermore, Parguasa venom had also the highest hemorrhagic activity and the lowest LD50. In relation to the fibrinolytic activity, Puerto Ayacucho 1 venom was the most active, equally for fibrin plates as for the amidolytic method (t-PA like). This venom had the lowest coagulant activity, which induced us to think that probably its procoagulant activity was interfered by its fibrinolytic activity.

  16. A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer.

    Directory of Open Access Journals (Sweden)

    Claudia Arce

    Full Text Available Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy.This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655. After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day -7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate.16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1-2. Five (31% patients had clinical CR and eight (50% PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6% had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5mC content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively.Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the

  17. SU-D-BRF-03: Improvement of TomoTherapy Megavoltage Topogram Image Quality for Automatic Registration During Patient Localization

    Energy Technology Data Exchange (ETDEWEB)

    Scholey, J; White, B [University of Pennsylvania, Philadelphia, PA (United States); Qi, S; Low, D [UCLA School of Medicine, Los Angeles, CA (United States)

    2014-06-01

    Purpose: To improve the quality of mega-voltage orthogonal scout images (MV topograms) for a fast and low-dose alternative technique for patient localization on the TomoTherapy HiART system. Methods: Digitally reconstructed radiographs (DRR) of anthropomorphic head and pelvis phantoms were synthesized from kVCT under TomoTherapy geometry (kV-DRR). Lateral (LAT) and anterior-posterior (AP) aligned topograms were acquired with couch speeds of 1cm/s, 2cm/s, and 3cm/s. The phantoms were rigidly translated in all spatial directions with known offsets in increments of 5mm, 10mm, and 15mm to simulate daily positioning errors. The contrast of the MV topograms was automatically adjusted based on the image intensity characteristics. A low-pass fast Fourier transform filter removed high-frequency noise and a Weiner filter reduced stochastic noise caused by scattered radiation to the detector array. An intensity-based image registration algorithm was used to register the MV topograms to a corresponding kV-DRR by minimizing the mean square error between corresponding pixel intensities. The registration accuracy was assessed by comparing the normalized cross correlation coefficients (NCC) between the registered topograms and the kV-DRR. The applied phantom offsets were determined by registering the MV topograms with the kV-DRR and recovering the spatial translation of the MV topograms. Results: The automatic registration technique provided millimeter accuracy and was robust for the deformed MV topograms for three tested couch speeds. The lowest average NCC for all AP and LAT MV topograms was 0.96 for the head phantom and 0.93 for the pelvis phantom. The offsets were recovered to within 1.6mm and 6.5mm for the processed and the original MV topograms respectively. Conclusion: Automatic registration of the processed MV topograms to a corresponding kV-DRR recovered simulated daily positioning errors that were accurate to the order of a millimeter. These results suggest the clinical

  18. Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

    Energy Technology Data Exchange (ETDEWEB)

    Corn, Paul G., E-mail: pcorn@mdanderson.org [Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Song, Danny Y. [Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland (United States); Heath, Elisabeth; Maier, Jordan [Karmanos Cancer Institute, Wayne State University, Detroit, Michigan (United States); Meyn, Raymond [Department of Experimental Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Kuban, Deborah [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); DePetrillo, Thomas A. [Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts (United States); Mathew, Paul, E-mail: pmathew@tuftsmedicalcenter.org [Department of Hematology-Oncology, Tufts Medical Center, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

    2013-07-01

    Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

  19. EFFECT OF RADIX SALVIAE MILTIORRHIZAE ON THE PROCOAGULANT AND FIBRINOLYTIC ACTIVITIES INDUCED BY ENDOTOXIN-TREATED BOVINE ENDOTHELIAL CELLS

    Institute of Scientific and Technical Information of China (English)

    沈传陆; 张彩英; 王振义

    1992-01-01

    Effect of endotoxin, and endotoxin plus Radix Salviae Miltiorrhizae (RSM) on bovine aortic endothelial cells (BAECs) for the production of tissue factor (TF), plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activities as well as prostacyclin (PGI2) content were studied. Stimulation of BAECs with endotoxin (1 μg/ ml) increased the expression of cell surface TF activity, the secretions of PAI activity and PGI2 content. However, PA activity in endotoxin-treated groups didn’t change significantly in comparison with that of the control. RSM could stimulate the secretion of PA activity and prevent the increase in TF and PAI activities from endotoxin-treated BAECs. However, there was no significant difference in PGI2 production between endotoxin-and endotoxin+RSM-treated BAECs. These results indicated that increased procoagulant function and decreased fibrinolytic activity of endothelial cells (ECs) might be one of the mechanisms of DIC in gram-negative septicemia and RSM would be a very important thug in the prevention and the treatment of DIC in gram-negative sepsis.

  20. Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ken, E-mail: keharada@ncc.go.jp [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Suzuki, Shigenobu [Department of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo (Japan); Tobinai, Kensei [Department of Hematologic Oncology, National Cancer Center Hospital, Tokyo (Japan); Uno, Takashi [Department of Radiology, Chiba University School of Medicine, Chiba (Japan); Itami, Jun [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)

    2014-03-01

    Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

  1. Role of radiation therapy in the treatment of pediatric non-Hodgkin's lymphomas. [Complications of local irradiation and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Carabell, S.C.; Cassady, J.R.; Weinstein, H.J.; Jaff, N.

    1978-11-01

    Between 1971 and 1976, 64 patients less than 18 years of age with non-Hodgkin's lymphoma were treated at Boston's Children's Hospital Medical Center-Joint Center for Radiation Therapy. A multimodality approach was used, consisting of radiation therapy (3500 to 4500 rad), surgery, and chemotherapy. Since 1973, all patients have received a regimen initially comprising Adriamycin, Prednisone, 6-Mercaptopurine, Vincristine, and L-Asparaginase. Methotrexate was substituted for Adriamycin following a cumulative total dose of 450 mg/m/sup 2/. The 5-year actuarial survival for all patients was 61%, while relapse-free survival was 54%. The actuarial and relapse-free survival for patients presenting with localized disease was 75% and 72%, respectively. Median follow-up was 40 months and all relapses occurred within 24 months of initial therapy. A multidisciplinary approach, such as the current regimen, offers a good prognosis for this disease.

  2. Locally advanced stage high-grade mucoepidermoid carcinoma of salivary gland in a 9-year-old girl: the controversy of adjuvant therapy

    Directory of Open Access Journals (Sweden)

    Olga Micol Martínez

    2016-10-01

    Full Text Available Malignant salivary gland tumors are rare in children, mostly represented by low-grade mucoepidermoid carcinomas. For these patients, long-term survival rates above 95% are reported after surgical resection. Here we report a case of a 9-year-old girl with a high grade locally advanced mucoepidermoid carcinoma undergoing adjuvant radiotherapy and chemotherapy after surgery. We emphasize the controversy and lack of evidence-based indication for these highly toxic adjuvant therapy modalities in children.

  3. Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT in combination with cetuximab and chemotherapy: the REACH protocol

    Directory of Open Access Journals (Sweden)

    Simon Christian

    2010-11-01

    Full Text Available Abstract Background Primary treatment of carcinoma of the oro-/hypopharynx or larynx may consist of combined platinum-containing chemoradiotherapy. In order to improve clinical outcome (i.e. local control/overall survival, combined therapy is intensified by the addition of the EGFR inhibitor cetuximab (Erbitux®. Radiation therapy (RT is carried out as intensity-modulated RT (IMRT to avoid higher grade acute and late toxicity by sparing of surrounding normal tissues. Methods/Design The REACH study is a prospective phase II study combining chemoradiotherapy with carboplatin/5-Fluorouracil (5-FU and the monoclonal epidermal growth factor-receptor (EGFR antibody cetuximab (Erbitux® as intensity-modulated radiation therapy in patients with locally advanced squamous-cell carcinomas of oropharynx, hypopharynx or larynx. Patients receive weekly chemotherapy infusions in the 1st and 5th week of RT. Additionally, cetuximab is administered weekly throughout the treatment course. IMRT is delivered as in a classical concomitant boost concept (bid from fraction 16 to a total dose of 69,9 Gy. Discussion Primary endpoint of the trial is local-regional control (LRC. Disease-free survival, progression-free survival, overall survival, toxicity, proteomic and genomic analyses are secondary endpoints. The aim is to explore the efficacy as well as the safety and feasibility of this combined radioimmunchemotherapy in order to improve the outcome of patients with advanced head and neck cancer. Trial registration ISRCTN87356938

  4. The Efficacy of Neoadjuvant Androgen Deprivation Therapy as a Prostate Volume Reduction before Brachytherapy for Clinically Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Miki,Kenta

    2007-12-01

    Full Text Available From September 2003 to December 2005, 188 patients who visited our hospital and allied institutions for the purpose of prostate brachytherapy were administrated hormonal therapy for volume reductions before brachytherapy. The pretreatment and posttreatment of prostate volume using a transrectal ultrasound volumetric study and the types and duration of hormonal therapy were analyzed. We administered 91 patients with Luteinizing hormone-releasing hormone (LH-RH agonist, 49 patients with anti-androgen (bicaltamide/flutamide, and 48 patients with maximum androgen blockade (MAB. The duration of the hormonal therapy was 1-3 months for 49 patients, 4-6 months for 59 patients, 7-9 months for 40 patients, 10-12 months for 32 patients, and over 13 months for 8 patients. Before the initiation of hormonal therapy, the mean prostate volume was 35.12 ml (11.04-78.71 ml, and the average of prostate volume before and after hormonal therapy was 36.79 ml and 24.79 ml, respectively (a 32.4% reduction. The prostate volume reduction rate was 32.0% for the LH-RH agonist only, 18.1% for the anti-androgen only and 41.2% for the MAB. No statistically significant difference was observed for the duration of hormonal therapy between 3 groups. A three-month course of the neoadjuvant LH-RH agonist indicated a sufficient volume reduction effectiveness for a large prostate volume.

  5. NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu [Massachusetts General Hospital, Boston, Massachusetts (United States); Moughan, Jennifer [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Garofalo, Michael C. [University of Maryland School of Medicine, Baltimore, Maryland (United States); Bendell, Johanna [Sarah Cannon Research Institute, Nashville, Tennessee (United States); Berger, Adam C. [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Oldenburg, Nicklas B.E. [North Main Radiation Oncology, Providence, Rhode Island (United States); Anne, Pramila Rani [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Perera, Francisco [London Regional Cancer Program/Western Ontario, London, Ontario (Canada); Lee, R. Jeffrey [Intermountain Medical Center, Salt Lake City, Utah (United States); Jabbour, Salma K. [Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Nowlan, Adam [Piedmont Hospital, Atlanta, Georgia (United States); DeNittis, Albert [Main Line Community Clinical Oncology Program, Wynnewood, Pennsylvania (United States); Crane, Christopher [University of Texas-MD Anderson Cancer Center, Houston, Texas (United States)

    2015-09-01

    Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

  6. Role of p53-fibrinolytic system cross-talk in the regulation of quartz-induced lung injury.

    Science.gov (United States)

    Bhandary, Yashodhar P; Shetty, Shwetha K; Marudamuthu, Amarnath S; Fu, Jian; Pinson, Barbara M; Levin, Jeffrey; Shetty, Sreerama

    2015-03-01

    Silica is the major component of airborne dust generated by wind, manufacturing and/or demolition. Chronic occupational inhalation of silica dust containing crystalline quartz is by far the predominant form of silicosis in humans. Silicosis is a progressive lung disease that typically arises after a very long latency and is a major occupational concern with no known effective treatment. The mechanism of silicosis is not clearly understood. However, silicosis is associated with increased cell death, expression of redox enzymes and pro-fibrotic cytokines and chemokines. Since alveolar epithelial cell (AEC) death and disruption of alveolar fibrinolysis is often associated with both acute and chronic lung injuries, we explored whether p53-mediated changes in the urokinase-type plasminogen activator (uPA) system contributes to silica-induced lung injury. We further sought to determine whether caveolin-1 scaffolding domain peptide (CSP), which inhibits p53 expression, mitigates lung injury associated with exposure to silica. Lung tissues and AECs isolated from wild-type (WT) mice exposed to silica exhibit increased apoptosis, p53 and PAI-1, and suppression of uPA expression. Treatment of WT mice with CSP inhibits PAI-1, restores uPA expression and prevents AEC apoptosis by suppressing p53, which is otherwise induced in mice exposed to silica. The process involves CSP-mediated inhibition of serine-15 phosphorylation of p53 by inhibition of protein phosphatase 2A-C (PP2A-C) interaction with silica-induced caveolin-1 in AECs. These observations suggest that changes in the p53-uPA fibrinolytic system cross-talk contribute to lung injury caused by inhalation of silica dust containing crystalline quartz and is protected by CSP by targeting this pathway.

  7. Trending Fibrinolytic Dysregulation: Fibrinolysis Shutdown in the Days After Injury Is Associated With Poor Outcome in Severely Injured Children.

