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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 SciELO Brazil | Language: English 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 p [...] ulmonares, hepáticas e retroperitoneais. Após orquiectomia radical, o paciente começou a receber quimioterapia de acordo com o protocolo BEP (sem profilaxia rotineira para 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 prophylaxis 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.

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

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Bleomycin  

Science.gov (United States)

Bleomycin injection is used alone or in combination with other medications to treat head and neck cancer ( ... and vulva (the outer part of the vagina). Bleomycin is also used to treat Hodgkin's lymphoma (Hodgkin's ...

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Bleomycin pneumonitis  

International Nuclear Information System (INIS)

The frequency of bleomycin-induced interstitial pneumonitis was evaluated retrospectively in 442 testicular cancer patients. Three case reports are presented to illustrate diagnostic problems associated with this complication. Bleomycin pneumonitis was encountered in 17 of 442 patients (3.8%). Median age (33 years) and median total dose (550 units) of those patients who developed bleomycin pneumonitis did not differ from the total group (34 years; 565 units). The lowest cumulative dose producing pulmonary damage was 300 units. The overall incidence of pneumonitis increased from 2.4% at cumulative doses below 500 units to 6.6% at total doses of more than 500 units. The lethality rate of pneumonitis was 11.7% (2/17 patients). While long-term bleomycin pulmonary toxicity must be expected in 1.3% (6/442) of all patients, substantial improvement of pulmonary damage was revealed in 9 of 15 patients (60%) after withdrawal of bleomycin therapy. (orig.)

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Iodinated bleomycin  

International Nuclear Information System (INIS)

Bleomycin was labelled with iodine-131 by the iodine monochloride method. Iodination did not alter the chemical and chromatographic features and ''in vitro'' stability studies on freeze-dried 131I-Bleomycin having a specific activity of 1 mCi/mg, stored at different temperatures, showed no appreciable variation of the free-iodine content. Tissue distribution of 131I-Bleomycin has been evaluated in tumor bearing rats. Patients have been injected with 0.5-1.0 mCi of 131I-Bleomycin corresponding to a maximum of 1.5 mg. No adverse reactions have been observed. Total body scans have been performed at 2, 6, 24 and 48 hours after injection. The iodinated Bleomycin was rapidly distributed and cleared from the body and showed an early uptake in the neoplastic tissue. A diagnostic accuracy of 90% has been observed in malignant deseases, while no false positive results have been, at the moment, recorded. (author)

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Bleomycin induced flagellate pigmentation  

Directory of Open Access Journals (Sweden)

Full Text Available Bleomycin frequently causes cutaneous toxicity in the form of pigmentary disturbances. We report 2 patients with testiculartumours who developed distinctive "flagellate" pigmentation on trunk and extremities during bleomycin therapy.

Gupta Lalit Kumar

2002-01-01

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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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Prognostic analysis of Japanese men with metastatic germ cell tumors showing favorable response to bleomycin, etoposide and cisplatin as first-line chemotherapy.  

Science.gov (United States)

The objective of this study was to evaluate the efficacy of first-line bleomycin, etoposide and cisplatin (BEP) chemotherapy in Japanese patients with metastatic germ cell tumors (GCTs). Between 1996 and 2006, 88 male patients with metastatic GCTs were treated with first-line BEP at our institution. Of these 88, 47 (16, seminoma; 31, nonseminoma), who did not receive high-dose chemotherapy following BEP because of the normalization of serum tumor markers, were included in this study. The primary site was the testis in 42 patients, retroperitoneum in 3, and mediastinum in 2. The full-dose regimen used for BEP consisted of cisplatin 20 mg/m2 on days 1 to 5, etoposide 100 mg/m2 on days 1 to 5, and bleomycin on days 2, 9 and 16. Therapeutic outcome was assessed according to several clinicopathological parameters. Following 2 to 4 cycles of BEP (median, 4 cycles), alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase were normalized in all 47 patients. Eighteen patients (38.3%) achieved a complete response (CR) after BEP alone, while BEP resulted in a partial response and stable disease in the remaining 23 (48.9%) and 6 (12.8%), respectively. In addition, surgical resection of the residual tumors following BEP was performed in 15 patients, of whom 12 (80.0%) and 3 (20.0%) achieved pathological and surgical CR, respectively. At a median follow-up of 27 months, all patients were alive; however, disease recurrence occurred in 5 (seminoma, 1; nonseminoma, 4), and all these 5 were subsequently treated with high-dose chemotherapy as salvage therapy. In this series, 1-, 3- and 5-year recurrence-free survival rates were 95.0, 91.4 and 79.2%, respectively, and, there was no significant difference in recurrence-free survival between patients with seminoma and those with nonseminoma. These findings suggested that patients with metastatic GCTs, regardless of histological subtype (i.e., seminoma or nonseminoma), who showed favorable response to first-line BEP chemotherapy, could achieve an excellent prognostic outcome. PMID:18203521

Kumano, Masafumi; Miyake, Hideaki; Hara, Isao; Muramaki, Mototsugu; Takenaka, Atsushi; Fujisawa, Masato

2007-12-01

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Astrophysical S factor for 9Be(p,?)10B  

International Nuclear Information System (INIS)

The 9Be(p,?)10B reaction plays an important role in primordial and stellar nucleosynthesis of light elements in the p shell, but the energy dependence of S(E) has not been well understood. We reanalyze the existing 9Be(p,?)10B experimental data within the framework of the R-matrix method. The direct capture part of the S factor is calculated using the experimentally measured asymptotic normalization coefficients for 10B?9Be+p. The fitted parameters of the low-lying 10B resonances are also required to be consistent with previous measurements of 6Li(?,?)10B. A good simultaneous fit to both radiative capture reactions is found, in contrast to previous analyses. These results demonstrate that experimentally measured asymptotic normalization coefficients, coupled to the R-matrix method, can provide a reasonable determination of direct radiative capture rates, even when the captured proton is tightly bound in the final nucleus. copyright 1999 The American Physical Society

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Effect of bleomycin-radiotherapy combination in management of head and neck squamous cell carcinoma  

International Nuclear Information System (INIS)

Twenty-five patients with head and neck squamous cell carcinoma were treated with bleomycin-radiotherapy protocol, 15 mg bleomycin I.V. on alternate days followed by radiation within half an hour. The average total dose of bleomycin was 150 mg. Radiotherapy was given daily. Two patients were lost to follow-up very early in the course of the treatment and were removed from the study for statistical purposes. Thirty-six patients with head and neck squamous cell carcinoma who were treated with radiotherapy alone during the same period were used as controls. The patients were followed for two years. The incidence of response rate did not differ significantly between regimens; however, the incidence of side effects with bleomycin-radiotherapy, 82.61%, is significantly more than that of radiotherapy alone (52.78%). Median survial time (MST) of those responding to bleomycin-radiotherapy protocol was seven months and 12 days and for radiotherapy responders was six months. Neither the response rate nor the MST improve significantly after pretreatment with bleomycin. On the contrary, the incidence of side effects increased significantly

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Fulminant hyperpyrexia induced by bleomycin.  

Science.gov (United States)

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 describe a fatal hyperpyrexial reaction after bleomycin in a patient with T-cell lymphoma who had had no febrile response when she received her initial injection 3 weeks earlier. Since the occurrence of this hyperpyrexial response is unpredictable, health care workers as well as patients and relatives should always be alert to this potentially lethal complication and prompt measures should be taken in any patient who develops fever after bleomycin use. PMID:2481850

Leung, W. H.; Lau, J. Y.; Chan, T. K.; Kumana, C. R.

1989-01-01

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Labeled bleomycin as a tumor localizing agent  

International Nuclear Information System (INIS)

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.)

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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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DNA interaction with 57Co-bleomycin  

International Nuclear Information System (INIS)

Tumor-diagnostic 57Co-bleomycin is a mixture of two isomers: types I and II. Interaction between these and DNA was studied by fluorescence spectrometry and thermal denaturation. The fluorescence study indicated that cobalt chelation resulted in a remarkable increase in the apparent DNA-bleomycin association constant and a slight increase in bleomycin-DNA binding; a remarkable difference was observed between the two isomers. In the thermal denaturation study, the difference of DNA binding behavior was also observed. The tumor affinity of these isomers was slightly different, and type I isomer showed higher tumor affinity than type II. These results indicate that cobalt chelation to bleomycin enhances DNA-bleomycin binding and its DNA binding stability, and these mechanisms, although not fully understood, appear to underline the difference in tumor affinity of cobalt-bleomycin isomers. (orig.)

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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

2013-09-01

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Action of bleomycin is affected by bleomycin hydrolase but not by caveolin-1.  

Science.gov (United States)

Bleomycin is a first-line clinically used antitumor antibiotic for effective treatment of certain types of cancer in combination with other antitumor agents. Its action is affected by bleomycin hydrolase (BLH), DNA repair enzymes, membrane transport proteins and other cellular factors. To clarify whether BLH confers the resistance to bleomycin in tumor cells, it is necessary to further investigate the roles of BLH and its combination with other factors such as caveolin-1 in the action of bleomycin. In this study fourteen human cell lines were used for determination of bleomycin action and roles of BLH and caveolin-1. The relationship between action of bleomycin and cellular amount of BLH was detected by the MTT method and western blotting in the human leukemia cell line HL-60, HeLa cervical cancer cells and HaCaT immortalized keratinocyte cells. The sensitivity to bleomycin was increased in HeLa cells after knockdown of BLH mRNA by RNA interference. There is no relationship between caveolin-1 levels and action of bleomycin, although the distribution of the cell cycle was altered in the caveolin-1-knockdown HeLa cells after treatment with bleomycin. In addition, regulation of BLH and caveolin-1 expression in HeLa and HaCaT cells was observed in a concentration-dependent manner after exposure to bleomycin. In conclusion, bleomycin hydrolase is one of the biomarkers for determination of bleomycin action. Although caveolin-1 can respond to bleomycin treatment, it is unrelated to bleomycin sensitivity. PMID:23076812

Chen, Jianguo; Chen, Yang; He, Qiyang

2012-12-01

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

International Nuclear Information System (INIS)

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)

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Bleomycin-related lung damage: CT evidence  

International Nuclear Information System (INIS)

Computed tomography (CT) examinations of the chest were evaluated in 100 patients treated with bleomycin. The CT findings were compared with those of conventional chest radiographs and lung-function tests. Lung damage due to bleomycin was detected in 38% of patients by CT, while damage was detected in only 15% by radiography. Changes in appearance seen on CT scans due to bleomycin damage were compared with measurements of lung volume and gas transfer per unit lung volume. There was good correlation between severity of damage shown on CT scans and changes in lung volume. Gas transfer capabilities were reduced in most patients regardless of changes observed on CT scans. Sequential CT studies showed that complete resolution of bleomycin damage may occur within 9 months in patients with minor or moderate damage. Residual abnormalities were seen in all patients with severe damage

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Stress Linearization and Strength Evaluation of the BEP's Flow Plates for a Dual Cooled Fuel Assembly  

International Nuclear Information System (INIS)

A fuel assembly is composed of 5 major components, such as a top end piece (TEP), a bottom end piece (BEP), spacer grids (SGs), guide tubes (GTs) and an instrumentation tube (IT) and fuel rods (FRs). There are no ASME criteria about all components except for a TEP/BEP. The TEP/BEP should satisfy stress intensity limits in case of condition A and B of ASME, Section III, Division 1 . Subsection NB. In a dual cooled fuel assembly, the array and position of fuels are changed from those of a conventional PWR fuel assembly to achieve a power uprating. The flow plates of top/bottom end pieces (TEP/BEP) have to be modified into proper shape to provide flow holes to direct the heated coolant into/out of the fuel assembly but structural intensity of these plates within a 22.241 kN axial loading should satisfy Tresca stress limits in ASME code. In this paper, stress linearization procedure and strength evaluation of a newly designed BEP for the dual cooled fuel assembly are described

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Measurement of the reaction ^7Be(p,?)^8B with a solid radioactive target  

Science.gov (United States)

The reaction ^7Be(p,?)^8B is regarded as a key to the understanding of the solar neutrino spectrum and thus most probably to the understanding of new neutrino properties. This contribution describes an experiment measuring the absolute cross section of ^7Be(p,?)^8B with a solid radioactive target in the energy range between 350 keV and 2.6 MeV. The experiment was performed at the Dynamitron Tandem Laboratory of the Ruhr-Universitaet Bochum, Germany.

Greife, Uwe

2000-04-01

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Intracellular distribution of 57Bleomycin  

International Nuclear Information System (INIS)

Since the first promising results of Nouel et al. 1972, additional positive experience has been obtained with 57Co-Bleomycin (57Co-BLM) as a tumour-localizing agent. In this preclinical study, mice with transplanted osteosarcoma and lymphosarcoma were used and rats with transplanted rhabdomyosarcoma. 57CoCl2 served as a control substance. 57Co-BLM had concentrated in the tumours with a factor 2 to 10 as compared to the (normal) liver of the animals. No preferential concentration in the tumours was found when 57CoCl2 was used. The highest specific activity of 57Co-BLM (cpm/mg protein) was found in a fraction containing mitochondria and lysosomes. Evidence for a lysosomal localization of this diagnostic compound was obtained from experiments in which the mitochondrial-lysosomal fraction was treated with hypertonic media of different osmolarities. Conditions could be found in which many lysosomes burst while almost all mitochondria were intact. From these experiments it appeared that the radioactivity in the particles obtained from animals injected with 57Co-BLM was released very rapidly. (Auth.)

 
 
 
 
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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

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Ultraviolet enhancement of DNA base release by bleomycin  

International Nuclear Information System (INIS)

The effect of UV irradiation on base-releasing activity of bleomycin was studied on bleomycin A2-DNA reaction mixture in the presence of Fe(II) and 2-mercaptoethanol. This effect was measured by the release of free bases from calf thymus DNA with high-performance liquid chromatography. UV irradiation enhanced DNA base-releasing activity of bleomycin and simultaneously caused disappearance of fluorescence emission maximum at 355 nm assigned to bithiazole rings and increase in the intensity of a peak at 400 nm. UV irradiation at 295 nm, the UV absorption maximum of bleomycin, is the most effective in releasing free bases and in changing fluorescence emission patterns. From these results, we suggest that some alterations in the bithiazole group of bleomycin molecule were initiated by UV irradiation and contributed to increased base-releasing activity of bleomycin through a yet unexplained mechanism, presumably through bleomycin dimer formation. (orig.)

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Radiative capture reaction 7Be(p,?)8B in the continuum shell model  

International Nuclear Information System (INIS)

We present here the first application of realistic shell model (SM) including coupling between many-particle (quasi-)bound states and the continuum of one-particle scattering states to the calculation of the total capture cross section and the astrophysical factor in the reaction 7Be(p,?)8B. (orig.)

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BLEOMYCIN EFFECTS ON MOUSE MEIOTIC CHROMOSOMES  

Science.gov (United States)

The effects of a radiomimetic chemical, bleomycin (BLM), on meiotic chromosomes was evaluated in mice. hromosome aberrations were analyzed at meiotic metaphase I, and damage to the synaptonemal complex was analyzed in meiotic prophase cells. n the metaphase aberration studies, an...

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PAC study of 111In-bleomycin complex in solutions  

International Nuclear Information System (INIS)

Bleomycin is an antibiotic with molecular weight of 1500 and is known as an anticancer medicine. Bleomycin forms complexes with a variety of metals such as Fe, Co, Cu, In etc. As a bleomycin molecule provides five bonds to the metal, the complex of a metal which favors six coordinations, is liable to bind with a molecule as O2, NO, CO etc. in the solution. Besides, the thiazole ring of Fe-bleomycin complex interacts electrostatically with a thymin base of DNA molecule and cleaves the DNA molecule giving rise to anticancer function. The oxidation-reduction process of Fe-bleomycin complex activated by the bound oxygen is believed to play an important role in the DNA cleavage. In3+ ion may be often regarded as a substitute of Fe3+ ion in the biochemical conditions. An In-bleomycin complex also interacts with a DNA molecule, but is unable to cleave the molecule due to the lack of the oxidation-reduction ability. Accordingly, In-bleomycin is an appropriate molecule to study the interaction of a bleomycin complex with a DNA molecule. A number of physicochemical techniques have been employed to elucidate the cleavage of DNA molecule by a bleomycin complex mostly in concentrated solutions of bleomycin complex compared with the living body conditions. In 1978, Sastry et al. measured the perturbed angular correlations of ? rays from 111Cd in a variety of solutions and reported an anomalous concentration dependence of the time integrated attenuation factor G2 in the lower concentration solution than 10-5 M of bleomycin containing DNA. This paper motivated us to investigate the system in more detail by means of time differential PAC. The present paper is concerned with the ?-? PAC of 111Cd in various solutions to study microscopically the interaction of In3+ ions with coexisting solute molecules especially bleomycin and DNA. (orig.)

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A modified MM2 force field for bleomycin analysis  

Science.gov (United States)

New MM2 parameters for the cobalt binding site in cobalt-bleomycin, a potent antitumor antibiotic, are presented. These force constants were successfully used to model crystal structures of two cobalt-bleomycin analogues. Calculations on the bithiazole part of bleomycin show that the trans form is more stable than the cis form. It is also shown that conformational searches are necessary even in small inorganic molecules.

Charles, Robert; Ganly-Cunningham, Marcela; Warren, Rachel; Zimmer, Marc

1992-02-01

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BEP Enhancement for Semi-Femtocell MIMO Systems Employing SC-QICs and OSTBCs  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In mobile cellular networks, it is estimated that more than 60% of voice and data services occur indoors. Therefore, cellular network operators have shown an unprecedented interest in research on femtocell systems from various aspects to extend the indoor wireless coverage for providing high-quality and high data-rate wireless multimedia services contents. In an effort for reducing the bit-error probabilities (BEPs) and also increasing bit/symbol capacity of bandwidth limited error-prone wire...

