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Extensive deep vein thrombosis as a complication of testicular cancer treated with the BEP protocol (bleomycin, etoposide and cisplatin): case report/ Trombose venosa profunda extensa como complicação de um tumor do testículo tratado com o protocolo BEP (cisplatina, bleomicina e etoposide): relato de caso  

Scientific Electronic Library Online (English)

Full Text Available Abstract in portuguese CONTEXTO: Não há relatos na literatura de trombose venosa profunda (TVP) extensa associada ao protocolo de quimioterapia cisplatina, bleomicina e etoposite (BEP). RELATO DO CASO: O paciente era um adolescente de 18 anos com um tumor germinativo não-seminomatoso no testículo direito, com metástases pulmonares, hepáticas e retroperitoneais. Após orquiectomia radical, o paciente começou a receber quimioterapia de acordo com o protocolo BEP (sem profilaxia rotineira p (more) ara TVP). No quarto dia do ciclo, TVP massiva foi diagnosticada, estendendo-se das veias poplíteas até o segmento inferior da veia cava torácica. Tratamento trombolítico foi iniciado imediatamente com estreptoquinase. No segundo dia da terapia trombolítica, o paciente desenvolveu insuficiência renal aguda, devido ao acometimento das veias renais pela trombose. Estroptoquinase foi mantida por seis dias e o paciente teve evolução surpreendentemente favorável. Abstract in english CONTEXT: There are no reports in the literature of massive deep venous thrombosis (DVT) associated with cisplatin, bleomycin and etoposide (BEP) cancer treatment. CASE REPORT: The patient was a 18-year-old adolescent with a nonseminomatous germ cell tumor of the right testicle, with the presence of pulmonary, liver, and massive retroperitoneal metastases. Following radical orchiectomy, the patient started chemotherapy according to the BEP protocol (without routine prophyl (more) axis for DVT). On day 4 of the first cycle, massive DVT was diagnosed, extending from both popliteal veins up to the thoracic segment of the inferior vena cava. Thrombolytic therapy with streptokinase was immediately started. On day 2 of thrombolytic therapy, the patient developed acute renal failure, due to extension of the thrombosis to the renal veins. Streptokinase was continued for six days and the outcome was remarkably favorable.

Mano, Max Senna; Guimarães, José Luiz Miranda; Sutmöller, Sören Franz Marian Chicata; Reiriz, André Borba; Sutmöller, Christian Sandor Svend Chicata; Di Leo, Angelo

2006-11-01

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The treatment of metastatic germ-cell testicular tumours with bleomycin, etoposide and cis-platin (BEP).  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Between July 1979 and December 1981, 43 patients with metastatic germ-cell tumours (36 testicular non-seminomas and 7 testicular seminomas) were treated with 2-6 cycles of bleomycin, etoposide and cis-platin (BEP). Forty (93%) are alive, 37 (86%) with no evidence of disease. Of 36 men with testicula...

Peckham, M. J.; Barrett, A.; Liew, K. H.; Horwich, A.; Robinson, B.; Dobbs, H. J.; McElwain, T. J.; Hendry, W. F.

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The Effects of Chemotherapy with Bleomycin, Etoposide, and Cis-Platinum (BEP) on Rat Sperm Chromatin Remodeling, Fecundity and Testicular Gene Expression in the Progeny.  

UK PubMed Central (United Kingdom)

During spermiogenesis histones are replaced first by transition proteins and then by protamines resulting in a very condensed sperm DNA structure that is absolutely critical for normal sperm function. We have demonstrated previously that, despite a 9-wk recovery period, mature sperm from rats treated for 9 wk with bleomycin, etoposide, and cis-platinum (BEP), the drugs used to treat testicular cancer, have reduced levels of protamine 1 and a concomitant upregulation of specific histones, highlighting a problem in histone eviction. Here, we demonstrate that regulators of histone removal are increased in elongating spermatids following recovery; however, Ac-H4 and gammaH2AX histones remain elevated in elongating spermatids or caudal epididymal spermatozoa 9 wk post-BEP treatment. This indicates that chromatin remodelers and effector proteins that respond to histone removal cues may be a target of BEP treatment. A decrease in the expression of SMARCE1 in elongating spermatids may explain the persistent retention of histones in cauda epididymal sperm 9 wk after the cessation of BEP treatment. Remarkably, proteins implicated in the translational control and post-translational processing of protamine 1 are also significantly elevated 9 wk post-BEP treatment, suggesting that histone eviction may dictate the DNA availability for protamine binding. Males mated to control females 9 wk after BEP-treatment have reduced litter sizes; moreover, the profile of gene expression in the developing testes of their pups is altered. Altering the proportion of histones to protamine in mature spermatozoa has an adverse impact on male fecundity, with modifications to epigenetic marks potentially threatening normal progeny development.

Maselli J; Hales BF; Robaire B

2013-08-01

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[Comparative study of 2 chemotherapy induction protocols. Cisplatinum-methotrexate-bleomycin and oncovin-methotrexate-bleomycin].  

UK PubMed Central (United Kingdom)

A prospective randomized study was conducted in 77 patients with stages III and IV epidermoid carcinomas of the buccal cavity, oropharynx, and pharyngolaryngeal regions to compare effects of two induction chemotherapy regimens: cisplatinum, methotrexate, bleomycin, and oncovin, methotrexate, bleomycin. Tumoral response and complications were analyzed as a function of the regimen, the tumoral site, and the stage. Chemotherapy including cisplatinum provided a tumoral response in 58.8 p.cent of stage III pharyngolaryngeal epitheliomas as against 38.4 p.cent with oncovin, methotrexate, bleomycin, but with a higher frequency of complications.

Laccourreye H; Beutter P; Brasnu D; Lacau-Saint-Guily J; Bassot V; Garabedian N; Jacquillat C

1983-01-01

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Accelerated BEP: a phase I trial of dose-dense BEP for intermediate and poor prognosis metastatic germ cell tumour.  

UK PubMed Central (United Kingdom)

BACKGROUND: We used bleomycin, etoposide, cisplatin (BEP), the most effective regimen in the treatment of germ cell tumours (GCTs) and increased dose-density by using pegfilgrastim to shorten cycle length. Our aim was to assess safety and tolerability. METHODS: Sixteen male patients with intermediate or poor prognosis metastatic GCT were treated with four cycles of 3-day BEP with G-CSF on a 14-day cycle for a planned relative dose-density of 1.5 compared with standard BEP. RESULTS: Eleven intermediate and five poor prognosis patients were treated. In all, 14 of 16 patients completed the study treatment. Toxicities were comparable to previous studies using standard BEP, except for mucositis and haematological toxicity that were more severe. The overall relative dose-density for all 16 patients was mean 1.38 (range 0.72-1.5; median 1.46). Complete response was achieved after chemotherapy alone in two patients (13%) and following chemotherapy plus surgery in nine additional patients (56%). Four patients (25%) had a partial response and normalised their marker levels. At a median follow-up of 4.4 years (range 2.1-6.8) the estimated 5-year progression-free survival probability is 81% (95% CI 64-100%). CONCLUSION: Accelerated BEP is tolerable without major additional toxicity. A randomised controlled trial will be required to obtain comparative efficacy data.

Rimmer Y; Chester J; Joffe J; Stark D; Shamash J; Powles T; White J; Wason J; Parashar D; Armstrong G; Mazhar D; Williams MV

2011-09-01

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[Preliminary results of a preoperative polychemotherapy protocol in carcinomas of the pharyngo-larynx. Oncovin, methotrexate and bleomycin (author's transl)  

UK PubMed Central (United Kingdom)

213 squamous carcinomas of the pharyngo-larynx (piriform fossa, pharyngo-laryngeal junction and larynx) received preoperative chemotherapy in the form of oncovin, methotrexate and bleomycin (OMB). All the patients then underwent total or partial laryngectomy, associated with lymph node excision of some sort, followed by radiotherapy. A symptomatic improvement after OMB was seen in 21.2% of cases. Overall tumour response regardless of the site was 32%. Tumour response was all the better when lymph nodes were histologically free of disease (38.7% tumour response in N- as against 26.7% in N+). There was no significant difference in 1 year survival rates between those patients in whom there was a tumour response and those in whom tumour size remained the same.

Laccourreye H; Brasnu D; Beutter P; Chabolle F; de Braquilanges E; Strunski W

1981-01-01

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Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.  

UK PubMed Central (United Kingdom)

PURPOSE: This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with good-risk nonseminomatous germ cell tumors. PATIENTS AND METHODS: Between September 1989 and May 1993, a total of 598 patients with good-risk nonseminomatous germ cell tumors were randomized to receive four cycles of either BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3, and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20 mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the carboplatin dose was calculated from the glomerular filtration rate to achieve a serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21-day intervals to a total of four cycles. RESULTS: Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P = .009). There were 30 treatment failures in the 300 patients allocated to BEP and 79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P < .001), which led to failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%) and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P = .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90% (95% CI, 86% to 94%), respectively. CONCLUSION: With these drug doses and schedules, combination chemotherapy based on carboplatin was inferior to that based on cisplatin. This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.

Horwich A; Sleijfer DT; Fosså SD; Kaye SB; Oliver RT; Cullen MH; Mead GM; de Wit R; de Mulder PH; Dearnaley DP; Cook PA; Sylvester RJ; Stenning SP

1997-05-01

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Bleomycin--electrical pulse delivery: electroporation therapy-bleomycin--Genetronics; MedPulser-bleomycin--Genetronics.  

Science.gov (United States)

Genetronics Biomedical is using its electroporation therapy technology to deliver bleomycin to tumour cells for the treatment of cancer. Genetronics have developed the MedPulser Electroporation Therapy System, which consists of an electrical pulse generator and disposable electrode applicators. The MedPulser system enables the delivery of large molecules into cells by briefly applying an electric field to the cell. This causes a transient permeability in the cell's outer membrane characterised by the appearance of pores across the membrane. After the field is discontinued, the pores close, trapping the therapeutic molecules inside the target cells. Genetronics is using the MedPulser System in conjunction with bleomycin, an antineoplastic antibiotic that binds to DNA causing strand scissions. Genetronics is seeking a licensing partner for the use of electroporation for the delivery of drugs in chemotherapy. In 1998, Genetronics entered a licensing and development agreement with Ethicon for electroporation and electrofusion. Under the terms of this agreement, Ethicon was to develop and clinically test the Genetronics electroporation delivery system and conduct all regulatory activities throughout the world except Canada. Ethicon would also market the products once regulatory approval has been obtained and Genetronics was to receive a percentage of the net sales and as license fees. However, in July 2000, Ethicon exercised its rights to terminate the agreement without cause. All rights were returned to Genetronics in January 2001. In 1997, Genetronics entered an agreement with Abbott Laboratories for the manufacture of bleomycin for use in the US in its MedPulsar system after regulatory approval had been granted for its use in the treatment of solid tumours. In a separate supply agreement, Faulding Inc. has agreed to manufacture bleomycin for Genetronic for use in Canada after regulatory approval had been granted. The MedPulsar Electroporation Therapy System with bleomycin is currently in phase III pivotal studies in the US as a treatment for recurrent and second primary squamous cell carcinomas of the head and neck. Genetronics received approval for the Electroporation Therapy system as a device in March 1999 when it achieved CE Mark certification. In February 2004, Genetronics announced that it had completed a Special Protocol Assessment review process with the US FDA for two new trials that will compare bleomycin electroporation therapy to surgery. The primary endpoint will be tissue and function preservation rather than survival. One proposal is for recurrent head and neck cancer, and the other is for disfiguring cutaneous cancer. Three Institutional Review Boards in the US have approved the two protocols and Genetronics has initiated enrollment. In June 2004, Genetronics was granted fast-track status for its MedPulsar Electroporation Therapy System clinical development programme for patients with head and neck cancer. Shifting from a primary endpoint of survival to a quality-of-life outcome will enable those clinical trials to be carried out faster with less cost and with a higher likelihood of success. As a result, Genetronic's phase III trials focussing on survival as a primary endpoint have been discontinued. This includes a phase III trial for late-stage, recurrent head and neck cancer in combination with the normal standard of treatment compared with normal standard of treatment alone. Interim results from this trial had suggested bleomycin electroporation therapy demonstrated local tumour control and preservation of organ function, as well as non-inferiority when compared with surgery. This trial was initiated in May 2002. In March 2004, Genetronics initiated a post-European regulatory approval clinical study in patients with primary or recurrent squamous cell carcinoma of the head and neck (SCCHN). This study aims to enroll approximately 100 patients at 12-15 hospitals located in the UK, Germany, Italy, France, Austria and other western European countries. The study is designed to support the commercialisation o

2004-01-01

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Treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs. VIP) for poor-prognosis metastatic germ cell tumors  

Directory of Open Access Journals (Sweden)

Full Text Available Background: In patients with small-volume disseminated disease of germ cell tumors, cure can be achieved with four cycles of bleomycin, etoposide, and cisplatin (BEP). However, around 20% of these cases are not curable. Strategies to improve cure rates have shown that none of the currently available modalities were superior to the others. Among the most used ones, BEP and VIP (etoposide, cisplatin, and ifosfamide) have been the most studied. However, there are no reports comparing the two, except for a few in abstract forms from southern India. Therefore, we did a treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs VIP) that are used in poor-prognosis metastatic germ cell tumors. Materials and Methods: All male patients with germ cell tumors, diagnosed as having poor risk by IGCCCG, between January 2002 and December 2004 were included in the study. Clinical, laboratory, and other data were recorded. The patients were stratified into two categories on the basis of the type of chemotherapeutic regimen they received. Results: In all, 46 patients were analyzed, with a median follow up of 26.6 months. The baseline characteristics (age, stage, PS, histology, and serum markers) were not different in the two treatment arms. There is no significant difference in the outcome with either of the chemotherapeutic modalities. VIP is less cost effective and more toxic compared to BEP. Conclusion: In view of the greater toxicity and cost of therapy, as well as lack of either overall or disease free survival advantage, VIP is not a preferred option for patients with high-risk germ cell tumors in the Indian setting and it is still advisable to treat patients with BEP.

Attili Venkata; Chandra Rama; Anupama G; Loknath D; Bapsy P; Dadhich Hemant; Babu Govind

2007-01-01

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Progress of Bep Treatments on Nb at JLAB  

Energy Technology Data Exchange (ETDEWEB)

Recent experimental results have indicated that Buffered Electropolishing (BEP) is a promising candidate for the next generation of surface treatment technique for Nb superconducting radio frequency (SRF) cavities to be used in particle accelerators. In order to lay the foundation for using BEP as the next generation surface treatment technique for Nb SRF cavities, some fundamental aspects of BEP treatments for Nb have to be investigated. In this report, recent progress on BEP study at JLab is shown. Improvements on the existing vertical BEP are made to allow water cooling from outside of a Nb single cell cavity in addition to cooling provided by acid circulation so that the temperature of the cavity can be stable during processing. Some investigation on the electrolyte mixture was performed to check the aging effect of the electrolyte. It is shown that good polishing results can still be obtained on Nb at a current density of 171 mA/cm when the BEP electrolyte was at the stationary condition and was more than 1.5 years old.

A.T. Wu, S. Jin, R.A. Rimmer,X.Y. Lu, K. Zhao

2010-05-01

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Incidence, outcome and predictors of bleomycin pulmonary toxicity in a university hospital in Oman.  

UK PubMed Central (United Kingdom)

OBJECTIVES: To determine the incidence and predictors of bleomycin pulmonary toxicity in a university hospital in Oman. METHODS: This retrospective chart review consisted of 46 patients treated with bleomycin-containing regimes at Sultan Qaboos University Hospital in Oman between January 2007 and December 2010. Data regarding patient age, chemotherapy protocol, cumulative bleomycin dose, smoking history, renal function and concurrent use of granulocyte colony stimulating factor (GCSF) were collected from the hospital's electronic database. Analyses were performed using univariate statistical techniques. RESULTS: Of the 46 patients, 22% (n = 10) experienced bleomycin pulmonary toxicity. There was an overall mortality of 4.3% (n = 2; N = 46), with significantly more deaths in the bleomycin pulmonary toxicity group compared to the cohort that did not have bleomycin pulmonary toxicity (20% versus 0%; p = 0.043). The bleomycin pulmonary toxicity group was significantly older compared to the cohort that did not have bleomycin pulmonary toxicity (48 versus 34 years; p = 0.017). Furthermore, adriamycin, bleomycin, vinblastine, dacarbazine, as front-line chemotherapy, was found to have a trend towards increased risk of bleomycin pulmonary toxicity (90% versus 56%; p = 0.067; power = 31%). There did not seem to be significant differences in bleomycin dose (143 versus 149 units; p = 0.727), smoking status (10% versus 14%; p = 1.000) and systolic blood pressure (133 versus 131 mmHg; p = 0.746) between the two study groups. CONCLUSION: This study confirms a relatively high incidence of bleomycin pulmonary toxicity in a tertiary hospital in Oman. Older patients were significantly more likely to suffer bleomycin pulmonary toxicity compared to younger patients.

Ahmed BM; Al-Zakwani IS

2013-03-01

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[Difficulty in evaluation of the effectiveness of BEP chemotherapy in a patient with testicular seminoma].  

UK PubMed Central (United Kingdom)

A 31-year-old man with a left testicular mass was treated with left high orchiectomy. Histological and immunohistochemical findings indicated a diagnosis ofseminoma. Computed tomography (CT) showed multiple enlarged lymph nodes. Serum biochemical examination showed an elevated serum lactate dehydrogenase (LDH) level. He was diagnosed with seminoma grade cT1N3M1aS2, stage IIIB. We administered four courses of bleomycin, etoposide and cisplatin (BEP) chemotherapy. Subsequent CT showed one residual lymph node measuring ?3 cm in diameter. His serum LDH level was transiently elevated at the end ofeach course ofchemotherapy. Two additional courses ofetoposide and cisplatin (EP) chemotherapy were administered because it was suspected that the elevated serum LDH levels indicated residual tumor. Another possible cause of the elevated serum LDH levels was an adverse effect of granulocyte colony stimulating factor (G-CSF) therapy. The first course of EP chemotherapy did not include G-CSF administration, and there was no subsequent increase in his serum LDH level. The second course included G-CSF administration, and his serum LDH level increased simultaneously with the increase in white blood cell count. We concluded that the transient elevations in serum LDH level were an adverse effect of G-CSF therapy rather than an indication of residual tumor. His serum LDH level did not increase significantly after subsequent courses of chemotherapy. Eight weeks after the end of chemotherapy, positron emission tomography-CT showed no evidence ofresidual or recurrent tumor.

Ohsugi H; Kinoshita H; Kawa G; Matsuda T

2013-06-01

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Nuclear Waste Disposal in Space: BEP's Best Hope?  

International Nuclear Information System (INIS)

[en] The best technology is worthless if it cannot find a market Beam energy propulsion (BEP) is a very promising technology, but faces major competition from less capable but fully developed conventional rockets. Rockets can easily handle projected markets for payloads into space. Without a new, huge demand for launch capability, BEP is unlikely to gain the resources it needs for development and application. Launching tens of thousands of tons of nuclear waste into space for safe and permanent disposal will provide that necessary demand while solving a major problem on earth. Several options exist to dispose of nuclear waste, including solar orbit, lunar orbit, soft lunar landing, launching outside the solar system, and launching into the sun

2006-05-02

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BEPS redesign of 168 commercial buildings: summary report  

Energy Technology Data Exchange (ETDEWEB)

The objective of this report is to present, in usable form, summary data from the Building Energy Performance Standards (BEPS) Phase II commercial buildings energy research conducted in 1978-1979. Summary data presented were obtained from two major research efforts: the BEPS Phase II Redesign experiment; and the related research on ASHRAE Standard 90-75R. The bulk of this report consists of data tabulations of key energy parameters for the 168 sample buildings, which were tabulated from computer-stored files of the 1978-1979 data. Two kinds of tabulations are included: numerical tabulations that extracted information from the computer-stored data base for the 168 sample buildings; and graphic presentations of the computer-generated data, plus data extracted from other sources. The intent is to provide a single data compendium of key energy-related factors from the 1978 redesign experiment and the associated 1978-1979 ASHRAE Standard 90-75R research. This report also supplements the information for which there was not space in the magazine articles. Thus, for some building types, additional analysis, comments, and data tabulations are included that could not be included in the articles because space was limited. These additional analysis items are not consistent across building types because both the energy conservation opportunities and the design strategies applied by the building designers varied considerably by building type. The chapters have been entered individually into EDB and ERA.

Stoops, J.L.; Deringer, J.J.; Moreno, S.; Misuriello, H.P.

1984-05-01

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Labeled bleomycin as a tumor localizing agent  

International Nuclear Information System (INIS)

[en] The antitumor antibiotics bleomycins labeled with 57Co are known to possess excellent tumor localizing properties but the rather long halflife of 57Co prevents its use in clinical routine. It is therefore desirable to label cobalt-bleomycin with a more suitable radionuclide, e.g. 123I. This thesis reports on further studies on cobalt-bleomycin. It appears from the studies on the structure of cobalt-bleomycin described in this thesis (Chapter B), that cobalt is able to form different complexes with bleomycin (the forms I and II). The difference in structure is not clear, but the biological behavior of both forms is studied (Chapter C). In Chapter D the iodination of cobalt-bleomycin is described. Iodination of free bleomycin yields a product with bad tumor localizing properties, and straight-on iodination of cobalt-bleomycin is prevented by the presence of cobalt. To retain the good tumor-localizing properties of cobalt-bleomycin, possibilities were explored to incorporate the iodine in the terminal amine (a side chain, not involved in complexation). Alkylation of cobalt-bleomycin demethyl A2 with N-bromoacetyl-3-iodoaniline yielded a product; unfortunately this product possessed bad tumor localizing properties and moreover, was not stable in vivo. The structure of a possibly successful iodinated cobalt-bleomycin is outlined but could not be realized during this research. (Auth.)

1982-01-01

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Assessment of BEP of MIMO-OFDMA systems  

Directory of Open Access Journals (Sweden)

Full Text Available MIMO antenna systems with OFDMA are used for high data rate systems for 4th generation wireless networks. Multi cell systems developed based on wireless standards such as WiMAX and 3GPP LTE. In this paper we are calculating average BEP (bit error probability) of MIMO-OFDMA systems. Multiuser access scenarios are two types those are co-ordination and randomization. For interference mitigation in co-ordinated scenario we arrange ULA (uniform linear array) with closely spaced antennas and beamforming process and in randomization we arrange OSTBC (orthogonal space time block coding) with antennas sufficiently spaced apart. Numerical results of analytical frame work is used for different applications and wide range system configurations.

Manohar Naik Ramavath#1 B.A.Sarath Manohar Babu

2013-01-01

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Fulminant hyperpyrexia induced by bleomycin  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Mild and self-limiting fever following bleomycin use is common, and a fatal hyperpyrexial response occurs rarely. In previously reported cases, such hyperpyrexia occurred either after the initial administration of the drug or during subsequent therapy following an initial pyrexial response. We descr...

Leung, WH; Lau, JY; Chan, TK; Kumana, CR

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Energy dependence of the 7Be(p,?)8B S factor, and charge symmetry in the 7Li+n and 7Be+p systems  

International Nuclear Information System (INIS)

[en] The measured energy dependence of the 7Be(p,?)8B S factor is fitted better by the cluster-model calculation of Descouvemont and Baye than by other models. It is suggested here that this may be connected with the cluster model predicting too high an absolute value of the S factor. Evidence for a breakdown of charge symmetry between the 7Li+n and 7Be+p systems is discussed and found not to be convincing. R-matrix formulae are used

2006-04-03

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Radiotherapy using bleomycin, ACNU, and vincristine for malignant brain tumors  

Energy Technology Data Exchange (ETDEWEB)

Radiotherapy combined with bleomycin, ACNU, and vincristine was performed on 106 patients with malignant brain tumors. The treatment protocol was based on the concept of combination chemotherapy or chemoradiotherapy and synchronized chemoradiotherapy. For the purpose of synchronized chemoradiotherapy, bleomycin, ACNU, and vincristine were used as G/sub 2/M cell cycle phase accumulator, and radiation and bleomycin were used as agents to which G/sub 2/M or G/sub 2/ phase cells are sensitive. The short-term results of the chemoradiotherapy were evaluated by measuring tumor regression by computerized tomography (CT) in 80 patients with evaluable CT lesions. The response rate was 67% (6/9) for astrocytoma, 29% (7/24) for anaplastic glioma, 67% (4/6) for pontine glioma, 100%(5/5) for malignant lymphoma, 100% (8/8) for germ cell tumors and 65% (15/23) for metastatic tumors. A control study was performed using radiation alone on another 18 patients with metastatic tumors, and the response rate was 50% (9/18). Among the 106 patients treated with chemoradiotherapy, the major side effects observed were as follows: leukopenia in 33 patients (31%), thrombocytopenia in 14 (13%), paralytic ileus in 2 (2%), peripheral neuropathy in 2 (2%), and lung fibrosis in 1 (1%). Contrary to expectation, low-grade astrocytomas responded much better to the chemoradiotherapy than high-grade astrocytomas.

Tanaka, Ryuichi; Murakami, Naoto; Suzuki, Yasuo; Takeda, Norio; Arai, Hiroyuki; Konno, Kimikazu; Tanimura, Ken-ichi

1984-08-01

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Adsorptive stripping voltammetry of bleomycin.  

Science.gov (United States)

In 0.05 M H2SO4 solution, two reductive peaks, P1 and P2, of bleomycin were obtained. The peak potentials E(P1) and E(P2) were -0.83 and -1.09 V (versus Ag/AgCl), respectively. The sensitivity of P2 was much higher than that of P1. The peak current of P2 was proportional to the concentration of bleomycin over the range 1.0 x 10(-9)-1.0 x 10(-7) M with a detection limit of 5.0 x 10(-10) M using adsorptive voltammetry at an accumulation time of 120 s (Ei = -0.80 V). The behaviour of the reduction wave was studied and applied to the determination of bleomycin in mouse serum. The reduction process of P1 was irreversible with adsorptive characteristics and the adsorption behavior obeyed the Frumkin adsorptive isotherm. The adsorptive coefficient beta was 8.9 x 10(5), the interaction factor alpha was 0.94 and the Gibbs energy of adsorption delta G degree was -33.93 kJ mol-1. P2 was an irreversible adsorption peak with catalytic hydrogen properties. PMID:9374029

Tan, X; Hu, J; Li, Q

1997-09-01

 
 
 
 
21

Adsorptive stripping voltammetry of bleomycin.  

UK PubMed Central (United Kingdom)

In 0.05 M H2SO4 solution, two reductive peaks, P1 and P2, of bleomycin were obtained. The peak potentials E(P1) and E(P2) were -0.83 and -1.09 V (versus Ag/AgCl), respectively. The sensitivity of P2 was much higher than that of P1. The peak current of P2 was proportional to the concentration of bleomycin over the range 1.0 x 10(-9)-1.0 x 10(-7) M with a detection limit of 5.0 x 10(-10) M using adsorptive voltammetry at an accumulation time of 120 s (Ei = -0.80 V). The behaviour of the reduction wave was studied and applied to the determination of bleomycin in mouse serum. The reduction process of P1 was irreversible with adsorptive characteristics and the adsorption behavior obeyed the Frumkin adsorptive isotherm. The adsorptive coefficient beta was 8.9 x 10(5), the interaction factor alpha was 0.94 and the Gibbs energy of adsorption delta G degree was -33.93 kJ mol-1. P2 was an irreversible adsorption peak with catalytic hydrogen properties.

Tan X; Hu J; Li Q

1997-09-01

22

Safe administration of hyperbaric oxygen after bleomycin: a case series of 15 patients.  

UK PubMed Central (United Kingdom)

INTRODUCTION: Supplemental oxygen has been reported to cause pulmonary complications after bleomycin. We describe the safe administration of hyperbaric oxygen (HBO2) after bleomycin in 15 patients. METHODS: Paper and electronic records were reviewed for bleomycin-exposed patients at the Duke Center for Hyperbaric Medicine and Environmental Physiology from 1979 to 2010. RESULTS: Fourteen bleomycin-exposed patients received HBO2 at Duke under a special-precautions protocol. One was treated for DCS elsewhere. The protocol included: pretreatment evaluation; chest radiograph; spirometry; blood gases; a single, 2-atmospheres absolute (atm abs), 120-minute HBO2 treatment; and a gradual acceleration over one week to a twice-daily schedule contingent on clinical and laboratory findings. Bleomycin indications were: head-and-neck squamous cell carcinomas (11), Hodgkin's lymphoma (2), other carcinomas (2). HBO2 indications were: osteoradionecrosis (10), soft-tissue radionecrosis (3), DCS (1) and a provocative oxygen toxicity test for a military aviator (1). Total bleomycin doses ranged from 40 to 225u/m2 (mean +/- SD, 105 +/- 57) given in conjunction with other chemotherapies and/or radiation. Radiation was 63.3 +/- 31.72 Gy (mean +/- SD), none to the chest with the exception of one patient treated for DCS elsewhere. Other chemotherapies included: vinblastine (11), methotrexate (11), CCNU (6) cisplatinum (7), dacarbazin (2), Adriamycin (1), and vincristine (1). Median age at time of HBO2 was 52 years (range 22-77). Median bleomycin-to-HBO2 latency was 34 months (range 1-279). Three patients received HBO2 within six months, and seven patients received HBO2 within two years of their last bleomycin exposure. There were no adverse pre-to-post HBO2 changes in: arterial blood gases, spirometry, chest radiograph findings or clinical reports. There were no persistent post-HBO2 pulmonary complications on follow-up. Post-HBO2 data were available for 40%, 53%, 87% and 100% of these parameters respectively. DISCUSSION: Bleomycin and oxygen can individually cause acute pulmonary toxicity. However, evidence for increased long-term susceptibility based on their synergy may be overstated.

Torp KD; Carraway MS; Ott MC; Stolp BW; Moon RE; Piantadosi CA; Freiberger JJ

2012-09-01

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BEP-relations for N2 dissociation over stepped transition metal and alloy surfaces  

DEFF Research Database (Denmark)

We present density functional theory (DFT) calculations for N(2) dissociation on stepped face-centred cubic (211) surface slabs. By using the same crystal structure, the same adsorption site for atomic nitrogen, and the same transition-state bond length of N(2) over a range of pure metal surfaces, a perfectly linear Bronsted-Evans-Polanyi (BEP) relation between the transition-state potential energy and the dissociative chemisorption energy is obtained. The perfect BEP relation, which extends over 12 eV in chemisorption energy, suggests that the manifestation of BEP relations for surface reactions is a general electronic structure effect, and that geometric effects are responsible for the scatter which is normally observed around the BEP line. The BEP relation is also shown to be valid for both surface and bulk alloys. The scatter is, however, larger than for the pure elements. This can be understood as a larger geometrical variance. To analyze the accuracy of the DFT calculations a detailed convergence study is performed for several adsorbates on stepped hexagonal close-packed and face-centred cubic Ru slabs.

Fronczek-Munter, Ture RØnved; Bligaard, Thomas

2008-01-01

24

To dive or not to dive with bleomycin: a practical algorithm.  

UK PubMed Central (United Kingdom)

BACKGROUND: Bleomycin is used in the treatment of different cancers, but possible side effects of interstitial pneumonitis and fibrosis are associated with increased concentrations of oxygen. Therefore, clinicians are reluctant to declare young people fit for scuba diving after bleomycin treatment, because scuba divers might be exposed to high partial pressures of oxygen. METHODS: Based on a survey, 16 patients treated with bleomycin for either testicular/germ cell cancer or Hodgkin's disease were evaluated according to an algorithm to assess their fitness to dive. The algorithm is based on a review of the literature related to oncology, anesthesiology, and diving medicine. RESULTS: According to our protocol, 12 of the 16 patients were fit for scuba diving. However, the two groups of cancer patients showed considerable difference with regard to fitness for diving, i.e., 10 of 11 patients with testicular/germ cell cancer compared with 2 of 5 patients with Hodgkin's disease. CONCLUSIONS: The algorithm can be used by physicians and diving organizations to assess fitness for scuba diving after bleomycin treatment. However, patients with Hodgkin's disease treated with a combination of bleomycin and radiation may be at higher risk of radiation-induced pulmonary problems and are therefore more likely to be unfit for scuba diving.

van Hulst RA; Rietbroek RC; Gaastra MT; Schlösser NJ

2011-08-01

25

Pressure loss tests for DR-BEP of fullsize 17 x 17 PWR fuel assembly  

International Nuclear Information System (INIS)

[en] This report describes the conditions, procedure and results in the pressure loss tests carried out for a double grid type debris resistance bottom end piece (DR-BEP) designed by KAERI. In this test, the pressure loss coefficients of the full size 17 x 17 PWR simulated fuel assembly with DR-BET and with standard-BEP were measured respectively, and the pressure loss coefficients of DR-BEP were compared with the coefficients of STD-BET. The test conditions fall within the ranges of loop pressure from 5.2 to 45 bar, loop temperature from 27 to 221 deg C and Reynolds number in fuel bundle from 2.17 x 104 to 3.85 x 105. (Author) 5 refs., 18 figs., 5 tabs

1993-01-01

26

Antioxidants enhance the recovery of three cycles of bleomycin, etoposide, and cisplatin-induced testicular dysfunction, pituitary-testicular axis, and fertility in rats.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To investigate the effects of an antioxidant cocktail (AC) on bleomycin, etoposide, and cisplatin (BEP)-induced testicular dysfunction. DESIGN: In vivo study. SETTING: Research laboratory. ANIMAL(S): Adult male and female Sprague-Dawley rats. INTERVENTION(S): The rats were treated with three cycles of 21 days each of therapeutically relevant dose levels of BEP (0.75, 7.5, and 1.5 mg/kg) with or without the AC (a mixture of ?-tocopherol, L-ascorbic acid, Zn, and Se). MAIN OUTCOME MEASURE(S): Sperm parameters, fertility, serum hormone levels (ELISA), testicular histopathology, and expression of proliferating cell nuclear antigen (PCNA), and transferrin (Western blotting and immunohistochemistry) were evaluated at the end of treatment and a 63-day recovery period. RESULT(S): At the end of treatment, the AC improved BEP-induced decrease in sperm motility and increase in abnormality but had no effect on reduced sperm count, fertility, and tubular atrophy, although it up-regulated germ cell proliferation. The AC normalized reduced inhibin B levels, but had no effect on decreased transferrin and testosterone and elevated LH levels. At the end of the recovery period, the AC enhanced the expression of PCNA and transferrin, repopulation of germ cells, LH-testosterone axis, and fertility, but had no effect on reduced FSH and elevated inhibin B levels. CONCLUSION(S): The antioxidants protect and then enhance the recovery of testicular and reproductive endocrine functions when administered concomitantly with BEP therapy. The AC may be beneficial to regain testicular functions after chemotherapy.

Kilarkaje N; Mousa AM; Al-Bader MM; Khan KM

2013-07-01

27

57Co-bleomycin and *I-bleomycin in Ehrlich's carcinoma model of the mouse  

International Nuclear Information System (INIS)

[en] The tumour concentration, distribution of activity and whole body retention of bleomycin labeled with iodine-125 or iodine-131 was contrasted with that of 57Co-bleomycin following administration to mice showing tumours. Additional investigations were carried out to determine the stability of iodinated bleomyin in vivo and in vitro. As regards the beahaviour of I-bleomycin in mice showing solid carcinomas according to Ehrlich it was established that its absolute tumour concentration was lower and its relative tumour concentration just slightly less pronounced than that of 57Co-bleomycin during the period between 2 and 48 hours following administration. Investigations into whole body retention showed the elimination of activity to be more rapid for 131I-bleomycin as compared to 57Co-bleomycin. Bleomycin that was radioiodinated according to the iodine monochloride method proved to be more stable in vivo than bleomycin labeled with 57Co. Further studies, in particular clinical trials, will have to be carried out before definite conclusions can be drawn as to the diagnostic value of radioiodinated bleomycin in tumour localisation. (TRV)

1983-01-01

28

GUM Analysis for TIMS Isotopic Ratios in BEP0 Graphite Qualification Samples, Round 2  

Energy Technology Data Exchange (ETDEWEB)

In May 2007, one set of three samples from NBL were addressed to Steve Petersen for TIMS analysis, and included BEP0 samples numbered 27008, 30986, and 50846. All cores were trimmed by tooling, and lightly cleaned by CO2 pellet blasting. Small discs were cut from the second set of samples for SIMS analysis, with the remainder of each used for TIMS preparation.

Gerlach, David C.; Heasler, Patrick G.; Reid, Bruce D.

2009-01-01

29

Extrapolation of the astrophysical S factor for 7Be(p,?)8B to solar energies  

International Nuclear Information System (INIS)

We investigate the energy dependence of the astrophysical S factor for the reaction 7Be(p,?)8B, the primary source of high-energy solar neutrinos in the solar pp chain. Below 400 keV the energy dependence is well understood in terms of a subthreshold pole arising from the binding of the valence proton to the 8B ground state.

1998-12-21

30

Investigations on the accumulation of radio bleomycin in gynaecological tumors  

International Nuclear Information System (INIS)

The indication for treatment with bleomycin in gynaecological tumors is as yet not well defined. At present bleomycin is primarily used for advanced gynaecological malignancies. Results of our investigations show that the individual affinity of gynaecological tumors to bleomycin is very variable. In subsequent investigations it should therefore be determined whether the accumulation of radio-bleomycin and the sensitivity of a gynaecological malignant tumor to bleomycin therapy show a positive correlation. The probable chances of success of a course of chemotherapy with bleomycin could then be predicted. (orig.)

1976-01-01

31

Fatal toxic effect of bleomycin on brain tissue after intracystic chemotherapy for a craniopharyngioma: case report.  

UK PubMed Central (United Kingdom)

OBJECTIVE AND IMPORTANCE: Craniopharyngiomas are benign neoplasms of epithelial origin that arise from the remnants of Rathke's pouch and are located in the sellar, parasellar, and third ventricular regions. Despite major advances in microsurgical techniques, total removal of these tumors is associated with a high risk of death, long-term endocrinological dependence, cognitive dysfunction, and behavioral disorders. For patients with monocystic craniopharyngiomas, encouraging postoperative survival rates and high rates of cyst regression after intracavitary administration of bleomycin have been reported. Moreover, only a few side effects have been reported for this treatment method. We report a patient with a cystic craniopharyngioma who was treated using intracavitary bleomycin administration and died as a result of the direct toxic effects of bleomycin on deep brain structures and the brainstem. CLINICAL PRESENTATION AND INTERVENTION: A 47-year-old woman with a cystic craniopharyngioma underwent stereotactic insertion of a catheter attached to a subcutaneous reservoir. Five months after the procedure, positive-contrast computed tomographic cystography was performed to confirm the absence of fluid leakage. Daily intracavitary injections of bleomycin were administered through the reservoir into the cyst, until a total dose of 56 mg had been administered in 8 days. After the treatment, the cystic cavity regressed but the patient exhibited neurological deterioration; magnetic resonance imaging scans revealed diffuse edema in the diencephalon and brainstem. The patient died 45 days after completion of the treatment. CONCLUSION: Intracavitary administration of bleomycin is not a treatment protocol without risks or side effects, even if there is no fluid leakage into the cerebrospinal fluid. Although this is known to be an effective treatment for cystic craniopharyngiomas, previous reports cannot be used to establish a standard treatment method, and more research is needed to yield a safer effective protocol.

Savas A; Erdem A; Tun K; Kanpolat Y

2000-01-01

32

Indirect measurement of 9Be(p, ?)6Li reaction by means of Trojan Horse Method  

International Nuclear Information System (INIS)

The beryllium abundance acts as a key role for understanding the inhomogeneous Big Bang nucleosynthesis. In order to measure the 9Be(p, ?)6Li bare nucleus cross section and S(E) factor at astrophysical energies, the Trojan Horse Method (THM) can be applied. The main feature of the method is that it allows to extract the energy dependence for the astrophysical S(E) factor of bare nuclei at very low energies without any extrapolation, by measuring the cross section of an appropriate three body process. Thus the 9Be(p, ?)6Li has been studied by means of the THM applied to the 2H(9Be, ?6Li)n at INFN-LNS, Catania, Italy. The two body reaction cross section has been studied in the energy range of Ecm=0-1000 keV, Preliminary results are discussed and a comparison with direct data is made. (authors)

2005-01-01

33

New determination of the 7Be(p,?)8B S-factor  

International Nuclear Information System (INIS)

We present new measurements of the 7Be(p,?)8B cross section from E-bar cm=116 to 2460 keV. Our new measurements lead to S17(0)=22.1+/-0.6(expt)+/-0.6(theor)eV-bar b based on data from E-bar cm=116 to 362 keV, where the central value is based on the theory of Descouvemont and Baye. We compare our results to other S17(0) values extracted from both direct (7Be(p,?)8B) and indirect (Coulomb dissociation and heavy-ion reaction) measurements, and show that the results of these 3 types of experiments are not mutually compatible. We recommend a 'best' value, S17(0)=21.4+/-0.5(expt)+/-0.6(theor)eV-bar b, based on the mean of all modern direct measurements below the 1+ resonance.

2004-12-27

34

The {sup 7}Be(p, {gamma}){sup 8}B astrophysical S-factor  

Energy Technology Data Exchange (ETDEWEB)

We present the results of the recent precise S{sub 17}(0) determination by the Seattle-TRIUMF {sup 7}Be(p, {gamma}){sup 8}B collaboration. We discuss new investigations of the robustness of our estimated extrapolation uncertainty. We comment on the comparison of direct and Coulomb dissociation determinations of S{sub 17}(E), and on neutrino physics and the Standard Solar Model.

Snover, K.A. [Center for Experimental Nuclear Physics and Astrophysics, University of Washington, Seattle WA 98195 (United States)]. E-mail: snover@npl.washington.edu; Junghans, A.R. [Center for Experimental Nuclear Physics and Astrophysics, University of Washington, Seattle WA 98195 (United States); Mohrmann, E.C. [Center for Experimental Nuclear Physics and Astrophysics, University of Washington, Seattle WA 98195 (United States); Steiger, T.D. [Center for Experimental Nuclear Physics and Astrophysics, University of Washington, Seattle WA 98195 (United States); Adelberger, E.G. [Center for Experimental Nuclear Physics and Astrophysics, University of Washington, Seattle WA 98195 (United States); Casandjian, J.M. [Center for Experimental Nuclear Physics and Astrophysics, University of Washington, Seattle WA 98195 (United States); Swanson, H.E. [Center for Experimental Nuclear Physics and Astrophysics, University of Washington, Seattle WA 98195 (United States); Buchmann, L. [TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, V6T 2A3 (Canada); Park, S.H. [TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, V6T 2A3 (Canada); Zyuzin, A. [TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, V6T 2A3 (Canada); Laird, A.M. [TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, V6T 2A3 (Canada)

2005-07-25

35

A favorable maternal and neonatal outcome following chemotherapy with etoposide, bleomycin, and cisplatin for management of grade 3 immature teratoma of the ovary.  

UK PubMed Central (United Kingdom)

Ovarian cancer rarely complicates pregnancy. Usually these malignancies consist of germ cell tumors. Preserving maternal safety along with favorable neonatal outcome is a subject of debate in the management of ovarian cancer during pregnancy. In this report, the authors describe a 25-year-old primigravid woman who was diagnosed to with an ovarian immature teratoma which was diagnosed at 13th weeks of pregnancy during a routine sonography. She underwent oophorectomy at week 21 of her gestation. Then she received three cycles of BEP regimen (bleomycin, etoposide, and cisplatin) during her pregnancy until week 37 of gestation. At 36 weeks she delivered a male baby with mild glandular hypospadia who was otherwise normal. Management of immature teratoma after the first trimester of pregnancy is similar to non-pregnant patients and is safe for both the mother and the fetus.

Ghaemmaghami F; Abbasi F; Abadi AG

2009-12-01

36

A favorable maternal and neonatal outcome following chemotherapy with etoposide, bleomycin, and cisplatin for management of grade 3 immature teratoma of the ovary.  

Science.gov (United States)

Ovarian cancer rarely complicates pregnancy. Usually these malignancies consist of germ cell tumors. Preserving maternal safety along with favorable neonatal outcome is a subject of debate in the management of ovarian cancer during pregnancy. In this report, the authors describe a 25-year-old primigravid woman who was diagnosed to with an ovarian immature teratoma which was diagnosed at 13th weeks of pregnancy during a routine sonography. She underwent oophorectomy at week 21 of her gestation. Then she received three cycles of BEP regimen (bleomycin, etoposide, and cisplatin) during her pregnancy until week 37 of gestation. At 36 weeks she delivered a male baby with mild glandular hypospadia who was otherwise normal. Management of immature teratoma after the first trimester of pregnancy is similar to non-pregnant patients and is safe for both the mother and the fetus. PMID:20041106

Ghaemmaghami, Fatemeh; Abbasi, Fatemeh; Abadi, Akram Ghahghai Nezam

2009-12-28

37

Photochemical internalization of bleomycin for glioma treatment  

Science.gov (United States)

We study the use of photochemical internalization (PCI) for enhancing chemotherapeutic response to malignant glioma cells in vitro. Two models are studied: monolayers consisting of F98 rat glioma cells and human glioma spheroids established from biopsy-derived glioma cells. In both cases, the cytotoxicity of aluminum phthalocyanine disulfonate (AlPcS2a)-based PCI of bleomycin was compared to AlPcS2a-photodynamic therapy (PDT) and chemotherapy alone. Monolayers and spheroids were incubated with AlPcS2a (PDT effect), bleomycin (chemotherapy effect), or AlPcS2a+bleomycin (PCI effect) and were illuminated (670 nm). Toxicity was evaluated using colony formation assays or spheroid growth kinetics. F98 cells in monolayer/spheroids were not particularly sensitive to the effects of low radiant exposure (1.5 J/cm2 @ 5 mW/cm2) AlPcS2a-PDT. Bleomycin was moderately toxic to F98 cells in monolayer at relatively low concentrations-incubation of F98 cells in 0.1 ?g/ml for 4 h resulted in 80% survival, but less toxic in human glioma spheroids respectively. In both in vitro systems investigated, a significant PCI effect is seen. PCI using 1.5 J/cm2 together with 0.25 ?g/ml bleomycin resulted in approximately 20% and 18% survival of F98 rat glioma cells and human glioma spheroids, respectively. These results show that AlPcS2a-mediated PCI can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas.

Mathews, Marlon S.; Blickenstaff, Joseph W.; Shih, En-Chung; Zamora, Genesis; Vo, Van; Sun, Chung-Ho; Hirschberg, Henry; Madsen, Steen J.

2012-05-01

38

Amino acid analysis and cell cycle dependent phosphorylation of an H1-like, butyrate-enhanced protein (BEP; H10; IP25) from Chinese hamster cells  

International Nuclear Information System (INIS)

A fraction enriched in the butyrate-enhanced protein (BEP) has been isolated from Chinese hamster (line CHO) cells by perchloric acid extraction and Bio-Rex 70 chromatography. Amino acid analyses indicate that the composition of BEP resembles that of CHO H1; however, BEP contains 11% less alanine than H1, and, in contrast to H1, BEP contains methionine. Treatment of BEP with cyanogen bromide results in the cleavage of a small fragment of approx. 20 amino acids so that the large fragment seen in sodium dodecyl sulfate-acrylamide gels has a molecular weight of approx. 20,000. Radiolabeling and electrophoresis indicate that BEP is phosphorylated in a cell cycle dependent fashion. These data suggest that (1) BEP is a specialized histone of the H1 class and (2) BEP is the species equivalent of calf lung histone H10, rat H10, and IP25, a protein enhanced in differentiated Friend erythroleukemia cells. The data also indicate that putative HMG1 and HMG2 proteins do not undergo the extensive cell cycle dependent phosphorylations measured for histone H1 and BEP

1980-01-01

39

Excretion and organic distribution of 57Co-bleomycin emulsions  

International Nuclear Information System (INIS)

[en] Excretion and organic distributions of 57Co-bleomycin were studied in normal and tumour-bearing mice with the objective of obtaining high 57Co-bleomycin concentrations in the tumour and the regional lymph nodes. Aqueous 57Co-bleomycin and various 57Co-bleomycin emulsions were used for the studies and applied either locally or systemically. Excretion of 57Co-bleomycin was slowest after local administration of 57Co-bleomycin oil-in-water emulsion and fastest after systemic application of aqueous 57Co-bleomycin. Organic distribution studies showed the highest values in the tumour and the regional lymph nodes after local injection of 57Co-bleomycin oil-in-water emulsion while the lowest values were measured after systemic application of aqueous 57Co-bleomycin. These kinetic studies suggest that intratumoral treatment with oil-in-water emulsions of bleomycin may be a new approach in the therapy of epithelial tumours with lymphogenic metastases. (orig.)

1982-01-01

40

Business Energy Plan (BEP-I) of the mental health care centre Losserhof in Almelo, Netherlands; Bedrijfs Energie Plan (BEP-I) van de Losserhof  

Energy Technology Data Exchange (ETDEWEB)

In 1995 a long-range agreement (MJA, abbreviated in Dutch) between the Dutch government and the title centre to improve the energy efficiency by 30% in the year 2000, compared to the year 1989. One of the obligations of a MJA is to draft a Business Energy Plan (BEP) in which an overview is given of the energy consumption in the past and in the future, and the energy saving measures that were taken in the period 1989-1995 and will be taken in the period 1996-2000. Also attention is paid to a motivation campaign and the notion Good Housekeeping by means of which energy can be saved effectively and cheap

Kaalverink, R.; Van Rees, C.

1997-05-01

 
 
 
 
41

The new Seattle-TRIUMF 7Be(p,?)8B S-factor determination  

International Nuclear Information System (INIS)

We present new measurements of the 7Be(p,?)8B cross section from E-bar cm=116 to 2460 keV. Our new measurements lead to S17(0) = 22.1 +/- 0.6(expt) +/- 0.6(theor) eV b, where the central value is based on the theory of Descouvemont and Baye. We recommend a 'best' value, S17(0) = 21.4 +/- 0.5(expt) +/- 0.6(theor) eV b, based on the mean of all modern direct measurements below the 1+ resonance.

2005-01-01

42

The 7Be(p,?)8B reaction in a microscopic three-cluster model  

International Nuclear Information System (INIS)

The 7Be(p,?)8B reaction is investigated through a microscopic three-cluster model, using the generator coordinate method. The 7Be nucleus is described by an ?+3He structure, projected on the 3/2- and 1/2- states of 7Be. The model is tested by the calculation of M1 transition probabilities in 8Li and 8B and of the 7Li(n,?)8Li cross section. At zero energy, we find an S-factor S(0)=0.030 keV.b, slightly larger than the currently accepted value. (orig.)

1988-10-10

43

The 7Be(p, ?)8B reaction in a microscopic three-cluster model  

Science.gov (United States)

The 7Be(p, ?)8B reaction is investigated through a microscopic three-cluster model, using the generator coordinate method. The 7Be nucleus is described by an ? +3He structure, projected on the 3/2- and 1/2- states of 7Be. The model is tested by the calculation of M1 transition probabilities in 8Li and 8B and of the 7Li(n, ?)8Li cross section. At zero energy, we find an S-factor S(0) = 0.030 keV.b, slightly larger than the currently accepted value.

Descouvemont, P.; Baye, D.

1988-10-01

44

A comment on the 7Be(p,?)8B cross section and the solar neutrino problem  

International Nuclear Information System (INIS)

Evidence is presented which indicates that the accepted value for the cross section of the 7Be(p,?)8B reaction at stellar energies is probably too large. It is suggested that the accepted value of the 7Li(d,p)8Li cross section, which has been used for normalization purposes, is too large; that the accepted value for the ratio of the 7Be(p,?)8B and 7Li(d,p)8Li cross sections is too large; and that the energy dependence used to extrapolate to stellar energies from the higher energies at which measurements have been made is inaccurate. The consequent reduction of the 7Be(p,?)8B cross section by about 30% would not be sufficient to resolve the solar neutrino problem but would significantly lessen the discrepancy between observation and calculation.

1986-01-01

45

Preparation of [111In]-Bleomycin radiopharmaceutical  

Directory of Open Access Journals (Sweden)

Full Text Available In this study, the preparation of 111In-Bleomycin complex was optimized for temperature, time, concentration and pH during several experiments. The results showed that by the addition of bleomycin to 111In-InCl3 sample (dried under flow of N2) and heating the mixture up to 90-100°C the radiopharmaceutical can be obtained in 99.5% yield and a specific activity of 1.745 Ci/mmol. The final sample was injected into fibrosarcoma-bearing mice via their tail vein. Satisfactory preliminary SPECT images were acquired between 2-4 hours post-injection showing suitable accumulation in fibrosarcoma tumors.

A. R. Jalilian; M. Mirzaii; A.R. Karimian; J. Moafian; G. Aslani; S. Moradkhani; M. Kamali-Dehghan; S. Daneshvari; F. Tabeie; G. Raisali

2005-01-01

46

Trojan horse method applied to 9Be(p,?)6Li at astrophysical energies  

International Nuclear Information System (INIS)

The low-energy bare-nucleus cross section for 9Be(p,?)6Li has been extracted by means of the Trojan horse method (THM) applied to the 2H(9Be, ?,6Li)n reaction at a beam energy of 9Be of 22.35 MeV. For the first time, we assume an intermediate process, 9Be+2H?9Be+p+n, and considered this process as one criterion of the quasifree condition. Accordingly, sequential decay processes were eliminated. The derived astrophysical S(E) factor for the two-body process 9Be(p,?)6Li is compared with that obtained from direct experiments. We have found good agreement between the two results, leading to an improved determination of the S(E) with S(0)=21.0±0.8 MeV b. Furthermore, the electron screening potential energy Ue=676±86 eV has also been extracted in a model-independent way by comparing the direct and THM data. The value is significantly higher than that predicted by current theoretical models, whereas it is lower than Ue?830 eV, which was extracted from direct measurements with inclusion of the Ec.m.=-23 keV subthreshold resonance.

2008-01-01

47

Indirect measurement of bare astrophysical S(E) factor for 9Be(p,?)6Li  

International Nuclear Information System (INIS)

The beryllium abundance acts as a key role for understanding the inhomogeneous Big Bang nucleosynthesis. In order to measure the 9Be(p,?)6Li bare nucleus cross section and S(E) factor at astrophysical energies, the Trojan Horse Method (THM) can be applied. The method can overcome the difficulties caused by Coulomb barrier and electronic screening effect in direct measurement, and it allows to extract the energy dependence for the bare astrophysical S(E) factor at very low energies without any extrapolation by measuring the cross section of an appropriate three body process under the quasi-free condition. The 9Be(p,?)6Li has been studied by means of the THM applied to the 2H(9Be,?6Li)n at China Institute of Atomic Energy. The two body reaction cross section and S(E) factor was extracted in the energy range of Ecm=0-300 keV. The electron screening potential Ue was then obtained by comparing the THM data with the direct ones. (authors)

2010-01-01

48

Bleomycin in verrucous squamous cell carcinoma of the oesophagus.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A case of verrucous squamous cell carcinoma of the oesophagus treated with bleomycin is reported. Bleomycin brought prompt reduction of the tumour and relief of symptoms. There have been no previous reports on experience with anti-cancer agents for verrucous carcinoma of the oesophagus. Administrati...

Sakurai, T.; Fuchigami, T.; Omae, T.; Iwashita, A.; Kume, K.; Asano, S.

49

BEP/SEP and Outage Performance Analysis of L-Branch Maximal-Ratio Combiner for ??? Fading  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Maximal-ratio combiner (MRC) performances in fading channels have been of interest for a long time, which can be seen by a number of papers concerning this topic. In this paper we treat bit error probability (BEP), symbol error probability (SEP) and outage probability of MRC in presence of ;...

Mirza Miliši?; Mirza Hamza; Mesud Hadžiali?

50

Bleomycin and radiotherapy in nonresectable thoracic oesophageal carcinoma  

Energy Technology Data Exchange (ETDEWEB)

The survival rates of nonresectable thoracic oesophageal carcinoma patients were studied in 50 patients treated by radiotherapy and by a combination to radiotherapy and bleomycin. The patients of two series were very similar. The one-year survival rates were 21 and 0 per cent, in radiotherapy and in radiotherapy with bleomycin group, respectively. In the literature, there were only few reports from survival figures of patients with oesophageal carcinoma treated with bleomycin in combination with radiotherapy. The authors concluded that the combination of bleomycin and radiotherapy has very limited effect on advanced oesophageal carcinoma. The survival rate after this combination therapy is not better than with radiotherapy alone, if bleomycin and radiotherapy are used with reduced doses and without severe complications.