    Science.gov (United States)

    Leeper, Christine M; Neal, Matthew D; McKenna, Christine J; Gaines, Barbara A

    2017-09-01

    To trend fibrinolysis after injury and determine the influence of traumatic brain injury (TBI) and massive transfusion on fibrinolysis status. Admission fibrinolytic derangement is common in injured children and adults, and is associated with poor outcome. No studies examine fibrinolysis days after injury. Prospective study of severely injured children at a level 1 pediatric trauma center. Rapid thromboelastography was obtained on admission and daily for up to 7 days. Standard definitions of hyperfibrinolysis (HF; LY30 ≥3), fibrinolysis shutdown (SD; LY30 ≤0.8), and normal (LY30 = 0.9-2.9) were applied. Antifibrinolytic use was documented. Outcomes were death, disability, and thromboembolic complications. Wilcoxon rank-sum and Fisher exact tests were performed. Exploratory subgroups included massively transfused and severe TBI patients. In all, 83 patients were analyzed with median (interquartile ranges) age 8 (4-12) and Injury Severity Score 22 (13-34), 73.5% blunt mechanism, 47% severe TBI, 20.5% massively transfused. Outcomes were 14.5% mortality, 43.7% disability, and 9.8% deep vein thrombosis. Remaining in or trending to SD was associated with death (P = 0.007), disability (P = 0.012), and deep vein thrombosis (P = 0.048). Median LY30 was lower on post-trauma day (PTD)1 to PTD4 in patients with poor compared with good outcome; median LY30 was lower on PTD1 to PTD3 in TBI patients compared with non-TBI patients. HF without associated shutdown was not related to poor outcome, but extreme HF (LY30 >30%, n = 3) was lethal. Also, 50% of massively transfused patients in hemorrhagic shock demonstrated SD physiology on admission. All with HF (fc31.2%) corrected after hemostatic resuscitation without tranexamic acid. Fibrinolysis shutdown is common postinjury and predicts poor outcomes. Severe TBI is associated with sustained shutdown. Empiric antifibrinolytics for children should be questioned; thromboelastography-directed selective use should be considered for

  8. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Eng-Yen [Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Chanchien, Chan-Chao; Lin, Hao [Department of Gynecologic Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Wang, Chung-Chi; Wang, Chong-Jong [Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Huang, Chao-Cheng, E-mail: huangcc@cgmh.org.tw [Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China)

    2013-12-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

  9. The Association of IFI27 Expression and Fatigue Intensification during Localized Radiation Therapy: Implication of a Para-Inflammatory Bystander Response

    Directory of Open Access Journals (Sweden)

    Leorey N. Saligan

    2013-08-01

    Full Text Available The mechanisms behind fatigue intensification during cancer therapy remain elusive. The interferon alpha-inducible protein 27 (IFI27 was the most up-regulated gene based on our previous microarray data in fatigued men with non-metastatic prostate cancer receiving localized external beam radiation therapy (EBRT. The purpose of this study was to confirm the IFI27 up-regulation and determine its association with fatigue intensification during EBRT. Peripheral blood samples and fatigue scores were collected at three time points—prior to EBRT, at midpoint, and at completion of EBRT. Confirmatory quantitative real time polymerase chain reaction (qPCR and enzyme-linked immunosorbent assay (ELISA were utilized to verify the microarray results. Subjects were a total of 40 Caucasian men with prostate cancer; 20 scheduled for EBRT (65.6 ± 7.5 years old, and 20 on active surveillance as controls (62.8 ± 6.1 years old. Significant IFI27 expression overtime during EBRT was confirmed by qPCR (p < 0.5, which correlated with fatigue scores during EBRT (R = −0.90, p = 0.006. Alterations in mechanisms associated with immune response and mitochondrial function that explain the up-regulation of IFI27 may provide an understanding of the pathways related to the intensification of fatigue during localized radiation therapy.

  10. Study on Blood Coagulant/Fibrinolytic Activity at Plasma andMonocytic Levels in Coronary Heart Disease Patients withBlood-Stasis Syndrome of Traditional Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To explore and compare the changes of coagulant/fibrinolytic activity in coronary heart disease (CHD) patients with Blood Stasis Syndrome of TCM and evaluate the roles of these changes. Methods: Eighty patients of CHD were divided into two groups by Syndrome Differentiation of TCM, the Blood-Stasis (BS) group (30 cases) and the non-Blood-Stasis (NBS) group (50 cases, including 27 cases of Phlegm-Dampness Syndrome and 23 cases of Qi-Stagnation Syndrome); and 20 healthy persons were enrolled as normal control group. Tissue type plasminogen activator (t-PA) and its inhibitor (PAI-1) in plasma and in human peripheral blood monocyte cell (PBMC), as well as the procoagulant activity (PCA) in PBMC were measured by chromogenic substrate method. Results: The plasma PAI-1 activity and PCA of PBMC in the BS group were significantly higher than those in the NBS group and the normal control group (P<0.01). PAI-1 activity of PBMC in the two groups of CHD patients was higher than those in the normal control group significantly (P<0.01), but no significant difference was found between the BS group and the NBS group (P>0.05). The difference of plasma t-PA activity between the two groups of CHD was insignificant. The PBMC t-PA activity in the BS group was lower than that in the NBS and normal control groups (P<0.01). Conclusion: In the CHD patients with BS, the PBMC PCA was increased and the fibrinolytic activity at both plasma and monocyte levels lowered significantly, these changes in coagulant/fibrinolytic activity may be the important pathologic factors in forming BS which suggests that CHD patients with BS were in the prothrombotic state.

  11. Evaluation of Local and Systemic Levels of Interleukin-17, Interleukin-23, and Myeloperoxidase in Response to Periodontal Therapy in Patients with Generalized Aggressive Periodontitis.

    Science.gov (United States)

    Cifcibasi, E; Koyuncuoglu, C; Ciblak, M; Badur, S; Kasali, K; Firatli, E; Cintan, S

    2015-10-01

    We aimed to investigate serum and gingival crevicular fluid levels of myeloperoxidase, interleukin-17, and interleukin-23 before and after nonsurgical periodontal therapy in generalized aggressive periodontitis patients and compare to those in healthy controls. Interleukin-17, interleukin-23, and myeloperoxidase levels were measured by enzyme-linked immunosorbent assay in gingival crevicular fluid and serum samples taken from 19 systemically healthy generalized aggressive periodontitis patients and 22 healthy controls. In addition, the levels of IL-17, IL-23, and myeloperoxidase were reassessed at 3 months after periodontal therapy in the generalized aggressive periodontitis (GAP) group. Periodontal clinical parameters were also evaluated at baseline and 3 months post-therapy. The investigated molecule levels in serum decreased significantly at 3 months as a result of the therapy (p = 0.014 for IL-17, p = 0.000 for IL-23, and p = 0.001 for myeloperoxidase (MPO)). Significant reductions were also observed in gingival crevicular fluid (GCF) IL-17, IL-23, and MPO levels at 3 months after therapy (p = 0.000 for all molecules). However, the GCF levels of IL-17, IL-23, and MPO in GAP patients were still higher than those in the controls at 3 months (p = 0.001). A significant decrease in the local and systemic levels of IL-17, IL-23, and MPO based on the therapy might indicate the role of these mediators for tissue destruction in periodontal tissues.

  12. Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.

    Science.gov (United States)

    Curtis, Ryan C; Custis, James T; Ehrhart, Nicole P; Ehrhart, E J; Condon, Keith W; Gookin, Sara E; Donahue, Seth W

    2016-01-01

    Clinical studies using definitive-intent stereotactic radiation therapy (SRT) for the local treatment of canine osteosarcoma (OSA) have shown canine patients achieving similar median survival times as the current standard of care (amputation and adjuvant chemotherapy). Despite this, there remains an unacceptable high risk of pathologic fracture following radiation treatment. Zoledronic acid (ZA) and parathyroid hormone (PTH) are therapeutic candidates for decreasing this fracture risk post-irradiation. Due to differing mechanisms, we hypothesized that the combined treatment with ZA and PTH would significantly improve bone healing more than ZA or PTH treatment alone. Using an orthotopic model of canine osteosarcoma in athymic rats, we evaluated bone healing following clinically-relevant doses of radiation therapy (12 Gy x 3 fractions, 36 Gy total). Groups included 36 Gy SRT only, 36 Gy SRT plus ZA, 36 Gy SRT plus ZA and PTH, 36 Gy SRT plus PTH, and 36 Gy SRT plus localized PTH treatment. Our study showed significant increases in bone volume and increased polar moments of inertia (in the distal femoral metaphysis) 8 weeks after radiation in the combined (ZA/PTH) treatment group as compared to radiation treatment alone. Histomorphometric analysis revealed evidence of active mineralization at the study endpoint as well as successful tumor-cell kill across all treatment groups. This work provides further evidence for the expanding potential indications for ZA and PTH therapy, including post-irradiated bone disease due to osteosarcoma.

  13. [Use of local injections of tolperisone (midocalm) in combination with tractional therapy in the treatment of vertebral static syndrome].

    Science.gov (United States)

    Zakharov, Ia Iu; Kutarev, R V; Shelkov, S N; Suslov, S A

    2007-01-01

    A randomized double-blind study of the efficacy of midocalm combined with tractional therapy has been carried out in 24 patients (indexed group) comparing to the tractional therapy without midocalm (the drug has been substituted with placebo) in 25 patients (comparison group). The effective number of injections was 3-6 in the indexed group and 7 in the comparison group. A quantitative assessment revealed that in the indexed group treatment efficacy was 1,56 times higher and the effect achieved sooner than in the comparison group.

  14. Proteomics study of extracellular fibrinolytic proteases from Bacillus licheniformis RO3 and Bacillus pumilus 2.g isolated from Indonesian fermented food

    Science.gov (United States)

    Nur Afifah, Diana; Rustanti, Ninik; Anjani, Gemala; Syah, Dahrul; Yanti; Suhartono, Maggy T.

    2017-02-01

    This paper presents the proteomics study which includes separation, identification and characterization of proteins. The experiment on Indonesian fermented food such as extracellular fibrinolytic protease from Bacillus licheniformis RO3 and Bacillus pumilus 2.g isolated from red oncom and tempeh gembus was conducted. The experimental works comprise the following steps: (1) a combination of one- and two-dimensional electrophoresis analysis, (2) mass spectrometry analysis using MALDI-TOF-MS and (3) investigation using protein database. The result suggested that there were new two protein fractions of B. licheniformis RO3 and three protein fractions of B. pumilus 2.g. These result has not been previously reported.

  15. 可口革囊星虫(Phascolosoma esculenta)纤溶酶PFE的分离纯化%Study on fibrinolytic enzyme from Phascolosoma Esculenta

    Institute of Scientific and Technical Information of China (English)

    牛荣丽; 熊亚楠; 吕佳美悦

    2011-01-01

    Objective To find a thrombolytic substance from Phascolosoma esculenta. Methods Detecting the fibrinolytic activity by fibrin plate method, the fibrinolytic enzyme from Phascolosoma esculenta was extracted by homogenization, centrifugation and purification by gel filtration column G-25 and DEAE. Then characterizations of the enzyme activity were observed including Ph, temperature, metal ion and inhibitors. Results The fibrinolytic enzyme from Phascolosoma esculenta was isolated and named PFE, which relative molecular mass was about 35 Kd. PFE could degrade directly fibrin. The optimal Ph of PFE was 7. 4, which activity was keep stable between Ph6. 6~9. 0 or the temperature 20~40 °C. The activity of PFE was inhibited by Ca2+、Mg2+、Fe2+、K+、EDTA and β-mercaptoethanol, esp. Strongly inhibited by Fe3+. Conclusion There was fibrinolytic enzyme which can directly degrade fibrin in Phascolosoma esculenta.%目的 从可口革囊星虫中分离纯化纤溶酶,并初步研究其酶学性质.方法 实验以纤维蛋白平板法检测纤溶活性,采用匀浆、抽提离心、G-25脱盐、DEAE梯度洗脱等方法从可口革囊星虫中分离纯化出纤溶酶PFE,并进一步研究pH、温度、金属离子及抑制剂对该酶活性的影响.结果 分离纯化得到纤溶酶PFE,SDSPAGE法测得相对分子质量为35 kDa左右.此外,其酶学性质研究结果表明:PFE的最适反应pH为7.4,酶活力在pH6.6~9.0时相对稳定;PFE在20~40℃条件下,酶活力保持相对稳定.Fe3+对酶活性有强烈的抑制作用,Ca2+、Mg2+、Fe2+、K+、EDTA和β-巯基乙醇对酶活性均具有一定的抑制作用.结论 可口革囊星虫中存在纤溶酶PFE,此酶可直接降解纤维蛋白,具有重要的临床开发价值.

  16. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Cengel, Keith A

    2014-02-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6-9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis.

  17. Incidence, causative mechanisms, and anatomic localization of stroke in pituitary adenoma patients treated with postoperative radiation therapy versus surgery alone

    NARCIS (Netherlands)

    Sattler, Margriet; Vroomen, Patrick; Sluiter, Wim J.; Schers, Henk J.; van den Berg, Gerrit; Langendijk, Johannes A.; Wolffenbuttel, Bruce H. R.; van den Bergh, Alphons C. M.; van Beek, Andre P.

    2013-01-01

    PURPOSE: To assess and compare the incidence of stroke and stroke subtype in pituitary adenoma patients treated with postoperative radiation therapy (RT) and surgery alone. METHODS AND MATERIALS: A cohort of 462 pituitary adenoma patients treated between 1959 and 2008 at the University Medical Cente

  18. Surgical outcomes after excision of pigmented villonodular synovitis localized to the ankle and hindfoot without adjuvant therapy.

    Science.gov (United States)

    Sung, Ki-Sun; Ko, Kyung Rae

    2015-01-01

    Although a benign disorder, pigmented villonodular synovitis (PVNS) has a high rate of recurrence. Because of the high incidence of recurrence and concern about destruction of the affected joint, several adjuvant therapies have been promoted without a clear standard treatment strategy. We reviewed cases of PVNS affecting the ankle and hindfoot joints (ankle and/or subtalar joints) treated with surgical resection without adjuvant therapy in an effort to identify the incidence of PVNS recurrence after excision without adjuvant therapy. Of the 10 cases with a mean follow-up duration of 33.2 ± 19.8 months, 4 (40%) developed a recurrence, with a mean interval of 6 (range 3 to 14) months. At the final follow-up visit, the mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 86.6 ± 12. The clinical outcomes of PVNS affecting the ankle and hindfoot joints are associated with a relatively high incidence of recurrence, and additional clinical investigation comparing the incidence of recurrence in patients undergoing excision versus excision with adjuvant therapy is needed for us to better understand this condition and provide more informed recommendations to our patients.

  19. Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer

    Science.gov (United States)

    2016-03-17

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Chemotherapeutic Agent Toxicity; Cognitive Side Effects of Cancer Therapy; Psychological Impact of Cancer; Radiation Toxicity; Sexual Dysfunction and Infertility; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  20. Gene expression profiling of breast cancer to identify subtypes and to predict local recurrence after breast conserving therapy

    NARCIS (Netherlands)

    Kreike, B.

    2011-01-01

    Bij sommige borstkankerpatiënten die een borstsparende therapie ondergingen, keert de kanker lokaal terug. Bas Kreike vond met behulp van microarray-genexpressieprofilering een groep genen die dit kan voorspellen. De vondst kan echter nog niet klinisch worden toegepast in verband met een lage specif

  1. Very low local recurrence rates after breast-conserving therapy : analysis of 8485 patients treated over a 28-year period

    NARCIS (Netherlands)

    Bosma, S C J; van der Leij, F; van Werkhoven, E; Bartelink, H; Wesseling, J.; Linn, S; Rutgers, E J; van de Vijver, M J; Elkhuizen, P H M

    The purpose of this study was to study the impact of changes in clinical practice on outcome in patients treated with breast-conserving therapy (BCT) over a period of 28 years. Patients with early invasive breast cancer, who were treated with BCT at the Netherlands Cancer Institute between 1980 and

  2. Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer.