Ardavan Rahimian; Farhad Mehran

2013-01-01

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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

2005-06-01

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Metal complexes of bleomycin: evaluation of [Rh-105]-bleomycin for use in targeted radiotherapy  

International Nuclear Information System (INIS)

Bleomycin has been used as a carrier for several radioisotopes; however, its potential for clinical use has been limited either by the in vivo stability of the complexes or the half-life of the isotope used. The chemical, biological, and radiological properties of 105Rhodium appear to make it an ideal choice for targeted radiotherapy. The synthesis and purification of a hereto unreported 105Rhodium-bleomycin (105Rh-BLM) complex is described. The stability of this complex in plasma is sufficient to allow targeted delivery of the radioisotope. 57Cobalt-bleomycin was studied under identical conditions for comparative purposes. The suitability of 105Rh-BLM for targeted therapy, which appears to be limited by the renal clearance of this agent, is discussed

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7Be(p, ?)8B and the high-energy solar neutrino flux  

International Nuclear Information System (INIS)

Despite thirty years of extensive experimental and theoretical work, the predicted solar neutrino flux is still in sharp disagreement with measurements. The solar neutrino measurements strongly suggest that the problem cannot be solved within the standard electroweak and astrophysical theories. Thus, the solar neutrino problem constitutes the strongest evidence for physics beyond the Standard Model. Whatever the solution of the solar neutrino problem turns out to be, it is of paramount importance that the input parameters of the underlying electroweak and solar theories rest upon solid ground. The most uncertain nuclear input parameter in standard solar models is the low-energy 7Be(p, ?)8B radiative capture cross section. This reaction produces 8B in the Sun, whose ?+ decay is the main source of the high-energy solar neutrinos. Here, the importance of the 7Be(p, ?)8B reaction in predicting the high energy solar neutrino flux is discussed. The author presents a microscopic eight-body model and a potential model for the calculation of the 7Be(p, ?)8B cross section

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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

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Copper-dependent cleavage of DNA of bleomycin  

International Nuclear Information System (INIS)

DNA strand scission by bleomycin in the presence of Cu and Fe was further characterized. It was found that DNA degradation occurred readily upon admixture of Cu(I) or Cu(II) + dithiothreitol + bleomycin, but only where the order of addition precluded initial formation of Cu(II)-bleomycin or where sufficient time was permitted for reduction of formed Cu(II)-bleomycin to Cu(I)-bleomycin. DNA strand scission mediated by Cu + dithiothreitol + bleomycin was inhibited by the copper-selective agent bathocuproine when the experiment was carried out under conditions consistent with Cu chelation by bathocuproine on the time scale of the experiment. Remarkably, it was found that the extent of DNA degradation obtained with bleomycin in the presence of Fe and Cu was greater than that obtained with either metal ion alone. A comparison of the sequence selectivity of bleomycin in the presence of Cu and Fe using32P-end-labeled DNA duplexes as substrates revealed significant differences in sites of DNA cleavage and in the extent of cleavage at sites shared in common. For deglycobleomycin and decarbamoylbleomycin, whose metal ligation is believed to differ from that of bleomycin itself, it was found that the relative extents of DNA cleavage in the presence of Cu were not in the same order as those obtained in the presence of Fe. The results of these experiments are entirely consistent with the work of Sugiura who first demonstrate the generation of reactive oxygen species upon admixture of O2 and Cu(I)-bleomycin

33

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

34

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

Directory of Open Access Journals (Sweden)

Full Text Available 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 ??? fading. We will present ??? fading model, probability density function (PDF, and cumulative distribution function (CDF. We will also present PDF, CDF, and outage probability of the L-branch MRC output. BEP/SEP will be evaluated for broad class of modulation types and for coherent and noncoherent types of detection. BEP/SEP and outage performances of the MRC will be evaluated for different number of branches via Monte Carlo simulations and theoretical expressions.

Mirza Miliši?

2009-01-01

35

Dermatite flagelada induzida pela bleomicina Bleomycin- induced flagellate dermatitis  

Directory of Open Access Journals (Sweden)

Full Text Available 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.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.

Júlio César Gomes Silveira

2006-02-01

36

The effects of Bleomycin A5 on infantile maxillofacial haemangioma  

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Full Text Available Abstract Objective To examine the effects of bleomycin A5 on infantile maxillofacial haemangiomas. Methods Bleomycin A5 was given by multiple intralesinoal injections and the dosage was given according to the age of the patient and size of the lesion. Parts of patients were accompanied by prednisone treatment(2-5 mg/kg, po, QOD. Results All the haemangiomas involuted completely after treated with bloemycin A5 with better recovery of skin color and less scar forming in small haemangiomas. Conclusion Infantile haemangioma could be effectively treated with bleomycin A5 without serious side effects.

Zhao Fu-yun

2011-07-01

37

Reanalysis of the 7Be(p,?)8B S factor in a microscopic model  

International Nuclear Information System (INIS)

A previous microscopic three-cluster calculation, applied to the 7Be(p,?)8B reaction, is updated in several ways: the 7Be description is improved, two nucleon-nucleon interactions are considered, and new experimental information about the scattering lengths is taken into account. Weak changes in the energy dependence of the S factor are obtained. A 'theoretical' uncertainty is estimated. It amounts to 5% near 1 MeV but reaches more than 10% when energy increases. We suggest that reducing the current uncertainty on the experimental scattering length would significantly reduce the error bar on S17(0). Elastic 7Be+p phase shifts are briefly discussed and analyzed for different 7Be deformations. We show that the differences with the potential model are due to shortcomings of that model, such as the lack of 7Be deformation, included in the present approach. We also investigate the 8Li and 8B spectroscopy, electromagnetic transition probabilities, and spectroscopic factors. The 5He+3H configuration (or mirror) is shown to be important in the ground-state structure

38

Labelling and pharmacokinetics of 131I-bleomycin with regard to tumor affinity and in comparison with 57Co- and 111In-bleomycin  

International Nuclear Information System (INIS)

Bleomycin was labelled with 131I and checked electrophoretically and chromatographically as to its activity. The pharmacokinetics of 131I-bleomycin were tested in mice bearing different tumors. Its whole-body retention and organ distribution were determined in comparison to 57Co- and 111In-bleomycin, resp

39

Human telomeric DNA sequences are a major target for the antitumour drug bleomycin.  

Science.gov (United States)

The DNA sequence specificity of the cancer chemotherapeutic agent bleomycin was examined in a human telomeric DNA sequence and compared with that of non-telomeric sequences. The target DNA sequence contained 17 repeats of the human telomeric sequence and other primary sites of bleomycin cleavage. The 377-base-pair target DNA was fluorescently labelled at the 3'-end, damaged with bleomycin and electrophoresed in an ABI 3730 automated capillary sequencer to determine the intensity and sequence specificity of bleomycin damage. The results revealed that bleomycin cleaved primarily at 5'-GT in the telomeric sequence 5'-GGGTTA. Maxam-Gilbert chemical sequencing reactions were utilised as DNA size markers to determine the precise sites of bleomycin cleavage. The telomeric region contained strong sites of bleomycin cleavage and constituted 57% of the 30 most intense bleomycin damage sites in the DNA sequence examined. These data indicated that telomeric DNA sequences are a major site for bleomycin damage. PMID:21761251

Nguyen, Trung V; Murray, Vincent

2012-01-01

40

Scintigraphic studies of malignant tumors using 111In-bleomycin  

International Nuclear Information System (INIS)

A study was made of the potentialities of 111In-bleomycin in the diagnosis of lung cancer, malignant lymphomas, breast, nasopharyngeal and colonic cancer, lung metastases of synovial sarcoma. There were examined patients operated on for lung cancer to detect metastases to mediastinal lymph nodes. A group of patients with benign tumors and chronic inflammatory lung processes was examined for differential diagnosis of malignant and benign tumors. A total of 135 patients were examined using 111In-bleomycin. The results of radioisotope studies were verified by operative, morphological, X-ray and endoscopic findings. A high sensitivity has been shown for 111In-bleomycin in the diagnosis of lung and colonic cancer, malignant lymphomas. No correlation has been shown between the accumulation of 111In-bleomycin and the histologic structure of malignant tumors

 
 
 
 
41

51Cr-bleomycin, a new oncophilic radiopharmaceutical. Pt. 2  

International Nuclear Information System (INIS)

51Cr-bleomycin was used for the scintigraphic detection of tumours and the assessment of the spread of the disease in 20 patients with various malignances: 7 with Hodgkin's lymphoma, 5 with other malignant lymphomas, 4 cases of cervix carcinoma and 4 other tumours. The scintigraphy was performed using a Toshiba GC 401 gamma camera coupled to an MDSI computer Trinary. Active foci were scored using a semiquantitative scale of 0 to 5. Results of these studies were compared with those of tests similarity carried out with 57Co-bleomycin (in 9 of the cases) and 67Ga-citrate (11 cases); they demonstrated that the properties of 51Cr-bleomycin for scintigraphic detection of neoplastic foci are similar to those of 57Co-bleomycin. (orig.)

42

Development of 166Ho bleomycin as a possible therapeutic complex  

International Nuclear Information System (INIS)

Due to interesting therapeutic properties of 166Ho and the antineoblastic antibiotic, bleomycin (BLM), 166Ho-bleomycin (166Ho-BLM) was developed as a possible therapeutic compound. 166Ho chloride was obtained by thermal neutron irradiation (1 x 1013 n cm-2 s-1) of natural Ho(NO3)3 samples (specific activity = 3-5 GBq mg-1), dissolved in acidic media. At optimized conditions (room temperature, 12 h, 0.15-0.3 mg bleomycin for 74 MBq 166HoCl3) a radiochemical purity of 94-97% was obtained as shown by ITLC and HPLC (specific activity, 700-740 GBq mmol-1). Biodistribution studies of 166Ho chloride and 166Ho-BLM were performed in wild-type rats. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins. (author)

43

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

2013-08-01

44

Effects of bone marrow depression on the development of bleomycin-induced pulmonary fibrosis  

International Nuclear Information System (INIS)

The effects of blood leukocyte depression on the development of bleomycin-induced pulmonary fibrosis were studied in F344/N rats injected with 89Sr to destroy bone marrow cells. The 89Sr injections were followed in 7 days by intratracheal instillation of bleomycin. At 3 to 30 days after bleomycin, the lung injury in rats given both 89Sr and bleomycin was compared to animals given bleomycin alone. The 89Sr treated rats had reduced numbers of circulating granulocytes, a less severe pulmonary inflammatory response, and a delayed, but not abrogated, pulmonary fibrosis compared to animals given bleomycin alone. 4 references, 4 figures, 2 tables

45

Resveratrol alleviates bleomycin-induced lung injury in rats.  

Science.gov (United States)

Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant balance such as pulmonary fibrosis. This study was designed to examine the effects of resveratrol, an antioxidant agents, against bleomycin-induced pulmonary fibrosis and oxidative damage. Wistar albino rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula) followed by either saline or resveratrol (10 mg/kg; orally) for 14 days. The effect of resveratrol on pulmonary oxidative damage was studied by cell count and analysis of cytokine levels (TGF-beta, TNF-alpha, IL-1beta and IL-6) in the bronchoalveolar lavage fluid (BALF) and biochemical measurements of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of neutrophil infiltration, in the lung tissue. Bleomycin-induced lung fibrosis was determined by lung collagen contents and also microscopically. Bleomycin caused a significant decrease in lung GSH, which was accompanied with significant increases in MDA level, MPO activity, and collagen contents of the lung tissue concomitant with increased levels of the pro-inflammatory mediators and cell count in BALF. On the other hand, resveratrol treatment reversed all these biochemical indices as well as histopathological alterations induced by bleomycin. The results demonstrate the role of oxidative mechanisms in bleomycin-induced pulmonary fibrosis, and resveratrol, by its antioxidant properties, ameliorates oxidative injury and fibrosis due to bleomycin. Thus, an effective supplement with resveratrol as an adjuvant therapy may be a very promising agent in alleviating the side effects of bleomycin, an effective chemotherapeutic agent. PMID:17035056

Sener, Göksel; Topalo?lu, Nurhayat; Sehirli, A Ozer; Ercan, Feriha; Gedik, Nursal

2007-01-01

46

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

2011-11-01

47

Absolute cross section of sup 7 Be(p, gamma) sup 8 B  

CERN Document Server

The absolute cross section sigma(E) for the radiative capture reaction sup 7 Be(p, gamma) sup 8 B at the center-of-mass energies E=0.32 to 2.61 MeV has been measured using a sup 7 Be target deposited on a Cu backing and observing the beta-delayed alpha-particles from sup 8 B. The backing causes a loss of less than 1% of the sup 8 B residual nuclides. The resulting astrophysical S(E) factor at zero energy, S(0)=18.4+-1.6 eV b, is consistent only with a restricted data set from previous work.

Strieder, F; Gyuerky, G; Schuemann, F; Bonetti, R; Broggini, C; Campajola, L; Corvisiero, P; Costantini, H; D'Onofrio, A; Formicola, A; Fülöp, Z; Gervino, G; Greife, U; Guglielmetti, A; Gustavino, C; Imbriani, G; Junker, M; Moroni, P G P; Ordine, A; Prati, P; Roca, V; Rogalla, D; Rolfs, C; Romano, M; Somorjai, E; Straniero, O; Terrasi, F; Trautvetter, H P; Zavatarelli, S

2001-01-01

48

Expression of bleomycin hydrolase in keratinization disorders.  

Science.gov (United States)

A neutral cysteine protease, bleomycin hydrolase (BH), is widely expressed in mammalian tissues, with the skin seeming to contain the highest level. Our previous study revealed that BH transcription is modulated both during differentiation and by cytokines. However, BH involvement in keratinization disorder is not well known. In the present study, we performed immunohistochemical studies of BH and other serine/cysteine proteases in human normal skin and lesional skin with keratinization disorders. BH-positive cells were detected in granular layers of orthokeratotic and hyperkeratotic skin diseases, such as erythrokeratoderma and lichen planus. In parakeratotic skin diseases with porokeratosis, pityriasis rubra pilaris and psoriasis, BH staining was decreased in lesional skins compared to that in normal skin. Similar results were obtained for cysteine proteases, caspase-14 and calpain I. On the other hand, cells positive for serine proteases kallikrein 5 and 7 were increased in parakeratotic and inflammatory skin diseases, such as psoriasis. Semi-quantification analysis revealed that BH- and caspase-14-positive staining had higher intensity than those of the other proteases in normal epidermis. As BH is the major citrulline aminopeptidase in normal granular layer, the alternation would have a significant effect on terminal differentiation processes, such as aberrant processing of deiminated peptides. Therefore, BH may play an important role during the late stage of epidermal differentiation. PMID:22037625

Kamata, Yayoi; Maejima, Hideki; Watarai, Akira; Saito, Norimitsu; Katsuoka, Kensei; Takeda, Atsushi; Ishihara, Kazuhiko

2012-01-01

49

Dermatite flagelada induzida pela bleomicina / Bleomycin- induced flagellate dermatitis  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese 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 clin [...] ical and etiopathogenic aspects in a brief blibliographic revision.

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

50

Detection of lung cancer with 55Co-bleomycin using a positron camera  

International Nuclear Information System (INIS)

57Co-bleomycin is useful in the detection and staging of lung cancer, but the long half-life of 57Co(270 days) has discouraged its widespread acceptance. We investigated the shorter living positron emitting 55Co(half-life 18.2 h) as a label for bleomycin. In eleven patients with proven lung cancer scintigraphy with 55Co-bleomycin, using a positron camera, demonstrated the tumor in ten cases. Tumor to lung ratios were calculated. The results were superior to those obtained with 55Co-bleomycin single photon imaging but inferior to those obtained with 57Co-bleomycin scintigraphy. (orig.)

51

Interaction of bleomycin and its oligonucleotide derivatives with nucleic acids  

Science.gov (United States)

Various aspects of interaction of the antitumour glycopeptide antibiotic bleomycin with nucleic acids are considered. Data on equilibrium binding parameters obtained by various physicochemical methods have been collected and compared. The contribution of N- and C-terminal domains of the glycopeptide molecule to the binding with DNA and sequence specificity of DNA cleavage are discussed. Data on a recently created new class of compounds — bleomycin — oligonucleotide conjugates — are presented. These compounds, like antibiotics, possess DNA-cleaving activity (also in a catalytic manner) together with high selectivity towards a selected nucleotide sequence. The bibliography includes 267 references.

Sergeyev, D. S.; Zarytova, V. F.

1996-04-01

52

Bleomycin Sclerotherapy for Severe Symptomatic and Persistent Pelvic Lymphocele  

Science.gov (United States)

Background. Pelvic lymphoceles are frequently described as a complication of pelvic lymphadenectomy performed for surgical staging of gynaecologic malignancies. Case Report. A 72-year-old woman presented with severe symptomatic and refractory lymphocele associated with persistent lower limb lymphedema and recurrent erysipelas. After four CT fluoroscopy scan guided percutaneous catheter drainages, the lymphocele complicated with infection finally resolved with two sessions of bleomycin sclerotherapy. Conclusion. Symptomatic persistent lymphoceles require treatment and nowadays the first option is interventional radiologic procedures. Bleomycin is a safe and effective sclerosing agent and therefore should be regarded as a first-line treatment choice. PMID:25105040

Fernandes, Ana Sofia; Costa, Antonia; Mota, Raquel; Paiva, Vera

2014-01-01

53

An angular momentum selection rule and the 9Be(?+,p)8Be reaction at 50 MeV  

International Nuclear Information System (INIS)

Angular distributions have been measured at 50 MeV for the 9Be(?+,p)8Be reaction leading to the 0+, 2+ and 4+ states of 8Be. An angular momentum selection rule is considered in order to account for the preferential excitation of high spin states. Two-step processes in the framework of the DWBA and momentum sharing in the two-nucleon model are also discussed

54

Effects of x-rays and bleomycin on cultured mammalian cells  

International Nuclear Information System (INIS)

The cultured brain tumor cells and established cell lines, HeLa S3 and L5, were exposed to X-rays, with and without combinations of bleomycin, and the reproductive capacity and growth curves of these treated cells were assayed. No enhancement of the cell killing effect was observed when cells were treated with bleomycin following irradiation, while preliminary bleomycin treatment sensitized the cells to irradiation. No division delay was observed in cell reproductively surviving the bleomycin treatment, even though the concentrations of bleomycin were sufficient to reduce the survivals to less than 10%. An attempt to determine the conversion factor for evaluating X-ray doses in bleomycin equivalents failed because the order of the radiosensitivity of these cells was different from that of the sensitivity to bleomycin treatment. (author)

55

Structure of 8B from elastic and inelastic 7Be+p scattering  

CERN Document Server

Motivation: Detailed experimental knowledge of the level structure of light weakly bound nuclei is necessary to guide the development of new theoretical approaches that combine nuclear structure with reaction dynamics. Purpose: The resonant structure of 8B is studied in this work. Method: Excitation functions for elastic and inelastic 7Be+p scattering were measured using a 7Be rare isotope beam. Excitation energies ranging between 1.6 and 3.4 MeV were investigated. An R-matrix analysis of the excitation functions was performed. Results: New low-lying resonances at 1.9, 2.5, and 3.3 MeV in 8B are reported with spin-parity assignment 0+, 2+, and 1+, respectively. Comparison to the Time Dependent Continuum Shell (TDCSM) model and ab initio no-core shell model/resonating-group method (NCSM/RGM) calculations is performed. This work is a more detailed analysis of the data first published as a Rapid Communication. [J.P. Mitchell, et al, Phys. Rev. C 82, 011601(R) (2010)] Conclusions: Identification of the 0+, 2+, 1+...