Appelqvist, P.; Silvo, J.

1981-06-01

51

7Be(p,?)8B cross section and the properties of 7Be  

International Nuclear Information System (INIS)

[en] We study the nonresonant part of the 7Be(p,?)8B reaction using a three-cluster resonating group model that is variationally converged and virtually complete in 4He+3He+p model space. The importance of using adequate nucleon-nucleon interaction is demonstrated. We find that the low-energy astrophysical S factor is linearly correlated with the quadrupole moment of 7Be. A range of parameters is found where the most important 8B, 7Be, and 7Li properties are reproduced simultaneously; the corresponding S factor at Ec.m.=20 keV is 24.6--26.1 eV b

1995-01-01

52

Mouse models of bleomycin-induced pulmonary fibrosis.  

UK PubMed Central (United Kingdom)

Pulmonary fibrosis is a component of many interstitial lung diseases, including idiopathic pulmonary fibrosis, a chronic, progressive disease for which there is currently no effective therapy. Bleomycin has been widely used in rodents to model pulmonary fibrosis for the study of mechanisms involved in fibrogenesis and for evaluation of potential therapies. Bleomycin induces DNA strand breaks, resulting in pulmonary inflammation, injury, and subsequent interstitial fibrosis. This unit describes methods for delivering bleomycin, either directly into the lung or systemically, to create models of pulmonary fibrosis in rodents. Also described is a rapid and easy procedure for measuring lung collagen content to quantify the severity of fibrosis.

Walters DM; Kleeberger SR

2008-03-01

53

Dermatite flagelada induzida pela bleomicina/ Bleomycin- induced flagellate dermatitis  

Scientific Electronic Library Online (English)

Full Text Available Abstract in portuguese A bleomicina é agente quimioterápico usado no tratamento de diferentes neoplasias. Apresenta vários efeitos colaterais, sendo um deles a hiperpigmentação cutânea de aspecto flagelado, considerada específica dessa droga. Relatam-se dois casos de dermatite flagelada induzida pela bleomicina. Discutem-se os aspectos clínicos e etiopatogênicos em breve revisão bibliográfica. Abstract in english Bleomycin is an antineoplastic drug used in the treatment of different tumors. It has several side effects, including a cutaneous hyperpigmentation with a flagellate aspect, which is considered specific to Bleomycin. We report two cases of Bleomycin-induced flagellate dermatitis and discuss the clinical and etiopathogenic aspects in a brief blibliographic revision.

Silveira, Júlio César Gomes; Cunha, Beatriz Moreira da; Estrella, Rogério Ribeiro

2006-02-01

54

Cleavage of bleomycin hydrolase by caspase-3 during apoptosis.  

Science.gov (United States)

Bleomycin hydrolase (BLH) affects bleomycin chemotherapy through inactivation of bleomycin with deamination. As a neutral cysteine protease, it also plays various roles in physiological conditions and diseases. However, its mechanism of degradation remains unclear. In the present study, we showed that the levels of BLH were significantly reduced during apoptosis induced by the antitumor agents bleomycin, etoposide and hydroxycamptothecin, and inhibited by the caspase inhibitors Q-VD-oph and Z-DEVD-FMK. Furthermore, the caspase-dependent cleavage of BLH was confirmed by cleavage of partly-purified human BLH with caspase-3 and caspase-9 in vitro. The stability of BLH at normal culture conditions was analyzed with the protein synthesis inhibitor cycloheximide and the proteasome inhibitor MG132. BLH was degraded at a rate lower than that of cyclin D1. This is the first report to demonstrate that BLH is cleaved by caspase-3 during apoptosis. PMID:23708668

Chen, Yang; Xu, Rong; Chen, Jianguo; Li, Xiaoyu; He, Qiyang

2013-05-23

55

Cleavage of bleomycin hydrolase by caspase-3 during apoptosis.  

UK PubMed Central (United Kingdom)

Bleomycin hydrolase (BLH) affects bleomycin chemotherapy through inactivation of bleomycin with deamination. As a neutral cysteine protease, it also plays various roles in physiological conditions and diseases. However, its mechanism of degradation remains unclear. In the present study, we showed that the levels of BLH were significantly reduced during apoptosis induced by the antitumor agents bleomycin, etoposide and hydroxycamptothecin, and inhibited by the caspase inhibitors Q-VD-oph and Z-DEVD-FMK. Furthermore, the caspase-dependent cleavage of BLH was confirmed by cleavage of partly-purified human BLH with caspase-3 and caspase-9 in vitro. The stability of BLH at normal culture conditions was analyzed with the protein synthesis inhibitor cycloheximide and the proteasome inhibitor MG132. BLH was degraded at a rate lower than that of cyclin D1. This is the first report to demonstrate that BLH is cleaved by caspase-3 during apoptosis.

Chen Y; Xu R; Chen J; Li X; He Q

2013-08-01

56

Extracellular matrix powder protects against bleomycin-induced pulmonary fibrosis.  

UK PubMed Central (United Kingdom)

Pulmonary fibrosis refers to a group of lung diseases characterized by inflammation, fibroblast proliferation, and excessive collagen deposition. Although the mechanisms underlying pulmonary fibrosis are poorly understood, current evidence suggests that epithelial injury contributes to the development of fibrosis. Regenerative medicine approaches using extracellular matrix (ECM) scaffolds have been shown to promote site-specific tissue remodeling. This led to the hypothesis that particulate ECM would promote normal tissue repair and attenuate bleomycin-induced pulmonary fibrosis. C57BL/6 mice were treated intratracheally with bleomycin or saline with or without a particulate form of ECM scaffold from porcine urinary bladder matrix (UBM-ECM) or enzymatically digested UBM-ECM. Mice were sacrificed 5 and 14 days after exposure. Compared to control mice, bleomycin-exposed mice had similar increases in inflammation in the bronchoalveolar lavage fluid regardless of UBM-ECM treatment. However, 14 days after exposure, lung histology and collagen levels revealed that mice treated with bleomycin and the particulate or digested UBM-ECM had negligible fibrosis, whereas mice given only bleomycin had marked fibrosis. Administration of the particulate UBM-ECM 24 h after bleomycin exposure also significantly protected against pulmonary injury. In vitro epithelial cell migration and wound healing assays revealed that particulate UBM-ECM promoted epithelial cell chemotaxis and migration. This suggests that promotion of epithelial wound repair may be one mechanism in which UBM-ECM limits pulmonary fibrosis.

Manni ML; Czajka CA; Oury TD; Gilbert TW

2011-11-01

57

Extracellular matrix powder protects against bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

Pulmonary fibrosis refers to a group of lung diseases characterized by inflammation, fibroblast proliferation, and excessive collagen deposition. Although the mechanisms underlying pulmonary fibrosis are poorly understood, current evidence suggests that epithelial injury contributes to the development of fibrosis. Regenerative medicine approaches using extracellular matrix (ECM) scaffolds have been shown to promote site-specific tissue remodeling. This led to the hypothesis that particulate ECM would promote normal tissue repair and attenuate bleomycin-induced pulmonary fibrosis. C57BL/6 mice were treated intratracheally with bleomycin or saline with or without a particulate form of ECM scaffold from porcine urinary bladder matrix (UBM-ECM) or enzymatically digested UBM-ECM. Mice were sacrificed 5 and 14 days after exposure. Compared to control mice, bleomycin-exposed mice had similar increases in inflammation in the bronchoalveolar lavage fluid regardless of UBM-ECM treatment. However, 14 days after exposure, lung histology and collagen levels revealed that mice treated with bleomycin and the particulate or digested UBM-ECM had negligible fibrosis, whereas mice given only bleomycin had marked fibrosis. Administration of the particulate UBM-ECM 24 h after bleomycin exposure also significantly protected against pulmonary injury. In vitro epithelial cell migration and wound healing assays revealed that particulate UBM-ECM promoted epithelial cell chemotaxis and migration. This suggests that promotion of epithelial wound repair may be one mechanism in which UBM-ECM limits pulmonary fibrosis. PMID:21797754

Manni, Michelle L; Czajka, Caitlin A; Oury, Tim D; Gilbert, Thomas W

2011-07-28

58

Research on 7Be(p,?)8Be reaction by Coulomb decomposition reaction  

International Nuclear Information System (INIS)

The measurement of solar neutrino flux has been carried out at four stations, and it has been known that it was considerably less than the expected neutrino flux by the standard solar model. This phenomenon is called solar neutrino problem. In the observation at Homestake and Kamiokande, it has been known that the threshold values of the measurable energy were high, and most of the neutrino flux were the high energy neutrinos formed by 8B?8Be+e++? reaction. The measurement of the reaction cross section for making 8B is considered as one of the keys for resolving the solar neutrino problem. The research on low energy 7Be(p,?)8B reaction carried out so far is reviewed. The author measured this cross section by using Coulomb decomposition method. The Coulomb decomposition reaction of 8B is discussed, and the calculated cross section is shown. The 8B beam supplied by the RIKEN projectile fragment separator (RIPS) was irradiated on a lead target in the atmosphere, and the decomposed 7Be and protons were measured with a telescope. The relative energy distributions of the protons and 7Be obtained by the experiment are shown. Also the Monte Carlo calculation was carried out. The resulted reaction cross section was compared with the other data. The effect of Coulomb acceleration was examined. (K.I.).

1994-01-01

59

Evaluating the inhibitory potential of sulindac against the bleomycin-induced pulmonary fibrosis in wistar rats.  

UK PubMed Central (United Kingdom)

The present study examined the protective effect of sulindac on bleomycin-induced lung fibrosis in rats. Animals were divided into saline group, bleomycin group (single intra-tracheal instillation of bleomycin) and bleomycin+sulindac (orally from day 1 to day 20). Bleomycin administration reduced the body weight, altered antioxidant status (such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione) while it increased the lung weight, hydroxyproline content, collagen deposition and lipid peroxidation. However, simultaneous administration of sulindac improved the body weight, antioxidant status and decreased the collagen deposition in lungs. Moreover, the levels of inflammatory cytokine tumour necrosis factor-? increased in bleomycin-induced group, whereas, on treatment with sulindac the levels of tumour necrosis factor-? were found reduced. Finally, histological evidence also supported the ability of sulindac to inhibit bleomycin-induced lung fibrosis. The results of the present study indicate that sulindac can be used as an agent against bleomycin-induced pulmonary fibrosis.

Verma R; Brahmankar M; Kushwah L; Suresh B

2013-07-01

60

Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice.  

UK PubMed Central (United Kingdom)

BACKGROUND: Antiflammin-1 (AF-1), a derivative of uteroglobin (UG), is a synthetic nonapeptide with diverse biological functions. In the present study, we investigated whether AF-1 has a protective effect against bleomycin-induced pulmonary fibrosis. METHODS: C57BL/6 mice were injected with bleomycin intratracheally to create an animal model of bleomycin-induced pulmonary fibrosis. On Day 7 and Day 28, we examined the anti-inflammatory effect and antifibrotic effect, respectively, of AF-1 on the bleomycin-treated mice. The effects of AF-1 on the transforming growth factor-beta 1 (TGF-beta1)-induced proliferation of murine lung fibroblasts (NIH3T3) were examined by a bromodeoxycytidine (BrdU) incorporation assay and cell cycle analysis. RESULTS: Severe lung inflammation and fibrosis were observed in the bleomycin-treated mice on Day 7 and Day 28, respectively. Administration of AF-1 significantly reduced the number of neutrophils in the bronchoalveolar lavage fluid (BALF) and the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in the lung homogenates on Day 7. Histological examination revealed that AF-1 markedly reduced the number of infiltrating cells on Day 7 and attenuated the collagen deposition and destruction of lung architecture on Day 28. The hydroxyproline (HYP) content was significantly decreased in the AF-1-treated mice. In vitro, AF-1 inhibited the TGF-beta1-induced proliferation of NIH3T3 cells, which was mediated by the UG receptor. CONCLUSIONS: AF-1 has anti-inflammatory and antifibrotic actions in bleomycin-induced lung injury. We propose that the antifibrotic effect of AF-1 might be related to its suppression of fibroblast growth in bleomycin-treated lungs and that AF-1 has potential as a new therapeutic tool for pulmonary fibrosis.

Liu W; Wan J; Han JZ; Li C; Feng DD; Yue SJ; Huang YH; Chen Y; Cheng QM; Li Y; Luo ZQ

2013-10-01

 
 
 
 
61

Combined bleomycin and radiotherapy in oral cancer  

Energy Technology Data Exchange (ETDEWEB)

A clinical trial comparing bleomycin (BLM) plus radiation against radiation alone is reported. One hundred and fifty-seven previously untreated T/sub 3/ and T/sub 4/ and N/sub 0/, N/sub 1/ or N/sub 2/ buccal squamous cell carcinomas were entered. Eighty-four of these received the combined therapy and 73 were controls. Cobalt-60 teletherapy using to opposing fields was employed. BLM was administered intra-arterially in 42 patients, intravenously in 22 patients and intramuscularly in 20 patients. The 73 controls received physiological saline as a placebo. Total clinical healing of the lesion within the volume of irradiation eight weeks after the end of radiotherapy was termed a favourable response. Anything else was a failure. Five-year recurrence-free rates and disease-free survival were also evaluated. The favourable response rate in the study group was 78.6% and in the control 19.1%. The corresponding recurrence-free rates and five-year survival rates were 71.8 and 17%, and 65.5 and 23.5% respectively. The main toxic features were acute mucositis, pneumonitis and dermatitis.

Shanta, V.; Krishnamurthi, S. (Cancer Inst., Madras (India))

1980-09-01

62

Effects of 8B size on the low-energy 7Be(p,?)8B cross section  

International Nuclear Information System (INIS)

[en] We calculate several ''size-like'' 8B observables within the microscopic three-cluster model and study their potential constraints on the zero-energy astrophysical S17(0) factor of the 7Be(p,?)8B reaction. We find within our three-cluster model that a simultaneous reproduction of the experimental data for the 8B radius and quadrupole moment and of the 8B-8Li Coulomb displacement energy implies S17(0)=(23-25) eV b. (orig.)

1998-06-22

63

The fabrication of metallic 7Be targets with a small diameter for 7Be(p,?)8B measurements  

International Nuclear Information System (INIS)

[en] The fabrication process for a metallic 7Be target of small diameter is described. Targets fabricated in this manner have been subjected to systematic tests and one of them has been used in a 7Be(p,?)8B measurement at the University of Washington. Target properties have been determined including the total amount of 7Be, the 7Be distribution over the target area derived via a decay ?-scan and the 7Be depth profile. The latter has been measured with the E?=1376 keV resonance in the 7Be(?,?)11C reaction

2002-01-01

64

51Cr-bleomycin in the diagnosis of ocular melanoma  

International Nuclear Information System (INIS)

[en] 51Cr-bleomycin was administered to 18 patients suspected of having an ocular melanoma with varying degree of development. The diagnosis was verified prior to surgical removal of the eye-ball by fluorescent angiography and computerized axial tomography. In operated patients histological diagnosis was also available. Scintigraphy after 51Cr-bleomycin administration appeared to be an effective diagnostic measure: sensitivity and specificity reached 90 and 87%, respectively. It is concluded that the method is useful in the preoperative diagnosis of ocular melanoma. (orig.)[de] In 18 diagnostisch schwierigen Faellen mit Verdacht auf ein Augenmelanom wurde 51Cr-Bleomycin verabreicht, wobei zur Verifikation die Fluoroszeinangiographie und die Computertomographie vor chirurgischer Entfernung des Auges dienten. Bei den operierten Patienten standen auch histologische Beobachtungen zur Verfuegung. Die Ergebnisse der szintigraphischen Untersuchungen zeigten deren hohe Empfindlichkeit (90%) und hohe Spezifitaet (87%). Auf Grund der erzielten Ergebnisse laesst sich schliessen, dass die angewandte Methode in solchen Faellen erfolgreich eingesetzt werden kann. (orig.)

1983-01-01

65

Combination chemotherapy of esophageal carcinoma using cisplatin, vindesine, and bleomycin.  

UK PubMed Central (United Kingdom)

Sixty-one patients with epidermoid carcinoma of the esophagus have been treated with a three drug combination of cisplatin, vindesine, and bleomycin. Of 53 patients currently evaluable for response, 29 (55%) have had partial remissions: 7/16 with metastatic, and 22/37 with local-regional disease. The median duration of response in metastatic patients is eight months. Of 28 patients treated preoperatively, 23 (82%) had resectable disease. The major toxicities seen were nephrotoxicity and myelosuppression. Cisplatin, vindesine and bleomycin is an effective combination in the treatment of esophageal carcinoma. Effects on long-term survival cannot yet be evaluated.

Kelsen DP; Bains M; Hilaris B; Chapman R; McCormack P; Alexander J; Hopfan S; Martini N

1982-03-01

66

[First clinical results of radiotherapy following partial synchronization by bleomycin  

UK PubMed Central (United Kingdom)

On the Ehrlich-ascites tumor and on the solide Ehrlich carcinoma of the mouse, bleomycin causes a large fixation in the (G2+M)-phase of the cell cycle of the tumor cells. Even in certain human solide tumors, after the application of bleomycin in a predetermined period an increase of the G2 portion of the proliferating cells can be observed. By individual control which can be peraformed rapidly and with high accuracy by impulse cytophotometry, this partial synchronisation effect can be used for radiotherapy.

Wannenmacher M; Esser E; Schumann J

1975-02-01

67

Distribution of 64Cu-Bleomycin in normal and tumor-bearing rats  

International Nuclear Information System (INIS)

[en] Accumulation of a radioactive label in tumor tissue is required for scintigraphic visualization of the tumor and has been achieved by application of bleomycin as carrier. This chemotherapeutic polypeptide drug has been labeled with 64Cu. Thin layer chromatography of 64Cu-bleomycin which was incubated for 22 hours at 370C showed no changes of the chelate. When urine of the 64Cu-bleomycin treated animals was chromatographed considerable amounts (9.3%) of free 64Cu appeared 2 hours after injection of the chelate and dissociation was found to be almost complete 4 hours after injection of labeled bleomycin. The distribution of 64Cu-bleomycin is similar to that found with sup(99m)Tc-bleomycin with long lasting accumulation in kidneys and liver. Highest concentration ratios of the activity in mesenchymal tumor (Yoshida) and blood respectively were found 6 hours after intravenous administration of 64Cu-bleomycin. (author)

1976-01-01

68

Interleukin-33 Potentiates Bleomycin-induced Lung Injury.  

UK PubMed Central (United Kingdom)

The mechanisms of interstitial lung disease (ILD) remain incompletely understood, though recent observations have suggested an important contribution by interleukin (IL)-33. Substantial elevation in IL-33 expression was found in the lungs of patients with idiopathic pulmonary fibrosis and scleroderma lung disease as well as in the bleomycin injury mouse model. Most of the observed IL-33 expression was intracellular and intranuclear, suggesting involvement of the full-length (fl) protein but not the proteolytically processed mature IL-33 cytokine. The effects of flIL-33 on mouse lungs were assessed independently and in combination with bleomycin injury using recombinant adenovirus-mediated gene delivery. Bleomycin-induced changes were not affected by gene deficiency of the IL-33 receptor T1/ST2. Combined flIL-33 expression and bleomycin injury had a synergistic effect on pulmonary lymphocyte and collagen accumulation, which could be explained by synergistic regulation of the cytokines TGF-?, IL-6, MCP-1, MIP-1?, and TNF-?. By contrast, there was no increase in the levels of the Th2 cytokines IL-4, IL-5, or IL-13. Also, flIL-33 was found to significantly increase expression of several heat shock proteins, particularly HSP70, which is known to be associated with ILD. Thus, full-length IL-33 is a synergistic proinflammatory and profibrotic regulator that acts by stimulating expression of several non-Th2 cytokines and activates expression of HSP70.

Luzina IG; Kopach P; Lockatell V; Kang PH; Nagarsekar A; Burke AP; Hasday JD; Todd NW; Atamas SP

2013-07-01

69

Haemodynamic sequelae of pulmonary fibrosis following intratracheal bleomycin in rats.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Intratracheal instillation of bleomycin in rats has been extensively used as an animal model of pulmonary fibrosis in humans, although it produces a patchy, airway based response. We proposed that the haemodynamic sequelae of the bleomycin model might be less severe than those associated with more diffuse lung injury. METHODS: Pulmonary and systemic haemodynamic indices were examined in adult Sprague-Dawley rats (approximately 400 g, n = 10) both at rest and during submaximal exercise on a rodent treadmill, approximately 60 days after intratracheal bleomycin (6 units.kg-1), and the results compared to a control group (n = 6). RESULTS: Compared to controls, mean pulmonary artery pressure (PPA) was increased by intratracheal bleomycin (p = 0.02) both at rest [24.5 (SEM 2.6) v 18.2(0.9) mm Hg] and during exercise [34.7(3.0) v 26.7(0.7) mm Hg]. PPA-pulse product was also increased, with a similar trend in right ventricular work index, but cardiac index was not altered. Right ventricular hypertrophy was noted on necropsy examination. Consistent with pulmonary fibrosis, lung dry weight, total protein, and hydroxyproline were also raised, and these values correlated strongly with (mean) PPA at rest (r2 = 0.86, 0.81, 0.69, respectively) and during exercise (r2 = 0.81, 0.79, 0.65, respectively). Packed cell volume was increased by intratracheal bleomycin, at 49(1) v 45(1)%, p = 0.02. CaO2 tended to decrease with exercise in the bleomycin group, although this was not statistically significant, while systemic oxygen delivery and consumption were not altered. CONCLUSIONS: Pulmonary hypertension and right ventricular hypertrophy occur in this model of lung fibrosis, and correlate with the severity of fibrosis. However, these sequelae were less severe than those previously demonstrated in association with crotalaria ingestion. We suggest that the haemodynamic sequelae of the intratracheal bleomycin model are consistent with patchy, airway based fibrosis, but reflect less well the haemodynamic sequelae of more diffuse fibrotic injury associated with systemic processes.

Williams JH Jr; Bodell P; Hosseini S; Tran H; Baldwin KM

1992-04-01

70

Targeting sphingosine kinase 1 attenuates bleomycin-induced pulmonary fibrosis.  

UK PubMed Central (United Kingdom)

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease, wherein transforming growth factor ? (TGF-?) and sphingosine-1-phosphate (S1P) contribute to the pathogenesis of fibrosis. However, the in vivo contribution of sphingosine kinase (SphK) in fibrotic processes has not been documented. Microarray analysis of blood mononuclear cells from patients with IPF and SphK1- or SphK2-knockdown mice and SphK inhibitor were used to assess the role of SphKs in fibrogenesis. The expression of SphK1/2 negatively correlated with lung function and survival in patients with IPF. Also, the expression of SphK1 was increased in lung tissues from patients with IPF and bleomycin-challenged mice. Knockdown of SphK1, but not SphK2, increased survival and resistance to pulmonary fibrosis in bleomycin-challenged mice. Administration of SphK inhibitor reduced bleomycin-induced mortality and pulmonary fibrosis in mice. Knockdown of SphK1 or treatment with SphK inhibitor attenuated S1P generation and TGF-? secretion in a bleomycin-induced lung fibrosis mouse model that was accompanied by reduced phosphorylation of Smad2 and MAPKs in lung tissue. In vitro, bleomycin-induced expression of SphK1 in lung fibroblast was found to be TGF-? dependent. Taken together, these data indicate that SphK1 plays a critical role in the pathology of lung fibrosis and is a novel therapeutic target.

Huang LS; Berdyshev E; Mathew B; Fu P; Gorshkova IA; He D; Ma W; Noth I; Ma SF; Pendyala S; Reddy SP; Zhou T; Zhang W; Garzon SA; Garcia JG; Natarajan V

2013-04-01

71

Peiminine ameliorates bleomycin-induced acute lung injury in rats.  

UK PubMed Central (United Kingdom)

The aim of this study was to investigate whether or not peiminine inhibits lung inflammation and pulmonary fibrosis in a rat model of bleomycin-induced lung injury. Rats were randomly divided into 4 groups. In 3 groups, intratracheal bleomycin (5 mg/kg) was used to induce acute lung injury, followed by administration of either carboxymethyl cellulose (control group, n=14), dexamethasone (DXS group, n=14) or peiminine (peiminine group, n=10). In the fourth group (sham-operated, n=12), normal saline was instilled instead of bleomycin, followed by administration of carboxymethyl cellulose. Drugs were administered intragastrically for 28 days. Lung sections were stained with hematoxylin and eosin (H&E) and Masson's trichrome, to grade the degree of alveolitis and pulmonary fibrosis. The lung index was calculated as the ratio of lung to body weight. Serum levels of interleukin-4 (IL-4), tumor necrosis factor-? (TNF-?) and interferon-? (IFN-?) were obtained using a radioimmunoassay. Immunocytochemical methods were employed to assess the expression of transforming growth factor-? (TGF-?), connective tissue growth factor (CTGF), NF-?B, extracellular signal-related kinase (ERK1/2), Fas and FasL in lung tissue. Peiminine and DXS significantly reduced alveolar inflammation and pulmonary interstitial inflammation in rats with bleomycin-induced lung injury. These protective effects were associated with significant (P<0.05) decreases in the levels of IFN-? in serum and of TGF-?, CTGF, ERK1/2, NF-?B and FasL in lung tissue. No effects were observed on serum TNF-? or IL-4. In conclusion, peiminine inhibits lung inflammation and pulmonary fibrosis in a rat model of bleomycin-induced lung injury, by reducing circulating IFN-? levels and inhibiting signal transduction pathways involving TGF-?, CTGF, ERK1/2, NF-?B and FasL.

Guo H; Ji F; Liu B; Chen X; He J; Gong J

2013-04-01

72

Study of the reactions 9Be(p, ?)6Li, 9Be(p,d)8Be from 300 keV to 900 keV  

International Nuclear Information System (INIS)

The experimental results concerning the two reactions 9Be(p,?)6Li and 9Be(p,d)8Be from 300 to 900 keV are presented. The angular distribution, excitation and total cross-section curves are expressed in absolute values after a normalization carried out using results given by Weber, Davis and Marion. (authors)

1968-01-01

73

Hyperthermic modification of bleomycin--DNA interaction detected by electron spin resonance.  

UK PubMed Central (United Kingdom)

Electron spin resonance spectra of DNA labeled with each of four spin-labeling compounds have been studied to detect interaction between the antibiotic bleomycin and DNA. Only one of these labels, compound IV, resulted in a modified spectrum when bound to DNA and the latter was subjected to bleomycin. This property has been used to monitor DNA-bleomycin interactions under physiological and hyperthermic conditions. Bleomycin produced an increase in rotational correlation time of the residue bound to DNA at 37 degrees C and a significantly higher increase at 43 degrees C. Some effect was still detected with bleomycin at 37 degrees C after preheating at 43 degrees C. Parallel studies have revealed enhanced binding of 59Fe-bleomycin to DNA during and after hyperthermic treatment.

Chapman IV; Leyko W; Gwozdzinski K; Koter M; Grzelinska E; Bartosz G

1983-12-01

74

89Strontium-induced bone marrow depression suppresses the early inflammatory response and fibrosis caused by intratracheal bleomycin  

International Nuclear Information System (INIS)

[en] To investigate the effect of bone marrow depression on the development of bleomycin-induced lung injury, F-344/Crl rats were given an intraperitoneal (IP) injection of 89SrCl2 (2 mCi/kg body weight) 7 days prior to the intratracheal (IT) instillation of 7.0 U/kg body weight bleomycin (Sr-bleomycin group). A second group of rats was given an IP injection of saline followed 7 days later by IT bleomycin (bleomycin group). Additional rats were given 89Sr IP and saline IT (Sr group) or saline IP and saline IT (saline group). Rats were sacrificed at 0, 3, 10, 21, and 30 days after the intratracheal instillations. 89Sr administration resulted in significantly lower numbers of circulating blood neutrophils and monocytes in the Sr-bleomycin group compared with the bleomycin group through at least the first 21 days following the IT instillations. Lymphocyte numbers were also depressed in the Sr-bleomycin group at days 3 and 21. Analysis of bronchoalveolar lavage fluid (BALF) revealed significantly reduced protein and lymphocyte numbers in the BALF from the 89Sr-bleomycin group compared with the bleomycin group at day 3, but not at later time points. Neutrophils in BALF were also lower (though not significantly) in the 89Sr-Bleomycin group at day 3. There was no difference in the number of BALF macrophages between the Sr-bleomycin and bleomycin groups at any time point throughout the study. Histology and morphometry showed the same trends as the BALF data with much less severe lesions in the 89SR-Bleomycin group compared with the bleomycin group at day 3, but not at later time points. At day 10, hydroxyproline values were significantly higher in the bleomycin group (47% increase above saline group) than the Sr-bleomycin group (only 18% increase above Sr group), but by day 21, there was no longer a significant difference between these two groups

1990-01-01

75

Antineoplastic Activity of Chloroacetohydroxamic Acid in Combination with Bleomycin Against Ehrlich Ascites Carcinoma (EAC) in Mice  

Directory of Open Access Journals (Sweden)

Full Text Available The research work has been undertaken in order to investigate the antineoplastic activity of chloroacetohydroxamic acid (CHA) in combination with bleomycin against Ehrlich ascites carcinoma (EAC) in Swiss Albino mice. Results showed that combination of treatment inhibits the tumor growth to more than 90% as against 56 and 65% for CHA and bleomycin, respectively. The combination treatment increases the life span of EAC bearing mice to 70% as against 30 and 50% for CHA and bleomycin, respectively. The combination treatment also recovers the hematological parameters and alkaline phosphatase (ALP) activity of tumor bearing mice more precisely than do CHA and bleomycin, individually.

J. A. Khanam; A. Y. K. M. Masud Rana

2001-01-01

76

Scuba diving post-bleomycin therapy: a case report.  

UK PubMed Central (United Kingdom)

Though there are theoretical risks to scuba diving after undergoing chemotherapy with bleomycin, this case report demonstrates that it may be done without obvious injury if one takes adequate precautions. In this case, one year was allowed to elapse prior to a return to diving. Subsequently 52 dives have been accomplished with no observable adverse effects. Studies are recommended to determine what precautions should be instituted.

Gray RN Jr

2010-11-01

77

Scuba diving post-bleomycin therapy: a case report.  

Science.gov (United States)

Though there are theoretical risks to scuba diving after undergoing chemotherapy with bleomycin, this case report demonstrates that it may be done without obvious injury if one takes adequate precautions. In this case, one year was allowed to elapse prior to a return to diving. Subsequently 52 dives have been accomplished with no observable adverse effects. Studies are recommended to determine what precautions should be instituted. PMID:21226396

Gray, Richard N

78

Pulmonary epithelial permeability in rats with bleomycin-induced pneumonitis  

International Nuclear Information System (INIS)

[en] This study was performed to investigate the mechanism by which 99mTc-DTPA molecules pass through the pulmonary epithelium following inhalation of 99mTc-DTPA aerosol. Interstitial pneumonitis was induced in 6-week-old male rats by instilling 1 mg/kg of bleomycin into the trachea. Disappearance of radioactivity from the lungs was measured with a gamma camera every 2 weeks to estimate pulmonary epithelial permeability, and light- and electron-microscopic histopathologic examinations were performed at the same intervals. There was a statistically significant increase in the pulmonary epithelial permeability at 2 weeks after the instillation of bleomycin. However, subsecquent changes in pulmonary epithelial permeability were not uniform; some animals showed recovery and some showed further increase and/or partial recovery. Microscopically, increase in the capillary bed, round cell infiltration, and widening of the interstitial space were observed in addition to the presence of macrophages in the alveolar spaces at 2 weeks. Electron microscopic examination revealed vacuolization, thinning and detachment of the alveolar epithelium, and denudation of the basement membrane. Prominent fibrosis, honeycombing, thinning of the pulmonary epithelium, and increase in collagen fibers were observed after 18 weeks. We consider that vacuolization, thinning, and detachment of the pulmonary epithelium and denudation of the basement membrane are related to the increase in pulmonary epithelial permeability in bleomycin-induced interstitial pneumonitis. (author)

1992-01-01

79

Cationic lipid:DNA complexes allow bleomycin uptake by melanoma cells.  

UK PubMed Central (United Kingdom)

Bleomycin is a chemotherapeutic agent barely diffusible through the plasmatic membrane. We evaluated DNA/cationic lipids complexes (lipoplexes) as mediators of its uptake in four spontaneous canine melanoma derived cell lines (Ak, Bk, Br and Rkb). Cell survival after lipofection plus or minus bleomycin was determined by the acid phosphatase method and the cellular uptake of lipoplexes, carrying the E. coli ?-galactosidase gene, was evidenced by SYBR Green I staining. The four cell lines resulted sensitive to the bleomycin/lipoplexes system in both spatial configurations. Survival rates values were lower than 20% in monolayers of the four tested lines and lower than 30% in three lines (Ak, Bk and Rkb) when grown as spheroids. The sensitization to bleomycin depended on lipoplexes in Ak and Rkb while Bk (in both spatial configurations) and Br (as monolayers) were sensitive to bleomycin alone. Although some degree of sensitivity to bleomycin was induced by cationic lipids alone in Ak and Rkb monolayers, the maximal bleomycin effects appeared in the presence of lipoplexes. The sensitization was independent of transcriptional activity. The co-administration of lipoplexes diminished bleomycin IC50: 10-fold in Ak and Rkb monolayers; and sensitized the Ak and Rkb resistant spheroids. The bleomycin cytotoxic effects depended on lipoplexes concentration and diminished when cells were incubated at 8°C. Our results suggest that lipoplexes sensitize cells to bleomycin, increasing its uptake by an active transport mechanism, such as endocytosis. The bleomycin/lipoplexes system appears as a promising combination of chemotherapy and non-viral cancer gene therapy.

Gil-Cardeza ML; Rossi ÚA; Villaverde MS; Glikin GC; Finocchiaro LM

2013-05-01

80

Cationic lipid:DNA complexes allow bleomycin uptake by melanoma cells.  

Science.gov (United States)

Bleomycin is a chemotherapeutic agent barely diffusible through the plasmatic membrane. We evaluated DNA/cationic lipids complexes (lipoplexes) as mediators of its uptake in four spontaneous canine melanoma derived cell lines (Ak, Bk, Br and Rkb). Cell survival after lipofection plus or minus bleomycin was determined by the acid phosphatase method and the cellular uptake of lipoplexes, carrying the E. coli ?-galactosidase gene, was evidenced by SYBR Green I staining. The four cell lines resulted sensitive to the bleomycin/lipoplexes system in both spatial configurations. Survival rates values were lower than 20% in monolayers of the four tested lines and lower than 30% in three lines (Ak, Bk and Rkb) when grown as spheroids. The sensitization to bleomycin depended on lipoplexes in Ak and Rkb while Bk (in both spatial configurations) and Br (as monolayers) were sensitive to bleomycin alone. Although some degree of sensitivity to bleomycin was induced by cationic lipids alone in Ak and Rkb monolayers, the maximal bleomycin effects appeared in the presence of lipoplexes. The sensitization was independent of transcriptional activity. The co-administration of lipoplexes diminished bleomycin IC50: 10-fold in Ak and Rkb monolayers; and sensitized the Ak and Rkb resistant spheroids. The bleomycin cytotoxic effects depended on lipoplexes concentration and diminished when cells were incubated at 8°C. Our results suggest that lipoplexes sensitize cells to bleomycin, increasing its uptake by an active transport mechanism, such as endocytosis. The bleomycin/lipoplexes system appears as a promising combination of chemotherapy and non-viral cancer gene therapy. PMID:23453489

Gil-Cardeza, María L; Rossi, Úrsula A; Villaverde, Marcela S; Glikin, Gerardo C; Finocchiaro, Liliana M E

2013-02-06

 
 
 
 
81

N-acetyl-L-cysteine inhibits bleomycin induced apoptosis in malignant testicular germ cell tumors.  

UK PubMed Central (United Kingdom)

Antioxidants may prevent apoptosis of cancer cells via inhibiting reactive oxygen species (ROS). However, to date no study has been carried out to elucidate the effects of strong antioxidant N-acetylcysteine (NAC) on Bleomycin induced apoptosis in human testicular cancer (NTERA-2, NT2) cells. For this reason, we studied the effects of Bleomycin and NAC alone and in combination on apoptotic signaling pathways in NT2 cell line. We determined the cytotoxic effect of bleomycin on NT2 cells and measured apoptosis markers such as Caspase-3, -8, -9 activities and Bcl-2, Bax, Cyt-c, Annexin V-FTIC and PI levels in NT2 cells incubated with different agents for 24 h. Early apoptosis was determined using FACS assay. We found half of the lethal dose (LD50) of Bleomycin on NT2 cell viability as 400, 100, and 20 µg/ml after incubations for 24, 48, and 72 h, respectively. Incubation with bleomycin (LD50 ) and H2O2 for 24 h increased Caspase-3, -8, -9 activities, Cyt-c and Bax levels and decreased Bcl-2 levels. The concurrent incubation of NT2 cells with bleomycin/H2O2 and NAC (5 mM) for 24 h abolished bleomycin/H2O2-dependent increases in Caspase-3, -8, -9 activities, Bax and Cyt-c levels and bleomycin/H2O2-dependent decrease in Bcl-2 level. Our results indicate that bleomycin/H2O2 induce apoptosis in NT2 cells by activating mitochondrial pathway of apoptosis, while NAC diminishes bleomycin/H2O2 induced apoptosis. We conclude that NAC has antagonistic effects on Bleomycin-induced apoptosis in NT2 cells and causes resistance to apoptosis which is not a desired effect in eliminating cancer cells.

Kucuksayan E; Cort A; Timur M; Ozdemir E; Yucel SG; Ozben T

2013-07-01

82

A validated HPLC method for the simultaneous determination of bleomycin A2 and B2 in human plasma  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Bleomycin is an anti-neoplastic drug that has recently been used for the treatment of vascular anomalies. The plasma concentration of bleomycin following intralesional injection into vascular lesions is unknown. An expedient method was developed for the determination of plasma bleomycin levels using...

Mabeta, Peace; Dippenaar, Nola; Shelver, Graham

83

DNA sequence and structure recognition by Fe(II)[center dot]bleomycin  

Energy Technology Data Exchange (ETDEWEB)

The bleomycins (BLMs) are a family of clinically-important antitumor antibiotics whose chemotherapeutic effects are believed to be expressed at the level of DNA degradation. Bleomycin-mediated DNA strand scission is sequence-selective, resulting in cleavage predominantly at [sup 5[prime

Kane, S.A.

1993-01-01

84

The crypto-OH radical in the damage of DNA by bleomycin-Fe2+?  

UK PubMed Central (United Kingdom)

1. Effects of various OH scavengers, superoxide dismutase and catalase on the formation of malondialdehyde-like products from DNA by bleomycin-Fe2+ were studied. In no case was a protective effect observed. 2. These results can be interpreted on the basis that a crypto-OH radical mediates the damage to DNA by bleomycin-Fe2+.

Bartkowiak A; Grzelinska E; Bartosz G; Zab?ocka J; Leyko W

1982-01-01

85

Pulmonary toxicity in patients with non-Hodgkin's lymphoma treated with bleomycin-containing combination chemotherapy  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Subclinical and clinical bleomycin-induced pulmonary toxicity (BIP) were investigated retrospectively in 109 patients with non-Hodgkin's lymphoma treated by combination chemotherapy containing bleomycin. A decrease in carbon monoxide diffusing capacity (DLCO) was found in 12.8% of patients. The cumu...

Ngan, HYS; Liang, RHS; Lam, WK; Chan, TK

86

Dermojet delivery of bleomycin for the treatment of recalcitrant plantar warts.  

UK PubMed Central (United Kingdom)

BACKGROUND: Plantar warts may cause significant morbidity. Intralesional bleomycin is effective. When bleomycin is injected with a needle and syringe, it is difficult to prevent the bleomycin from infiltrating the dermis adjacent to the wart, producing unnecessary acute pain, persistent pain, and potential sloughing of normal adjacent skin. Efficacy of delivery by dermojet is not yet established. OBJECTIVES: To assess the response of recalcitrant plantar warts to bleomycin delivered by dermojet. METHODS: A total of 47 patients with 138 plantar warts present for more than 2 years and resistant to 10 cycles of cryosurgery, were recruited. Bleomycin (1 U/ml) was delivered intralesionally by dermojet at 5-week intervals for 25 weeks. RESULTS: Out of 138, 124 (89.9%) plantar warts showed complete or partial clearance after one to five sets of bleomycin injections. The recurrence rate was 6/138 (4.4%), and 8/138 (5.8%) warts failed to clear. The reduction in mean surface area of the plantar warts after each set of bleomycin injections compared to baseline surface area was statistically significant. Local side effects were similar to other methods of delivery. No systemic side effects were reported. CONCLUSIONS: This study assesses therapeutic efficacy of bleomycin delivered by dermojet in solely recalcitrant plantar warts. It provides preliminary evidence that this method of delivery may benefit a group of patients with particularly recalcitrant plantar warts and is safe and easy to use in routine dermatology practice.

Agius E; Mooney JM; Bezzina AC; Yu RC

2006-01-01

87

Effects of intratracheal instillation of bleomycin on phospholipid synthesis in hamster lung tissue slices  

International Nuclear Information System (INIS)

[en] Bleomycin, an antineoplastic drug, is known to produce interstitial pulmonary fibrosis (IPF). As a result, it is commonly employed in various species to produce animal models of fibrosis. We have examined the uptake of [14C] acetate by lung slices and its incorporation into lipids in the slices at various times following intratracheal administration of a fibrogenic dose of bleomycin in hamsters. As compared to saline controls, bleomycin had no effect on [14C] acetate uptake at 4 and 7 days but it increased the uptake at 2 and 14 days after treatment. The incorporation of [14C] acetate into total lipid was significantly reduced to 44, 62, 62, and 75% of the control at 2, 4, 7, and 14 days after bleomycin treatment, respectively. The incorporation into lipid as a percentage of the uptake was 12.2 in control animals whereas in bleomycin-treated animals, it was 4.7, 8.0, 7.3, and 6.9 at the corresponding times. Separation of lipids into various fractions revealed that bleomycin treatment specifically inhibited the synthesis of phosphatidylcholine and neutral lipid at all times of the study. The synthesis of all other phospholipids except phosphatidylethanolamine was depressed at 2 days. The latter was, however, depressed at 7 and 14 days after bleomycin treatment. It was concluded from the present study that bleomycin treatment inhibits the synthesis of phospholipid and neutral lipid and this may eventually lead to decreased surfactant production

1987-01-01

88

Ultrasensitive fluorescence detection of bleomycin via exonuclease III-aided DNA recycling amplification.  

Science.gov (United States)

A "signal on" approach for ultrasensitive detection of bleomycin was developed by bleomycin-Fe(II) induced hairpin DNA scission to release its loop, which was subsequently recycled with the aid of exonuclease III and a probe to amplify the detectable fluorescent signal. PMID:23872711

Gao, Fenglei; Lei, Jianping; Ju, Huangxian

2013-09-01

89

Extensive pneumothorax, pneumomediastinum and surgical emphysema as a complication of bleomycin therapy  

International Nuclear Information System (INIS)

[en] Bleomycin is a commonly used chemotherapeutic agent and one of the commonest cytotoxic drugs leading to pulmonary parenchymal damage. It generally leads to interstitial pneumonitis and fibrosis, hypersensitivity reactions and acute respiratory distress syndrome. We describe an 8-year-old boy who, following prolonged bleomycin therapy, demonstrated extensive air dissection and extrapulmonary air, an unusual and fatal complication. (orig.)

2005-01-01

90

Effects of intratracheal instillation of bleomycin on phospholipid synthesis in hamster lung tissue slices  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin, an antineoplastic drug, is known to produce interstitial pulmonary fibrosis (IPF). As a result, it is commonly employed in various species to produce animal models of fibrosis. We have examined the uptake of (/sup 14/C) acetate by lung slices and its incorporation into lipids in the slices at various times following intratracheal administration of a fibrogenic dose of bleomycin in hamsters. As compared to saline controls, bleomycin had no effect on (/sup 14/C) acetate uptake at 4 and 7 days but it increased the uptake at 2 and 14 days after treatment. The incorporation of (/sup 14/C) acetate into total lipid was significantly reduced to 44, 62, 62, and 75% of the control at 2, 4, 7, and 14 days after bleomycin treatment, respectively. The incorporation into lipid as a percentage of the uptake was 12.2 in control animals whereas in bleomycin-treated animals, it was 4.7, 8.0, 7.3, and 6.9 at the corresponding times. Separation of lipids into various fractions revealed that bleomycin treatment specifically inhibited the synthesis of phosphatidylcholine and neutral lipid at all times of the study. The synthesis of all other phospholipids except phosphatidylethanolamine was depressed at 2 days. The latter was, however, depressed at 7 and 14 days after bleomycin treatment. It was concluded from the present study that bleomycin treatment inhibits the synthesis of phospholipid and neutral lipid and this may eventually lead to decreased surfactant production.

Giri, S.N.

1987-12-01

91

Study of the 7Be(p,?)8B and 7Li(n,?)8Li capture reactions using the shell model embedded in the continuum  

International Nuclear Information System (INIS)

[en] We apply the realistic shell model which includes the coupling between many-particle (quasi-) bound states and the continuum of one-particle scattering states to the spectroscopy of mirror nuclei 8B and 8Li, as well as to the description of low-energy cross sections (the astrophysical S-factors) in the capture reactions 7Be(p,?)8B and 7Li(n,?)8Li

1999-05-17

92

Development and time-course of bleomycin-induced pulmonary fibrosis in NMRI mice  

Directory of Open Access Journals (Sweden)

Full Text Available Bleomycin-induced pulmonary fibrosis is a widely used experimental model for human lung fibrosis. The severity of fibrosis varies among different strains of mice and investigation on different strains and finding the mechanisms of variation is important in understanding the pathogenesis of human lung fibrosis. In the present study, NMRI mice were used to investigate the severity and also time-course of bleomycin-induced pulmonary fibrosis in comparison with C57BL/6 mice. After single dose administration of intratracheal bleomycin, the fibrotic response was studied by biochemical measurement of collagen deposition and semiquantitative analysis of pathological lung changes. NMRI mice developed lung fibrosis from 1 to 4 week after bleomycin instillation, with significant increases in lung collagen content and significant morphological changes (P < 0.05). These findings indicate that NMRI mice might be suitable as an experimental model of bleomycin-induced lung fibrosis.

Jafarian-Dehkordi A.; Rabbani M.; Mir Mohammad Sadeghi H.; Afshar-Moghaddam N.; Alavi S.A.; Mahmoodi F; Safaeian L

2007-01-01

93

Study of Low Temperature Baking Effect on Field Emission on Nb Samples Treated by BEP, EP, and BCP  

Energy Technology Data Exchange (ETDEWEB)

Field emission is still one of the major obstacles facing Nb superconducting radio frequency (SRF) community for allowing Nb SRF cavities to reach routinely accelerating gradient of 35 MV/m that is required for the international linear collider. Nowadays, the well know low temperature backing at 120 oC for 48 hours is a common procedure used in the SRF community to improve the high field Q slope. However, some cavity production data have showed that the low temperature baking may induce field emission for cavities treated by EP. On the other hand, an earlier study of field emission on Nb flat samples treated by BCP showed an opposite conclusion. In this presentation, the preliminary measurements of Nb flat samples treated by BEP, EP, and BCP via our unique home-made scanning field emission microscope before and after the low temperature baking are reported. Some correlations between surface smoothness and the number of the observed field emitters were found. The observed experimental results can be understood, at least partially, by a simple model that involves the change of the thickness of the pent-oxide layer on Nb surfaces.

Andy Wu, Song Jin, Robert Rimmer, Xiang Yang Lu, K. Zhao, Laura MacIntyre, Robert Ike

2010-05-01

94

Electromagnetic dissociation of 8B and the astrophysical S factor for 7Be(p,?) 8 B  

International Nuclear Information System (INIS)

We present S factor data obtained from the Coulomb dissociation of 83 MeV /nucleon 8B , and analyze 7Be longitudinal momentum distributions measured at 44 and 81 MeV /nucleon using a potential model, first-order perturbation theory, and dynamical solution of the time-dependent Schroedinger equation. Comparing our results with independent continuum-discretized coupled channels calculations, we study the reaction model and beam energy dependence of the E2 contribution to the dissociation cross section. By fitting radiative capture and Coulomb breakup data taken below relative energies of 400 keV with potential models constrained by 7Li+n and 7Be+p elastic scattering data, we examine the mutual consistency of recent S 17 measurements and obtain a recommended value for S 17 (0) of 18.6±0.4 (experimental) ±1.1 (extrapolation) eV b (1?) . This result is in good agreement with recent experimental determinations of the asymptotic normalization coefficient of the valence proton wave function in 8B .

2003-01-01

95

Bleomycin lung toxicity detected by technetium-99m diethylene triamine penta-acetic acid aerosol scintigraphy  

International Nuclear Information System (INIS)

In this study we investigated bleomycin-induced pulmonary toxicity in patients with germ-cell tumour by means of technetium-99m DTPA aerosol scintigraphy. Twenty untreated patients who had no clinical or radiological evidence of pulmonary disease received four courses of etoposide, cisplatin and bleomycin chemotherapy. Aerosol lung scinitgraphy and pulmonary function tests were performed in all patients before bleomycin treatment and after administration of 180 and 360 mg bleomycin. On the basis of the scintigrams the percentage decline in activity per minute (Kep) was evaluated, which represented an accurate parameter of lung membrane permeability. Pretreatment Kep values (0.891±0.286) were significantly lower than those obtained following 180 and 360 mg bleomycin treatment (1.176±0.336 and 1.389±0.477, respectively. The Kep values obtained with 180 and 360 mg bleomycin treatments were also significantly different. In contrast no significant change was observed in the results of pulmonary function tests. Our results demonstrate that evaluation of the pulmonary clearance of 99mTc-DTPA represents a useful mean of monitoring the functional status of the lung epithelial membrane during bleomycin treatment. (orig./MG).

1993-01-01

96

DTIC, CCNU, bleomycin and vincristine (BOLD) in metastatic melanoma.  

UK PubMed Central (United Kingdom)

Treatment of 91 consecutive patients having metastatic, Stage IV melanoma who had not received any previous chemotherapy was begun between January 1977 and April 1978. The therapy included bleomycin (B) at 7.5 units subcutaneously in the first course and 15 units in subsequent courses on days 1 and 4; vincristine or Oncovin (O) at 1 mg/m2 intravenously on days 1 and 5; CCNU or lomustine (L) at 80 mg/m2 p.o. on day 1 and DTIC (D) 200 mg/m2 intravenously on days 1 through 5. Evaluable patients (72) were those who had measurable tumours in the viscera and on the skin. Seven patients (9%) responded with complete tumor regression (CR), 22 (31%) with partial regression (PR) (50% or more tumor regression), 12 (17%) with stabilization of disease, and 31 (43%) with progression of the disease. Patients who responded with CR, PR, and stable disease (41 patients) had a median survival of 67 weeks, while those who did not respond (31 patients) had a median survival of 20 weeks (P < .0001). Overall median survival was 31 weeks. The bleomycin-Oncovin-lomustine-DTIC (BOLD) regimen is an effective alternative treatment for metastatic melanoma; there is good tumor response and prolongation of survival in the responding patients. Its overall toxicity is mild to moderate.

Seigler HF; Lucas VS Jr; Pickett NJ; Huang AT

1980-12-01

97

Synthesis of samarium binding bleomycin - a possible NCT radiosensitizer  

International Nuclear Information System (INIS)

Bleomycin (BLM) is a drug that has attractive features for the development of a new radiopharmaceutical, particularly with regard to neutron capture therapy (NCT) sensitized by Sm-149. It has the ability to chelate many metal ions. In vitro studies have shown that up to 78% of BLM present in a cell is accumulated inside the nucleus or in the nuclear membrane. In addition, this drug has higher affinity for tumor tissues than for normal tissues. Radioactive isotopes carried by this antibiotic would be taken preferentially to one important cellular targets DNA. Besides, BLM displays intrinsic anti-tumor activity - it is a chemotherapic antibiotic clinically used against some cancers. This study aimed to obtain bleomycin molecules bound to samarium (BLM-Sm) for NCT studies in vitro and in vivo. The binding technique employed in this work has great simplicity and low cost. Thin layer chromatography, high performance liquid chromatography, fast protein liquid chromatography and analysis by ICP-AES were applied to verify the binding molecule. ICP-AES results showed the presence of samarium in the sample peaks related to BLM-Sm. However, efficiency and stability of this bond needs to be investigated. (author)

2011-01-01

98

Synthesis of samarium binding bleomycin - a possible NCT radiosensitizer  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin (BLM) is a drug that has attractive features for the development of a new radiopharmaceutical, particularly with regard to neutron capture therapy (NCT) sensitized by Sm-149. It has the ability to chelate many metal ions. In vitro studies have shown that up to 78% of BLM present in a cell is accumulated inside the nucleus or in the nuclear membrane. In addition, this drug has higher affinity for tumor tissues than for normal tissues. Radioactive isotopes carried by this antibiotic would be taken preferentially to one important cellular targets DNA. Besides, BLM displays intrinsic anti-tumor activity - it is a chemotherapic antibiotic clinically used against some cancers. This study aimed to obtain bleomycin molecules bound to samarium (BLM-Sm) for NCT studies in vitro and in vivo. The binding technique employed in this work has great simplicity and low cost. Thin layer chromatography, high performance liquid chromatography, fast protein liquid chromatography and analysis by ICP-AES were applied to verify the binding molecule. ICP-AES results showed the presence of samarium in the sample peaks related to BLM-Sm. However, efficiency and stability of this bond needs to be investigated. (author)

Mendes, B.M., E-mail: bmm@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Mendes, T.M.; Campos, T.P.R., E-mail: campos@nuclear.ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2011-07-01

99

Effect of bleomycin and irradiation on G2 progression  

International Nuclear Information System (INIS)

[en] The interaction of bleomycin and x-irradiation on the induction of G2 delay in Chinese hamster ovary cells was investigated utilizing the mitotic selection procedure for cell cycle analysis. Following the addition of BLM, the number of cells selected in mitosis remained at control level for a refractory period and then decreased. The location of the transition point, i.e., the age in G2 at which cells become refractory to a progression blockade, was concentration-dependent, ranging from the S/G2 boundary at low concentrations to the G2/M boundary at high concentrations. Depending upon the concentration of the drug used and the duration of exposure, the mitotic rate either decreased to zero or else leveled off at some intermediate value and then recovered to the control level. The duration of BLM-induced division delay was thus dependent upon the concentration used and the duration of exposure. When cells were treated with pulses of bleomycin (10-500 ?g/ml) in addition to x-irradiation, the mitotic rate declined as with exposure to x-ray alone. However, the recovery from radiation-induced division delay and the subsequent reappearance of mitotic cells in the selection window was delayed until the cells had recovered from their BLM-induced division delay. This implies that, in contrast to the synergistic effects observed for cell lethality, BLM and radiation do not interact in the production of a progression blockade and the resultant division delay

1978-11-15

100

Assessment of DNA strand breaks induced by bleomycin in barley by the comet assay.  

Science.gov (United States)

Comet assay was applied to study induction and repair of DNA damage produced by bleomycin in barley genome. Experimental conditions were adapted to achieve efficient detection of both DNA single- and double-strand breaks. Substantial increase of the parameter "% of DNA in tail" was observed coupled with almost linear dependence from bleomycin concentration, more pronounced for the induction of DNA double-strand breaks. Data obtained at different recovery periods displayed rapid restoration of breakage, revealing that efficient mechanisms for repair of strand discontinuities induced by bleomycin are functional in barley DNA loop domains. PMID:18418872

Georgieva, Mariyana; Stoilov, Lubomir

2008-06-01

 
 
 
 
101

Assessment of DNA strand breaks induced by bleomycin in barley by the comet assay.  

UK PubMed Central (United Kingdom)

Comet assay was applied to study induction and repair of DNA damage produced by bleomycin in barley genome. Experimental conditions were adapted to achieve efficient detection of both DNA single- and double-strand breaks. Substantial increase of the parameter "% of DNA in tail" was observed coupled with almost linear dependence from bleomycin concentration, more pronounced for the induction of DNA double-strand breaks. Data obtained at different recovery periods displayed rapid restoration of breakage, revealing that efficient mechanisms for repair of strand discontinuities induced by bleomycin are functional in barley DNA loop domains.