    Science.gov (United States)

    Ohno, Shinji

    2016-08-01

    For women with hormone receptor-positive advanced breast cancer, endocrine therapies, including the selective estrogen receptor modulator tamoxifen, the aromatase inhibitors anastrozole, letrozole, and exemestane, and the selective estrogen receptor degrader fulvestrant, are recommended in clinical guidelines. The addition of targeted agents such as everolimus or palbociclib to aromatase inhibitors are also recommended as treatment options. Chemotherapy remains an option, although clinical guidelines have recommended these agents be reserved for patients with immediately life-threatening disease or if resistance to endocrine therapy is known or suspected. The present review has consolidated the tolerability profiles of the agents approved for use in the treatment of hormone receptor-positive advanced or metastatic breast cancer based on phase III registration trial data. Endocrine therapies are generally well tolerated, although the addition of targeted therapies to aromatase inhibitors or fulvestrant appears to increase the proportion of patients experiencing adverse events, and palbociclib and chemotherapy appear to be more closely associated with serious adverse events, including neutropenia.

  3. Propensity Score–Matched Analysis of Comprehensive Local Therapy for Oligometastatic Non-Small Cell Lung Cancer That Did Not Progress After Front-Line Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Sheu, Tommy [University of Texas School of Public Health, Houston, Texas (United States); Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rao, Ganesh; Weinberg, Jeffrey S. [Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mehran, Reza [Department of Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); McAleer, Mary Frances; Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Aloia, Thomas A. [Department of Gastrointestinal Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-11-15

    Purpose: To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. Methods and Materials: We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assess the efficacy of CLT. Results: Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. Conclusions: Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score–matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population.

  4. Prognostic Value of External Beam Radiation Therapy in Patients Treated With Surgical Resection and Intraoperative Electron Beam Radiation Therapy for Locally Recurrent Soft Tissue Sarcoma: A Multicentric Long-Term Outcome Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, Felipe A. [Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); School of Medicine, Complutense University, Madrid (Spain); Sole, Claudio V., E-mail: cvsole@uc.cl [Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); School of Medicine, Complutense University, Madrid (Spain); Service of Radiation Oncology, Instituto de Radiomedicina, Santiago (Chile); Cambeiro, Mauricio [Service of Radiation Oncology, Clínica Universitaria, Universidad de Navarra, Pamplona (Spain); Montero, Angel; Polo, Alfredo [Service of Radiation Oncology, Hospital Universitario Ramón y Cajal, Universidad de Alcala, Madrid (Spain); Gonzalez, Carmen [School of Medicine, Complutense University, Madrid (Spain); Service of Radiation Oncology, Instituto de Radiomedicina, Santiago (Chile); Service of Radiation Oncology, Clínica Universitaria, Universidad de Navarra, Pamplona (Spain); Service of Radiation Oncology, Hospital Universitario Ramón y Cajal, Universidad de Alcala, Madrid (Spain); Service of Radiation Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Cuervo, Miguel [Service of Orthopedics and Traumatology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); San Julian, Mikel [Service of Orthopedics and Traumatology, Clínica Universitaria, Universidad de Navarra, Pamplona (Spain); and others

    2014-01-01

    Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy.

  5. A Phase 3 Protocol of Total Androgen Suppression and Radiation Therapy (RT) vs. TAS and RT Followed by Chemotherapy with Paclitaxel, Estramustine, and Etoposide for Localized, High Risk, Prostate Cancer

    Science.gov (United States)

    2014-05-13

    Paclitaxelkestramustine, and Etopside (TEE) for Localized, High-Risk, Society of Clinical Rajan R, Kerlin K, Prostate Cancer Oncology (ASCO) Michalski J...Therapy and Radiation Therapy (RT) vs. Kerlin K, Michalski J, Long-Term AS+ RT Alone in the Management of High-Risk Prostate Sandler H. Cancer

  6. Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapy.

    Science.gov (United States)

    Ferreira, Luís; Alexandrino, Henrique; Soares Leite, Júlio; Castro Sousa, Francisco

    2015-12-16

    Colorectal cancer is a common malignant neoplasm and its treatment usually involves surgery associated, in some cases, depending on the staging, with chemoradiotherapy. Necrotising fasciitis of the perineum is a highly lethal infection of the perineum, perirectal tissues and genitals, requiring emergency surgical debridement, broad-spectrum antibiotics and control of sepsis. We present the case of a 59-year-old man with necrotising fasciitis of the perineum as the first clinical manifestation of locally advanced adenocarcinoma of the rectum, in which successful management consisted of early and aggressive surgical debridement, followed by multimodal therapy with curative intent. 2 years and 6 months after surgery the patient is well, with no evidence of local or systemic relapse.

  7. Dual pancreas- and lung-targeting therapy for local and systemic complications of acute pancreatitis mediated by a phenolic propanediamine moiety.

    Science.gov (United States)

    Li, Jianbo; Zhang, Jinjie; Fu, Yao; Sun, Xun; Gong, Tao; Jiang, Jinghui; Zhang, Zhirong

    2015-08-28

    To inhibit both the local and systemic complications with acute pancreatitis, an effective therapy requires a drug delivery system that can efficiently overcome the blood-pancreas barrier while achieving lung-specific accumulation. Here, we report the first dual pancreas- and lung-targeting therapeutic strategy mediated by a phenolic propanediamine moiety for the treatment of acute pancreatitis. Using the proposed dual-targeting ligand, an anti-inflammatory compound Rhein has been tailored to preferentially accumulate in the pancreas and lungs with rapid distribution kinetics, excellent tissue-penetrating properties and minimum toxicity. Accordingly, the drug-ligand conjugate remarkably downregulated the proinflammatory cytokines in the target organs thus effectively inhibiting local pancreatic and systemic inflammation in rats. The dual-specific targeting therapeutic strategy may help pave the way for targeted drug delivery to treat complicated inflammatory diseases.

  8. Postoperative intensity-modulated radiation therapy provides favorable local control and low toxicities in patients with soft tissue sarcomas in the extremities and trunk wall

    Directory of Open Access Journals (Sweden)

    Wang JY

    2015-10-01

    Full Text Available Jianyang Wang, Shulian Wang, Yongwen Song, Xinfan Liu, Jing Jin, Weihu Wang, Zihao Yu, Yueping Liu, Yexiong Li Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Purpose: To investigate the efficacy and toxicity of postoperative intensity-modulated radiation therapy (IMRT for patients with soft tissue sarcomas (STSs in the extremities and trunk wall. Patients and methods: Eighty patients with localized STSs in the extremities and trunk wall treated with function-conserving surgery and postoperative IMRT were analyzed. The primary locations were in the extremities in 51 patients and in the trunk wall in 29 patients. The margins were positive in nine patients and negative in 71 patients. The median dose of IMRT was 64 Gy. Results: At a median follow-up time of 38 months, eight patients developed local recurrences. The 5-year local control (LC rate was 88.1%. The patients with negative margins exhibited much better LC than did those with positive margins (90% vs 64.8%, P=0.023. Multivariate analysis revealed that positive margin was an independent risk factor for LC. The 5-year distant metastasis-free survival, disease-free survival, and overall survival rates were 75.2%, 72.6%, and 83.6%, respectively. Large tumor size (>5 cm was significantly associated with poor overall survival. Edema and joint stiffness were observed in 17.6% and 9.8% of patients with extremity STSs, respectively. Conclusion: IMRT provides excellent LC and low toxicity for patients with STSs in the extremities and trunk wall. Keywords: soft tissue sarcoma, extremities and trunk wall, intensity-modulated radiation therapy, local control, toxicitiess

  9. Fibrinolytic, anti-inflammatory and anti-microbial properties of α-(1-3)-glucans produced from Streptococcus mutans (MTCC 497).

    Science.gov (United States)

    Buddana, Sudheer Kumar; Varanasi, Yaswanth Venkata Naga; Shetty, Prakasham Reddy

    2015-01-22

    Streptococcus mutans (MTCC 497) cell associated α-(1-3)-glucans were isolated, characterized and evaluated for their bioactivity profile. Acid hydrolysis of α-(1-3)-glucans revealed presence of glucose moieties. Water insoluble α-(1-3)-glucans (WIG) were sulfated to convert them into water soluble glucans which were characterized by FT-IR spectral studies. The sulfation of WIG was confirmed by the presence of -O-SO3- and C-O-SO3- characteristic peaks at 1240 and 820 cm(-1). MALDI-TOF analysis of sulfated α-(1-3)-glucan revealed 1.2 to 9kDa fragmentation. Antibacterial profile studies revealed higher growth inhibitory activity against Gram negative than Gram positive bacterial strains by sulfated α-(1-3)-glucans. One-fold higher anti-inflammatory activity with IC50 value of 0.11mg/ml was observed with sulfated α-(1-3)-glucans over WIG. Time dependent fibrinolytic potential without requirement of tissue plasminogen activators was observed for sulfated α-(1-3)-glucans. This is the first report demonstrating the fibrinolytic and anti-inflammatory property for sulfated α-(1-3)-glucans.

  10. Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model

    Directory of Open Access Journals (Sweden)

    Arianna B. Lovati

    2016-01-01

    Full Text Available S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs at day 3 and in vancomycin systemically injected rats (l-VANC at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics.

  11. Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model

    Science.gov (United States)

    Drago, Lorenzo; Bottagisio, Marta; Bongio, Matilde; Ferrario, Marzia; Perego, Silvia; Sansoni, Veronica; De Vecchi, Elena; Romanò, Carlo L.

    2016-01-01

    S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs) died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs) at day 3 and in vancomycin systemically injected rats (l-VANC) at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics. PMID:27478310

  12. Role of p53–fibrinolytic system cross-talk in the regulation of quartz-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Bhandary, Yashodhar P.; Shetty, Shwetha K.; Marudamuthu, Amarnath S. [Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States); Fu, Jian [Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States); Center for Research on Environmental Disease and Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Pinson, Barbara M. [Occupational Medicine, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States); Center for Research on Environmental Disease and Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Levin, Jeffrey [Occupational Medicine, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States); Shetty, Sreerama, E-mail: sreerama.shetty@uthct.edu [Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708 (United States)

    2015-03-01

    Silica is the major component of airborne dust generated by wind, manufacturing and/or demolition. Chronic occupational inhalation of silica dust containing crystalline quartz is by far the predominant form of silicosis in humans. Silicosis is a progressive lung disease that typically arises after a very long latency and is a major occupational concern with no known effective treatment. The mechanism of silicosis is not clearly understood. However, silicosis is associated with increased cell death, expression of redox enzymes and pro-fibrotic cytokines and chemokines. Since alveolar epithelial cell (AEC) death and disruption of alveolar fibrinolysis is often associated with both acute and chronic lung injuries, we explored whether p53-mediated changes in the urokinase-type plasminogen activator (uPA) system contributes to silica-induced lung injury. We further sought to determine whether caveolin-1 scaffolding domain peptide (CSP), which inhibits p53 expression, mitigates lung injury associated with exposure to silica. Lung tissues and AECs isolated from wild-type (WT) mice exposed to silica exhibit increased apoptosis, p53 and PAI-1, and suppression of uPA expression. Treatment of WT mice with CSP inhibits PAI-1, restores uPA expression and prevents AEC apoptosis by suppressing p53, which is otherwise induced in mice exposed to silica. The process involves CSP-mediated inhibition of serine-15 phosphorylation of p53 by inhibition of protein phosphatase 2A-C (PP2A-C) interaction with silica-induced caveolin-1 in AECs. These observations suggest that changes in the p53–uPA fibrinolytic system cross-talk contribute to lung injury caused by inhalation of silica dust containing crystalline quartz and is protected by CSP by targeting this pathway. - Highlights: • Chronic exposure to quartz dusts is a major cause of lung injury and silicosis. • The survival of patients with silicosis is bleak due to lack of effective treatments. • This study defines a new role of

  13. Local co-administration of gene-silencing RNA and drugs in cancer therapy: State-of-the art and therapeutic potential.

    Science.gov (United States)

    Larsson, Mikael; Huang, Wei-Ting; Liu, Dean-Mo; Losic, Dusan

    2017-04-01

    Gene-silencing miRNA and siRNA are emerging as attractive therapeutics with potential to suppress any genes, which could be especially useful in combination cancer therapy to overcome multidrug resistant (MDR) cancer. Nanomedicine aims to advance cancer treatment through functional nanocarriers that delivers one or more therapeutics to cancer tissue and cells with minimal off-target effects and suitable release kinetics and dosages. Although much effort has gone into developing circulating nanocarriers with targeting functionality for systemic administration, another alternative and straightforward approach is to utilize formulations to be administered directly to the site of action, such as pulmonary and intratumoral delivery. The combination of gene-silencing RNA with drugs in nanocarriers for localized delivery is emerging with promising results. In this review, the current progress and strategies for local co-administration of RNA and drug for synergistic effects and future potential in cancer treatment are presented and discussed. Key advances in RNA-drug anticancer synergy and localized delivery systems were combined with a review of the available literature on local co-administration of RNA and drug for cancer treatment. It is concluded that advanced delivery systems for local administration of gene-silencing RNA and drug hold potential in treatment of cancer, depending on indication. In particular, there are promising developments using pulmonary delivery and intratumoral delivery in murine models, but further research should be conducted on other local administration strategies, designs that achieve effective intracellular delivery and maximize synergy and feasibility for clinical use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Comparison of intraoperative radiation therapy-containing multimodality treatment with historical treatment modalities for locally recurrent rectal cancer

    NARCIS (Netherlands)

    Mannaerts, GHH; Rutten, HJT; Martijn, H; Hanssens, PEJ; Wiggers, T

    2001-01-01

    PURPOSE: Treatment protocols for patients with locally recurrent rectal cancer have changed in the last two decades. Subsequently, treatment goals shifted from palliation to possible cure. In this retrospective study, we explored the treatment variables that may have contributed to the improvement i

  15. Prostate-specific antigen kinetics after primary stereotactic body radiation therapy using CyberKnife for localized prostate cancer

    Directory of Open Access Journals (Sweden)

    Yong Hyun Park

    2015-03-01

    Conclusions: PSA decline occurred rapidly in the first month, and then the rate of PSA decline fell off steadily over time throughout 2 years after treatment. Also, SBRT using CyberKnife leads to long-term favorable BCR-free survival in localized prostate cancer.