Mitchell, J P; Johnson, E D; Baby, L T; Kemper, K W; Moro, A M; Peplowski, P; Volya, A S; Wiedenhoever, I

2013-01-01

56

7Be(p, ?)8B S-factor from ab initio wave functions  

International Nuclear Information System (INIS)

Nuclear structure of 7Be, 8B and 7,8Li is studied within the ab initio no-core shell model (NCSM). Starting from the high-precision CD-Bonn 2000 nucleon-nucleon (NN) interaction, wave functions of 7Be and 8B bound states are obtained in basis spaces up to 10-bar ? and used to calculate channel cluster form factors (overlap integrals) of the 8B ground state with 7Be-bar +-bar p. Due to the use of the harmonic oscillator (HO) basis, the overlap integrals have incorrect asymptotic properties. We fix this problem in two alternative ways. First, by a Woods-Saxon (WS) potential solution fit to the interior of the NCSM overlap integrals. Second, by a direct matching with the Whittaker function. The corrected overlap integrals are then used for the 7Be(p, ?)8B S-factor calculation. We study the convergence of the S-factor with respect to the NCSM HO frequency and the model space size. Our S-factor results are in agreement with recent direct measurement data

57

Corilagin Attenuates Aerosol Bleomycin-Induced Experimental Lung Injury  

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Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressing lethal disease with few clinically effective therapies. Corilagin is a tannin derivative which shows anti-inflammatory and antifibrotics properties and is potentiated in treating IPF. Here, we investigated the effect of corilagin on lung injury following bleomycin exposure in an animal model of pulmonary fibrosis. Corilagin abrogated bleomycin-induced lung fibrosis as assessed by H&E; Masson’s trichrome staining and lung hydroxyproline content in lung tissue. Corilagin reduced the number of apoptotic lung cells and prevented lung epithelial cells from membrane breakdown, effluence of lamellar bodies and thickening of the respiratory membrane. Bleomycin exposure induced expression of MDA, IKK?, phosphorylated IKK? (p-IKK?, NF-?B P65, TNF-? and IL-1?, and reduced I-?B expression in mice lung tissue or in BALF. These changes were reversed by high-dose corilagin (100 mg/kg i.p more dramatically than by low dose (10 mg/kg i.p. Last, corilagin inhibits TGF-?1 production and ?-SMA expression in lung tissue samples. Taken together, these findings confirmed that corilagin attenuates bleomycin-induced epithelial injury and fibrosis via inactivation of oxidative stress, proinflammatory cytokine release and NF-?B and TGF-?1 signaling. Corilagin may serve as a promising therapeutic agent for pulmonary fibrosis.

Zheng Wang

2014-05-01

58

Acute respiratory failure induced by bleomycin and hyperoxia  

International Nuclear Information System (INIS)

Bleomycin, a chemotherapeutic agent, and oxygen at concentrations greater than 20%, induce acute pulmonary damage separately and when administered together. The interaction of 5 U/kg intratracheal bleomycin and 24 hours of exposure to 80% oxygen in hamsters produces delayed onset acute respiratory distress syndrome three days after treatment. As little as 12 hours of 80% O2 exposure, after intratracheal bleomycin, induces severe pulmonary damage. Lung lesions are characterized as diffuse alveolar damage. Significantly pulmonary edema, measured by iodine-125-bovine serum albumin and technetium-99m-diethylenetriaminepentaacetate, occurs 72 hours after treatment. Lesions progress from focal mild alveolar interstitial and air-space macrophage and granulocyte infiltrates at 24 hours to marked infiltrates and severe interstitial and air space edema with hemorrhages and hyaline membranes at 96 hours. Significant changes measured by electron microscopy morphometry are increases in volume fractions of neutrophils, alveolar tissue and mononuclear leukocytes. Surfactant assay of bronchoalveolar lavage fluid shows a marked decrease in the lecithin/sphingomyelin ratio at 72 hours. Proposed mechanisms of bleomycin and hyperoxia synergism include enhanced production of superoxide radicals either directly or indirectly by increasing neutrophil activity or numbers, or by alteration of cell mediators. The pulmonary edema, without evidence of severe morphological changes, may be secondary to alterations of transalveolar transport mechanisms

59

Structure of 8B from elastic and inelastic 7Be+p scattering  

Science.gov (United States)

Background: Detailed experimental knowledge of the level structure of light weakly bound nuclei is necessary to guide the development of new theoretical approaches that combine nuclear structure with reaction dynamics.Purpose: The resonant structure of 8B is studied in this work.Method: Excitation functions for elastic and inelastic 7Be+p scattering were measured using a 7Be rare isotope beam. Excitation energies ranging between 1.6 and 3.4 MeV were investigated. An R-matrix analysis of the excitation functions was performed.Results: New low-lying resonances at 1.9, 2.54, and 3.3 MeV in 8B are reported with spin-parity assignment 0+, 2+, and 1+, respectively. Comparison to the time-dependent continuum shell (TDCSM) model and ab initio no-core shell model/resonating-group method (NCSM/RGM) calculations is performed. This work is a more detailed analysis of the data first published as a Rapid Communication. J. P. Mitchell, G. V. Rogachev, E. D. Johnson, L. T. Baby, K. W. Kemper , [Phys. Rev. CPRVCAN0556-281310.1103/PhysRevC.82.011601 82, 011601(R) (2010)].Conclusions: Identification of the 0+, 2+, 1+ states that were predicted by some models at relatively low energy but never observed experimentally is an important step toward understanding the structure of 8B. Their identification was aided by having both elastic and inelastic scattering data. Direct comparison of the cross sections and phase shifts predicted by the TDCSM and ab initio no-core shell model coupled with the resonating group method is of particular interest and provides a good test for these theoretical approaches.

Mitchell, J. P.; Rogachev, G. V.; Johnson, E. D.; Baby, L. T.; Kemper, K. W.; Moro, A. M.; Peplowski, P.; Volya, A. S.; Wiedenhöver, I.

2013-05-01

60

Effect of glutathione on radioactivity and antibacterial activity of 14C-bleomycin in organs  

International Nuclear Information System (INIS)

I performed an experiment on the relationship between 14C-bleomycin and glutathione in vivo, especially on the relationship of radioactivity and antibacterial activity, and the results will be reported here. 1) When bleomycin and glutathione were administered simultaneously and animals were killed after 30 minutes, decrease in bleomycin concentration in every organ was observed. The decrease rate in tumor was especially great (radioactivity: 80.3%, antibacterial activity: 78.4%). 2) When glutathione is administered 15 minutes after administration of bleomycin and the animals were sacrificed after 30 minutes, the decrease rate was highest in the skin followed by that in tumor and extremely low in the lung. 3) When glutathion was given 30 minutes after bleomycin administration and the animals sacrificed after 60 minutes, the decrease rate of intraorgan bleomycin concentration was in the order of lung>tumor>skin. (auth.)

 
 
 
 
61

Large angle proton emission in the 9Be(p,2p) reaction at 300 MeV  

International Nuclear Information System (INIS)

A 9Be(p,2p) coincidence experiment performed to to further elucidate the reaction mechanism for the production of energetic wide-angle protons in intermediate energy proton induced reactions is reported. Detectors in a coplanar geometry were used to measure coincidences between trigger protons at 90 degrees to the beam and forward angle protons on the opposite side of the beam. The incident proton energy was 300 MeV. The authors report both the inclusive spectra for the trigger protons and the differential mean multiplicities for the coincidence events

62

Radioiodinated bleomycin: stoichiometry of iodination and structural characterization by 1H-nuclear magnetic resonance  

International Nuclear Information System (INIS)

Bleomycin was iodinated by reaction with iodine monochloride (ICl). A direct relationship was found to exist between the average number of iodine atoms bound per molecule of bleomycin and the ICl:bleomycin molar ratio. Characterization by 1H-NMR analysis denoted that mono, di-, tri- and tetraiodobleomycin are formed when the reacting molar ratios, respectively, are 2:1, 4:1, 6.8:1 and 8.5:1 or greater. The sites of iodination of the bleomycin molecule have been identified to be the imidazole ring which iodinates first, followed by the bithiazole ring system which iodinates last. (author)

63

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

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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

2001-01-01

64

Stability of 111In-bleomycin in vivo - properties compared with 57Co-bleomycin  

International Nuclear Information System (INIS)

111Indium-belomycin (111In-BLM) and 57Co-bleomycin (57Co-BLM) were prepared and their distributions were compared in the tissues, blood, and urine in tumor-bearing and in untreated mice and rats. Autoradiographs of electrophoresis gels showed that patterns for urine from untreated and tumor-bearing animals, collected 1-3 h or 48 h after injection of 111In-BLM were similar to those for in vitro mixtures of urine and 111In-BLM, but differed from the patterns obtained with 111InCl3 under in vivo or in vitro conditions. In rats bearing mammary adenocarcinoma, 48 h after administration of the radio-pharmaceutical, the activity ratio of tumor to eleven different tissues was 1.2-4.6 times higher for injected 111In-BLM than for 111InCl3 (P111In-BLM than with 111InCl3. These findings were interpreted as reflecting the stability of 111In-BLM in vivo. The tumor concentration (%dose/g) was higher for the viable area than for the necrotic area for 111In-BLM, but the reverse was true for 57Co-BLM. (orig.)

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Pharmacology and therapeutic efficacy of bleomycin administered by continuous infusion  

International Nuclear Information System (INIS)

A study was done at Memorial Hospital in which Bleomycin was given by continuous intravenous infusion to radiation therapy patients with a variety of far advanced unresectable malignant neoplastic diseases. Smaller doses than usual were administered initially, approximately 1/10 the dose that had been previously studied. The dose was gradually escalated when it was shown that there was no acute toxicity from the smaller dose. Bleomycin blood levels were measured by bioassay and pulmonary function was studied by measurement of total lung capacity and carbon monoxide diffusing capacity. In this study, therapeutic activity in cervix cancer appeared to be significantly better than in earlier studies by the same group of investigators. However, in vitro and animal studies in the author's own clinical pharmacologic studies support the logic of continuous intravenous administration in the effort to decrease pulmonary toxicity and to improve therapeutic effect

66

Re-186-bleomycine: Radiopharmaceutic for diagnosis and therapy  

International Nuclear Information System (INIS)

Bleomycine is an antibiotic used for chemotherapy of several neoplasms. Earlier studies with labelling of bleomycine (BLM) with different radionuclide were done. It was tested for different kind of tumours imaging. Due to previous encouraging imaging results with BLM-Tc-99m , BLM-Co-57 and BLM-In-111 authors decided to check the possibility and methods of labelling BLM with Re-186 to obtain radiopharmaceuticals potentially suitable for diagnosis and treatment of some neoplastic tumours. Different methods of labelling were investigated. The best one are electrolytic and with use of cationic-Sn complex modified by using of gentisic acid and incubation of the reaction mixture at 100 deg. C for 10 min. (author)

67

Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase.  

Science.gov (United States)

Homocysteine (Hcy) editing by methionyl-tRNA synthetase results in the formation of Hcy-thiolactone and initiates a pathway that has been implicated in human disease. In addition to being cleared from the circulation by urinary excretion, Hcy-thiolactone is detoxified by the serum Hcy-thiolactonase/paraoxonase carried on high density lipoprotein. Whether Hcy-thiolactone is detoxified inside cells was unknown. Here we show that Hcy-thiolactone is hydrolyzed by an intracellular enzyme, which we have purified to homogeneity from human placenta and identified by proteomic analyses as human bleomycin hydrolase (hBLH). We have also purified an Hcy-thiolactonase from the yeast Saccharomyces cerevisiae and identified it as yeast bleomycin hydrolase (yBLH). BLH belongs to a family of evolutionarily conserved cysteine aminopeptidases, and its only known biologically relevant function was deamidation of the anticancer drug bleomycin. Recombinant hBLH or yBLH, expressed in Escherichia coli, exhibits Hcy-thiolactonase activity similar to that of the native enzymes. Active site mutations, C73A for hBLH and H369A for yBLH, inactivate Hcy-thiolactonase activities. Yeast blh1 mutants are deficient in Hcy-thiolactonase activity in vitro and in vivo, produce more Hcy-thiolactone, and exhibit greater sensitivity to Hcy toxicity than wild type yeast cells. Our data suggest that BLH protects cells against Hcy toxicity by hydrolyzing intracellular Hcy-thiolactone. PMID:16769724

Zimny, Jaroslaw; Sikora, Marta; Guranowski, Andrzej; Jakubowski, Hieronim

2006-08-11

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Clinical evaluation of radio-labelled bleomycin for tumor detection  

International Nuclear Information System (INIS)

Investigations with bleomycin labelled with radionuclides other than 57Co in patients with cancer and in tumor-bearing animals are described. In patients 57Co-bleo appears to be a better tumor-seeking radiopharmaceutical than 111In-bleo, sup(99m)Tc-bleo or 197Hg-bleo. This can be explained by a higher stability in vivo and a better tumor-seeking property of 57Co-bleo and less disturbing activity in the cardiac pool and in bone and other normal tissues when assessing the scintigram. Results with 111In-bleo labelled in acidic solution are not essentially different from those with 111In-bleo labelled in neutral solution. Results of 197Hg-bleo are almost identical with those of 197HgCl2 regarding the tumor-seeking effect as well as the distribution in normal tissues and organs. Probably the complex of 197Hg to bleomycin is not stable in vivo. The superiority of 57Co-bleo over sup(99m)Tc-bleo, 197Hg-bleo and also over 67Cu-bleo is confirmed by experiments on tumor bearing animals. We may conclude that the indication for use of bleomycin as a tumor-seeking pharmaceutical labelled with 111In, sup(99m)Tc, 197Hg or 67Cu seems to be very limited. (orig.)

69

Astrophysical S-factor of the 7Be(p,?)8B reaction from Coulomb dissociation of 8B  

Science.gov (United States)

The Coulomb dissociation method to obtain the astrophysical S-factor, S17(0), for the7 Be(p, ?)8B reaction at solar energies is investigated by analysing the recently measured data on the breakup reaction 208Pb(8B,7Bep ) 208Pb at 46.5 MeV/A beam energy. Breakup cross sections corresponding to E1, E2 and M1 transitions are calculated with a theory of Coulomb excitation that includes the effects of the Coulomb recoil as well as relativistic retardation. The interplay of nuclear and Coulomb contributions to the breakup process is studied by performing a full quantum mechanical calculation within the framework of the distorted-wave Born approximation. In the kinematical regime of the present experiment, both nuclear as well as Coulomb-nuclear interference processes affect the pure Coulomb breakup cross sections very marginally. TheE 2 cross sections are strongly dependent on the model used to describe the structure of 8B. The value ofS17 (0) is deduced with and without E2 and M1 contributions added to the E1 cross sections and the results are discussed.

Shyam, R.; Thompson, I. J.; Dutt-Mazumder, A. K.

1996-02-01

70

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

Science.gov (United States)

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. PMID:23386420

Kucuksayan, Ertan; Cort, Aysegul; Timur, Mujgan; Ozdemir, Evrim; Yucel, Suleyman Gultekin; Ozben, Tomris

2013-07-01

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Radiotherapy Does Not Influence the Severe Pulmonary Toxicity Observed With the Administration of Gemcitabine and Bleomycin in Patients With Advanced-Stage Hodgkin's Lymphoma Treated With the BAGCOPP Regimen: A Report by the German Hodgkin's Lymphoma Study Group  

International Nuclear Information System (INIS)

Purpose: To evaluate the effect of radiotherapy on the severe pulmonary toxicity observed in the pilot study of BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine) for advanced-stage Hodgkin's lymphoma. Methods and Materials: Patients with Stage III or IV Hodgkin's lymphoma or Stage IIB with risk factors participated in this single-arm, multicenter pilot study. Results: Twenty-seven patients were enrolled on the study before its premature closure as a result of the development of serious pulmonary toxicity in 8 patients. The pulmonary toxicity occurred either during or immediately after the BAGCOPP chemotherapy course. Pulmonary toxicity contributed to one early fatality but resolved in the other 7 patients after cessation of gemcitabine and bleomycin, allowing continuation of therapy. Fifteen patients received consolidative radiotherapy, including 4 who previously had pulmonary toxicity. There were no reported cases of radiation pneumonitis and no exacerbation of pulmonary symptoms in the 4 patients who had had previous pulmonary toxicity. Conclusions: The severe pulmonary toxicity observed in this study has been attributed to an interaction between gemcitabine and bleomycin. Gemcitabine (when administered without bleomycin) remains of interest in Hodgkin's lymphoma and is being incorporated into a new German Hodgkin's Lymphoma Study Group protocol that also includes consolidative radiotherapy. This study supportolidative radiotherapy. This study supports the concept of the integration of radiotherapy in gemcitabine-containing regimens in Hodgkin's lymphoma if there is an interval of at least 4 weeks between the two modalities and with a schedule whereby radiotherapy follows the chemotherapy

72

Extensive chemical degradation of bleomycin during attempted labelling with 51-Cr  

International Nuclear Information System (INIS)

Aim: Labelling of the cytostatic agent bleomycin with 51-Cr and use of the product for biodistribution studies have been reported in the literature. The labelling procedure involves incubation for 40 min at 130 C. Since bleomycins are polar glycopeptides sensitive to hydrolytic cleavage we were concerned about possible degradation of the drug during these unfavourable conditions. We have therefore investigated the stability of bleomycin as a function of temperature and pH of the solution and attempted to achieve the maximum labelling efficiency with minimal degradation of the two principal bleomycin components. Methods: The chemical stability of unlabelled bleomycin was investigated under labelling conditions at 130 C and in buffer of pH 1-6 at room temperature (23 C) and 60 C. The samples were assayed by high-performance liquid chromatography (HPLC). The labelling efficiency of the 51-Cr-bleomycin complex was determined by thin layer chromatography and activity measurement with a high pure Germanium (HPGe)-detector at various incubation temperatures and times. Results: Comparisons of rates of degradation of bleomycin with labelling efficiency as functions of temperature and time showed that under no condition could satisfactory labelling (>97%) be obtained without considerable degradation of bleomycin. Conclusion: Labelling of bleomcyin with 51-Cr does not yield a product suitable for investigations in patients. (orig.)

73

Comparative study of effects of bleomycin and x-rays on cultured mammalian cells  

International Nuclear Information System (INIS)

The responses of in vitro cultured mammalian cells to X-rays and bleomycin were compared for establishing a general rule to convert X-ray dose to bleomycin dose for a given biological effect. There was no significant difference in the radiosensitivities according to cell lines used in this experiment, while the responses of cells to bleomycin varied from cell to cell. The X-ray dose-response curves for the cells were convex upward if plotted on a semilogarithmical scale, while bleomycin dose-response curves were convex downward. These results indicated that the ratio of X-ray dose and bleomycin dose required for a comparable biological effect would vary with the X-ray dose and from cell to cell. Preliminary treatment with bleomycin sensitized mammalian L5 cells to X-rays. When the cells were exposed to bleomycin following irradiation, no significant synergestic effect was observed, in spite of the fact that the bleomycin dose was sufficient to result in a survival of 4.5%. (author)

74

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

Energy Technology Data Exchange (ETDEWEB)

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.)