Georgieva M; Stoilov L

2008-06-01

102

Bleomycin labelled with sup(99m)Tc for differentiation of breast tumors  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin labelled with sup(99m)Tc was used to differentiate benign and malignant breast tumors. Breast scintigraphy was performed 15 and 60 min following the IV injection of 5 mCisup(99m)Tc bleomycin. Thirty-two patients with breast tumor (14 carcinomas and 18 benign nodular lesions) were examined. Cytologic or histologic verification of the tumor was carried out in all cases. All malignant tumors of the breast in the investigated group of patients revealed significantly increased accumulation of sup(99m)Tc-bleomycin.

Warczyglowa, D.; Szostak, S.; Marzecki, Z.; Tustanowski, S.

1981-02-01

103

Bleomycin labelled with 99mTc for differentiation of breast tumors.  

UK PubMed Central (United Kingdom)

Bleomycin labelled with 99mTc was used to differentiate benign and malignant breast tumors. Breast scintigraphy was performed 15 and 60 min following the IV injection of 5 mCi99mTc bleomycin. Thirty-two patients with breast tumor (14 carcinomas and 18 benign nodular lesions) were examined. Cytologic or histologic verification of the tumor was carried out in all cases. All malignant tumors of the breast in the investigated group of patients revealed significantly increased accumulation of 99mTc-bleomycin.

Warczyglowa D; Szostak S; Marzecki Z; Tustanowski S

1981-02-01

104

Bleomycin labelled with sup(99m)Tc for differentiation of breast tumors  

International Nuclear Information System (INIS)

[en] Bleomycin labelled with sup(99m)Tc was used to differentiate benign and malignant breast tumors. Breast scintigraphy was performed 15 and 60 min following the IV injection of 5 mCisup(99m)Tc bleomycin. Thirty-two patients with breast tumor (14 carcinomas and 18 benign nodular lesions) were examined. Cytologic or histologic verification of the tumor was carried out in all cases. All malignant tumors of the breast in the investigated group of patients revealed significantly increased accumulation of sup(99m)Tc-bleomycin. (orig.)

1981-01-01

105

Efficient repair of bleomycin-induced double-strand breaks in barley ribosomal genes.  

Science.gov (United States)

Ability of barley ribosomal genes to cope with damage produced in vivo by the radiomimetic agent bleomycin was investigated. Repair kinetics of bleomycin-induced double-strand breaks in ribosomal and total genomic DNA was compared. Induction and repair of double-strand breaks in defined regions of the ribosomal genes was also analyzed. Preferential sensitivity of barley linker DNA towards bleomycin treatment in vivo was established. Relatively higher yield of initially induced double-strand breaks in genomic DNA in comparison to ribosomal DNA was also found. Fragments containing intergenic spacers of barley rRNA genes displayed higher sensitivity to bleomycin than the coding sequences. No heterogeneity in the repair of DSB between transcribed and non-transcribed regions of ribosomal genes was detected. Data indicate that DSB repair in barley rDNA, although more efficient than in genomic DNA, does not correlate with the activity of nucleolus organizer regions. PMID:16930631

Manova, Vasilissa; Gecheff, Kostadin; Stoilov, Lubomir

2006-08-22

106

Efficient repair of bleomycin-induced double-strand breaks in barley ribosomal genes.  

UK PubMed Central (United Kingdom)

Ability of barley ribosomal genes to cope with damage produced in vivo by the radiomimetic agent bleomycin was investigated. Repair kinetics of bleomycin-induced double-strand breaks in ribosomal and total genomic DNA was compared. Induction and repair of double-strand breaks in defined regions of the ribosomal genes was also analyzed. Preferential sensitivity of barley linker DNA towards bleomycin treatment in vivo was established. Relatively higher yield of initially induced double-strand breaks in genomic DNA in comparison to ribosomal DNA was also found. Fragments containing intergenic spacers of barley rRNA genes displayed higher sensitivity to bleomycin than the coding sequences. No heterogeneity in the repair of DSB between transcribed and non-transcribed regions of ribosomal genes was detected. Data indicate that DSB repair in barley rDNA, although more efficient than in genomic DNA, does not correlate with the activity of nucleolus organizer regions.

Manova V; Gecheff K; Stoilov L

2006-10-01

107

The effect of ionizing radiation and bleomycin on transfecting ability of Bacillus subtilis phage DNA  

International Nuclear Information System (INIS)

Infectious DNA of Bacillus subtilis phage 029 and SPP1 has been subjected to ionizing radiation and/or bleomycin treatment. The extent of degradation of the treated DNA was determined on sucrose gradients and biological activity was analyzed using the transfection principle. It was found that loss of biological activity following irradiation or bleomycin treatment of the DNA cannot be accounted for by the production of single- or double-strand breaks. Furthermore, it was observed that pre-irradiation exhibits a synergistic effect on loss of biological activity and production of strand breaks following bleomycin treatment. The authors propose here a simple system capable of detecting biological damage in DNA following irradiation doses as low as 0.5 Gy prior to bleomycin treatment. (Auth.)

1979-01-05

108

Protocol engineering  

CERN Multimedia

Communication protocols form the operational basis of computer networks and tele communication systems. They are behavior conventions that describe how com munication systems inter act with each other, defining the temporal order of the interactions and the formats of the data units exchanged - essentially they determine the efficiency and reliability of computer networks. Protocol Engineering is an important discipline covering the design, validation, and implementation of communication protocols. Part I of this book is devoted to the fundamentals of communication protocols, describing their

König, Hartmut

2012-01-01

109

Photochemical internalization enhances the efficacy of bleomycin in malignant glioma cells  

Science.gov (United States)

The utility of photochemical internalization (PCI) for the treatment of malignant gliomas was investigated in vitro using: (1) monolayers consisting of F98 rat glioma cells, and (2) human glioma spheroids established from biopsy-derived glioma cells. In both cases, the cytotoxicity of AlPcS2a- based PCI of bleomycin was compared to: (1) AlPcS2a-PDT, and (2) bleomycin. In all cases, monolayers and spheroids were incubated in AlPcS2a (18 h), bleomycin (4 h), or AlPcS2a (18 h) + bleomycin (4 h) and were subsequently exposed to 670 nm light. Toxicity was evaluated using colony formation assays or spheroid growth kinetics. Neither F98 rat glioma cells in monolayer nor human glioma spheroids were found to be particularly sensitive to the effects of low irradiance (5 mW cm-2), low radiant exposure (1.5 J cm-2) AlPcS2a -PDT. Bleomycin was found to be moderately toxic to F98 cells in monolayer at relatively low concentrations - incubation of F98 cells in 0.1 ?g ml-1 for 4 hours resulted in 80% survival. Under similar incubation conditions, the effects of bleomycin on human glioma spheroids were negligible. In both in vitro systems investigated, the PCI effect was found to be significant. For example, PCI consisting of a radiant exposure of 1.5 J cm-2 together with 0.25 ?g ml-1 bleomycin resulted in approximately 20 and 65 % survival of F98 rat glioma cells and human glioma spheroids respectively. These results show that AlPcS2a-mediated PCI can be used to enhance the efficacy of chemotherapeutic agents such as bleomycin in malignant gliomas.

Madsen, Steen J.; Blickenstaff, Joseph W.; Vo, Van; Angell-Petersen, Even; Hirschberg, Henry

2009-02-01

110

Bleomycin induced pulmonary to cytotoxicity in patients with germ cell tumours  

International Nuclear Information System (INIS)

Background: Bleomycin is a cytotoxic drug used in treatment of Germ Cell Tumours (GCTs) and is associated with pulmonary toxicity. Bleomycin pulmonary toxicity (BPT) manifests predominantly as pulmonary fibrosis, organising pneumonia (OP) or Nonspecific Interstitial Pneumonitis (NSIP). Our objectives were to determine the incidence of BPT, describe the common HRCT patterns of pulmonary toxicity and to find out the correlation of variables (cumulative dose of bleomycin, age and glomerular filtration rate) with pulmonary toxicity. Methods: The study included the data of 96 patients from March 2006 to September 2008. All patients had histologically proven GCT and received bleomycin containing regimes. Variables age, GFR at the time of initial presentation along with cumulative dose of bleomycin at completion of chemotherapy or at the time of BPT were recorded. The High resolution CT chest (HRCT) of these patients was independently reviewed by two radiologists. Bleomycin toxicity was reported on the radiologic features of pulmonary fibrosis, OP or NSIP. Results : Fourteen patients (14.6%) developed BPT. Common patterns of BPT were, pulmonary fibrosis (5.2%), OP (5.2%) and NSIP (4.2%). Using the Univariate regression analysis there was significant relationship between BPT and age, cumulative bleomycin dose an d initial GFR at the beginning of treatment. Conclusions: Because BPT can be progressive and fatal, early recognition is important. The diagnosis of pulmonary toxicity should be considered in any patient with new or progressive respiratory complaints. BPT can be difficult to diagnose; therefore, knowledge and understanding of radiologic manifestations of toxicity caused by Bleomycin are necessary for institution of appropriate treatment. There is increasing incidence of BPT with increasing age, cumulative dose and decreasing GFR. (author)

2010-01-01

111

?-catenin in the alveolar epithelium protects from lung fibrosis after intratracheal bleomycin.  

UK PubMed Central (United Kingdom)

RATIONALE: Alveolar epithelial cells (AECs) play central roles in the response to lung injury and the pathogenesis of pulmonary fibrosis. Objectives: We aimed to determine the role of ?-catenin in alveolar epithelium during bleomycin-induced lung fibrosis. METHODS: Genetically modified mice were developed to selectively delete ?-catenin in AECs and were crossed to cell fate reporter mice that express ?-galactosidase (?gal) in cells of AEC lineage. Mice were given intratracheal bleomycin (0.04 units) and assessed for AEC death, inflammation, lung injury, and fibrotic remodeling. Mouse lung epithelial cells (MLE12) with small interfering RNA knockdown of ?-catenin underwent evaluation for wound closure, proliferation, and bleomycin-induced cytotoxicity. MEASUREMENTS AND MAIN RESULTS: Increased ?-catenin expression was noted in lung parenchyma after bleomycin. Mice with selective deletion of ?-catenin in AECs had greater AEC death at 1 week after bleomycin, followed by increased numbers of fibroblasts and enhanced lung fibrosis as determined by semiquantitative histological scoring and total collagen content. However, no differences in lung inflammation or protein levels in bronchoalveolar lavage were noted. In vitro, ?-catenin-deficient AECs showed increased bleomycin-induced cytotoxicity as well as reduced proliferation and impaired wound closure. Consistent with these findings, mice with AEC ?-catenin deficiency showed delayed recovery after bleomycin. CONCLUSIONS: ?-Catenin in the alveolar epithelium protects against bleomycin-induced fibrosis. Our studies suggest that AEC survival and wound healing are enhanced through ?-catenin-dependent mechanisms. Activation of the developmentally important ?-catenin pathway in AECs appears to contribute to epithelial repair after epithelial injury.

Tanjore H; Degryse AL; Crossno PF; Xu XC; McConaha ME; Jones BR; Polosukhin VV; Bryant AJ; Cheng DS; Newcomb DC; McMahon FB; Gleaves LA; Blackwell TS; Lawson WE

2013-03-01

112

Bleomycin-induced DNA repair by Saccharomyces cerevisiae ATP-dependent polydeoxyribonucleotide ligase  

Energy Technology Data Exchange (ETDEWEB)

In contrast to ligase-deficient (cdc9) Saccharomyces cerevisiae, which did not rejoin bleomycin-induced DNA breaks, ligase-proficient (CDC9) yeast cells eliminated approximately 90% of DNA breaks within 90 to 120 min after treatment. Experimental conditions restricted enzymatic removal of the unusual 3{prime}-phosphoglycolate terminal in DNA cleaved by bleomycin and involved doses producing equivalent numbers of DNA breaks or doses producing equivalent killing.

Moore, C.W. (Univ. of Rochester School of Medicine and Dentistry, NY (USA))

1988-10-01

113

Contributions of NMR to the Understanding of the Coordination Chemistry and DNA Interactions of Metallo-Bleomycins  

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Full Text Available Bleomycins are a family of glycopeptide antibiotics that have the ability to bind and degrade DNA when bound to key metal ions, which is believed to be responsible for their antitumor activity. Knowledge of the structures of metallo-bleomycins is vital to further characterize their mechanism of action. To this end, numerous structural studies on metallo-bleomycins have been conducted. NMR spectroscopy has had a key role in most of these studies, and has led to very important findings involving the coordination chemistry of metallo-bleomycins, and the details of many metallo-bleomycin-DNA spatial correlations for this important drug. This paper reviews the most important contributions of NMR to the bleomycin field.

Teresa Lehmann; Elena Topchiy

2013-01-01

114

Combination therapy of esophageal carcinoma with radiation and bleomycin  

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The concurrent combination therapy of radiation and Bleomycin was performed in a total of 175 cases of esophageal carcinoma. In 107 (63%) cases of them, in which the scheduled curative treatment was completed, yearly survival rates were 60% in one, 30% in two, 20% in three and 7% in five years. The local recurrence was noted in 60% and remote metastases were observed in 38% of them. These results were intimately correlated to tumor advancement and cancer type. From the results, it was concluded that this combination therapy should be valuable to prolong the life of a cancer patient, improving one to three year survival rates, and that the curable indications for this treatment should be T1 M0 and T2 M0 with tumorous or some ulcerous types of carcinoma.

Asakawa, H.; Otawa, H.; Yamada, S.; Matsumoto, K. (Miyagi Prefectural Adult Disease Center, Natori (Japan))

1981-08-01

115

Mice lacking neutrophil elastase are resistant to bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

Neutrophil elastase is a serine protease stored in the azurophilic granules of leukocytes. It has been implicated in the pathology of several lung diseases and is generally presumed to contribute to the tissue destruction and extracellular matrix damage associated with these conditions. To delineate the role of neutrophil elastase in pulmonary inflammation and fibrosis, neutrophil elastase-null mice were intratracheally instilled with bleomycin. In neutrophil elastase-null mice, biochemical and morphological characteristics of pulmonary fibrosis were attenuated for at least 60 days after bleomycin administration despite a typical response to bleomycin as evidenced by assessment of indices of DNA and cell damage. Neutrophil burden of bleomycin-treated wild-type and neutrophil elastase-null mice was comparable, and marked neutrophilic alveolitis was manifest in bleomycin-treated neutrophil elastase-null mice. An absence of immunostaining for active transforming growth factor (TGF)-beta in lung tissue from bleomycin-treated neutrophil elastase-null mice suggested a defect in TGF-beta activation, which was confirmed by biochemical assessment of TGF-beta levels in bronchoalveolar lavage fluid and lung tissue. These data point to novel and unexpected fibrogenic consequences of neutrophil elastase activity in the inflamed lung. PMID:17200183

Chua, Felix; Dunsmore, Sarah E; Clingen, Peter H; Mutsaers, Steven E; Shapiro, Steven D; Segal, Anthony W; Roes, Jürgen; Laurent, Geoffrey J

2007-01-01

116

The Effects of Silymarin in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Full Text Available AbstractBackground and Objectives: Silymarin, the active principle of Silybum marianum, has antifibrotic effects in hepatic fibrosis by several mechanisms. Since the pathogenesis of fibroproliferative diseases is similar, the effect of silymarin in bleomycin-induced pulmonary fibrosis was evaluated in this study.Methods: Silymarin (50 mg/kg, i.p.) was administered two days before the bleomycin instillation (3 U/kg) and throughout the test interval in mice. After two weeks, lung tissues of mice were evaluated for fibrosis by biochemical measurement of collagen deposition and histological analysis of pathological lung changes. Data were evaluated by one-way ANOVA and Dunnett analysis. P<0.05 was considered as significant. Results: Pretreatment with Silymarin significantly (P<0.05) prevented the increase in lung collagen content and also partially inhibited the histologic changes induced by bleomycin. The wet lung weight in silymarin group was similar to that of control group and significantly lower than bleomycin group (P<0.001). Conclusion: The results of this study indicate that silymarin may prevent the collagen deposition and inflammation and may be protective in fibrogenic effects of bleomycin on lung.Keywords: Silymarin; Bleomycin; Pulmonary Fibrosis; Hydroxyproline.

L. Safaeian; A.Jafarian Dehkordi; N. Afshar-Moghaddam; S. Sarahroodi

2009-01-01

117

Baicalein attenuates bleomycin-induced pulmonary fibrosis in rats through inhibition of miR-21.  

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Currently, there is no satisfactory treatment for pulmonary fibrosis, and effective agents urgently need to be developed. The aim of the present study was to investigate the effects of baicalein on bleomycin-induced pulmonary fibrosis, and the novel mechanisms involved in the anti-fibrosis effects. Pulmonary fibrosis was induced by a single intratracheal instillation of 5 mg/kg bleomycin. Two bleomycin-treated groups were orally administered daily with 50 and 100 mg/kg of baicalein from day 1 to 28. The results showed baicalein decreased hydroxyproline content and ?-SMA levels and increased lung index. Histopathological examinations demonstrated baicalein could obviously lower the degree of alveolitis and lung fibrosis. The total antioxidant capacity in bleomycin-treated rats with baicalein was also remarkably higher than in those without baicalein. Baicalein remarkably decreased miR-21 levels and inhibited the increased expression of TGF-?1 and p-Smad-2/3 in bleomycin-treated rats. Baicalein can attenuate bleomycin-induced pulmonary fibrosis. The attenuation is partly achieved by improving antioxidant activity, alleviating inflammation, repressing miR-21, and inhibiting TGF-?/Smad signaling. PMID:23523661

Gao, Yan; Lu, Jia; Zhang, Yu; Chen, Yafen; Gu, Zhenlun; Jiang, Xiaogang

2013-03-19

118

Response of the 9L rat brain tumor to combination treatment with radiation and bleomycin  

International Nuclear Information System (INIS)

[en] The therapeutic efficacy of combined modality treatment with radiation therapy and bleomycin was investigated in rats burdened with the intracerebral 9L bliosarcoma. Both radiation (single or fractioned exposures) and bleomycin (injected intracerebrally directly into the tumor region) are effective in prolonging survival when used as single agents. Bleomycin (1.0 mg/kg/week) combined with low-dose radiation therapy (15.3 By in 6 fractions in 2 weeks) prolonged survival over that of radiation alone, but not to the extent of high-dose radiation therapy (30.6 Gy in the same schedule). Bleomycin was effective whether given simultaneously or following fractionated radiation therapy - the important factor being delivery of radiation therapy early in the disease process. The greatest enhancement in survival caused by combination therapy compared to that by single agent therapy was observed when single exposure radiation therapy (20 Gy) followed single bleomycin administration by 4 hr. These results suggest the possibility of using bleomycin as an adjunct to radiation therapy for the treatment of patients with malignant brain tumors

1981-01-01

119

Response of the 9L rat brain tumor to combination treatment with radiation and bleomycin  

Energy Technology Data Exchange (ETDEWEB)

The therapeutic efficacy of combined modality treatment with radiation therapy and bleomycin was investigated in rats burdened with the intracerebral 9L bliosarcoma. Both radiation (single or fractioned exposures) and bleomycin (injected intracerebrally directly into the tumor region) are effective in prolonging survival when used as single agents. Bleomycin (1.0 mg/kg/week) combined with low-dose radiation therapy (15.3 By in 6 fractions in 2 weeks) prolonged survival over that of radiation alone, but not to the extent of high-dose radiation therapy (30.6 Gy in the same schedule). Bleomycin was effective whether given simultaneously or following fractionated radiation therapy - the important factor being delivery of radiation therapy early in the disease process. The greatest enhancement in survival caused by combination therapy compared to that by single agent therapy was observed when single exposure radiation therapy (20 Gy) followed single bleomycin administration by 4 hr. These results suggest the possibility of using bleomycin as an adjunct to radiation therapy for the treatment of patients with malignant brain tumors.

Kimler, B.F.; Vats, T.S.; Morantz, R.A.; Henderson, S.D.

1981-08-01

120

Effects of iloprost on bleomycin-induced pulmonary fibrosis in rats compared with methyl-prednisolone.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Prostacyclin (PGI2) has been shown to inhibit the expression of pro-inflammatory and pro-fibrotic mediators in pulmonary fibrosis. In this study, we aimed to test the preventive effects of intraperitoneally administered iloprost, a stable PGI2 analog, on bleomycin-induced pulmonary fibrosis in rats and to compare the effects of iloprost with the effects of methyl-prednisolone, a traditional therapy. METHODS: Rats were randomly allocated into four groups: 1. Saline alone (n=6); 2. Bleomycin+placebo (n=7); 3. Bleomycin+methyl-prednisolone (n=7); 4. Bleomycin+iloprost (n=7). Fibrotic changes in the lungs were demonstrated by analyzing the cellular composition of bronchoalveolar lavage fluid, histological evaluation and lung hydroxyproline content. RESULTS: Fibrosis was made in the lungs of rats by bleomycin experimentally. Fibrosis scores in the methyl-prednisolone and the iloprost groups were significantly lower than in the placebo group (p<0.05). Furthermore, the score of the iloprost group was significantly lower than the score of the methyl-prednisolone group. The hydroxyproline content was significantly less in the methyl-prednisolone and the iloprost groups (p<0.05). In the placebo group, the neutrophil percentage in bronchoalveolar lavage was significantly higher than in the other groups, whereas the macrophage percentage in placebo group was significantly lower (p<0.05). CONCLUSION: Iloprost has protective effect on the pulmonary fibrosis induced by bleomycin and it may be more effective in decreasing fibrotic changes than methyl-prednisolone.

Aytemur ZA; Hacievliyagil SS; Iraz M; Samdanci E; Ozerol E; Kuku I; Nurkabulov Z; Yildiz K

2012-11-01

 
 
 
 
121

Baicalein attenuates bleomycin-induced pulmonary fibrosis in rats through inhibition of miR-21.  

UK PubMed Central (United Kingdom)

Currently, there is no satisfactory treatment for pulmonary fibrosis, and effective agents urgently need to be developed. The aim of the present study was to investigate the effects of baicalein on bleomycin-induced pulmonary fibrosis, and the novel mechanisms involved in the anti-fibrosis effects. Pulmonary fibrosis was induced by a single intratracheal instillation of 5 mg/kg bleomycin. Two bleomycin-treated groups were orally administered daily with 50 and 100 mg/kg of baicalein from day 1 to 28. The results showed baicalein decreased hydroxyproline content and ?-SMA levels and increased lung index. Histopathological examinations demonstrated baicalein could obviously lower the degree of alveolitis and lung fibrosis. The total antioxidant capacity in bleomycin-treated rats with baicalein was also remarkably higher than in those without baicalein. Baicalein remarkably decreased miR-21 levels and inhibited the increased expression of TGF-?1 and p-Smad-2/3 in bleomycin-treated rats. Baicalein can attenuate bleomycin-induced pulmonary fibrosis. The attenuation is partly achieved by improving antioxidant activity, alleviating inflammation, repressing miR-21, and inhibiting TGF-?/Smad signaling.

Gao Y; Lu J; Zhang Y; Chen Y; Gu Z; Jiang X

2013-03-01

122

Intralesional bleomycin in the treatment of cutaneous warts: A randomized clinical trial comparing it with cryotherapy  

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Full Text Available Background: Though not in regular practice, intralesional (IL) bleomycin has been used for the treatment of warts since the 1970s and on the other hand, till now cryotherapy is quite regularly used to treat warts. Aim: Our aim was to assess the evidence for the efficacy of IL bleomycin, in comparison with a control group of similar sample receiving cryotherapy, in the treatment of cutaneous warts. Methods: Patients were randomized using computer-generated codes to receive either cryotherapy (double freeze-thaw cycle) or IL bleomycin (0.1% solution with concurrent anesthesia) for a maximum of four treatments 3 weeks apart and a maximum of five warts treated in each visit for both groups. Patients had their warts measured at base-line and with each return visit including a post treatment follow-up that was 8 weeks apart from last treatment taken. Results: Of the 73 patients completing the study, 39 (53%) were treated with IL bleomycin and 34 (47%) were treated with cryotherapy. Out of 155 treated warts, 87 (56%) were treated with IL beomycin and 68 (44%) were treated with cryotherapy. The clearance rates in context of number of patients and number of warts were 94.9% and 97% for bleomycin and 76.5% and 82% for cryotherapy respectively ( P 2 analysis and RR = 7.67). Conclusion: IL bleomycin injection was significantly more effective than cryotherapy for treatment of cutaneous wart.

Dhar S; Rashid M; Islam AZMM; Bhuiyan MSI

2009-01-01

123

Characterization of iron (II).bleomycin-mediated RNA strand scission.  

UK PubMed Central (United Kingdom)

The ability of iron(II).bleomycin to mediate RNA degradation was further characterized. At micromolar concentrations, FeII.BLM was shown to effect cleavage of Escherichia coli tRNA(1His) and a Schizosaccharomyces pombe amber suppressor tRNA construct in an efficient fashion. In contrast, E. coli tRNA(Cys) and yeast mitochondrial tRNA(Asp) and tRNA(fMet) precursors were not substrates for FeII.BLM. Also shown to be a good substrate for cleavage by FeII.BLM was yeast 5S ribosomal RNA. Since HIV-1 reverse transcriptase mRNA has previously been shown to be degraded by Fe.BLM (Carter et al., 1990a), members of the three major classes of RNA have now been shown to undergo Fe.BLM-mediated strand scission. For each of the substrate RNAs, cleavage occurred at sites unique to that substrate. Although RNA cleavage occurred at numerous sequences, 5'-G-pyr-3' sites were prominent. Likewise, while cleavage was noted in regions anticipated to be double-stranded, as well as in single-stranded regions, a disproportionate number of cleavages were noted at the junction between single- and double-stranded regions. As found in earlier studies, RNA cleavage was much more selective than DNA cleavage. Further, when RNA cleavage was carried out in the presence of reagents such as Mg2+, spermidine, and NaCl, the selectivity of cleavage was further enhanced. The highly selective and efficient cleavage of a number of RNA molecules reinforces our earlier suggestion that RNA may constitute a therapeutically relevant target for bleomycin.

Holmes CE; Carter BJ; Hecht SM

1993-04-01

124

Investigation of Therapeutic Efficiency of Bleomycin and Bleomycin-Glucuronide Labeled with (131)I on the Cancer Cell Lines.  

UK PubMed Central (United Kingdom)

Abstract The aim of this study is to determine the incorporations of radiolabeled bleomycin ((131)I-BLM) and bleomycin-glucuronide ((131)I-BLMGLU) on PC-3 (human prostate carcinoma cell line), Caco-2 (human colon adenocarcinoma cell line), Hutu-80 (Human Duodenum adenocarcinoma cell line), and A549 (Human lung adenocarcinoma epithelial cell line) cancerous cell lines. For this purpose, BLM and BLMGLU enyzmatically synthesized were labeled with (131)I, quality control studies were done and the incorporation yields of (131)I-BLM and (131)I-BLMGLU on these cell lines were measured. Quality-control studies showed that the radiolabeling yields were obtained as 95% and 90% for (131)I-BLM and (131)I-BLMGLU, respectively. Also, as a result of the cell culture studies, it was found that (131)I-BLM and (131)I-BLMGLU had higher incorporation on PC-3 cells than that of other cell lines. In addition to this, it was reported that the incorporation yield of (131)I-BLMGLU was higher than that (131)I-BLM. At the end of the study, cytotoxicities of BLM and BLMGLU on PC-3 cancerous cell line were inspected and fluorescent images of BLM and BLMGLU were taken on PC-3 cells by using fluorescein isothiocyanate. In conclusion, cell culture studies demonstrated that the incorporation values of (131)I-BLMGLU on the four cell lines were about five to six times higher than (131)I-BLM. Radiolabeled glucuronide derivatives can be used in cancer therapy and tumor imaging, depending on the properties of radioiodine for the ?-glucuronidase-rich tissues because glucuronidation leads to rapid and higher incorporation on adenocarcinoma cells.

Ediz M; Avc?ba?? U; Unak P; Müftüler FZ; Medine EI; Yurt K?lçar A; Demiro?lu H; Gümü?er FG; Sakarya S

2013-01-01

125

A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation  

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Full Text Available Objective: To study the approach for developing a rat model of pulmonary fibrosis induced by bleomycin (BLM).Method: Different doses (7, 6, 5, 3.4, 2, 1 mg/kg) of bleomycin A5-saline were infused into the rats' lung in bleomycin-treated group through tracheal intubation, and rats in sham-operated group were infused with same volume of saline. The living state and lung pathology of the rats were observed. The author deeply studied the condition of the rats in 1 mg/kg bleomycin-treated group, and the changes of body weight and lung pathology were observed. Lung quotient, the content of transforming growth factor ?1?TGF-?1?and platelet-derived growth factor (PDGF) in serum were measured on the 14th, 28th and 45th day of the experiment.Results: The study demonstrated that infusing large doses of bleomycin A5 quickly through tracheal intubation had a high mortality, and infusing 1 mg/kg quickly could successfully develop an animal model of pulmonary fibrosis. Compared with the sham-operated group, fibrosis was appeared obviously in the rats' lung in 1 mg/kg bleomycin A5-treated group after 14 days of experiment, diffuse fibrosis was appeared after 28 days of experiment, and the fibrosis became more severe after 45 days of experiment. The body weight of the rats in bleomycin-treated group was declined after 3, 7 and 14 days of experiment as compared with the sham-operated group (P0.05). Lung quotient was increased 14, 28 and 45 days after the experiment (P<0.01), the level of serum TGF-?1 began to increase since 28 days after the experiment (P<0.05, P<0.01), and the level of serum PDGF also increased gradually 45 days after the experiment (P<0.05). And the mortality rate of 1 mg/kg bleomycin A5-treated group was lower than those of the other doses of bleomycin A5-treated groups.Conclusion: A rat model of pulmonary fibrosis can be duplicated successfully by infusing 1 mg/kg bleomycin A5 quickly through tracheal intubation.

Wei ZHANG; Liang-duo JIANG

2008-01-01

126

Microscopic study of the 7Li(n,?)8Li and 7Be(p,?)8B reactions in a multiconfiguration three-cluster model  

International Nuclear Information System (INIS)

[en] The three-cluster generator coordinate method is applied to the 7Li(n,?)8Li and 7Be(p,?)8B capture reactions. The 8B (or 8Li) nucleus is defined by a mixing of (?+3He)+p and (?+p)+3He (or mirror) configurations. We investigate the sensitivity of different observables with respect to the nucleon-nucleon interaction by considering four different Volkov forces. For all of them, the model fairly reproduces most of the experimentally known spectroscopic properties of the 8B and 8Li mirror nuclei. Recent measurements of the quadrupole moments are well explained without a halo structure. The 7Li(n,?)8Li cross section supports the data of Imhof et al. rather than those of Wiescher et al. At zero energy, the 7Be(p,?)8B astrophysical S-factors slightly depend on the nucleon-nucleon interaction. They are consistent with the currently accepted value, but contradict lower estimates. (orig.)

1994-01-17

127

Studies on increase of intracellular reactive oxygen species and oxidative DNA damage in 60Co ? ray irradiated BEP2D cells  

International Nuclear Information System (INIS)

HPV-16 immortalized human bronchial epithelial cells (BEP2D) were irradiated by 60Co gamma rays. 2',7'-dichlorofluorescein and ethidium bromide, fluorescent products of the membrane-permeable dyes 2',7'-dichlorofluorescein diacetate and hydro-ethine, respectively, were used to monitor the intracellular production of hydrogen peroxides (H2O2) and superoxide anions (O2.-) respectively, by flow cytometry. 8-hydroxy-deoxy-gunosine (OH8dG), a production of oxidative DNA damage, was examined with HPLC-ECD from extracted DNA. The results shoed that the ROS productions and DNA adduct OH8dG in 60Co gamma rays irradiated BEP2D cells increased remarkably, and revealed better dose-response correlation. Further analysis indicated the positive correlation between intracellular ROS and content of OH8dG induced by 60Co gamma rays. Therefore, the effects of radiation on cell were involved increase of intracellular ROS and its production of oxidative DNA damage

2001-01-01

128

Dual effect of AMD3100, a CXCR4 antagonist, on bleomycin-induced lung inflammation.  

Science.gov (United States)

The chemokine receptor CXCR4, which binds the chemokine stromal cell-derived factor 1, has been reported to be involved in the chemotaxis of inflammatory cells. In addition, AMD3100, an antagonist of CXCR4, has been reported to be an attractive drug candidate for therapeutic intervention in several disorders in which CXCR4 is critically involved. However, little is known about the therapeutic value of AMD3100 in the treatment of pulmonary fibrosis. In this study, we examined the effects of AMD3100 on a murine bleomycin-induced pulmonary fibrosis model. Concurrent administration of AMD3100 and bleomycin apparently attenuated bleomycin-induced pulmonary inflammation. In this process, an inhibition of neutrophil recruitment at early stage followed by the decrease of other inflammatory cell recruitment in the lung were observed. In addition, it also inhibited the expression of cytokines, including MCP-1, MIP-2, MIP-1alpha, and TGF-beta. In contrast, when AMD3100 was administered following bleomycin treatment, the bleomycin-induced lung inflammation progressed and resulted in severe pulmonary fibrosis. In this process, an increase of inflammatory cell recruitment, an up-regulation of lung MCP-1 and TGF-beta, and a remarkable activation of p44/42 MAPK in neutrophils were observed. U0126, an inhibitor of p44/42 MAPK, significantly abolished these effects. Thus, AMD3100 has dual effect on bleomycin-induced pulmonary fibrosis. Difference of inflammatory cell recruitment and activation might be associated with the dual effect of AMD3100 on bleomycin-induced pulmonary fibrosis. PMID:17442973

Watanabe, Masaki; Matsuyama, Wataru; Shirahama, Yuko; Mitsuyama, Hideo; Oonakahara, Ken-ichi; Noma, Satoshi; Higashimoto, Ikkou; Osame, Mitsuhiro; Arimura, Kimiyoshi

2007-05-01

129

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin-treated rats.  

UK PubMed Central (United Kingdom)

AIM: Pulmonary fibrosis is often complicated by pulmonary hypertension. Statins reduce fibroblast activity in vitro and pulmonary hypertension in vivo. We investigated whether Simvastatin exerts beneficial effects on pulmonary fibrosis and pulmonary hypertension in Bleomycin-treated rats in vivo. METHODS: Rats were randomly assigned to controls, Bleomycin, Bleomycin plus Simvastatin from day 1 to 28 and Bleomycin plus Simvastatin from day 13 to 28. 28 days after Bleomycin instillation, right ventricular systolic pressure (RVSP), right ventricular mass (RV/(LV+S)), right ventricular and circulating brain natriuretic peptide (BNP) levels were determined to assess pulmonary hypertension. Pulmonary hydroxyproline content (HPC), pulmonary connective tissue growth factor (CTGF) transcription and lung compliance (LC) were analysed to characterize pulmonary fibrosis. Exercise capacity was determined by treadmill tests. RESULTS: Compared with controls, Bleomycin increased RVSP, RV/(LV+S), BNP levels, HPC and CTGF transcription and decreased LC significantly. Simvastatin administered from day 1 to 28 normalized all these parameters. Simvastatin administered from day 13 to 28 had no effect on HPC and LC, but reduced RV/(LV+S) significantly and induced a strong trend to lower RVSP and BNP levels. Exercise capacity was reduced by Bleomycin. Simvastatin significantly improved exercise intolerance in both treatment groups. CONCLUSIONS: Simvastatin prevents the development of pulmonary fibrosis, but fails to attenuate already established pulmonary fibrosis. In contrast, it ameliorates pulmonary hypertension and thereby exercise capacity in the prevention and the treatment group regardless of its effects on pulmonary fibrosis. Whether statins are a treatment option in humans with pulmonary fibrosis needs to be investigated by further study.

Schroll S; Lange TJ; Arzt M; Sebah D; Nowrotek A; Lehmann H; Wensel R; Pfeifer M; Blumberg FC

2013-06-01

130

Genetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury.  

UK PubMed Central (United Kingdom)

Caveolar domains act as platforms for the organization of molecular complexes involved in signal transduction. Caveolin proteins, the principal structural components of caveolae, have been involved in many cellular processes. Caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are highly expressed in the lung. Cav-1-deficient mice (Cav-1 (-/-) ) and Cav-2-deficient mice (Cav-2 (-/-) ) exhibit severe lung dysfunction attributed to a lack of Cav-2 expression. Recently, Cav-1 has been shown to regulate lung fibrosis in different models. Here, we show that Cav-2 is also involved in modulation of the fibrotic response, but through distinct mechanisms. Treatment of wild-type mice with the pulmonary fibrosis-inducer bleomycin reduced the expression of Cav-2 and its phosphorylation at tyrosine 19. Importantly, Cav-2 (-/-) mice, but not Cav-1 (-/-) mice, were more sensitive to bleomycin-induced lung injury in comparison to wild-type mice. Bleomycin-induced lung injury was characterized by alveolar thickening, increase in cell density, and extracellular matrix deposition. The lung injury observed in bleomycin-treated Cav-2 (-/-) mice was not associated with alterations in the TGF-? signaling pathway and/or in the ability to produce collagen. However, apoptosis and proliferation were more prominent in lungs of bleomycin-treated Cav-2 (-/-) mice. Since Cav-1 (-/-) mice also lack Cav-2 expression and show a different outcome after bleomycin treatment, we conclude that Cav-1 and Cav-2 have distinct roles in bleomycin induced-lung fibrosis, and that the balance of both proteins determines the development of the fibrotic process.

de Almeida CJ; Jasmin JF; Del Galdo F; Lisanti MP

2013-06-01

131

The Effects of Silymarin in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Full Text Available Background and Objectives: Silymarin, the active principle of Silybum marianum, has antifibrotic effects in hepatic fibrosis by several mechanisms. Since the pathogenesis of fibroproliferative diseases is similar, the effect of silymarin in bleomycin-induced pulmonary fibrosis was evaluated in this study.Methods: Silymarin (50 mg/kg, i.p.) was administered two days before the bleomycin instillation (3 U/kg) and throughout the test interval in mice. After two weeks, lung tissues of mice were evaluated for fibrosis by biochemical measurement of collagen deposition and histological analysis of pathological lung changes. Data were evaluated by one-way ANOVA and Dunnett analysis. P<0.05 was considered as significant. Results: Pretreatment with Silymarin significantly (P<0.05) prevented the increase in lung collagen content and also partially inhibited the histologic changes induced by bleomycin. The wet lung weight in silymarin group was similar to that of control group and significantly lower than bleomycin group (P<0.001).     Conclusion: The results of this study indicate that silymarin may prevent the collagen deposition and inflammation and may be protective in fibrogenic effects of bleomycin on lung

L Safaeian

2012-01-01

132

Characterization of the association of radiolabeled bleomycin A2 with HeLa cells  

Energy Technology Data Exchange (ETDEWEB)

The association of (/sup 3/H)bleomycin A2 and Cu(II):(/sup 3/H)bleomycin A2 with HeLa cells has been characterized. Under the conditions of our experiments, approximately 0.1% of the total drug in the medium associates with HeLa cells. Both forms of the drug bind to HeLa cells in a specific and saturable manner, with a Km of 20 microM and a Vmax of 2.5 pmol/min/10(6) cells. Scatchard analysis of the specific binding data demonstrates a single set of high-affinity binding sites. Cytotoxic activities of both forms of the drug are similar, with a 50% lethal dose of 0.5 microM at 48 hr. The specific binding in HeLa cells of either the labeled metal-free drug or its copper complex is reversible by a 100-fold excess of either unlabeled drug. Interaction of the drug with cells is temperature sensitive but is unaffected by metabolic poisons, suggesting that this process is not energy dependent. Isolation of DNA from HeLa cells incubated with the drug indicates that 1 mol of either (/sup 3/H)bleomycin A2 or Cu(II):(/sup 3/H)bleomycin A2 binds per 10(8) nucleotides. Further studies with the radiolabeled drug are required to define precisely the mechanisms involved in bleomycin uptake and compartmentalization within the cell.

Roy, S.N.; Horwitz, S.B.

1984-04-01

133

Study of the cellular uptake and distribution of 57cobalt bleomycin in Ehrlich ascites tumor cells  

International Nuclear Information System (INIS)

We investigated the dependence of the cellular uptake of 57 cobalt-bleomycin on the exposure time and on the dose. In addition we observed the influences due to the incubation temperature, to the growth phase of the tumor cells and due to the composition of the suspensory medium. In supplementary experiments we investigated the binding of the labelled cytostatic agent to erythrocytes, its adsorption to broken Ehrlich ascites tumor cells and the 57 cobalt-bleomycin outflow from pre-loaded intact Ehrlich ascites tumor cells. The 57 cobalt-bleomycin uptake of intact Ehrlich ascites tumor cells is determined by characteristic kinetics. Moreover, the erythrocytes and injured Ehrlich ascites tumor cells show a qualitatively similar graph of the 57 cobalt-bleomycin binding, which can clearly be distinguished from the kinetics found with intact Ehrlich ascites tumor cells. The uptake of this cytostatic agent depends on an unequivocal time-dose-temperature relationship. The transport mechanism of the 57 cobalt-bleomycin uptake was considered as endocytosis. An endocytosis-stimulating inducer could not be detected. However, we obtained indications that the cell-bound cytostatic agent is taken up in two compartments: on the cellular surface and in the interior of the cell. (orig./MG)

1980-01-01

134

CXCL6 antibody neutralization prevents lung inflammation and fibrosis in mice in the bleomycin model.  

UK PubMed Central (United Kingdom)

IPF is a chronic, progressive pulmonary disease, leading to respiratory failure. In search of mechanisms of IPF, we used the bleomycin-induced lung-injury model in mice, which causes acute inflammation that may progress to chronic lung inflammation and fibrosis. Here, we asked whether CXCL6/GCP-2, a member of the CXC chemokine superfamily, may be involved in IPF development. First, we reported an increase of CXCL6 levels in BALF from patients with IPF, as well as in the lung of mice, 24 h after bleomycin administration. To investigate whether CXCL6 played a role in experimental bleomycin-induced pulmonary fibrosis, we treated mice with an anti-mCXCL6 mAb that has been shown to inhibit neutrophil chemotaxis in vitro. CXCL6 antibody blockade attenuated acute inflammation with a reduced pulmonary neutrophil influx, IL-1?, CXCL1, and TIMP-1 production. In the later phase (14 days after bleomycin exposure), lymphocyte recruitment and fibrosis markers, such as collagen and TIMP-1, were diminished, as well as collagen deposition and fibrotic lesion the lung. Therefore, the data suggest that CXCL6 contributes to experimental pulmonary fibrosis, and CXCL6 inhibition might be used to reduce lung toxicity associated with bleomycin treatment.

Besnard AG; Struyf S; Guabiraba R; Fauconnier L; Rouxel N; Proost P; Uyttenhove C; Van Snick J; Couillin I; Ryffel B

2013-08-01

135

Bleomycin Induces Molecular Changes Directly Relevant to Idiopathic Pulmonary Fibrosis: A Model for "Active" Disease  

Science.gov (United States)

The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGF? was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease.

Tyagi, Gaurav; Phillips, Jonathan E.; Garrido, Rosario; Harris, Paul; Burns, Lisa; Renteria, Lorena; Woods, John; Chen, Leena; Allard, John; Ravindran, Palanikumar; Bitter, Hans; Liang, Zhenmin; Hogaboam, Cory M.; Kitson, Chris; Budd, David C.; Fine, Jay S.; Bauer, Carla MT.; Stevenson, Christopher S.

2013-01-01

136

Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease.  

UK PubMed Central (United Kingdom)

The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGF? was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease.

Peng R; Sridhar S; Tyagi G; Phillips JE; Garrido R; Harris P; Burns L; Renteria L; Woods J; Chen L; Allard J; Ravindran P; Bitter H; Liang Z; Hogaboam CM; Kitson C; Budd DC; Fine JS; Bauer CM; Stevenson CS

2013-01-01

137

The Role of Strain Variation in BAX and BCL-2 Expression in Murine Bleomycin-Induced Pulmonary Fibrosis  

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This study hypothesized that the expression of apoptosis-regulatory genes, such as BCL-2 and BAX may be affected by genetic variation in bleomycin-induced pulmonary fibrosis in C57BL/6 and NMRI mice. Pulmonary fibrosis induced by single intratracheal dose of bleomycin (3 U kg-1). After 2 ...

L. Safaeian; A. Jafarian; M. Rabbani; H.M. Sadeghi; N. Torabinia; S.A. Alavi

138

Biological basis of combination therapy with radiation and bleomycin  

International Nuclear Information System (INIS)

The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C2W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C2W cells were irradiated, incubated at 370C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising. (J.P.N.)

1976-01-01

139

Simple colorimetric sensing of trace bleomycin using unmodified gold nanoparticles.  

UK PubMed Central (United Kingdom)

A simple colorimetric sensing platform for trace bleomycin (BLM) was proposed with the unmodified gold nanoparticles (AuNPs) as the sensing element. BLM has multiple N-donor functionality and exhibited strong coordination effect on AuNPs, which made it possible for the occurrence of ligand exchange of BLM with the weakly surface-bound citrate ions on AuNPs. Meanwhile, the positively charged BLM molecules further neutralized the surface charge, leading to increased van der Waals attractive force among AuNPs for rapid aggregation. This was reflected by the obvious color change from wine red to blue and rapid aggregation kinetics within 7.5 min. The BLM sensing based on unmodified AuNPs can be seen with the naked eye and monitored by UV-vis extinction spectra. The linear range of the colorimetric sensor for BLM was from 2 to 150 nM. The as-established colorimetric strategy opened a new avenue for trace BLM determination.

Li F; Feng Y; Zhao C; Tang B

2011-07-01

140

Interleukin-22 inhibits bleomycin-induced pulmonary fibrosis.  

UK PubMed Central (United Kingdom)

Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL-) 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM-) induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced ?? T cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT) and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker ( ? -smooth muscle actin ( ? -SMA)) and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis.

Liang M; Wang J; Chu H; Zhu X; He H; Liu Q; Qiu J; Zhou X; Guan M; Xue Y; Chen X; Zou H

2013-01-01

 
 
 
 
141

Long term follow-up in patients with a naso-pharynx carcinoma after induction chemotherapy by cisplatin, 5-fluoro-uracil and bleomycin (pbf) followed by a bi-fractionated radiotherapy and a consolidation chemotherapy; Survie a long terme chez des patients atteints d'un carcinome du nasopharynx apres chimiotherapie d'induction par cisplatine, 5-fluoro-uracile et bleomycine (pbf) suivie d'une radiotherapie bifractionnee et une chimiotherapie de consolidation  

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The purpose of this study was to evaluate the efficiency and the long term survival after neoadjuvant chemotherapy by cisplatin, 5-fluoro-uracil and bleomycin, followed by a bi fractionated radiotherapy and an adjuvant chemotherapy. The protocol associating a P.B.F. type chemotherapy in the locally evolved disease is justified by its efficiency in terms of objective response rate and local control rate, that expressed by an improvement of the global survival rate and survival without disease at five and ten years. The adjuvant chemotherapy is very toxic and did not show any benefit. (N.C.)

Djekkoun, R.; Boudaoud, K.; Ferdi, N.; Filali, T. [CAC CHU, Constantine (Algeria)

2009-10-15

142

The effect of bleomycin on DNA synthesis in ataxia telangiectasia lymphoid cells  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin, a radiomimetic glycopeptide, inhibits de novo DNA synthesis in ataxia telangiectasia lymphoblastoid B cells to a markedly lesser extent than in normal and xeroderma pigmentosum lymphoid cells. This observation is similar to that following ionizing radiation; however, the effect is slower following the chemical treatment. Recovery of the normal cells occurs 15-18 hours after treatment, whereas the ataxia telangiectasia lines do not attain normal levels of DNA synthesis during the entire 24-hour observation period. Similar differences were not observed following treatment with mitomycin C, a bifunctional alkylating agent, indicating a specific effect of bleomycin on DNA synthesis in ataxia telangiectasia cells. Following bleomycin treatment and preincubation with hydroxyurea, residual DNA synthesis in ataxia telangiectasia cells was similar to that in both normal and xeroderma pigmentosum lymphoid lines, suggesting that the capacity to repair the induced DNA lesion is present.

Cohen, M.M.; Simpson, S.J.

1982-01-01

143

Cystic craniopharyngioma: trans-sphenoidal surgery and intra-cystic apposition of "bleomycin wax".  

UK PubMed Central (United Kingdom)

BACKGROUND: The current therapeutic approach to craniopharyngioma is multidisciplinary. Sub-total removal, followed by adjuvant treatments, especially in large cystic tumours, is an accepted regime reported by many authors. CASE REPORT: A young patient with an intra- and suprasellar cystic craniopharyngioma was operated on via a microsurgical trans-sphenoidal approach, achieving sub-total removal and bleomycin mixed with bone wax ("bleomycin wax") applied to the capsular remnant. RESULTS: Pre-operative neurological and endocrinological deficit improved after surgery. There was no evidence of tumour recurrence after a follow-up period of 5.4 years. CONCLUSIONS: The intra-operative use of "bleomycin-wax" should be limited to those patients in whom intra-operative CSF fistula does not occur.

Fraioli MF; Moschettoni L; Catena E; Fraioli C

2010-02-01

144

Chelating, DNA-binding and DNA-cleaving properties of a synthetic model for bleomycin.  

UK PubMed Central (United Kingdom)

We have previously described a simplified model of the complexing part of bleomycin, namely methyl 2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidinate (AMPHIS), and disubstituted bithiazoles structurally related to the 'tripeptide S' moiety of bleomycin. The present work is devoted to the study of a new derivative, [3-[2-[2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidyl-3 -aminobutyryl-glycyl]-2',4-bithiazole-4-carboxamido]-propyl]- dimethylsulphonium iodide (AMBI-A2), which includes both AMPHIS and a judiciously chosen synthetic bithiazole. This compound, the synthesis of which is described here, has been shown to mimic the chelating and binding properties of the parent drug bleomycin A2, but to cleave DNA at higher concentration.

Kenani A; Lohez M; Houssin R; Helbecque N; Bernier JL; Lemay P; Hénichart JP

1987-08-01

145

Chelating, DNA-binding and DNA-cleaving properties of a synthetic model for bleomycin.  

Science.gov (United States)

We have previously described a simplified model of the complexing part of bleomycin, namely methyl 2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidinate (AMPHIS), and disubstituted bithiazoles structurally related to the 'tripeptide S' moiety of bleomycin. The present work is devoted to the study of a new derivative, [3-[2-[2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidyl-3 -aminobutyryl-glycyl]-2',4-bithiazole-4-carboxamido]-propyl]- dimethylsulphonium iodide (AMBI-A2), which includes both AMPHIS and a judiciously chosen synthetic bithiazole. This compound, the synthesis of which is described here, has been shown to mimic the chelating and binding properties of the parent drug bleomycin A2, but to cleave DNA at higher concentration. PMID:2452643

Kenani, A; Lohez, M; Houssin, R; Helbecque, N; Bernier, J L; Lemay, P; Hénichart, J P

1987-08-01

146

Clinical Evaluation of 57Co-labelled Bleomycin for Tumor Localization  

International Nuclear Information System (INIS)

Investigation with 57Co-Bleomycin in patients with the various cancers and in tumor bearing animals are described. In the patients, 57Co-Bleomycin appears to be one of the useful tumor- seeking radiopharmaceuticals, and worth applicable to clinical uses. Labelled yield of 57Co-Bleo was about 97% by thin layer chromatography. The pyrogen free tests were performed to meet U.S.P. critical ranges. In clinical studies with 57Co-Bleo, 4 cases out of 5 patients with lung cancer, 2 cases among 3 thyroid cancer patients, and all 3 hepatoma patients showed positive tumor scans. The patients with stomach cancer, and the esophageal cancer showed false negative scintigraphy. A case with pulmonary tuberculosis showed a positive scan while liver abscess showed a negative picture. The merits of 57Co-Bleomycin scintigraphy seems to be its relatively high affinity to tumors and low radiation hazard in spite of long physical half life.

1987-01-01

147

Hsp90 inhibition by NVP-AUY922 and NVP-BEP800 decreases migration and invasion of irradiated normoxic and hypoxic tumor cell lines.  

Science.gov (United States)

This study explores the impact of Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 in combination with ionizing radiation (IR) on the migration and invasion of lung carcinoma A549 and glioblastoma SNB19 cells, under normoxia or hypoxia. Independent of oxygen concentration, both drugs decreased the migration and invasion rates of non-irradiated tumor cells. Combined drug-IR treatment under hypoxia inhibited cell invasion to a greater extent than did each treatment alone. Decreased migration of cells correlated with altered expression of several matrix-associated proteins (FAK/p-FAK, Erk2, RhoA) and impaired F-actin modulation. The anti-metastatic efficacy of the Hsp90 inhibitors could be useful in combinational therapies of cancer. PMID:23340178

Hartmann, Susanne; Günther, Nadine; Biehl, Marlene; Katzer, Astrid; Kuger, Sebastian; Worschech, Eike; Sukhorukov, Vladimir L; Krohne, Georg; Zimmermann, Heiko; Flentje, Michael; Djuzenova, Cholpon S

2013-01-20

148

Resonances in 11C observed in the 4He(7Be,?)7Be and 4He(7Be,p)10B reactions  

International Nuclear Information System (INIS)

[en] Measurements of the 4He(7Be,?)7Be and 4He(7Be,p)10B reactions were performed using 7Be beam energies of 7.1 and 23 MeV and a helium-4 target, employing the thick target technique. Resonances were observed between Ex(11C) = 8.6 to 13.8 MeV. An R-matrix analysis was performed to characterize the spins and partial widths. This analysis showed that the observed sequence of states was consistent with that found for 7Li + ? resonant scattering populating resonances in 11B. A comparison of the proposed partial widths for decay with the Wigner limit indicates that several of the states are associated with cluster-like structures.

2012-01-01

149

The elastic scattering 7Be + p at low energies: implications on the 7Be(p, ?)8Be S-factor  

International Nuclear Information System (INIS)

[en] The 7Be + p elastic cross section has been measured at the Centre de Recherches du Cyclotron RIB facility at Louvain-la-Neuve in the c.m. energy region from 0.3 to 0.75 MeV by bombarding a proton-rich target with a radioactive 7Be beam. The recoil protons have been detected in the angular range ?c.m. = 120.2 deg. - 131.1 deg. and ?c.m. = 156.6 deg. - 170.2 deg. using the LEDA system. From a R-matrix analysis of the cross section data, we extract the energy and the width of the 1+ resonance. The scattering lengths ?01 = 25 ± 9 fm (channel spin I = 1) and ?02 = -7 ± 3 fm (channel spin I = 2) are deduced. Implications on the low energy S-factor of the 7Be(p, ?)8B reaction are discussed

2003-05-19

150

Pharmacological inhibition of leukotrienes in an animal model of bleomycin-induced acute lung injury  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Leukotrienes are increased locally in idiopathic pulmonary fibrosis. Furthermore, a role for these arachidonic acid metabolites has been thoroughly characterized in the animal bleomycin model of lung fibrosis by using different gene knock-out settings. We investigated the efficacy of pharmacological inhibition of leukotrienes activity in the development of bleomycin-induced lung injury by comparing the responses in wild-type mice with mice treated with zileuton, a 5-lipoxygenase inhibitor and MK-571, a cys-leukotrienes receptor antagonist. Mice were subjected to intra-tracheal administration of bleomycin or saline and were assigned to receive either MK-571 at 1 mg/Kg or zileuton at 50 mg/Kg daily. One week after bleomycin administration, BAL cell counts, lung histology with van Gieson for collagen staining and immunohistochemical analysis for myeloperoxidase, IL-1 and TNF-? were performed. Following bleomycin administration both MK-571 and zileuton treated mice exhibited a reduced degree of lung damage and inflammation when compared to WT mice as shown by the reduction of:(i) loss of body weight, (ii) mortality rate, (iii) lung infiltration by neutrophils (myeloperoxidase activity, BAL total and differential cell counts), (iv) lung edema, (v) histological evidence of lung injury and collagen deposition, (vi) lung myeloperoxidase, IL-1 and TNF-? staining. This is the first study showing that the pharmacological inhibition of leukotrienes activity attenuates bleomycin-induced lung injury in mice. Given our results as well as those coming from genetic studies, it might be considered meaningful to trial this drug class in the treatment of pulmonary fibrosis, a disease that still represents a major challenge to medical treatment.