  16. The Effect of Local Heat and Cold Therapy on the Intraarticular and Skin Surface Temperature of the Knee

    NARCIS (Netherlands)

    Oosterveld, F.G.J.; Rasker, J.J.; Jacobs, J.W.G.; Overmars, H.J.A.

    1992-01-01

    Objective. To evaluate the effects of local application of ice chips, ligno-paraffin, short-wave diathermy, and nitrogen-cold air on skin and intraarticular temperature. Methods. Forty-two healthy subjects were divided into 4 treatment groups. A temperature probe was inserted into the knee joint ca

  17. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer.

    LENUS (Irish Health Repository)

    Armstrong, John G

    2010-08-24

    PURPOSE: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. METHODS AND MATERIALS: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng\\/mL, Gleason score >\\/=7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. RESULTS: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. CONCLUSION: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  18. Localized cortical thickening of the femoral diaphysis captured on an X-ray before alendronate therapy in two cases of atypical femoral fracture

    Energy Technology Data Exchange (ETDEWEB)

    Iizuka, Yoichi [Gunma University Graduate School of Medicine, Department of Orthopedic Surgery, Maebashi, Gunma (Japan); Shibukawa General Hospital, Department of Orthopedic Surgery, Shibukawa, Gunma (Japan); Takechi, Rumi [Gunma University Graduate School of Medicine, Department of Orthopedic Surgery, Maebashi, Gunma (Japan); Gunma Cardiovascular Center, Department of Orthopaedic Surgery, Maebashi, Gunma (Japan); Iizuka, Haku; Takagishi, Kenji [Gunma University Graduate School of Medicine, Department of Orthopedic Surgery, Maebashi, Gunma (Japan); Omodaka, Takuya [Gunma University Graduate School of Medicine, Department of Orthopedic Surgery, Maebashi, Gunma (Japan); Gunma Central Hospital, Department of Orthopedic Surgery, Maebashi, Gunma (Japan)

    2016-10-15

    We herein report two cases of atypical femoral fracture (AFF). X-ray examinations at the first visit of these two female patients showed a complete fracture of the femoral diaphysis diagnosed as an atypical femoral fracture (AFF). X-rays of these two cases also showed localized cortical thickening of the femoral diaphysis. Both patients had been taking alendronate for more than 3 years because of postmenopausal osteoporosis. We assumed that both of the fractures were associated with the long-term use of alendronate. However, we retrospectively identified localized cortical thickening of the femoral diaphysis on an X-ray taken before the alendronate therapy in both of these cases. Therefore, we suspected a pathogenesis of AFFs in which preexisting stress or an insufficient fracture unrelated to bisphosphonate (BP) therapy and subsequent suppression of bone turnover due to BP administration led to the occurrence of an AFF. The patient underwent surgery using intramedullary nails in both of these cases, followed by the administration of teriparatide, and they were able to walk without any support at the final follow-up examination. (orig.)

  19. Local and Systemic Cardiovascular Effects from Monochromatic Infrared Therapy in Patients with Knee Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Study

    Directory of Open Access Journals (Sweden)

    Ru-Lan Hsieh

    2012-01-01

    Full Text Available Infrared (IR therapy is used for pain relief in patients with knee osteoarthritis (OA. However, IR’s effects on the cardiovascular system remain uncertain. Therefore, we investigated the local and systemic cardiovascular effects of monochromatic IR therapy on patients with knee OA in a double-blind, randomized, placebo-controlled study. Seventy-one subjects with knee OA received one session of 40 min of active or placebo monochromatic IR treatment (with power output of 6.24 W, wavelength of 890 nm, power density of 34.7 mW/cm2 for 40 min, total energy of 41.6 J/cm2 per knee per session over the knee joints. Heart rate, blood pressure, and knee arterial blood flow velocity were periodically assessed at the baseline, during, and after treatment. Data were analyzed by repeated-measure analysis of covariance. Compared to baseline, there were no statistically significant group x time interaction effects between the 2 groups for heart rate (P=0.160, blood pressure (systolic blood pressure: P=0.861; diastolic blood pressure: P=0.757, or mean arterial blood flow velocity (P=0.769 in follow-up assessments. The present study revealed that although there was no increase of knee arterial blood flow velocity, monochromatic IR therapy produced no detrimental systemic cardiovascular effects.

  20. uPAR as anti-cancer target: evaluation of biomarker potential, histological localization, and antibody-based therapy

    DEFF Research Database (Denmark)

    Lund, Ida K; Illemann, Martin; Sørensen, Tine Thurison

    2011-01-01

    PAR on the cell surface and/or by direct inhibition of the catalytic activity of uPA. Both strategies have been pursued and inhibition of these functions has shown effect in xenogenic cancer models. Pericellular proteolysis has also been inhibited in vivo in mouse models of wound healing and hepatic fibrinolysis......, and a potential diagnostic and predictive impact of the different uPAR forms has been reported. Hence, pericellular proteolysis seems to be a suitable target for anti-cancer therapy and numerous approaches have been pursued. Targeting of this process may be achieved by preventing the binding of uPA to u...

  1. Clinical outcomes of radiotherapy as initial local therapy for Graves’ ophthalmopathy and predictors of the need for post-radiotherapy decompressive surgery

    Directory of Open Access Journals (Sweden)

    Prabhu Roshan S

    2012-06-01

    Full Text Available Abstract Background The optimal initial local treatment for patients with Graves’ ophthalmopathy (GO is not fully characterized. The purpose of this retrospective study is to describe the clinical outcomes of RT as initial local therapy for GO and define predictors of the need for post-RT salvage bony decompressive surgery. Methods 91 patients with active GO and without prior surgery were treated with RT as initial local therapy between 01/1999 and 12/2010, with a median follow-up period of 18.3 months (range 3.7 - 142 months. RT dose was 24 Gy in 12 fractions. 44 patients (48.4% had prior use of steroids, with 31 (34.1% being on steroids at the initiation of RT. The most common presenting symptoms were diplopia (79%, proptosis (71% and soft tissue signs (62%. Results 84 patients (92.3% experienced stabilization or improvement of GO symptoms. 58 patients (64% experienced improvement in their symptoms. 19 patients (20.9% underwent salvage post-RT bony decompressive surgery. Smoking status and total symptom score at 4 months were independent predictors of post-RT bony decompression with odds ratios of 3.23 (95% CI 1.03 – 10.2 and 1.59 (95% CI 1.06 – 2.4, respectively. Persistent objective vision loss at 4 months post-RT was the most important symptom type in predicting salvage decompression. Chronic dry eye occurred in 9 patients (9.9% and cataracts developed in 4 patients (4.4%. Conclusions RT is effective and well tolerated as initial local therapy for active GO, with only 21% of patients requiring decompressive surgery post RT. Most patients experience stabilization or improvement of GO symptoms, but moderate to significant response occurs in the minority of patients. Smoking status and total symptom severity at 4 months, primarily persistent objective vision loss, are the primary determinants of the need for post-RT salvage bony decompression. Patients who smoke or present with predominantly vision loss symptoms should be

  2. A 5-Year Investigation of Children's Adaptive Functioning Following Conformal Radiation Therapy for Localized Ependymoma

    Energy Technology Data Exchange (ETDEWEB)

    Netson, Kelli L.; Conklin, Heather M. [Department of Psychology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie; Xiong Xiaoping [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Merchant, Thomas E., E-mail: thomas.merchant@stjude.org [Division of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2012-09-01

    Purpose: Conformal and intensity modulated radiation therapies have the potential to preserve cognitive outcomes in children with ependymoma; however, functional behavior remains uninvestigated. This longitudinal investigation prospectively examined intelligence quotient (IQ) and adaptive functioning during the first 5 years after irradiation in children diagnosed with ependymoma. Methods and Materials: The study cohort consisted of 123 children with intracranial ependymoma. Mean age at irradiation was 4.60 years (95% confidence interval [CI], 3.85-5.35). Serial neurocognitive evaluations, including an age-appropriate IQ measure and the Vineland Adaptive Behavior Scales (VABS), were completed before irradiation, 6 months after treatment, and annually for 5 years. A total of 579 neurocognitive evaluations were included in these analyses. Results: Baseline IQ and VABS were below normative means (P<.05), although within the average range. Linear mixed models revealed stable IQ and VABS across the follow-up period, except for the VABS Communication Index, which declined significantly (P=.015). Annual change in IQ (-.04 points) did not correlate with annual change in VABS (-.90 to +.44 points). Clinical factors associated with poorer baseline performance (P<.05) included preirradiation chemotherapy, cerebrospinal fluid shunt placement, number and extent of surgical resections, and younger age at treatment. No clinical factors significantly affected the rate of change in scores. Conclusions: Conformal and intensity modulated radiation therapies provided relative sparing of functional outcomes including IQ and adaptive behaviors, even in very young children. Communication skills remained vulnerable and should be the target of preventive and rehabilitative interventions.

  3. Efficacy of neoadjuvant therapy and surgical rescue for locally advanced hepatoblastomas: 10 year single-center experience and literature review

    Science.gov (United States)

    Ayllon Teran, Dolores; Gómez Beltran, Oscar; Ciria Bru, Rubén; Mateos González, Elena; Peña Rosa, María José; Luque Molina, Antonio; López Cillero, Pedro; Briceño Delgado, Javier

    2014-01-01

    AIM: To report our experience with long-term outcomes after multimodal management therapy. METHODS: An observational retrospective study was performed containing seven patients with hepatoblastoma (Hbl) treated in our institution, a tertiary referral center, from 2003 to 2011. Demographic, preoperative, surgical, and outcome variables were collected. A survival analysis and a review of the current literature related to combination neoadjuvant chemotherapy and surgical resection on Hbl were performed. RESULTS: The median age at surgery was 14.4 mo, with a male to female ratio of 4:3. Pretext staging at diagnosis was as follows: stage I, 4 cases; stage II, 2 patients; and stage III, 1 case. Mean pretreatment tumor volume was 735 cm3. Five out of seven patients received neoadjuvant chemotherapy according to SIOPEL-3 or SIOPEL-6 protocols. Tumor volume and alpha-fetoprotein levels significantly dropped after neoadjuvant therapy. Surgical procedures performed included hemihepatectomies, segmentectomies and atypical resection. All patients received chemotherapy after surgery. Median postoperative hospital stay was 8 d. All patients were alive and disease-free after a median follow-up period of 23 mo. With regards to the literature review, seventeen articles were found that were related to our search. CONCLUSION: Our series shows how multimodal management of Hbl, exhaustive control and a meticulous surgical approach leads to almost 100% complete resection with optimal postoperative results. PMID:25110441

  4. A 5-Year Investigation of Children’s Adaptive Functioning Following Conformal Radiation Therapy for Localized Ependymoma

    Science.gov (United States)

    Netson, Kelli L.; Conklin, Heather M.; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E.

    2012-01-01

    Purpose Conformal and intensity modulated radiation therapies have the potential to preserve cognitive outcomes in children with ependymoma; however, functional behavior remains uninvestigated. This longitudinal investigation prospectively examined intelligence quotient (IQ) and adaptive functioning during the first 5 years after irradiation in children diagnosed with ependymoma. Methods and Materials The study cohort consisted of 123 children with intracranial ependymoma. Mean age at irradiation was 4.60 years (95% confidence interval [CI], 3.85–5.35). Serial neurocognitive evaluations, including an age-appropriate IQ measure and the Vineland Adaptive Behavior Scales (VABS), were completed before irradiation, 6 months after treatment, and annually for 5 years. A total of 579 neurocognitive evaluations were included in these analyses. Results Baseline IQ and VABS were below normative means (PVABS across the follow-up period, except for the VABS Communication Index, which declined significantly (P=.015). Annual change in IQ (−.04 points) did not correlate with annual change in VABS (−.90 to +.44 points). Clinical factors associated with poorer baseline performance (P<.05) included preirradiation chemotherapy, cerebrospinal fluid shunt placement, number and extent of surgical resections, and younger age at treatment. No clinical factors significantly affected the rate of change in scores. Conclusions Conformal and intensity modulated radiation therapies provided relative sparing of functional outcomes including IQ and adaptive behaviors, even in very young children. Communication skills remained vulnerable and should be the target of preventive and rehabilitative interventions. PMID:22541967

  5. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers.

    Science.gov (United States)

    Glynne-Jones, Rob; Hadaki, Maher; Harrison, Mark

    2013-09-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore-with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of 'on target' effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments or

  6. Stereotactic Ablative Radiosurgery for Locally-Advanced or Recurrent Skull Base Malignancies with Prior External Beam Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Karen Mann Xu

    2015-03-01

    Full Text Available Purpose: Stereotactic ablative radiotherapy (SABR is an attractive modality to treat malignancies invading the skull base as it can deliver a highly conformal dose with minimal toxicity. However, variation exists in the prescribed dose and fractionation. The purpose of our study is to examine the local control, survival and toxicities in SABR for the treatment of malignant skull base tumors. Methods and Materials: A total of 31 patients and 40 locally-advanced or recurrent head and neck malignancies involving the skull base treated with a common SABR regimen which delivers a radiation dose of 44 Gy in 5 fractions from January 1st, 2004 to December 31st, 2013 were retrospectively reviewed. The local control rate (LC, progression-free survival rate (PFS, overall survival rate (OS and toxicities were reported.Results: The median follow-up time of all patients was 11.4 months (range: 0.6-67.2 months. The median tumor volume was 27 cm3 (range: 2.4-205 cm3. All patients received prior EBRT with a median radiation dose of 64 Gy (range: 24-75.6 Gy delivered in 12 to 42 fractions. 20 patients had surgeries prior to SABR. 19 patients received chemotherapy. Specifically, 8 patients received concurrent cetuximab (ErbituxTM with SABR. The median time-to-progression (TTP was 3.3 months (range: 0-16.9 months. For the 29 patients (93.5% who died, the median time from the end of first SABR to death was 10.3 months (range: 0.5-41.4 months. The estimated 1-year overall survival (OS rate was 35%. The estimated 2-year OS rate was 12%. Treatment was well-tolerated without grade 4 or 5 treatment-related toxicities.Conclusions: SABR has been shown to achieve low toxicities in locally-advanced or recurrent, previously irradiated head and neck malignancies invading the skull base.