Jain, Tarun P.; Thulkar, Sanjay; Saha, Sanchita [All India Institute of Medical Sciences, Department of Radiology, New Delhi (India); Bakhshi, Sameer; Dominic, Joseph [All India Institute of Medical Sciences, Department of Medical Oncology, New Delhi (India)

2005-12-01

75

The place of 57Co-bleomycin in the evaluation of tumours  

International Nuclear Information System (INIS)

162 patients were investigated by 57Co-bleomycin scintigraphy. 62 of these patients were also studied with 67Ga. 142 were suspected for malignant neoplastic disease, 20 for a focal inflammatory process. Good visualization with 57Co-bleomycin was obtained in 75% of malignant tumours and in 66% with 67Ga. Most of the patients were studied for abdominal disease and in this region 57Co-bleomycin was found to be qualitatively superior to 67Ga. The principal advantage of 57Co-bleomycin is a very low tissue background specially concerning the bowel. Neither 57Co-bleomycin nor 67Ga are tumour-specific. Both radiopharmaceuticals are taken up by inflammatory processes. This is a disadvantage in tumour diagnostics but the radionuclides can be useful for localizing inflammatory foci. The possibilities of studying the localisation of radionuclides at the cellular level will be discussed. (orig.)

76

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

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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.

2007-04-01

77

Work in progress: the effect of heat on bleomycin cytotoxicity in vitro and on the accumulation of 57Co-bleomycin in heat-treated rat tumors  

International Nuclear Information System (INIS)

The cytotoxic effects of the sequence and timing in combined hyperthermia and bleomycin treatment were tested in vitro using V79 Chinese hamster cells. The order of treatment was important; heat treatment followed by the administration of bleomycin yielded greater cytotoxicity than when the opposite order was used. To determine whether heat-treated tumors have an altered uptake of bleomycin, rat rhabdomyosarcoma (BA 1112) tumors were heated locally with RF current (43 degrees C, 90 min.), injected with 57Co-bleomycin, and imaged on a radioisotope camera. Results of tumor-to-background (T/B) ratio analysis indicate that local hyperthermia (43 degrees C) does not appear to alter tumor uptake patterns of 57Co-bleomycin; and intravenous and intraperitoneal injections produce similar T/B uptake ratios, typically between 2 and 3 at 120 minutes postinjection. In the BA 1112/WAG/Rij tumor system, local hyperthermia treatment does not seem to interfere with the subsequent accumulation of bleomycin in the tumor

78

The sup 9 Be(p, gamma) sup 1 sup 0 B cross section at low energies  

CERN Document Server

Data for the sup 9 Be(p, gamma) sup 1 sup 0 B reaction with proton energies up to 1800 keV are fitted using R-matrix formulae that include channel contributions where appropriate. The data include values of the astrophysical S factor, the branching ratios for gamma-transitions to the four lowest states of sup 1 sup 0 B, angular distributions and analysing powers. Use is made of experimental values of asymptotic normalization constants obtained from sup 9 Be( sup 1 sup 0 B, sup 9 Be) sup 1 sup 0 B. A good fit is obtained with two 1 sup - levels, two 2 sup - levels, one 0 sup + level and one 2 sup + level.

Barker, F C

2002-01-01

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57Co-bleomycin and 67Ga-citrate in detecting and staging lung cancer  

International Nuclear Information System (INIS)

In the investigation of suspected lung cancer, bleomycin labelled with cobalt-57, and gallium-67 labelled with citrate are currently used to detect the primary tumour and to establish the presence of metastases in the lung hilum and mediastinum. A comparative study of these radiopharmaceuticals was performed in 63 patients with proved lung cancer. 57Co-bleomycin showed the primary tumour in 58 patients (92%) and 67Ga-citrate in 34 (54%) (p 57Co-bleomycin and 1.5 with 67Ga-citrate. Proved metastases in the hilum or the mediastinum were visualised with 57Co-bleomycin scintigraphy in 16 out of 18 patients (89%) and with 67Ga-citrate scintigraphy in only eight (45%) (p 57Co-bleomycin scintigraphy is more suitable for detecting and staging lung cancer than is 67Ga-citrate. 57Co-bleomycin is valuable in the detection of peripheral lesions, in which a pathological diagnosis is difficult to achieve, since a positive scintigram indicates malignancy. When 57Co-bleomycin scintigraphy suggests hilar or mediastinal metastases mediastinoscopy should be carried out; but when no metastases are apparent it is reasonable to proceed directly to thoracotomy without mediastinoscopy. (author)

80

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)

 
 
 
 
81

Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice  

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Full Text Available Abstract Background Bleomycin is poorly permeant but potent cytotoxic and radiosensitizing drug. The aim of the study was to evaluate whether a physical drug delivery system – electroporation can increase radiosensitising effect of bleomycin in vitro and in vivo. Methods LPB sarcoma cells and tumors were treated either with bleomycin, electroporation or ionizing radiation, and combination of these treatments. In vitro, response to different treatments was determined by colony forming assay, while in vivo, treatment effectiveness was determined by local tumor control (TCD50. Time dependence of partial oxygen pressure in LPB tumors after application of electric pulses was measured by electron paramagnetic oxyimetry. Results Electroporation of cells in vitro increased radiosensitising effect of bleomycin for 1.5 times, in vivo radiation response of tumors was enhanced by 1.9 fold compared to response of tumors that were irradiated only. Neither treatment of tumors with bleomycin nor application of electric pulses only, affected radiation response of tumors. Application of electric pulses to the tumors induced profound but transient reduction of tumor oxygenation. Although tumor oxygenation after electroporation partially restored at the time of irradiation, it was still reduced at the level of radiobiologically relevant hypoxia. Conclusion Our study shows that application of electric pulses to cells and tumors increases radiosensitising effect of bleomycin. Furthermore, our results demonstrate that the radiobiologically relevant hypoxia induced by electroporation of tumors did not counteract the pronounced radiosensitising effect of electrochemotherapy with bleomycin.

Sentjurc Marjeta

2005-09-01

82

Expression and mechanism of BRP-39 in bleomycin-induced pulmonary fibrosis in rat.  

Science.gov (United States)

The purpose of the study was to explore the effects of breast regression protein 39 (BRP-39) in bleomycin-induced pulmonary fibrosis and its mechanism in pulmonary fibrosis by studying change in BRP-39 to provide a novel direction for the treatment of idiopathic pulmonary fibrosis. SPF grade male C57BL/6 rats were randomly divided into three groups, including bleomycin group, bleomycin+ BRP-39 recombinant protein group and control group. HE and Masson staining were applied to test the change in lung tissue after being treated by BRP-39, ELISA was applied to test the expression of TGF-?1 in different groups, and Western blot was used to test the expression of BRP-39 in rat lung tissue. Expression of BRP-39 increased, the fibrosis was obvious, and lung tissue collagen increased in bleomycin-induced pulmonary fibrosis in rat lung tissue. Increasing BRP-39 protein level and intratracheal bleomycin medication to establish pulmonary fibrosis model can aggravate pulmonary fibrosis. Along with the increase in BRP-39 protein level, TGF-?1 expression level also increased in lung tissue. Western blot results showed the expression of BRP-39, and TGF-?1 had the same trend in different groups. BRP-39 has effects in bleomycin-induced rat pulmonary fibrosis. Change in BRP-39 can affect the process of bleomycin-induced pulmonary fibrosis. The mechanism of BRP-3 in pulmonary fibrosis may work by regulating TGF-?1. PMID:24659093

Du, Chunxian; Yang, Yibing; Lin, Yuhui; Yang, Jiong

2014-09-01

83

Effects of ICRF-187 and L-Carnitine on bleomycin-induced lung toxicity in rats  

International Nuclear Information System (INIS)

The possible modulatory effects of ICRF-187 and L-carnitine against bleomycin-induced pulmonary toxicity in male rats were investigated. Repeated administration of bleomycin (10 mg/kg, twice weekly for 6 consecutive weeks) produced significant lung toxicity. The toxicity was manifested by significant increase in normal contents of lipid peroxide (LPO, 91.7%) reduced glutathione (GSH, 73.2%) and oxidized glutathione (GSSG, 135.4%) as well as the activity of superoxide dismutase (SOD, 222.7%). Thirty minutes prior to bleomycin treatment, other groups of rats received either ICRF-187 (95 mg/kg) or L-carnitine (500 mg/kg) adopting the same schedule of treatment as in bleomycin-treated group. L-carnitine decreased bleomycin-induced elevations in SOD activity, GSH and GSSG contents, however, it failed to suppress the increase in LPO level. On the other hand, treatment with ICRF-187 returned back all the elevated biochemical parameters induced by bleomycin to nearly normal levels. In conclusion, the results of this study showed a potential capability of ICRF-187 to mitigate the bleomycin-induced lung injury. Moreover, despite the inability of L-carnitine to change the elevated LPO content, it was able however, to decrease the elevated endogenous antioxidant parameters. (author)

84

The concentration of bleomycin labeled with Co-57 in primary and metastatic tumors  

International Nuclear Information System (INIS)

The concentration over time of bleomycin labeled with Co-57 was measured in 39 primary and metastatic tumor sites in 16 patients using a newly developed and validated single photon emission computed tomography (SPECT) method. There were nine primary tumors, 15 metastatic tumors, and five multifocal lymphomas. Co-bleomycin concentrations also were measured in primary and metastatic B-16 melanoma tumors in mice. In humans, metastases to lymph nodes (1.58 +/- 0.51 %ID/ml X minutes) showed significantly higher (P less than 0.01) tumor cumulative concentrations of Co-bleomycin than metastases to liver, bone, lung, and brain (0.76 +/- 0.20 %ID/ml X minutes). The cumulative concentrations of Co-bleomycin in human lymphomas (1.1 +/- 0.25 %ID/ml X minutes) also were significantly higher (P less than 0.01) than the concentrations in human metastases other than lymph nodes. The cumulative concentration in cerebral metastases (0.65 +/- 0.18 %ID/ml X minutes) was significantly lower (P less than 0.05) than in noncerebral metastases (1.22 +/- 0.53 %ID/ml X minutes). Primary tumors in humans showed higher concentrations of Co-bleomycin than metastases, except for lymph nodes. In contrast with humans, murine metastases showed higher concentrations of Co-bleomycin (6.20 +/- 2.65 %ID/g) than primary tumors (2.94 +/- 0.90 %ID/g) (P less than 0.001). The concentrations of Co-bleomycin in murine tumors that were affected by bleomycin were about three orders of magnitude higher than in human tumors. The results of this in vivo study document the differences in drug delivery of Co-57-labeled bleomycin to human primary and metastatic tumors and show differences in drug delivery between human and murine tumors

85

[{sup 201}Tl](III)-bleomycin for tumor imaging  

Energy Technology Data Exchange (ETDEWEB)

Due to interesting physical properties and wide availability of thallium-201 as a SPECT radionuclide, the idea of incorporation of this nuclide into biologically active compounds was targeted. Thallium-201 (T{sub 1/2} = 3.04d) in Tl{sup +} form was converted to Tl{sup 3+} cation in presence of O{sub 3} in 6 M HCl controlled by RTLC/gel electrophoresis methods. The final evaporated activity was reacted with bleomycin in normal saline to yield [{sup 201}Tl]BLM at room temperature after 0.5 h (radiochemical yield > 999%) followed by HPLC analysis. The studies showed that thallic ion is mostly incorporated into bleomycin A{sub 2} while other species in the pharmaceutical sample almost remain unlabeled. Radiochemical purity of more than 99% was obtained using RTLC, HPLC with specific activity of about 7 Ci/mmol. The stability of the tracer was checked in the final product in presence of human serum at 37 C up to 3 d. The tracer accumulated in tumors of fibrosarcoma-bearing mice after 72 h. (orig.)

Jalilian, A.R.; Akhlaghi, M.; Shirazi, B.; Aboudzadeh, R.; Raisali, G.; Salouti, G.; Babaii, M. [Cyclotron and Nuclear Medicine Dept., Nuclear Research Center for Agriculture and Medicine, Karaj (Iran)

2006-07-01

86

Simultaneous treatment of tongue cancer with interstitial brachytherapy and bleomycin  

International Nuclear Information System (INIS)

During a period of 5 years, from 1977 to 1982, twenty five patients with tongue cancer were treated by radium needle implantation and bleomycin at Yamagata University Hospital. In this paper, authors analysed seventeen patients followed over two years. All had biopsy proven squamous cell carcinoma. According to the TNM system (UICC, 1978), primary tumor was classified into 4 cases of T1, 8 cases of T2 and 5 cases of T3. The main purpose of this study was to obtain a high local control rate and reduce subsequent regional lymphnode metastasis. Our curative treatment method was simultaneous combination of 70 Gy of brachy-therapy and 40 mg of bleomycin. The results of this study were as follows: 1. A control rate in the primary lesion was 91% (10/11) in survivors having survived more than 2 years. 2. Radioosteonecrosis of mandible was found in 6% (1/17) and transient ulcer formation in the primary site was observed in 35% (6/17) of patients treated. However, all patients were cured by conservative treatment. 3. This treatment method did not reduce subsequent lymph node metastasis. (author)

87

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)

88

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

89

Complete Resolution of Cystic Hygroma with Single Session of Intralesional Bleomycin  

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Full Text Available Intralesional sclerotherapy as a primary modality of management for cystic hygroma is successfully described in literature. It has many benefits over surgical approach; recurrence being the concern of as much as 20% of patients in which apparent complete excision has been performed. Bleomycin is one of sclerosing agents used as intralesional therapy in cystic hygroma. Complete response usually occurs in multiple sessions of sclerotherapy. Rarely, complete resolution occurs with single session of bleomycin sclerotherapy. We share our experience of managing a case of cystic hygroma of neck that completely resolved with single session of bleomycin sclerotherapy.

Fadi Atwan

2012-07-01

90

Experience in staging testis tumors with bleomycin cobalt 57 and present role of gallium 67 scan  

International Nuclear Information System (INIS)

A technique was developed using bleomycin and cobalt 57 to study nodal metastases in testis tumors. Comparative studies were made on 15 cases with gallium 67, lymphangiography, supraclavicular node biopsy, liver and spleen scans, chest x-ray, excretory urogram, bone survey and pathological study of surgical specimens when possible. The results with the bleomycin-cobalt 57 complex and gallium 67 were discouraging. The bleomycin-cobalt 57 study was discontinued. Pathological staging is still the most accurate of all modalities available for staging testicular malignancies

91

A method for labelling bleomycin and mannitol using a solid reductant  

International Nuclear Information System (INIS)

Bleomycin and mannitol seem to localize particularly in animal neoplastic tissue. Analyzing the structure of the two molecules, the presence of sites combining /sup 99m/Tc can be hypothesized, particularly for bleomycin. Many methods for labelling bleomycin with /sup 99m/Tc have been reported, but these radiopharmaceuticals have not often been used clinically. The aims of this study were: (1) to compare a method based on the utilization of a solid reductant (SnO) with a more often used method involving the utilization of Sn Cl/sub 2/ as a reductant; (2) to propose two reliable labelling methods which prove easy to perform in any laboratory

92

Effects of Recombinant Activated Protein C Derived From Drotrecogin-Alpha on Bleomycin-Induced Pulmonary Fibrosis in Rats Compared with Methyl-Prednisolone  

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Full Text Available OBJECTIVE: In this study, we aimed to test the preventive effects of intraperitoneally administered drotrecogin alpha which is derived from activated protein C (APC, on bleomycin-induced pulmonary fibrosis in rats, and to compare the effects of APC with the effects of methyl-prednisolone, a traditional therapy. MATERIAL AND METHODS: Thirty male Wistar albino 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+APC (n=10. The rats (except for the control group were given intratracheal bleomycin (2.5 mg/kg. The bleomycin+APC group was given APC (100 µg/kg/day and methyl-prednisolone treated rats were injected with 5mg/kg/day methyl-prednisolone intraperitoneally two days before the bleomycin injection; the drug was administered at the same dose for 16 days. All of the rats were killed 14 days after the intratracheal injection of bleomycin. Fibrotic changes in the lungs were demonstrated by analysing the cellular composition of bronchoalveolar lavage fluid, histological evaluation and lung hydroxyproline content.RESULTS: Fibrosis was experimentally induced in the lungs of rats using bleomycin. Fibrosis scores in the bleomycin+methyl-prednisolone and the bleomycin+APC groups were significantly lower than in the bleomycin+placebo group (p<0.05. The scores of the bleomycin+APC group and the bleomycin+methyl-prednisolone group were similar. The lung tissue hydroxyproline contents in the bleomycin+placebo and bleomycin+methyl-prednisolone groups were significantly higher than the control group (p<0.05, but the hydroxyproline content in the bleomycin+APC group was significantly lower than in the other groups (p<0.05. CONCLUSION: Drotrecogin alpha that is derived from recombinant APC has a protective effect on the pulmonary fibrosis induced by bleomycin. The protective effect seen with methyl-prednisolone is similar.

Kadir Y?ld?z

2013-04-01

93

Eosinophilic pneumonia associated with bleomycin in a patient with mediastinal seminoma: a case report  

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Full Text Available Abstract Introduction Lung toxicities resulting from the chemotherapeutic agent bleomycin encompass a variety of pathological changes, including bronchiolitis obliterans organizing pneumonia, interstitial pneumonitis and progressive interstitial fibrosis. We report a rare case of eosinophilic pneumonia associated with bleomycin. Case presentation A 44-year-old Hispanic man with a primary mediastinal seminoma complicated by superior vena cava syndrome underwent treatment with four cycles of bleomycin, etoposide and cisplatin. He had a complete positive response to the chemotherapy. However, three months after treatment he presented with shortness of breath and severe hypoxemia associated with peripheral eosinophilia. Computed tomography showed bilateral diffuse interstitial infiltrates that were refractory to antibiotic treatment. A lung biopsy showed eosinophilic pneumonia. He was subsequently treated with high-dose prednisone, resulting in a complete resolution of his symptoms and lung infiltrates. Conclusion This case illustrates that eosinophilic pneumonia may be a late sequela of bleomycin toxicity, and may respond dramatically to steroid treatment.