Failla Marco; Genovese Tiziana; Mazzon Emanuela; Gili Elisa; Muià Carmelo; Sortino Mariangela; Crimi Nunzio; Caputi Achille P; Cuzzocrea Salvatore; Vancheri Carlo

2006-01-01

151

In-vitro and in-vivo characterization of ruthenium-bleomycin compared to cobalt- and copper-bleomycin  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin (BLM) has undergone extensive investigation both as a cancer chemotherapeutic agent, and as a carrier for radionuclides for tumor imaging. The available methods or the radionuclides used, however, have had limited effectiveness. Although labeling of BLM with /sup 103/Ru has been reported earlier, we carried out a study to develop a more reproducible method of labeling particularly for use with Brookhaven Linac Isotope Producer produced /sup 97/Ru. Ruthenium-97 has favorable physical properties that make it ideal for imaging applications: decay by electron capture; ..gamma.. 216 keV, 85%; t/sub 1/2/ 2.9 d. A novel method based on the reduction of Ru/sup 3 +/ to Ru/sup 2 +/ using stannous chloride was investigated for labeling BLM with /sup 97/Ru and/or /sup 103/Ru. In-vitro and in vivo comparisons of the product(s) with /sup 57/Co and /sup 67/Cu-labeled BLM were also carried out. 4 refs., 3 tabs.

Shao, H.S.; Meinken, G.E.; Srivastava, S.C.; Slosman, D.; Sacker, D.F.; Som, P.; Brill, A.B.

1986-01-01

152

A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors.  

UK PubMed Central (United Kingdom)

BACKGROUND: Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification. PATIENTS AND METHODS: PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers. RESULTS: No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03). CONCLUSION: This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.

Bokemeyer C; Köhrmann O; Tischler J; Weissbach L; Räth U; Haupt A; Schöffski P; Harstrick A; Schmoll HJ

1996-12-01

153

Carcinoma of the penis; Treatment by surgery or combined bleomycin and radiation therapy  

Energy Technology Data Exchange (ETDEWEB)

Forty-four patients with squamous cell carcinoma of the penis stage T1-T2, N0 were either treated surgically (n=19) or with a combination of irradiation and bleomycin (n=25). The overall actuarial survival rate was 80% at 3 years, 77% at 5 years and 60% at 10 years. The result of irradiation treatment combined with bleomycin was in stage N0 equivalent to that of surgical therapy. The non-surgical treatment had the advantage of preserved sexual ability. (orig.).

Modig, H. (Dept. of Oncology and Urology and Andrology, Univ. Hospital, Umeaa (Sweden)); Duchek, M. (Dept. of Oncology and Urology and Andrology, Univ. Hospital, Umeaa (Sweden)); Sjoedin, J.G. (Dept. of Oncology and Urology and Andrology, Univ. Hospital, Umeaa (Sweden))

1993-01-01

154

Induction of micronuclei by bleomycin in G[sub 0] human lymphocytes: II. Potentiation by radioprotectors  

Energy Technology Data Exchange (ETDEWEB)

Dimethylsulfoxide (DMSO) and WR-1065 are radioprotectors, in that they reduce the effectiveness with which ionizing radiation causes genetic damage. Unlike their protective effects with radiation, these agents potentiate the induction of micronuclei by bleomycin in the cytokinesis-block assay in G[sub 0] human lymphocytes. High concentrations of DMSO (1 M) are required to cause potentiation. In contrast, WR-1065 causes dose-dependent potentiation at relatively low concentrations (1.25 to 10 mM). Cytogenetic analysis supports higher levels of genetic damage induced by the combination of blemycin with DMSO or WR-1065 than by bleomycin alone. Possible mechanisms of potentiation are proposed. 38 refs., 6 tabs.

Hoffmann, G.R.; Colyer, S.P.; Littlefield, L.G. (Oak Ridge Associated Universities, TN (United States))

1993-01-01

155

Antifibrotic activity of hyaluronidase immobilized on polyethylenoxide under conditions of bleomycin-induced pneumofibrosis.  

UK PubMed Central (United Kingdom)

Hyaluronidase immobilized on polyethylenoxide obtained by electron bean synthesis was administered intranasally and intravenously to C57Bl/6 mice after intratracheal bleomycin and the enzyme effects on the development of pneumofibrosis in animals were studied. Intranasal immobilized hyaluronidase prevented connective tissue growth in the lungs exposed to bleomycin and virtually did not modulate the infiltration of the alveolar and alveolar duct interstitium by inflammatory cells (lymphocytes, macrophages, neutrophils, plasma cells). The antifibrotic effect developed sooner after intranasal inoculation of immobilized hyaluronidase and was more pronounced than after intranasal native hyaluronidase. Intravenous injection of immobilized hyaluronidase did not modify the inflammatory process and deposition of collagen fibrils in the lung parenchyma in pneumofibrosis.

Dygai AM; Skurikhin EG; Ermakova NN; Pershina OV; Krupin VA; Reztsova AM; Ermolaeva LA; Khmelevskaya ES; Artamonov AV; Bekarev AA; Madonov PG; Kinsht DN

2013-01-01

156

Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study  

Directory of Open Access Journals (Sweden)

Full Text Available Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP) showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM) during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP) vs. 10 normal individuals (P = 0.67). Individuals that exhibited an average number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.

Sales Magaly M.; Lucca Edmundo J. de; Yamashita Seizo; Saad Luis Henrique Cury

1999-01-01

157

Lung fibrosis 10 years after cessation of bleomycin therapy.  

Science.gov (United States)

Bleomycin (BLM) is a chemotherapeutic agent used for the treatment of several types of malignancy, including germ cell tumors, lymphoma, and certain types of squamous-cell carcinoma. The common adverse effect of BLM is interstitial pneumonitis, followed by pulmonary fibrosis. BLM-induced pneumonitis occurs in up to 46% of patients treated with BLM-containing chemotherapy and lung toxicity usually appears during treatment. Here we describe a patient with lung fibrosis, who presented with slow progressive breathlessness and pneumothorax more than 10 years after cessation of BLM therapy. A 15 year-old girl presented with abnormal shadows on chest X-ray. The patient had a yolk sac carcinoma in the sacral region at 1 year of age and obtained complete remission after being treated with tumor resection, radiation, and several anti-cancer drugs including BLM. There were no abnormal findings in chest X-ray until she reached 3 years of age, when she had developed respiratory distress that worsened with age. The patient had experienced an episode of pneumothorax at 13 years of age. Chest CT at the time revealed interstitial reticular opacities. Radiological findings and pathological examination of the lung tissue obtained during bullectomy with video-assisted thoracic surgery were compatible with BLM-induced pneumonitis. The present study suggests that lung fibrosis may surface more than 10 years after cessation of BLM therapy at the age of 1 year, with no chest radiographic findings 1 year after completion of chemotherapy. The use of BLM in infants requires strict supervision and observation and careful long-term follow up. PMID:18719341

Tashiro, Masato; Izumikawa, Koichi; Yoshioka, Daisuke; Nakamura, Shigeki; Kurihara, Shintaro; Sakamoto, Noriho; Seki, Masafumi; Kakeya, Hiroshi; Yamamoto, Yoshihiro; Yanagihara, Katunori; Mukae, Hiroshi; Hayashi, Tomayoshi; Fukushima, Kiyoyasu; Tashiro, Takayoshi; Kohno, Shigeru

2008-09-01

158

Inhibition or knock out of Inducible nitric oxide synthase result in resistance to bleomycin-induced lung injury  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background In the present study, by comparing the responses in wild-type mice (WT) and mice lacking (KO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the role played by iNOS in the development of on the lung injury caused by bleomycin administration. When compared to bleomycin-treated iNOSWT mice, iNOSKO mice, which had received bleomycin, exhibited a reduced degree of the (i) lost of body weight, (ii) mortality rate, (iii) infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv) edema formation, (v) histological evidence of lung injury, (vi) lung collagen deposition and (vii) lung Transforming Growth Factor beta1 (TGF-?1) expression. Methods Mice subjected to intratracheal administration of bleomycin developed a significant lung injury. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in lungs from bleomycin-treated iNOSWT mice. Results The intensity and degree of nitrotyrosine staining was markedly reduced in tissue section from bleomycin-iNOSKO mice. Treatment of iNOSWT mice with of GW274150, a novel, potent and selective inhibitor of iNOS activity (5 mg/kg i.p.) also significantly attenuated all of the above indicators of lung damage and inflammation. Conclusion Taken together, our results clearly demonstrate that iNOS plays an important role in the lung injury induced by bleomycin in the mice.

Genovese Tiziana; Cuzzocrea Salvatore; Di Paola Rosanna; Failla Marco; Mazzon Emanuela; Sortino Maria; Frasca Giuseppina; Gili Elisa; Crimi Nunzio; Caputi Achille P; Vancheri Carlo

2005-01-01

159

Lymphangioma circumscriptum of the tongue in children: successful treatment using intralesional bleomycin.  

UK PubMed Central (United Kingdom)

Lymphangioma circumscriptum is an uncommon congenital skin disorder occurring commonly in limbs and genitals, and is extremely rare in tongue. Although complete surgical excision is the most widely used treatment, more conservative procedures such as sclerotherapy are being increasingly used for treatment of lymphangiomas. We present a series of two cases of lymphangioma circumscriptum of tongue which were treated successfully with intralesional bleomycin injection.

Chakravarti A; Bhargava R

2013-08-01

160

Noncovalent intermolecular crosslinks are produced by bleomycin reaction with duplex DNA.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Reaction of covalently closed circular PM2 bacteriophage DNA with the anticancer drug bleomycin produces nicked circular (form II) and linear duplex (form III) DNA [Lloyd, R.S., Haidle, C.W. & Robberson, D.L. (1978) Biochemistry 17, 1890-1896]. As the reaction proceeds, the frequencies of both form ...

Lloyd, R S; Haidle, C W; Robberson, D L

 
 
 
 
161

Bleomycin induces upregulation of lysyl oxidase in cultured human fetal lung fibroblasts.  

UK PubMed Central (United Kingdom)

AIM: To investigate the mechanism of bleomycin (BLM)-induced pulmonary fibrosis. METHODS: Cultured human fetal lung fibroblast (HLF) cells were exposed to bleomycin (BLM) at 0-30 microg/mL for 24 h. Western blot analysis was used to detect lysyl oxidase (LO) protein expression. Real-time RT-PCR was used to detect LO mRNA level. LO catalytic activity was measured using diaminopentane as a substrate and Amplex red as a hydrogen peroxide probe. Copper (Cu) concentration was detected by flame atomic absorption spectrophotometry. RESULTS: Exposure of HLF cells to BLM at 10 microg/mL and 30 microg/mL increased LO catalytic activity to 130% and 158% of the control in the conditioned media. The expression of LO mRNA was increased to 5.5-fold of the control in HLF cells exposure to BLM at 3 microg/mL. BLM at 3 microg/mL also increased the expression of 46 kDa preproLO, 50 kDa proLO and 32 kDa mature LO to 219%, 130%, and 135% of the control, respectively. The Cu concentrations in conditioned media of cultured HLF cells exposed to BLM (10 and 30 microg/mL) were increased significantly to 1.48 and 2.46-fold of the control, respectively. CONCLUSION: Bleomycin induces upregulation of LO in cultured human fetal lung fibroblasts, which may be the mechanism of bleomycin-induced pulmonary fibrosis.

Chen LJ; Li WD; Li SF; Su XW; Lin GY; Huang YJ; Yan GM

2010-05-01

162

The encapsulation of bleomycin within chitosan based polymeric vesicles does not alter its biodistribution.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Polymeric vesicles have recently been developed from an amphiphilic chitosan derivative--palmitoyl glycol chitosan. Their potential as a drug delivery system was evaluated using the anti-cancer compound bleomycin as a model drug. Palmitoyl glycol chitosan (GCP41) was synthesised by conjugation of pa...

Sludden, J; Uchegbu, IF; Schätzlein, AG

163

Enzymes of collagen synthesis in lung tissues of bleomycin-induced pulmonary fibrosis.  

UK PubMed Central (United Kingdom)

The activities of prolyl hydroxylase (Pro-OHase), galactosylhydroxylysyl glucosyltransferase (Glu-Gal-Hyl-Tase), and hydroxylysyl galactosyltransferase (Gal-Hyl-Tase) were assayed in lung tissues of hamsters with bleomycin-induced experimental pulmonary fibrosis. Serum Glu-Gal-Hyl-Tase and aspartate transaminase (Asp-NH2-Tase) were measured in the same animals. Lung fibrosis was induced by intratracheal bleomycin instillation, and the enzyme activities were assayed 2, 3, and 4 weeks after bleomycin administration. The activities of the three lung enzymes increased significantly after bleomycin instillation. However, no difference in the values of serum Glu-Gal-Hyl-Tase or Asp-NH2-Tase were observed. Histologic examination of lung sections indicated progressive fibrotic foci. These results thus indicate that the activities of collagen processing enzymes are elevated in the fibrotic lung tissues as a reflection of the increased rate of collagen synthesis during the period of active fibrogenesis, but unlike liver fibrosis, the elevation of tissue Glu-Gal-Hyl-Tase is not predicted by a corresponding increase in serum levels of this enzyme.

Bolarin DM; Palicharla P; Fuller GC

1984-03-01

164

Enzymes of collagen synthesis in lung tissues of bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

The activities of prolyl hydroxylase (Pro-OHase), galactosylhydroxylysyl glucosyltransferase (Glu-Gal-Hyl-Tase), and hydroxylysyl galactosyltransferase (Gal-Hyl-Tase) were assayed in lung tissues of hamsters with bleomycin-induced experimental pulmonary fibrosis. Serum Glu-Gal-Hyl-Tase and aspartate transaminase (Asp-NH2-Tase) were measured in the same animals. Lung fibrosis was induced by intratracheal bleomycin instillation, and the enzyme activities were assayed 2, 3, and 4 weeks after bleomycin administration. The activities of the three lung enzymes increased significantly after bleomycin instillation. However, no difference in the values of serum Glu-Gal-Hyl-Tase or Asp-NH2-Tase were observed. Histologic examination of lung sections indicated progressive fibrotic foci. These results thus indicate that the activities of collagen processing enzymes are elevated in the fibrotic lung tissues as a reflection of the increased rate of collagen synthesis during the period of active fibrogenesis, but unlike liver fibrosis, the elevation of tissue Glu-Gal-Hyl-Tase is not predicted by a corresponding increase in serum levels of this enzyme. PMID:6200953

Bolarin, D M; Palicharla, P; Fuller, G C

1984-03-30

165

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients  

Directory of Open Access Journals (Sweden)

Full Text Available Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS) exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2, when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS showed free trisomy 21 (47,XX + 21 or 47,XY + 21). Individuals that showed an average number of chromatid breaks per cell higher than 0.8 were considered sensitive to the drug. No control child showed susceptibility to bleomycin, and among the 24 patients with DS, only one was sensitive to the drug. No significant difference was observed between the two groups, regarding chromatid break frequencies in treated G2 lymphocytes. The distribution of bleomycin-induced breaks in each group of chromosomes was similar for DS and controls. No significant difference was found in the response to bleomycin between male and female subjects. Probably, the main factor involved in chromosome sensitivity of lymphocytes from patients with DS is the phase of the cell cycle in which the cell is treated.

Bartholomei-Santos Marlise Ladvocat; Lucca Edmundo José de

1997-01-01

166

Development and time-course of bleomycin-induced pulmonary fibrosis in NMRI mice  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Bleomycin-induced pulmonary fibrosis is a widely used experimental model for human lung fibrosis. The severity of fibrosis varies among different strains of mice and investigation on different strains and finding the mechanisms of variation is important in understanding the pathogenesis of human lun...

Jafarian-Dehkordi A.; Rabbani M.; Mir Mohammad Sadeghi H.; Afshar-Moghaddam N.; Alavi S.A.; Mahmoodi F; Safaeian L

167

The counter regulatory response induced by CpG oligonucleotides prevents bleomycin induced pneumopathy  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Bleomycin (BLM) induces life-threatening pneumonitis and pulmonary fibrosis in 20% of patients, limiting its use as a chemotherapeutic agent. Oligonucleotides expressing immunostimulatory CpG motifs (CpG ODN) stimulate cells that express Toll-like receptor 9 to initiate an inflammatory response. Thi...

Kinjo, Takeshi; Tomaru, Koji; Haines, Diana C; Klinman, Dennis M

168

Intralesional bleomycin in the treatment of cutaneous warts: A randomized clinical trial comparing it with cryotherapy  

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Background: Though not in regular practice, intralesional (IL) bleomycin has been used for the treatment of warts since the 1970s and on the other hand, till now cryotherapy is quite regularly used to treat warts. Aim: Our aim was to assess the evidence for the efficacy of IL bleomy...

Dhar S; Rashid M; Islam AZMM; Bhuiyan MSI

169

Preparation and Quality Control of Scandium-46 Bleomycin as a Possible Therapeutic Agent  

Directory of Open Access Journals (Sweden)

Full Text Available Introduction: Due to interesting therapeutic properties of 46Sc and antineoblastic antibiotic, bleomycin (BLM), 46Sc-bleomycin (46Sc-BLM) was developed as a possible therapeutic compound. Methods: In this work, Sc-46 chloride was obtained by thermal neutron flux (4 × 1013 n.cm-2.s-1) of natural metallic scandium sample followed by dissolution in acidic media as a substitute for 47Sc in radiolabeling studies which was further used for labeling of bleomycin (BLM) followed by stability studies as well as biodistribution in wild-type rats. Results: Sc-46 was obtained in high radiochemical purity (ITLC, >99%, two systems) as well as acceptable specific activity. At optimized conditions a radiochemical purity of 98% was obtained for 46Sc-BLM shown by ITLC (Specific activity, 740 GBq/mmole). The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins. Conclusion: Sc-BLM is a possible therapeutic agent in human malignancies and the efficacy of the compound should be tested in various tumor-bearing models.

Leila Moghaddam-Banaem; Amir Reza Jalilian; Mohammadreza Pourjavid; Ali Bahrami-Samani; Mohammad Mazidi; Mohammad Ghannadi-Maragheh

2012-01-01

170

Development of 153Sm-bleomycin as a possible therapeutic complex  

International Nuclear Information System (INIS)

Due to interesting therapeutic properties of 153Sm and antineoplastic antibiotic, bleomycin(BLM), 153Sm-bleomycin (153Sm-BLM) was developed as a possible therapeutic compound using 153SmCl3 and BLM. The 153SmCl3 was obtained by thermal neutron flux (5 x 1013 n · cm-2 · s-1) of an enriched 152Sm2O3 sample,dissolved in acidic media.Under optimized conditions (room temperature, 45 min, 0.1 mg bleomycin for 740-3700 MBq 153SmCl3) a radiochemical purity over 98% was obtained shown by HPLC (Specific activity = 55 TBq/mM). The 153SmCl3 and 153Sm-BLM were administered into wild-type rats up to 96 h followed by biodistribution. The SPECT imaging of labeled compound in wild-type rats was performed and significant image pattern was observed for a radiolabeled bleomycin compound. The 153Sm-BLM is a potential therapeutic compound and our experiments on this compound have shown satisfactory quality, and stability suitable for future therapeutic studies. (authors)

2010-01-01

171

Hyperoxia, but not thoracic X-irradiation, potentiates bleomycin- and cyclophosphamide-induced lung damage in mice  

Energy Technology Data Exchange (ETDEWEB)

The intraperitoneal administration of cyclophosphamide or bleomycin to BALB/c mice resulted in lung cell damage followed by cellular proliferation, which was quantitated by measuring the increase in thymidine incorporation into pulmonary DNA. We have previously shown that administration of the antioxidant butylated hydroxytoluene produces lung damage that can be potentiated by both hyperoxia and thoracic X-irradiation. In the present study we show that hyperoxic exposure also potentiates bleomycin- and cyclophosphamide-induced acute lung damage. However, thoracic X-irradiation does not potentiate bleomycin- and cyclophosphamide-induced lung toxicity.

Hakkinen, P.J.; Whiteley, J.W.; Witschi, H.R.

1982-08-01

172

Voip Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available This article focuses on existing technologies in telecommunications but also on a comparative analysis of VoIP protocols. There will also be listed ways to extend networks and processes that contribute to the steady operation of the network as a set SLA with the support of a large number of simultaneous connections

Floriana GEREA; Adrian GHENCEA

2012-01-01

173

The use of isotopic labels to probe the mechanism of DNA oxidation by iron bleomycin  

International Nuclear Information System (INIS)

When the antitumor antibiotic bleomycin is activated anaerobically with Fe(III) and hydrogen peroxide or with Fe(II) and limiting oxygen, the DNA products are free nucleic acid base and an oxidatively damaged sugar lesion which undergoes strand scission when treated with alkali. Stabilization of the initial product by borohydride reduction and digestion by P1 nuclease and alkaline phosphatase afforded 2 double-prime-deoxypentitol-3 double-prime-O-5'-phospho-2'-deoxypurine nucleosides that accounted for 99, 81 and 48% of the pyrimidine base released from d(CGCGCG), poly(dA-dU) and poly(dG-dC), respectively. Further enzymatic degradation yielded 2-deoxy-D-erythro-pentitol and 2-deoxy-L-threo-pentitol which were identified by mass spectrometry. The 2'-deoxypentos-4'-ulose product arising from the interaction of d(CGCGCG) with bleomycin was 86 and 97% 18O-labeled at C-4' at pH 9.0 and 7.8, respectively, when limiting 16O-labeled oxygen was used to activate bleomycin in 18O-water. Either complete isotopic exchange between solvent and a high-valent iron-oxo species of bleomycin or the equivalent of a 1e- oxidation of the presumed 4 carbon-centered radical of DNA are required to account for these findings. When oxygen is supplied in excess of what is required to activate bleomycin, the C3'-C4' bond of DNA is ruptured to yield transbase propenals and oligonucleotides bearing 5-phosphate and 3-phosphoglycolate termini. Kinetics study of base propenal formation from a DNA-bound precursor and release of 3H from pro R and pro S poly(dA-[2-3H]dU) showed that reported rapid release compared penal formation was the result of specific release from the pro R position and was not a consequence of the base release pathway nor nonstereospecific enolization of 2' hydrogens.

1990-01-01

174

Bleomicina: un modelo de fibrosis pulmonar/ Bleomycin: a lung fibrosis animal model  

Scientific Electronic Library Online (English)

Full Text Available Abstract in spanish La bleomicina es un glicopéptido utilizado para el tratamiento del cáncer cuyo potencial terapéutico está limitado por su toxicidad pulmonar. El efecto citotóxico depende de la dosis e involucra el desarrollo de neumonitis que progresa a fibrosis; las células epiteliales alveolares son el blanco principal del daño inducido por la bleomicina. Se considera que la muerte de células epiteliales alveolares por apoptosis es un evento clave en el inicio y la progresión (more) de la fibrosis pulmonar (FP) que se caracteriza por el depósito excesivo de moléculas de la matriz extracelular, principalmente de colágenas fibrilares en el parénquima pulmonar. En la investigación básica de la FP, la bleomicina se ha utilizado como el principal agente fibrogénico en modelos animales. Durante los últimos años, el modelo de bleomicina desarrollado en ratones trasgénicos se ha empleado para elucidar in vivo el papel de un gran número de biomoléculas involucradas en la FP. Abstract in english Bleomycin is a glycopeptide used for cancer treatment, but the therapeutic potencial of this drug is limited by its lung toxicity. The cytotoxic effect of bleomycin is dose-dependent and involves pneumonitis that proceeds to lung fibrosis (LF). Alveolar epithelial cells are the main target of bleomycin induced injury. Alveolar epithelial cell death by apoptosis is considered as a key event in the initiation and progression of LF, that is characterized by excessive deposit (more) ion of extracellular matrix, mainly fibrilar collagens in the lung parenchyma. Bleomycin has been used as the main fibrogenic agent in animal models in LF basic research; in recent years, a bleomycin model developed in transgenic mice has been used to elucidate the in vivo role of a great number of biomolecules involved in LF.

Cabrera Benítez, Sandra

2006-03-01

175

Gene expression profiling of human dermal fibroblasts exposed to bleomycin sulphate does not differentiate between radiation sensitive and control patients  

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Abstract Background Gene expression profiling of the transcriptional response of human dermal fibroblasts to in vitro radiation has shown promise as a predictive test of radiosensitivity. This study tested if treatment with the radiomimetic drug bleomycin sulphate could be ...

Westbury Charlotte B; Sahlberg Kristine; Borresen-Dale Anne-Lise; Isacke Clare M; Yarnold John R

176

cdc9 Ligase-defective mutants of Saccharomyces cerevisiae exhibit lowered resistance to lethal effects of bleomycin  

Energy Technology Data Exchange (ETDEWEB)

Conditional ligase-deficient mutants of Saccharomyces cerevisiae were more sensitive than their parental (CDC9) strain to dose-dependent killing by bleomycin, even when mutant cells were pregrown and exposed to the antibiotic at permissive temperatures. Pretreatment incubation at the restrictive temperature (37/sup 0/C) under growing or nongrowing conditions enhanced bleomycin killing of both cdc9-1 and cdc9-9 mutants. This sensitization could be relieved by incubation at the permissive temperature before treatment.

Moore, C.W.

1982-09-01

177

Cross section measurement of the reaction 7Be(p,?)8B at low energy and its applications to the solar neutrino problem  

International Nuclear Information System (INIS)

The 8B production through the 7Be(p,?)8B reaction is the main sources of high energy solar electron neutrinos. The cross section of this reaction at energies of the order of 20 KeV is essential to the solar models. We have measured this cross section between 0.4 MeV and 1.5 MeV by means of a Van de Graaff accelerator, using a radioactive 7Be target. The alpha particle production due to 8Be radioactive decay is used in order to deduce the reaction cross section. The total cross section has a total uncertainty lower than 10%. The results are given. These are in agreement and disagreement with Filiponne and Kavannagh, respectively. The data analysis leads to an astrophysical factor corresponding to this reaction, S17(0), within the interval 16.6 ± 1.0 to 20.1 ± 1 eV barn. The uncertainty comes essentially from the implied different energy depending quantities, as predicted by different models

1997-01-01

178

Histology protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Tim D. Hewitson & Ian A. Darby (Eds) Humana press, Totowa, New Jersey (USA) Series: Springer Protocols Methods in Molecular Biology, Volume 611, 2010 Pages: 230; € 83.15 ISBN: 978-1-60327-344-2 Impressive as it can sounds in the era that Biology see a clear dominance of reductionism with the idea that complexity can be disentagled more and more thanks to the use of molecular tools, the reader will remain fascinated by this slim and agile volume devoted to bring together what apparently are two separeted words: molecular biology and histology. Simply remembering to the youngest scientists.....

CarloAlberto Redi

2010-01-01

179

Mobile Internet Protocol Analysis.  

Science.gov (United States)

Mobile Internet Protocol (IP) is a proposed standard that builds on the current Internet Protocol by making the fact that a user is mobile transparent to applications and higher level protocols such as Transmission Control Protocol (TCP) and User Datagram...

L. J. Brachfeld

1999-01-01

180

Radiochemotherapy of head and neck cancers. Dose reduction through the combination of cisplatin, bleomycin and tegafur  

Energy Technology Data Exchange (ETDEWEB)

Twenty-four cases of squamous cell carcinomas of the larynx and maxillary sinus were irradiated with or without cisplatin during a period from April 1973 through March 1984. Both bleomycin in oil and tegafur were administered irrespective of cisplatin. Therapeutic effectiveness was critically evaluated by means of serial biopsy and/or surgery. Radiotherapy alone could not bring about negative conversion of the biopsies, but ultimate negative conversion was observed in 18 out of the 24 cases when chemotherapeutics were appropriately combined. The five positives underwent surgery. In the cases of maxillary cancer, mixed infections appeared to interfere with the curative effectiveness of the radiochemotherapy. A resulting dosage reduction of 15Gy was observed in radiotherapy for negative conversion and one of 10mg for bleomycin as a result of incorporation of cisplatin.

Mishina, Hitoshi; Okuyama, Shinichi; Yuasa, Ryo; Saijo, Shigeru; Kaneko, Yutaka

1985-04-01

 
 
 
 
181

Structural studies on metallobleomycins: The interaction of Pt(II) and Pd(II) with bleomycin  

Directory of Open Access Journals (Sweden)

Full Text Available Two of the most successful chemotherapeutic agents used in the treatment of several neoplasias are bleomycin and cisplatin. Both drugs attack the DNA leading to the cancer cells death via different mechanisms. In view of the fact that the combination with each other leads to enhanced activity with less sever side effects, we have undertaken NMR studies on the complexes formed between bleomycin and PtII, PdII, cisplatin and transplatin. Herein we present a brief review of the studies on metallobleomycins which were carried out by our lab and others, as an outline of the results obtained using NMR in combination to circular dichroism spectroscopy. Our data indicate that in most cases and under several conditions studied, both metal ions form similar complexes with BLM, while more than one species are present in the solution. Structural implications and comparisons with other metallobleomycins are being discussed.

ATHANASIOS PAPAKYRIAKOU; IOANNIS BRATSOS; NIKOS KATSAROS

2003-01-01

182

What has happened to VBM (vinblastine, bleomycin, and methotrexate) chemotherapy for early-stage Hodgkin lymphoma?  

Science.gov (United States)

The VBM (vinblastine, bleomycin, methotrexate) chemotherapy combined with involved-field radiotherapy in early-stage Hodgkin lymphoma has not become popular in spite of its excellent results. Nine small trials with this combined therapy were carried out and described in eleven reports. VBM+ radiotherapy offered complete remission rates of 94-100%, with 5-year progression-free survival of 75-95% (elderly patients included). Considerable pulmonary toxicity was recorded in the first trials, but was fully controlled in the later studies through slight modifications of the schedule. The pulmonary toxicity was found related to mediastinal radiotherapy, bleomycin dose and administration of chemotherapy after radiotherapy; it is mitigated by low doses of prednisone. The very good results, the abated side effects on the lungs, the low extrapulmonary toxicity, and the anthracycline-free formulation make this combination therapy worth considering for early-stage Hodgkin lymphoma, particularly in the case of mediastinal involvement or in elderly patients. PMID:21592816

Gobbi, Paolo G; Federico, Massimo

2011-05-17

183

What has happened to VBM (vinblastine, bleomycin, and methotrexate) chemotherapy for early-stage Hodgkin lymphoma?  

UK PubMed Central (United Kingdom)

The VBM (vinblastine, bleomycin, methotrexate) chemotherapy combined with involved-field radiotherapy in early-stage Hodgkin lymphoma has not become popular in spite of its excellent results. Nine small trials with this combined therapy were carried out and described in eleven reports. VBM+ radiotherapy offered complete remission rates of 94-100%, with 5-year progression-free survival of 75-95% (elderly patients included). Considerable pulmonary toxicity was recorded in the first trials, but was fully controlled in the later studies through slight modifications of the schedule. The pulmonary toxicity was found related to mediastinal radiotherapy, bleomycin dose and administration of chemotherapy after radiotherapy; it is mitigated by low doses of prednisone. The very good results, the abated side effects on the lungs, the low extrapulmonary toxicity, and the anthracycline-free formulation make this combination therapy worth considering for early-stage Hodgkin lymphoma, particularly in the case of mediastinal involvement or in elderly patients.

Gobbi PG; Federico M

2012-04-01

184

Molecular dynamics simulations exploring the interaction between DNA and metalated bleomycin  

Directory of Open Access Journals (Sweden)

Full Text Available Bleomycin (Blm) is a natural antibiotic with antitumour activity, used as a combination drug in treatment of various types of cancers. Blm intercalates with DNA and will in the presence of a redox metal ion and molecular oxygen form an activated bleomycin complex capable of releasing free radicals and subsequently leading to DNA cleavage. The present theoretical work was carried out to better understand the interaction between DNA and Blm using different metal co-factors (Co and Fe). Binding energies and structural properties were analysed for both the complexes. The results show that Blm binds stronger to DNA when complexed with Fe, and provides a better structural orientation compared to the CoBlm complex in order to abstract the H4' hydrogen of deoxyribose that initiates the DNA strand cleavage process. The short distance between the iron-bound peroxide and the deoxyribose H4' furthermore supports the previously proposed direct abstraction mechanism.

Viraja R. Palwai; Leif A. Eriksson

2011-01-01

185

Lymphangioma circumscriptum of the tongue in children: successful treatment using intralesional bleomycin.  

Science.gov (United States)

Lymphangioma circumscriptum is an uncommon congenital skin disorder occurring commonly in limbs and genitals, and is extremely rare in tongue. Although complete surgical excision is the most widely used treatment, more conservative procedures such as sclerotherapy are being increasingly used for treatment of lymphangiomas. We present a series of two cases of lymphangioma circumscriptum of tongue which were treated successfully with intralesional bleomycin injection. PMID:23732020

Chakravarti, A; Bhargava, R

2013-05-31

186

Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma.  

UK PubMed Central (United Kingdom)

Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen.

Kelsen D; Hilaris B; Coonley C; Chapman R; Lesser M; Dukeman M; Heelan R; Bains M

1983-10-01

187

Relationship between the time of doubling of pulmonary tumours and the uptake of labelled bleomycin  

International Nuclear Information System (INIS)

[en] The correlations between the uptake of cobalt 57 labelled bleomycin and, firstly, survival and, secondly, the time necessary for a primary bronchial carcinoma to double in volume were studied. Analysis of 22 cases showed significant correlations to p=0,001. The greater the fixation index, the shorter was the doubling time and the survival. One may consider that this finding permits measurement of the cellular proliferation of carcinomas, the clinical interest of which is obvious

1975-01-01

188

Aneuploidy induced by bleomycin in oocytes of Drosophila melanogaster: studies with the aneuploidy pattern method  

Energy Technology Data Exchange (ETDEWEB)

The induction of aneuploidy (numerical chromosome aberrations) in oocytes of Drosophila melanogaster by the antitumor drug bleomycin (BLM) was studied with the aneuploidy pattern method. The aneuploidy pattern obtained after feeding BLM at a concentration of 50 ..mu..g/ml to Drosophila females resembles the pattern obtained after X-irradiation (3000 R). This emphasizes the radiomimetic nature of BLM. In addition, new control material is presented. The new control pattern agrees well with that obtained earlier.

Traut, H.

1984-01-01

189

Sequence-specific isotope effects on the cleavage of DNA by bleomycin  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin is a metal- and oxygen-dependent DNA cleaver. The chemistry of DNA damage has been proposed to involve rate-limiting abstraction of the 4'-hydrogen. A DNA fragment has been prepared that contains (4'-2H)thymidine residues of high isotopic content. Primary kinetic isotope effects have been directly observed at individual thymidine residues with DNA sequencing technology.

Kozarich, J.W.; Worth, L. Jr.; Frank, B.L.; Christner, D.F.; Vanderwall, D.E.; Stubbe, J. (Univ. of Maryland, College Park, MD (USA))

1989-09-22

190

Efficacy of Intralesional Bleomycin in Palmo-plantar and Periungual Warts.  

UK PubMed Central (United Kingdom)

BACKGROUND/AIM: Intralesional bleomycin gained increasing popularity in the recent past for treatment of warts particularly in palmo-plantar and periungual regions as other modalities are not very effective. Hence we evaluated the role of intralesional bleomycin in periungual and palmo-plantar warts to know its efficacy in Indian patients. SETTINGS AND DESIGN: This was a placebo-controlled study. MATERIALS AND METHODS: Fifty patients of multiple palmo-plantar and periungual warts were included in this study and categorized in groups A and B of 25 each. Alternate patients were included in groups A and B and treated respectively with intralesional bleomycin (1 mg/mL solution) and normal saline as placebo, fortnightly for maximum up to two injections. Patients were followed up weekly for 1 month, fortnightly up to 12 weeks, and then quarterly for 1 year. If warts persisted after 12 weeks of starting treatment, it was considered a failure. Statistical analysis was done by the chi-square test using M-stat software. RESULTS: Group A and B patients were having 85 warts and 72 warts, respectively. The cure rate in group A and B patients was 96.47% (82/85 warts) and 11.11% (8/72 warts), respectively, after one or two injections within 12 weeks. The difference in the cure rate between two groups was statistically highly significant (<0.0001). In group A patients, a haemorrhagic eschar was formed which gradually healed in 8-12 weeks without atrophy or pigmentation; this phenomenon was not seen in group B. Only moderate pain was observed by most of the patients during injection in both groups. CONCLUSION: The intralesional injection of bleomycin is highly effective, safe, and non-toxic in periungual and palmo-plantar warts.

Soni P; Khandelwal K; Aara N; Ghiya BC; Mehta RD; Bumb RA

2011-09-01

191

Targeting protease activated receptor-1 with P1pal-12 limits bleomycin-induced pulmonary fibrosis.  

UK PubMed Central (United Kingdom)

BACKGROUND: Idiopathic pulmonary fibrosis is the most devastating fibrotic diffuse parenchymal lung disease which remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. Protease-activated receptor (PAR)-1 is a G-protein-coupled receptor that mediates critical signalling pathways in pathology and physiology. Bleomycin-induced lung fibrosis has been shown to be diminished in PAR-1-deficient mice. The purpose of this study is to investigate whether pharmacological PAR-1 inhibition is a potential therapeutic option to combat pulmonary fibrosis. METHODS: Pulmonary fibrosis was induced by intranasal instillation of bleomycin into wild-type mice with or without a specific PAR-1 antagonist (ie, P1pal-12, a pepducin that blocks the PAR-1/G-protein interaction). Fibrosis was assessed by hydroxyproline analysis, immunohistochemistry, quantitative PCR and western blot for fibrotic markers expression. RESULTS: We first show that P1pal-12 effectively inhibits PAR-1-induced profibrotic responses in fibroblasts. Next, we show that once daily treatment with 0.5, 2.5 or 10 mg/kg P1pal-12 reduced the severity and extent of fibrotic lesions in a dose-dependent manner. These findings correlated with significant decreases in fibronectin, collagen and ? smooth muscle actin expression at the mRNA and protein level in treated mice. To further establish the potential clinical applicability of PAR-1 inhibition, we analysed fibrosis in mice treated with P1pal-12 1 or 7 days after bleomycin instillation. Interestingly, when administered 7 days after the induction of fibrosis, P1pal-12 was as effective in limiting the development of pulmonary fibrosis as when administration was started before bleomycin instillation. CONCLUSIONS: Overall, targeting PAR-1 may be a promising treatment for pulmonary fibrosis.

Lin C; Duitman J; Daalhuisen J; Ten Brink M; von der Thüsen J; van der Poll T; Borensztajn K; Spek CA

2013-09-01

192

Bleomycin-induced pulmonary fibrosis is attenuated by an antibody against KL-6.  

UK PubMed Central (United Kingdom)

BACKGROUND: Elevated levels of KL-6 are reported in the serum and/or bronchoalveolar lavage fluid (BALF) of patients with interstitial lung disease (ILD) and are useful to estimate the severity and prognosis of the disease. However, whether the anti-KL-6 antibody could attenuate pulmonary fibrosis remains unclear. OBJECTIVES: This study aims to investigate the therapeutic effects and mechanisms of anti-KL-6 antibody on bleomycin-induced pulmonary fibrosis. METHODS: A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (5 mg/kg). Mouse received anti-KL-6 antibody (20 ug/day, once a day) from day 7 to 21 after bleomycin injection. The effects of anti-KL-6 antibody were evaluated by pathological examination, measuring hydroxyproline measurements in lung tissues, leukocyte counts in BALF and the expression of collagen type I and type III using qRT-PCR. The expression of profibrotic cytokine (transforming growth factor-?1, TGF-?1), antifibrotic cytokine (hepatocyte growth factor, HGF), and KL-6 in lung tissues were analyzed by ELISA. The apoptosis of epithelial cell was examined by TUNEL staining. RESULTS: Anti-KL-6 antibody significantly reduced the number of alveolar inflammatory leukocytes (total and differential counts) in BALF of mice with bleomycin-induced pulmonary fibrosis as well as the content of hydroxyproline in the lung tissues. Treatment with anti-KL-6 antibody downregulated the expression of collagen type I, TGF-?1 and KL-6, upregulated the expression of HGF and inhibited the apoptosis of epithelial cells. CONCLUSIONS: These findings indicated the anti-KL-6 antibody may potentially be developed as a useful inhibitor of pulmonary fibrosis.

Xu L; Yang D; Zhu S; Gu J; Ding F; Bian W; Rong Z; Shen C

2013-08-01

193

Aneuploidy induced by bleomycin in oocytes of Drosophila melanogaster: studies with the aneuploidy pattern method  

International Nuclear Information System (INIS)

The induction of aneuploidy (numerical chromosome aberrations) in oocytes of Drosophila melanogaster by the antitumor drug bleomycin (BLM) was studied with the aneuploidy pattern method. The aneuploidy pattern obtained after feeding BLM at a concentration of 50 ?g/ml to Drosophila females resembles the pattern obtained after X-irradiation (3000 R). This emphasizes the radiomimetic nature of BLM. In addition, new control material is presented. The new control pattern agrees well with that obtained earlier.

1984-01-01

194

57Co-bleomycin scintigraphy for the staging of lung cancer  

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The value of Cobalt-57 bleomycin (57Co-BLM) scintigraphy in the detection of lymph node metastases in the hilum and mediastinum was investigated in 132 patients with peripherally located lung cancer. In one half of the patients with metastases, these were visualized. Specificity was 98%. These results were better than those obtained with chest radiography and conventional roentgen tomography. 57Co-BLM scintigraphy is routinely used in the staging of patients with lung cancer, obviating the need for mediastinoscopy.

1989-01-01

195

Images of liposarcoma using technetium-99m bleomycin and technetium (V)-99m DMSA  

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The effectiveness of Tc-99m bleomycin (BLM) and Tc(V)-99m DMSA are compared with that of Ga-67 citrate, which is currently the most widely used agent. In four patients with lipomatous tumors, the clinical significance of tumor imaging with each of these three agents is discussed and compared. Results indicate that both Tc-99m BLM and Tc(V)-99m DMSA are superior in detecting the extension or localization of liposarcomas.

Ohta, H.; Shane, F.I.; Endo, K.; Torizuka, K.; Horiuchi, K.; Yokoyama, A.; Ishii, M.

1986-12-01

196

Images of liposarcoma using technetium-99m bleomycin and technetium (V)-99m DMSA  

International Nuclear Information System (INIS)

The effectiveness of Tc-99m bleomycin (BLM) and Tc(V)-99m DMSA are compared with that of Ga-67 citrate, which is currently the most widely used agent. In four patients with lipomatous tumors, the clinical significance of tumor imaging with each of these three agents is discussed and compared. Results indicate that both Tc-99m BLM and Tc(V)-99m DMSA are superior in detecting the extension or localization of liposarcomas

1986-01-01

197

Local delivery of biodegradable pirfenidone nanoparticles ameliorates bleomycin-induced pulmonary fibrosis in mice  

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Our purpose was to assess sustained delivery and enhanced efficacy of pirfenidone-loaded nanoparticles after intratracheal instillation. Poly(lactide-co-glycolide) nanoparticles containing pirfenidone (NPs) were prepared and characterized. Biodistribution of NPs and solution was assessed using LC-MS after intratracheal administration in C57Bl/6 mice at 3 and 24 h and 1 week post-administration. Efficacy was tested in C57Bl/6 mice in a bleomycin-induced pulmonary fibrosis model. Mice received 10 ?g pirfenidone intratracheally in solution or NPs, once a week, for 3 weeks after bleomycin administration. Drug effects were monitored on day 28. Lung hydroxyproline content, total number of cells, and numbers of macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage (BAL) were assessed. Numbers of macrophages, lymphocytes, and neutrophils were assessed in the lung as well. NPs sustained significantly higher levels of pirfenidone in the lungs and BAL at 24 h and 1 week, compared to the solution group. Pirfenidone solution and NPs significantly reduced hydroxyproline levels by 57 and 81%, respectively, compared to bleomycin alone. At the end of 4 weeks, BAL cellularity was reduced by 25.4% and 56% with solution and NP treatment, respectively. The numbers of lymphocytes and neutrophils in the BAL were also reduced by 58.9 and 82.4% for solution and 74.5% and 89.7% for NPs, respectively. The number of inflammatory macrophages in the lung was reduced by 62.8% and the number of neutrophils was reduced by 59.1% in the NP group and by 37.7% and 44.5%, respectively, in the solution group, compared to bleomycin alone. In conclusion, nanoparticles sustain lung pirfenidone delivery and enhance its anti-fibrotic efficacy.

Trivedi, Ruchit; Redente, Elizabeth F.; Thakur, Ashish; Riches, David W. H.; Kompella, Uday B.

2012-12-01

198

Pharmacokinetics of 57Co-bleomycin A5 in animals with different inoculated tumors  

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The examination of rats with different inoculated tumors rhabdomyosarcoma M-1 (RMS), sarcoma 45 (S-45), Pliss lymphosarcoma (PLS) and Walker carcinoma (WK) revealed, that the pharmacokinetics of 57Co-bleomycin in tumor-bearing animals did not essentially depend on the histological type of the tumor. The specific activity quotients in the tumors as well as in the muscle tissue did not show differences and had their maxima 3 h after application of the preparation (RMS = 11.7 +- 2.70; S-45 = 10.9 +- 2.05; PLS = 9.52 +- 1.14; WK = 9.16 +- 1.93). The storage maximum of 57Co-bleomycin A5 per g tumor tissue was for RMS and PLS after 5 min. (0.83 +- 0.10 and 0.71 +- 0.06 %, resp., of the applied activity), for S-45 and WK after one hour (0.87 +- 0.14 and 0.86 +- 0.15 %, resp.). The results of the kinetic distribution of the labelled bleomycin A5 showed that the moments of visualization of the tumors varied in the different inoculated tumors in intervals from 3 to 48 h after application. (author)

1983-01-01

199

miR-29 inhibits bleomycin-induced pulmonary fibrosis in mice.  

UK PubMed Central (United Kingdom)

Loss of microRNA-29 (miR-29) is known to be a mechanism of transforming growth factor-? (TGF-?)-mediated pulmonary fibrosis, but the therapeutic implication of miR-29 for pulmonary fibrosis remains unexplored. The present study investigated whether miR-29 had therapeutic potential for lung disease induced by bleomycin in mice. In addition, the signaling mechanisms that regulated miR-29 expression were investigated in vivo and in vitro. We found that miR-29 was a downstream target gene of Smad3 and negatively regulated by TGF-?/Smad signaling in fibrosis. This was evidenced by the findings that mice or pulmonary fibroblasts null for Smad3 were protected against bleomycin or TGF-?1-induced loss of miR-29 along with fibrosis in vivo and in vitro. Interestingly, overexpression of miR-29 could in turn negatively regulated TGF-? and connective tissue growth factor (CTGF) expression and Smad3 signaling. Therefore, Sleeping Beauty (SB)-mediated miR-29 gene transfer into normal and diseased lung tissues was capable of preventing and treating pulmonary fibrosis including inflammatory macrophage infiltration induced by bleomycin in mice. In conclusion, miR-29 is negatively regulated by TGF-?/Smad3 and has a therapeutic potential for pulmonary fibrosis. SB-mediated miR-29 gene therapy is a non-invasive therapeutic strategy for lung disease associated with fibrosis.

Xiao J; Meng XM; Huang XR; Chung AC; Feng YL; Hui DS; Yu CM; Sung JJ; Lan HY

2012-06-01

200

Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice  

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The mechanisms underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF) involve multiple pathways, such as inflammation, epithelial mesenchymal transition, coagulation, oxidative stress, and developmental processes. The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK), may interact with other signaling pathways known to contribute to pulmonary fibrosis. This study aimed to determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice. Our results showed that the Aschcroft score and hydroxyproline content of the bleomycin-treated mouse lung decreased in response to fasudil treatment. The number of infiltrated inflammatory cells in the bronchoalveolar lavage fluid (BALF) was attenuated by fasudil. In addition, fasudil reduced the production of transforming growth factor-?1 (TGF-?1), connective tissue growth factor (CTGF), alpha-smooth muscle actin (?-SMA), and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein expression in bleomycin-induced pulmonary fibrosis. These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary fibrosis.

Jiang, Chunguo; Huang, Hui; Liu, Jia; Wang, Yanxun; Lu, Zhiwei; Xu, Zuojun

2012-01-01

 
 
 
 
201

miR-29 inhibits bleomycin-induced pulmonary fibrosis in mice.  

Science.gov (United States)

Loss of microRNA-29 (miR-29) is known to be a mechanism of transforming growth factor-? (TGF-?)-mediated pulmonary fibrosis, but the therapeutic implication of miR-29 for pulmonary fibrosis remains unexplored. The present study investigated whether miR-29 had therapeutic potential for lung disease induced by bleomycin in mice. In addition, the signaling mechanisms that regulated miR-29 expression were investigated in vivo and in vitro. We found that miR-29 was a downstream target gene of Smad3 and negatively regulated by TGF-?/Smad signaling in fibrosis. This was evidenced by the findings that mice or pulmonary fibroblasts null for Smad3 were protected against bleomycin or TGF-?1-induced loss of miR-29 along with fibrosis in vivo and in vitro. Interestingly, overexpression of miR-29 could in turn negatively regulated TGF-? and connective tissue growth factor (CTGF) expression and Smad3 signaling. Therefore, Sleeping Beauty (SB)-mediated miR-29 gene transfer into normal and diseased lung tissues was capable of preventing and treating pulmonary fibrosis including inflammatory macrophage infiltration induced by bleomycin in mice. In conclusion, miR-29 is negatively regulated by TGF-?/Smad3 and has a therapeutic potential for pulmonary fibrosis. SB-mediated miR-29 gene therapy is a non-invasive therapeutic strategy for lung disease associated with fibrosis. PMID:22395530

Xiao, Jun; Meng, Xiao-Ming; Huang, Xiao R; Chung, Arthur Ck; Feng, Yu-Lin; Hui, David Sc; Yu, Cheuk-Man; Sung, Joseph Jy; Lan, Hui Y

2012-03-06

202

Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Full Text Available The mechanisms underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF) involve multiple pathways, such as in?ammation, epithelial mesenchymal transition, coagulation, oxidative stress, and developmental processes. The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK), may interact with other signaling pathways known to contribute to pulmonary ?brosis. This study aimed to determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice. Our results showed that the Aschcroft score and hydroxyproline content of the bleomycin-treated mouse lung decreased in response to fasudil treatment. The number of infiltrated inflammatory cells in the bronchoalveolar lavage fluid (BALF) was attenuated by fasudil. In addition, fasudil reduced the production of transforming growth factor-?1 (TGF-?1), connective tissue growth factor (CTGF), alpha-smooth muscle actin (?-SMA), and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein expression in bleomycin-induced pulmonary fibrosis. These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary ?brosis.

Chunguo Jiang; Hui Huang; Jia Liu; Yanxun Wang; Zhiwei Lu; Zuojun Xu

2012-01-01

203

Intratumoral (i.t.) application of 57Co-bleomycin. Results of pharmacodynamic and autoradiographic investigations  

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57Co-labeled bleomycin in aqueous solution was applied intratumorally (i.t.) in 51 tumor-bearing nude mice (tissue from a carcinoma of the tongue, from the lymph node metastasis of the tongue carcinoma, and from a cystic carcinoma of the submandibular gland, as well as to 11 patients with a squamous cell carcinoma of the oral cavity. Animal experiments showed that the intratumoral radioactivity accumulation is 10 times higher after i.t. application than after intravenous injection, that the tongue carcinoma accumulates bleomycin to a higher degree than the other tumors, and that a considerable portion of the radioactive bleomycin is found in necrotic tumor areas only 5 hours p.i. The clinical study showed that large amounts of the radiopharmaceutical are eliminated from the tumor within 1 hour of injection. Retention of the pharmaceutical seems to depend on tumor localization and/or the vascularity of the adjacent tissue. The radiographic findings were compatible with the results gained in animal experiments. (orig.)

1985-01-01

204

Evaluation of the Effects of Nicotinamide on the Bleomycin-induced Pulmonary Fibrosis in Rat  

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Full Text Available Fibrosis is the abnormal production of collagen fibers following tissue damage. This accounts for the formation of scar tissue. Lung fibrosis is one of the typical ways in which the lung reacts to damaging stimuli. In this study we tried to investigate the involving phenomena during the process of bleomycin-induced fibrosis in murine lung. We have evaluated this process at three levels, namely, at (1) cellular level (cells with contraction activity of pulmonary tissue), (2) intercellular signaling agents (e.g., IL-8, TNF-?, TGF-?), tissue index factors (collagen, hydroxyproline) and some inorganic elements which may hypothetically be engaged as efficient enzymatic cofactors (e.g., copper), (3) pathophysiological or exaggerated physiological processes (inflammation and fibrosis). The pharmacological agent which have been selected for evaluating in this study is Nicotinamide, which their selection rationale will be discussed in detail separately in the discussion section. Bleomycin-induced pulmonary fibrosis is a widely used animal model for lung injury and fibrosis. After single dose instillation of intratracheal bleomycin, the fibrotic responses were studied by biochemical measurement of collagen deposition and analysis of pathological lung changes in different treatment groups. The results of this study showed that administrated agents in different doses, had satisfactorily healing effects on fibrosis process, ranging from good to moderate, through significant decreasing in lung collagen content (p<0.05).

Peyman Mikaili; Ali Asghar Hemmati; Mohammad Javad Khodayar; Mehri Ghafurian; Iran Rashidi

2011-01-01

205

Intratumoral (i. t. ) application of /sup 57/Co-bleomycin. Results of pharmacodynamic and autoradiographic investigations  

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/sup 57/Co-labeled bleomycin in aqueous solution was applied intratumorally (i.t.) in 51 tumor-bearing nude mice (tissue from a carcinoma of the tongue, from the lymph node metastasis of the tongue carcinoma, and from a cystic carcinoma of the submandibular gland, as well as to 11 patients with a squamous cell carcinoma of the oral cavity. Animal experiments showed that the intratumoral radioactivity accumulation is 10 times higher after i.t. application than after intravenous injection, that the tongue carcinoma accumulates bleomycin to a higher degree than the other tumors, and that a considerable portion of the radioactive bleomycin is found in necrotic tumor areas only 5 hours p.i. The clinical study showed that large amounts of the radiopharmaceutical are eliminated from the tumor within 1 hour of injection. Retention of the pharmaceutical seems to depend on tumor localization and/or the vascularity of the adjacent tissue. The radiographic findings were compatible with the results gained in animal experiments.

Henke, E.; Franke, W.G.; Froehlich, M.; Gens, J.; Arnold, W.; Naundorf, H.

1985-12-01

206

Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis  

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Full Text Available To investigate simultaneously localization and relative activity of MMPs during extracellular matrix (ECM) remodeling in bleomycin-induced pulmonary fibrosis in rat, we analyzed the time course of the expression, activity and/or concentration of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and TIMP-2, both in alveolar space (cellular and extracellular compartments) and in lung tissue. MMP and TIMP expression was detected (immunohistochemistry) in lung tissue. MMP activity (zymography) and TIMP concentration (ELISA) were evaluated in lung tissue homogenate (LTH), BAL supernatant (BALs) and BAL cell pellet (BALp) 3, 7, 14, and 28 days after bleomycin intratracheal instillation. Immunohistochemistry showed an extensive MMP and TIMP expression from day 7 in a wide range of structural and inflammatory cells in treated rats. MMP-2 was present mainly in epithelia, MMP-9 in inflammatory cells. MMP-2 and MMP-9 activity was increased respectively in BAL fluid and BAL cells, with a peak at day 7. TIMP-1 and TIMP-2 concentration (ELISA) enhancement was delayed at day 14. In conclusion gelatinases and their inhibitors are significantly activated during bleomycin-induced pulmonary fibrosis. Marked changes in gelatinases activity are observed early in the alveolar compartment, with a prevailing extracellular activity of MMP-2 and a predominant intracellular distribution of MMP-9, while enzyme activity changes in lung parenchyma were less evident. In the repairing phase the reduction of gelatinases activity is synchronous with a peak of alveolar concentration of their inhibitors.