  7. Impact of Pretreatment Combined {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging on Radiation Therapy Treatment Decisions in Locally Advanced Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Sweet Ping, E-mail: sweet.ng@petermac.org [Peter MacCallum Cancer Centre, Melbourne (Australia); David, Steven [Peter MacCallum Cancer Centre, Melbourne (Australia); Alamgeer, Muhammad; Ganju, Vinod [Monash Cancer Centre, Melbourne (Australia)

    2015-09-01

    Purpose: To assess the diagnostic performance of pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC). Methods and Materials: Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body {sup 18}F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings. Results: A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2. Conclusions: Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary

  8. Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: A phase I-II study

    Energy Technology Data Exchange (ETDEWEB)

    Amichetti, M.; Graiff, C.; Fellin, G.; Pani, G.; Bolner, A.; Maluta, S. (Divisione di Radioterapia Oncologica, Trento (Italy)); Valdagni, R. (Divisione di Radioterapia Oncologica, Trento (Italy) Istituto per la Ricerca Scientifica e Tecnologica, Trento (Italy))

    1993-08-01

    Hyperthermia is now being widely used to treat clinical malignancies, especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I-II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplantin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m[sup 2] iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5[degrees]C for 30 min). Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systematic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, they observed a complete response rate of 72.2% (95% confidence interval 51-93.4%), 16.6% of partial response and 11.1% of no change. The study confirms the feasibility of the combination of cisplantin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors. 43 refs., 3 figs., 4 tabs.

  9. Positron-emission tomography CT to identify local recurrence in stage I lung cancer patients 1 year after stereotactic body radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Essler, M.; Wantke, J.; Mayer, B.; Scheidhauer, K. [Klinikum Rechts der Isar, Muenchen (Germany). Dept. of Nuclear Medicine; Bundschuh, R.A. [Universitaetsklinikum Wuerzburg (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Haller, B. [Klinikum rechts der Isar, Muenchen (Germany). Inst. fuer Medizinische Statistik und Epidemiologie; Astner, S.T.; Molls, M.; Andratschke, N. [Klinikum Rechts der Isar, Muenchen (Germany). Klinik fuer Strahlentherapie und Radioonkologie

    2013-06-15

    Purpose: To evaluate the diagnostic value of positron-emission tomography/computed tomography (PET/CT) in stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT), who have suspicious or unclear local recurrence findings in CT 1 year after treatment. Patients and methods: A group of 29 patients with unclear or suspicious CT findings 1 year after SBRT were examined with PET/CT. The ability of standard uptake values (SUV{sub max}, SUV{sub mean} and posttherapeutic reduction in SUV) to detect local failure and identify patients at a high risk of disease-specific death was evaluated using logrank statistics. Histology and clinical follow-up were the gold standards for local recurrence. Results: SUV{sub mean} greater than 3.44 (p = 0.001); SUV{sub max} greater than 5.48 (p = 0.009) or a relative reduction in SUV{sub mean} or SUV{sub max} of less than 43 (p = 0.030) or 52 % (p = 0.025), respectively, was indicative of local recurrence. These parameters also correlated with an increased risk of disease-specific death: SUV{sub mean} greater than 2.81 (p = 0.023); SUV{sub max} greater than 3.45 (p = 0.007) or a relative reduction in SUV{sub mean} or SUV{sub max} of less than 32 (p = 0.015) or 52 % (p = 0.013), respectively, was indicative of an increased risk of disease-specific death. Conclusion: PET/CT performed 1 year after SBRT can reliably identify local recurrence and therefore help to clarify unclear CT findings. As posttherapeutic glucose metabolism also correlates with disease-specific survival, PET/CT may help to stratify lung cancer patients for additional treatment 1 year after SBRT. (orig.)

  10. Topical Tacrolimus and Periodontal Therapy in the Management of a Case of Oral Chronic GVHD Characterized by Specific Gingival Localization

    Directory of Open Access Journals (Sweden)

    Davide Conrotto

    2014-01-01

    Full Text Available Background. Chronic graft versus host disease (cGVHD is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

  11. Topical tacrolimus and periodontal therapy in the management of a case of oral chronic GVHD characterized by specific gingival localization.

    Science.gov (United States)

    Conrotto, Davide; Broccoletti, Roberto; Carcieri, Paola; Giaccone, Luisa; Arduino, Paolo G

    2014-01-01

    Background. Chronic graft versus host disease (cGVHD) is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

  12. 广西莪术及其茎叶多糖的体外纤溶活性研究%Vitro fibrinolytic activities of polysaccharides from Rhizome and stem and its leaf of Curcuma kwangsiensis

    Institute of Scientific and Technical Information of China (English)

    曾金强; 潘小姣; 陈秋燕; 唐璐

    2012-01-01

    目的 考察广西莪术及其茎叶多糖的体外纤溶活性.方法 用分步沉淀法,分离广西莪术及其茎叶的多糖,然后用纤维蛋白琼脂平板法考察不同醇沉多糖的纤溶活性.结果 广西莪术只有10%醇浓度沉淀多糖的体外纤溶效果稳定.广西莪术茎叶10%~30%的醇浓度沉淀多糖体外纤溶作用稳定,40%~60%的醇浓度沉淀多糖在高、中浓度时作用稳定,在低浓度时作用不稳定;在有纤溶活性的分步沉淀多糖中,除了10%和30%的醇浓度沉淀多糖具有浓度依赖性之外(P < 0.05),其余纤溶活性多糖均无浓度依赖性.结论 广西莪术及其茎叶的多糖成分具有体外纤溶活性.%Objective To observe the vitro fibrinolytic activities of polysaccharides from Rhizome and its stem and leaf of Curcuma kwangsiensis. Methods Fractional precipitation was used to separate the different polysaccharides and fibrin plate method was used to detect their vitro fibrinolytic activities. Results Only the 10% alcohol precipitated polysaccharides from Rhizome of Curcuma kwangsiensis had stable vitro fibrinolytic activities. The polysaccharides having.stable vitro fibrinolytic activities from stem and leaf of Curcuma kwangsiensis were the 10% to 30% alcohol precipitated polysaccharides and the high and medium concetration of 40% to 60% alcohol precipitated polysaccharides. 10% and 30% alcohol precipitated polysaccharides had vitro fibrinolytic activities in concentration dependent manner (P < 0.05). Other fibrinolytic activities polysaccharides had no concentra-tion-dependent. Conclusion Polysaccharides from rhizome, stem and leaf of Curcuma kwangsiensis has vitro fibrinolytic activities.

  13. The Effect of Local Heat and Cold Therapy on the Intraarticular and Skin Surface Temperature of the Knee

    OpenAIRE

    1992-01-01

    Objective. To evaluate the effects of local application of ice chips, ligno-paraffin, short-wave diathermy, and nitrogen-cold air on skin and intraarticular temperature. Methods. Forty-two healthy subjects were divided into 4 treatment groups. A temperature probe was inserted into the knee joint cavity and another placed on the overlying skin, and changes in temperature over 3 hours, by treatment group, were recorded. Results. The mean skin surface temperature dropped from 27.9°C to 11.5°C af...

  14. Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck. First clinical experience with vismodegib for locally advanced disease

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, Bjoern; Roedel, Claus; Balermpas, Panagiotis [University Hospital Johann Wolfgang Goethe University, Department of Radiation Oncology, Frankfurt (Germany); Meissner, Markus [University Hospital Johann Wolfgang Goethe University, Department of Dermatology, Frankfurt (Germany); Ghanaati, Shahram [University Hospital Johann Wolfgang Goethe University, Department of Craniofacial and Plastic Surgery, Frankfurt (Germany); Burck, Iris [University Hospital Johann Wolfgang Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany)

    2016-01-15

    Definitive radiotherapy and vismodegib, an oral inhibitor of the hedgehog pathway, are both established treatment options for locally advanced basal cell carcinomas (BCC). Both have shown good results in local tumor control; however, the effects concerning advanced tumors are often not of a lasting nature and to date no systematic data about the combination of the two modalities are available. We retrospectively analyzed four patients who received vismodegib and radiotherapy in combination. Radiation doses varied between 50.4 Gy and 66.0 Gy. Three patients had recurrent BCC. One patient had locoregional lymph node involvement. Vismodegib was taken once a day (150 mg) during the entire time of irradiation and beyond upon instructions of the attending dermatologist. In three cases a persistent complete response was observed, in one case the tumor remained stable for approximately 6 months until further tumor progression was documented. The combined therapy was well tolerated in all cases. No exceptional side effects pointing at a drug-radiation interaction were observed. The combination of vismodegib and radiation seems feasible and the initial results are promising. In our cohort, there was no increase in unexpected side effects. Further research is needed to evaluate the significance of this combined therapy. (orig.) [German] Sowohl definitive Radiotherapie als auch Vismodegib, ein oraler Inhibitor der Hedgehog-Signalkaskade, sind etablierte Behandlungsoptionen fuer lokal fortgeschrittene Basalzellkarzinome (BCC). Beide Therapien zeigen fuer sich gute Ansprechraten, aber die lokale Tumorkontrolle ist oft nicht dauerhaft und bis heute existieren kaum Daten ueber eine Kombination der beiden Modalitaeten. Wir analysierten retrospektiv vier Patientenfaelle nach simultaner Applikation von Vismodegib und Bestrahlung. Die Bestrahlungsdosis variierte zwischen 50,4 Gy und 66,0 Gy. Drei der Patienten hatten ein rezidiviertes BCC. Ein Patient hatte einen befallenen regionalen

  15. Fiducial-free CyberKnife stereotactic body radiation therapy (SBRT for single vertebral body metastases: acceptable local control and normal tissue tolerance with 5 fraction approach

    Directory of Open Access Journals (Sweden)

    Beant S Gill

    2012-04-01

    Full Text Available This retrospective analysis examines the local control and toxicity of 5 fraction fiducial-free CyberKnife stereotactic body radiation therapy (SBRT for single vertebral body metastases. All patients had favorable performance status (ECOG 0-1, oligometastatic disease and no prior spine irradiation. A prescribed dose of 30 to 35 Gy was delivered in 5 fractions to the planning treatment volume (PTV using the CyberKnife with X-sight spine tracking. Suggested maximum spinal cord and esophagus point doses were 30 Gy and 40 Gy, respectively. A median 30 Gy (range, 30 - 35 Gy dose was delivered to a median prescription isodose line of 70% (range, 60 - 80% to 20 patients. At 34 months median follow-up (range, 12-62 months for surviving patients, the 1- and 2-year Kaplan-Meier local control estimates were 80% and 73%, respectively. Two of the 5 local failures were infield in patients who had received partial vertebral body irradiation and 3 were paravertebral failures just outside the PTV in patients with prior corpectomy. No local failures occurred in patients who completed total vertebral body radiation alone. The 1- and 2-year Kaplan-Meier overall survival estimates were 80% and 57%, respectively. Most deaths were attributed to metastatic disease; one death was attributed to local recurrence. The mean maximum point doses were 26.4 Gy (range, 16.3 - 31.8 Gy to the spinal cord and 30.7 Gy (15.4- 40.0 Gy to the esophagus. Patients receiving maximum esophagus point doses greater than 35 Gy experienced acute dysphagia (Grade I/II. No spinal cord toxicity was documented. Five fraction fiducial-free CyberKnife SBRT is an acceptable treatment option for newly diagnosed vertebral body metastases with promising local control rates and minimal toxicity despite the close proximity of such tumors to the spinal cord and esophagus. A prospective study aimed at further enhancing local control by targeting the entire intact vertebral body and escalating the total dose

  16. Implementation of a Computerized Decision Support System to Improve the Appropriateness of Antibiotic Therapy Using Local Microbiologic Data

    Directory of Open Access Journals (Sweden)

    Manuel Rodriguez-Maresca

    2014-01-01

    Full Text Available A prospective quasi-experimental study was undertaken in 218 patients with suspicion of nosocomial infection hospitalized in a polyvalent ICU where a new electronic device (GERB has been designed for antibiotic prescriptions. Two GERB-based applications were developed to provide local resistance maps (LRMs and preliminary microbiological reports with therapeutic recommendation (PMRTRs. Both applications used the data in the Laboratory Information System of the Microbiology Department to report on the optimal empiric therapeutic option, based on the most likely susceptibility profile of the microorganisms potentially responsible for infection in patients and taking into account the local epidemiology of the hospital department/unit. LRMs were used for antibiotic prescription in 20.2% of the patients and PMRTRs in 78.2%, and active antibiotics against the finally identified bacteria were prescribed in 80.0% of the former group and 82.4% of the latter. When neither LMRs nor PMRTRs were considered for empiric treatment prescription, only around 40% of the antibiotics prescribed were active. Hence, the percentage appropriateness of the empiric antibiotic treatments was significantly higher when LRM or PMRTR guidelines were followed rather than other criteria. LRMs and PMRTRs applications are dynamic, highly accessible, and readily interpreted instruments that contribute to the appropriateness of empiric antibiotic treatments.

  17. COMPARITIVE STUDY OF LOCAL STEROID INJECTION VERSUS AUTOLOGOUS BLOOD INJECTION THERAPY FOR THE MANAGEMENT OF LATERAL EPICONDYLITI S

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    Partap

    2015-03-01

    Full Text Available OBJECTIVES : Local corticosteroid infiltration is a common practice of treatment for lateral epicondylitis. In recent studies no statistically significant or clinically relevant results in favour of corticosteroid injections were found. The injection of autologous blood has been reported to be effective for both intermediate and long - term outcomes. It is hypothesized that blood contains growth factors, which induce the healing cascade. METHODS : A total of 50 patients were included in this prospective randomized study. Patients were divided in 2 groups of 25 patients each. Group I received 2 ml local corticosteroid +1 ml 2% lignocaine, Group II received 2 ml autologous blood drawn from ipsilateral upper limb vein +1 ml 2% lignocaine, and at the lateral epicondyle. Outcome was measured using a pain score (VAS . Follow - up was continued for tota l of six months. RESULTS : The corticosteroid injection group showed a statistically significant decrease in pain compared with autologous blood injection group at six weeks follow up. At final six - month follow - up, autologous blood injection group showed st atistically significant decrease in pain compared with corticosteroid injection group. CONCLUSIONS : Autologous blood injection is efficient compared with corticosteroid injection, with less side - effects and minimum recurrence rate in long term.