Chu David

2010-04-01

94

HRCT findings of bleomycin-related lung toxicity: a report of 2 cases  

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Many drugs can result in a variety of pathologic reactions in the lung, especially the cytotoxic drugs. Among cytotoxic drugs bleomycin is a prototype. Bleomycin-related pulmonary toxicity is usually known as dose-dependent and can be enhanced with concurrent oxygen therapy, irradiation, or other chemotherapeutic agents. The incidence of bleomycin-induced pulmonary toxicity has been reported as varying from 2 to 46%, and 1% of fatal lung disease. We describe the radiographic and HRCT findings of bleomycin-related pulmonary toxicity developed in two patients: one in ovarian teratocarcinoma, the other malignant lymphoma patient. Chest radiographs and HRCT of these patients showed ground-glass opacities, consolidation, linear and reticular opacities, and interlobular septal thickening. These abnormalities were bilateral, and symmetrical and were found predominantly in the area of mid- and lower-lung zone

95

In-111 BLEDTA: a conjugate of bleomycin with a bifunctional chelating agent for tumor localization  

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BLEDTA, a bleomycin A2 analog containing an EDTA group was labeled in the EDTA group to a specific activity of 70 mCi/mg and used for animal and human studies. KHJJ mouse tumor uptake was higher than the orange Co-57 bleomycin isomer and the tumor/organ ratios were >1 for all organs except the kidney. In 29 biopsy proven cancer patients the scan done 24 hours post I.V. with 1-2 mCi of In-111 BLEDTA was positive in all clinically known sites in 18, and in some clinically known sites in 11. The In-111 BLEDTA clinical results are similar to reported Co-57 bleomycin clinical studies, and the method is proposed as an alternate way to produce a stable biologically active bleomycin labeled with In-111

96

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

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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 morphometoughout 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

97

Bleomycin induced pulmonary to cytotoxicity in patients with germ cell tumours  

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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)

98

Photochemical internalization enhances the efficacy of bleomycin in malignant glioma cells  

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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

99

Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice  

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Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ?Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ?Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ?TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

Lee, Ye-Ji [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Lee, Seung-Hae [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Youn, Young-So; Choi, Ji-Yeon [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Song, Keung-Sub [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Cho, Min-Sun [Department of Pathology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Kang, Jihee Lee, E-mail: jihee@ewha.ac.kr [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of)

2012-08-15

100

Characteristics of mutagenesis by bleomycin and adriamycin in salmonella typhimurium: action of superoxide dismutase.  

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The role of reactive oxygen species in adriamycin and bleomycin-induced mutagenicity was investigated in Salmonella typhimurium TA98 and TA102 respectively. Activity of superoxide dismutase (SOD) was inhibited by preincubation of bacteria with diethyldithiocarbamate (DEDTC). Results of Ames test may suggest the involvement of active oxygen species in bleomycin induced mutagenesis and an absence of their participation in adriamycin induced mutagenesis. PMID:8960280

Ejchart, A; Marczewska, J; Ch?opkiewicz, B

1996-01-01

 
 
 
 
101

A Systematic Review of Talc Compared with Bleomycin for Patients with Malignant Pleural Effusions  

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Background and objective Malignant pleural effusions are a common complication in advanced malignancy. Talc, bleomycin and the tetracyclines are the three most frequently used sclerosants. The aim of this study is to evaluate the efficacy and adverse effects of patients with malignant pleural effusions treated with talc and bleomycin. Methods We searched PubMed, Embase, the Cochrane Library, Chinese biomedicine literature database (CBM), CNKI, VIP, references of included studies for randomize...

Wei, Yonggang; Yu, Qin; Luo, Hongtao

2009-01-01

102

Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice  

International Nuclear Information System (INIS)

Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ?Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ?Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ?TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

103

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.

Elena Topchiy

2013-08-01

104

Fic domain-catalyzed adenylylation: Insight provided by the structural analysis of the type IV secretion system effector BepA  

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Numerous bacterial pathogens subvert cellular functions of eukaryotic host cells by the injection of effector proteins via dedicated secretion systems. The type IV secretion system (T4SS) effector protein BepA from Bartonella henselae is composed of an N-terminal Fic domain and a C-terminal Bartonella intracellular delivery domain, the latter being responsible for T4SS-mediated translocation into host cells. A proteolysis resistant fragment (residues 10–302) that includes the Fic domain sho...

Palanivelu, Dinesh V.; Goepfert, Arnaud; Meury, Marcel; Guye, Patrick; Dehio, Christoph; Schirmer, Tilman

2011-01-01

105

Results of combined therapy of irradiation and bleomycin suppository for advanced uterine cervical cancer  

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Efficacy, survival rats and adverse effects of the combined therapy of irradiation with intravaginal bleomycin suppositories were analyzed and discussed in 49 patients with uterine cervical cancer. The results were as follows: 1. Histological examination of biopsy specimens from the uterine cervix taken just after the completion of this treatment showed favorable control over the primary lesions. However, the efficacy of the bleomycin suppositories was too mild to form a basis for treatment without intracavitary irradiation. Because of the low concentration of bleomycin in serum after suppository administration, it is thought that bleomycin would have little effect on distant metastases. 2. Survival rates in stage III patients were 83% at 12 months, 77% at 24 months and 70% at 36 months. These were superior to those for irradiation alone. 3. The major adverse effect of bleomycin suppositories was fever, reduction of the bleomycin dose in each suppository but controlled this to some extent Lung fibrosis or severe damage to the liver, kidney and bone marrow were not found. (author)

106

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

2009-08-01

107

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 < 0.05 by x 2 analysis and RR = 7.67. Conclusion: IL bleomycin injection was significantly more effective than cryotherapy for treatment of cutaneous wart.

Dhar S

2009-01-01

108

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

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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

109

Enhancement of bleomycin-mediated DNA damage by epidermal microsomal enzymes.  

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The role of epidermal microsomal enzymes in catalyzing bleomycin-mediated chain breakage in calf-thymus DNA and in DNA isolated from neonatal rat epidermis was studied. Aerobic incubation of bleomycin with epidermal microsomes, epidermal or calf-thymus DNA and NADPH caused substantial chain breakage of the DNA which was dependent upon concentrations of drug, microsomal protein and NADPH. The reactive oxygen scavenger superoxide dismutase, the metal chelator EDTA, and cytochrome c each inhibited the enzyme-mediated chain breakage reaction. Scavengers of hydrogen peroxide and hydroxyl radicals, including catalase and benzoate and inhibitors of microsomal cytochrome P-450-dependent monooxygenases such as 1-benzylimidazole, metyrapone and alpha-naphthoflavone, had no inhibitory effects on bleomycin-mediated DNA chain breakage. In contrast, ascorbic acid significantly enhanced DNA damage by bleomycin. These studies indicate that mammalian epidermis possesses membrane-bound enzyme activity capable of enhancing bleomycin-mediated chain breakage of DNA and that oxidation/reduction of adventitious iron and generation of reactive oxygen participate in the reaction. These responses in the epidermis could directly relate to the mechanism of action of intralesional injections of bleomycin which are used quite effectively in the management of recalcitrant human warts. Either epidermal or wart virus DNA or both could be targets for this pharmacologic effect of the drug which is augmented by epidermal microsomal enzymes. PMID:6200138

Bickers, D R; Dixit, R; Mukhtar, H

1984-04-01

110

"Preparation, biodistribution and stability of [65zn]bleomycin complex "  

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Full Text Available Bleomycin (BLM has been labeled with various radioisotopes and widely used in therapy and diagnosis. In this study BLM was labeled with [65Zn] zinc chloride and its distribution and stability in normal and tumor bearing mice was determined. The complex was obtained at the pH=2 in normal saline at 90 °C in 60 minutes. Radio-TLC showed an overall radiochemical yield of 95-97% (radiochemical purity >97%. The in vitro stability of the complex was determined in mice and human plasma. Preliminary studies were performed to determine distribution of [65Zn]BLM in normal and tumor bearing mice on the basis of these results. [65Zn]BLM may be used in therapeutic studies due to its suitable physico-chemical properties.

Amir Reza Jalilian

2004-08-01

111

The disaccharide moiety of bleomycin facilitates uptake by cancer cells.  

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The disaccharide moiety is responsible for the tumor cell targeting properties of bleomycin (BLM). While the aglycon (deglycobleomycin) mediates DNA cleavage in much the same fashion as bleomycin, it exhibits diminished cytotoxicity in comparison to BLM. These findings suggested that BLM might be modular in nature, composed of tumor-seeking and tumoricidal domains. To explore this possibility, BLM analogues were prepared in which the disaccharide moiety was attached to deglycobleomycin at novel positions, namely, via the threonine moiety or C-terminal substituent. The analogues were compared with BLM and deglycoBLM for DNA cleavage, cancer cell uptake, and cytotoxic activity. BLM is more potent than deglycoBLM in supercoiled plasmid DNA relaxation, while the analogue having the disaccharide on threonine was less active than deglycoBLM and the analogue containing the C-terminal disaccharide was slightly more potent. While having unexceptional DNA cleavage potencies, both glycosylated analogues were more cytotoxic to cultured DU145 prostate cancer cells than deglycoBLM. Dye-labeled conjugates of the cytotoxic BLM aglycons were used in imaging experiments to determine the extent of cell uptake. The rank order of internalization efficiencies was the same as their order of cytotoxicities toward DU145 cells. These findings establish a role for the BLM disaccharide in tumor targeting/uptake and suggest that the disaccharide moiety may be capable of delivering other cytotoxins to cancer cells. While the mechanism responsible for uptake of the BLM disaccharide selectively by tumor cells has not yet been established, data are presented which suggest that the metabolic shift to glycolysis in cancer cells may provide the vehicle for selective internalization. PMID:25184545

Schroeder, Benjamin R; Ghare, M Imran; Bhattacharya, Chandrabali; Paul, Rakesh; Yu, Zhiqiang; Zaleski, Paul A; Bozeman, Trevor C; Rishel, Michael J; Hecht, Sidney M

2014-10-01

112

Effects of a calmodulin inhibitor on bleomycin-induced lung inflammation in hamsters. Biochemical, morphometric, and bronchoalveolar lavage data.  

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Previous studies have shown that bleomycin-induced pulmonary fibrosis is accompanied by elevated levels of calcium and calmodulin, which are important in the regulation of many biologic processes. The authors have further extended these observations and assessed the effect of a calmodulin inhibitor, trifluoperazine, on bleomycin-induced lung damage with biochemical, morphometric, and bronchoalveolar lavage techniques. The cumulative mortality due to bleomycin was not significantly reduced in ...

Nakashima, J. M.; Hyde, D. M.; Giri, S. N.

1986-01-01

113

Structure of the excited states of 11Be reached through the reaction d(10Be,p)11Be  

International Nuclear Information System (INIS)

The one-neutron transfer reaction d(10Be,p)11Be has been studied at 32 A.MeV at GANIL with a 10Be secondary beam. Protons were detected by the silicon strip array MUST. The ground state and excited states of 11Be at 0.32, 1.78 and 3.41 MeV were populated, demonstrating the feasibility of transfer reactions induced by radioactive beams leading to bound and unbound states. A DWBA (distorted wave born approximation) analysis indicates for the 3.41 MeV state spin and parity 3/2+ or 5/2+ and a spectroscopic factor of 0.18 or 0.11, respectively. A broad structure centered at 10 MeV is also observed and corresponds to transfer to the 1d sub-shells. If one assumes that only the 1d3/2 orbital contributes to this structure, the splitting of the 1d neutron states in 11Be is estimated to be 6.3 MeV. Using a 2-particle-RPA (random phase approximation) model, we have shown that neutron-neutron correlations play an important role in the inversion between the 2s1/2 and 1p1/2 neutron states in 11Be. (author)

114

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

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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 baking at 120 C 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.

115

Mutational spectrum of bleomycin in lacZ mouse kidney: a possible model for mutational spectrum of reactive oxygen species  

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The mutational spectrum of bleomycin was compared with the spontaneous mutational spectrum in lacZ mouse kidney. Mice were treated with four 20 mg/kg of doses of bleomycin over a two-week period, leading to a mutant fraction several times greater than that of controls. The major class of bleomycin-induced mutations consisted of small deletions, in particular -1 deletions at AT base pairs and hot spots for deletions at 5'-GTC-3' sequences. Smaller, but significant fractions of GC > AT followed by GC > TA substitutions were also observed. In untreated mice, the major class of mutations consisted of GC > AT substitutions followed by GC > TA mutations, and a much smaller fraction of deletions. Other than the specificity of bleomycin for AT base pairs and the 5'-GTC-3' hotspots, the mutational spectrum of bleomycin in mice is similar to that reported for ionizing radiation. However, bleomycin initially mediates the formation of oxidized DNA via reduction of molecular oxygen, as opposed to the radiolysis of water. In this respect mutagenesis induced by bleomycin may be more similar to that induced by endogenous reactive oxygen species (ROS) than mutagenesis induced by ionizing radiation. If bleomycin-induced mutagenesis is an appropriate model for mutagenesis induced by ROS, then, based on the difference between the mutational spectrum of bleomycin and spontaneous mutagenesis, the latter appears not to result predominantly from ROS, at least in mouse kidney.

Guttenplan, Joseph B.; Khmelnitsky, Michael; Haesevoets, Roderick; Kosinska, Wieslawa

2004-10-04

116

Mutational spectrum of bleomycin in lacZ mouse kidney: a possible model for mutational spectrum of reactive oxygen species  

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The mutational spectrum of bleomycin was compared with the spontaneous mutational spectrum in lacZ mouse kidney. Mice were treated with four 20 mg/kg of doses of bleomycin over a two-week period, leading to a mutant fraction several times greater than that of controls. The major class of bleomycin-induced mutations consisted of small deletions, in particular -1 deletions at AT base pairs and hot spots for deletions at 5'-GTC-3' sequences. Smaller, but significant fractions of GC > AT followed by GC > TA substitutions were also observed. In untreated mice, the major class of mutations consisted of GC > AT substitutions followed by GC > TA mutations, and a much smaller fraction of deletions. Other than the specificity of bleomycin for AT base pairs and the 5'-GTC-3' hotspots, the mutational spectrum of bleomycin in mice is similar to that reported for ionizing radiation. However, bleomycin initially mediates the formation of oxidized DNA via reduction of molecular oxygen, as opposed to the radiolysis of water. In this respect mutagenesis induced by bleomycin may be more similar to that induced by endogenous reactive oxygen species (ROS) than mutagenesis induced by ionizing radiation. If bleomycin-induced mutagenesis is an appropriate model for mutagenesis induced by ROS, then, based on the difference between the mutational spectrum of bleomycin and spontaneous mutagenesis, the latter appears not to result predominantly from ROS, at least in mouse kidney

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

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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 103Ru 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 97Ru. Ruthenium-97 has favorable physical properties that make it ideal for imaging applications: decay by electron capture; ? 216 keV, 85%; t/sub 1/2/ 2.9 d. A novel method based on the reduction of Ru3+ to Ru2+ using stannous chloride was investigated for labeling BLM with 97Ru and/or 103Ru. In-vitro and in vivo comparisons of the product(s) with 57Co and 67Cu-labeled BLM were also carried out. 4 refs., 3 tabs

118

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

2008-01-01

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Localization of bleomycin in a single living cell using three-photon excitation microscopy  

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Bleomycin has been used in the clinic as a chemotherapeutic agent for the treatment of several neoplasms, including non-Hodgkins lymphomas, squamous cell carcinomas, and testicular tumors. The effectiveness of bleomycin is believed to be derived from its ability to bind and oxidatively cleave DNA in the presence of a iron cofactor in vivo. A substantial amount of data on BLM has been collected, there is little information concerning the effects of bleomycin in living cells. In order to obtain data pertinent to the effects of BLM in intact cells, we have exploited the intrinsic fluorescence property of bleomycin to monitor the uptake of the drug in mammalian cells. We employed two light microscopy techniques, a wide-field and three-photon excitation (760 nm) fluorescence microscopy. Treatment of HeLa cells with bleomycin resulted in rapid to localization within the cells. In addition data collected from the wide field experiments, three-photon excitation of BLM which considerably reduced the phototoxic effect compared with UV light excitation in the wide-field microscopy indicated co-localization of the drug to regions of the cytoplasm occupied by the endoplasmic reticulum probe, DiOC5. The data clearly indicates that the cellular uptake of bleomycin after one minute includes the nucleus as well as in cytoplasm. Contrary to previous studies, which indicate chromosomal DNA as the target of bleomycin, the current findings suggest that the drug is distributed to many areas within the cell, including the endoplasmic reticulum, an organelle that is known to contain ribonucleic acids.

Abraham, Anil T.; Brautigan, David L.; Hecht, Sidney M.; Periasamy, Ammasi

2001-04-01

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The solution structure of the Ga(III)-bleomycin A2 complex resolved by NMR and molecular modeling; interaction with d(CCAGGCCTGG).  

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The solution structure of the Ga(III)-bleomycin A2 complex (GaBLM) has been determined using 2D NMR methods in combination with molecular dynamics calculations. Complete assignment of the amide and amine protons, observation of 80 NOEs and measurement of 15 (3)JH(-H) coupling constants provided us with a well-defined structure using a restrained simulated annealing protocol. On the basis of distance and dihedral angle constraints agreement, along with potential energy considerations, the favored model is a five-coordinate complex with the primary amine of beta-aminoalanine holding the axial position of a distorted tetragonal pyramid. The disaccharide moiety of GaBLM is not a ligand, sharing the same side of the equatorial plane with the axial amine ligand. Titration of the self-complementary oligonucleotide d(CCAGGCCTGG) with GaBLM results in the formation of only one 1:1 complex in slow exchange on the NMR time scale. Our data indicate that the bithiazole moiety intercalates between the C6*G15 and C7*G14 base pairs, in a similar mode to that reported by earlier studies. Structural implications and comparisons to other metallo-bleomycins are discussed. PMID:12632272

Papakyriakou, Athanasios; Mouzopoulou, Barbara; Katsaros, Nikos

2003-05-01

 
 
 
 
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Treatment of advanced seminoma with Dactinomycin, Cyclophosphamide, vinblastine, Bleomycin and Cisplatinum (The Vab-6 protocol)  

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Eighteen patients with advanced seminoma (Stages IIC-III) were treated with chemotherapy. Surgery and/or radiotheraphy were used in some cases that presented residual masses or recurrences. The therapeutic methods are discussed. (M.A.C.)

122

Static and dynamic mechanics of the murine lung after intratracheal bleomycin  

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Full Text Available Abstract Background Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure. Methods Single intratracheal injections of saline (50 ?L or bleomycin (2 mg/Kg in 50 ?L saline were administered to C57BL/6 (n = 40 and Balb/c (n = 32 mice. Injury/fibrosis score, tissue volume density (TVD, collagen content, airway resistance (RN, tissue damping (G and elastance coefficient (H, hysteresivity (?, and area of pressure-volume curve (PV-A were determined after 7 and 21 days (inflammation and fibrosis stage, respectively. Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests. Results Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls. Conclusions Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.