T Oggionni; P Morbini; S Inghilleri; G Palladini; R Tozzi; P Vitulo; C Fenoglio

2006-01-01

207

Overexpression of cathepsin K in mice decreases collagen deposition and lung resistance in response to bleomycin-induced pulmonary fibrosis  

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Full Text Available Abstract Background Lung fibrosis is a devastating pulmonary disorder characterized by alveolar epithelial injury, extracellular matrix deposition and scar tissue formation. Due to its potent collagenolytic activity, cathepsin K, a lysosomal cysteine protease is an interesting target molecule with therapeutic potential to attenuate bleomycin-induced pulmonary fibrosis in mice. We here tested the hypothesis that over-expression of cathepsin K in the lungs of mice is protective in bleomycin-induced pulmonary fibrosis. Methods Wild-type and cathepsin K overexpressing (cathepsin K transgenic; cath K tg) mice were challenged intratracheally with bleomycin and sacrificed at 1, 2, 3 and 4 weeks post-treatment followed by determination of lung fibrosis by estimating lung collagen content, lung histopathology, leukocytic infiltrates and lung function. In addition, changes in cathepsin K protein levels in the lung were determined by immunohistochemistry, real time RT-PCR and western blotting. Results Cathepsin K protein levels were strongly increased in alveolar macrophages and lung parenchymal tissue of mock-treated cathepsin K transgenic (cath K tg) mice relative to wild-type mice and further increased particularly in cath K tg but also wild-type mice in response to bleomycin. Moreover, cath K tg mice responded with a lower collagen deposition in their lungs, which was accompanied by a significantly lower lung resistance (RL) compared to bleomycin-treated wild-type mice. In addition, cath K tg mice responded with a lower degree of lung fibrosis than wild-type mice, a process that was found to be independent of inflammatory leukocyte mobilization in response to bleomycin challenge. Conclusion Over-expression of cathepsin K reduced lung collagen deposition and improved lung function parameters in the lungs of transgenic mice, thereby providing at least partial protection against bleomycin-induced lung fibrosis.

Srivastava Mrigank; Steinwede Kathrin; Kiviranta Riku; Morko Jukka; Hoymann Heinz-Gerd; Länger Florian; Buhling Frank; Welte Tobias; Maus Ulrich A

2008-01-01

208

Novel regulatory role for Kaposi's sarcoma-associated herpesvirus-encoded vFLIP in chemosensitization to bleomycin.  

Science.gov (United States)

Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is associated with malignancy. KSHV-derived vFLIP is structurally related to cellular FLIP and binds to NEMO/I?B kinase (IKK?) to activate NF-?B signaling. NF-?B activation is postulated to confer chemoresistance to various anticancer drugs. However, here we showed that vFLIP expression uniquely sensitized HEK293 cells to bleomycin and its derivatives. Chemosensitization to bleomycin by vFLIP accompanied accumulation of ?-H2AX and G2/M-arrest of cells, while bleomycin-induced DNA damage checkpoints, such as phosphorylation of Chk2 and foci formation of Rad51, were similarly detected in both parental and vFLIP-expressing cells, suggesting that primary DNA damage was not affected by vFLIP. Paradoxically, while NF-?B activity was little affected by bleomycin treatment, vFLIP-stimulated NF-?B activity was suppressed by it. Additionally, cAMP-response element (CRE)- and p53-dependent transcriptional reporter activity was negatively regulated by vFLIP in the presence of bleomycin. Interestingly, a negative regulatory phosphatase essential for G2 checkpoint recovery and for dephosphorylation of ?-H2AX, Wip1/PPM1D, whose gene promoter is regulated by p53, CRE and NF-?B, was selectively downregulated in vFLIP-expressing cells after bleomycin treatment. These results suggest that vFLIP-mediated transcriptional regulation such as Wip1/PPM1D repression is involved in chemosensitization to bleomycin. PMID:22037577

Masuda, Yuri; Noguchi, Kohji; Segawa, Hatsune; Tanaka, Noritaka; Katayama, Kazuhiro; Mitsuhashi, Junko; Sugimoto, Yoshikazu

2011-10-21

209

Novel regulatory role for Kaposi's sarcoma-associated herpesvirus-encoded vFLIP in chemosensitization to bleomycin.  

UK PubMed Central (United Kingdom)

Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is associated with malignancy. KSHV-derived vFLIP is structurally related to cellular FLIP and binds to NEMO/I?B kinase (IKK?) to activate NF-?B signaling. NF-?B activation is postulated to confer chemoresistance to various anticancer drugs. However, here we showed that vFLIP expression uniquely sensitized HEK293 cells to bleomycin and its derivatives. Chemosensitization to bleomycin by vFLIP accompanied accumulation of ?-H2AX and G2/M-arrest of cells, while bleomycin-induced DNA damage checkpoints, such as phosphorylation of Chk2 and foci formation of Rad51, were similarly detected in both parental and vFLIP-expressing cells, suggesting that primary DNA damage was not affected by vFLIP. Paradoxically, while NF-?B activity was little affected by bleomycin treatment, vFLIP-stimulated NF-?B activity was suppressed by it. Additionally, cAMP-response element (CRE)- and p53-dependent transcriptional reporter activity was negatively regulated by vFLIP in the presence of bleomycin. Interestingly, a negative regulatory phosphatase essential for G2 checkpoint recovery and for dephosphorylation of ?-H2AX, Wip1/PPM1D, whose gene promoter is regulated by p53, CRE and NF-?B, was selectively downregulated in vFLIP-expressing cells after bleomycin treatment. These results suggest that vFLIP-mediated transcriptional regulation such as Wip1/PPM1D repression is involved in chemosensitization to bleomycin.

Masuda Y; Noguchi K; Segawa H; Tanaka N; Katayama K; Mitsuhashi J; Sugimoto Y

2011-11-01

210

Effects of acronycine, bleomycin and cytosine arabinoside on the cell cycle  

International Nuclear Information System (INIS)

[en] The influence of three chemotherapeutic agents, acronycine, bleomycin and cytosine arabinoside, alone and combined with radiation, on cell cycle progression and viability of L-cells was examined. The percentages of cells in G1, S and (G2 + M)-phases as derived from pulse cytophotometric DNA distribution patterns were recorded as a function of exposure time. After 24-h treatment with 10 ?g/ml acronycine, 46.4% of cells were accumulated in (G2 + M)-phase compared to 12.1% in the controls. This accumulation was significantly enhanced by an irradiation with 150 rads of X-rays resulting in arresting 63.1% of cells in this phase. Similar findings were obtained after a 24-h treatment with 100 ?g/ml bleomycin. 54.4 % of cells were arrested in (G2 + M)-phase by the chemical treatment alone, while the combined treatment, bleomycin and radiation, yielded an accumulation of 66.3% of cells in G2 + M. A 24-h exposure to 0.2 ?g/ml cytosine arabinoside (Ara-C) produced a reversible block of 72.8% of cells in S phase compared to 27.4% in the control cultures. This S block was less pronounced after the combined treatment (51.1%). Some implications of the results for combined therapy are discussed. (orig.)[de] Die Wirkung von Acronycin, Bleomycin und Cytosinarabinosid auf den Zellzyklus / Impulszytophotometrische Bestimmung zellkinetischer Effekte und ihrer Beeinflussung durch Bestrahlung. Es wurde der Einfluss der drei Chemotherapeutika Acronycin, Bleomycin und Cytosinarabinosid allein und in der Kombination mit ionisierenden Strahlen auf die Progression von L-Zellen durch den Zellzyklus und auf die Zellviabilitaet untersucht. Der Anteil der Zellen in der G1-, S- und (G2 + M)-Phase wurde impulszytophotometrisch in Abhaengigkeit von der Einwirkungsdauer bestimmt. Nach 24 h Behandlung mit 10 ?g/ml Acronycin wurden 46,4% der Zellen in der (G2 + M)-Phase des Zellzyklus akkumuliert (Kontrollwert 12,1%). Dieser G2-Block wurde durch eine Bestrahlung mit 150 rd 200 kV Roentgenstrahlen statistisch signifikant verstaerkt. Die Kombinationsbehandlung fuehrte zu einer Blockade von 63,1% der Zellen in der (G2 + M)-Phase. Aehnliche Befunde wurden nach Behandlung mit 100 ?g/ml Bleomycin erhoben. Eine Behandlung mit Bleomycin allein fuehrte zu einer Arretierung von 54,4 % der Zellen in der (G2 + M)-Phase, waehrend der Anteil (G2 + M)-Zellen nach der kombinierten Behandlung 66,3% betrug. Cytosinarabinosid in einer Konzentration Von 0,2 ?g/ml bewirkte eine reversible Ansammlung von 72,8% der Zellen in der S-Phase verglichen mit einem S-Anteil der Kontrollen von 27,4%. Diese Ansammlung von Zellen in der S-Phase war nach der kombinierten Behandlung weniger ausgepraegt (51,1%). Die Bedeutung der Ergebnisse fuer eine zellzyklusspezifische Therapie wird diskutiert. (orig.)

1978-01-01

211

Comparing the Effect of Physical Modalities on Permeabilisation of Cells to Bleomycin in Balb/C Mice  

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Full Text Available Background: Some physical factors may facilitate the entry of chemotherapeutic drugs to the cells. In this study, permeability level of tumor cells of murine breast adenocarcinoma to Bleomycin was compared with 5 minutes ultrasonic exposure vs. magnetic field of 3.5 Tesla in Balb/c mice.Materials and Methods: In this experimental-applied study, 80 five-week female Balb/c mice were purchased from Pasteur Institute of Tehran. After 10 days, skin tumors of mice were induced through Homograft, and they were randomly classified after tumor reached a treatable size. In ultrasound combination group, intratumoral injection of bleomycin was performed on anesthetized mice and three minutes later, the mice, which were placed in the sonication chamber, were put in a water tank in the exposure position, and the tumor was exposed to ultrasound for 5 minutes. In the magnetic field group, mice were placed in a handmade chamber after intratumoral injection of bleomycin. Three minutes after injection of bleomycin, eight pulses of 3.5 Tesla magnetic fields with 1Hz frequency were applied to each one of the tumors.Results: It yield that, eight 3.5 Tesla pulses of magnetic field, was slightly more effective than 5 min ultrasonic irradiation in cells permeability to bleomycin, but these two physical factors had no statistically significant difference.Conclusion: Tests showed that these two physical factors have similar effects and use of each depends on the position of the patient and the medical center's facilities.

Bahram Yousefian; S. Mohammad Firoozabadi; Manijheh Mokhtari-Dizaji

2012-01-01

212

Photochemical Internalization of Bleomycin Before External-Beam Radiotherapy Improves Locoregional Control in a Human Sarcoma Model  

International Nuclear Information System (INIS)

Purpose: The aim of this study was to explore the tumor growth response of the combination photochemical internalization and external-beam radiotherapy. Photochemical internalization is a technology to improve the utilization of therapeutic macromolecules in cancer therapy by photochemical release of endocytosed macromolecules into the cytosol. Methods and Materials: A human sarcoma xenograft TAX-1 was inoculated subcutaneously into nude mice. The photosensitizer AlPcS2a and bleomycin were intraperitoneally administrated 48 h and 30 min, respectively, before diode laser light exposure at 670 nm (20 J/cm2). Thirty minutes or 7 days after photochemical treatment, the animals were subjected to 4 Gy of ionizing radiation. Results: Using photochemical internalization of bleomycin as an adjunct to ionizing radiation increased the time to progression for the tumors from 17 to 33 days as compared with that observed with photodynamic therapy combined with ionizing radiation as well as for radiochemotherapy with bleomycin. The side effects observed when photochemical internalization of bleomycin was given shortly before ionizing radiation were eliminated by separating the treatment modalities in time. Conclusion: Photochemical internalization of bleomycin combined with ionizing radiation increased the time to progression and showed minimal toxicity and may therefore reduce the total radiation dose necessary to obtain local tumor control while avoiding long-term sequelae from radiotherapy.

2009-11-01

213

A cell-free system for studying a priming factor involved in repair of bleomycin-damaged DNA.  

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Full Text Available A simple cell-free system for studying a priming factor involved in the repair of bleomycin-damaged DNA was established. The template-primer used for the repair DNA synthesis was prepared by treating the closed circular, superhelical form of pUC19 plasmid DNA with 2.2 microM bleomycin and 20 microM ferrous ions. Single-strand breaks were introduced into pUC19 DNA by the bleomycin treatment, and the DNA was consequently converted largely into the open circular form. A system for repair of this bleomycin-damaged DNA was constructed with a priming factor, DNA polymerase (DNA polymerase beta or Klenow fragment of DNA polymerase I), ATP, T4 DNA ligase and four deoxynucleoside triphosphates. After incubation, the conformation of the DNA was analyzed by agarose gel electrophoresis and electron microscopy. The open circular DNA was largely converted to the closed circular DNA, indicating that the single-strand breaks of DNA were repaired. When the priming factor was omitted, DNA repair did not occur. The present system seemed to be applicable to the study of priming factors involved in the repair of DNA with single-strand breaks caused not only by bleomycin but also by ionizing radiation or active oxygen.

Seki,Shuji; Arakaki,Yusei; Oda,Takuzo

1989-01-01

214

Attenuation of bleomycin induced pulmonary fibrosis in mice using the heme oxygenase inhibitor Zn-deuteroporphyrin IX-2,4-bisethylene glycol  

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Methods: Zndtp (10 µmol/kg) was administered subcutaneously twice daily to mice 1 week following the intratracheal instillation of 0.025 U bleomycin. Animals were killed 10 or 21 days after bleomycin instillation and indices of lung damage and fibrosis were evaluated.

Atzori, L; Chua, F; Dunsmore, S; Willis, D; Barbarisi, M; McAnulty, R; Laurent, G

215

Stimulation of toll-like receptor 2 with bleomycin results in cellular activation and secretion of pro-inflammatory cytokines and chemokines  

International Nuclear Information System (INIS)

The clinical use of bleomycin results in systemic and pulmonary inflammatory syndromes that are mediated by the production of cytokines and chemokines. In this study, we demonstrate that cell activation is initiated upon the recognition of bleomycin as a pathogen-associated molecular pattern by toll-like receptor (TLR) 2. The THP1 human monocytic cell line, which constitutively expresses high levels of TLR2, secretes interleukin (IL)-1?, IL-8, and tumor necrosis factor (TNF)-? during bleomycin exposure. The TLR2-dependent nature of cell activation and cytokine secretion is supported by (1) the inability of TLR2-deficient human embryonic kidney (HEK) 293 cells to exhibit nuclear factor-kappa B (NF-?B) activation and secrete IL-8 in response to bleomycin; (2) the acquired ability of HEK293 to exhibit NF-?B activation and secrete IL-8 upon experimental expression of TLR2; and (3) the inhibition of cell activation in TLR2-expressing HEK293 and THP1 by anti-TLR2 monoclonal antibody. Collectively, these observations identify TLR2 activation as a critical event that triggers NF-?B activation and secretion of cytokines and chemokines during bleomycin exposure. Our in vitro findings could serve as a molecular mechanism underlying the pro-inflammatory toxicity associated with bleomycin. Whether bleomycin engages with other cellular receptors that results in activation of alternate signaling pathways and whether the TLR2-agonist activity of bleomycin contribute to its anti-neoplastic property deserve further study.

2006-02-01

216

[Scanning with bleomycin-57Co and microspheres of albumin-99mTc in the diagnosis of pulmonary thickening (author's transl)  

UK PubMed Central (United Kingdom)

152 lung scans carried out with two indicators, bleomycin labelled with 57 Co and microspheres of albumin labelled with 99mTc have been examined. The results show a high bleomycin specificity in the diagnosis of bronchogenic tumours; the association of the two indicators seems to permit improved diagnostic selectivity.

Colombo L; Puricelli G; Spreafico GL

1978-05-01

217

The growth of hemopoietic precursor cells (CFU-C) of adriamycin-treated or whole-body-irradiated dogs with or without bleomycin in vitro  

International Nuclear Information System (INIS)

[en] The effect of the cytostatic drug bleomycin (BLM) on the growth of canine hemopoietic stem-cells in vitro was tested in order to detect a stem-cell deficiency after in vivo-treatment with adriamycin (ADM) or whole-body-irradiation. Stem-cells damaged by irradiation or cytostatics are suppressed by bleomycin-induced strand-breaks in vitro. After stem-cell recovery the increased sensitivity towards bleomycin can no longer be detected. After whole-body-irradiation and cytostatical treatment the stem-cells who remained intact have to compensate the quantitative change of the stem-cells by increased proliferation. The proliferating cells show a particular bleomycin-sensitivity. Especially after irradiation a long persistence of the bleomycin-sensitivity can be reckoned on. (orig./MG)

1984-01-01

218

Preparation of [66Ga]bleomycin complex as a possible PET radiopharmaceutical  

International Nuclear Information System (INIS)

Several radiolabeled bleomycin derivatives have been developed for imaging and/or therapy of neoplastic tissues. The most important imaging compounds contain indium-111, cobalt- 57, and rhodium-105. In our previous studies we have prepared radiolabeled bleomycin complexes such as gallium-67 as therapeutic and/or imaging agents. Our recent studies on the preparation and tumour imaging properties of [67Ga]bleomycin in normal and tumour-bearing mice showed a good tumour/blood and tumour/muscle ratio suggesting that it is an appropriate diagnostic agent. Due to the interesting properties and increasing importance of positron emission tomography, we investigated the possibility of incorporating 66Ga as a positron emitter with an antineoplastic compound, bleomycin, for use in tumour imaging. We optimized 66Ga complex formation conditions with bleomycin, to develop [66Ga]BLM. We hereby report the production of 66Ga, preparation, optimization, stability, and formulation studies of [66Ga]-bleomycin complex. Targetry: An electroplated 66Zn target on a copper backing plate was irradiated at an angle of 6 degrees toward the proton beam in order to achieve higher production yield. The target was cooled by a flow of 18 deg. C distilled water with a rate of 50 Lit/min. Chemical Separation: The irradiated target was dissolved by 10 N HCl (15 ml, H2O2 added) and the solution was passed through a cation exchange resin (Dowex 50 Wx8, H+ form) (h:10 cm, diameter:1 cm). The resulting high-purity [66Ga]GaCl3 solution was used directly in the labeling step. Labeling of bleomycin with [66Ga]GaCl3: [66Ga]GaCl3 (0.25-2.5 mCi) dissolved in acidic medium obtained above (0.5-2 ml) was transferred to a 2 ml-vial and pH was adjusted to various pHs (1-7) using 1M HCl and/or 1M NaOH. The mixture was evaporated by slight warming under a nitrogen flow. A mixture of BLM (0.25-2.5 mg) in normal saline (0.1 ml) was then added and was heated at different temperatures (25, 50, 80, and 100 deg. C) and was cooled in an ice bath, and rapidly sent for use. The active solution was checked for radiochemical purity by polymer-backed silica gel layer chromatography using a 1:1 mixture of 10% ammonium acetate and methanol as mobile phase. The final solution was then passed through a 0.22 ?m filter and pH was adjusted to 5-7 by the addition of 1 M sodium acetate buffer. Radionuclide purity: The gamma spectroscopy of the final sample was carried out by HPGe detector, and showed a radionuclidic purity higher than 99 % showing the presence of 511, 834, and 1039 keV gamma energies, all of which are resulted from 66Ga. [66Ga]BLM complex in final product: Stability studies were based on the previous studies performed for other radiolabeled bleomycins (5). A sample of [66Ga]BLM (0.5 mCi) was kept at room temperature for 5 hrs while checked by RTLC every half an hour. A micropipet sample (50 ?l) was taken from the shaking mixture and the ratio of free radiogallium to [66Ga]BLM was checked by radio thin layer chromatography (eluent: 10% NH4OAc buffer and methanol (1:1). Total labeling and formulation of [66Ga]BLM took about 60 min, with a yield of 97%. A suitable specific activity product was formed via insertion of [66Ga]gallium cation. No unlabelled and/or labeled by-products were observed upon RTLC analysis of the final preparations. The radio-labeled complex was stable in aqueous solutions for at least 24 h and no significant amount of other radioactive species were detected by HPLC 24 h after labeling. Trace amounts of [66Ga]gallium chloride (?2%) were detected by TLC. RTLC showed that radiochemical purity of the [66Ga]labeled components was higher than 98%. In contrast to other labeled bleomycins, [66Ga]bleomycin, is a PET radiotracer with a rather long half life, and the high chemical stability of this radiopharmaceutical makes it a very suitable diagnostic agent

2005-01-01

219

Bleomycin-induced DNA synthesis in a cell-free system using a permeable mouse sarcoma cell Extract.  

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Full Text Available To investigate factors involved in excision repair DNA synthesis, a soluble extract was prepared from permeable mouse sarcoma (SR-C3H/He) cells by homogenization and ultracentrifugation. DNA synthesis measured by using native calf thymus DNA as the template-primer and the extract as the polymerase source showed low activity. The DNA synthesis was enhanced more than ten-fold by the addition of an appropriate concentration of bleomycin, a radiomimetic DNA-damaging drug. Using selective inhibitors of DNA polymerases, it was shown that the DNA polymerase involved in the bleomycin-induced DNA synthesis was DNA polymerase beta. In addition to DNA polymerase beta, an exonuclease which converts bleomycin-damaged DNA into suitable template-primers for repair DNA synthesis appeared to be present in the permeable cell extract.

Seki,Shuji; Mori,Shigeru; Oda,Takuzo

1987-01-01

220

Comparison of radiotherapy alone and the combination of bleomycin and radiation in carcinoma of the lower gum  

Energy Technology Data Exchange (ETDEWEB)

A clinical study comparing the use of radiation to the combination of bleomycin and radiation was carried out in 61 patients with carcinoma of the lower gum. For the 28 patients treated by radiation, the dose was 30-74 Gy, and, for the 33 treated by combination therapy, the dose of bleomycin was 45-120 mg and that of radiation was 20-52 Gy. The 5-year survival rate of the radiation-alone group was 0/12 (0%), and that of patients undergoing surgery after radiation was 7/16 (44%), whereas that of the combined bleomycin and radiation alone was 7/15 (47%) and that of surgery after combined treatment was 14/18 (78%).

Masaki, Norie; Nishiyama, Kinji; Ikeda, Hiroshi; Shigematsu, Yasushi; Fuchihata, Hajime; Tanaka, Yoshihiro

1984-08-01

 
 
 
 
221

Vanillin as a modulator agent in SMART test: inhibition in the steps that precede N-methyl-N-nitrosourea-, N-ethyl-N-nitrosourea-, ethylmethanesulphonate- and bleomycin-genotoxicity.  

UK PubMed Central (United Kingdom)

Vanillin (VA), the world's major flavoring compound used in food industry and confectionery products - that has antimutagenic and anticarcinogenic activity against a variety of mutagenic/carcinogenic agents - was tested for the interval between the formation of premutational lesion and it is finalization as a DNA lesion. The overall findings using co-treatment protocols in SMART test suggest that VA can lead to a significant protection against the general genotoxicity of ethylmethanesulphonate (EMS), N-ethyl-N-nitrosourea (ENU), N-methyl-N-nitrosourea (MNU) and bleomycin sulphate (BLEO). Considering MNU, ENU and EMS the desmutagenic activity observed could result from VA-stimulation of detoxification, via induction of glutathione S-transferase. However, the protector effect related to BLEO could be attributed to its powerful scavenger ability, which has the potential to prevent oxidative damage induced by BLEO.

Sinigaglia M; Lehmann M; Baumgardt P; do Amaral VS; Dihl RR; Reguly ML; de Andrade HH

2006-09-01

222

The effect of AT1 receptor blockade on bax and bcl-2 expression in bleomycin-induced pulmonary fibrosis  

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Full Text Available ABSTRACT Background and the purpose of the study: Recent studies have indicated the role of apoptosis and angiotensin in the pathogenesis of bleomycin induced-pulmonary fibrosis. Losartan, an angiotensin type 1 receptor (AT1R) antagonist, has ameliorated apoptosis and fibrosis from bleomycin. In this study, alterations in the expression of apoptosis-regulatory genes (bcl-2 and bax) were investigated in different cells of lung tissue of mice treated with bleomycin in the presence of losartan. Methods: Losartan (10 mg/kg, i.p.) was given to mice two days before administration of bleomycin (3 U/kg) and throughout the test period. After two weeks, lung tissues of mice were evaluated for fibrosis by biochemical measurement of collagen deposition and semiquantitative analysis of pathological changes of the lung. The expression of bcl-2 and bax was assessed by immunohistochemical assay using biotin-streptavidin staining method on paraffin-embedded lung tissues. Results and major conclusion: Pre-treatment with losartan significantly (P < 0.05) reduced the increase in lung collagen content and also inhibited the histological changes induced by bleomycin. Immunohistochemical studies showed that losartan significantly (P < 0.05) reduced the bax/bcl-2 expression ratio in the alveolar epithelial cells, lymphocytes, macrophages and interstitial myofibroblasts. Losartan also inhibited the bcl-2 upregulation which was educed by bleomycin in neutrophils. By reduction of bax/bcl-2 ratio as a determinant of susceptibility of a cell to apoptosis, losartan exerted protective effects on the alveolar epithelial cells that may be important in the amelioration of pulmonary fibrosis. These results may help to better understanding of the role of angiotensin II and apoptosis in pulmonary fibrosis.

L Safaeian; A Jafarian; M Rabbani; H Mirmohammad Sadeghi; N Torabinia; SA Alavi

2009-01-01

223

Diagnostic value of thermography and sup(99m)Tc bleomycin scintigraphy for nodules of the thyroid  

International Nuclear Information System (INIS)

[en] The combined interest of thermography and sup(99m)Tc bleomycin scintigraphy in the differential diagnosis of a cold thyroid nodule was evaluated in 86 patients. In all cases a histological examination was performed. Of the 30 malignant nodules (clinically suspect and solitary nodules) 21 (70%) showed concentrations of sup(99m)Tc bleomycin while only 7 of the 12 solitary malignant nodules did so. Among the 54 benign nodules the false positive rate was 54%. Thermography was positive in 26 (87%) of the 30 malignant nodules and in only 8 (67%) of the 12 solitary malignant nodules. For the 54 benign nodules the false positive rate was 72%. The combined results of the study do not provide any improvement in diagnostic accuracy. Thus it can be said that applications of sup(99m)Tc bleomycin and thermography in the diagnosis of solitary hypofixiant nodules are of limited value[fr] L'interet combine de la thermographie et de la bleomycine sup(99m)Tc dans le diagnostic differentiel d'un nodule froid de la thyroide a ete etudie chez 86 malades. Dans tous les cas le diagnostic a ete etabli par l'examen anatomo-pathologique. Sur les 30 nodules neoplasiques (nodules solitaires et cliniquement suspects) 21 (70%) fixent la bleomycine sup(99m)Tc et seulement 7 sur les 12 nodules solitaires. Pour les 54 nodules benins le taux de faux positifs est de 54%. La thermographie est positive 26 fois (87%) pour les 30 nodules malins et seulement 8 fois (67%) pour les 12 nodules solitaires. En ce qui concerne les 54 nodules benins le taux de faux positifs est de 72%. Les resultats conjugues des deux examens n'ameliorent pas la fiabilite diagnostique. On peut donc en conclure que l'utilisation de la scintigraphie a la bleomycine sup(99m)Tc et de la thermographie dans le diagnostic des nodules thyroidiens solitaires presente un interet limite

1977-01-01

224

Tissue uptakes of 67 Ga-bleomycin and carrier free 67 Ga in fibrosarcoma-bearing mic  

International Nuclear Information System (INIS)

[en] 67Gallium-bleomycin complex was prepared using Thakour method. Radio-thin-layer-chromatography of prepared complex showed A2 and B2 radio peaks with Rf at 0.7 and 0.4 respectively with a purity of above % 95. Tissue uptake of 67 Gallium-bleomycin complex and 67GaCl3 in twelve tissues including tumor, blood, liver, lung, spleen, muscle, skin, heart, kidney, colon, colon content, bladder and the total body were counted by well counter at 1,2,4,24 and 48 hours post injection of radiopharmaceuticals. Uptakes of tissues are expressed as percent injected dose per gram of tissue. The clearance rate of 67 Gallium-bleomycin complex was 1.75 - 1.95 times faster than 67GaCl3 at all time intervals. Bladder uptakes of 67 Gallium-bleomycin complex were highest among twelve tissues at 1,2 and 4 hours after injection, then falling rapidly after 24 and 48 hours. Blood uptake of 67 Gallium-bleomycin complex was lower than 67GaCl3 in all time intervals. Colon content uptake of 67 Gallium-bleomycin complex was highest among twelve tissues at 2 and 4 hours post injection. Tumor to tissue activity ratios were also calculated, showing an increase of tumor to blood and muscle ratios. Tumor to blood ratio increased from 0.3 at 1 hour to 5.3 at 48 hours. Activity ratios of muscle increased from 0.5 at 1 hour to 5.5 at 48 hours. Whole body counting of animals showed that effective half lives of 67 Gallium-bleomycin complex and 67GaCl3 were about 1 and 15 hours respectively, which renders faster excretion of 67 Gallium-bleomycin complex. Biodistribution data clearly indicates that prepared complex in comparison with carrier free 67Ga (67GaCl3) has two main advantages: 1) high tumor to soft tissue uptake ratio that make it suitable for tumor imaging. 2) faster excretion specially at first three hours post injection.In addition complex is stable in vitro and in vivo

2004-01-01

225

Imbalance of receptor-regulated and inhibitory Smads in lung fibroblasts from bleomycin-exposed rats.  

UK PubMed Central (United Kingdom)

Transforming growth factor (TGF)-beta plays a central role in lung fibrosis, stimulating extracellular matrix deposition. Intracellular signaling of TGF-beta is mediated by Smad proteins. We questioned whether the expression and activation of Smads would be altered in lung fibroblasts from rats exposed to bleomycin, an agent used to provoke an experimental model of lung fibrosis. Fibroblasts were isolated from rat lungs 14 d after intratracheal instillation of bleomycin (BLF) or saline (NLF), and cell cultures established. Whole cell lysates were obtained at baseline, and after stimulation with TGF-beta1 (10 ng/ml). Western blot analysis was performed to measure levels of phosphorylated Smad3 (p-Smad3) and Smad7. Real-time PCR was used to determine changes in Smad7 mRNA after TGF-beta stimulation. We found increased baseline levels of p-Smad3 in BLF versus NLF (P < 0.05). In contrast, baseline levels of Smad7 were comparable. The ratio of stimulatory to inhibitory Smads was increased in BLF compared with NLF (P < 0.05). After stimulation with TGF-beta, levels of p-Smad3 were increased in both groups, with maximal responses at 30 min (P < 0.01). While Smad7 mRNA levels were significantly upregulated (at 1 h) after TGF-beta in both groups, the increase in Smad7 protein was significant in NLF only. We conclude there is sustained activation of Smad signaling in lung fibroblasts isolated from bleomycin-exposed rats, with an imbalance between the levels of p-Smad3 and Smad7. Insufficient levels of the inhibitory Smad7 at baseline, and inadequate response to TGF-beta, may contribute to the fibrotic phenotype characteristic of BLF.

Gonzalez AV; Le Bellego F; Ludwig MS

2007-02-01

226

Imbalance of receptor-regulated and inhibitory Smads in lung fibroblasts from bleomycin-exposed rats.  

Science.gov (United States)

Transforming growth factor (TGF)-beta plays a central role in lung fibrosis, stimulating extracellular matrix deposition. Intracellular signaling of TGF-beta is mediated by Smad proteins. We questioned whether the expression and activation of Smads would be altered in lung fibroblasts from rats exposed to bleomycin, an agent used to provoke an experimental model of lung fibrosis. Fibroblasts were isolated from rat lungs 14 d after intratracheal instillation of bleomycin (BLF) or saline (NLF), and cell cultures established. Whole cell lysates were obtained at baseline, and after stimulation with TGF-beta1 (10 ng/ml). Western blot analysis was performed to measure levels of phosphorylated Smad3 (p-Smad3) and Smad7. Real-time PCR was used to determine changes in Smad7 mRNA after TGF-beta stimulation. We found increased baseline levels of p-Smad3 in BLF versus NLF (P < 0.05). In contrast, baseline levels of Smad7 were comparable. The ratio of stimulatory to inhibitory Smads was increased in BLF compared with NLF (P < 0.05). After stimulation with TGF-beta, levels of p-Smad3 were increased in both groups, with maximal responses at 30 min (P < 0.01). While Smad7 mRNA levels were significantly upregulated (at 1 h) after TGF-beta in both groups, the increase in Smad7 protein was significant in NLF only. We conclude there is sustained activation of Smad signaling in lung fibroblasts isolated from bleomycin-exposed rats, with an imbalance between the levels of p-Smad3 and Smad7. Insufficient levels of the inhibitory Smad7 at baseline, and inadequate response to TGF-beta, may contribute to the fibrotic phenotype characteristic of BLF. PMID:16931807

Gonzalez, Anne V; Le Bellego, Frédérique; Ludwig, Mara S

2006-08-24

227

Bleomycin, vincristine, mitomycin-C, and cisplatin in the management of gynecological squamous cell carcinomas.  

UK PubMed Central (United Kingdom)

Twenty-one patients with squamous carcinoma of the genital tract were treated with bleomycin, Oncovin, mitomycin-C, and cisplatin (BOMP). Six patients received BOMP as primary therapy. Five of six responded with one patient having an autopsy-proven complete response after treatment for a disseminated adenosquamous carcinoma. Eight patients were treated for early recurrence, none responded. Seven patients were treated for late recurrences and one responded. We believe that BOMP has significant potential for primary treatment, but not for early or late recurrent disease.

Belinson JL; Stewart JA; Richards AL; McClure M

1985-03-01

228

Impedimetric detection of in situ interaction between anti-cancer drug bleomycin and DNA.  

UK PubMed Central (United Kingdom)

Surface confined interaction of anti-cancer drug bleomycin (BLM) with nucleic acids: single stranded and double stranded DNA was investigated herein by using electrochemical impedance spectroscopy (EIS) technique in combination with a graphite sensor technology. The experimental conditions were optimized: such as, dsDNA concentration, BLM concentration and interaction time. The main features of impedimetric DNA biosensor, such as its detection limit and the repeatability, were also discussed. The in situ interaction of BLM with dsDNA was also tested impedimetrically in the absence or presence of other chemotherapeutic agents, such as mitomycin C (MC) and cis-platin (cis-DDP) for testing the selectivity.

Erdem A; Congur G

2013-10-01

229

Modulation of the clastogenic activity of ionizing radiation and bleomycin by the aminothiol WR-1065  

International Nuclear Information System (INIS)

WR-1065 (2-[(aminopropyl)amino]ethanethiol) reduces the induction by ionizing radiation of genetic damage, including DNA single- and double-strand breaks, chromosomal aberrations, micronuclei, and hprt mutations in mammalian cells. The effectiveness of WR-1065 as a radioprotector is apparently enhanced by its tendency, a a cationic thiol, to concentrate near DNA. The authors have studied the modulation by WR-1065 of the induction of chromosome aberrations and micronuclei in G0 human lymphocytes by ionizing radiation and by the radiomimetic chemical bleomycin

1993-01-01

230

Modulation of the clastogenic activity of ionizing radiation and bleomycin by the aminothiol WR-1065  

Energy Technology Data Exchange (ETDEWEB)

WR-1065 (2-[(aminopropyl)amino]ethanethiol) reduces the induction by ionizing radiation of genetic damage, including DNA single- and double-strand breaks, chromosomal aberrations, micronuclei, and hprt mutations in mammalian cells. The effectiveness of WR-1065 as a radioprotector is apparently enhanced by its tendency, a a cationic thiol, to concentrate near DNA. The authors have studied the modulation by WR-1065 of the induction of chromosome aberrations and micronuclei in G[sub 0] human lymphocytes by ionizing radiation and by the radiomimetic chemical bleomycin.

Littlefield, L.G. (Oak Ridge Institute for Science and Education, TN (United States)); Hoffmann, G.R. (College of the Holy Cross, Worcester, MA (United States))

1993-01-01

231

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients  

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Full Text Available Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS) exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2, when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS showed free trisomy 21 (47,XX + 21 or 47,XY + 21). Individuals that showed an average number of chromatid breaks per cell higher than 0.8 were considered sensitive to the drug. No control child showed susceptibility to bleomycin, and among the 24 patients with DS, only one was sensitive to the drug. No significant difference was observed between the two groups, regarding chromatid break frequencies in treated G2 lymphocytes. The distribution of bleomycin-induced breaks in each group of chromosomes was similar for DS and controls. No significant difference was found in the response to bleomycin between male and female subjects. Probably, the main factor involved in chromosome sensitivity of lymphocytes from patients with DS is the phase of the cell cycle in which the cell is treated.Inúmeros trabalhos têm demonstrado que linfócitos de pacientes com síndrome de Down apresentam uma maior freqüência de aberrações cromossômicas quando expostos a radiação ionizante ou agentes químicos nas fases G0 ou G1 do ciclo celular, mas não em G2, quando comparados com controles normais. Para determinar a sensibilidade de linfócitos de pacientes com síndrome de Down, na fase G2, usou-se o radiomimético bleomicina em culturas de linfócitos de 24 pacientes. Todos os pacientes mostraram trissomia livre do cromossomo 21 (47,XX + 21 ou 47,XY + 21). Indivíduos que apresentaram freqüência média de quebras cromatídicas por célula superior a 0,8 foram considerados sensíveis à droga. Nenhum controle apresentou suscetibilidade à bleomicina e entre os 24 pacientes com síndrome de Down somente um foi sensível à droga. Não se observou qualquer diferença significativa entre os dois grupos em relação às freqüências de quebras cromatídicas em linfócitos em G2, o que está de acordo com outros trabalhos. A distribuição das quebras induzidas pela bleomicina, em cada grupo cromossômico, foi igual para pacientes e controles. Nenhuma diferença significativa foi observada na resposta à bleomicina entre homens e mulheres, nos dois grupos. Provavelmente, o principal fator envolvido na sensibilidade cromossômica de linfócitos de pacientes com síndrome de Down seja a fase do ciclo celular na qual a célula é tratada.

Marlise Ladvocat Bartholomei-Santos; Edmundo José de Lucca

1997-01-01

232

Tumor localization with gallium, radiolabeled bleomycin, thallium, selenium, carbon and nitrogen radionuclides. Oncology overview  

International Nuclear Information System (INIS)

[en] Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Gallium scans; Radiolabeled bleomycin scans; Thallium scans; Selenium scans; Carbon radionuclide scans; Nitrogen radionuclide scans; Multiagent studies

1981-01-01

233

SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice  

Directory of Open Access Journals (Sweden)

Full Text Available Diagnosis and management of interstitial lung diseases (ILDs), caused by lung epithelial injury followed by apoptosis, are often challenging. It has been controversial whether the SIRT1 protein, a principal modulator of longevity due to caloric restriction, ameliorates or aggravates ILD in animal models. Here we examined the effect of SRT1720, a syn- thetic activator of SIRT1, on bleomycin-induced lung injury in a mouse model and apoptosis in cultured epithelial cells. Oral intubation of SRT1720 over a period of 15 days caused body weight loss and a high mortality rate among bleomy- cin-treated mice. Histological examinations showed that the SRT1720 load increased fibrosis in the bleomycin-treated lung. An analysis of bronchoalveolar lavage fluid revealed remarkably increased numbers of inflammatory cells in the SRT1720-treated group. Moreover, the apoptosis of A549 lung cancer cells, caused by X-ray irradiation and an anti-Fas activating antibody, was promoted by SRT1720. These results indicate that SRT1720 not only aggravates bleomy- cin-induced ILD, but stimulates the apoptosis of physically and biologically stimulated A549 cells. While SIRT1 acti- vators are considered promising for the treatment of conditions such as diabetes mellitus, fatty liver, and chronic ob- structive pulmonary diseases, an excess of food containing SIRT1 activators may be harmful depending on the disease state, especially in the case of acute inflammation.

Shingo Imanishi; Ryuji Hayashi; Tomomi Ichikawa; Kensuke Suzuki; Masakiyo Sasahara; Takashi Kondo; Hirofumi Ogawa; Kazuyuki Tobe

2012-01-01

234

Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma  

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Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor) is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT), treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy). Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 ?s each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

Spugnini Enrico P; Dotsinsky Ivan; Mudrov Nikolay; Citro Gennaro; D'Avino Alfredo; Baldi Alfonso

2008-01-01

235

Antifibrotic effects of CXCR4 antagonist in bleomycin-induced pulmonary fibrosis in mice.  

UK PubMed Central (United Kingdom)

Circulating fibrocytes had been reported to migrate into the injured lungs, and contribute to fibrogenesis via chemokine-chemokine receptor systems including CXCL12-CXCR4 axis. Here we hypothesized that blockade of CXCR4 might inhibit the migration of fibrocytes to the injured lungs and the subsequent pulmonary fibrosis. To explore the antifibrotic effects of blockade of CXCR4, we used a specific antagonist for CXCR4, AMD3100, in bleomycin-induced pulmonary fibrosis model in mice. Administration of AMD3100 significantly improved the loss of body weight of mice treated with bleomycin, and inhibited the fibrotic lesion in subpleural areas of the lungs. The quantitative analysis demonstrated that treatment with AMD3100 reduced the collagen content and fibrotic score (Aschcroft score) in the lungs. Although AMD3100 did not affect cell classification in bronchoalveolar lavage fluid on day 7, the percentage of lymphocytes was reduced by AMD3100 on day 14. AMD3100 directly inhibited the migration of human fibrocytes in response to CXCL12 in vitro, and reduced the trafficking of fibrocytes into the lungs treated with bleocmycin in vivo. These results suggest that the blockade of CXCR4 might be useful strategy for therapy of patients with pulmonary fibrosis via inhibiting the migration of circulating fibrocytes.

Makino H; Aono Y; Azuma M; Kishi M; Yokota Y; Kinoshita K; Takezaki A; Kishi J; Kawano H; Ogawa H; Uehara H; Izumi K; Sone S; Nishioka Y

2013-01-01

236

Host predisposition by endogenous Transforming Growth Factor-?1 overexpression promotes pulmonary fibrosis following bleomycin injury  

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Full Text Available Abstract Background Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGF?1 as a key effector cytokine in the development of lung fibrosis. Methods In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18) of transgenic mice (Tr+) that overexpressed active TGF?1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically. Results The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGF?1 associated pulmonary fibrosis. Conclusion This data emphasises the importance of a host predisposition in the form of endogenous TGF?1, in the development of pulmonary fibrosis in response to an exogenous injury.

Haider Yussef; Malizia Andrea P; Keating Dominic T; Birch Mary; Tomlinson Annette; Martin Gail; Ferguson Mark WJ; Doran Peter P; Egan Jim J

2007-01-01

237

Serum bleomycin-detectable iron in patients with thalassemia major with normal range of serum iron.  

Directory of Open Access Journals (Sweden)

Full Text Available "Free" iron, a potentially radical-generating low mass iron, and not found in normal human blood, was increased in the serum of blood-transfused thalassemia major patients seen in the Yangon General Hospital, Yangon, Myanmar (Burma). The low mass iron was detected by the bleomycin assay. Fifty-one blood samples were analyzed (from 28 males and 23 females). High "free" iron was detected in 47 sera samples from thalassemia patients. Serum ferritin, which reflects the body store iron, was higher than the normal range (10-200 ng/ml) in 49 patients. On the other hand, serum iron of 39 sera samples fell within the normal range (50-150 micrograms/dl). Four were less than 50 micrograms/dl and eight were more than 150 micrograms/dl. Almost all the patients' sera of normal or higher serum iron level contained "free" iron. Thus, almost all the sera from thalassemic patients from Myanmar contain bleomycin-detectable iron, even when serum iron is within the normal range. In developing countries where undernutrition is prevalent (serum albumin in these patients was 3.6 +/- 0.4 g/dl, P < 0.0001 vs. control value of 4.0 - 4.8 g/dl), normal serum iron does not preclude the presence of free iron in the serum.

Han,Khin Ei; Okada,Shigeru

1995-01-01

238

Administered dose and tumor dose of bleomycin labeled with cobalt-57 in mice and men  

International Nuclear Information System (INIS)

Tumor concentrations of the chemotherapeutic drug, bleomycin, labeled with cobalt-57 (Co-bleo) were compared in mouse tumor models and in human lung tumors using quantitative single-photon emission computed tomography. Drug concentrations in histologically similar human tumors showed marked variability for the same injected dose (ID). Small cell carcinomas showed concentrations between 1.09 and 8.85 %ID/cc x 10(-3) while non-small cell lung tumors showed a concentration variation between 0.36 and 6.75 %ID/cc x 10(-3). In contrast to the situation in human tumors, uptake in mouse tumors showed only slight variability in animals with the same tumor model. EMT-6 tumors in mice showed at 6 hr significantly higher uptake of Co-bleo (p less than 0.001) and significantly higher tumor-to-lung ratio (p less than 0.001) when compared to murine fibrosarcomas. The EMT-6 tumors in contrast to the fibrosarcomas responded to bleomycin treatment in a dose dependent manner. The results indicate that while in mice the tumor dose closely follows the administered dose, in humans, the tumor dose and the tumor-to-lung ratio in the individual patient cannot be predicted from the administered dose

1990-01-01

239

Effect of 0.25 ppm Ozone exposure on pulmonary damage induced by bleomycin  

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Full Text Available To study the effect of ozone in a chronically damaged lung, we used a bleomycin (BLM) induced pulmonary fibrosis model. Both endotracheal instillation of BLM and O3 exposure both produce lung inflammation and fibrosis. Oxidative stress would be a common mechanism of damage for both BLM and O3. Our aim was to assess lung injury induced by 5 and 60 days of intermittent exposure to 0.25 ppm O3 in rats with bleomycin-induced pulmonary fibrosis. Thirty-day-old Sprague Dawley rats were endotracheally instilled with BLM (1 U/100 g body weight) and, 30 days later, exposed to 0.25 ppm O3 (0.25 ppm 4 h per day, 5 days a week). Histopatology controls were instilled with saline and breathing room air. Histopathological evaluation of lungs was done 5 and 60 days after O3 exposure. BLM-induced lung damage did not change after 60 days of intermittent O3 exposure. Five days of O3 exposure increased the mean score of BLM-induced pulmonary inflammation and fibrosis (p=0.06). Frequency of bronchopneumonia increased from 1/7 to 6/6 (p <0.001), suggesting that a short-term exposure to O3 in a previously damaged lung might be a risk factor for developing further lung injury

MANUEL OYARZÚN; NELSON DUSSAUBAT; SERGIO GONZÁLEZ

2005-01-01

240

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells  

Scientific Electronic Library Online (English)

Full Text Available Abstract in portuguese Antioxidantes de ocorrência natural têm sido exaustivamente estudados quanto a sua capacidade de proteger organimos e células contra danos oxidativos. Muitos constituintes das plantas, incluindo cúrcuma e curcumina, parecem ser potentes antimutágenos e antioxidantes. Os efeitos de cúrcuma e curcumina na freqüência de aberrações cromossômicas induzidas pelo agente radiomimético bleomicina (BLM) foram investigados em células do ovário de hamster chinês (CHO). (more) Três concentrações de cada droga, cúrcuma (100, 250 e 500 mg/ml) e curcumina (2,5, 5,0 e 10 mg/ml), foram combinadas com BLM (10 mg/ml) em células CHO tratadas durante as fases G1/S, S ou G2/S do ciclo celular. Nem cúrcuma nem curcumina evitaram o dano cromossômico induzido pela BLM em fase alguma do ciclo celular. Ao contrário, a potenciação da clastogenicidade da BLM pelo curcumina foi nitidamente observada em células tratadas durante as fases S e G2/S. A curcumina também se mostrou clastogênica na dose de 10 mg/ml nos protocolos de tratamento de 9 e 13 h. Contudo, o mecanismo exato pelo qual a curcumina produziu efeitos potenciadores e clastogênicos permanece desconhecido. Abstract in english Naturally occurring antioxidants have been extensively studied for their capacity to protect organisms and cells from oxidative damage. Many plant constituents including turmeric and curcumin appear to be potent antimutagens and antioxidants. The effects of turmeric and curcumin on chromosomal aberration frequencies induced by the radiomimetic agent bleomycin (BLM) were investigated in Chinese hamster ovary (CHO) cells. Three concentrations of each drug, turmeric (100, 25 (more) 0 and 500 mg/ml) and curcumin (2.5, 5 and 10 mg/ml), were combined with BLM (10 mg/ml) in CHO cells treated during the G1/S, S or G2/S phases of the cell cycle. Neither turmeric nor curcumin prevented BLM-induced chromosomal damage in any phases of the cell cycle. Conversely, a potentiation of the clastogenicity of BLM by curcumin was clearly observed in cells treated during the S and G2/S phases. Curcumin was also clastogenic by itself at 10 µg/ml in two protocols used. However, the exact mechanism by which curcumin produced clastogenic and potentiating effects remains unknown.

Araújo, Maria Cristina P.; Dias, Francisca da Luz; Kronka, Sergio N.; Takahashi, Catarina S.

1999-09-01

 
 
 
 
241

Essential Roles for Angiotensin Receptor AT1a in Bleomycin-Induced Apoptosis and Lung Fibrosis in Mice  

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Apoptosis of alveolar epithelial cells (AECs) has been implicated as a key event in the pathogenesis of lung fibrosis. Recent studies demonstrated a role for the synthesis and binding of angiotensin II to receptor AT1 in the induction of AEC apoptosis by bleomycin (BLEO) and other proapoptotic stimu...

Li, Xiaopeng; Rayford, Heather; Uhal, Bruce D.

242

Bleomycin-resistance gene derived from the transposon Tn5 confers selective advantage to Escherichia coli K-12.  

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The plasmid pRAB2 contains a silent operon derived from the transposon Tn5 and carrying the gene neo for neomycin-kanamycin resistance and a truncated ble gene (ble333) for bleomycin resistance. Spontaneous mutants that express the two resistances provide Escherichia coli cells an improved fitness d...

Blot, M; Meyer, J; Arber, W

243

The Role of Strain Variation in BAX and BCL-2 Expression in Murine Bleomycin-Induced Pulmonary Fibrosis  

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Full Text Available This study hypothesized that the expression of apoptosis-regulatory genes, such as BCL-2 and BAX may be affected by genetic variation in bleomycin-induced pulmonary fibrosis in C57BL/6 and NMRI mice. Pulmonary fibrosis induced by single intratracheal dose of bleomycin (3 U kg-1). After 2 weeks, lung samples were analyzed for collagen deposition, pathological changes and expression of BCL-2 and BAX. The fibrotic lung changes were similar in both strains. The immunohistochemical assay using a biotin-streptavidin technique showed no significant difference in immunoreactivity for BCL-2 protein between the controls and bleomycin-treated C57BL/6 mice. However, in NMRI mice, the expression of BCL-2 was significantly (p<0.05) upregulated in myofibroblasts and neutrophils. The expression of BAX protein was significantly (p<0.05) upregulated in alveolar epithelial cells of both strains and downregulated in myofibroblasts and lymphocytes of the lung tissues of C57BL/6 mice and also in lymphocytes of NMRI mice at 2 weeks after bleomycin instillation. These results confirm the role of BCL-2 and BAX proteins in the pathogenesis of pulmonary fibrosis and suggest that the expression of apoptotic regulatory genes may be specific in different cell types in various strains.

L. Safaeian; A. Jafarian; M. Rabbani; H.M. Sadeghi; N. Torabinia; S.A. Alavi

2008-01-01

244

Gene expression profiling of human dermal fibroblasts exposed to bleomycin sulphate does not differentiate between radiation sensitive and control patients  

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Full Text Available Abstract Background Gene expression profiling of the transcriptional response of human dermal fibroblasts to in vitro radiation has shown promise as a predictive test of radiosensitivity. This study tested if treatment with the radiomimetic drug bleomycin sulphate could be used to differentiate radiation sensitive patients and controls in patients who had previously received radiotherapy for early breast cancer. Findings Eight patients who developed marked late radiation change assessed by photographic breast appearance and 8 matched patients without any change were selected from women entered in a prospective randomised trial of breast radiotherapy fractionation. Gene expression profiling of primary skin fibroblasts exposed in vitro to bleomycin sulphate and mock treated fibroblast controls was performed. 973 genes were up-regulated and 923 down-reguated in bleomycin sulphate treated compared to mock treated control fibroblasts. Gene ontology analysis revealed enriched groups were cellular localisation, apoptosis, cell cycle and DNA damage response for the deregulated genes. No transcriptional differences were identified between fibroblasts from radiation sensitive cases and control patients; subgroup analysis using cases exhibiting severe radiation sensitivity or with high risk alleles present in TGF ?1 also showed no difference. Conclusions The transcriptional response of human dermal fibroblasts to bleomycin sulphate has been characterised. No differences between clinically radiation sensitive and control patients were detected using this approach.

Westbury Charlotte B; Sahlberg Kristine; Borresen-Dale Anne-Lise; Isacke Clare M; Yarnold John R

2011-01-01

245

Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars.  

UK PubMed Central (United Kingdom)

While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per cm2 (BTA). In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29%) softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids). The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..

Camacho-Martínez FM; Rey ER; Serrano FC; Wagner A

2013-05-01

246

Amniotic Fluid Stem Cells Inhibit the Progression of Bleomycin-Induced Pulmonary Fibrosis via CCL2 Modulation in Bronchoalveolar Lavage  

Science.gov (United States)

The potential for amniotic fluid stem cell (AFSC) treatment to inhibit the progression of fibrotic lung injury has not been described. We have previously demonstrated that AFSC can attenuate both acute and chronic-fibrotic kidney injury through modification of the cytokine environment. Fibrotic lung injury, such as in Idiopathic Pulmonary Fibrosis (IPF), is mediated through pro-fibrotic and pro-inflammatory cytokine activity. Thus, we hypothesized that AFSC treatment might inhibit the progression of bleomycin-induced pulmonary fibrosis through cytokine modulation. In particular, we aimed to investigate the effect of AFSC treatment on the modulation of the pro-fibrotic cytokine CCL2, which is increased in human IPF patients and is correlated with poor prognoses, advanced disease states and worse fibrotic outcomes. The impacts of intravenous murine AFSC given at acute (day 0) or chronic (day 14) intervention time-points after bleomycin injury were analyzed at either day 3 or day 28 post-injury. Murine AFSC treatment at either day 0 or day 14 post-bleomycin injury significantly inhibited collagen deposition and preserved pulmonary function. CCL2 expression increased in bleomycin-injured bronchoalveolar lavage (BAL), but significantly decreased following AFSC treatment at either day 0 or at day 14. AFSC were observed to localize within fibrotic lesions in the lung, showing preferential targeting of AFSC to the area of fibrosis. We also observed that MMP-2 was transiently increased in BAL following AFSC treatment. Increased MMP-2 activity was further associated with cleavage of CCL2, rendering it a putative antagonist for CCL2/CCR2 signaling, which we surmise is a potential mechanism for CCL2 reduction in BAL following AFSC treatment. Based on this data, we concluded that AFSC have the potential to inhibit the development or progression of fibrosis in a bleomycin injury model during both acute and chronic remodeling events.

Garcia, Orquidea; Carraro, Gianni; Turcatel, Gianluca; Hall, Marisa; Sedrakyan, Sargis; Roche, Tyler; Buckley, Sue; Driscoll, Barbara; Perin, Laura; Warburton, David

2013-01-01

247

Secure Wireless Payment Protocol  

UK PubMed Central (United Kingdom)

With the convergence of wireless datacommunication and the Internet, more and moreInternet services are now being used in the wirelessarea. Mobile payment protocols are necessary foronline transactions. A good payment protocol shouldbalance the requirements of security and convenience.

Hong Wang; Evangelos Kranakis

248

Some transplantable substance in spent medium obtained from the plateau culture of HeLa cells affecting the sensitivity to bleomycin  

Energy Technology Data Exchange (ETDEWEB)

The cytotoxic effect of bleomycin (BLM) on HeLa cells grown at plateau phase was investigated and compared with that at exponential phase. Cells were cultured in F10 medium supplemented 10% calf serum and antibiotics before exposure to BLM. Results show that the sensitivity seen at low dose and short time exposures was extended in the spent medium. It is suggested that there is some unknown substance in the spent medium that enhances cell killing by bleomycin.

Miyamoto, T.; Terasima, T.

1986-05-01

249

The Effects of Bleomycin on the Structural Abnormalities of Chromosomes in Smokers  

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Full Text Available Bleomycin in doses 0.3, 3 and 30 ?g/ml was used with periods 6, 24 and48 hours on 5 male samples who were smokers, in in-vitro conditions andunder control so totally 3000 metaphases were evaluated.Structural chromosome aberrations were influenced by the increases indosage. While the ratio total structural aberrations to the number ofmetaphases examined was 25.2% in control groups, It was 47.3% in 0.3?g/ml group, 76% in 3 ?g/ml and rose up to 116.8% in 30 ?g/ml experimentgroup. In addition due to the increases in dosage, there was an increase instructural aberration quantities and qualities.

Diclehan Öktüren Oral; Hilmi ?si

2004-01-01

250

Effect of thiol compounds on bleomycin-induced DNA and chromosome damage in human cells.  