  18. 华广虻肠道溶纤活性蛋白的纯化和性质%CHARACTERIZATION AND PURIFICATION OF GUT FIBRINOLYTIC PROTEASE FROM TABANUS AMAENUS

    Institute of Scientific and Technical Information of China (English)

    杨星勇; 卢晓风; 程惊秋; 裴炎

    2001-01-01

    After ammonium sulphate precipitation, Sephadex G-75 gel filtration, Lys-Sepharose 4B affinity chromatography and elution from electrophoresis, the fibrinolytic protease (TAFP) was isolated and purified from the extract of T. amaenus Walker gut. It appeared a single band corresponding to molecular weight of approximately 67kD on SDS-PAGE and an probably pI of 7.2 on IEF. On fibrin plate and plasminogen-free fibrin plate (heated at 85℃ for 30 minutes to eliminate plasminogen), TAFP showed same fibrinolytic activity. The result might indicate that TAFP is a fibrinolytic enzyme degrading fibrin, as well as a plasminogen activator degrading fibrin via activating plasminogen. The result of chromogenic substrates indicated that TAFP possesses trypsin-like activity specifically degrading argininyl amide bond or peptide bond, but has no chymotrypsin activity. TAFP was almost inhibited powerfully by antipain, PMSF, soybean trypsin inhibitor and soybean Bowman-Birk inhibitor. However, leupeptin, antitrypsin and TLCK was more powerful effective inhibitors of TAFP. Optimal reaction pH of TAFP was 7.5, and it was stable in 5.5 - 7.0 of pH range.%经过75%饱和度硫酸铵沉淀、Sephadex G-75凝胶过滤层析、Lys-Sepharose 4B亲和层析和电泳制备洗脱,从华广虻(Tabanus amaenus Walker)腹部组织匀浆液中分离纯化出分子量约为67KD的溶纤活性蛋白TAFP.经纤维蛋白平板测定表明,TAFP不仅具有纤溶酶作用,还具有激活纤溶酶原的作用;通过三肽生色底物测定发现,TAFP能分解纤溶酶原激活剂的生色底物-Chromozym UK及S-2288.还能水解胰蛋白酶专-底物Bz-Phe-Val-Arg-NA及CBZ-Gly-Pro-Arg-NA,表明TAFP具有类胰蛋白酶活性,专-水解精氨酸形成的酰胺键(或肽键).TAFP无胰凝乳蛋白酶活性.

  19. 木瓜中纤溶活性蛋白的分离与鉴定%Isolation and identification of a fibrinolytic protein in papaya

    Institute of Scientific and Technical Information of China (English)

    孟爱霞; 邱顺华; 钱民章

    2012-01-01

    从木瓜中分离出能溶解纤维蛋白的活性蛋白。木瓜新鲜乳汁经浸提、盐析、透析得蛋白粗提物;SephadexG-75凝胶层析分离蛋白粗提物,收集蛋白质的洗脱液,依序集合为共1~10个样品,纤维蛋白平板法筛选纤溶活性蛋白;SDS-PAGE电泳检测蛋白纯度及分子量;体外观察该蛋白对血凝块的溶解效果。木瓜蛋白粗提物有纤溶作用,经层析后得到的4、5、6号样品均有纤溶活性,5号样品SDS-PAGE电泳为单一蛋白条带,分子量为26ku,以尿激酶为标准标定该蛋白纤溶活性为17.85IU/mL。该蛋白在体外可通过激活纤溶酶原或直接降解纤维蛋白溶解血栓。木瓜中含有一种分子量为26ku的纤溶活性蛋白。%To isolate proteins from papaya with the ability to digest fibrin. Obtain the crude protein extracts from fresh papaya milk via the process of leaching, salting out and dialysis. Collect fractions No.1-10 as the results of submitting the protein extracts to a Sephadex G-75 chromatographic system and screen fibrinolytic proteins by the method of fibrin plate. Then test the molecule weight (MW) and purity of the protein by SDS-PAGE. The digesting effect of the protein on blood clots was observed in vitro. The crude protein extracts of papaya have the ability of fibrinolysis for which fra.4, 5 and 6 mainly account. And fra.5 appears to be single band in SDS-PAGE with the MW of 26 ku and has the fibrinolytic ability of 17.85 IU/ mL with urokinase as the standard. The protein could dissolve thrombus by either activating plasminogen in vitro or direct digestion of fibrin. We have found a fibrinolytic protein with the MW of 26 ku in papaya.

  20. Systemic Thrombolytic Therapy Alone and in Combination with Mechanical Revascularization in Acute Ischemic Stroke in Two Children

    Directory of Open Access Journals (Sweden)

    B. Modrau

    2011-04-01

    Full Text Available Thrombolytic therapy is not recommended for acute ischemic stroke (AIS in patients under the age of 18 and published experience is limited. In this case report, we describe two children treated with systemic thrombolytic therapy. One child received additional mechanical revascularization and achieved a good clinical outcome. The differences in the fibrinolytic system and the different etiology of AIS in childhood may limit a simple extrapolation of the adult guidelines for systemic thrombolytic therapy. Acute multimodal imaging to clarify the etiology of AIS might help to select the most appropriate treatment modality.

  1. Immunoendocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin of locally advanced or metastatic endocrine tumors.

    Science.gov (United States)

    Lissoni, P; Barni, S; Tancini, G; Mainini, E; Piglia, F; Maestroni, G J; Lewinski, A

    1995-01-01

    Recent evidence has shown that endocrine tumors are under an endocrine and an immune regulation, and that biotherapies with interferon or the long-acting somatostatin analog octreotide may be effective in the control of tumor growth and clinical symptomatology. Within the biotherapies of tumors, interleukin-2(IL-2) has appeared to play an essential role in the antitumor immune response. Despite its important antitumor role, very few studies have been carried out to investigate the possible use of IL-2 in the treatment of advanced endocrine tumors. Its potential toxicity would represent the main limiting factor for the clinical experiments with IL-2. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify the antitumor activity of IL-2, either through immunomodulating mechanisms or through a direct cytostatic activity by inhibiting tumor growth factor production. On this basis, we have performed a phase II pilot study with low-dose IL-2 plus MLT in 14 patients with untreatable endocrine tumors because of disseminated disease, lack of response to previous standard biotherapies or chemotherapies, or tumors for whom no effective therapy is available. Thyroid cancers, carcinoid and endodrine pancreatic tumors were the most frequent neoplasms. IL-2 was given at 3 million IU/day s.c. at 8 p.m. for 6 days/week for 4 weeks, corresponding to one cycle. MLT was given orally at 40 mg/day at 8 p.m. every day. In nonprogressed patients, a second cycle was given after a 21-day rest period. Patients were considered as evaluable when they received at least one complete cycle, and 12 patients were fully evaluable. According to WHO criteria, a partial response was achieved in 3/12 (25%) patients (carcinoid tumor: 1; neuroendocrine lung tumor: 1; pancreatic islet cell tumor: 1). Another patient with gastrinoma had a more than 50% reduction of tumor markers. Toxicity was low in all patients. This preliminary study suggests that low-dose IL-2 immunotherapy in

  2. Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure

    Science.gov (United States)

    Peck, Amy R.; Witkiewicz, Agnieszka K.; Liu, Chengbao; Stringer, Ginger A.; Klimowicz, Alexander C.; Pequignot, Edward; Freydin, Boris; Tran, Thai H.; Yang, Ning; Rosenberg, Anne L.; Hooke, Jeffrey A.; Kovatich, Albert J.; Nevalainen, Marja T.; Shriver, Craig D.; Hyslop, Terry; Sauter, Guido; Rimm, David L.; Magliocco, Anthony M.; Rui, Hallgeir

    2011-01-01

    Purpose To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy. Patients and Methods Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. Results Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). Conclusion Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy. PMID:21576635

  3. The impact of age on local control in women with pT1 breast cancer treated with conservative surgery and radiation therapy.

    Science.gov (United States)

    Jobsen, J J; van der Palen, J; Meerwaldt, J H

    2001-10-01

    The aim of the study was to evaluate the importance of young age with regard to local control in a prospective cohort of 1085 women with pathological T1 tumours treated with breast conservative treatment (BCT). Patients were divided into two age groups: 40 years or younger, 7.8%, and older than 40 years, 92.2%. With a median follow-up of 71 months, the local recurrence rate was 10.6% in women 40 years (P=0.0046). A separate analysis showed a significantly decreased LRFS for young women with a positive family history, 75.4% versus 98.4% 5-year LRFS for older women. A worse LRFS for young women with a negative lymph node status was also observed, respectively 84% versus 98% 5-year LRFS (both P<0.001). In a multivariate analysis, taking into account the pre-treatment and treatment factors, age < or =40 years, was the only significant predictor of a decreased LRFS. Thus, young age is an important factor in relation to local control. In a subset analysis, this significant adverse effect of young age on outcome appears to be limited to the node-negative patients and those with a positive family history. To date, there is no evidence that young women with pT1 breast cancer, treated by mastectomy have an improved outcome when compared with those treated with conservative surgery and radiotherapy. Taking into account results from a subset analysis suggests that giving systemic therapy to a subgroup of women who are < or =40 years, node-negative and/or have a positive family history might give a better local control.

  4. Prognostic comparison of operative and non-operative therapies for intracerebral hemorrhage in a local hospital: Case retrospection

    Institute of Scientific and Technical Information of China (English)

    Deming Zhao; Zenghong Jiang; Bin Wang

    2006-01-01

    BACKGROUND: At present, it is satisfactory for micro-trauma craniopuncture therapy for cerebral hemor rhage to treat spontaneous intracerebral hemorrhage (ICH). Surgical treatment can decrease fatality rate of ICH patients; however, some reports suggest that there are no obvious differences of therapeutic effects between surgical treatment and medical therapy because of various states, operative indications, contraindi cations and operative styles.OBJECTIVE: To observe the effect of surgical treatment on ICH prognosis, especially on fatality rate. DESIGN: Retrospective-case study.SETTING: Huaibei People's Hospital. PARTICIPANTS: ① A total of 241 ICH patients selected from Huaibei People's Hospital from January 1988 to May 1989 were regarded as group A. They were all coincidence with Diagnostic Criteria of Intracerebral Hemorrhage in the National Cerebrovascular Disease Academic Meeting. There were 154 males and 87 females aged 34-94 years, and among them, 230 patients were older than 50 years (95.4%). Hemorrhage sites: Among 142 patients, 85 cases had internal capsule hemorrhage, 18 external capsule hemorrhage, 15 thalamic hemorrhage, 9 cerebellar hemorrhage, 7 brain stem hemorrhage, 7 cerebral lobe hemorrhage, and 1 corpus callosum hemorrhage. Hemorrhage volume: Among 89 clear records, 44 cases had of 1-10 mL, 35 of 11-30 mL, 5 of 31-40 mL, and 5 of 41-80 mL. Except 2 patients, other ones were treated with medical operation. ② A total of 203 ICH patients selected from the same hospital from January 2003 to December 2005 were regarded as group B. Among them, 72 cases were treated with operation, but other 131 ones were treated with non-operation. They were all diagnosed with CT. There were 113 males and 90 females aged 30-88 years, and among them, 183 patients were older than 50 years (90.1%). Hemorrhage sites: Among 203 patients, 104 cases had internal capsule hemorrhage, 17 external capsule hemorrhage, 19 thalamic hemorrhage, 9 cerebellar hemorrhage, 12 brain

  5. Protocol-based image-guided salvage brachytherapy. Early results in patients with local failure of prostate cancer after radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lahmer, G.; Lotter, M.; Kreppner, S.; Fietkau, R.; Strnad, V. [University Hospital Erlangen (Germany). Dept. of Radiation Oncology

    2013-08-15

    Purpose: To assess the overall clinical outcome of protocol-based image-guided salvage pulsed-dose-rate brachytherapy for locally recurrent prostate cancer after radiotherapy failure particularly regarding feasibility and side effects. Patients and methods: Eighteen consecutive patients with locally recurrent prostate cancer (median age, 69 years) were treated during 2005-2011 with interstitial PDR brachytherapy (PDR-BT) as salvage brachytherapy after radiotherapy failure. The treatment schedule was PDR-BT two times with 30 Gy (pulse dose 0.6 Gy/h, 24 h per day) corresponding to a total dose of 60 Gy. Dose volume adaptation was performed with the aim of optimal coverage of the whole prostate (V{sub 100} > 95 %) simultaneously respecting the protocol-based dose volume constraints for the urethra (D{sub 0.1} {sub cc} < 130 %) and the rectum (D{sub 2} {sub cc} < 50-60 %) taking into account the previous radiation therapy. Local relapse after radiotherapy (external beam irradiation, brachytherapy with J-125 seeds or combination) was confirmed mostly via choline-PET and increased PSA levels. The primary endpoint was treatment-related late toxicities - particularly proctitis, anal incontinence, cystitis, urinary incontinence, urinary frequency/urgency, and urinary retention according to the Common Toxicity Criteria. The secondary endpoint was PSA-recurrence-free survival. Results: We registered urinary toxicities only. Grade 2 and grade 3 toxicities were observed in up to 11.1 % (2/18) and 16.7 % (3/18) of patients, respectively. The most frequent late-event grade 3 toxicity was urinary retention in 17 % (3/18) of patients. No late gastrointestinal side effects occurred. The biochemical PSA-recurrence-free survival probability at 3 years was 57.1 %. The overall survival at 3 years was 88.9 %; 22 % (4/18) of patients developed metastases. The median follow-up time for all patients after salvage BT was 21 months (range, 8-77 months). Conclusion: Salvage PDR

  6. Five-year Local Control in a Phase II Study of Hypofractionated Intensity Modulated Radiation Therapy With an Incorporated Boost for Early Stage Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Freedman, Gary M., E-mail: Gary.Freedman@uphs.upenn.edu [Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Anderson, Penny R. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Bleicher, Richard J. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Litwin, Samuel; Li Tianyu [Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Swaby, Ramona F. [Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Ma, Chang-Ming Charlie; Li Jinsheng [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Sigurdson, Elin R. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Watkins-Bruner, Deborah [School of Nursing, Emory University, Atlanta, Georgia (United States); Morrow, Monica [Department of Surgical Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goldstein, Lori J. [Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States)

    2012-11-15

    Purpose: Conventional radiation fractionation of 1.8-2 Gy per day for early stage breast cancer requires daily treatment for 6-7 weeks. We report the 5-year results of a phase II study of intensity modulated radiation therapy (IMRT), hypofractionation, and incorporated boost that shortened treatment time to 4 weeks. Methods and Materials: The study design was phase II with a planned accrual of 75 patients. Eligibility included patients aged {>=}18 years, Tis-T2, stage 0-II, and breast conservation. Photon IMRT and an incorporated boost was used, and the whole breast received 2.25 Gy per fraction for a total of 45 Gy, and the tumor bed received 2.8 Gy per fraction for a total of 56 Gy in 20 treatments over 4 weeks. Patients were followed every 6 months for 5 years. Results: Seventy-five patients were treated from December 2003 to November 2005. The median follow-up was 69 months. Median age was 52 years (range, 31-81). Median tumor size was 1.4 cm (range, 0.1-3.5). Eighty percent of tumors were node negative; 93% of patients had negative margins, and 7% of patients had close (>0 and <2 mm) margins; 76% of cancers were invasive ductal type: 15% were ductal carcinoma in situ, 5% were lobular, and 4% were other histology types. Twenty-nine percent of patients 29% had grade 3 carcinoma, and 20% of patients had extensive in situ carcinoma; 11% of patients received chemotherapy, 36% received endocrine therapy, 33% received both, and 20% received neither. There were 3 instances of local recurrence for a 5-year actuarial rate of 2.7%. Conclusions: This 4-week course of hypofractionated radiation with incorporated boost was associated with excellent local control, comparable to historical results of 6-7 weeks of conventional whole-breast fractionation with sequential boost.