Papiris Spyridon

2011-05-01

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

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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

2012-05-01

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Treatment of hypovascular hepatic cavernous hemangiomas by percutaneous intratumoral bleomycin injection after selective hepatic arterial embolization  

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Objective: To assess the safety and effectiveness of treatment of cavernous hemangiomas of liver(CHL) by percutaneous intratumoral bleomycin injection after transarterial embolization (TAE). Methods: 9 cases of hypovascular CHL treated by percutaneous intratumoral bleomycin injection after TAE were studied prospectively. All the cases were diagnosed as hypovascular CHL(diameter > 5 cm) by CT/MRI. With only spotty or few patchy enhancement in arterial phase persisting into the delayed phase were shown on enhanced CT. TAE with emulsion of ultra-fluid lipiodol(10 ml) and bleomycin(8 mg) was performed in every patient, with dosage of 5-10 ml depending on the vascular space of different lesions. Percutaneous intratumoral multi- point injection with bleomycin (8-16 mg) solution was undertaken 4 days after TAE, and repeated every 3-4 days for 2-3 times. Each case undertook upper abdominal CT scan 1 month later, and then with 3, 6 month to 1 year periodic follow-up. Results: DSA features of all the 9 cases demonstrated as same as those on enhanced CT scanning with dispersion of lipiodol within the lesions. All the lesions decreased in volume markedly 1 month after the therapy, and kept on until 1 year later. 2 patients developed post-TAE acute cholecystitis and one intrahepatic biloma. Conclusion: TAE combined with percutaneous intra-tumoral bleomycin injection is a safe and effective method in treating hypovascular CHL. (authors)

125

Effects of bleomycin on the reproductive capacity of cultured brain tumor cells  

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The effects of bleomycin were studied on the colony forming ability of cultured mammalian cells, including two cell lines established from human glioblastoma multiform, one cell line from mouse glioma induced by methylcholanthrene, HeLa S3 from human carcinoma coli and L5 from mouse fibroblast. Both the bleomycin treatment time survival curves and the bleomycin dose response curves for each cell line were in general upward concave. There was a big difference of response to bleomycin in the cell lines used, and the brain tumor cells were more sensitive than HeLa and L5, while there was no significant difference of radiosensitivity in these cell lines. Treatment with 12 ?g/ml bleomycin for one hour prior to x-ray irradiation resulted in a decrease of Do in the x-ray dose response curve for L5 cells. The dose modifying factor calculated by using Do, 10% survival, and 1% survival was 1.1, 1.2, and 1.1, respectively. (author)

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Experience and results in the treatment of ORL tumours with bleomycin and radiotherapy  

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Since 1974 Bleomycin has been applied in our hospital in combination with radiotherapy to treat advanced ORL-carcinomas. In a 1st phase (X.74-VII.77), Bleomycin (6D 60 mg) was applied to 20 patients by infusion before starting radiotherapy. In a second group of patients, from II.78, the principle of simultaneous treatment was adhered to, 30-60 min. prior to starting radiotherapy max. 5 mg Bleomycin i.m.. For 10 patients, treatment was finished at least 2 months ago. The rate of at least partial clinical remission 70% (45% complete remission), in the 2nd group it was 100% (50% complete remission). In fixed lymphomas, the rate of clinically total tumour reduction dropped to 25%; in NO-2-findings, however, it was 70%. The substantial characteristic of the combined treatment with Bleomycin was the spontaneous easing of the pain, especially in the group of the simultaneously treated patients. An early fibrinous mucositis cannot be avoided. The theories of the differing techniques of application were explained. Finally, an attempt is made to define the indications for Bleomycin in treating ORL-tumours. After finishing this paper, the number of the patients treated according to scheme 2 increased to more than 40. (orig./MG) 891 MG/orig. 892 RDG

127

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

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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)

128

Asialoerythropoietin ameliorates bleomycin-induced acute lung injury in rabbits by reducing inflammation  

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Acute lung injury, a critical illness characterized by acute respiratory failure with bilateral pulmonary infiltrates, remains unresponsive to current treatments. The condition involves injury to the alveolar capillary barrier, neutrophil accumulation and the induction of proinflammatory cytokines followed by lung fibrosis. In the present study, a rabbit model of bleomycin-induced acute lung injury was established to examine the effects of asialoerythropoietin (AEP), an agent with tissue-protective activities, on pulmonary inflammation. Six Japanese white rabbits were randomly divided into two equal groups. Acute lung injury was induced in all rabbits by intratracheally injecting bleomycin. The control group was injected with bleomycin only; the experimental (AEP) group was injected intravenously with AEP (80 ?g/kg) prior to the bleomycin injection. Computed tomography (CT) studies were performed seven days later. The CT inflammatory scores of areas exhibiting abnormal density and the pathological inflammatory scores were recorded as a ratio on a 7×7 mm grid. The CT and pathological inflammatory scores were significantly different between the control and AEP groups [122±10 and 16.3±1.5 (controls) vs. 71±8.5 and 9.7±1.4 (AEP), respectively; P<0.01]. Thus, the present study revealed that AEP prevents bleomycin-induced acute lung injury in rabbits. PMID:25289037

SONODA, AKINAGA; NITTA, NORIHISA; TSUCHIYA, KEIKO; OTANI, HIDEJI; WATANABE, SHOBU; MUKAISHO, KENICHI; TOMOZAWA, YUKI; NAGATANI, YUKIHIRO; OHTA, SHINICHI; TAKAHASHI, MASASHI; MURATA, KIYOSHI

2014-01-01

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Characterization of the association of radiolabeled bleomycin A2 with HeLa cells  

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The association of [3H]bleomycin A2 and Cu(II):[3H]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 [3H]bleomycin A2 or Cu(II):[3H]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

130

Characterization of the association of radiolabeled bleomycin A2 with HeLa cells  

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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

131

Modified bleomycin disaccharides exhibiting improved tumor cell targeting.  

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The bleomycins (BLMs) are a family of antitumor antibiotics used clinically for anticancer chemotherapy. Their antitumor selectivity derives at least in part from their ability to target tumor cells, a property that resides in the carbohydrate moiety of the antitumor agent. In earlier studies, we have demonstrated that the tumor cell selectivity resides in the mannose carbamoyl moiety of the BLM saccharide and that both the BLM disaccharide and monosaccharide containing the carbamoyl moiety were capable of the delivery/uptake of a conjugated cyanine dye into cultured cancer cell lines. Presently, the nature of the participation of the carbamoyl moiety has been explored further to provide compounds of utility for defining the nature of the mechanism of tumor cell recognition and uptake by BLM saccharides and in the hope that more efficient compounds could be identified. A library of seven disaccharide-Cy5** dye conjugates was prepared that are structural analogues of the BLM disaccharide. These differed from the natural BLM disaccharide in the position, orientation, and substitution of the carbamoyl group. Studies of these compounds in four matched sets of tumor and normal cell lines revealed a few that were both tumor cell selective and internalized 2-4-fold more efficiently than the natural BLM disaccharide. PMID:25272367

Madathil, Manikandadas M; Bhattacharya, Chandrabali; Yu, Zhiqiang; Paul, Rakesh; Rishel, Michael J; Hecht, Sidney M

2014-11-01

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Labelling of bleomycin with cobalt-57, indium-111, technetium-99m, mercury-197, lead-203, and copper-67  

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The radiochemical purity of the cobalt-57 complex of bleomycin could be enhanced by adjusting the pH of the final product to a value between 5 and 6. This radiopharmaceutical appeared to have better tumor visualizing properties compared to the not neutralized preparation. The clinical use of the cobalt-57 bleomycin complex is however limited by the long physical half-life of the label, causing a risk of radioactive contamination. It appeared to be possible to label bleomycin with radioactive cations (111In3+, sup(99m)Tc4+, 197Hg2+ and 67Cu2+) having suitable gamma ray energies and short half-lifes. These bleomycin complexes showed a high radiochemical purity judged by their behaviour on thin layer chromatography, paper chromatography, and electrophoresis, but their application as tumor visualizing radiopharmaceutical turned out to be disappointing compared with cobalt-57 bleomycin. (orig.)

133

Enhanced pulmonary toxicity with bleomycin and radiotherapy in oat cell lung cancer  

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In a recently completed study, combination chemotherapy consisting of bleomycin, adriamycin, cyclophosphamide, and vincristine was given to 29 patients with oat cell lung cancer. There were no cases of pulmonary fibrosis in these 29 patients. Although several of these patients had prior radiotherapy, none had concomitant radiotherapy and chemotherapy. This same four-drug chemotherapy regimen was combined with concomitant radiotherapy in 13 patients with oat cell lung cancer. There were three cases of fatal pulmonary fibrosis and two other cases of clinically significant pulmonary fibrosis. All five cases of pulmonary fibrosis occurred several weeks after completion of a six-week course of bleomycin (total dosage 90 units). It is concluded that bleomycin cannot be safely administered while patients are receiving radiotherapy of the lung

134

Contribution of cobalt 57 labelled bleomycin in the diagnosis of pulmonary round intraparenchymatous lesions  

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One hundred and eleven patients with a round lesion within the lung parenchyma were submitted to a lung scan using cobalt 57 labelled bleomycin. In all cases, the diagnosis of benign or malignant disease was made definitely by bronchoscopy, fiber endoscopy, transparietal needle biopsy or thoracotomy. Out of 89 neoplasic foci, 87 took up labelled bleomycin with a fixation ratio greater than 13. On the other hand, the 22 benign round foci, except for the large silico-tuberculous nodule, remained silent on radio-isotope scanning. The great value of scanning using cobalt 57 labelled bleomycin in the detection of the malignant or benign nature of round images within the lung is emphasized, the clinical and radiological pre-operative diagnosis remains one of the most difficult in lung disease problems

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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

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The absence of reactive oxygen species production protects mice against bleomycin-induced pulmonary fibrosis  

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Full Text Available Abstract Background Reactive oxygen species and tissue remodeling regulators, such as metalloproteinases (MMPs and their inhibitors (TIMPs, are thought to be involved in the development of pulmonary fibrosis. We investigated these factors in the fibrotic response to bleomycin of p47phox -/- (KO mice, deficient for ROS production through the NADPH-oxidase pathway. Methods Mice are administered by intranasal instillation of 0.1 mg bleomycin. Either 24 h or 14 days after, mice were anesthetized and underwent either bronchoalveolar lavage (BAL or lung removal. Results BAL cells from bleomycin treated WT mice showed enhanced ROS production after PMA stimulation, whereas no change was observed with BAL cells from p47phox -/- mice. At day 1, the bleomycin-induced acute inflammatory response (increased neutrophil count and MMP-9 activity in the BAL fluid was strikingly greater in KO than wild-type (WT mice, while IL-6 levels increased significantly more in the latter. Hydroxyproline assays in the lung tissue 14 days after bleomycin administration revealed the absence of collagen deposition in the lungs of the KO mice, which had significantly lower hydroxyproline levels than the WT mice. The MMP-9/TIMP-1 ratio did not change at day 1 after bleomycin administration in WT mice, but increased significantly in the KO mice. By day 14, the ratio fell significantly from baseline in both strains, but more in the WT than KO strains. Conclusions These results suggest that NADPH-oxidase-derived ROS are essential to the development of pulmonary fibrosis. The absence of collagen deposition in KO mice seems to be associated with an elevated MMP-9/TIMP-1 ratio in the lungs. This finding highlights the importance of metalloproteinases and protease/anti-protease imbalances in pulmonary fibrosis.

Boichot Elisabeth

2005-01-01

137

Changes in pulmonary surfactant function and composition in bleomycin-induced pneumonitis and fibrosis  

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Bleomycin is a widely accepted cancer drug but may induce life-threatening interstitial lung disease in a subset of patients. We evaluated the effect of bleomycin administration on pulmonary surfactant function and composition in rabbit lungs. In order to obtain a uniform response to bleomycin, aerosol technology was employed for bronchoalveolar delivery of 1.8 U/kg b.w. bleomycin. On days 4, 8, 16, 24, 32, and 64 after challenge, bronchoalveolar lavages were performed. Sham-aerosolized rabbits served as controls. In the early acute respiratory distress syndrome (ARDS)-like post-bleomycin period (4-16 days), marked loss of surface activity of the large surfactant aggregate (LA) fraction of surfactant was noted. In parallel, reduced percentages of LA, but only minor changes in surfactant apoproteins (SP)-A, SP-B, and SP-C, were encountered. Analysis of the surfactant lipid profile showed impressively enhanced cholesterol and significantly decreased phosphatidylglycerol (PG) levels. The relative content of dipalmitoyl-PC (DPPC) was slightly increased, and a several-fold increase within the 1-O-alkyl-2-acyl subclass of PC was observed. During the prolonged fibroproliferative period, a highly significant downregulation of SP-B and SP-C levels was observed. This was paralleled by an upregulation of the total extracellular phospholipid pool, with a far-reaching normalization of the (phospho)-lipid profile. The biophysical surfactant function never fully normalized within the 64-day observation period. In conclusion, bleomycin caused marked abnormalities of pulmonary surfactant, with the profile of changes being different between the early ARDS and the late fibrotic phase

138

Induction of Apoptosis and Micronuclei by Bleomycin Sulfate in Different Cell Cycle Stages of Human Lymphocytes  

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Full Text Available Introduction: Bleomycin sulfate is a DNA damaging agent used in cancer chemotherapy. The effect of this drug on various cell cycle stages might be different, thus inducing different modes of death (apoptotic or mitotic death. The aim of this investigation was to study the effects of bleomycin on human peripheral blood lymphocytes at various cell cycle stages by two different end points (induction of apoptosis or micronuclei. Material and Methods: Human peripheral blood lymphocytes were treated with various doses of bleomycin at G0, G1, and G2 phases of the cell cycle and the percentages of apoptosis (AP and micronuclei (MN were determined. The peripheral lymphocytes were isolated by ficoll hypaque and suspended in RPMI-1640 containing 15 % fetal calf serum. The isolated lymphocytes were stimulated by phytohemagglutinin (PHA, cultured again inRPMI-1640, harvested after 64 hrs and 96 hrs, and stained with acridine orange and ethidiumbromide to determine the percentage of apoptotic cells. MN assay was done according to the standard in vitro micronucleus assay. Results: The results showed that the percentages of apoptotic cells and MN at G2 stage were significantly higher than those of G0 and G1 stages. At higher doses, MN formation and apoptotic cells were increased; however with increasing time, the percentage of MN decreased while the percentage of apoptotic cells generally increased in all the cell cycle stages. Conclusion: The results indicate that bleomycin is a potent inducer of both micronuclei and apoptosis. The incidence of apoptotic cells following bleomycin treatment in G0 and G1 was much higher than the incidence of micro nucleated cells at the two sampling times. The percentage of AP cells following bleomycin treatment remained constant across cell cycle stages.

Saify B

2004-01-01

139

Protective role of andrographolide in bleomycin-induced pulmonary fibrosis in mice.  

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Idiopathic pulmonary fibrosis (IPF) is a chronic devastating disease with poor prognosis. Multiple pathological processes, including inflammation, epithelial mesenchymal transition (EMT), apoptosis, and oxidative stress, are involved in the pathogenesis of IPF. Recent findings suggested that nuclear factor-?B (NF-?B) is constitutively activated in IPF and acts as a central regulator in the pathogenesis of IPF. The aim of our study was to reveal the value of andrographolide on bleomycin-induced inflammation and fibrosis in mice. The indicated dosages of andrographolide were administered in mice with bleomycin-induced pulmonary fibrosis. On day 21, cell counts of total cells, macrophages, neutrophils and lymphocytes, alone with TNF-? in bronchoalveolar lavage fluid (BALF) were measured. HE staining and Masson's trichrome (MT) staining were used to observe the histological alterations of lungs. The Ashcroft score and hydroxyproline content of lungs were also measured. TGF-?1 and ?-SMA mRNA and protein were analyzed. Activation of NF-?B was determined by western blotting and electrophoretic mobility shift assay (EMSA). On day 21 after bleomycin stimulation, andrographolide dose-dependently inhibited the inflammatory cells and TNF-? in BALF. Meanwhile, our data demonstrated that the Ashcroft score and hydroxyproline content of the bleomycin-stimulated lung were reduced by andrographolide administration. Furthermore, andrographloide suppressed TGF-?1 and ?-SMA mRNA and protein expression in bleomycin-induced pulmonary fibrosis. Meanwhile, andrographolide significantly dose-dependently inhibited the ratio of phospho-NF-?B p65/total NF-?B p65 and NF-?B p65 DNA binding activities. Our findings indicate that andrographolide compromised bleomycin-induced pulmonary inflammation and fibrosis possibly through inactivation of NF-?B. Andrographolide holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis. PMID:24300094

Zhu, Tao; Zhang, Wei; Xiao, Min; Chen, Hongying; Jin, Hong

2013-01-01

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Protective Role of Andrographolide in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic devastating disease with poor prognosis. Multiple pathological processes, including inflammation, epithelial mesenchymal transition (EMT, apoptosis, and oxidative stress, are involved in the pathogenesis of IPF. Recent findings suggested that nuclear factor-?B (NF-?B is constitutively activated in IPF and acts as a central regulator in the pathogenesis of IPF. The aim of our study was to reveal the value of andrographolide on bleomycin-induced inflammation and fibrosis in mice. The indicated dosages of andrographolide were administered in mice with bleomycin-induced pulmonary fibrosis. On day 21, cell counts of total cells, macrophages, neutrophils and lymphocytes, alone with TNF-? in bronchoalveolar lavage fluid (BALF were measured. HE staining and Masson’s trichrome (MT staining were used to observe the histological alterations of lungs. The Ashcroft score and hydroxyproline content of lungs were also measured. TGF-?1 and ?-SMA mRNA and protein were analyzed. Activation of NF-?B was determined by western blotting and electrophoretic mobility shift assay (EMSA. On day 21 after bleomycin stimulation, andrographolide dose-dependently inhibited the inflammatory cells and TNF-? in BALF. Meanwhile, our data demonstrated that the Ashcroft score and hydroxyproline content of the bleomycin-stimulated lung were reduced by andrographolide administration. Furthermore, andrographloide suppressed TGF-?1 and ?-SMA mRNA and protein expression in bleomycin-induced pulmonary fibrosis. Meanwhile, andrographolide significantly dose-dependently inhibited the ratio of phospho-NF-?B p65/total NF-?B p65 and NF-?B p65 DNA binding activities. Our findings indicate that andrographolide compromised bleomycin-induced pulmonary inflammation and fibrosis possibly through inactivation of NF-?B. Andrographolide holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis.

Tao Zhu

2013-12-01

 
 
 
 
141

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

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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.

Crimi Nunzio

2006-11-01

142

Protocol Online  

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Protocol Online is a database of research protocols in a variety of life science fields. It contains protocols contributed by worldwide researchers as well as links to web protocols hosted by worldwide research labs, biotech companies, personal web sites. The data is stored in a MySql relational database. Protocol Online also hosts discipline specific discussion forums (BioForum), and provides a free PubMed search and alerting service (PubAlert).

Long-Cheng Li (Protocol Online)

2012-01-06

143

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

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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.

1999-01-01

144

Problems in the differentiation of lung infiltrates following bleomycin therapy from metastases  

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Sixty patients with malignant testicular tumours were treated with bleomycin according to the Einhorn regime. Following treatment, pulmonary infiltrates were seen on the chest X-ray of three patients and the CT of six patients. Altogether 24 infiltrates resembling metastases were seen in five patients. Five round foci were combined with infiltrates in other parts of the lung. Regression of the infiltrates after stopping bleomycin, negative tumour markers, the timing of the development of the infiltrates and the regression of the infiltrates in three patients without treatment make it extremely unlikely that the appearances were due to metastases. (orig.)