UK PubMed Central (United Kingdom)

Non-protein thiols are considered radioprotectors, preventing DNA damage by ionizing radiation. As bleomycin (BLM) is a radiomimetic agent it was proposed that thiols may prevent DNA damage produced by this antibiotic. However, results obtained with thiols and BLM-combined treatments in living cells are contradictory. The goal of this work was to assess the influence of five non-protein thiols of different electrical charge and chemical composition, on the DNA damage, DNA repair, chromosomal aberrations and cell killing induced by BLM. We found that, at the chromosomal level and cell killing, Glutathione, ?-Mercaptoethanol and cysteine showed a protective effect, while ditiothreitol and cysteamine increased them, whereas at the DNA level all thiols potentiated the DNA damage induced by BLM, most probably due to a reactivation of the BLM complex.

Mira A; Gimenez EM; Bolzán AD; Bianchi MS; López-Larraza DM

2013-01-01

251

Preparation of [66Ga]bleomycin complex as a possible PET radiopharmaceutical  

International Nuclear Information System (INIS)

Gallium-66 (T1/2 = 9.49 h) is an interesting radionuclide that has potential use for positron emission tomography (PET) imaging of biological processes in intermediate to slow target tissue uptake. 66Ga was produced in the NRCAM cyclotron as a result of 15 MeV proton bombardment of 66Zn with current intensity of 180 ?A (yield 11.2 mCi/?Ah). Bleomycin (BLM) was labeled with [66Ga]GaCl3 for its possible diagnostic properties. The complex formation yield was optimized for pH, time, temperature, and ligand : radioactivity ratio. Radio-TLC showed an overall radiochemical yield of >98% (radiochemical purity >98%). The stability of the complex was checked in vitro. (author)

2005-01-01

252

The counter regulatory response induced by CpG oligonucleotides prevents bleomycin induced pneumopathy  

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Full Text Available Abstract Bleomycin (BLM) induces life-threatening pneumonitis and pulmonary fibrosis in 20% of patients, limiting its use as a chemotherapeutic agent. Oligonucleotides expressing immunostimulatory CpG motifs (CpG ODN) stimulate cells that express Toll-like receptor 9 to initiate an inflammatory response. This short-lived inflammation is physiologically suppressed by a counter-regulatory process that peaks five days later. Using a murine model of BLM-induced lung injury, the effect of CpG ODN treatment on pulmonary inflammation, fibrosis and mortality was examined. Administering CpG ODN 5?days before BLM (so that the peak of the counter-regulatory process induced by CpG ODN coincided with BLM delivery) resulted in a dose-dependent reduction in pulmonary toxicity (p?

Kinjo Takeshi; Tomaru Koji; Haines Diana C; Klinman Dennis M

2012-01-01

253

Response of mouse sarcoma- 180 to bleomycin in combination with radiation and hyperthermia  

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The response of a transplantable mouse tumor, S-180, grown intradermally in inbred Balb/c mice, to bleomycin (BLM), irradiation (RT) and hyperthermia (HT) was studied by observing tumor growth changes up to 120 days after treatment. BLM, at 20 mg/kg body weight, and 10 Gy gamma radiation individually produced identical tumor cure, while hyperthermia at 42 C, 60' or 43 C, 30' resulted in a higher tumor response. Treatment with 43 C, 30' after BLM was more effective than hyperthermia after radiation in effecting tumor cure as well as in inducing regrowth delay. In the drug+HT combination the low drug dose was almost equal in effect as the higher drug dose when followed by 43 C, 30'. Combining the three modalities resulted in 100% tumor cure without any local recurrence during the observation period. The micronucleus study 24 h after treatment indicated enhanced cytogenetic damage by the combination treatments. (orig.)

Uma Devi, P. (Department of Radiobiology, Kasturba Medical Coll., Manipal (India)); Satish Rao, B.S. (Department of Radiobiology, Kasturba Medical Coll., Manipal (India))

1993-10-01

254

Irradiation, bleomycin and hyperbaric oxygen in the treatment of oral carcinoma  

Energy Technology Data Exchange (ETDEWEB)

The present report is the sixth in a series of combination therapy trials in oral carcinoma in South India conducted since 1960. In the fifth trial a combination of bleomycin (BLM) and irradiation was compared with irradiation alone. The results gained and the subsequent experience in an unselected series demonstrated in buccal mucosal squamous cell carcinomas a highly superior effect with the irradiation-BLM combination, but still revealed a failure rate of around 30 percent. The present clinical trial - irradiation + BLM was compared with irradiation + BLM + hyperbaric oxygen (HbO) and irradiation + placebo + HbO - was undertaken in an attempt to eliminate or at least reduce these failures. The results were unexpectedly disappointing in that the irradiation combined with BLM + HbO proved to be inferior to irradiation + BLM. An attempt has been made to elucidate the possible reasons for this surprising outcome.

Shanta, V.; Krishnamurthi, S.; Sharma, M. (Cancer Inst., Madras (India))

1983-01-01

255

The effect of antioxidants on bleomycin treatment in in vitro and in vivo genotoxicity assays.  

Science.gov (United States)

Antioxidants are thought to be important in protecting against damage from active oxygen species. The effects of the antioxidant nutrients vitamins C and E have been investigated after bleomycin treatment in the Salmonella typhimurium bacterial mutation assay, in the human peripheral lymphocyte chromosome aberration assay, and in the mouse micronucleus assay in peripheral blood and bone marrow cells. There were no protective effects from vitamins C and E in the bacterial mutation assay, but vitamin C and not vitamin E abolished chromosome damaging responses in human peripheral lymphocytes, and both vitamins reduced responses in micronuclei from peripheral blood cells in mice. This would suggest that in human cells in vitro and mouse cells in vivo these vitamins could have a protective role. PMID:7539522

Anderson, D; Basaran, N; Blowers, S D; Edwards, A J

1995-06-01

256

The effect of antioxidants on bleomycin treatment in in vitro and in vivo genotoxicity assays.  

UK PubMed Central (United Kingdom)

Antioxidants are thought to be important in protecting against damage from active oxygen species. The effects of the antioxidant nutrients vitamins C and E have been investigated after bleomycin treatment in the Salmonella typhimurium bacterial mutation assay, in the human peripheral lymphocyte chromosome aberration assay, and in the mouse micronucleus assay in peripheral blood and bone marrow cells. There were no protective effects from vitamins C and E in the bacterial mutation assay, but vitamin C and not vitamin E abolished chromosome damaging responses in human peripheral lymphocytes, and both vitamins reduced responses in micronuclei from peripheral blood cells in mice. This would suggest that in human cells in vitro and mouse cells in vivo these vitamins could have a protective role.

Anderson D; Basaran N; Blowers SD; Edwards AJ

1995-06-01

257

Positional cloning reveals strain-dependent expression of Trim16 to alter susceptibility to bleomycin-induced pulmonary fibrosis in mice.  

Science.gov (United States)

Pulmonary fibrosis is a disease of significant morbidity, with no effective therapeutics and an as yet incompletely defined genetic basis. The chemotherapeutic agent bleomycin induces pulmonary fibrosis in susceptible C57BL/6J mice but not in mice of the C3H/HeJ strain, and this differential strain response has been used in prior studies to map bleomycin-induced pulmonary fibrosis susceptibility loci named Blmpf1 and Blmpf2. In this study we isolated the quantitative trait gene underlying Blmpf2 initially by histologically phenotyping the bleomycin-induced lung disease of sublines of congenic mice to reduce the linkage region to 13 genes. Of these genes, Trim16 was identified to have strain-dependent expression in the lung, which we determined was due to sequence variation in the promoter. Over-expression of Trim16 by plasmid injection increased pulmonary fibrosis, and bronchoalveolar lavage levels of both interleukin 12/23-p40 and neutrophils, in bleomycin treated B6.C3H-Blmpf2 subcongenic mice compared to subcongenic mice treated with bleomycin only, which follows the C57BL/6J versus C3H/HeJ strain difference in these traits. In summary we demonstrate that genetic variation in Trim16 leads to its strain-dependent expression, which alters susceptibility to bleomycin-induced pulmonary fibrosis in mice. PMID:23341783

Stefanov, Anguel N; Fox, Jessica; Haston, Christina K

2013-01-17

258

Positional Cloning Reveals Strain-Dependent Expression of Trim16 to Alter Susceptibility to Bleomycin-Induced Pulmonary Fibrosis in Mice  

Science.gov (United States)

Pulmonary fibrosis is a disease of significant morbidity, with no effective therapeutics and an as yet incompletely defined genetic basis. The chemotherapeutic agent bleomycin induces pulmonary fibrosis in susceptible C57BL/6J mice but not in mice of the C3H/HeJ strain, and this differential strain response has been used in prior studies to map bleomycin-induced pulmonary fibrosis susceptibility loci named Blmpf1 and Blmpf2. In this study we isolated the quantitative trait gene underlying Blmpf2 initially by histologically phenotyping the bleomycin-induced lung disease of sublines of congenic mice to reduce the linkage region to 13 genes. Of these genes, Trim16 was identified to have strain-dependent expression in the lung, which we determined was due to sequence variation in the promoter. Over-expression of Trim16 by plasmid injection increased pulmonary fibrosis, and bronchoalveolar lavage levels of both interleukin 12/23-p40 and neutrophils, in bleomycin treated B6.C3H-Blmpf2 subcongenic mice compared to subcongenic mice treated with bleomycin only, which follows the C57BL/6J versus C3H/HeJ strain difference in these traits. In summary we demonstrate that genetic variation in Trim16 leads to its strain-dependent expression, which alters susceptibility to bleomycin-induced pulmonary fibrosis in mice.

Stefanov, Anguel N.; Fox, Jessica; Haston, Christina K.

2013-01-01

259

Positional cloning reveals strain-dependent expression of Trim16 to alter susceptibility to bleomycin-induced pulmonary fibrosis in mice.  

UK PubMed Central (United Kingdom)

Pulmonary fibrosis is a disease of significant morbidity, with no effective therapeutics and an as yet incompletely defined genetic basis. The chemotherapeutic agent bleomycin induces pulmonary fibrosis in susceptible C57BL/6J mice but not in mice of the C3H/HeJ strain, and this differential strain response has been used in prior studies to map bleomycin-induced pulmonary fibrosis susceptibility loci named Blmpf1 and Blmpf2. In this study we isolated the quantitative trait gene underlying Blmpf2 initially by histologically phenotyping the bleomycin-induced lung disease of sublines of congenic mice to reduce the linkage region to 13 genes. Of these genes, Trim16 was identified to have strain-dependent expression in the lung, which we determined was due to sequence variation in the promoter. Over-expression of Trim16 by plasmid injection increased pulmonary fibrosis, and bronchoalveolar lavage levels of both interleukin 12/23-p40 and neutrophils, in bleomycin treated B6.C3H-Blmpf2 subcongenic mice compared to subcongenic mice treated with bleomycin only, which follows the C57BL/6J versus C3H/HeJ strain difference in these traits. In summary we demonstrate that genetic variation in Trim16 leads to its strain-dependent expression, which alters susceptibility to bleomycin-induced pulmonary fibrosis in mice.

Stefanov AN; Fox J; Haston CK

2013-01-01

260

Regulation of myofibroblast differentiation and bleomycin-induced pulmonary fibrosis by adrenomedullin.  

Science.gov (United States)

Myofibroblast differentiation induced by transforming growth factor-? (TGF-?) is characterized by the expression of smooth muscle ?-actin (SMA) and extracellular matrix proteins. We and others have previously shown that these changes are regulated by protein kinase A (PKA). Adrenomedullin (ADM) is a vasodilator peptide that activates cAMP/PKA signaling through the calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying proteins (RAMP). In this study, we found that recombinant ADM had little effect on cAMP/PKA in quiescent human pulmonary fibroblasts, whereas it induced a profound activation of cAMP/PKA signaling in differentiated (by TGF-?) myofibroblasts. In contrast, the prostacyclin agonist iloprost was equally effective at activating PKA in both quiescent fibroblasts and differentiated myofibroblasts. TGF-? stimulated a profound expression of CRLR with a time course that mirrored the increased PKA responses to ADM. The TGF-? receptor kinase inhibitor SB431542 abolished expression of CRLR and attenuated the PKA responses of cells to ADM but not to iloprost. CRLR expression was also dramatically increased in lungs from bleomycin-treated mice. Functionally, ADM did not affect initial differentiation of quiescent fibroblasts in response to TGF-? but significantly attenuated the expression of SMA, collagen-1, and fibronectin in pre-differentiated myofibroblasts, which was accompanied by decreased contractility of myofibroblasts. Finally, sensitization of ADM signaling by transgenic overexpression of RAMP2 in myofibroblasts resulted in enhanced survival and reduced pulmonary fibrosis in the bleomycin model of the disease. In conclusion, differentiated pulmonary myofibroblasts gain responsiveness to ADM via increased CRLR expression, suggesting the possibility of using ADM for targeting pathological myofibroblasts without affecting normal fibroblasts. PMID:23585227

Kach, Jacob; Sandbo, Nathan; Sethakorn, Nan; Williams, Jesse; Reed, Eleanor B; La, Jennifer; Tian, Xinyong; Brain, Susan D; Rajendran, Kavitha; Krishnan, Ramaswamy; Sperling, Anne I; Birukov, Konstantin; Dulin, Nickolai O

2013-04-12

 
 
 
 
261

Protective effect of dexpanthenol on bleomycin-induced pulmonary fibrosis in rats.  

UK PubMed Central (United Kingdom)

Despite extensive studies, there is no effective treatment currently available other than pirfenidone for idiopathic pulmonary fibrosis. A protective effect of pantothenic acid and its derivatives on cell damage produced by oxygen radicals has been reported, but it has not been tested in bleomycin (BLM)--induced pulmonary fibrosis in rats. Therefore, we aimed to investigate the preventive effect of dexpanthenol (Dxp) on pulmonary fibrosis. Thirty-two rats were assigned to four groups as follows: (1) control group, (2) dexpanthenol (Dxp) group; 500 mg/kg Dxp continued intraperitoneally for 14 days, (3) bleomycin (BLM) group; a single intratracheal injection of BLM (2.5 mg/kg body weight in 0.25-ml phosphate buffered saline), and (4) BLM + Dxp-treated group; 500 mg/kg Dxp was administered 1 h before the intratracheal BLM injection and continued for 14 days i.p. The histopathological grades of lung inflammation and collagen deposition, tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and myeloperoxidase (MPO) were measured. BLM provoked inflammation and collagen deposition (p??0.05). We showed that Dxp significantly prevents BLM-induced lung fibrosis in rats. Further studies are required to evaluate the role of Dxp in the treatment of lung fibrosis.

Ermis H; Parlakpinar H; Gulbas G; Vardi N; Polat A; Cetin A; Kilic T; Aytemur ZA

2013-08-01

262

Association analysis reveals genetic variation altering bleomycin-induced pulmonary fibrosis in mice.  

UK PubMed Central (United Kingdom)

Pulmonary fibrosis is a disease of significant morbidity, with an incompletely defined genetic basis. Here, we combine linkage and association studies to identify genetic variations associated with pulmonary fibrosis in mice. Mice were treated with bleomycin by osmotic minipump, and pulmonary fibrosis was histologically assessed 6 weeks later. Fibrosis was mapped in C57BL6/J (fibrosis-susceptible) × A/J (fibrosis-resistant) F2 mice, and the major identified linkage intervals were evaluated in consomic mice. Genome-wide and linkage-interval genes were assessed for their association with fibrosis, using phenotypic data from 23 inbred strains and the murine single-nucleotide polymorphism map. Susceptibility to pulmonary fibrosis mapped to a locus on chromosome 17, which was verified with consomic mice, and to three additional suggestive loci that may interact with alleles on chromosome 17 to affect the trait in F2 mice. Two of the loci, including the region on chromosome 17, are homologous to previously mapped loci of human idiopathic fibrosis. Of the 23 phenotyped murine strains, four developed significant fibrosis, and the majority presented minimal disease. Genome-wide and linkage region-specific association studies revealed 11 pulmonary expressed genes (including the autophagy gene Cep55, and Masp2, which is a complement component) to contain polymorphisms significantly associated with bleomycin-induced fibrotic lung disease. In conclusion, genomic approaches were used to identify linkage intervals and specific genetic variations associated with pulmonary fibrosis in mice. The common loci and similarities in phenotype suggest these findings to be of relevance to clinical pulmonary fibrosis.

Paun A; Lemay AM; Tomko TG; Haston CK

2013-03-01

263

Regulation of myofibroblast differentiation and bleomycin-induced pulmonary fibrosis by adrenomedullin.  

UK PubMed Central (United Kingdom)

Myofibroblast differentiation induced by transforming growth factor-? (TGF-?) is characterized by the expression of smooth muscle ?-actin (SMA) and extracellular matrix proteins. We and others have previously shown that these changes are regulated by protein kinase A (PKA). Adrenomedullin (ADM) is a vasodilator peptide that activates cAMP/PKA signaling through the calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying proteins (RAMP). In this study, we found that recombinant ADM had little effect on cAMP/PKA in quiescent human pulmonary fibroblasts, whereas it induced a profound activation of cAMP/PKA signaling in differentiated (by TGF-?) myofibroblasts. In contrast, the prostacyclin agonist iloprost was equally effective at activating PKA in both quiescent fibroblasts and differentiated myofibroblasts. TGF-? stimulated a profound expression of CRLR with a time course that mirrored the increased PKA responses to ADM. The TGF-? receptor kinase inhibitor SB431542 abolished expression of CRLR and attenuated the PKA responses of cells to ADM but not to iloprost. CRLR expression was also dramatically increased in lungs from bleomycin-treated mice. Functionally, ADM did not affect initial differentiation of quiescent fibroblasts in response to TGF-? but significantly attenuated the expression of SMA, collagen-1, and fibronectin in pre-differentiated myofibroblasts, which was accompanied by decreased contractility of myofibroblasts. Finally, sensitization of ADM signaling by transgenic overexpression of RAMP2 in myofibroblasts resulted in enhanced survival and reduced pulmonary fibrosis in the bleomycin model of the disease. In conclusion, differentiated pulmonary myofibroblasts gain responsiveness to ADM via increased CRLR expression, suggesting the possibility of using ADM for targeting pathological myofibroblasts without affecting normal fibroblasts.

Kach J; Sandbo N; Sethakorn N; Williams J; Reed EB; La J; Tian X; Brain SD; Rajendran K; Krishnan R; Sperling AI; Birukov K; Dulin NO

2013-06-01

264

MicroRNA profiling implicates the insulin-like growth factor pathway in bleomycin-induced pulmonary fibrosis in mice.  

UK PubMed Central (United Kingdom)

BACKGROUND: Idiopathic pulmonary fibrosis is a disease characterized by alveolar epithelial cell injury, inflammatory cell infiltration and deposition of extracellular matrix in lung tissue. As mouse models of bleomycin-induced pulmonary fibrosis display many of the same phenotypes observed in patients with idiopathic pulmonary fibrosis, they have been used to study various aspects of the disease, including altered expression of microRNAs. RESULTS: In this work, microRNA expression profiling of the lungs from treated C57BL/6J mice, relative to that of untreated controls, was undertaken to determine which alterations in microRNAs could in part regulate the fibrosis phenotype induced by bleomycin delivered through mini-osmotic pumps. We identified 11 microRNAs, including miR-21 and miR-34a, to be significantly differentially expressed (P < 0.01) in lungs of bleomycin treated mice and confirmed these data with real time PCR measurements. In situ hybridization of both miR-21 and miR-34a indicated that they were expressed in alveolar macrophages. Using a previously reported gene expression profile, we identified 195 genes to be both predicted targets of the 11 microRNAs and of altered expression in bleomycin-induced lung disease of C57BL/6J mice. Pathway analysis with these 195 genes indicated that altered microRNA expression may be associated with hepatocyte growth factor signaling, cholecystokinin/gastrin-mediated signaling, and insulin-like growth factor (IGF-1) signaling, among others, in fibrotic lung disease. The relevance of the IGF-1 pathway in this model was then demonstrated by showing lung tissue of bleomycin treated C57BL/6J mice had increased expression of Igf1 and that increased numbers of Igf-1 positive cells, predominantly in macrophages, were detected in the lungs. CONCLUSIONS: We conclude that altered microRNA expression in macrophages is a feature which putatively influences the insulin-like growth factor signaling component of bleomycin-induced pulmonary fibrosis.

Honeyman L; Bazett M; Tomko TG; Haston CK

2013-08-01

265

EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-? signaling in lung fibroblasts  

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Full Text Available Abstract Background Fourteen-membered ring macrolides have been effective in reducing chronic airway inflammation and also preventing lung injury and fibrosis in bleomycin-challenged mice via anti-inflammatory effects. EM703 is a new derivative of erythromycin (EM) without the bactericidal effects. We investigated the anti-inflammatory and antifibrotic effects of EM703 in an experimental model of bleomycin-induced lung injury and subsequent fibrosis in mice. Methods Seven-week-old male ICR mice were used. All experiments used eight mice/group, unless otherwise noted in the figure legends. Bleomycin was administered intravenously to the mice on day 0. EM703 was orally administered daily to mice. All groups were examined for cell populations in the bronchoalveolar lavage (BAL) fluid and for induction of messenger RNA (mRNA) of Smad3 and Smad4 in the lung tissues by reverse transcriptase (RT)-polymerase chainreaction (PCR) on day 7. Fibroblastic foci were assessed histologically, and the hydroxyproline content was chemically determined in the lung tissues on day 28. We performed assay of proliferation and soluble collagen production, and examined the induction of mRNA of Smad3 and Smad4 by RT-PCR in murine lung fibroblast cell line MLg2908. We also examined Smad3, Smad4 and phosphorylated Smad2/3 (p-Smad2/3) protein assay by western blotting in MLg2908. Results Bleomycin-induced lung fibrosis, and the infiltration of macrophages and neutrophils into the airspace were inhibited by EM703. The expression of Smad3 and Smad4 mRNA was clearly attenuated by bleomycin, but was recovered by EM703. EM703 also inhibited fibroblast proliferation and the collagen production in lung fibroblasts induced by Transforming growth factor-beta (TGF-?). The expression of Smad3 and Smad4 mRNA in murine lung fibroblasts disappeared due to TGF-?, but was recovered by EM703. EM703 inhibited the expression of p-Smad2/3 and Smad4 protein in murine lung fibroblasts induced by TGF-?. Conclusion These findings suggest that EM703 improves bleomycin-induced pulmonary fibrosis in mice by actions of anti-inflammation and regulation of TGF-? signaling in lung fibroblasts.

Li Ying Ji; Azuma Arata; Usuki Jiro; Abe Shinji; Matsuda Kuniko; Sunazuka Toshiaki; Shimizu Takako; Hirata Yukiyo; Inagaki Hirofumi; Kawada Tomoyuki; Takahashi Satoru; Kudoh Shoji; Omura Satoshi

2006-01-01

266

MicroRNA profiling implicates the insulin-like growth factor pathway in bleomycin-induced pulmonary fibrosis in mice  

Science.gov (United States)

Background Idiopathic pulmonary fibrosis is a disease characterized by alveolar epithelial cell injury, inflammatory cell infiltration and deposition of extracellular matrix in lung tissue. As mouse models of bleomycin-induced pulmonary fibrosis display many of the same phenotypes observed in patients with idiopathic pulmonary fibrosis, they have been used to study various aspects of the disease, including altered expression of microRNAs. Results In this work, microRNA expression profiling of the lungs from treated C57BL/6J mice, relative to that of untreated controls, was undertaken to determine which alterations in microRNAs could in part regulate the fibrosis phenotype induced by bleomycin delivered through mini-osmotic pumps. We identified 11 microRNAs, including miR-21 and miR-34a, to be significantly differentially expressed (P < 0.01) in lungs of bleomycin treated mice and confirmed these data with real time PCR measurements. In situ hybridization of both miR-21 and miR-34a indicated that they were expressed in alveolar macrophages. Using a previously reported gene expression profile, we identified 195 genes to be both predicted targets of the 11 microRNAs and of altered expression in bleomycin-induced lung disease of C57BL/6J mice. Pathway analysis with these 195 genes indicated that altered microRNA expression may be associated with hepatocyte growth factor signaling, cholecystokinin/gastrin-mediated signaling, and insulin-like growth factor (IGF-1) signaling, among others, in fibrotic lung disease. The relevance of the IGF-1 pathway in this model was then demonstrated by showing lung tissue of bleomycin treated C57BL/6J mice had increased expression of Igf1 and that increased numbers of Igf-1 positive cells, predominantly in macrophages, were detected in the lungs. Conclusions We conclude that altered microRNA expression in macrophages is a feature which putatively influences the insulin-like growth factor signaling component of bleomycin-induced pulmonary fibrosis.

2013-01-01

267

Adaptation of TURN protocol to SIP protocol  

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Full Text Available Today, SIP is a protocol par Excellence in the field of communication over Internet. But, the fact that it belongs to the application layer constitutes a weakness vis-a-vis the NAT traversal. This weakness is due to the way in which the server replies to the requests of clients on the one hand. On the other, it is caused by the dynamic allocation of UDP ports for emission and reception of packets RTP/RTCP. The TURN Protocol may face this weakness. However, its use requires a certain number of exchanges between the clients and a TURN server before establishing the multimedia sessions and this increase the latent time. In this article, we propose to adapt TURN protocol for applications based on SIP protocol such as telephony over Internet, conference video, etc. This adaptation optimises the establishment of multimedia sessions by integrating a manager of TCP connections and multimedia flow controller into SIP Proxy server.

Mustapha Guezouri; Ahmed Blaha; Mokhtar Keche

2010-01-01

268

Adaptation of TURN protocol to SIP protocol  

CERN Document Server

Today, SIP is a protocol par Excellence in the field of communication over Internet. But, the fact that it belongs to the application layer constitutes a weakness vis-a-vis the NAT traversal. This weakness is due to the way in which the server replies to the requests of clients on the one hand. On the other, it is caused by the dynamic allocation of UDP ports for emission and reception of packets RTP/RTCP. The TURN Protocol may face this weakness. However, its use requires a certain number of exchanges between the clients and a TURN server before establishing the multimedia sessions and this increase the latent time. In this article, we propose to adapt TURN protocol for applications based on SIP protocol such as telephony over Internet, conference video, etc. This adaptation optimises the establishment of multimedia sessions by integrating a manager of TCP connections and multimedia flow controller into SIP Proxy server.

Guezouri, Mustapha; Keche, Mokhtar

2010-01-01

269

Bleomycin/cis-platin as neoadjuvant chemotherapy before radical radiotherapy in localized, inoperable carcinoma of the esophagus  

International Nuclear Information System (INIS)

[en] Survival and swallowing were studied in a randomized trial of 97 patients with inoperable, localized esophageal carcinoma. Radical radio -therapy was given to 51 patients, while 46 patients had 2 courses of bleomycin/cisplatin before radiotherapy. The survival was 29% after one year, and 6% after 3 year in the radiotherapy group. The survival in the combined treatment group was 18 and 0%, respectively; p=0.1895. The number of patients who could swallow any food increased from 6% before treatment to 38% after 3 months in the radiotherapy group, and from 0% to 23% in the combined group. No benefit was found by combining bleomycin/cisplatin with radiotherapy. (author). 16 refs.; 1 fig.; 1 tab

1992-01-01

270

Low dose irradiation, tegafur and bleomycin in oil for rectal cancer. An evaluation of the surgical materials  

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A histopathological survey of surgical materials from 143 patients with rectal carcinoma subjected to chemotherapy or to low-dose radiotherapy combined with tegafur and bleomycin in oil was carried out. The radiotherapy brought about better results than chemotherapy alone. In 4 out of the 58 patients treated with the radiochemotherapy, no cancer cells could be found. Exfoliation of cohorts of cancer cells may occur into the rectal lumina in selected cases of rectal carcinoma thus treated, resulting in cancer cell elimination. (author).

Okuyama, Shinichi; Mishina, Hitoshi; Hariu, Tsuneo; Yamamoto, Kyoji; Matsushiro, Takashi; Yamagata, Rin; Taima, Tadashi

1984-10-01

271

Direct isolation of myofibroblasts and fibroblasts from bleomycin-injured lungs reveals their functional similarities and differences  

Science.gov (United States)

Background Myofibroblasts play a crucial role in tissue repair. The functional similarities and differences between myofibroblasts and fibroblasts are not fully understood because they have not been separately isolated from a living body. The purpose of this study was to establish a method for the direct isolation of myofibroblasts and fibroblasts from injured lungs by using fluorescence-activated cell sorting and to compare their functions. Results We demonstrated that lineage-specific cell surface markers (lin), such as CD31, CD45, CD146, EpCAM (CD326), TER119, and Lyve-1 were not expressed in myofibroblasts or fibroblasts. Fibroblasts of bleomycin-injured lungs and saline-treated lungs were shown to be enriched in linneg Sca-1high, and myofibroblasts of bleomycin-injured lungs were shown to be enriched in linneg Sca-1low CD49ehigh. Results from in-vitro proliferation assays indicated in-vitro proliferation of fibroblasts but not myofibroblasts of bleomycin-injured lungs and of fibroblasts of saline-treated lungs. However, fibroblasts and myofibroblasts might have a low proliferative capacity in vivo. Analysis of genes for collagen and collagen synthesis enzymes by qRT-PCR showed that the expression levels of about half of the genes were significantly higher in fibroblasts and myofibroblasts of bleomycin-injured lungs than in fibroblasts of saline-treated lungs. By contrast, the expression levels of 8 of 11 chemokine genes of myofibroblasts were significantly lower than those of fibroblasts. Conclusions This is the first study showing a direct isolation method of myofibroblasts and fibroblasts from injured lungs. We demonstrated functional similarities and differences between myofibroblasts and fibroblasts in terms of both their proliferative capacity and the expression levels of genes for collagen, collagen synthesis enzymes, and chemokines. Thus, this direct isolation method has great potential for obtaining useful information from myofibroblasts and fibroblasts.

2013-01-01

272

Successful treatment of plantar warts with very diluted bleomycin using a translesional multipuncture technique: pilot prospective study.  

UK PubMed Central (United Kingdom)

BACKGROUND: Plantar warts are common and often painful. Treatment of plantar warts is difficult and requires multiple treatments. Several clinical trials have proven the efficacy of bleomycin, but relatively high concentrations have been required and considerable side effects have been experienced. OBJECTIVE: To evaluate the efficacy and safety of low-concentration (0.1 U/mL) bleomycin using a translesional injection technique for the treatment of plantar warts. METHODS: The study included 23 patients with single or multiple plantar warts. Very low-concentration bleomycin was injected into a single wart or the largest plantar wart in the case of multiple lesions. Injections were performed at 4-week intervals until resolution of the warts or development of side effects. The translesional multipuncture technique was used. RESULTS: Thirteen patients were male (56.5%), and the mean age was 27.7 years. The results revealed complete clearance of warts in 17 of 23 (74%) patients, partial response in 1 (4.3%) patient, and no response in 3 (13%) patients. Recurrence was observed in 2 patients at 3 months of follow-up. Among those two, one patient showed complete clearance after the second injection at 6 months of follow-up. All patients were followed for 6 months after the initial treatment. No significant long-term adverse effects were noted. Only three patients (13%) had localized moderate pain for 2 to 3 days after the injection. CONCLUSION: Translesional injection by very low-concentration (0.1 U/mL) bleomycin appears to be a simple, effective, and safe treatment modality for plantar warts.

Alghamdi KM; Khurram H

2012-07-01

273

Gene expression profiles reveal molecular mechanisms involved in the progression and resolution of bleomycin-induced lung fibrosis.  

UK PubMed Central (United Kingdom)

Lung fibrosis is the final result of a large number of disorders and is usually considered an irreversible process. However, some evidence suggests that fibrosis could eventually be reversible. In this study we aimed to document the time-related reversibility of bleomycin-induced lung fibrosis and to examine the gene expression profile associated with its initial progression and subsequent resolution. C57BL/6 mice were instilled with a single dose of bleomycin and euthanized at 1, 4, 8, 12, and 16 wk. Control animals received an equal volume of saline. Lung fibrosis was examined by morphology and hydroxyproline content and the transcriptional signature by gene microarray analysis. Our results showed that bleomycin-injured mice developed prominent inflammation at 1 wk, followed by fibrosis that peaked at 2 mo. Then fibrosis resolved until lungs displayed almost normal architecture at 4 mo. Genomewide transcriptional profiling revealed 533 significantly changed genes. Self-organizing maps analysis of these genes identified four clusters based on the temporal pattern of gene expression. Clusters 1 and 2 contained genes upregulated during the inflammatory and fibrotic response and were enriched for extracellular matrix-related genes including several collagens, matrix metalloproteinases, and TIMP-1. Cluster 3 identified upregulated genes during the fibrotic response, and cluster 4 contained genes decreased during inflammation and fibrosis that increased during resolution. Most enriched pathways included genes involved in cell cycle and in regulation of transcription. Our findings corroborate the reversibility of bleomycin-induced lung fibrosis and reveal transcriptional signatures that characterize the progression and resolution.

Cabrera S; Selman M; Lonzano-Bolaños A; Konishi K; Richards TJ; Kaminski N; Pardo A

2013-05-01

274

Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury.  

UK PubMed Central (United Kingdom)

Thiazolidinedione rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), are two peroxisome proliferator-activated receptor (PPAR)-gamma ligands. The aim of this study was to investigate the effect of rosiglitazone and 15d-PGJ2 on the lung injury caused by bleomycin administration. Mice subjected to intratracheal administration of bleomycin developed significant lung injury. An increase in immunoreactivity to nitrotyrosine, poly(ADP ribose) polymerase (PARP) and inducible nitric oxide synthase as well as a significant loss of body weight and mortality was observed in the lung of bleomycin-treated mice. Administration of the two PPAR-gamma agonists rosiglitazone (10 mg x kg(-1) i.p.) and 15d-PGJ2 (30 microg x kg(-1) i.p.) significantly reduced the: 1) loss of body weight, 2) mortality rate, 3) infiltration of the lung with polymorphonuclear neutrophils (myeloperoxidase activity), 4) oedema formation, and 5) histological evidence of lung injury. Administration of rosiglitazone and 15d-PGJ2 also markedly reduced the nitrotyrosine, PARP and inducible nitric oxide synthase formation. In addition, treatment with the PPAR-gamma antagonist bisphenol A diglycidyl ether (1 mg x kg(-1) i.p. 30 min before the rosiglitazone or 15d-PGJ2) significantly antagonised the effect of the two PPAR-gamma agonists. These results demonstrate that the two peroxisome proliferator-activated receptor-gamma agonists, rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2, significantly reduce lung injury induced by bleomycin in mice.

Genovese T; Cuzzocrea S; Di Paola R; Mazzon E; Mastruzzo C; Catalano P; Sortino M; Crimi N; Caputi AP; Thiemermann C; Vancheri C

2005-02-01

275

Direct isolation of myofibroblasts and fibroblasts from bleomycin-injured lungs reveals their functional similarities and differences.  

UK PubMed Central (United Kingdom)

BACKGROUND: Myofibroblasts play a crucial role in tissue repair. The functional similarities and differences between myofibroblasts and fibroblasts are not fully understood because they have not been separately isolated from a living body. The purpose of this study was to establish a method for the direct isolation of myofibroblasts and fibroblasts from injured lungs by using fluorescence-activated cell sorting and to compare their functions. RESULTS: We demonstrated that lineage-specific cell surface markers (lin), such as CD31, CD45, CD146, EpCAM (CD326), TER119, and Lyve-1 were not expressed in myofibroblasts or fibroblasts. Fibroblasts of bleomycin-injured lungs and saline-treated lungs were shown to be enriched in linneg Sca-1high, and myofibroblasts of bleomycin-injured lungs were shown to be enriched in linneg Sca-1low CD49ehigh. Results from in-vitro proliferation assays indicated in-vitro proliferation of fibroblasts but not myofibroblasts of bleomycin-injured lungs and of fibroblasts of saline-treated lungs. However, fibroblasts and myofibroblasts might have a low proliferative capacity in vivo. Analysis of genes for collagen and collagen synthesis enzymes by qRT-PCR showed that the expression levels of about half of the genes were significantly higher in fibroblasts and myofibroblasts of bleomycin-injured lungs than in fibroblasts of saline-treated lungs. By contrast, the expression levels of 8 of 11 chemokine genes of myofibroblasts were significantly lower than those of fibroblasts. CONCLUSIONS: This is the first study showing a direct isolation method of myofibroblasts and fibroblasts from injured lungs. We demonstrated functional similarities and differences between myofibroblasts and fibroblasts in terms of both their proliferative capacity and the expression levels of genes for collagen, collagen synthesis enzymes, and chemokines. Thus, this direct isolation method has great potential for obtaining useful information from myofibroblasts and fibroblasts.

Akamatsu T; Arai Y; Kosugi I; Kawasaki H; Meguro S; Sakao M; Shibata K; Suda T; Chida K; Iwashita T

2013-01-01

276

A young male with shortness of breath  

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Full Text Available We report a case of primary mediastinal seminoma, which presented initially with shortness of breath and a swelling in upper part of anterior chest wall. The diagnosis of primary mediastinal seminoma was established on the basis of histologic findings and was confirmed by immunohistochemical analysis. Abdominal, pelvis and cerebral CT scan, testicular ultrasound and TC-99 MDP bone scintigraphy were negative. Chemotherapy was initiated with B.E.P. protocol (Bleomycin, Etoposide, Cisplatinum); the patient received four cycles of chemotherapy. After 8 months, the patient was seen in the clinic; he was well.

Khan Fahmi; Al Ani Ahmed; Allaithy Mustafa; Al-Bozom Issam

2008-01-01

277

A Hybrid NRPS-PKS Gene Cluster Related to the Bleomycin Family of Antitumor Antibiotics in Alteromonas macleodii Strains  

Science.gov (United States)

Although numerous marine bacteria are known to produce antibiotics via hybrid NRPS-PKS gene clusters, none have been previously described in an Alteromonas species. In this study, we describe in detail a novel hybrid NRPS-PKS cluster identified in the plasmid of the Alteromonasmacleodii strain AltDE1 and analyze its relatedness to other similar gene clusters in a sequence-based characterization. This is a mobile cluster, flanked by transposase-like genes, that has even been found inserted into the chromosome of some Alteromonasmacleodii strains. The cluster contains separate genes for NRPS and PKS activity. The sole PKS gene appears to carry a novel acyltransferase domain, quite divergent from those currently characterized. The predicted specificities of the adenylation domains of the NRPS genes suggest that the final compound has a backbone very similar to bleomycin related compounds. However, the lack of genes involved in sugar biosynthesis indicates that the final product is not a glycopeptide. Even in the absence of these genes, the presence of the cluster appears to confer complete or partial resistance to phleomycin, which may be attributed to a bleomycin-resistance-like protein identified within the cluster. This also suggests that the compound still shares significant structural similarity to bleomycin. Moreover, transcriptomic evidence indicates that the NRPS-PKS cluster is expressed. Such sequence-based approaches will be crucial to fully explore and analyze the diversity and potential of secondary metabolite production, especially from increasingly important sources like marine microbes.

Mizuno, Carolina Megumi; Kimes, Nikole E.; Lopez-Perez, Mario; Auso, Eva; Rodriguez-Valera, Francisco; Ghai, Rohit

2013-01-01

278

Pharmacokinetics of /sup 57/Co-bleomycin A/sub 5/ in animals with different inoculated tumors  

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The examination of rats with different inoculated tumors rhabdomyosarcoma M-1 (RMS), sarcoma 45 (S-45), Pliss lymphosarcoma (PLS) and Walker carcinoma (WK) revealed, that the pharmacokinetics of /sup 57/Co-bleomycin in tumor-bearing animals did not essentially depend on the histological type of the tumor. The specific activity quotients in the tumors as well as in the muscle tissue did not show differences and had their maxima 3 h after application of the preparation (RMS = 11.7 +- 2.70; S-45 = 10.9 +- 2.05; PLS = 9.52 +- 1.14; WK = 9.16 +- 1.93). The storage maximum of /sup 57/Co-bleomycin A/sub 5/ per g tumor tissue was for RMS and PLS after 5 min. (0.83 +- 0.10 and 0.71 +- 0.06 %, resp., of the applied activity), for S-45 and WK after one hour (0.87 +- 0.14 and 0.86 +- 0.15 %, resp.). The results of the kinetic distribution of the labelled bleomycin A/sub 5/ showed that the moments of visualization of the tumors varied in the different inoculated tumors in intervals from 3 to 48 h after application.

Petriev, V.M.; Khachirov, D.G.; Prusova, R.M. (Nauchno-Issledovatel' skij Inst. Metallurgii, Chelyabinsk (USSR))

1983-01-01

279

Comparison of therapeutic response of keloids and hypertrophic scars to cryotherapy plus intralesional steroid and bleomycin tattoo  

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Full Text Available Keloids and hypertrophic scars are abnormal responses of body to skin injuries. Overproduction of compacted fibrous tissue is the basic cause of these lesions. In this study the result of treatment of these skin conditions with bleomycin tattoo are compared with cryotherapy and triamcinolone injection. This study involved 45 patients with hypertrophic scar or keloid. Patients were divided into two groups consecutively. Group A (23 patients) was treated with bleomycin tattoo and the group B with cryotherapy and triamcinolone injection. There were four therapeutic sessions one month apart. All patients were followedup for three month after the end of treatment .The therapeutic response was determined as reduction of lesion size or flattening relative to initial size. Therapeutic response was 88.3±14% in group A and 67.4 ±22.5% in group B (p<0.001). In group A 69%, but in group B only 49% of patients were asymptomatic after the end of treatment. In group A there was no relation between therapeutic response and lesion size (p=0.58) but in group B lesions those were smaller (<100mm2) had better therapeutic response than larger ones (p=0.007). It was concluded that bleomycin tattoo is more effective in treatment of hypertrophic scar and keloid than traditional treatment, cryotherapy plus triamcinolone injection especially in larger ones.

Farahnaz Fatemi; Jamshid Najafian; Koroush Ahmadpour

2005-01-01

280

Effects of bleomycin and x irradiation on the frequency of chromosomal aberrations in selected connective tissue diseases  

International Nuclear Information System (INIS)

[en] Whole blood lymphocytes from 28 patients with selected connective tissue disorders (6 progressive systemic sclerosis (PSS), 6 anti-nuclear antibody positive rheumatoid arthritis, 6 anti-nuclear antibody negative rheumatoid arthritis, 6 systemic lupus erythematosus, and 4 mixed connective tissue disease) and 17 controls matched for sex, age, and race were studied to determine the frequency of spontaneous as well as bleomycin and/or x-irradiation induced chromosomal aberrations. The effects of bleomycin on cultured lymphocytes were tested, but differential susceptibilities to this clastogen were not demonstrated among the disease groups and controls investigated. However, the combined effect of bleomycin and x irradiation were found to be additive in control lymphocytes, nearly additive in PSS, RA+, and SLE cultures, but reduced considerably from the expected additive value in Ra- cultures. This study indicated that peripheral blood lymphocytes from patients with connective tissue disease, as a whole, possess greater frequencies of spontaneous chromosomal aberrations than matched controls and that x rays can produce greater frequencies of chromosomal aberrations in whole blood lymphocytes of PSS patients than in suitably matched control individuals

1978-01-01

 
 
 
 
281

Sprague Dawley response to the cyclophosphamide and bleomycin in the alkaline comet assay of peripheral blood leukocytes  

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Full Text Available In this article we decide to evaluate genotoxic effect of the cyclophosphamide and bleomycin in the individual cells by means of alkaline comet assay using the Sprague Dawley rats in both sexes as experimental biomodel. Which were formed 5 experimental groups per sex, the first administered with NaCl 0,9 % by intraperitoneal (i.p) route, the second and third groups were administered with cyclophosphamide by i.p route, with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at doses of 40 mg/kg. At the end of the experience bigger induction of damage was obtained with the use of the cyclophosphamide and bleomycin, both in the design of 48 and 24 hours administration before the sacrifice. This constitutes under our experimental conditions the two better experimental designs to induce the strand breaks (SB) or alkali-labile sites formation on DNA, increasing considerably the frequency spontaneous present in this species of rat, being useful in studies of drugs evaluation that they have not been explored in to the in vivo antigenotoxicity and genotoxicity environment.

Daniel Francisco Arencibia Arrebola; Alexis Vidal Novoa; Luis Alfredo Rosario Fernández; Yolanda Emilia Suárez Fernández

2010-01-01

282

PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression.  

UK PubMed Central (United Kingdom)

The mortality rate for acute lung injury (ALI) is reported to be between 35-40%, and there are very few treatment strategies that improve the death rate from this condition. Previous studies have suggested that signaling through the prostaglandin (PG) I(2) receptor may protect against bleomycin-induced ALI in mice. We found that mice that overexpress PGI synthase (PGIS) in the airway epithelium were significantly protected against bleomycin-induced mortality and had reduced parenchymal consolidation, apoptosis of lung tissue, and generation of F(2)-isoprostanes compared with littermate wild-type controls. In addition, we show for the first time in both in vivo and in vitro experiments that PGI(2) induced the expression of NADP (H): quinoneoxidoreductase 1 (Nqo 1), an enzyme that prevents the generation of reactive oxygen species. PGI(2) induction of Nqo 1 provides a possible novel mechanism by which this prostanoid protects against bleomycin-induced mortality and identifies a potential therapeutic target for human ALI.

Zhou W; Dowell DR; Geraci MW; Blackwell TS; Collins RD; Polosukhin VV; Lawson WE; Wu P; Sussan T; Biswal S; Goleniewska K; O'Neal J; Newcomb DC; Toki S; Morrow JD; Peebles RS Jr

2011-10-01

283

Point- To- Point Protocol  

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Full Text Available The telephone line provides a physical link, but to control and manage the transfer of data, there is a need for point-to-point connection. The first protocol devised for this purpose was serial line internet protocol (SLIP). However, SLIP has some deficiencies: it does not support protocols other than internet protocol (IP). It does not allow the IP addresses to be assigned dynamically, and it does not support authentication of the user. The POINT-TO-POINT (PPP) is a protocol designed to respond to respond to the deficiencies. Today the PPP protocol standard finds wide use in asynchronous and synchronous connections between computers, bridges, routers and other intermediate devices.PPP is gaining acceptance as a standard for Integrated Services Digital Network(ISDN), and many implementations of X.25 also support PPP connection.

Immadisetty L V Chandrika,; Venkata Videhi Balusupati,; A.Rama Krishna,

2012-01-01

284

Secure Selection Protocols  

UK PubMed Central (United Kingdom)

The process of selection is omnipresent in the real world and modeling this process as a cryptologic protocol will enable cross use of techniques among similar protocol applications, which will eventually lead to better understanding and re nement of these applications. We present a proposal for a specialised selection protocol with anonymity as the security service. An area for its application is anonymous peer review, where no peer should know the identity of the reviewer.

Kapali Viswanathan; Colin Boyd

285

The triterpenoid CDDO-Me inhibits bleomycin-induced lung inflammation and fibrosis.  

Science.gov (United States)

Pulmonary Fibrosis (PF) is a devastating progressive disease in which normal lung structure and function is compromised by scarring. Lung fibrosis can be caused by thoracic radiation, injury from chemotherapy and systemic diseases such as rheumatoid arthritis that involve inflammatory responses. CDDO-Me (Methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, Bardoxolone methyl) is a novel triterpenoid with anti-fibrotic and anti-inflammatory properties as shown by our in vitro studies. Based on this evidence, we hypothesized that CDDO-Me would reduce lung inflammation, fibrosis and lung function impairment in a bleomycin model of lung injury and fibrosis. To test this hypothesis, mice received bleomycin via oropharyngeal aspiration (OA) on day zero and CDDO-Me during the inflammatory phase from days -1 to 9 every other day. Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested on day 7 to evaluate inflammation, while fibrosis and lung function were evaluated on day 21. On day 7, CDDO-Me reduced total BALF protein by 50%, alveolar macrophage infiltration by 40%, neutrophil infiltration by 90% (p?0.01), inhibited production of the inflammatory cytokines KC and IL-6 by over 90% (p?0.001), and excess production of the pro-fibrotic cytokine TGF? by 50%. CDDO-Me also inhibited ?-smooth muscle actin and fibronectin mRNA by 50% (p?0.05). On day 21, CDDO-Me treatment reduced histological fibrosis, collagen deposition and ?SMA production. Lung function was significantly improved at day 21 by treatment with CDDO-Me, as demonstrated by respiratory rate and dynamic compliance. These new findings reveal that CDDO-Me exhibits potent anti-fibrotic and anti-inflammatory properties in vivo. CDDO-Me is a potential new class of drugs to arrest inflammation and ameliorate fibrosis in patients who are predisposed to lung injury and fibrosis incited by cancer treatments (e.g. chemotherapy and radiation) and by systemic autoimmune diseases. PMID:23741300

Kulkarni, Ajit A; Thatcher, Thomas H; Hsiao, Hsi-Min; Olsen, Keith C; Kottmann, Robert Matthew; Morrissette, Jason; Wright, Terry W; Phipps, Richard P; Sime, Patricia J

2013-05-31

286

Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study  

Scientific Electronic Library Online (English)

Full Text Available Abstract in portuguese Inúmeros estudos têm mostrado que fibroblastos de pacientes com adenomatose hereditária de cólon e reto, que inclui polipose adenomatosa familial (FAP) e a síndrome de Gardner, apresentam uma freqüência aumentada de aberrações cromossômicas após exposição a agentes físicos ou químicos, quando comparados aos controles normais. Para determinar a sensibilidade de linfócitos de pacientes com FAP e também com pólipos adenomatosos esporádicos (AP) usou-se o r (more) adiomimético bleomicina (BLM). Foram estudados citogeneticamente 10 indivíduos com AP, 10 com FAP e 20 controles normais, pareados por sexo e idade. Indivíduos que apresentaram valores médios de quebras cromatídicas por célula superiores a 0,80 foram considerados sensíveis à droga. Observou-se uma diferença significativa entre pacientes com FAP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados na fase G2. Entretanto, nenhuma diferença significativa foi observada entre pacientes com AP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados. Nenhum indivíduo do grupo controle foi sensível à BLM e, entre os 20 pacientes, três mostraram suscetibilidade à droga. Não foi encontrada diferença significativa quanto a resposta à bleomicina entre indivíduos do sexo masculino e feminino. Entretanto, a distribuição de quebras induzidas por bleomicina em cada grupo cromossômico não foi similar nos pacientes do sexo feminino e controles normais. É possível que a sensibilidade cromossômica à BLM encontrada nos pacientes com FAP esteja relacionada a deficiência de reparo de DNA. Abstract in english Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP) showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM) during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP) vs. 10 normal individuals (P = 0.67). Individuals that exhibited an average (more) number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.

Sales, Magaly M.; Lucca, Edmundo J. de; Yamashita, Seizo; Saad, Luis Henrique Cury

1999-03-01

287

Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study  

Directory of Open Access Journals (Sweden)

Full Text Available Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP) showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM) during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP) vs. 10 normal individuals (P = 0.67). Individuals that exhibited an average number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.Inúmeros estudos têm mostrado que fibroblastos de pacientes com adenomatose hereditária de cólon e reto, que inclui polipose adenomatosa familial (FAP) e a síndrome de Gardner, apresentam uma freqüência aumentada de aberrações cromossômicas após exposição a agentes físicos ou químicos, quando comparados aos controles normais. Para determinar a sensibilidade de linfócitos de pacientes com FAP e também com pólipos adenomatosos esporádicos (AP) usou-se o radiomimético bleomicina (BLM). Foram estudados citogeneticamente 10 indivíduos com AP, 10 com FAP e 20 controles normais, pareados por sexo e idade. Indivíduos que apresentaram valores médios de quebras cromatídicas por célula superiores a 0,80 foram considerados sensíveis à droga. Observou-se uma diferença significativa entre pacientes com FAP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados na fase G2. Entretanto, nenhuma diferença significativa foi observada entre pacientes com AP e controles quanto às freqüências de quebras cromatídicas nos linfócitos tratados. Nenhum indivíduo do grupo controle foi sensível à BLM e, entre os 20 pacientes, três mostraram suscetibilidade à droga. Não foi encontrada diferença significativa quanto a resposta à bleomicina entre indivíduos do sexo masculino e feminino. Entretanto, a distribuição de quebras induzidas por bleomicina em cada grupo cromossômico não foi similar nos pacientes do sexo feminino e controles normais. É possível que a sensibilidade cromossômica à BLM encontrada nos pacientes com FAP esteja relacionada a deficiência de reparo de DNA.

Magaly M. Sales; Edmundo J. de Lucca; Seizo Yamashita; Luis Henrique Cury Saad

1999-01-01

288

Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Pulmonary fibrosis (PF) is a group of devastating and largely irreversible diseases. Phosphodiesterase (PDE) 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis. The aim of the study was, therefore, to investigate the effect of PDE4 inhibition in experimental model of PF. Methods PF was induced in C57BL/6N mice by instillation of bleomycin. Pharmacological inhibition of PDE4 was achieved by using cilomilast, a selective PDE4 inhibitor. Changes in either lung inflammation or remodeling were evaluated at different stages of experimental PF. Lung inflammation was assessed by bronchoalveolar lavage fluid (BALF) differential cell count and reverse transcription quantitative polymerase chain reaction (RT-qPCR) for inflammatory cytokines. Changes in tissue remodeling were evaluated by pulmonary compliance measurement, quantified pathological examination, measurement of collagen deposition and RT-qPCR for late remodeling markers. Survival in all groups was analyzed as well. Results PDE4 inhibition significantly reduced the total number of alveolar inflammatory cells in BALF of mice with bleomycin-induced PF at early fibrosis stage (days 4 and 7). Number of macrophages and lymphocytes, but not neutrophils, was significantly reduced as well. Treatment decreased lung tumor necrosis factor (TNF)-? mRNA level and increased mRNA level of interleukin (IL)-6 but did not influence IL-1?. At later stage (days 14 and 24) cilomilast improved lung function, which was shown by increase in lung compliance. It also lowered fibrosis degree, as was shown by quantified pathological examination of Hematoxilin-Eosin stained lung sections. Cilomilast had no significant effect on the expression of late remodeling markers such as transforming growth factor (TGF)-?1 and collagen type Ia1 (COL(I)?1). However, it tended to restore the level of lung collagen, assessed by SIRCOL assay and Masson's trichrome staining, and to improve the overall survival. Conclusions Selective PDE4 inhibition suppresses early inflammatory stage and attenuates the late stage of experimental pulmonary fibrosis.

Udalov Sergey; Dumitrascu Rio; Pullamsetti Soni S; Al-tamari Hamza M; Weissmann Norbert; Ghofrani Hossein A; Guenther Andreas; Voswinckel Robert; Seeger Werner; Grimminger Friedrich; Schermuly Ralph T

2010-01-01

289

Adaptation of TURN protocol to SIP protocol  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Today, SIP is a protocol par Excellence in the field of communication over Internet. But, the fact that it belongs to the application layer constitutes a weakness vis-a-vis the NAT traversal. This weakness is due to the way in which the server replies to the requests of clients on the one hand. On t...

Mustapha Guezouri; Ahmed Blaha; Mokhtar Keche

290

Vertical Protocol Composition  

DEFF Research Database (Denmark)

The security of key exchange and secure channel protocols, such as TLS, has been studied intensively. However, only few works have considered what happens when the established keys are actually used—to run some protocol securely over the established “channel”. We call this a vertical protocol composition, and it is truly commonplace in today’s communication with the diversity of VPNs and secure browser sessions. In fact, it is normal that we have several layers of secure channels: For instance, on top of a VPN-connection, a browser may establish another secure channel (possibly with a different end point). Even using the same protocol several times in such a stack of channels is not unusual: An application may very well establish another TLS channel over an established one. We call this selfcomposition. In fact, there is nothing that tells us that all these compositions are sound, i.e., that the combination cannot introduce attacks that the individual protocols in isolation do not have. In this work, we provea composability result in the symbolic model that allows for arbitrary vertical composition (including self-composition). It holds for protocols from any suite of channel and application protocols that fulfills a number of sufficient preconditions. These preconditions are satisfied for many practically relevant protocols such as TLS.

Groß, Thomas; Mödersheim, Sebastian Alexander

2011-01-01

291

RATS Control Protocol (RCP).  

Science.gov (United States)

RATS is the real-time scheduler used in the server of the DSTO theatre Broadcast System demonstrator. This document describes the RATS Control Protocol which is used for all communications with RATS. RCP is based on the User Datagram Protocol (UDP) and is...