  7. Four-Week Neoadjuvant Intensity-Modulated Radiation Therapy With Concurrent Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer Patients: A Validation Phase II Trial

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    Arbea, Leire, E-mail: larbea@unav.es [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain); Martinez-Monge, Rafael; Diaz-Gonzalez, Juan A.; Moreno, Marta; Rodriguez, Javier [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain); Hernandez, Jose Luis [Department of General Surgery, Clinica Universidad de Navarra, Navarra (Spain); Sola, Jesus Javier [Department of Pathology, Clinica Universidad de Navarra, Navarra (Spain); Ramos, Luis Isaac [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain); Subtil, Jose Carlos [Department of Gastroenterology, Clinica Universidad de Navarra, Navarra (Spain); Nunez, Jorge [Department of Preventive Medicine and Public Health, Clinica Universidad de Navarra, Navarra (Spain); Chopitea, Ana; Cambeiro, Mauricio; Gaztanaga, Miren; Garcia-Foncillas, Jesus; Aristu, Javier [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain)

    2012-06-01

    Purpose: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. Methods and Materials: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m{sup 2} b.i.d., Monday to Friday) and oxaliplatin (60 mg/m{sup 2} on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. Results: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. Conclusions: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.

  8. Urethrogram-directed Stereotactic Body Radiation Therapy (SBRT for Clinically Localized Prostate Cancer in Patients with Contraindications to Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Ima ePaydar

    2015-09-01

    Full Text Available Purpose: Magnetic resonance imaging (MRI-directed stereotactic body radiation therapy (SBRT has been established as a safe and effective treatment for prostate cancer. For patients with contraindications to MRI, CT-urethrogram is an alternative imaging approach to identify the location of the prostatic apex to guide treatment. This study sought to evaluate the safety of urethrogram-directed SBRT for prostate cancer.Methods: Between February 2009 and January 2014, 31 men with clinically localized prostate cancer were treated definitively with urethrogram-directed SBRT with or without supplemental intensity modulated radiation therapy (IMRT at Georgetown University Hospital. SBRT was delivered either as a primary treatment of 35-36.25 Gray (Gy in 5 fractions or as a boost of 19.5 Gy in 3 fractions followed by supplemental conventionally fractionated intensity modulated radiation therapy (45-50.4 Gy. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0.Results: The median patient age was 70 years with a median prostate volume of 38 cc. The median follow-up was 3.7 years. The patients were elderly (Median age = 70, and comorbidities were common (Carlson Comorbidity Index > 2 in 36%. 71% of patients utilized alpha agonists prior to treatment, and 9.7% had prior procedures for benign prostatic hyperplasia (BPH. The 3-year actuarial incidence rates of > Grade 3 GU toxicity and > Grade 2 GI toxicity were 3.2% and 9.7%, respectively. There were no Grade 4 or 5 toxicities.Conclusions: MRI is the preferred imaging modality to guide prostate SBRT treatment. However, urethrogram-directed SBRT is a safe alternative for the treatment of patients with prostate cancer who are unable to undergo MRI.

  9. High-grade acute organ toxicity as positive prognostic factor in primary radio(chemo)therapy for locally advanced, inoperable head and neck cancer

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    Wolff, Hendrik Andreas; Bosch, Jan; Hennies, Steffen; Hess, Clemens F.; Christiansen, Hans [Dept. of Radiotherapy and Radiooncology, Univ. Medicine Goettingen (Germany); Jung, Klaus [Dept. of Medical Statistics, Univ. Medicine Goettingen (Germany); Overbeck, Tobias [Dept. of Haematology and Oncology, Univ. Medicine Goettingen (Germany); Matthias, Christoph; Roedel, Ralph M. [Dept. of Otorhinolaryngology, Univ. Medicine Goettingen (Germany)

    2010-05-15

    Purpose: to test for a possible correlation between high-grade acute organ toxicity during primary radio(chemo)therapy and treatment outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Patients and methods: from 05/1994 to 01/2009, 216 HNSCC patients were treated with radio(chemo)therapy in primary approach. They received normofractionated (2 Gy/fraction) irradiation including associated nodal drainage sites to a cumulative dose of 70 Gy. 151 patients received additional concomitant chemotherapy (111 patients 5-fluorouracil/mitomycin C, 40 patients cisplatin-based). Toxicity during treatment was monitored weekly according to the Common Toxicity Criteria (CTC), and any toxicity grade CTC {>=} 3 of mucositis, dysphagia or skin reaction was assessed as high-grade acute organ toxicity for later analysis. Results: a statistically significant coherency between high-grade acute organ toxicity and overall survival as well as locoregional control was found: patients with CTC {>=} 3 acute organ toxicity had a 5-year overall survival rate of 4% compared to 8% in patients without (p < 0.01). Thereby, multivariate analyses revealed that the correlation was independent of other possible prognostic factors or factors that may influence treatment toxicity, especially concomitant chemotherapy and radiotherapy technique or treatment-planning procedure. Conclusion: these data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, as high-grade acute organ toxicity during radio(chemo)therapy showed to be an independent prognostic marker in the own patient population. However, the authors are aware of the fact that a multivariate analysis in a retrospective study generally has statistical limitations. Therefore, their hypothesis should be further analyzed on biomolecular and clinical levels and other tumor entities in prospective trials. (orig.)

  10. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Feddock, Jonathan, E-mail: jmfedd0@uky.edu [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States); Arnold, Susanne M. [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States); Department of Medical Oncology, University of Kentucky, Lexington, Kentucky (United States); Shelton, Brent J. [Department of Biostatistics, University of Kentucky, Lexington, Kentucky (United States); Sinha, Partha; Conrad, Gary [Department of Radiology, University of Kentucky, Lexington, Kentucky (United States); Chen, Li [Department of Biostatistics, University of Kentucky, Lexington, Kentucky (United States); Rinehart, John [Department of Medical Oncology, University of Kentucky, Lexington, Kentucky (United States); McGarry, Ronald C. [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States)

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ≥3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  11. Health-Related Quality of Life After Stereotactic Body Radiation Therapy for Localized Prostate Cancer: Results From a Multi-institutional Consortium of Prospective Trials

    Energy Technology Data Exchange (ETDEWEB)

    King, Christopher R., E-mail: crking@mednet.ucla.edu [Department of Radiation Oncology, University of California, Los Angeles, California (United States); Collins, Sean [Department of Radiation Oncology, Georgetown University, Washington, District of Columbia (United States); Fuller, Donald [Genesis Healthcare Partners, San Diego, California (United States); Wang, Pin-Chieh; Kupelian, Patrick; Steinberg, Michael [Department of Radiation Oncology, University of California, Los Angeles, California (United States); Katz, Alan [Flushing Radiation Oncology, Flushing, New York (United States)

    2013-12-01

    Purpose: To evaluate the early and late health-related quality of life (QOL) outcomes among prostate cancer patients following stereotactic body radiation therapy (SBRT). Methods and Materials: Patient self-reported QOL was prospectively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer. Data from the Expanded Prostate Cancer Index Composite (EPIC) instrument were obtained at baseline and at regular intervals up to 6 years. SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions. A short course of androgen deprivation therapy was given to 14% of patients. Results: Median follow-up was 3 years and 194 patients remained evaluable at 5 years. A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years. The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities. Sexual QOL decline was predominantly observed within the first 9 months, a pattern not altered by the use of androgen deprivation therapy or patient age. Conclusion: Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL. A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels. With a large number of patients evaluable up to 5 years following SBRT, it is unlikely that unexpected late adverse effects will manifest themselves.

  12. Clinical Usefulness of {sup 18}F-Fluorodeoxyglucose-Positron Emission Tomography in Patients With Locally Advanced Pancreatic Cancer Planned to Undergo Concurrent Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jee Suk; Choi, Seo Hee; Lee, Youngin; Kim, Kyung Hwan [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Jeong Youp; Song, Si Young [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Arthur; Yun, Mijin; Lee, Jong Doo [Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil, E-mail: jsseong@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-09-01

    Purpose: To assess the role of coregistered {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting radiographically occult distant metastasis (DM) at staging in patients with locally advanced pancreatic cancer (LAPC) and to study whether FDG-PET parameters can predict relatively long-term survival in patients who are more likely to benefit from chemoradiation therapy (CRT). Methods and Materials: From our institutional database, we identified 388 LAPC patients with M0 on conventional computed tomography (CT) who were planned to undergo CRT. Coregistered FDG-PET staging was offered to all patients, and follow-up FDG-PET was used at the clinical discretion of the physician. Results: FDG-PET detected unsuspected CT-occult DM in 33% of all 388 patients and allowed them to receive systemic therapy immediately. The remaining 260 patients (PET-M0) underwent CRT selectively as an initial treatment. Early DM arose in 13.1% of 260 patients, and the 1-year estimated locoregional recurrence rate was 5.4%. Median overall survival (OS) and progression-free survival (PFS) were 14.6 and 9.3 months, respectively, at a median follow-up time of 32.3 months (range, 10-99.1 months). Patients with a baseline standardized uptake value (SUV) <3.5 and/or SUV decline ≥60% had significantly better OS and PFS than those having none, even after adjustment for all potential confounding variables (all P<.001). Conclusions: FDG-PET can detect radiographically occult DM at staging in one-third of patients and spare them from the potentially toxic therapy. Additionally, FDG-PET parameters including baseline SUV and SUV changes may serve as useful clinical markers for predicting the prognosis in LAPC patients.

  13. The prognostic value of expression of HIF1α, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy

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    Weber Damien C

    2012-04-01

    Full Text Available Abstract Purpose Androgens stimulate the production of hypoxia-inducible factor (HIF1α and ultimately vascular endothelial growth factor (VEGF-A. Additionally, epithelial growth factor (EGF mediates HIF1α production. Carbonic anhydrase IX (CAIX expression is associated with tumor cell hypoxia in a variety of malignancies. This study assesses the prognostic relation between HIF1α, VEGF-A, EGF Receptor and CAIX expression by immunochemistry in diagnostic samples of patients with intermediate- and high-risk localized prostate cancer treated with radiation therapy, with or without androgen deprivation therapy (ADT. Materials and methods Between 1994 and 2004, 103 prostate cancer patients (mean age, 68.7 ± 6.2, with prostate cancer (mean PSA, 13.3 ± 3.7, were treated with radiation therapy (RT, median dose, 74 Gy. Fifty seven (55.3% patients received ADT (median duration, 6 months; range, 0 – 24. Median follow-up was 97.6 months (range, 5.9 – 206.8. Results Higher EGFR expression was significantly (p = 0.04 correlated with higher Gleason scores. On univariate analysis, HIF1α nuclear expression was a significant (p = 0.02 prognostic factor for biological progression-free survival (bPFS. A trend towards significance (p = 0.05 was observed with EGFR expression and bPFS. On multivariate analysis, low HIF1α nuclear (p = 0.01 and high EGFR (p = 0.04 expression remained significant adverse prognostic factors. Conclusions Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis.

  14. Local tumor control and toxicity in HIV-associated anal carcinoma treated with radiotherapy in the era of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Lütolf Urs M

    2006-08-01

    Full Text Available Abstract Purpose To investigate the outcome of HIV-seropositive patients under highly active antiretroviral treatment (HAART with anal cancer treated with radiotherapy (RT alone or in combination with standard chemotherapy (CT. Patients and methods Clinical outcome of 81 HIV-seronegative patients (1988 – 2003 and 10 consecutive HIV-seropositive patients under HAART (1997 – 2003 that were treated with 3-D conformal RT of 59.4 Gy and standard 5-fluorouracil and mitomycin-C were retrospectively analysed. 10 TNM-stage and age matched HIV-seronegative patients (1992 – 2003 were compared with the 10 HIV-seropositive patients. Pattern of care, local disease control (LC, overall survival (OS, cancer-specific survival (CSS, and toxicity were assessed. Results RT with or without CT resulted in complete response in 100 % of HIV-seropositive patients. LC was impaired compared to matched HIV-seronegative patients after a median follow-up of 44 months (p = 0.03. OS at 5 years was 70 % in HIV-seropositive patients receiving HAART and 69 % in the matched controls. Colostomy-free survival was 70 % (HIV+ and 100 % (matched HIV- and 78 % (all HIV-. No HIV-seropositive patient received an interstitial brachytherapy boost compared to 42 % of all HIV-seronegative patients and adherence to chemotherapy seemed to be difficult in HIV-seropositive patients. Acute hematological toxicity reaching 50 % was high in HIV-seropositive patients receiving MMC compared with 0 % in matched HIV-seronegative patients (p = 0.05 or 12 % in all HIV-seronegative patients. The rate of long-term side effects was low in HIV-seropositive patients. Conclusion Despite high response rates to organ preserving treatment with RT with or without CT, local tumor failure seems to be high in HIV-positive patients receiving HAART. HIV-seropositive patients are subject to treatment bias, being less likely treated with interstitial brachytherapy boost probably due to HIV-infection, and they are at

  15. Gene expression of fibrinolytic factors urokinase plasminogen activator and plasminogen activator inhibitor-1 in rabbit temporo-mandibular joint cartilage with disc displacement

    Institute of Scientific and Technical Information of China (English)

    ZHAN Jing; GU Zhi-yuan; WU Li-qun; ZHANG Yin-kai; HU Ji-an

    2005-01-01

    Background The urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling. Methods Disc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques. Results The expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks. Conclusions The expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.