145

Rac2 is involved in bleomycin-induced lung inflammation leading to pulmonary fibrosis  

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Background Pulmonary fibrotic diseases induce significant morbidity and mortality, for which there are limited therapeutic options available. Rac2, a ras-related guanosine triphosphatase expressed mainly in hematopoietic cells, is a crucial molecule regulating a diversity of mast cell, macrophage, and neutrophil functions. All these cell types have been implicated in the development of pulmonary fibrosis in a variety of animal models. For the studies described here we hypothesized that Rac2 deficiency protects mice from bleomycin-induced pulmonary fibrosis. Methods To determine the role of Rac2 in pulmonary fibrosis we used a bleomycin-induced mouse model. Anesthetized C57BL/6 wild type and rac2 -/- mice were instilled intratracheally with bleomycin sulphate (1.25 U/Kg) or saline as control. Bronchoalveolar lavage (BAL) samples were collected at days 3 and 7 of treatment and analyzed for matrix metalloproteinases (MMPs). On day 21 after bleomycin treatment, we measured airway resistance and elastance in tracheotomized animals. Lung sections were stained for histological analysis, while homogenates were analyzed for hydroxyproline and total collagen content. Results BLM-treated rac2 -/- mice had reduced MMP-9 levels in the BAL on day 3 and reduced neutrophilia and TNF and CCL3/MIP-1? levels in the BAL on day 7 compared to BLM-treated WT mice. We also showed that rac2 -/- mice had significantly lower mortality (30%) than WT mice (70%) at day 21 of bleomycin treatment. Lung function was diminished in bleomycin-treated WT mice, while it was unaffected in bleomycin-treated rac2 -/- mice. Histological analysis of inflammation and fibrosis as well as collagen and hydroxyproline content in the lungs did not show significant differences between BLM-treated rac2 -/- and WT and mice that survived to day 21. Conclusion Rac2 plays an important role in bleomycin-induced lung injury. It is an important signaling molecule leading to BLM-induced mortality and it also mediates the physiological changes seen in the airways after BLM-induced injury. PMID:24970330

2014-01-01

146

Evaluation of cold areas on the thyroid scan with sup(99m)Tc-bleomycin  

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The value of sup(99m)Tc-bleomycin scintigraphy in the evaluation of cold areas on a sup(99m)Tc-pertechnetate scan was investigated in 35 patients. A histological diagnosis was obtained in 31 patients. Only one of the six malignant lesions was considered as positive and two as doubtful. Of the remaining 25 patients with non-toxic colloid goitre, one was clearly positive and four were doubtful. These results indicate that sup(99m)Tc-bleomycin scintigraphy is not a valuable procedure in the further evaluation of patients with cold lesions. (orig.)

147

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

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Full Text Available 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, 250 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.

1999-01-01

148

Antisense oligonucleotide inhibition of Heat Shock Protein (HSP 47 improves bleomycin-induced pulmonary fibrosis in rats  

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Full Text Available Abstract Background The most common pathologic form of pulmonary fibrosis arises from excessive deposition of extracellular matrix proteins such as collagen. The 47 kDa heat shock protein 47 (HSP47 is a collagen-specific molecular chaperone that has been shown to play a major role during the processing and/or secretion of procollagen. Objectives To determine whether inhibition of HSP47 could have beneficial effects in mitigating bleomycin-induced pulmonary fibrosis in rats. Methods All experiments were performed with 250–300 g male Wistar rats. Animals were randomly divided into five experimental groups that were administered: 1 saline alone, 2 bleomycin alone, 3 antisense HSP47 oligonucleotides alone, 4 bleomycin + antisense HSP47 oligonucleotides, and 5 bleomycin + sense control oligonucleotides. We investigated lung histopathology and performed immunoblot and immunohistochemistry analyses. Results In rats treated with HSP47 antisense oligonucleotides, pulmonary fibrosis was significantly reduced. In addition, treatment with HSP47 antisense oligonucleotides significantly improved bleomycin-induced morphological changes. Treatment with HSP47 antisense oligonucleotides alone did not produce any significant changes to lung morphology. Immunoblot analyses of lung homogenates confirmed the inhibition of HSP47 protein by antisense oligonucleotides. The bleo + sense group, however, did not exhibit any improvement in lung pathology compared to bleomycin alone groups, and also had no effect on HSP47 expression. Conclusion These findings suggest that HSP47 antisense oligonucleotide inhibition of HSP47 improves bleomycin-induced pulmonary fibrosis pathology in rats.

Noguchi Takayuki

2007-05-01

149

Effects of a combined Bleomycin/radiotherapy on the increase of cell numbers in Ehrlich ascitic carcinoma  

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The effects of separate and combined application of the cytostatic Bleomycin and X-radiation on the multiplication of the Ehrlich ascitic tumour cells in vivo and on the survival time of tumourous mice was examined by applying automatic, electronic cell counting. If this cytostatic is administered alone up to 100 mg/kg the growth curve of the EAT-cells shows, after a 24 hours' delay, hardly any difference to that of untreated tumour cells. The separate administration of such Bleomycin doses and the separate X-radiation of the EAT cells with doses of up to 1000 rad had no significant influence on the survival time of tumourous mice. The combined application of Bleomycin and X-radiation elongates the 50%-survival time of the tumourous mice. If the X-radiation takes place 12 hours after the Bleomycin treatment the animals survive longer than is the case with simultaneous treatment. Although no dose effect curves could be set up the results obtained let assume a synergistic effect of Bleomycin and irradiation which is especially significant if the radiation is carried out 12 hours after a Bleomycin treatment. The reasons of this are assumed to lie in the increased radiation sensitivity of the tumour cells caused by the bleomycin-induced partial synchronisation of the EAT cells. (orig.)

150

Effect of local bleomycin sulfate application on seroma formation in a rat mastectomy and axillary lymph node dissection model.  

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Seroma formation is one of the most common complications following breast cancer surgery. It may lead to delay of adjuvant therapies and increasement of therapy costs. Bleomycin sulfate is a sclerosing antibiotic with antineoplastic efficacy. It is locally used in the treatment of pleural effusion. The present study aimed to investigate seroma-reducing effect of local bleomycin application after mastectomy. Sixteen female Wistar Albino rats were used in this study. The rats were divided into two equal groups. Under general anesthesia all rats underwent unilateral mastectomy as definition by Harada. Serum physiologic was applied to animals in Group 1 (control group) and bleomycin to Group 2. Mastectomized localization was explored on the 10th day postoperatively. Seroma and tissue samples were obtained from axilla and thoracic wall for histopathological examination. The amount of seroma was significantly lower in the bleomycin group as compared to the control group (P=0.002). Fibrosis, PNL infiltration and the number of fibroblasts were significantly higher in the bleomycin group. No difference was identified between the groups in terms of angiogenesis, edema, congestion, and monocyte, lymphocyte and macrophage infiltration. Local bleomycin sulfate application might be a therapeutic option in patients with seroma formation, as well as in the patients with malignant pleural effusion. Nonetheless, further studies that compare the efficacy and adverse effects (benefit-to-harm ratio) of bleomycin sulfate are needed. PMID:24231620

Eser, Mehmet; Gökçeimam, Mehmet; Eyvaz, Kemal; Tutal, F?rat; Geçer, Melin Özgün; Gökta?, Selçuk; Uzun, Hüseyin; Kaptanoglu, Levent; Kurt, N

2014-01-15

151

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

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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.

Crimi Nunzio

2005-06-01

152

P-selectin upregulation in bleomycin induced lung injury in rats: effect of N-acetyl-L-cysteine  

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Background: A number of adhesion molecules are involved in the process of neutrophil infiltration into the lung. P-selectin is one of these neutrophil-endothelial cell adhesion molecules. A study was undertaken to examine the involvement of P-selectin in the development of bleomycin induced inflammation and the ability of N-acetyl-L-cysteine to reduce the potential expression of this selectin in rats. Methods: N-acetyl-L-cysteine (3 mmol/kg po) was administered daily for seven days prior to bleomycin administration (2.5 U/kg). The kinetics of P-selectin expression and the effect of N-acetyl-L-cysteine after bleomycin treatment were measured using radiolabelled antibodies. P-selectin localisation was evaluated by immunohistochemistry and neutrophil infiltration was assessed by myeloperoxidase activity. Results: Bleomycin administration resulted in an upregulation of P-selectin at 1 hour, returning to baseline at 3 hours. Myeloperoxidase activity showed a significant increase at 6 hours after bleomycin administration that lasted for 3 days. N-acetyl-L-cysteine treatment completely prevented these increases. Conclusion: Upregulation of P-selectin in the lung is associated with neutrophil recruitment in response to bleomycin. The beneficial effect of N-acetyl-L-cysteine on bleomycin induced lung injury may be explained in part by the prevention of neutrophil recruitment in the inflammatory stage of the disease. PMID:12096208

Serrano-Mollar, A; Closa, D; Cortijo, J; Morcillo, E; Prats, N; Gironella, M; Panes, J; Rosello-Catafau, J; Bulbena, O

2002-01-01

153

Deficiency in the divalent metal transporter 1 augments bleomycin-induced lung injury  

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Exposure to bleomycin can result in an inflammatory lung injury. The biological effect of this anti-neoplastic agent is dependent on its coordination of iron with subsequent oxidant generation. In lung cells, divalent metal transporter 1 (DMT1) can participate in metal transport ...

154

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

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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.

Mohammad Ghannadi-Maragheh

2012-09-01

155

Isolation and characterization of Chinese hamster ovary cell lines sensitive to mitomycin C and bleomycin  

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Seven Chinese hamster ovary K1 cell lines exhibiting sensitivity to anticancer drugs have been isolated by a replica-plating technique. Five of the mutants are hypersensitive to the DNA cross-linking agent mitomycin C. Of these, one is also appreciably sensitive to UV light. Significant variations in their cross-sensitivity to cis-platinum(II) diammine dichloride, chlorambucil, and Adriamycin have also been observed. Two additional mutants have been isolated on the basis of sensitivity to the radiomimetic agent bleomycin. One of these shows greater than 6-fold sensitivity to bleomycin, while the other is approximately 14 times more sensitive than the parental strain to bleomycin and is also hypersensitive to a number of other DNA-damaging agents, including cis-platinum(II) diammine dichloride, chlorambucil, X-rays, and UV light. Both bleomycin-sensitive mutants also exhibit some degree of sensitivity to Adriamycin. In all cases, the cell lines have been grown in continuous culture for 3 months without evidence of reversion and should act as suitable recipients in DNA transfection experiments aimed at identifying human DNA repair genes

156

The role of bleomycin combination in radiation therapy for squamous cell carcinoma in the oral cavity  

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In an effort to improve tumor control by radiation therapy, a treatment regimen consisting of concurrent combination of bleomycin (90 mg/3 weeks) and radiation (30 Gy/3 weeks) was applied. Between 1972 and 1981, 287 patients with squamous cell carcinoma in the oral cavity were subjected to this bleomycin-radiation combination regimen. All except 4 patients experienced marked response after treatment using the bleomycin-radiation combination alone. One hundred thirty-four patients (47 %) obtained CR and 149 (53 %) PR. Higher CR rates were obtained in patients with carcinoma of the lower gum (62 %), of the upper gum (68 %), and of the cheek mucosa (43 %), compared to patients with carcinoma of the floor of the mouth (21 %), and of the tongue (15 %). In each of the tumor sites, small lesions (T1, T2) obtained higher CR rates, compared with large lesions (T3, T4). Of the 134 patients who experienced CR, 83 were observed without any further treatment after bleomycin-radiation combination alone. Local recurrence-free rates of these patients were 72 % for T1, T2 lesions and 48 % for T3, T4 lesions. Local control rates were increased to 85 % and 78 %, respectively, with successful salvage treatment involving surgery or interstitial radiotherapy for post-irradiation failures. (author)

157

Comparison of gamma radiation and radiomimmetic chemical, bleomycin in leukocytes from certain genetic disorders  

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Full text: To compare the frequency and distribution pattern of bleomycin and gamma radiation induced chromosomal aberrations in human genetic disorders. To study if the induced chromosomal break points are specific for specific human genetic disorders. Human genetics disorders such as; retinitis pigmentosa, retinoblastoma, xeroderma pigmentosa and gonadal dysgenesis were used in our study. Suitable controls were maintained. The frequency and distribution pattern of chromosomal break points in individual chromosomes were determined in lymphocytes exposed to 50r of gamma radiation and 10?g/ml of bleomycin for 3h at G2. In normal individuals none of the unirradiated leukocyte cultures of any syndrome showed any accountable number of chromosomal aberrations. The frequency of radiation induced chromosomal break points showed a non random distribution pattern and frequently clustered at some specific chromosome regions to form hot spots. Lack of linear-quadratic dose response was observed in the lymphocyte exposed to bleomycin in normal individual. The frequency of chromosomal aberrations in the whole genome for the genetic disorders were higher than the controls and a varying distribution pattern of bleomycin induced breaks per cell was observed

158

Studies on bleomycin-induced repair DNA synthesis in permeable mouse ascites sarcoma cells.  

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Full Text Available To study the mechanism of DNA excision repair, a DNA repair system employing permeable mouse sarcoma (SR-C3H/He cells was established and characterized. SR-C3H/He cells were permeabilized with a 0.0175% Triton X-100 solution. The permeable cells were treated with 1 mM ATP and 0.11 mM bleomycin, and then washed thoroughly to remove ATP and bleomycin. Repair DNA synthesis occurred in the bleomycin-damaged, permeable SR-C3H/He cells when incubated with ATP and four deoxyribonucleoside triphosphates. The repair nature of the DNA synthesis was confirmed by the BrdUMP density shift technique, and by the reduced sensitivity of the newly synthesized DNA to Escherichia coli exonuclease III. The DNA synthesis was optimally enhanced by addition of 0.08 M NaCl. Studies using selective inhibitors of DNA synthesis showed that aphidicolin-sensitive DNA polymerase (DNA polymerase alpha and/or delta and DNA polymerase beta were involved in the repair process. The present DNA repair system is thought to be useful to study nuclear DNA damage by bleomycin, removal of the damaged ends by an exonuclease, repair DNA synthesis by DNA polymerases and repair patch ligation by DNA ligase(s.

Mori,Shigeru

1989-04-01

159

Oxy radical formation during redox cycling of the bleomycin-iron (III) complex by NADPH-cytochrome P-450 reductase.  

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Bleomycin was aerobically incubated with FeCl3, NADPH, isolated rat-liver microsomal cytochrome P-450 reductase and methional. The conversion of methional to ethene, which indicates oxy radicals, was determined. Ethene formation depended on oxygen, NADPH, FeCl3 and the enzyme. About equimolar concentrations of bleomycin and FeCl3 resulted in optimal ethene formation. Dimethyl sulfoxide, mannitol, glycerol, glutathione and glutathione disulfide inhibited ethene formation. These results indicate that oxy radicals are formed after reduction of the bleomycin-Fe-complex by NADPH-cytochrome P-450 reductase. PMID:2412562

Mahmutoglu, I; Kappus, H

1985-09-01

160

Macrophage metalloelastase (MMP-12 deficiency does not alter bleomycin-induced pulmonary fibrosis in mice  

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Full Text Available Abstract Background Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix in the interstitium resulting in respiratory failure. The role of remodeling mediators such as metalloproteinases (MMPs and their inhibitors (TIMPs in the fibrogenic process remains misunderstood. In particular, macrophage metalloelastase, also identified as MMP-12, is known to be involved in remodeling processes under pathological conditions. However, MMP-12 involvement in pulmonary fibrosis is unknown. Here we investigated fibrotic response to bleomycin in MMP-12 deficient mice. Materials and methods C57BL/6 mice, Balb/c mice and MMP-12 -/- mice with a C57BL/6 background received 0.3 mg bleomycin by intranasal administration. 14 days after, mice were anesthetized and underwent either bronchoalveolear lavage (BAL or lung removal. Collagen deposition in lung tissue was determined by Sircol™ collagen assay, MMP activity in BAL fluid was analyzed by zymography, and other mediators were quantified in BAL fluid by ELISA. Real time PCR was performed to assess gene expression in lung removed one or 14 days after bleomycin administration. Student t test or Mann & Whitney tests were used when appropriate for statistical analysis. Results The development of pulmonary fibrosis in "fibrosis prone" (C57BL/6 mice was associated with prominent MMP-12 expression in lung, whereas MMP-12 expression was weak in lung tissue of "fibrosis resistant" (Balb/c mice. MMP-12 mRNA was not detected in MMP-12 -/- mice, in conformity with their genotype. Bleomycin elicited macrophage accumulation in BAL of MMP-12 -/- and wild type (WT mice, and MMP-12 deficiency had no significant effect on BAL cells composition. Collagen content of lung was increased similarly in MMP-12 -/- and WT mice 14 days after bleomycin administration. Bleomycin elicit a raise of TGF-? protein, MMP-2 and TIMP-1 protein and mRNA in BAL fluids and lung respectively, and no significant difference was observed between MMP-12 -/- and WT mice considering those parameters. Conclusion The present study shows that MMP-12 deficiency has no significant effect on bleomycin-induced fibrosis.

Boichot Elisabeth

2006-02-01

 
 
 
 
161

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

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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

162

A Systematic Review of Talc Compared with Bleomycin for Patients with Malignant Pleural Effusions  

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Full Text Available Background and objective Malignant pleural effusions are a common complication in advanced malignancy. Talc, bleomycin and the tetracyclines are the three most frequently used sclerosants. The aim of this study is to evaluate the efficacy and adverse effects of patients with malignant pleural effusions treated with talc and bleomycin. Methods We searched PubMed, Embase, the Cochrane Library, Chinese biomedicine literature database (CBM, CNKI, VIP, references of included studies for randomized controlled trials comparing talc with bleomycin for patients with malignant pleural effusions. The quality of included studies was assessed independently by two reviewers, discrepancies were resolved by discussion with the third person. We analyzed the data using Review Manager (version 5.0 software. Results Six studies totaling 224 patients were included. Meta analysis results were as follows: there was significantdifference in treatment success (RR=1.22, 95%CI: 1.05-1.42, recurrence rate (RR=0.31, 95%CI: 0.11-0.87 between talc group and bleomycin group, there was no significant difference between the two groups in case fatality rate (RR=1.39, 95%CI: 0.84-2.30, fever (RR=0.68, 95%CI: 0.24-1.94, pain (RR=0.22, 95%CI: 0.01-4.32. Conclusion Current evidence indicate that talc is super to bleomycin for patients with malignant pleural effusions in terms of improvingtreatment success and reducing recurrence rate, there is no significant difference between the two group with regard to casefatality rate, fever, pain, the results mentioned above still need to be confirmed by high quality, large sample, multicenter randomized controlled trial.

Yonggang WEI

2009-03-01

163

Preparation of [6lCu]Bleomycin Complexes as a Potential PET radiopharmaceutical and it's biological evaluation in normal and tumor-bearing rodents  

International Nuclear Information System (INIS)

[61Cu]Bleomycin ([61Cu]Bleomycin) was prepared using [61Cu]CuCl2, produced via natZn(p,x)61Cu (180?A proton irradiation, 22 MeV, 3.2 h), purified by ion chromatography method. [61Cu]Bleomycin was prepared at optimized conditions (room temperature, 45 min, 0.1 mg bleomycin for 2-10 mCi 61CuCl2) with radiochemical purity over 98% determined by HPLC and radio-thin layer chromatography. [61Cu]Bleomycin was administered into the normal and tumor bearing rodents up to 210 minutes followed by biodistribution and co incidence imaging studies. A significant tumor/non tumor accumulation was observed either by animal scarification or imaging method. [61Cu] Bleomycin can be a potential PET radiotracer for tumor imaging.