P. A. Blackmore

2001-01-01

292

Transport Protocol Throughput Fairness  

Directory of Open Access Journals (Sweden)

Full Text Available Interest continues to grow in alternative transport protocols to the Transmission Control Protocol (TCP). These alternatives include protocols designed to give greater efficiency in high-speed, high-delay environments (so-called high-speed TCP variants), and protocols that provide congestion control without reliability. For the former category, along with the deployed base of ‘vanilla’ TCP – TCP NewReno – the TCP variants BIC and CUBIC are widely used within Linux: for the latter category, the Datagram Congestion Control Protocol (DCCP) is currently on the IETF Standards Track. It is clear that future traffic patterns will consist of a mix of flows from these protocols (and others). So, it is important for users and network operators to be aware of the impact that these protocols may have on users. We show the measurement of fairness in throughput performance of DCCP Congestion Control ID 2 (CCID2) relative to TCP NewReno, and variants Binary Increase Congestion control (BIC), CUBIC and Compound, all in “out-of-the box” configurations. We use a testbed and endto- end measurements to assess overall throughput, and also to assess fairness – how well these protocols might respond to each other when operating over the same end-to-end network path. We find that, in our testbed, DCCP CCID2 shows good fairness with NewReno, while BIC, CUBIC and Compound show unfairness above round-trip times of 25ms.

Saleem Bhatti; Martin Bateman

2009-01-01

293

SIP: Session Initiation Protocol  

UK PubMed Central (United Kingdom)

The Session Initiation Protocol (SIP) is an application-layer control (signaling) protocol for creating, modifying and terminating sessions with one or more participants. These sessions include Internet multimedia conferences, Internet telephone calls and multimedia distribution. Members in a session can communicate via multicast or via a mesh of unicast relations, or a combination of these.

294

CD19 regulates skin and lung fibrosis via Toll-like receptor signaling in a model of bleomycin-induced scleroderma.  

UK PubMed Central (United Kingdom)

Mice subcutaneously injected with bleomycin, in an experimental model of human systemic sclerosis, develop cutaneous and lung fibrosis with autoantibody production. CD19 is a general "rheostat" that defines signaling thresholds critical for humoral immune responses, autoimmunity, and cytokine production. To determine the role of CD19 in the bleomycin-induced systemic sclerosis model, we investigated the development of fibrosis and autoimmunity in CD19-deficient mice. Bleomycin-treated wild-type mice exhibited dermal and lung fibrosis, hyper-gamma-globulinemia, autoantibody production, and enhanced serum and skin expression of various cytokines, including fibrogenic interleukin-4, interleukin-6, and transforming growth factor-beta1, all of which were inhibited by CD19 deficiency. Bleomycin treatment enhanced hyaluronan production in the skin, lung, and sera. Addition of hyaluronan, an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4, stimulated B cells to produce various cytokines, primarily through TLR4; CD19 deficiency suppressed this stimulation. These results suggest that bleomycin induces fibrosis by enhancing hyaluronan production, which activates B cells to produce fibrogenic cytokines mainly via TLR4 and induce autoantibody production, and that CD19 deficiency suppresses fibrosis and autoantibody production by inhibiting TLR4 signals.

Yoshizaki A; Iwata Y; Komura K; Ogawa F; Hara T; Muroi E; Takenaka M; Shimizu K; Hasegawa M; Fujimoto M; Tedder TF; Sato S

2008-06-01

295

CD19 regulates skin and lung fibrosis via Toll-like receptor signaling in a model of bleomycin-induced scleroderma.  

Science.gov (United States)

Mice subcutaneously injected with bleomycin, in an experimental model of human systemic sclerosis, develop cutaneous and lung fibrosis with autoantibody production. CD19 is a general "rheostat" that defines signaling thresholds critical for humoral immune responses, autoimmunity, and cytokine production. To determine the role of CD19 in the bleomycin-induced systemic sclerosis model, we investigated the development of fibrosis and autoimmunity in CD19-deficient mice. Bleomycin-treated wild-type mice exhibited dermal and lung fibrosis, hyper-gamma-globulinemia, autoantibody production, and enhanced serum and skin expression of various cytokines, including fibrogenic interleukin-4, interleukin-6, and transforming growth factor-beta1, all of which were inhibited by CD19 deficiency. Bleomycin treatment enhanced hyaluronan production in the skin, lung, and sera. Addition of hyaluronan, an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4, stimulated B cells to produce various cytokines, primarily through TLR4; CD19 deficiency suppressed this stimulation. These results suggest that bleomycin induces fibrosis by enhancing hyaluronan production, which activates B cells to produce fibrogenic cytokines mainly via TLR4 and induce autoantibody production, and that CD19 deficiency suppresses fibrosis and autoantibody production by inhibiting TLR4 signals. PMID:18467694

Yoshizaki, Ayumi; Iwata, Yohei; Komura, Kazuhiro; Ogawa, Fumihide; Hara, Toshihide; Muroi, Eiji; Takenaka, Motoi; Shimizu, Kazuhiro; Hasegawa, Minoru; Fujimoto, Manabu; Tedder, Thomas F; Sato, Shinichi

2008-05-08

296

The Wireless Application Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available The Wireless Application Protocol WAP is a protocol stack for wireless communication networks. WAP uses WTLS, a wireless variant of the SSL/TLS protocol, to secure the communication between the mobile phone and other parts of the WAP architecture. This paper describes the security architecture of WAP and some important properties of the WTLS protocol. There are however some security problems with WAP and the WTLS protocol. Privacy, data protection and integrity are not always provided. Users and developers of WAP-applications should be aware of this. In this paper, we address the security weaknesses of WAP and WTLS and propose some countermeasures and good practices when using WAP. We conclude with advising when to use WAP and when not.

Dave Singelee; Bart Preneel

2005-01-01

297

Cisplatin and bleomycin in the treatment of esophageal carcinoma. A final report.  

UK PubMed Central (United Kingdom)

During the period from September, 1976 to June, 1979, 70 patients with locoregional or extensive epidermoid carcinoma of the esophagus were treated with the two-drug combination of cisplatin and bleomycin (DB). For the 43 patients with locoregional disease (LRD), DB was used prior to surgery and/or radiation therapy; it was the primary treatment for 27 patients with extensive disease (ED). The major objective response rates [complete remission (CR) and partial remission (PR)] to DB for the LRD and ED groups were 14% and 17%, respectively, for an overall response rate of 15%. For the LRD group, the minimum follow-up was 42 months; four patients (10%) remain alive and free of disease. The median survival of 34 patients treated with DB preoperatively was 10 months, which did not differ significantly from that of a historic control group receiving preoperative radiation therapy. The median duration of response for ED patients was 6 months, and the median survival for the entire ED group was 4 months. DB alone had only modest activity in epidermoid carcinoma of the esophagus.

Coonley CJ; Bains M; Hilaris B; Chapman R; Kelsen DP

1984-12-01

298

Cisplatin and bleomycin in the treatment of esophageal carcinoma. A final report.  

Science.gov (United States)

During the period from September, 1976 to June, 1979, 70 patients with locoregional or extensive epidermoid carcinoma of the esophagus were treated with the two-drug combination of cisplatin and bleomycin (DB). For the 43 patients with locoregional disease (LRD), DB was used prior to surgery and/or radiation therapy; it was the primary treatment for 27 patients with extensive disease (ED). The major objective response rates [complete remission (CR) and partial remission (PR)] to DB for the LRD and ED groups were 14% and 17%, respectively, for an overall response rate of 15%. For the LRD group, the minimum follow-up was 42 months; four patients (10%) remain alive and free of disease. The median survival of 34 patients treated with DB preoperatively was 10 months, which did not differ significantly from that of a historic control group receiving preoperative radiation therapy. The median duration of response for ED patients was 6 months, and the median survival for the entire ED group was 4 months. DB alone had only modest activity in epidermoid carcinoma of the esophagus. PMID:6208990

Coonley, C J; Bains, M; Hilaris, B; Chapman, R; Kelsen, D P

1984-12-01

299

Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva  

Energy Technology Data Exchange (ETDEWEB)

Forty-two patients with advanced squamous cell carcinoma of the vulva were treated with a combination regimen of bleomycin 180 mg and external irradiation 30-45 Gy. Twenty patients had primary lesions, and 22 patients had recurrent disease. Fifteen (75%) of the patients with primary disease showed objective response (five complete and ten partial response). Four underwent surgery. Of these, one is alive after 60 months with no evidence of disease. Two have died of unrelated causes without signs of recurrence. Seventeen relapsed and died of carcinoma of the vulva. Median survival for patients treated for primary disease was 8.0 months. Thirteen (59%) of 22 patients treated for recurrence showed objective response (two complete and eleven partial responses). None underwent surgery. All these patients died of carcinoma of the vulva. Median survival was 6.4 months. Toxicity was acceptable, and there were no treatment-related deaths. Even taking into account that our patients had very advanced disease, the results are disappointing. An increase of the radiation dose beyond the maximum of 45 Gy given, and more aggressive surgery, might have improved the results. (orig.).

Scheistroeen, M. (Norwegian Radium Hospital, Oslo (Norway)); Trope, C. (Norwegian Radium Hospital, Oslo (Norway))

1993-01-01

300

Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva  

International Nuclear Information System (INIS)

[en] Forty-two patients with advanced squamous cell carcinoma of the vulva were treated with a combination regimen of bleomycin 180 mg and external irradiation 30-45 Gy. Twenty patients had primary lesions, and 22 patients had recurrent disease. Fifteen (75%) of the patients with primary disease showed objective response (five complete and ten partial response). Four underwent surgery. Of these, one is alive after 60 months with no evidence of disease. Two have died of unrelated causes without signs of recurrence. Seventeen relapsed and died of carcinoma of the vulva. Median survival for patients treated for primary disease was 8.0 months. Thirteen (59%) of 22 patients treated for recurrence showed objective response (two complete and eleven partial responses). None underwent surgery. All these patients died of carcinoma of the vulva. Median survival was 6.4 months. Toxicity was acceptable, and there were no treatment-related deaths. Even taking into account that our patients had very advanced disease, the results are disappointing. An increase of the radiation dose beyond the maximum of 45 Gy given, and more aggressive surgery, might have improved the results. (orig.)

1993-01-01

 
 
 
 
301

Killing lung cancer cells at cell-cycle phase by a new indium-111-bleomycin complex  

International Nuclear Information System (INIS)

The efficacy of killing small cell lung cancer (SCLC) cells at the G1, S, and G2-M phase of the cell-cycle by a new 111In-bleomycin complex (111In-BLMC) was investigated. SCLC cells (N417, H526, H209) were synchronized by double thymidine block and assessed by DNA content with flow cytometry, and the period for the maximal accumulation of cells in S, G1, or G2-M phase was determined. Cells in different cell cycle phases were exposed to 0.9% NaCl, BLM, or 111In-BLMC for 1 hour and observed for colony formation. The survival of H526 cells treated with 111In-BLMC was 71% (for enriched S phase), 46% (G1), and 31% (G2-M). For N417 cells, it was 25% (S), 20% (G1), and 8% (G2-M) for 111In-BLMC and 18% (S), 33% (G1), and 10% (G2-M) for BLM. These results indicated that SCLC cells in G2-M were most sensitive and those in S phase were least sensitive to 111In-BLMC; cells in G1 phase were the least sensitive to BLM.

1989-01-01

302

Killing lung cancer cells at cell-cycle phase by a new indium-111-bleomycin complex  

Energy Technology Data Exchange (ETDEWEB)

The efficacy of killing small cell lung cancer (SCLC) cells at the G1, S, and G2-M phase of the cell-cycle by a new /sup 111/In-bleomycin complex (/sup 111/In-BLMC) was investigated. SCLC cells (N417, H526, H209) were synchronized by double thymidine block and assessed by DNA content with flow cytometry, and the period for the maximal accumulation of cells in S, G1, or G2-M phase was determined. Cells in different cell cycle phases were exposed to 0.9% NaCl, BLM, or /sup 111/In-BLMC for 1 hour and observed for colony formation. The survival of H526 cells treated with /sup 111/In-BLMC was 71% (for enriched S phase), 46% (G1), and 31% (G2-M). For N417 cells, it was 25% (S), 20% (G1), and 8% (G2-M) for /sup 111/In-BLMC and 18% (S), 33% (G1), and 10% (G2-M) for BLM. These results indicated that SCLC cells in G2-M were most sensitive and those in S phase were least sensitive to /sup 111/In-BLMC; cells in G1 phase were the least sensitive to BLM.

Hou, D.Y.; Ordonez, J.V.; Cross, R.J.; Ross, D.D.; Maruyama, Y.

1989-02-01

303

Bleomycin/interleukin-12 electrochemogenetherapy for treating naturally occurring spontaneous neoplasms in dogs.  

UK PubMed Central (United Kingdom)

On the basis of superior outcomes from electrochemogenetherapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in the size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform, was associated with repair of bone lysis in cured dogs, improved quality of life for dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

Reed SD; Fulmer A; Buckholz J; Zhang B; Cutrera J; Shiomitsu K; Li S

2010-08-01

304

Indium-111 bleomycin complex for radiochemotherapy of head and neck cancer - dosimetric and biokinetic aspects  

International Nuclear Information System (INIS)

Bleomycin (BLM) is used for the treatment of head and neck cancer. In order to improve the effectiveness of this chemotherapeutic drug, BLM was combined with indium-111. A complex of these agents (111In-BLMC), formed at low pH, was injected intravenously into ten head and neck cancer patients in escalating activities of 75, 175 and 375 MBq. The internally delivered dose to the tumours varied from 0.20 to 2.73 mGy at 75 MBq, from 0.33 to 2.51 mGy at 175 MBq, and from 0.87 to 31.3 mGy at the 375 MBq activity level. Uptake of radioactivity was 0.45±0.24x10-3% ID/g in primary tumours and 0.52±0.20x10-3% ID/g in metastases (at 48 h). Tumour volumes varied from 0.51 to 49.0 cm-3. The radioactivity half-lives in the tumours were 30±7 h. The activity distribution and penetration into tumour tissue were not affected by increasing the injected activity. There was a positive correlation between BLMC uptake and Ki-67/Mib activity as well as number of mitoses in tumour tissue. These data indicate that 111In-BLMC has potential as a radiochemotherapeutic agent in head and neck cancer and that adjuvant Auger-electron therapy is possible using 114mIn-labelled BLMC. (orig.)

1996-01-01

305

Bleomycin Loaded Magnetite Nanoparticles Functionalized by Polyacrylic Acid as a New Antitumoral Drug Delivery System  

Science.gov (United States)

Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs) coated with polyacrylic acid (PAA) as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR). The loading and release behaviors of BLM-MNPs were examined by a mathematical formula and in vitro release profile at pH 7.5. Results. The sphere Fe3O4 nanoparticles with the size of approximately 30?nm exhibit a saturation magnetization of 87?emu/g. The noncoordinated carboxylate groups of PAA confer on the good dispersibility in the aqueous solution and lead to a good loading efficiency of BLM reaching 50% or higher. Approximately 98% of immobilized BLM could be released within 24?h, of which 22.4% was released in the first hour and then the remaining was released slowly and quantitatively in the next 23?hours. Conclusion. BLM-MNPs were prepared and characterized successfully. The particles show high saturation magnetization, high drug loading capacity, and favorable release property, which could contribute to the specific delivery and controllable release of BLM, and the BLM-MNPs could be a potential candidate for the development of treating solid tumors.

2013-01-01

306

Bleomycin loaded magnetite nanoparticles functionalized by polyacrylic Acid as a new antitumoral drug delivery system.  

UK PubMed Central (United Kingdom)

Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs) coated with polyacrylic acid (PAA) as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR). The loading and release behaviors of BLM-MNPs were examined by a mathematical formula and in vitro release profile at pH 7.5. Results. The sphere Fe3O4 nanoparticles with the size of approximately 30?nm exhibit a saturation magnetization of 87?emu/g. The noncoordinated carboxylate groups of PAA confer on the good dispersibility in the aqueous solution and lead to a good loading efficiency of BLM reaching 50% or higher. Approximately 98% of immobilized BLM could be released within 24?h, of which 22.4% was released in the first hour and then the remaining was released slowly and quantitatively in the next 23?hours. Conclusion. BLM-MNPs were prepared and characterized successfully. The particles show high saturation magnetization, high drug loading capacity, and favorable release property, which could contribute to the specific delivery and controllable release of BLM, and the BLM-MNPs could be a potential candidate for the development of treating solid tumors.

Xu Y; Lin Y; Zhuang L; Lin J; Lv J; Huang Q; Sun J

2013-01-01

307

Bleomycin, cyclophosphamide and radiotherapy in regionally advanced epidermoid carcinoma of the head and neck  

Energy Technology Data Exchange (ETDEWEB)

Twenty four patients with squamous carcinoma of the head and neck and advanced regional (N/sub 2//sub -//sub 3/) disease were treated. The regimen consisted of 3 cycles, each of 28 days. Cyclophosphamide (I gm/m/sup 2/ I.V.) were given on day 1, bleomycin (15 ..mu.. I.M.) on days 2, 4, 9 and 11, and ionizing radiation (/sup 60/Co, 180 rad/fraction) days 1-5, and 8-12. No therapy was given on days 13-28. After three cycles of therapy, 13 patients had a complete response; following further therapy (surgery, interstitial or extenal beam radiation), 16 patients were free of disease. However, remissions were not durable and 11/16 patients recurred loco-regionally with a median time to recurrence of 5 months; most (7/11) also developed distant metastases. These patients have biologically aggressive disease and may have a worse prognosis than patients who are Stage IV based on a T/sub 4/ primary lesion only.

Seagren, S.L.; Byfield, J.E.; Davidson, T.M.; Sharp, T.R.

1982-01-01

308

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats  

Scientific Electronic Library Online (English)

Full Text Available Abstract in english Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effect of simvastatin on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate (more) -buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-?, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p

Tulek, Baykal; Kiyan, Esen; Kiyici, Aysel; Toy, Hatice; Bariskaner, Hulagu; Suerdem, Mecit

2012-01-01

309

Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation ({approx}0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM.

Benkhaled, L.; Xuncla, M.; Caballin, M.R. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain); Barrios, L. [Universitat Autonoma de Barcelona, Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia (Spain); Barquinero, J.F. [Universitat Autonoma de Barcelona, Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, E-08193 Bellaterra (Spain)], E-mail: Francesc.Barquinero@uab.es

2008-01-01

310

Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes  

International Nuclear Information System (INIS)

Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation (?0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM.

2008-01-01

311

Ultrasensitive electrogenerated chemiluminescent DNA-based biosensing switch for the determination of bleomycin.  

UK PubMed Central (United Kingdom)

An ultrasensitive electrogenerated chemiluminescent (ECL) DNA-based biosensing switch for the determination of bleomycin (BLM) was developed based on Fe(II) · BLM-mediated hairpin DNA strand cleavage and a structure-switching ECL-dequenching mechanism. A thiolated ss-DNA was used as a substrate for BLMs: one terminus was tethered onto an electrode surface, and the other terminus was labelled with the ECL quencher ferrocene to form a hairpin structure. This thiolated ss-DNA self-assembled on to the tris(2,2'-bipyridine)ruthenium-gold nanoparticle composite modified gold electrode. In the presence of Fe(II) · BLM, the ECL DNA biosensing switch undergoes an irreversible cleavage event that can trigger a significant increase in ECL intensity. The relationship of ECL intensity and the concentration of BLMs was found to be linear in the range of 5 fM - 5000 fM with a detection limit of 2 fM. This work demonstrates that the design of a highly sensitive ECL DNA-based biosensing switch that uses the sequence selectivity of DNA cleavage mediated by the antitumor drug BLM in combination with a chemical quencher, such as ferrocene, to quench ECL signal(s), offers a promising approach for the determination of ultratrace amounts of antitumor drugs.

Li Y; Huang C; Zheng J; Qi H

2013-01-01

312

Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice  

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Full Text Available Abstract Background The role of angiotensin II type 2 receptor (AT2) in pulmonary fibrosis is unknown. To evaluate the influence of angiotensin II type 1 receptor (AT1) and AT2 antagonists in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. Methods We examined effects of the AT1 antagonist (AT1A) olmesartan medoxomil (olmesartan) and the AT2 antagonist (AT2A) PD-123319 on BLM-induced pulmonary fibrosis, which was evaluated by Ashcroft's pathological scoring and hydroxyproline content of lungs. We also analyzed the cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF). Results With olmesartan, the lung fibrosis score and hydroxyproline level were significantly reduced, and lymphocyte and neutrophil counts and tumor necrosis factor (TNF)-? levels in BALF were reduced on day 7. On day 14, macrophage and lymphocyte counts in BALF were reduced, accompanied by a reduction in the level of transforming growth factor (TGF)-?1. With PD-123319, the lung fibrosis score and hydroxyproline level were reduced. On day 7, macrophage, lymphocyte, and neutrophil counts in BALF were reduced, accompanied by reductions in TNF-? and monocyte chemoattractant protein (MCP)-1 levels. On day 14, macrophage, lymphocyte, and neutrophil counts in BALF were also reduced, accompanied by a reduction in the level of macrophage inflammatory protein (MIP)-2 level but not TGF-?1. Conclusion Both AT1 and AT2 are involved in promoting interstitial pneumonia and pulmonary fibrosis via different mechanisms of action.

Waseda Yuko; Yasui Masahide; Nishizawa Yoriko; Inuzuka Kanako; Takato Hazuki; Ichikawa Yukari; Tagami Atsuro; Fujimura Masaki; Nakao Shinji

2008-01-01

313

Overcoming suppression of antitumor immune reactivity in tumor-bearing rats by treatment with bleomycin.  

UK PubMed Central (United Kingdom)

We investigated the immunological role of bleomycin (BLM) in the treatment of KMT-17 fibrosarcoma-bearing rats. We were able to detect antitumor immune reactivity by using a mixed-lymphocyte tumor culture in spleen cells shortly after the transplantation of a KMT-17 fibrosarcoma in syngeneic Wistar King Aptekman/HMK rats. The reactivity declined following the progression of the tumor and was completely inhibited 11 days after the tumor transplantation. After the 11th day, however, spleen cells from BLM-treated KMT-17-bearing rats demonstrated higher antitumor immune reactivity. This result corresponds to those we obtained from an in vivo tumor-neutralizing assay (Winn assay). Macrophages from untreated tumor bearers were unable to inhibit the immune reactivity against KMT-17 cells in the mixed-lymphocyte tumor culture. Neither the tumor-bearing state nor the BLM treatment seemed to have any significant influence on another macrophage function, the antigen-presenting cell activity. However, a T-enriched fraction from untreated KMT-17 bearers showed a definite suppression activity on the generation of cytotoxic T-lymphocyte activity against KMT-17 tumor in the mixed-lymphocyte tumor culture; in contrast, no T-suppressor activity could be detected in the same fraction taken from BLM-treated tumor bearers. Our investigation suggests that BLM eliminates the tumor-specific T-suppressor activity without having any influence on responder T-lymphocytes in the cell-mediated antitumor immune reactivity.

Xu ZY; Hosokawa M; Morikawa K; Hatakeyama M; Kobayashi H

1988-12-01

314

Qualitative rather than quantitative changes are hallmarks of fibroblasts in bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

Pulmonary fibrosis is characterized by accumulation of activated fibroblasts that produce excessive amounts of extracellular matrix components such as collagen type I. However, the dynamics and activation signatures of fibroblasts during fibrogenesis remain poorly understood, especially in vivo. We examined changes in lung tissue cell populations and in the phenotype of activated fibroblasts after acute injury in a model of bleomycin-induced pulmonary fibrosis. Despite clustering of collagen type I-producing fibroblasts in fibrotic regions, flow cytometry-based quantitative analysis of whole lungs revealed that the number of fibroblasts in the lungs remained constant. At the peak of inflammation, fibroblast proliferation and apoptosis were both increased, suggesting that the clustering was not merely a result of proliferation, but also of fibroblast migration from nearby alveolar walls. Parabiosis experiments demonstrated that fibroblasts were not supplied from the circulation. Comprehensive gene expression analysis of freshly isolated fibroblasts revealed a detailed activation signature associated with fibrogenesis, including changes in genes responsible for migration and extracellular matrix construction. The Spp1 gene, which encodes osteopontin, was highly up-regulated and was an identifying characteristic of activated fibroblasts present at the sites of remodeling. Osteopontin may serve as a useful marker of profibrotic fibroblasts. These results provide insights into the cellular and molecular mechanisms underlying pulmonary fibrosis and provide a foundation for development of specific antifibrotic therapies. PMID:23886891

Tsukui, Tatsuya; Ueha, Satoshi; Abe, Jun; Hashimoto, Shin-Ichi; Shichino, Shigeyuki; Shimaoka, Takeshi; Shand, Francis H W; Arakawa, Yasuka; Oshima, Kenshiro; Hattori, Masahira; Inagaki, Yutaka; Tomura, Michio; Matsushima, Kouji

2013-07-22

315

Qualitative rather than quantitative changes are hallmarks of fibroblasts in bleomycin-induced pulmonary fibrosis.  

UK PubMed Central (United Kingdom)

Pulmonary fibrosis is characterized by accumulation of activated fibroblasts that produce excessive amounts of extracellular matrix components such as collagen type I. However, the dynamics and activation signatures of fibroblasts during fibrogenesis remain poorly understood, especially in vivo. We examined changes in lung tissue cell populations and in the phenotype of activated fibroblasts after acute injury in a model of bleomycin-induced pulmonary fibrosis. Despite clustering of collagen type I-producing fibroblasts in fibrotic regions, flow cytometry-based quantitative analysis of whole lungs revealed that the number of fibroblasts in the lungs remained constant. At the peak of inflammation, fibroblast proliferation and apoptosis were both increased, suggesting that the clustering was not merely a result of proliferation, but also of fibroblast migration from nearby alveolar walls. Parabiosis experiments demonstrated that fibroblasts were not supplied from the circulation. Comprehensive gene expression analysis of freshly isolated fibroblasts revealed a detailed activation signature associated with fibrogenesis, including changes in genes responsible for migration and extracellular matrix construction. The Spp1 gene, which encodes osteopontin, was highly up-regulated and was an identifying characteristic of activated fibroblasts present at the sites of remodeling. Osteopontin may serve as a useful marker of profibrotic fibroblasts. These results provide insights into the cellular and molecular mechanisms underlying pulmonary fibrosis and provide a foundation for development of specific antifibrotic therapies.

Tsukui T; Ueha S; Abe J; Hashimoto S; Shichino S; Shimaoka T; Shand FH; Arakawa Y; Oshima K; Hattori M; Inagaki Y; Tomura M; Matsushima K

2013-09-01

316

Internal parameters monitored during intraarterial cytostatic therapy with methotrexate and bleomycin combined with radiotherapy  

International Nuclear Information System (INIS)

Over a period of ten years, i.e., 1973 to 1983, the Vienna Clinic of Mandibular and Facial Surgery treated 109 patients with primary inoperable malignant tumors using regional chemotherapy, i.e., a combination of methotrexate and bleomycin. 95 patients in the groups were also irradiated. The aim of the internal examinations was to assess whether from the beginning of cytostatic therapy it would be possible to deduct from laboratory chemical examinations some prognostic factors, or whether changes in internal parameters during therapy correspond to the further development of the growth. The examination of chemical parameters showed that the permanently reduced levels of Fe and anemia are demonstrably adverse factors for prognosis. The drop in leukocyte and thrombocyte counts and the toxic damage of bone marrow also proved to be such an adverse factor. On the other hand the rise in serum levels of LDH, AST and ALT in the process of therapy may be assessed as favourable factors for the prognosis of the disease. (author). 1 fig., 12 refs

1988-01-01

317

Treatment of orbital venous malformations with intralesional injection of bleomycin lipiodol emulsion  

International Nuclear Information System (INIS)

Objective: To evaluate the efficacy and safety of intralesional injection with bleomycin lipiodol emulsion (BLE) for the treatment of orbital venous malformation (OVM). Methods: There were 15 cases with left- sided OVM (n=9 ) and right- sided OVM (n=6). All patients had proptosis. The pr optosis was less than 5 mm in 11 cases, >5 mm and ?8 mm in 4 cases. The mean value was 4.2 mm. Four patients noticed reduction in their vision and two had diplopia. Those patients were examined by CT or MR. Direct venography was performed in each patient. After the diagnosis of OVM was confirmed, intralesional injection of BLE was performed. The efficacy of the treatment and complications were observed during the following 8 to 42 months (mean 23 months). Results: The BLE were successfully injected in all the patients. All patients had resolution of proptosis and diplopia. Three patients gained improvement of visual acuity. The periorbital swelling occurred in all patients after operation and resolved within 1 week without special treatment. Other complications, such as orbital hemorrhage and periorbital scar, were not observed during following-up. Conclusion: Intralesional injection with BLE is convenient, safe and efficient for the treatment of OVM. (authors)

2007-01-01

318

Bleomycin DNA damage: Anomalous mobility of 3'-phosphoglycolate termini in an automated capillary DNA sequencer.  

UK PubMed Central (United Kingdom)

An automated capillary DNA sequencer with laser-induced fluorescence detection can be utilised for DNA fragment analysis. The precise mobilities of DNA fragments with different chemical termini are especially important in the determination of the sequence specificity of DNA damaging agents. The aim of this study was to examine the electrophoretic mobility profile of DNA fragments with different 3'-termini. The nature of the 3'-teminal residue was found to have a major effect on the electrophoretic mobility of the DNA fragment, especially for 3'-phosphoglycolate termini that migrated anomalously by 3-6 nucleotides. Using the automated capillary sequencer, the electrophoretic mobilities of DNA fragments with different 3'-termini including 3'-hydrogen, 3'-hydroxyl, 3'-phosphate, and 3'-phosphoglycolate were extensively quantified and compared relative to each other. The 3'-hydrogen termini were generated by dideoxy sequencing; 3'-hydroxyl ends by minus sequencing; 3'-phosphate by Maxam-Gilbert chemical sequencing; and 3'-phosphoglycolate by bleomycin cleavage. The mobilities of these DNA fragments with different 3'-termini were found to be: (slowest) 3'-hydroxyl<3'-hydrogen<3'-phosphate<3'-phosphoglycolate (fastest); with average relative mobilities of 0.00<0.12<0.63<4.42 nucleotides, respectively. The possible causes of the unusual electrophoretic mobility of the 3'-phosphoglycolate termini were discussed.

Nguyen TV; Chen JK; Murray V

2013-01-01

319

Cloning and characterization of the bleomycin biosynthetic gene cluster from Streptomyces verticillus ATCC15003.  

UK PubMed Central (United Kingdom)

Bleomycin (BLM) biosynthesis has been studied as a model for hybrid peptide-polyketide natural product biosynthesis. Cloning, sequencing, and biochemical characterization of the blm biosynthetic gene cluster from Streptomyces verticillus ATCC15003 revealed that (1) the BLM hybrid peptide-polyketide aglycon is assembled by the BLM megasynthetase that consists of both nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules; (2) BlmIX/BlmVIII/BlmVII constitute a natural hybrid NRPS/PKS/NRPS system, serving as a model for both hybrid NRPS/PKS and PKS/NRPS systems; (3) the catalytic sites appear to be conserved in both hybrid NRPS/PKS and nonhybrid NRPS or PKS systems, with the exception of the KS domains in the hybrid NRPS/PKS systems that are unique; (4) specific interpolypeptide linkers may play a critical role in intermodular communication to facilitate the transfer of the growing intermediates between the interacting NRPS and/or PKS modules; (5) post-translational modification of the BLM megasynthetase has been accomplished by a single PPTase with broad carrier protein specificity; and (6) BlmIV/BlmIII-templated assembly of the BLM bithiazole moiety requires intriguing protein juxtaposition and modular recognition. These results lay the foundation to investigate the molecular basis for intermodular communication between NRPS and PKS in hybrid peptide-polyketide natural product biosynthesis and set the stage for engineering novel BLM analogues by genetic manipulation of genes governing BLM biosynthesis.

Shen B; Du L; Sanchez C; Edwards DJ; Chen M; Murrell JM

2002-03-01

320

Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69-/-) mice. Methods The mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi). Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor ?1 (TGF-?1) in the lungs of BLM-treated mice. Results CD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1) loss of body weight, (2) wet/dry ratio of lung, (3) cytokine levels in BALF, (4) histological evidence of lung injury, (5) lung collagen deposition, and (6) TGF-?1 mRNA expression in the lung. Conclusion The present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM.

Yamauchi Keita; Kasuya Yoshitoshi; Kuroda Fuminobu; Tanaka Kensuke; Tsuyusaki Junichi; Ishizaki Shunsuke; Matsunaga Hirofumi; Iwamura Chiaki; Nakayama Toshinori; Tatsumi Koichiro

2011-01-01

 
 
 
 
321

The Singapore protocol  

International Nuclear Information System (INIS)

Full text: We present a new qubit protocol for quantum key distribution which exploits the potential of minimal state tomography and proves to be more efficient than other tomographic protocols. Under ideal circumstances the efficiency is 0.415 key-bits per qubit sent 25 % higher than the efficiency of 0.333 for the standard 6-state protocol of BB84 type. We describe a simple two-way communication scheme that extracts 0.4 key bits per qubit and thus gets close to the information theoretical limit and report noise thresholds for secure key bit generation in the presence of unbiased noise under various eavesdropping attacks. (author)

2005-01-01

322

CTEP & CC Protocols - Credit Report  

Science.gov (United States)

CTEP & CC Protocols - Credit Report Community Clinical Oncology Program Research Base Protocol Credit Assignment Approved, Active, and Closed Protocols Research Base Cancer Trials Support Unit (CTSU) qry_Credit_Report_Output_HTML_CTSU

323

SIP: Session Initiation Protocol  

UK PubMed Central (United Kingdom)

The Session Initiation Protocol (SIP) is an application-layer control (signaling) protocol for creating,modifying and terminating sessions with one or more participants. These sessions include Internetmultimedia conferences, Internet telephone calls and multimedia distribution. Members in a session cancommunicate via multicast or via a mesh of unicast relations, or a combination of these.SIP invitations used to create sessions carry session descriptions which allow participants to agreeon a set of compatible media types. SIP supports user mobility by proxying and redirecting requeststo the user's current location. Users can register their current location. SIP is not tied to any particularconference control protocol. SIP is designed to be independent of the lower-layer transport protocol andcan be extended with additional capabilities.Contents1

324

SIP: Session Initiation Protocol  

UK PubMed Central (United Kingdom)

The Session Initiation Protocol (SIP) is an application-layer control (signaling) protocol for creating,modifying and terminating sessions with one or more participants. These sessions include Internetmultimedia conferences, Internet telephone calls and multimedia distribution. Members in a session cancommunicate via multicast or via a mesh of unicast relations, or a combination of these.SIP invitations used to create sessions carry session descriptions which allow participants to agreeon a set of compatible media types. SIP supports user mobility by proxying and redirecting requeststo the user's current location. Users can register their current location. SIP is not tied to any particularconference control protocol. SIP is designed to be independent of the lower-layer transport protocol andcan be extended with additional capabilities.Contents1 Introduction 71.1 Overview of SIP Functionality . . ............................... 71.2 Terminology.......................

325

Wireless Token Ring Protocol  

UK PubMed Central (United Kingdom)

The Wireless Token Ring Protocol (WTRP) is a medium access control protocol for wireless networks in Unmanned Aerial Vehicles. It supports quality of service in terms of bounded latency and reserved bandwidth. This quality of service guarantee is critical in mesh stability of the formation of the vehicles. The communication of the speed and the velocity of the lead vehicle to all other vehicles in the formation had been shown to be sufficient for mesh stability of the system.

Mustafa Ergen; Duke Lee; Anuj Puri; Pravin Varaiya; Roberto Attias; Raja Sengupta; Stavros Tripakis

326

Upgrading Transport Protocols using  

UK PubMed Central (United Kingdom)

In this paper, we present STP, a system in which communicatingend hosts use untrusted mobile code to remotely upgrade eachother with the transport protocols that they use to communicate.New transport protocols are written in a type-safe version of C,distributed out-of-band, and run in-kernel. Communicating peersselect a transport protocol to use as part of a TCP-like connectionsetup handshake that is backwards-compatible with TCP and incursminimum connection setup latency. New transports can beinvoked by unmodified applications. By providing a late bindingof protocols to hosts, STP removes many of the delays and constraintsthat are otherwise commonplace when upgrading the transportprotocols deployed on the Internet. STP is simultaneously ableto provide a high level of security and performance. It allows eachhost to protect itself from untrusted transport code and to ensurethat this code does not harm other network users by sending significantlyfaster than a compliant TCP. It runs untrusted code withlow enough overhead that new transport protocols can sustain neargigabit rates on commodity hardware. We believe that these properties,plus compatibility with existing applications and transports,complete the features that are needed to make STP useful in practice.Categories and Subject DescriptorsD.4.4 [Operating Systems]: Communications Management; D.4.6[Operating Systems]: Security and Protection; C.2.2 [NetworkProtocols]: Protocol architectureGeneral TermsDesign, Implementation, DeploymentKeywordsTransport Protocols, TCP-friendliness, Untrusted Mobile CodePermission to make digital or hard copies of all or part of this work forpersonal or classroom use is granted without fee provided that copies arenot made or distributed for profit or ...

Parveen Patel; Andrew Whitaker; David Wetherall; Jay Lepreau; Tim Stack

327

The effects of combined radiation and bleomycin therapy on the cervical lymph nodes metastasized with oral cancer  

International Nuclear Information System (INIS)

Effects of the concomitantly combined therapy of radiation and Bleomycin (60Co : 22.5 Gy and Bleomycin : 110 mg, i.m.) on the metastatic lymph nodes of cervical region in carcinoma of the oral cavity were examined histologically. The specimens studied were 44 metastatic lymph nodes obtained from 19 patients. Thirty six of the 44 metastatic lymph nodes were within irradiated field and they could be classified by Shimosato's grading system into 5 as Grade IV (no tumor cells remain), 11 as Grade III (non viable tumor cells only remain), 8 as Grade IIb (viable cells are few in number), 6 as Grade IIa (destruction of tumor structure is mild) and 6 as Grade I, 0 (no effects). Marked effects were noted in 16 lymph nodes (44.4 %) out of 36 irradiated metastatic lymph nodes, but there were no observable effects on the 8 lymph nodes which had not been included in the irradiated field. Marked effects were selectively in the superior internal jugular nodes, while the effect on the submandibular nodes was poor. Although the therapeutic potentiality was not affected by the size of the lymph nodes, histological features of the large metastatic nodes were not uniform but various in degenerative changes of the tumor cells within the same metastatic focus. The effectiveness of this combined therapy on the primary lesion and the metastatic foci, as evaluated by the histological examination, was almost parallel. Radiation dose of the present combination therapy in 50 % tumor disappearance rate was 7.7 Gy less than that of the radiation only. Accordingly, it was considered that the effect of one course of this combination therapy with 60Co 22.5 Gy and Bleomycin 110 mg on the metastatic lymph nodes corresponded to 60Co 30 Gy of single irradiation. (author).

1986-01-01

328

Effect of antiserotonin drug on the development of lung fibrosis and blood system reactions after intratracheal administration of bleomycin.  

UK PubMed Central (United Kingdom)

The effects of antiserotonin preparation on the development of the connective tissue in the lungs, reaction of the blood system, and the content of hemopoietic stem cells, committed hemopoietic and stromal precursors in BM, spleen, and peripheral blood were studied on C57Bl/6 mice with experimental toxic lung fibrosis caused by intratracheal administration of bleomycin. It was demonstrated that the antiserotonin drug inhibits the growth of the connective tissue in the lungs and attenuates the course inflammatory process primarily due to inhibition of the granulocytic lineage, which was related to suppression of hemopoietic stem cells. Reduced content of the stromal precursor cells in BM and spleen was noted.

Skurikhin EG; Andreeva TV; Khmelevskaya ES; Ermolaeva LA; Pershina OV; Krupin VA; Ermakova NN; Reztsova AM; Stepanova IE; Gol'dberg VE; Dygai AM

2012-02-01

329

Effect of nordihydroguaiaretic acid and ibuprofen on bleomycin and hyperoxia-induced changes in lung superoxide dismutase, prostaglandins and lethality.  

UK PubMed Central (United Kingdom)

Mortality in hamsters injected intratracheally with bleomycin (bleo) (0.25 units) and exposed to 70% oxygen is significantly increased over 14 days when they receive nordihydroguaiaretic acid (NDGA, 10 mg/kg per day S.C.). Mortality in bleo +O2 challenged hamsters treated with ibuprofen (10 mg/kg per day) subcutaneously was not significantly increased. The increased mortality in NDGA treated animals is not the result of augmented superoxide formation, since no change in lung superoxide dismutase occurred. Among the prostaglandins measured, NDGA produced the greatest elevation in 6-keto-PGF1 alpha (stable product of prostacyclin) and thromboxane B2 (stable product of thromboxane A2).

Giri SN; Hollinger MA

1996-01-01

330

Induction of micronuclei by bleomycin in G[sub 0] human lymphocytes: 1. Dose-response and distribution  

Energy Technology Data Exchange (ETDEWEB)

The cytokinesis-block, micronucleus assay was used to investigate the induction of chromosomal damage by bleomycin in G[sub 0] human lymphocytes. A dose-dependent increase in the frequency of micronuclei was observed in binucleate cells, and the frequency approached 0.5 micronuclei per cell at the highest dosage tested. The distribution of micronuclei among cells was overdispersed, rather than fitting a Poisson distribution. Even at the highest dosage, more than two-thirds of the cells did not contain micronuclei, while some cells were highly damaged, containing more than 4 micronuclei per cell. 32 refs., 4 tabs.

Hoffmann, G.R.; Colyer, S.P.; Littlefield, L.G. (Oak Ridge Associated Universities, TN (United States))

1993-01-01

331

Preventive and therapeutic effects of physical exercise on bleomycin-induced lung injury and oxidative stress  

Directory of Open Access Journals (Sweden)

Full Text Available Studies have shown that regular physical exercise of moderate intensity is an important tool for the control of pulmonary oxidative stress. The objective of this study was to examine the preventive and therapeutic effect of physical exercise on oxidative stress in the lungs of mice exposed to bleomycin (BLM). Thirty-six male mice (CF1, 30-35 g) received a single endotracheal dose of BLM (2.5 U/kg body weight dissolved in 0.25 mL 0.9% NaCl) or saline (0.9% NaCl) and were divided into six groups (n=6): untrained saline or BLM, preventive training saline or BLM, and therapeutic training saline or BLM. The trained groups underwent a program of progressive exercise on a treadmill for 8 weeks (up to 17 m.min-1, 50 min.day-1). The preventive group started the exercise program 62 days before the administration of BLM and the therapeutic group 62 days after the administration of BLM. All animals were killed by decapitation 48 hours after the experimental period, and the right lung was surgically removed for the determination of biochemical parameters. Hydroxyproline content, TBARS level, protein carbonylation, and superoxide dismutase (SOD) and catalase (CAT) activities were analyzed. The results showed that preventive and therapeutic training led to a significant reduction in hydroxyproline content and inhibited the increase in oxidative damage to lipids and proteins. However, only therapeutic training decreased SOD and CAT activities in mice exposed to BLM. The results suggest that preventive and therapeutic physical exercise is able to minimize pulmonary oxidative stress induced by BLM.

Ricardo Aurino Pinho; Fernanda Schuveitzer Soares; Luís Gustavo Rocha; Cleber Aurino Pinho; Luciano Acordi da Silva las Acordi; Paulo César Look da Silveira

2009-01-01

332

Uptake of /sup 67/Ga in the lung of mice during bleomycin treatment  

Energy Technology Data Exchange (ETDEWEB)

Changes of /sup 67/Ga uptake in the lungs and changes of components of the so-called ground substance of the lung connective tissues of mice were followed for 7 weeks after the start of bleomycin (BLM) administration (20 mg/kg body weight IP, twice weekly for 5 weeks; this treatment induced fibrosis of the lung). /sup 67/Ga uptake of the lung was elevated at 1 week, and reached a maximum at 5 weeks (3.00+-0.11% dose/g lung), and then decreased slightly at 7 weeks. The uronic acid content in the 1.2 M NaCl-soluble fraction, which contained predominantly heparan sulfate (HS), was increased at 1 week, peaked at 3 weeks, and then remained unchanged up to 7 weeks. This pattern was similar to that of /sup 67/Ca acumulation in the lungs. The uronic acid content of the 0.4 M NaCl-fraction, which contained predominantly hyaluronic acid (HA), was decreased at 1 week, but increased to a maximum at 3 weeks, then decreased to about the initial level at 5 weeks and decreased further at 7 weeks. Lung hydroxyproline content, an index of collagen content, was increased at 3 weeks and continued to increase rapidly thereafter, reaching approximately 1.5 times the control value at 7 weeks. Serum, iron, measured as an indicator of iron metabolism, was slightly increased at 3 weeks and there was corresponding decrease of unsaturated iron-binding capacity (UIBC). No corresponding change of /sup 67/Ga uptake was apparent. These results indicate that HS increased before the collagen accumulation at an early stage of pulmonary fibrosis of the lung during BLM treatment of mice, and support our earlier proposal that HS is a major acceptor for /sup 67/Ga accumulation.

Sasaki, T.; Kohima, S.; Kubodera, A.

1984-02-01

333

Indium-111 bleomycin complex for radiochemotherapy of head and neck cancer - dosimetric and biokinetic aspects  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin (BLM) is used for the treatment of head and neck cancer. In order to improve the effectiveness of this chemotherapeutic drug, BLM was combined with indium-111. A complex of these agents ({sup 111}In-BLMC), formed at low pH, was injected intravenously into ten head and neck cancer patients in escalating activities of 75, 175 and 375 MBq. The internally delivered dose to the tumours varied from 0.20 to 2.73 mGy at 75 MBq, from 0.33 to 2.51 mGy at 175 MBq, and from 0.87 to 31.3 mGy at the 375 MBq activity level. Uptake of radioactivity was 0.45{+-}0.24x10{sup -3}% ID/g in primary tumours and 0.52{+-}0.20x10{sup -3}% ID/g in metastases (at 48 h). Tumour volumes varied from 0.51 to 49.0 cm{sup -3}. The radioactivity half-lives in the tumours were 30{+-}7 h. The activity distribution and penetration into tumour tissue were not affected by increasing the injected activity. There was a positive correlation between BLMC uptake and Ki-67/Mib activity as well as number of mitoses in tumour tissue. These data indicate that {sup 111}In-BLMC has potential as a radiochemotherapeutic agent in head and neck cancer and that adjuvant Auger-electron therapy is possible using {sup 114m}In-labelled BLMC. (orig.)

Kairemo, K.J.A. [Dept. of Clinical Chemistry, Univ. Central Hospital of Helsinki (Finland)]|[Dept. of Oncology, Univ. Central Hospital of Helsinki (Finland); Ramsay, H.A. [Dept. of Otorhinolaryngology, Univ. Central Hospital of Helsinki (Finland); Tagesson, M. [Dept. of Physics, Lund Univ. (Sweden); Jekunen, A.P. [Dept. of Oncology, Univ. Central Hospital of Helsinki (Finland); Paavonen, T.K. [Dept. of Pathology, Helsinki Univ. (Finland); Jaeaeskelae-Saari, H.A. [Dept. of Otorhinolaryngology, Univ. Central Hospital of Helsinki (Finland); Liewendahl, K. [Dept. of Clinical Chemistry, Univ. Central Hospital of Helsinki (Finland); Ljunggren, K. [Dept. of Radiation Physics, Lund Univ. (Sweden); Savolainen, S. [Dept. of Physics, Lund Univ. (Sweden); Strand, S.E. [Dept. of Radiation Physics, Lund Univ. (Sweden)

1996-06-01

334

Lung Inflammation and Thymic Atrophy After Bleomycin are Controlled by the PGD2 Receptor DP1.  

UK PubMed Central (United Kingdom)

Acute lung injury (ALI) can be accompanied by secondary systemic manifestations. In a model of ALI induced by bleomycin (bleo), we examined the response of D prostanoid receptor 1 (DP1) deficient mice (DP1-/-) to better understand these processes. DP1 deficiency aggravated the toxicity of bleo as indicated by enhanced body weight loss, mortality and lung inflammation including bronchoalveolar permeability and neutrophilia. Thymic atrophy was also observed after bleo and was strongly exacerbated in DP1-/- mice. This resulted from the enhanced depletion of immature T lymphocytes in the thymus of deficient mice, a phenomenon usually related to increased glucocorticoid release in blood. Serum corticosterone was more elevated in DP1-/- mice after bleo than in wt. Thymocytes of DP1-/- mice were not more sensitive to dexamethasone (dex) in vitro and systemic delivery of dex or peritoneal inflammation after LPS induced a similar thymic atrophy in wt and DP1-/-, indicating that pulmonary DP1 was critical to control thymic atrophy after bleo. DP1 deficient mice showed increased lung and/or blood mediators involved in neutrophil recruitment and/or glucocorticoid production/thymic atrophy (osteopontin, leukemia inhibitory factor and keratinocyte-derived chemokine) after bleo. Finally, local pulmonary DP1 activation or inhibition in wt mice abrogated or amplified thymic atrophy after bleo, respectively. Altogether, our data reveal that ALI can perturb the systemic T cell pool by inducing thymic atrophy and that both pathological processes are controlled by the pulmonary DP1 receptor. This new pathway represents a potential therapeutic target in ALI.

van den Brule S; Huaux F; Uwambayinema F; Ibouraadaten S; Yakoub Y; Palmai-Pallag M; Trottein F; Renauld JC; Lison D

2013-09-01

335

Ultrastructural changes of human esophageal carcinoma induced by preoperative treatments with bleomycin and/or radiation  

Energy Technology Data Exchange (ETDEWEB)

In the present study, 44 cases of esophageal carcinoma were electron-microscopically examined. Nuclear bodies of various types observed in carcinoma cells or in normal mucosa of the esophagus treated by bleomycin and radiation, single or combined (BLM/R), were classified into seven types. Types A and B were observed in carcinoma cells of both conditions of untreated or treated with BLM/R. Types C, D and E were specific findings in squamous carcinoma cells after BLM/R treatment. Types F and G were considered to be far advanced in terms of other nuclear bodies and were observed in strongly affected carcinoma cells. These nucleolar changes were considered to be specific alterations induced by BLM in esophageal carcinoma cells. The appearance of various nuclear bodies and a series of nucleolar segregation after BLM/R treatments were confirmed as well in metastatic lesions of abdominal lymph nodes that may be affected only with minimal or disregardable scattered radiation, if any, giving no sifnificant influence to cell activity. This fact has suggested that types C, D and E nuclear bodies and nucleolar segregation are changes specific to BLM/R treatments, some solely to BLM. Other nuclear changes consisted in the appearance of fibrillar structures of three different types that were considered to have been produced by disturbed ribosomal activity in the nuclei. On the basis of results in the present study, BLM apparently showed serious evidence of remarkable influences or effects, although not constantly and generally available, on certain squamous carcinoma cells of the esophagus. Some of the evidence was represented by nucleolar segregation and characteristic nuclear bodies of different types, particularly of types C, D and E.

Kohro, T. (Niigata Univ. (Japan). School of Medicine)

1982-01-01

336

Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats.  

UK PubMed Central (United Kingdom)

BACKGROUND: Recent evidence has demonstrated the role of angiogenesis in the pathogenesis of pulmonary fibrosis. Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis. The aim of our study was to assess whether endostatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in rats. METHODS: The rats were randomly divided into five experimental groups: (A) saline only, (B) BLM only, (C) BLM plus early endostatin treatment, (D) BLM plus late endostatin treatment, and (F) BLM plus whole-course endostatin treatment. We investigated the microvascular density (MVD), inflammatory response and alveolar epithelial cell apoptosis in rat lungs in each group at different phases of disease development. RESULTS: Early endostatin administration attenuated fibrotic changes in BLM-induced pulmonary fibrosis in rats. Endostatin treatment decreased MVD by inhibiting the expression of VEGF/VEGFR-2 (Flk-1) and the activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). Endostatin treatment also decreased the number of inflammatory cells infiltrating the bronchoalveolar lavage fluid during the early inflammatory phase of BLM-induced pulmonary fibrosis. In addition, the levels of tumour necrosis factor-? (TNF-?) and transforming growth factor ?1 (TGF-?1) were reduced by endostatin treatment. Furthermore, endostatin decreased alveolar type II cell apoptosis and had an epithelium-protective effect. These might be the mechanism underlying the preventive effect of endostatin on pulmonary fibrosis. CONCLUSIONS: Our findings suggest that endostatin treatment inhibits the increased MVD, inflammation and alveolar epithelial cell apoptosis, consequently ameliorating BLM-induced pulmonary fibrosis in rats.

Wan YY; Tian GY; Guo HS; Kang YM; Yao ZH; Li XL; Liu QH; Lin DJ

2013-01-01

337

Bleomycin-induced alterations in DNA replication: relationship to DNA damage.  

UK PubMed Central (United Kingdom)

Bleomycin (BLM), a well-known DNA scission agent, is assumed to inhibit intracellular DNA replication by damaging the DNA template (cis-acting mechanism), although other DNA damaging compounds can alter DNA replication through modulation of crucial replication factor(s) (trans-acting mechanism). The present study examines the relationship between DNA damage and inhibition of replication caused by BLM in the well-defined simian virus 40 (SV40) intracellular and cell-free in vitro systems. Treatment of SV40-infected BSC-1 cells for 2 h with BLM at 50 microg/mL, induced 0.3 break/viral genome. Under the same treatment conditions, analysis of replication intermediates on two-dimensional gels showed a decrease in both mass of SV40 replication intermediates and replication activity. The mass of SV40 intermediates was decreased to about 30%, whereas replication activity was reduced to less than 5%. These results suggest that BLM inhibits both initiation and elongation phases of SV40 replication. In a cell-free DNA replication system, extracts from BLM-treated cells (50 micro/mL) were able to support SV40 DNA replication by only 50%. In this study, non-drug-treated DNA template was used, implying that BLM can induce a trans-acting effect. Finally, the drug-induced effects on SV40 DNA replication in cell-free and intracellular viral systems were compared to the effects on genomic DNA replication in BSC-1 cells. Overall, the results support the concept that BLM-induced inhibition of DNA replication occurs by both trans- (inhibition of replication of nondamaged template) and cis-acting mechanisms (template damage).

Dziegielewski J; Melendy T; Beerman TA

2001-01-01

338

Bleomycin-induced alterations in DNA replication: relationship to DNA damage.  

Science.gov (United States)

Bleomycin (BLM), a well-known DNA scission agent, is assumed to inhibit intracellular DNA replication by damaging the DNA template (cis-acting mechanism), although other DNA damaging compounds can alter DNA replication through modulation of crucial replication factor(s) (trans-acting mechanism). The present study examines the relationship between DNA damage and inhibition of replication caused by BLM in the well-defined simian virus 40 (SV40) intracellular and cell-free in vitro systems. Treatment of SV40-infected BSC-1 cells for 2 h with BLM at 50 microg/mL, induced 0.3 break/viral genome. Under the same treatment conditions, analysis of replication intermediates on two-dimensional gels showed a decrease in both mass of SV40 replication intermediates and replication activity. The mass of SV40 intermediates was decreased to about 30%, whereas replication activity was reduced to less than 5%. These results suggest that BLM inhibits both initiation and elongation phases of SV40 replication. In a cell-free DNA replication system, extracts from BLM-treated cells (50 micro/mL) were able to support SV40 DNA replication by only 50%. In this study, non-drug-treated DNA template was used, implying that BLM can induce a trans-acting effect. Finally, the drug-induced effects on SV40 DNA replication in cell-free and intracellular viral systems were compared to the effects on genomic DNA replication in BSC-1 cells. Overall, the results support the concept that BLM-induced inhibition of DNA replication occurs by both trans- (inhibition of replication of nondamaged template) and cis-acting mechanisms (template damage). PMID:11170387

Dziegielewski, J; Melendy, T; Beerman, T A

2001-01-23

339

The DNA cleavage pathway of iron bleomycin. Strand scission precedes deoxyribose 3-phosphate bond cleavage.  

UK PubMed Central (United Kingdom)

DNA strand scission initiated by bleomycin is a multistep process. Three C-C or C-O bonds are broken, releasing base propenal, a nucleic base derivative with deoxyribose carbons 1-3. Either C-3'-(phosphate-O) cleavage or C-3'-C-4' plus C-1'-(ring-O) bond cleavages could cause strand cleavage. To determine the sequence of bond breakage, d(CAAGCTTG) duplex was examined for rates of 1) strand scission, monitored by the hyperchromicity of cleavage-induced denaturation; 2) base propenal formation, monitored by 1H NMR spectroscopy; 3) 5'-terminal phosphomonoester formation, monitored by 31P NMR spectroscopy. Strand scission occurred with t 1/2 = 4.1 +/- 0.5 min at 4 degrees C, faster than base propenal formation (t 1/2 = 6.7 +/- 0.3 min). Thus newly cleaved DNA includes a base propenal precursor (t 1/2 = 2-3 min). The 5'-phosphate terminus forms (t 1/2 = 7.4 +/- 0.8 min) concurrently with base propenal. Since strand scission precedes phosphomonoester formation, strand scission cannot arise from C-3'-(phosphate-O) cleavage. Instead, the base propenal precursor must be linked to the future 5'-phosphate terminus, with strand scission arising from a combination of C-3'-C-4' and C-1'-(ring-O) bond cleavages. These results provide experimental support for a recently proposed mechanism that accommodates an early oxygen attack at C-4' and 2'-deprotonation without requiring simultaneous strand scission and 5'-phosphate terminus formation.