  16. The biotechnological potential of subtilisin-like fibrinolytic enzyme from a newly isolated Lactobacillus plantarum KSK-II in blood destaining and antimicrobials.

    Science.gov (United States)

    Kotb, Essam

    2015-01-01

    An antimicrobial oxidative- and SDS-stable fibrinolytic alkaline protease designated as KSK-II was produced by Lactobacillus plantarum KSK-II isolated from kishk, a traditional Egyptian food. Maximum enzyme productivity was obtained in medium containing 1% lactose and 0.5% soybean flour as carbon and nitrogen sources, respectively. Purification of enzyme increased its specific activity to 1,140-fold with a recovery of 33% and molecular weight of 43.6 kDa. Enzyme activity was totally lost in the presence of ethylenediaminetetraacetic acid and was restored after addition of Fe(2+) suggesting that KSK-II is a metalloprotease and Fe(2+) acts as cofactor. Enzyme hydrolyzed not only the natural proteins but also synthetic substrates, particularly Suc-Ala-Ala-Pro-Phe-pNA. KSK-II can hydrolyze the Lys-X easier than Arg-X; thus, it was considered as a subtilisin-family protease. Its apparent Km , Vmax , and Kcat were 0.41 mM, 6.4 µmol mg(-1) min(-1) , and 28.0 s(-1) , respectively. KSK-II is industrially important from the perspectives of its maximal activity at 50°C (stable up to 70°C), ability to function at alkaline pH (10.0), stability at broad pH ranges (7.5-12.0) in addition to its stability toward SDS, H2 O2 , organic solvents, and detergents. We emphasize for the first time the potential of fibrinolytic activity for alkaline proteases used in detergents especially in blood destaining. © 2014 American Institute of Chemical Engineers.

  17. Combined treatment of ulinastatin and tranexamic acid provides beneficial effects by inhibiting inflammatory and fibrinolytic response in patients undergoing heart valve replacement surgery.

    Science.gov (United States)

    Chen, Ting-Ting; Jiandong-Liu; Wang, Gang; Jiang, Sheng-Li; Li, Li-Bing; Gao, Chang-Qing

    2013-02-01

    To investigate the effect of ulinastatin and tranexamic acid administered alone or in combination on inflammatory cytokines and fibrinolytic system in patients undergoing heart valve replacement surgery during cardiopulmonary bypass (CPB). CPB-induced fibrinolytic hyperfunction and systemic inflammatory response syndrome (SIRS) are the leading causes responsible for the occurrence of postsurgical complications such as postsurgical cardiac insufficiency and lung injury, which may lead to an increase in postsurgical bleeding, prolongation of hospital stay, and increased costs. One hundred twenty patients undergoing heart valve replacement surgery during CPB were randomly assigned into 4 groups of 30 patients each: blank control group (Group C), tranexamic acid group (Group T), ulinastatin group (Group U), and tranexamic acid-ulinastatin combination group (Group D). Physiological saline, tranexamic acid, ulinastatin, and a combination of tranexamic acid and ulinastatin were given to each group, respectively. Arterial blood was collected from the radial artery at 4 time points: after induction of anesthesia (T1), unclamping the ascending aorta (T2), and at 1 hour (T3) and 24 hours (T4) after CPB. The levels of plasma tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), neutrophil elastase (NE), and the concentrations of tissue plasminogen activator (t-PA) and α2-antiplasmin (α2-AP) were detected. The changes in the volume of pericardial mediastinal drainage after surgery were observed and recorded. The plasma TNF-α, IL-6, and NE levels significantly increased in patients from all 4 groups at time points of T2, T3, and T4 in comparison to those before CPB (P surgery (P surgery.

  18. Low in vitro third-body wear on total hip prostheses induced by calcium sulphate used for local antibiotic therapy

    Directory of Open Access Journals (Sweden)

    R Heuberger

    2014-10-01

    Full Text Available In case of implant associated infection, implant preservation is associated with high failure rates. Therefore, a removal or exchange of the implant is most often mandatory for treatment success. Alternatively, under certain conditions, local antibiotic delivery can be applied – preserving the implant, using for example calcium sulphate as a resorbable carrier. In this work, third-body wear on total hip prostheses caused by calcium sulphate particles was tested in a hip simulator. Inlays made of ultra-high-molecular-weight polyethylene (UHMWPE and cross-linked polyethylene (XLPE against 28 mm CoCrMo heads and 36 mm alumina pairings were tested in triplicate, both with and without calcium sulphate particles in the test liquid. Neither the alumina articulations nor the CoCrMo heads were affected by the calcium sulphate particles since calcium sulphate is a relatively soft material. The polyethylene inlays showed 39-89 % higher wear during exposure compared to references, but wear returned to normal when no more particles were added. Thus, calcium sulphate might be used as antibiotic carrier even in the presence of total hip prostheses without fearing excessive third-body wear.

  19. Low in vitro third-body wear on total hip prostheses induced by calcium sulphate used for local antibiotic therapy.

    Science.gov (United States)

    Heuberger, R; Wahl, P; Krieg, J; Gautier, E

    2014-10-23

    In case of implant associated infection, implant preservation is associated with high failure rates. Therefore, a removal or exchange of the implant is most often mandatory for treatment success. Alternatively, under certain conditions, local antibiotic delivery can be applied - preserving the implant, using for example calcium sulphate as a resorbable carrier. In this work, third-body wear on total hip prostheses caused by calcium sulphate particles was tested in a hip simulator. Inlays made of ultra-high-molecular-weight polyethylene (UHMWPE) and cross-linked polyethylene (XLPE) against 28 mm CoCrMo heads and 36 mm alumina pairings were tested in triplicate, both with and without calcium sulphate particles in the test liquid. Neither the alumina articulations nor the CoCrMo heads were affected by the calcium sulphate particles since calcium sulphate is a relatively soft material. The polyethylene inlays showed 39-89 % higher wear during exposure compared to references, but wear returned to normal when no more particles were added. Thus, calcium sulphate might be used as antibiotic carrier even in the presence of total hip prostheses without fearing excessive third-body wear.

  20. Multiorganelle Localization of Metallated Phthalocyanine Photosensitizer in Colorectal Cancer Cells (DLD-1 and CaCo-2 Enhances Efficacy of Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Palesa Rose Sekhejane

    2014-01-01

    Full Text Available Colorectal cancer is the third most commonly diagnosed cancer. Amongst treatments that have been explored, photodynamic therapy (PDT is a treatment that is of interest as it poses ideal advantages such as affinity for cancer cells. This study aimed to determine the correlation between the localization site of a sulfonated zinc phthalocyanine (ZnPcSmix photosensitizer (PS and its associated cell death pathway in vitro in colorectal cancer cell lines (DLD-1 and CaCo-2. Visible morphological changes were observed in PDT treated cells after 24 h. Reactive oxygen species (ROS were detected and visualized 1 h after PDT. ZnPcSmix was predominantly localized in lysosomes and partially in the mitochondria. FITC Annexin V staining showed a significant decrease in the percentage of viable DLD-1 and CaCo-2 cells 24 h after PDT, with an increase in apoptotic cell population. Moreover, there was a significant increase in both cathepsin D and cytochrome C at 1 and 24 h. In conclusion, ZnPcSmix showed the ability of inducing apoptotic cell death features in PDT treated cells.

  1. Salvage brachytherapy in combination with interstitial hyperthermia for locally recurrent prostate carcinoma following external beam radiation therapy: a prospective phase II study.

    Science.gov (United States)

    Kukiełka, Andrzej M; Strnad, Vratislav; Stauffer, Paul; Dąbrowski, Tomasz; Hetnał, Marcin; Nahajowski, Damian; Walasek, Tomasz; Brandys, Piotr; Matys, Robert

    2015-06-01

    Optimal treatment for patients with only local prostate cancer recurrence after external beam radiation therapy (EBRT) failure remains unclear. Possible curative treatments are radical prostatectomy, cryosurgery, and brachytherapy. Several single institution series proved that high-dose-rate brachytherapy (HDRBT) and pulsed-dose-rate brachytherapy (PDRBT) are reasonable options for this group of patients with acceptable levels of genitourinary and gastrointestinal toxicity. A standard dose prescription and scheme have not been established yet, and the literature presents a wide range of fractionation protocols. Furthermore, hyperthermia has shown the potential to enhance the efficacy of re-irradiation. Consequently, a prospective trial is urgently needed to attain clear structured prospective data regarding the efficacy of salvage brachytherapy with adjuvant hyperthermia for locally recurrent prostate cancer. The purpose of this report is to introduce a new prospective phase II trial that would meet this need. The primary aim of this prospective phase II study combining Iridium-192 brachytherapy with interstitial hyperthermia (IHT) is to analyze toxicity of the combined treatment; a secondary aim is to define the efficacy (bNED, DFS, OS) of salvage brachytherapy. The dose prescribed to PTV will be 30 Gy in 3 fractions for HDRBT, and 60 Gy in 2 fractions for PDRBT. During IHT, the prostate will be heated to the range of 40-47°C for 60 minutes prior to brachytherapy dose delivery. The protocol plans for treatment of 77 patients.

  2. Hyperbaric oxygen therapy ameliorates local brain metabolism, brain edema and inflammatory response in a blast-induced traumatic brain injury model in rabbits.

    Science.gov (United States)

    Zhang, Yongming; Yang, Yanyan; Tang, Hong; Sun, Wenjiang; Xiong, Xiaoxing; Smerin, Daniel; Liu, Jiachuan

    2014-05-01

    Many studies suggest that hyperbaric oxygen therapy (HBOT) can provide some clinically curative effects on blast-induced traumatic brain injury (bTBI). The specific mechanism by which this occurs still remains unknown, and no standardized time or course of hyperbaric oxygen treatment is currently used. In this study, bTBI was produced by paper detonators equivalent to 600 mg of TNT exploding at 6.5 cm vertical to the rabbit's head. HBO (100% O2 at 2.0 absolute atmospheres) was used once, 12 h after injury. Magnetic resonance spectroscopy was performed to investigate the impact of HBOT on the metabolism of local injured nerves in brain tissue. We also examined blood-brain barrier (BBB) integrity, brain water content, apoptotic factors, and some inflammatory mediators. Our results demonstrate that hyperbaric oxygen could confer neuroprotection and improve prognosis after explosive injury by promoting the metabolism of local neurons, inhibiting brain edema, protecting BBB integrity, decreasing cell apoptosis, and inhibiting the inflammatory response. Furthermore, timely intervention within 1 week after injury might be more conducive to improving the prognosis of patients with bTBI.

  3. Imaging of Caenorhabditis elegans samples and sub-cellular localization of new generation photosensitizers for photodynamic therapy, using non-linear microscopy

    Science.gov (United States)

    Filippidis, G.; Kouloumentas, C.; Kapsokalyvas, D.; Voglis, G.; Tavernarakis, N.; Papazoglou, T. G.

    2005-08-01

    Two-photon excitation fluorescence (TPEF) and second-harmonic generation (SHG) are relatively new promising tools for the imaging and mapping of biological structures and processes at the microscopic level. The combination of the two image-contrast modes in a single instrument can provide unique and complementary information concerning the structure and the function of tissues and individual cells. The extended application of this novel, innovative technique by the biological community is limited due to the high price of commercial multiphoton microscopes. In this study, a compact, inexpensive and reliable setup utilizing femtosecond pulses for excitation was developed for the TPEF and SHG imaging of biological samples. Specific cell types of the nematode Caenorhabditis elegans were imaged. Detection of the endogenous structural proteins of the worm, which are responsible for observation of SHG signals, was achieved. Additionally, the binding of different photosensitizers in the HL-60 cell line was investigated, using non-linear microscopy. The sub-cellular localization of photosensitizers of a new generation, very promising for photodynamic therapy (PDT), (Hypericum perforatum L. extracts) was achieved. The sub-cellular localization of these novel photosensitizers was linked with their photodynamic action during PDT, and the possible mechanisms for cell killing have been elucidated.

  4. Imaging of Caenorhabditis elegans samples and sub-cellular localization of new generation photosensitizers for photodynamic therapy, using non-linear microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Filippidis, G [Institute of Electronic Structure and Laser, Foundation of Research and Technology-Hellas, PO Box 1527, 71110 Heraklion (Greece); Kouloumentas, C [Institute of Electronic Structure and Laser, Foundation of Research and Technology-Hellas, PO Box 1527, 71110 Heraklion (Greece); Kapsokalyvas, D [Institute of Electronic Structure and Laser, Foundation of Research and Technology-Hellas, PO Box 1527, 71110 Heraklion (Greece); Voglis, G [Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion 71110, Crete (Greece); Tavernarakis, N [Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion 71110, Crete (Greece); Papazoglou, T G [Institute of Electronic Structure and Laser, Foundation of Research and Technology-Hellas, PO Box 1527, 71110 Heraklion (Greece)

    2005-08-07

    Two-photon excitation fluorescence (TPEF) and second-harmonic generation (SHG) are relatively new promising tools for the imaging and mapping of biological structures and processes at the microscopic level. The combination of the two image-contrast modes in a single instrument can provide unique and complementary information concerning the structure and the function of tissues and individual cells. The extended application of this novel, innovative technique by the