Burger RM; Drlica K; Birdsall B

1994-10-01

340

The counter regulatory response induced by CpG oligonucleotides prevents bleomycin induced pneumopathy.  

UK PubMed Central (United Kingdom)

Bleomycin (BLM) induces life-threatening pneumonitis and pulmonary fibrosis in 20% of patients, limiting its use as a chemotherapeutic agent. Oligonucleotides expressing immunostimulatory CpG motifs (CpG ODN) stimulate cells that express Toll-like receptor 9 to initiate an inflammatory response. This short-lived inflammation is physiologically suppressed by a counter-regulatory process that peaks five days later. Using a murine model of BLM-induced lung injury, the effect of CpG ODN treatment on pulmonary inflammation, fibrosis and mortality was examined. Administering CpG ODN 5?days before BLM (so that the peak of the counter-regulatory process induced by CpG ODN coincided with BLM delivery) resulted in a dose-dependent reduction in pulmonary toxicity (p?

Kinjo T; Tomaru K; Haines DC; Klinman DM

2012-01-01

 
 
 
 
341

T regulatory cells and attenuated bleomycin-induced fibrosis in lungs of CCR7-/- mice  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background C-C chemokine receptor (CCR)7 is a regulator of dendritic cell and T cell migration, and its role in tissue wound healing has been investigated in various disease models. We have previously demonstrated that CCR7 and its ligand, chemokine (C-C motif) ligand (CCL)21, modulates wound repair in pulmonary fibrosis (PF) but the mechanism of this is unknown. The objective of this study was to investigate whether the absence of CCR7 protects against bleomycin (BLM)-induced PF. CCR7-/- mice failed to mount a fibrotic pulmonary response as assessed by histologic collagen staining and quantification by hydroxyproline. We hypothesized that the prominent characteristics of CCR7-/- mice, including elevated levels of cytokine and chemokine mediators and the presence of bronchus-associated lymphoid tissue (BALT) might be relevant to the protective phenotype. Results Pulmonary fibrosis was induced in CCR7+/+ and CCR7-/- mice via a single intratracheal injection of BLM. We found that the lung cytokine/chemokine milieu associated with the absence of CCR7 correlated with an increase in BALT, and might be attributable to regulatory T cell (Treg) homeostasis and trafficking within the lungs and lymph nodes. In response to BLM challenge, CCR7-/- mice exhibited an early, steady increase in lung CD4+ T cells and increased CD4+ CD25+ FoxP3+ Tregs in the lungs 21 days after challenge. These findings are consistent with increased lung expression of interleukin-2 and indoleamine 2,3-dioxygenase in CCR7-/- mice, which promote Treg expansion. Conclusions Our study demonstrates that the protective phenotype associated with BLM-treated CCR7-/- mice correlates with the presence of BALT and the anchoring of Tregs in the lungs of CCR7-/- mice. These data provide novel evidence to support the further investigation of CCR7-mediated Treg trafficking in the modulation of BLM-induced PF.

Trujillo Glenda; Hartigan Adam J; Hogaboam Cory M

2010-01-01

342

Debunking myths of protocol registration  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Developing and registering protocols may seem like an added burden to systematic review investigators. This paper discusses benefits of protocol registration and debunks common misperceptions on the barriers of protocol registration. Protocol registration is easy to do, reduces duplication of effort and benefits the review team by preventing later confusion.

Chang Stephanie M; Slutsky Jean

2012-01-01

343

Optimal Protocols for Nonlocality Distillation  

CERN Multimedia

Forster, Winkler, and Wolf recently showed that weak nonlocality can be amplified by giving the first protocol that distills a class of nonlocal boxes (NLBs) [Phys. Rev. Lett. 102, 120401 (2009)]. We first show that their protocol is optimal among all non-adaptive protocols. We next consider adaptive protocols. We show that the depth 2 protocol of Allcock et al. [Phys. Rev. A 80, 062107, (2009)] performs better than previously known adaptive depth 2 protocols for all symmetric NLBs. We present a new depth 3 protocol that extends the known region of distillable NLBs. We give examples of NLBs for which each of Forster et al.'s, Allcock et al.'s, and our protocol performs best. The new understanding we develop is that there is no single optimal protocol for NLB distillation. The choice of which protocol to use depends on the noise parameters for the NLB.

Hoyer, Peter

2010-01-01

344

Failure of mechanical properties to parallel changes in lung connective tissue composition in bleomycin-induced pulmonary fibrosis in hamsters.  

UK PubMed Central (United Kingdom)

Lung volumes and volume pressure (V-P) relationships were measured in anesthetized hamsters 8, 30, 60, and 90 days after induction of interstitial pulmonary fibrosis by intratracheal administration of bleomycin. Subsequently, total collagen, elastin, protein, deoxyribonucleic acid (DNA), and dry weight were determined in the lungs of each animal. The mean volume of air in the lungs at a transpulmonary pressure of 25 cm H2O and mean quasi-static compliance were decreased at 8 and 30 days and had returned toward normal by 60 and 90 days. Dry lung weight and total protein content were increased at 8 days, peaked at 30 days, and were still greater than normal at 90 days; DNA peaked at 8 days, remained unchanged through day 60, and returned to normal by day 90. Collagen and elastin content, although not significantly different from control at day 8, was increased at day 30 with peak values attained at day 90. Ratios of collagen or elastin to dry weight, total protein, and DNA were decreased at 8 days, normal at 30 days, and increased at 90 days. The ratios of collagen or elastin to total protein, dry lung weight, or DNA cannot be used as indicators of the amounts of these proteins in the whole lung. We conclude that in interstitial pulmonary fibrosis induced with bleomycin the pattern of changing biochemical composition of the lungs cannot be inferred from the lung volumes or V-P relations.

Goldstein RH; Lucey EC; Franzblau C; Snider GL

1979-07-01

345

Genotoxicity testing of combined treatment with cisplatin, bleomycin, and 5-fluorouracil in somatic cells of Drosophila melanogaster.  

Science.gov (United States)

The simultaneous treatment with the cross-linking agent cisplatin, the radiomimetic antitumoral drug bleomycin, and the anti-metabolite drug 5-fluorouracil has been used as a regimen to treat patients with squamous cell carcinoma of the head and neck. Considering that these drugs interact directly with DNA, one of the important late-occurring complications from treatment of primary malignancies is the therapy-related secondary cancers as a result of the genotoxic activity of the drugs on normal cells. In this sense, the genotoxicity of this combination was evaluated using the wing somatic mutation and recombination test in Drosophila melanogaster. The mutant spots observed in marker-heterozygous and balancer-heterozygous flies were compared in order to quantitatively and qualitatively estimate the genotoxic effect of these drugs. Cisplatin (0.003 and 0.006mM), bleomycin (0.005 and 0.01mM), and both combinations preferentially induced recombinational events, while mutation is the major event regarding the genetic toxicity of 5-fluorouracil (0.025 and 0.05mM). The combination of these drugs produced synergistic and antagonistic genotoxic effects, depending on the concentrations used, which could impose a higher risk of secondary effects associated with their genotoxic effects, emphasizing the importance of long-term monitoring in patients being treated with these drugs. PMID:22640881

Danesi, Cristiane Cademartori; Dihl, Rafael Rodrigues; Bellagamba, Bruno Corrêa; de Andrade, Heloísa Helena Rodrigues; Cunha, Kênya Silva; Guimarães, Nilza Nascimento; Lehmann, Mauricio

2012-05-26

346

Definition of the intermediates and mechanism of the anticancer drug bleomycin using nuclear resonance vibrational spectroscopy and related methods.  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin (BLM) is a glycopeptide anticancer drug capable of effecting single- and double-strand DNA cleavage. The last detectable intermediate prior to DNA cleavage is a low spin Fe{sup III} peroxy level species, termed activated bleomycin (ABLM). DNA strand scission is initiated through the abstraction of the C-4{prime} hydrogen atom of the deoxyribose sugar unit. Nuclear resonance vibrational spectroscopy (NRVS) aided by extended X-ray absorption fine structure spectroscopy and density functional theory (DFT) calculations are applied to define the natures of Fe{sup III}BLM and ABLM as (BLM)Fe{sup III}-OH and (BLM)Fe{sup III}({eta}{sup 1}-OOH) species, respectively. The NRVS spectra of Fe{sup III}BLM and ABLM are strikingly different because in ABLM the {delta}Fe-O-O bending mode mixes with, and energetically splits, the doubly degenerate, intense O-Fe-N{sub ax} transaxial bends. DFT calculations of the reaction of ABLM with DNA, based on the species defined by the NRVS data, show that the direct H-atom abstraction by ABLM is thermodynamically favored over other proposed reaction pathways.

Liu, L. V.; Bell, C. B., III; Wong, S. D.; Wilson, S. A.; Kwak, Y.; Chow, M.S.; Zhao, J.; Hodgson, K.O.; Hedman, B.; Solomon, E.I. (X-Ray Science Division); (Stanford Univ.); (SLAC)

2010-12-28

347

The Sprague Dawley rats as biomodel in the induction of micronuclei in bone marrow cells by cyclophosphamide and bleomycin  

Directory of Open Access Journals (Sweden)

Full Text Available The micronuclei assay in bone marrow is easily to reproduce and its offer clear information on the cellular proliferation in bone marrow. This system allow registering in vivo the capacity of the chemical substances to induce chromosomics ruptures to interfere or the chromosomes metaphases migration during the mitosis of the somatic cells. In this article wedecide to evaluate the Sprague Dawley rats in both sexes as biomodel in the induction of micronuclei in bone marrow cells by cyclophosphamide and bleomycin. Which were formed 5 experimental groups per sex, the first administered with NaCl 0,9 % by intraperitoneal (i.p) route, the second and third groups were administered with cyclophosphamide by i.p route,with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at doses of 40 mg/kg. At the end of the experience obtained higher results of the micronucleis inductions with the use of cyclophosphamide was administered 48 and 24 hours beforesacrifice in SD rats of both sexes. That which constitutes in our experimental conditions the best experimental design to induce the micronucleis formation in bone marrow cells of rodents, increasing considerably the spontaneous frequency to present in this species of rat, useful in evaluation studies on in vivo antigenotoxic drugs effects.

Daniel Francisco Arencibia Arrebola; Luis Alfredo Rosario Fernández

2010-01-01

348

Interest of Co57 labelled bleomycin in assessment of local and regional dissemination carcinoma of the lung  

International Nuclear Information System (INIS)

[en] 165 cases of lung carcinoma were studied with signs on radio-isotope scanning, either of local or regional spread (81 cases) or relapse after treatment (13 cases), or metastases (90 cases). A scan using Co57 labelled bleomycin permitted the discovery: in almost 50% of cases, of mediastinal spread, and in 33% of cases, spread to the clavicular lymph nodes, unnoticed on clinical examination; in 7 cases out of 13, relapse after surgery; in 3 cases, in the presence of clinical metastases, primary lung tumour; 67 metastatic lesions[fr] 165 cancers du poumon ont ete etudies. presentant des signes scintigraphiques soit d'extension loco-regionale (81 cas), soit de recidive apres traitement (13 cas), soit de metastases (90 cas). La scintigraphie a la bleomycine marquee (Co57) a permis de decouvrir: dans presque la moitie des cas, une atteinte mediastinale et, dans un tiers des cas, une extension sus-claviculaire, passees inapercues; 7 fois sur 13, une recidive post-chirurgicale; 3 fois, devant une metastase clinique, la tumeur primitive pulmonaire; 67 lesions metastatiques

1975-01-01

349

SD rats response to the cyclophosphamide and bleomycin administration by means of the chromosomal aberration assay in bone marrow.  

Directory of Open Access Journals (Sweden)

Full Text Available In this study we decided to evaluate and compare the SD rats response of both sexes in theadministration of two mutagenic substances by chromosomal aberrations assay in bonemarrow cells. Which were formed 5 experimental groups per sex, the first administered withNaCl 0,9 % by intraperitoneal (i.p) route, the second and third groups were administered with cyclophosphamide by i.p route, with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at doses of 40 mg/kg. At the end of the experience obtained higher results of inductions of numeric and structural chromosome aberrations with the use of cyclophosphamide and bleomycin were administered 48 and 24 hours before sacrifice in SD rats of both sexes. This constitutes the best experimental design to induce a considerable number of chromosomal aberrations. Nevertheless high sensibility of this rat line in both sexes was evidenced to the action of both mutagens independently of the outline of used treatment.

Daniel Francisco Arencibia Arrebola; Luis Alfredo Rosario Fernández

2010-01-01

350

Some Timestamping Protocol Failures  

UK PubMed Central (United Kingdom)

Protocol failures are presented for two timestamping schemes. These failures emphasize the importance and difficulty of implementing a secure protocol even though there exist secure underlying algorithms. As well, they indicate the importance of clearly defining the goals for a protocol. For the scheme of Benaloh and de Mare (Eurocrypt '93), it is shown that although an indication of time can be included during the computation of the timestamp, the verifiation of the timestamp does not allow for the recovery of this temporal measure. For the scheme of Haber and Stornetta (Journal of Cryptology '91), we demonstrate how a collusion attack between a single user and a timestamping service allows for the backdating of timestamps. This attack is successful despite the claim that the timestamping service need not be trusted. For each of these schemes we discuss methods for improvement.

Mike Just

351

Cytoskeleton - Methods and Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Cytoskeleton - Methods and ProtocolsSecond edition, 2010; Ray H. Gavin (Ed); Springer Protocols methods in molecular biology, vol. 586 Humana press, Totowa, New Jersey (USA); Pages: 390; €95.44; ISBN: 978-1-60761-375-6Ray H. Gavin, from the Brooklyn College of The City University of New York, Brooklyn, NY, USA, wrote a few line as preface of this book. This is quite understandable: there is not a great need of words when there are facts that sustain and favour the dissemination of a cultural product. This is the case of the second edition of Cytoskeleton - Methods and Protocols, which appears just ten years after the first edition...

CarloAlberto Redi

2010-01-01

352

Session Initiation Protocol  

UK PubMed Central (United Kingdom)

Session Initiation Protocol, SIP, provides controlplanesignaling for the IP networks. SIP enables initiating,modifying and terminating sessions for a user, while maintainingneutrality to physical media capabilities and using otherprotocols to negotiate these. SIP assumes that the transport layeris inherently unreliable and as such provides transport layermechanisms. For target device discovery SIP requires the use ofapplication layer routing. Besides these, the protocol is extensibleand has already been extended to support IETF presenceframework and instant messaging. However, in order to performin its core area, IP telephony call signaling, in regards to PSTNIPTelephony integration, the protocol requires further workespecially in the area of emergency calls. 3GPP has decided touse SIP for signaling and work is ongoing to meet 3GPP networkand IP multimedia system requirements.

Tuomas Nurmela

353

SIP: Session Initiation Protocol  

UK PubMed Central (United Kingdom)

Many styles of multimedia conferencing are likely to co-exist on the Internet, and many of themshare the need to invite users to participate. The Session Initiation Protocol (SIP) is a simple protocoldesigned to enable the invitation of users to participate in such multimedia sessions. It is not tied to anyspecific conference control scheme, providing support for either loosely or tightly controlled sessions.In particular, it aims to enable user mobility by relaying and redirecting invitations to a user's currentlocation.This document is a product of the Multiparty Multimedia Session Control (MMUSIC) working groupof the Internet Engineering Task Force. Comments are solicited and should be addressed to the workinggroup's mailing list at confctrl@isi.edu and/or the authors.Authors' NoteThis document is the result of a merger of the Session Invitation Protocol (draft-ietf-mmusic-sip-00.txt) andthe Simple Conference Invitation Protocol (draft-ietf-mmusic-scip-00.txt), ...

Internet-draft M. H; H. Schulzrinne; E. Schooler

354

SIP: Session Initiation Protocol  

UK PubMed Central (United Kingdom)

The Session Initiation Protocol (SIP) is an application-layer control (signaling) protocol for creat- 15ing, modifying and terminating sessions with one or more participants. These sessions include Internet 16telephone calls, multimedia distribution and multimedia conferences. 17SIP invitations used to create sessions carry session descriptions which allow participants to agree on 18a set of compatible media types. SIP makes use of elements called proxy servers to help route requests 19to the users current location, assist in firewall traversal, and provide features to users. SIP also provides a 20registration function that allows them to upload their current location for use by proxy servers. SIP runs 21ontop of several different transport protocols. 22Contents231

355

Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Using short-term cultures of hamster embryo cells, we have examined the effects of the free-radical scavenger superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and the enzyme catalase (hydrogen-peroxide:hydrogenperoxide oxidoreductase, EC 1.11.1.6) on x-ray- and bleomycin-indu...

Borek, C; Troll, W

356

Effects of intratracheal administration of bleomycin on prostaglandins and thromboxane-B2 and collagen levels of the lung in hamsters.  

UK PubMed Central (United Kingdom)

The effects of intratracheal administration of one unit of bleomycin on the lung levels of different prostaglandins (PGs), thromboxane B2 (TxB2), and total collagen were investigated in hamsters in two separate sets of this study. Averaging the values from two sets, the lung levels of 6-keto-PGF1 alpha (stable metabolite of PGI2), TxB2 (stable metabolite of TXA2), PFG2 alpha, and PGE in bleomycin-treated animals were increased by 11-, 7.5-, 7-, and 3-fold over the saline control at 14 days post treatment, respectively. The total lung collagen content in bleomycin-treated animals was significantly increased to 180% of the control during the same period. A number of possibilities for a marked variation in the levels of rise for different PGs and TxB2 and their significance in bleomycin-induced lung fibrosis have been discussed. It was concluded from the findings of the present study that there is a relationship between the lung levels of various metabolites of arachidonic acid cascade and bleomicin-induced increases in the synthesis and accumulation of lung collagen. The nature of this relationship, however, remains to be elucidated.

Giri SN; Witt TC

1985-01-01

357

Apoptosis - Methods and Protocols  

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Full Text Available Apoptosis - Methods and ProtocolsSecond edition, 2009; Peter Erhardt and Ambrus Toth (Eds); Springer Protocols - Methods in molecular biology, vol. 559; Humana press, Totowa, New Jersey (USA); Pages: 400; €88.35; ISBN: 978-1-60327-016-8The editors rightly begin the preface telling us that: “The ability to detect and quantify apoptosis, to understand its biochemistry and to identify its regulatory genes and proteins is crucial to biomedical research”. Nowadays this is a grounding concept of biology and medicine. What is particularly remarkable...

CarloAlberto Redi

2010-01-01

358

Security Protocol Design: A Case Study Using Key Distribution Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Nowadays security protocols are a key component in providing security services for fixed and mobile networks. These services include data confidentiality, radio link encryption, message integrity, mobile subscriber authentication, electronic payment, certified e-mail, contract signing and nonrepudiation. This paper is concerned with design of effective security protocols. Security protocols are introduced and some common attacks against security protocols are discussed. The vulnerabilities that lead to theattacks are analyzed and guidelines for effective security protocol design are proposed. The presented guidelines are applied to the Andrew Secure RPC protocol and its adapted versions. It is demonstrated that compliance with the guidelines successfully avoidsfreshness and parallel session attacks.

Anca Jurcut; Tom Coffey; Reiner Dojen; Robert Gyorodi

2009-01-01

359

Long-term treatment with fasudil improves bleomycin-induced pulmonary fibrosis and pulmonary hypertension via inhibition of Smad2/3 phosphorylation.  

UK PubMed Central (United Kingdom)

Pulmonary hypertension (PH) associated with pulmonary fibrosis (PF) considerably worsens prognosis of interstitial lung diseases (ILD). RhoA/Rho-kinases (ROCK) pathway is implicated in high pulmonary vascular tone and pulmonary fibrosis but the effect of ROCK inhibitors on PH associated with PF is not known. We therefore aimed to determine whether long-term treatment with fasudil, a selective ROCK inhibitor, could attenuate PF and PH induced by bleomycin in mice. Male C57BL/6 mice received a single dose of intratracheal bleomycin (3.3 U/kg) to induce PF. Treatment with fasudil (30 mg kg(-1) day(-1)) was given intraperitoneally for 7, 14 or 21 days until mice underwent hemodynamic measurements. Right ventricular systolic pressure (RVSP) and RV/(LV + S) ratio were assessed. Lung inflammatory cells profiles, including macrophages, neutrophils, lymphocytes B and lymphocytes T were assessed by immunohistochemistry. Lung fibrosis was evaluated by histological and biochemical methods. Pulmonary arteriole muscularization and medial wall thickness (MWT) were evaluated by immunohistochemical staining for ?-SMA. Bleomycin induced severe PF and PH in mice, associated with an increased RhoA/ROCK activity in the lung. Fasudil reduced lung inflammation and lung collagen content, and attenuated the increased RVSP, RV hypertrophy, and pulmonary vascular remodeling in bleomycin-intoxicated mice. Fasudil inhibited the increased activity of RhoA/ROCK pathway, and partly altered bleomycin-associated activation of TGF-?1/Smad pathway, via inhibition of Smad2/3 phosphorylation. The efficacy of long-term treatment with fasudil suggests that the blockade of RhoA/ROCK pathway may be a promising therapy for patients with ILD-associated PH.

Bei Y; Hua-Huy T; Duong-Quy S; Nguyen VH; Chen W; Nicco C; Batteux F; Dinh-Xuan AT

2013-08-01

360

Coagulase Test Protocol  

Science.gov (United States)

This protocol describes the history and procedures of the coagulase test.  The coagulase test isused to differentiate species of Staphylococcus, especially the coagulase-positive Staphylococcus aureus from coagulase-negative staphylococcal species.  Both common versions of the test, the slide method and the test tube method, are described, and the mechanisms of the reactions are discussed.

American Society For Microbiology;

2010-11-11

 
 
 
 
361

WOODSTOVE DURABILITY TESTING PROTOCOL  

Science.gov (United States)

The report discusses the development of an accelerated laboratory test to simulate in-home woodstove aging and degradation. nown as a stress test, the protocol determines the long-term durability of woodstove models in a 1- to 2-week time frame. wo avenues of research have been t...

362

Urease Test Protocol  

Science.gov (United States)

Production of the enzyme urease is characteristic of the Proteeae and a few other members of the Enterobacteriaceae among others. Urease is a constitutively produced enzyme that hydrolyzes urea with the resultant release of ammonia and carbon dioxide. The use of urea agar and urea broth for the detection of urease activity is described in this protocol.

American Society For Microbiology;

2010-11-11

363

Clinical Protocol Information System  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The Clinical Protocol Information System (CPIS) supports the clinical research and patient care objectives of the SouthEastern Cancer Study Group (SEG). The information system goals are to improve the evaluability of clinical trials, decrease the frequency of adverse patient events, implement drug t...

Wirtschafter, David D.; Gams, Richard; Ferguson, Carol; Blackwell, William; Boackle, Paul

364

Session Initiation Protocol (SIP)  

UK PubMed Central (United Kingdom)

ice only services, voice and video services, voice and data services or all voice, data andSession Initiation Protocol (SIP) December 3, 1999 3video services. ITU H.323 also provides the necessary signaling requirement functionslike SIP does. As for MGCP, a central coordinator is used to monitor events in IP phonesand gateways and then instructs them to deliver the media to the specific addresses.Finally, SIP, being a signaling protocol, is the dicussion below of this survey paper.2.0 SIP2.1 Signaling Protocol FunctionsIn VoIP, also known as the Internet Telephony, there are certain functions or characteristicsthat a signaling protocol should be capable of performing. They are1. User Location Function:It is essential that the Caller should be able to locate the Callee with the User LocationFunction. The Callee could be at different places at different times and he/she could bereached by several means (eg. Callee's PC or Mobile Pho

Zach Wong; Voip Motivation

365

[Studies on the role of colchicine in bleomycin-induced pulmonary fibrosis in rats  

UK PubMed Central (United Kingdom)

OBJECTIVE: It has well been known that cytokines and extracellular matrix protein (ECM) have played an important role in pulmonary fibrosis in animal model as well as in patients. The purpose of this study was to evaluate the suppressive effect of colchicine (Colc.) in bleomycin (BLM)-treated rats. METHOD: Consecutive changes of interleukin-6(IL-6) and interleukin-8 (IL-8) released by alveolar macrophage (AM) were measured with murine B-cell hybridoma 7TD1 cells and micro membrane filter test. ECM and lipid peroxidation were observed with radioimmunoassay and biochemical assay respectively. RESULT: (1) Colc. significantly suppressed release of IL-6 by AM from day 7 to 28 (P < 0.05). But the level of IL-6 remained higher than that of the control. On the day 1 to 3, IL-8 released by AM markedly decreased (P < 0.01) and the peak of IL-8 secretion had not appeared. (2) Colc. had no protective effects on AM lipid peroxidation injury. (3) Colc. markedly decreased the level of fibronectin (FN) by AM on day 7, 14 (P < 0.01), as well as the level of laminin (LN) in bronchoalveolar lavage fluid (BALF) on day 7 to 28. However, the level of LN remained higher than that of control. (4) Colc. lessened the collagen deposition, and the lung hydroxyproline (HYP) content decreased on day 7, 14 and 28 (P < 0.05) compared with that of the control. (5) Colc. decreased exudation of inflammatory cells in the early response, as well as the degree of fibrosis in the late stage. CONCLUSION: Lipid peroxidation of AM might be one of the mechanisms of tissue injury and of AM activation, which increases the release of cytokines (IL-6, IL-8) and deposition of extracellular matrix proteins (FN, LN). Colc. exertes somewhat inhibitory effects on the process of pulmonary fibrosis in animal model. Factors other than AM and its cytokines might also be involved in the pathogenesis of pulmonary fibrosis in experimental rats.

Jiang L; Chen B; Li Z

1998-06-01

366

Protocol Monitoring Energy Conservation; Protocol Monitoring Energiebesparing  

Energy Technology Data Exchange (ETDEWEB)

On request of the Dutch ministry of Economic Affairs five institutes have collaborated to create a 'Protocol Monitoring Energy Conservation', a common method and database to calculate the amount of energy savings realised in past years. The institutes concerned are the Central Bureau of Statistics (CBS), the Netherlands Bureau for Economic Policy Analysis (CPB), the Energy research Centre of the Netherlands (ECN), the National Agency for Energy and Environment (Novem) and the Netherlands Institute of Public Health and the Environment (RIVM). The institutes have agreed upon a clear definition of energy use and energy savings. The demarcation with renewable energy, the saving effects of substitution between energy carriers and the role of import and export of energy have been elaborated. A decomposition method is used to split up the observed change in energy use in a number of effects, on a national and sectoral level. This method includes an analysis of growth effects, effects of structural changes in production and consumption activities and savings on end use or with more efficient conversion processes. To calculate these effects the total energy use is desegregated as much as possible. For each segment a reference energy use is calculated according to the trend in a variable which is supposed to be representative for the use without savings. The difference with the actual energy use is taken as the savings realised. Results are given for the sectors households, industry, agriculture, services and government, transportation and the energy sector; as well as a national figure. A special feature of the protocol method is the application of primary energy use figures in the determination of savings for end users. This means that the use of each energy carrier is increased with a certain amount, according to the conversion losses caused elsewhere in the energy system. The losses concern the base year energy sector and losses abroad for imports of secondary energy carriers. The calculated savings for end users not only encompass the direct savings but also the indirect savings from less conversion losses in the energy sector. Because of the lack of suitable representative variables or energy use data in some sectors, it is not always possible to desegregate to the desired level. Therefore the calculated figures in this 'top-down' protocol method are an estimation of the true savings. The uncertainty margin in the results is also calculated, based on the uncertainty in the input data and the 'quality' of the representative variable. This gives the policy maker an impression of the robustness of the figures; moreover it is useful to detect the weak parts in the analysis. To demonstrate the method in practice an analysis has been carried out for the period 1990-1998. Because of the uncertainties in the figures the sectoral results are given as a mean yearly percentage over the period 1990-1996/1997/1998. The protocol method is compared with existing evaluation methods for renewable energy and the emission of green house gases, and with methods used in policy measure evaluation. The final chapter contains suggestions for maintaining or improving the quality of the results. [Dutch] Op het gebied van energieverbruik en besparing zijn in het verleden door de beleidsmakers (ministeries van EZ en VROM) en de betrokken instituten (CPB, RIVM, CBS, Novem en ECN) niet altijd op een eenduidige en uniforme wijze cijfers bepaald en gepresenteerd. Dit heeft zijn oorzaak in zowel verschillen in definities en gebruikte data als in de methode van bepalen van besparing; daarnaast is er weinig aandacht geweest voor de onzekerheden in de cijfers. Dit heeft soms geleid tot problemen met de interpretatie van de besparingscijfers en het trekken van beleidsconclusies. Op verzoek van het ministerie van Economische Zaken hebben de genoemde instituten een gezamenlijke aanpak uitgewerkt in het project 'Protocol Monitoring Energiebesparing'. Doel van de samenwerking was de ontwikkeling van een eenduidige methode en

Boonekamp, P.G.M. [ECN Beleidsstudies, Petten (Netherlands); Mannaerts, H. [Centraal Planburea CPB, Den Haag (Netherlands); Tinbergen, W. [Centraal Bureau voor de Statistiek CBS, Den Haag (Netherlands); Vreuls, H.H.J. [Nederlandse onderneming voor energie en milieu Novem, Utrecht (Netherlands); Wesselink, B. [Rijksinstituut voor Volksgezondheid en Milieuhygiene RIVM, Bilthoven (Netherlands)

2001-12-01

367

Model Additional Protocol  

International Nuclear Information System (INIS)

Since the end of the cold war a series of events has changed the circumstances and requirements of the safeguards system. The discovery of a clandestine nuclear weapons program in Iraq, the continuing difficulty in verifying the initial report of Democratic People's Republic of Korea upon entry into force of their safeguards agreement, and the decision of the South African Government to give up its nuclear weapons program and join the Treaty on the Non-Proliferation of Nuclear Weapons have all played a role in an ambitious effort by IAEA Member States and the Secretariat to strengthen the safeguards system. A major milestone in this effort was reached in May 1997 when the IAEA Board of Governors approved a Model Protocol Additional to Safeguards Agreements. The Model Additional Protocol was negotiated over a period of less than a year by an open-ended committee of the Board involving some 70 Member States and two regional inspectorates. The IAEA is now in the process of negotiating additional protocols, State by State, and implementing them. These additional protocols will provide the IAEA with rights of access to information about all activities related to the use of nuclear material in States with comprehensive safeguards agreements and greatly expanded physical access for IAEA inspectors to confirm or verify this information. In conjunction with this, the IAEA is working on the integration of these measures with those provided for in comprehensive safeguards agreements, with a view to maximizing the effectiveness and efficiency, within available resources, the implementation of safeguards. Details concerning the Model Additional Protocol are given. (author)

2001-10-05

368

Interface of Montreal Protocol with Kyoto Protocol. Some issues  

Energy Technology Data Exchange (ETDEWEB)

The presentation identifies some of the issues relating to the interface between the Montreal Protocol and the Kyoto Protocol with special attention for the use of CFCs by the refrigerating and air conditioning sector in India.

Sharma, V.; Bagai, A. [Ministry of Environment and Forests, Government of India, New Delhi (India)

1999-07-01

369

Phototherapy Modalities and Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Over the past few years, the development of irradiation devices with new emission spectra has led to an expanded role for phototherapy in the treatment of skin diseases. This development is best illustrated by the increasing frequency with which 311 nm UVB phototherapy is used for the treatment of psoriasis and vitiligo, especially. Another example is UVA1 340-400 nm. UVA1 was first used to treat patients with atopic dermatitis, but it has been found to be efficacious in several other skin diseases. This is overview of the protocols for phototherapy with UV in the treatment of skin diseases as currently used according to recent literature review. There are, of course, other protocols in use that are effective.

Ayten Ferahba?

2010-01-01

370

Peptidomics - Methods and protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Nearly ten years ago the scientific community added another discipline to the big –omics family, peptidomics, i.e., “the study of the complement of peptides from a cell, organelle, tissue or organism”. This fact derives from the exceptional capacity to produce data by high-throughput techniques and machines that allow us to pass from proteomics analysis of complex biological systems to the capacity to resolve their peptides content even at the single cell level. Thus, the time is set to have this Peptidomics: Methods and protocols edited by Mikhail Soloviev. I think the editor did a great job; I was reading a very usefull book, a great collection of protocols (that widely range as for the organisms studied, from Bacteria to Man !) both for those are newcomer potential users, as I am, and for those are already acquiented to .....

CarloAlberto Redi

2010-01-01

371

Methods for automatic protocol selection  

UK PubMed Central (United Kingdom)

A method and apparatus for imaging a patient is provided. The method includes receiving patient information, automatically selecting an imaging protocol based on the received information, and performing an imaging scan of the patient using the automatically selected imaging protocol.

WOLLENWEBER SCOTT D; STEARNS CHARLES W; MIESBAUER DIANE M; WOLLENWEBER SCOTT DAVID; STEARNS CHARLES WILLIAM; MIESBAUER DIANE MARIE

372

On Consensus under Polynomial Protocols  

CERN Multimedia

In this paper we explore the possibility of using computational algebraic methods to analyze a class of consensus protocols. We state some necessary conditions for convergence under consensus protocols that are polynomials.

Manathara, Joel George; Ghose, Debasish

2011-01-01

373

[Protocols and procedures  

UK PubMed Central (United Kingdom)

Evidence-based nursing increases behavior uniformity during everyday activities and in critical or complex situations. A recorded and programmed activity, the foreseeing of resources, the checking of application modalities and outcome evolution, and warning of complications, are the basis for a good pre-ordered flow chart. Nurses themselves build valuable protocols for every care procedure. This study describes central venous catheter (CVC) care as an example of a useful procedure.

Peafrini M; Fabris R; Bianchi M

2005-01-01

374

Bleomycin, methotrexate and vincristine before irradiation of stage III and IV laryngeal and pharyngeal squamous cell carcinoma  

International Nuclear Information System (INIS)

Primary treatment with bleomycin, methotrexate and vincristine for two weeks followed by curatively intended 60Co irradiation was administered to 153 patients consecutively referred to the three main treatment centres in Denmark over more than a two-year period. Seventy-one laryngeal and 82 pharyngeal squamous cell carcinomas were evaluated. According to the TNM classification (UICC) 76 patients had stage III and 77 patients stage IV disease. The immediate response (complete + partial) to chemotherapy was 20%. Judging from frequency of local recurrence, metastases as well as survival the treatment results were not obviously improved. A high frequency of complications was observed after this combination of chemotherapy and irradiation, and it was often impossible to fulfil the irradiation to the planned dose in appropriate time. (orig.)

1987-01-01

375

The Effects of Bleomycin on the Structural Abnormalities of Human Chromosomes who were Exposed to Radition (X-Ray) Chronically  

Directory of Open Access Journals (Sweden)

Full Text Available Bleomycin in doses 0.3, 3 and 30 ?g/ml was used with periods 6, 24 and48 hours on 5 samples who were exposed to radiation chronically, in invitroconditions and under control so totally 2639 metaphases wereevaluated.Structural chromosome aberrations were influenced by the increases indosage. While the ratio total structural aberrations to the number ofmetaphases examined was 9.7% in control groups (individual werechronically-exposed to radiation). It was 44.8% in 0.3 ?g/ml group, 180.8%in 3 ?g/ml and rose up to 205.1% in 30 ?g/ml experiment group. In additiondue to the increases in dosage, there was an increase in structuralaberration quantities and qualities.

Hilmi ?si; Ay?egül Bengisu Türky?lmaz; Turgay Budak

2004-01-01

376

Preparation, distribution, stability and tumor imaging properties of [62Zn] Bleomycin complex in normal and tumor-bearing mice  

International Nuclear Information System (INIS)

Backgrounds: Bleomycin (BLM) has been labeled with radioisotopes and widely used in therapy and diagnosis. In this study BLM was labeled with [62Zn] zinc chloride for oncologic PET studies. Materials and methods: The complex was obtained at the P H=2 normal saline at 90degC in 60 min. Radio-TLC showed on overall radiochemical yield of 95-97% (radiochemical purity>97%). Stability of complex was checked in vitro in mice and human plasma/urine. Results: Preliminary in vitro studies performed to determined complex stability and distribution of [62Zn] BLM in normal and fibrosarcoma tumors in mice according to bio-distribution/imaging studies. Conclusion: [62Zn] BLM can be used in PET oncology studies due to its suitable physico-chemical propertied as a diagnostic complex behavior in higher animals.

2003-01-01

377

Isolation and partial characterization of mutants of Saccharomyces cerevisiae altered in sensitivities to lethal effects of bleomycins  

Energy Technology Data Exchange (ETDEWEB)

Two of eight mutants (bmr) isolated in Saccharomyces cerevisiae on the basis of their increased resistance to lethal effects of antitumor bleomycins (BM), and about two-thirds of 180 yeast mutants (bms) isolated on the basis of their increased sensitivities to cell-killing by phleomycins (PM) or BM were sensitive to one or more of the agents uv, x-rays or hydrogen peroxide. Thus these mutants are likely to be altered in processes acting directly or indirectly on DNA damage. The remaining six bmr mutants and approximately 60 bms mutants appear as resistant as the parent strain to cell-killing by uv or x-rays, and are likely therefore, to be altered in cell wall or membrane function. A genetic basis for the phenotypes of some of the bmr and bms mutants has been established.

Moore, C.W.

1980-11-01

378

Preparation of porous PLGA microspheres with thermoreversible gel to modulate drug release profile of water-soluble drug: bleomycin sulphate.  

Science.gov (United States)

Bleomycin sulphate-loaded porous microspheres were prepared using modified solvent evaporation method (w/o/w) using PLGA50:50 as a polymeric system. The prepared microspheres were incorporated in pluronic (F127) based thermoreversible gel to develop a depot formulation. Various process parameters as solvent evaporation temperature and formulation parameters such as surfactant concentration, volume of internal and external phase and drug-to-polymer ratio were optimized for enhancing percentage drug entrapment, percentage drug loading and desired release profile by controlling size and porosity of the microspheres. Microspheres were characterized for particle size, zeta potential, surface morphology, percentage drug loading and in vitro drug release study after incorporated in gel. The formulated microspheres were porous in nature and showed biphasic in vitro drug release profile. The microspheres incorporated in pluronic (F127) gel showed sustained release up to 1 week and may be useful for treatment of squamous cell carcinoma with better therapeutic effect. PMID:20128747

Chaudhari, Kiran R; Shah, Neha; Patel, Hetal; Murthy, Rayasa

2010-01-01

379

Preparation of porous PLGA microspheres with thermoreversible gel to modulate drug release profile of water-soluble drug: bleomycin sulphate.  

UK PubMed Central (United Kingdom)

Bleomycin sulphate-loaded porous microspheres were prepared using modified solvent evaporation method (w/o/w) using PLGA50:50 as a polymeric system. The prepared microspheres were incorporated in pluronic (F127) based thermoreversible gel to develop a depot formulation. Various process parameters as solvent evaporation temperature and formulation parameters such as surfactant concentration, volume of internal and external phase and drug-to-polymer ratio were optimized for enhancing percentage drug entrapment, percentage drug loading and desired release profile by controlling size and porosity of the microspheres. Microspheres were characterized for particle size, zeta potential, surface morphology, percentage drug loading and in vitro drug release study after incorporated in gel. The formulated microspheres were porous in nature and showed biphasic in vitro drug release profile. The microspheres incorporated in pluronic (F127) gel showed sustained release up to 1 week and may be useful for treatment of squamous cell carcinoma with better therapeutic effect.

Chaudhari KR; Shah N; Patel H; Murthy R

2010-01-01

380

Stable [57Co]-bleomycin complex with a very high specific radioactivity for use at very low concentrations  

International Nuclear Information System (INIS)

A method for the preparation of 57Co-labelled bleomycin (BLM) possessing very high specific radioactivity and suitable for use at the nanomolar concentration range is described, and validated using a biological assay. Chelation of BLM with Co(II) results in a very stable complex. However, association does not occur below the micromolar concentration range. A nanomolar [57Co]BLM solution with maximal specific radioactivity can be easily prepared, without handling unreasonable amounts of radioactivity, provided that: equimolar solutions of BLM and [57Co]Cl2 are first mixed at the micromolar concentration range and that the mixture is then diluted a thousand times to reach the nanomolar concentration range

1990-11-30

 
 
 
 
381

Effectiveness of carboplatin, etoposide, and bleomycin combination chemotherapy in good-prognosis metastatic testicular nonseminomatous germ cell tumors.  

UK PubMed Central (United Kingdom)

The combination of carboplatin, etoposide, and bleomycin (CEB) was evaluated as initial chemotherapy in 76 patients with good-prognosis metastatic nonseminomatous germ cell tumors (NSGCT) between 1984 and 1988. The classification of eligible patients included Royal Marsden Hospital (RMH) stages IM, IIA, IIB, IIC, IIIA, IIIB, IV0ABCL1, and IV0ABL2. Four courses of combination chemotherapy were administered in a 21-day cycle, and surgical excision of residual mass was performed in 27 cases (23 laparotomies and four thoracotomies). At the time of analysis, median follow-up was 24 months from start of chemotherapy (range, 6 to 54 months). The 2-year cause-specific survival probability was 98.5%, the single cause-related mortality being caused by bleomycin pneumonitis. Five patients failed CEB chemotherapy, but all have been successfully salvaged with a combination of surgery and intensive chemotherapy, follow-up from completion of all treatment being 35 to 44 months. The toxicity of CEB included bone marrow suppression and alopecia in all patients but no significant neurotoxicity or ototoxicity, and minimal renal toxicity. Only four (5%) patients had a decrease in the glomerular filtration rate greater than 15%. In 51% of patients, the hemoglobin fell below 10 g/dL. The WBC count nadir was less than 1,500/microL in 11% of treatment cycles and in 16% the platelet nadir fell below 50,000/microL. Decreases in the WBC and platelet counts were of very brief duration. Only one of 310 CEB cycles was complicated by neutropenic sepsis, and there were no episodes of thrombocytopenic purpura or bleeding. We conclude that the CEB combination represents an effective alternative to cisplatin-based chemotherapy in good-prognosis NSGCT and that the replacement of cisplatin by carboplatin leads to reduced toxicity.

Horwich A; Dearnaley DP; Nicholls J; Jay G; Mason M; Harland S; Peckham MJ; Hendry WF

1991-01-01

382

New Robust Bleomycin Analogues: Synthesis, Spectroscopy, and Crystal Structures of the Copper(II) Complexes.  

Science.gov (United States)

Two new bleomycin analogues, 2-[((2-(4-imidazolyl)ethyl)amino)carbonyl]-6-[((2-amino-2-methylpropyl)amino)methyl]pyridine = L(3)() and 2-[((2-(4-imidazolyl)ethyl)amino)carbonyl]-6-[((2-amino-1,1,2-trimethylpropyl)amino)methyl]pyridine = L(4)(), were synthesized in order to create air-stable ligands of their Cu(I) (and Fe(II)) complexes. The protonation constants (log K(n)()) of the ligands at 25 degrees C and I = 0.1 M NaNO(3) were 9.9, 6.9, and 5.2 for L(3)() and 10.0, 6.7, and 3.9 for L(4)(). The complexation of the triprotonated L(3)() and L(4)() with Cu(II) started at pH 3sigma(I)] reflections. Crystal data for 7.BF(4): monoclinic, space group P2(1)/n (No. 14), a = 16.092 (4) Å, b = 7.974(4) Å, c = 16.819(2) Å, beta = 99.64(1) degrees, V = 2127(1) Å(3), Z = 4, R = 0.040, and R(w) = 0.025 for 1633 [I > 4sigma(I)] reflections. The coordination geometry around the copper was a distorted square-pyramid in 5, while that of 7 was the intermediate between a trigonal-bipyramid and a square-pyramid. The distortion is influenced strongly by the number of the methyl group. The EPR spectral data for both copper(II) complexes were consistent with the retention of the solid-state structure in frozen DMF/MeOH (1:1) solution at 77 K. The visible absorption spectra of 10% DMF/aqueous solutions (pH 9.5) of 5 and 7 at I = 0.1 M NaNO(3) showed absorption maxima at 646 nm with a shoulder at ca. 900 nm for 5 and at 658 and 888 nm for 7. The red-shift of 7 by ca. 12 nm relative to 5 reflects the distortion toward the trigonal-bipyramidal geometry of 7 in solution. Both complexes displayed irreversible redox behavior in DMF at I = 0.1 M tetra(n-butyl)ammonium tetrafluoroborate. The anodic and cathodic peak potentials obtained by cyclic voltammetry for 5 and 7 were -0.14 and -0.76 V for 5 and -0.17 and -0.80 for 7 vs Ag/AgCl. The cathodic potentials of copper(II) complexes were shifted toward the anodic direction by ca. 20-60 mV compared to the nonsubstituted 5-coordinate, [Cu(II)(H(-)(1)L(1))](+) complex, 16 (-0.82 V vs Ag/AgCl). The Cu(I) complexes (9and 10) are air-oxidized to the corresponding Cu(II) complexes, 5 and 7, respectively. PMID:11671027

Kurosaki, Hiromasa; Hayashi, Kentarou; Ishikawa, Yoshinobu; Goto, Masafumi; Inada, Kazufumi; Taniguchi, Isao; Shionoya, Mitsuhiko; Kimura, Eiichi

1999-06-14

383

Injecting Heterogeneity Through Protocol Randomization  

Directory of Open Access Journals (Sweden)

Full Text Available In this paper, we argue that heterogeneity should be an important principle in design and use of cryptographic protocols. We use automated formal analysis tools to randomly generate security protocols as a method of introducing heterogeneity. We present the results of simulations for the case of two party authentication protocols and argue that choosing protocols randomly out of sets numbering in the hundreds of millions is practical and achievable with an acceptable overhead. To realize the simulation, we implemented a highly efficient protocol verifier, achieving approximately two orders of magnitude improvement in performance compared to previous work.

Li Zhuang; J. D. Tygar; Rachna Dhamija

2007-01-01

384

FRENCH PROTOCOL CARDS  

CERN Document Server

Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.1999, are requested to return these cards and those of family members, for extension to:Bureau des cartes, bâtiment 33.1-025Should the 3 spaces for authentication on the back of the card be full, please enclose 2 passport photographs for a new card.In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.Personnel DivisionTel. 79494/74683

Division du Personnel

1999-01-01

385

Transfusion protocol in trauma  

Directory of Open Access Journals (Sweden)

Full Text Available Blood and blood components are considered drugs because they are used in the treatment of diseases. As with any drug, adverse effects may occur, necessitating careful consideration of therapy. Like any other therapeutic decision, the need for transfusion should be considered on the basis of risks and benefits and alternative treatments available to avoid over- and under-transfusion. This review is focused on the blood transfusion protocol in trauma patients with hemorrhagic shock. Besides, issues related to emergency and massive transfusion have also been elaborated. We conducted a comprehensive MEDLINE search and reviewed the relevant literature, with particular reference to emergency medical care in trauma.

Kaur Paramjit; Basu Sabita; Kaur Gagandeep; Kaur Ravneet

2011-01-01

386

Hektoen Enteric Agar Protocol  

Science.gov (United States)

Hektoen enteric agar is a selective and differential media for the recovery of enteric gram-negative rods from mixed microbiota.  The growth of gram-positive organisms and nonpathogenic enteric coliforms is inhibited through the use of bile salts and dyes, allowing intestinal pathogens, such as Salmonella and Shigella, to be more easily recovered.  The media can also differentiate between organisms that produce H2S and those that do not due to the presence of an iron-containing compound.  The use and interpretation of growth on this media is discussed in this protocol.

American Society For Microbiology;

2010-11-11

387

FRENCH PROTOCOL CARDS  

CERN Document Server

Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.2000, are requested to return these cards and those of family members, for extension to: Bureau des cartes, Bât 33.1-009/1-015 Should the three spaces for authentication on the back of the card be full, please enclose two passport photographs for a new card. In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.

Division des Ressources Humaines; Human Resources Division; Tel. 74683-79494

2000-01-01

388

Determination of hidden chromosome instability in persons suffered from the action of factors of the Chernobyl accident by the modified 'G2 bleomycin sensitivity assay'  

International Nuclear Information System (INIS)

With the help of the modified 'G2-bleomycin sensitivity assay' the voluntary investigation of hidden chromosome instability in 53 persons with different radiation exposures had been fulfilled. In all examined groups, the individual levels of chromosome injuries under identical bleomycin exposure varied in a wide range and didn't depend on their initial values in intact cultures. Among control donors and individuals with low radiation exposure, ? 33 % hypertensive persons had been identified that can be considered as a genetically caused phenomenon. In patients recovered from acute radiation, 57.9 % persons expressed the hidden chromosome instability. The data obtained allow us to assume that high doses of ionizing radiation can modify the inherited susceptibility of human chromosomes to a mutagen exposure.

2009-01-01

389

Influence of radiotherapy upon tumor accumulation and organ distribution of 57Co-bleomycin in mice with chemically induced squamous cell carcinoma  

International Nuclear Information System (INIS)

Squamous cell carcinoma was induced in male 6 to 8-week old NMRI-mice by application of 9,10-dimethyl-1,2-benzanthracene on the skin. 15 weeks later macroscopically visible skin tumors are developed. Then organ distribution and tumor accumulation of 57Co-Bleomycin (spec. activity 1 mCi/3.3 mg) were studied 1 to 48 hours after injection. In squamous cell carcinoma a high uptake of this tumor-seeking agent can be demonstrated (n = 46). After radiotherapy (100 kV; 1.7 mm Al-filter; 18.8 Gy)(n=26), however, a significantly reduced uptake of 57Co-Bleomycin in tumor tissue is observed. Possible consequences from these animal studies for tumor scintigraphy with this radiopharmaceutical in man are discussed. (orig.)

1979-01-01

390

Security and SCADA protocols  

Energy Technology Data Exchange (ETDEWEB)

Supervisory control and data acquisition (SCADA) networks have replaced discrete wiring for many industrial processes, and the efficiency of the network alternative suggests a trend toward more SCADA networks in the future. This paper broadly considers SCADA to include distributed control systems (DCS) and digital control systems. These networks offer many advantages, but they also introduce potential vulnerabilities that can be exploited by adversaries. Inter-connectivity exposes SCADA networks to many of the same threats that face the public internet and many of the established defenses therefore show promise if adapted to the SCADA differences. This paper provides an overview of security issues in SCADA networks and ongoing efforts to improve the security of these networks. Initially, a few samples from the range of threats to SCADA network security are offered. Next, attention is focused on security assessment of SCADA communication protocols. Three challenges must be addressed to strengthen SCADA networks. Access control mechanisms need to be introduced or strengthened, improvements are needed inside of the network to enhance security and network monitoring, and SCADA security management improvements and policies are needed. This paper discusses each of these challenges. This paper uses the Profibus protocol as an example to illustrate some of the vulnerabilities that arise within SCADA networks. The example Profibus security assessment establishes a network model and an attacker model before proceeding to a list of example attacks. (authors)

Igure, V. M.; Williams, R. D. [Dept. of Electrical and Computer Engineering, Univ. of Virginia, Box 400743, 351 McCormick Rd., Charlottesville, VA 22904-4743 (United States)

2006-07-01

391

The mouse splenocyte assay, an in vivo/in vitro system for biological monitoring; Studies with X-rays, fission neutrons and bleomycin  

Energy Technology Data Exchange (ETDEWEB)

A modified mouse splenocyte culture system was standardized after testing different mitogens (phytohemagglutinin (PHA), concanavalin A (Con A)). The mitotic index was determined for comparison between different mitogens. Following selection of appropriate mitogen (PHA 16, Flow), some experiments were conducted to evaluate application of cytokinesis-block for scoring micro -nuclei and assays for chromosomal aberrations produced by treatment in G[sub 0] and G[sub 2] for purposes of biological dosimetry following in vivo and/or in vitro exposure to X-rays, fission neutrons and bleomycin. In X-irradiation studies, frequencies of micronuclei and chromosomal aberrations (dicentrics and rings) increased in a dose-dependent manner. These data could be fitted to a linear- quadratic model. No difference was observed between irradiation in vivo and in vitro, suggesting that measurement of dicentrics and micronuclei in vitro after X-irradiation can be used as an in vivo dosimeter. Following in vivo irradiation with 1 MeV fission neutrons and in vivo culturing of mouse splenocytes, linear dose-response curves were obtained for induction of micro -nuclei and chromosomal aberrations. Lethal effects of neutrons were shown to be significantly greater than for a similar dose X-rays. Relative biological effectiveness was 6-8 in a dose range of 0.25-3 Gy for radiation-induced asymmetrical exchanges (dicentrics and rings), and about 8 for micronuclei in dose range of 0.25-2 Gy. Furthermore, induction of chromosomal aberrations by bleomycin was investigated in mouse G[sub 0] splenocytes (in vitro) and compared with X-ray data. Following bleomycin treatment (2 h) similar pattern of dose- response curve was obtained as with X-rays. In this context a bleomycin rad equivalent of 20 [mu]g/ml = 0.50 Gy was estimated. (author). 32 refs., 8 figs., 6 tabs.

Darroudi, F.; Natarajan, A.T. (Rijksuniversiteit Leiden (Netherlands). Lab. voor Stralengenetica en Chemische Mutagenese Cohen (J.A.) Inst. voor Radiopathologie en Stralenbescherming, Leiden (Netherlands)); Farooqi, Z. (Rijksuniversiteit Leiden (Netherlands). Lab. voor Stralengenetica en Chemische Mutagenese); Benova, D. (Rijksuniversiteit Leiden (Netherlands). Lab. voor Stralengenetica en Chemische Mutagenese Meditsinska Akademiya, Sofia (Bulgaria). Nauchen Inst. po Rentgenologiya i Radiobiologiya)

1992-12-01

392

Escleroterapia con bleomicina en malformaciones vasculares de bajo flujo: Experiencia y revisión del tema Bleomycin sclerotherapy for low-flow vascular malformations: our experience and literature review  

Directory of Open Access Journals (Sweden)

Full Text Available Las anomalías vasculares son lesiones típicas de los pacientes pediátricos y se dividen en dos categorías: tumores vasculares y malformaciones vasculares de alto y bajo flujo. Estas últimas pueden tratarse de diversos modos: laserterapia, drenaje, aspiración, cirugía o escleroterapia, dependiendo del tipo de lesión y de su localización. Entre los agentes esclerosantes utilizados, la bleomicina ha demostrado tener buenos resultados en el tratamiento de estas lesiones. En este artículo presentamos nuestra experiencia en el tratamiento de las malformaciones vasculares de bajo flujo mediante escleroterapia con bleomicina intralesional. Desarrollamos un estudio descriptivo retrospectivo sobre 30 pacientes que presentaban malformación vascular de bajo flujo y fueron tratados con bleomicina intralesional. Los resultados fueron buenos o excelentes en 22 pacientes y regulares o malos en los 8 restantes. De acuerdo a nuestra casuística y a la literatura revisada, la escleroterapia con bleomicina es una alternativa terapéutica eficaz y segura en el tratamiento de las malformaciones vasculares de bajo flujo.Vascular anomalies are common in children and can be divided into two categories, vascular tumours and vascular malformations: high-flow or low-flow. The latter can be treated in different ways such as lasertherapy, drainage, aspiration, surgery or sclerotherapy depending on the type and location of the lesion. Among the accepted sclerosing agents, bleomycin has proven good results in the treatment of this condition. Herein we present our experience in the treatment of low-flow vascular malformations with intralesional bleomycin injection. This is a retrospective, descriptive study with 30 patients presenting a low-flow vascular malformation treated with intralesional bleomycin injection. Our results are good or excellent in 22 patients and poor in the other 8. According to our case series and the consulted literature, sclerotherapy with intralesional bleomycin injection is an effective and safe treatment for low-flow vascular malformations.

F. Lobo Bailón; B. Berenguer Fröhner; B. González Meli; C. Marín Molina; E. De Tomás y Palacios; C. Alonso Bañuelos

2012-01-01

393