164

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

International Nuclear Information System (INIS)

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.

165

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

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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

2013-05-01

166

The synthesis of radioiodinated cobalt-bleomycin and its in vivo distributions in tumor-bearing animals  

International Nuclear Information System (INIS)

This study is the addition of radioactive iodine on cobalt-bleomycin without changing its tumor-localizing properties. Cobalt-bleomycin demethy-A2 was synthesized by adding CoCl2 to bleomycin demethyl-A2 aqueous solution. On the other side, 3-125I-iodobenzylalcohol was prepared by replacing iodine of 3-iodobenzylalcohol with iodine-125I. And 3-125I-iodobenzyliodide was produced by adding P2I4 to 3-125I-iodobenzylalcohol in CH2Cl2. 3-125I-iodobenzyl-cobalt-bleomycin was synthesized by coupling 3-125I-iodobenzyliodide to cobalt-bleomycin demethyl-A2. 3-125I-iodobenzyl-cobalt-bleomycin was injected intravenously to tumor-bearing mice. In vivo distributions of this compound were measured from 60 minutes to 24 hours after injection. Accumulation of this compound in tumor tissue was much more than other normal organs except kidney and liver. This new labeled compound showed considerably strong affinity to malignant tumor. (author)

167

Proliferative kinetics and chromosome damage in trisomy 21 lymphocyte cultures exposed to gamma-rays and bleomycin  

International Nuclear Information System (INIS)

Lymphocytes from patients with Down's syndrome (trisomy 21) have been investigated for cell cycle kinetics, cell proliferation delays, and chromosomal aberrations after exposure to gamma-rays or bleomycin. Analysis by sister chromatid differential staining revealed that trisomy 21 lymphocytes started cell cycling about 5 hr earlier than did normal diploid lymphocytes after phytohemagglutinin stimulation as a whole, but that cycling trisomic and normal cells had the same mean cell cycle times. When exposed to gamma-rays or bleomycin in G0, trisomy 21 lymphocytes showed a 30% or, on average, 50% longer duration of cell turnover times, respectively, than normal cells; only bleomycin-treated trisomic cells had a biphasic dose-response. Frequencies of dicentrics and rings in first-division cells after gamma-ray or bleomycin exposure were twice as high in trisomic cells as in normal cells. The frequency of aberrations decreased by 50% (gamma-ray-exposed) or 65 to 85% (bleomycin-treated) through successive divisions; trisomic cells showed a more marked decline in aberration yields compared to normal cells after bleomycin treatment. These data support the idea that circulating lymphocytes in trisomy 21 patients have a shorter average life span or a younger average age

168

Extreme cytotoxicity and susceptibility to hprt mutagenesis in Ku-deficient xrs-6 cells treated with bleomycin in plateau phase.  

Science.gov (United States)

In an attempt to determine the possible role of Ku-dependent end joining in mutagenesis resulting from DNA double-strand breaks, mutations induced by bleomycin at the hprt locus in plateau phase normal CHO-K1 and Ku-deficient xrs-6 cells were examined. Plateau phase xrs-6 cells were 500-fold more sensitive to chronic bleomycin treatment than were CHO-K1 cells. XRCC4-deficient XR-1 cells were approximately 100-fold and DNA-PKcs-deficient XR-C1 and V-3 cells 15- to 30-fold more sensitive than CHO-K1 cells. These hypersensitivities are much greater than those previously reported for acute treatments with bleomycin or ionizing radiation. While the induced mutation frequencies at comparable levels of survival were slightly lower in xrs-6 cells, mutations were induced by bleomycin at much lower concentrations in xrs-6 than in CHO-K1 cells. For both cell lines bleomycin treatment resulted in a marked increase in the incidence of complete hprt deletions, while point mutations in hprt cDNA were rare. The results suggest that bleomycin-induced double-strand breaks tend to generate very large deletions in both cell lines and that this effect occurs at much lower levels of double-strand breaks in Ku-deficient than in normal cells. PMID:15671058

Zhou, Tong; Povirk, Lawrence F

2005-01-01

169

Suppression of a DNA base excision repair gene, hOGG1, increases bleomycin sensitivity of human lung cancer cell line  

International Nuclear Information System (INIS)

Bleomycin (BLM) has been found to induce 8-oxoguanine and DNA strand breaks through producing oxidative free radicals, thereby leading to cell cycle arrest, apoptosis and cell death. Cellular DNA damage repair mechanisms such as single strand DNA break repair/base excision repair (BER) are responsible for removing bleomycin-induced DNA damage, therefore confer chemotherapeutic resistance to bleomycin. In this study, we have investigated if down-regulation of human 8-oxoguanine DNA glycosylase (hOGG1), an important BER enzyme, could alter cellular sensitivity to bleomycin, thereby reducing chemotherapeutic resistance in human tumor cell. A human lung cancer cell line with hOGG1 deficiency (A549-R) was created by ribozyme gene knockdown technique. Bleomycin cellular sensitivity and DNA/chromosomal damages were examined using MTT, colony forming assay, comet assay as well as micronucleus assay. We demonstrated that hOGG1 gene knockdown enhanced bleomycin cytotoxicity and reduced the ability of colony formation of the lung cancer cell lines. We further demonstrated that bleomycin-induced DNA strand breaks resulted in an increase of micronucleus rate. hOGG1 deficiency significantly reduced DNA damage repair capacity of the lung cancer cell lines. Our results indicated that hOGG1 deficiency allowed the accumulation of bleomycin-induced DNA damage and chromosomal breaks by compromising DNA damage repair capacity, thereby increasing cellular sensitivity to bleomycin

170

Folk medicine Terminalia catappa and its major tannin component, punicalagin, are effective against bleomycin-induced genotoxicity in Chinese hamster ovary cells.  

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Terminalia catappa L. is a popular folk medicine for preventing hepatoma and treating hepatitis in Taiwan. In this paper, we examined the protective effects of T. catappa leaf water extract (TCE) and its major tannin component, punicalagin, on bleomycin-induced genotoxicity in cultured Chinese hamster ovary cells. Pre-treatment with TCE or punicalagin prevented bleomycin-induced hgprt gene mutations and DNA strand breaks. TCE and punicalagin suppressed the generation of bleomycin-induced intracellular free radicals, identified as superoxides and hydrogen peroxides. The effectiveness of TCE and punicalagin against bleomycin-induced genotoxicity could be, at least in part, due to their antioxidative potentials. PMID:10773401

Chen, P S; Li, J H; Liu, T Y; Lin, T C

2000-05-01

171

Investigation of the Local Structure of Feii Bleomycin And Peplomycins Using Theoretical Analysis of XANES  

Energy Technology Data Exchange (ETDEWEB)

The active site geometry of Fe(II)-bleomycin, peplomycin and its derivatives have been studied on the basis of theoretical multiple scattering simulations of the Fe K-edge x-ray absorption near edge structure. Comparisons of the experimental and theoretical spectra calculated for the different models of Fe(II)-bleomycin reveal serious distortions of the ligands nearest to Fe. This includes the presence of one ligand with a very short bond length as well as angular distortions. Reconstruction of the nearest environment of the Fe during perturbation of axial ligand was investigated for peplomycin. It was found that replacement of carbamoyl group of the mannose with solvent molecule led to a small increase of average radius (0.03 {angstrom}) of the first atomic shell around Fe ion and elongation of the shortest bond length (0.10 {angstrom}).

Smolentsev, G.; Soldatov, E.; Wasinger, E.; Solomon, E.; Hodgson, K.; Hedman, B.

2006-10-27

172

Molecular dynamics simulations exploring the interaction between DNA and metalated bleomycin  

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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.

Leif A. Eriksson

2011-05-01

173

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

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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.

NIKOS KATSAROS

2003-05-01

174

Survival of diploid yeast cells to bleomycin in combination with UV-light or hyperthermia  

International Nuclear Information System (INIS)

In the present work we have investigated the possible interaction between Bleomycin (B) and UV light or hyperthermia (HT) in the induction of lethal events in diploid yeast populations in the stationary phase of growth. UV and B acting as single agents determine sigmoid survival curves. The combination of UV+B produces different degrees of sensitization depending on dose ranges. For [B]=7.5 ?g/ml combined with different UV fluences an exponential course is observed, suggesting overlapping lesion specificity of the involved repair pathways (excision and recombination). The hyperthermia plus Bleomycin treatment produces different degrees of inactivation depending on the sequences. Maximal inactivation effect was obtained for the sequence B+HT. In the case of HT+B ([B]>7.5 ?g/ml) the obtained sensitization is lower. (orig.)

175

Radiogenic male breast cancer with in vitro sensitivity to ionizing radiation and bleomycin  

International Nuclear Information System (INIS)

A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis

176

Microsomal Prostaglandin E Synthase-1 Deficiency Exacerbates Pulmonary Fibrosis Induced by Bleomycin in Mice  

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Full Text Available Microsomal prostaglandin E2 synthase-1 (mPGES-1, an inducible enzyme that converts prostaglandin H2 (PGH2 to prostaglandin E2 (PGE2, plays an important role in a variety of diseases. So far, the role of mPGES-1 in idiopathic pulmonary fibrosis (IPF remained unknown. The current study aimed to investigate the role of mPGES-1 in pulmonary fibrosis induced by bleomycin in mice. We found that mPGES-1 deficient (mPGES-1?/? mice exhibited more severe fibrotic lesions with a decrease in PGE2 content in lungs after bleomycin treatment when compared with wild type (mPGES-1+/+ mice. The mPGES-1 expression levels and PGE2 content were also decreased in bleomycin-treated mPGES-1+/+ mice compared to saline-treated mPGES-1+/+ mice. Moreover, in both mPGES-1?/? and mPGES-1+/+ mice, bleomycin treatment reduced the expression levels of E prostanoid receptor 2 (EP2 and EP4 receptor in lungs, whereas had little effect on EP1 and EP3. In cultured human lung fibroblast cells (MRC-5, siRNA-mediated knockdown of mPGES-1 augmented transforming growth factor-?1 (TGF-?1-induced ?-smooth muscle actin (?-SMA protein expression, and the increase was reversed by treatment of PGE2, selective EP2 agonist and focal adhesion kinase (FAK inhibitor. In conclusion, these findings revealed mPGES-1 exerts an essential effect against pulmonary fibrogenesis via EP2-mediated signaling transduction, and activation of mPGES-1-PGE2-EP2-FAK signaling pathway may represent a new therapeutic strategy for treatment of IPF patients.

Bo Wei

2014-04-01

177

Combination therapy for advanced oral squamous cell carcinoma with radiation and bleomycin, 1  

International Nuclear Information System (INIS)

Twenty-five patients of advanced oral cancers (squamous cell carcinoma) were treated with combination of radiation and bleomycin in the first course of treatment, and then treated with either Ra needle or 198Au grain implantation, 2 to 3 weeks after the first course of treatment for severe mucositis. The treatments were performed during 1975 to 1977. In the combination therapy, external irradiation (daily 250 rad) of Telecobalt ?-ray or Betatron electron beam was given by 4 fractionations per week during 2.5 to 3 weeks (2,500 to 3,000 rad). Bleomycin (5 mg) was injected intramuscularly about 30 min before the irradiation, giving a total of 50 to 60 mg during therapy. In the second course of therapy, Ra needle or 198Au grain implants were employed in 14 cases and further external irradiation was given for the remaining cases except one which had two primary origins of cancer in the tongue and liver. As a result of the combination therapy, 12 primary tumors out of 25 cases markedly regressed (more than 50% regression) and by subsequent radiotherapy, 11 primary tumors out of 24 were completely controlled during more than 14 months of follow-up observation. The tongue cancer in one exceptional case was controlled by the combination of radiation (3,000 rad) and bleomycin (60 mg) alone. Fifteen of 25 patients are still alive, while 10 patients died of cancer. This therapy of combined irradiation and bleomycin seems to be effective on advanced oral cancers because the local tumor control rate increased markedly. (author)

178

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

179

Complete Resolution of Cystic Hygroma with Single Session of Intralesional Bleomycin  

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Intralesional sclerotherapy as a primary modality of management for cystic hygroma is successfully described in literature. It has many benefits over surgical approach; recurrence being the concern of as much as 20% of patients in which apparent complete excision has been performed. Bleomycin is one of sclerosing agents used as intralesional therapy in cystic hygroma. Complete response usually occurs in multiple sessions of sclerotherapy. Rarely, complete resolution occurs with single session...

Fadi Atwan; Isam Elamin Elsiddig; Muhammad Sharif

2012-01-01

180

Gallium and bleomycin scans in the clinical staging of testis tumor  

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Twenty-one patients with testicular tumors had gallium scans prior to retroperitoneal lymph node dissection. Eleven of 14 patients found to have nodal involvement had positive scans, and 2 of 7 patients with negative nodes had false positive scans. Bleomycin scans were positive in 4 of 5 patients with nodal metastases. While these scans provide a simple, noninvasive and occasionally useful technique for the clinical staging of testis neoplasms, they do not, in our experience, significantly supplement other staging procedures.

Yeh, S.D.; Whitmore, W.F. Jr.; Grabstald, H.

1978-01-01

 
 
 
 
181

A prostacyclin analogue, iloprost, protects from bleomycin-induced pulmonary fibrosis in mice  

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Full Text Available Abstract Background Metabolites of arachidonic acid such as prostacyclin (PGI2 have been shown to participate in the pathogenesis of pulmonary fibrosis by inhibiting the expression of pro-inflammatory and pro-fibrotic mediators. In this investigation, we examined whether iloprost, a stable PGI2 analogue, could prevent bleomycin-induced pulmonary inflammation and fibrosis in a mouse model. Methods Mice received a single intratracheal injection of bleomycin with or without intraperitoneal iloprost. Pulmonary inflammation and fibrosis were analysed by histological evaluation, cellular composition of bronchoalveolar lavage (BAL fluid, and hydroxyproline content. Lung mechanics were measured. We also analysed the expression of inflammatory mediators in BAL fluid and lung tissue. Results Administration of iloprost significantly improved survival rate and reduced weight loss in the mice induced by bleomycin. The severe inflammatory response and fibrotic changes were significantly attenuated in the mice treated with iloprost as shown by reduction in infiltration of inflammatory cells into the airways and pulmonary parenchyma, diminution in interstitial collagen deposition, and lung hydroxyproline content. Iloprost significantly improved lung static compliance and tissue elastance. It increased the expression of IFN? and CXCL10 in lung tissue measured by RT-PCR and their levels in BAL fluid as measured by ELISA. Levels of TNF?, IL-6 and TGF?1 were lowered by iloprost. Conclusions Iloprost prevents bleomycin-induced pulmonary fibrosis, possibly by upregulating antifibrotic mediators (IFN? and CXCL10 and downregulating pro-inflammatory and pro-fibrotic cytokines (TNF?, IL-6, and TGF?1. Prostacyclin may represent a novel pharmacological agent for treating pulmonary fibrotic diseases.

Guo Zijian

2010-03-01

182

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

183

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

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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

184

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Mexico | Language: Spanish 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 pri [...] ncipal 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 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 bleomy [...] cin 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 deposition 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.

Sandra, Cabrera Benítez.

185

Microsomal prostaglandin E synthase-1 deficiency exacerbates pulmonary fibrosis induced by bleomycin in mice.  

Science.gov (United States)

Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), plays an important role in a variety of diseases. So far, the role of mPGES-1 in idiopathic pulmonary fibrosis (IPF) remained unknown. The current study aimed to investigate the role of mPGES-1 in pulmonary fibrosis induced by bleomycin in mice. We found that mPGES-1 deficient (mPGES-1-/-) mice exhibited more severe fibrotic lesions with a decrease in PGE2 content in lungs after bleomycin treatment when compared with wild type (mPGES-1+/+) mice. The mPGES-1 expression levels and PGE2 content were also decreased in bleomycin-treated mPGES-1+/+ mice compared to saline-treated mPGES-1+/+ mice. Moreover, in both mPGES-1-/- and mPGES-1+/+ mice, bleomycin treatment reduced the expression levels of E prostanoid receptor 2 (EP2) and EP4 receptor in lungs, whereas had little effect on EP1 and EP3. In cultured human lung fibroblast cells (MRC-5), siRNA-mediated knockdown of mPGES-1 augmented transforming growth factor-?1 (TGF-?1)-induced ?-smooth muscle actin (?-SMA) protein expression, and the increase was reversed by treatment of PGE2, selective EP2 agonist and focal adhesion kinase (FAK) inhibitor. In conclusion, these findings revealed mPGES-1 exerts an essential effect against pulmonary fibrogenesis via EP2-mediated signaling transduction, and activation of mPGES-1-PGE2-EP2-FAK signaling pathway may represent a new therapeutic strategy for treatment of IPF patients. PMID:24756129

Wei, Bo; Cai, Linhong; Sun, Dan; Wang, Yanhua; Wang, Cairui; Chai, Xiaoyu; Xie, Feng; Su, Ming; Ding, Fangrui; Liu, Jie; Yang, Jichun; Guan, Youfei; Liu, Xinmin

2014-01-01

186

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

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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 ?g/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 ?g/mL and 30 ?g/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 ?g/mL. BLM at 3 ?g/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 ?g/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. PMID:20418892

Chen, Li-jun; Li, Wan-de; Li, Shi-feng; Su, Xing-wen; Lin, Guang-yun; Huang, Yi-jun; Yan, Guang-mei

2010-01-01

187

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

188

Protective effect of royal jelly on fertility and biochemical parameters in bleomycin-?induced male rats  

Science.gov (United States)

Background: Bleomycin (BL) is a glycopeptide antibiotic obtained from the bacterium Streptomyces verticillus which is routinely used for treatment of human cancers. Royal jelly (RJ) is a production from the hypo pharyngeal, mandibular and post cerebral glands of nurse bees. RJ consists of 66% water, 15% sugars, 5% lipids, and 13% proteins, essential amino acids and vitamins. Objective: The aim of present study was to evaluate protective effect of royal jelly on sperm parameters and malondialdehyde (MDA) production in rat. Materials and Methods: Forty adult male wistar rats (220±20gr) were randomly divided into 4 groups (n=10). Control group (CG) received normal saline 10 ml/kg twice a week with Intraperitoneal (I.P) for 48 days (0.3 ml/rat(. Royal Jelly group (RJG) received jelly (100 mg/kg daily) for 48 days orally. Bleomycin group (BLG) received BL (10 mg/kg twice a week) with I.P for 48 days. Royal Jelly+ Bleomycin group (RJ+BLG) received royal Jelly (100 mg/kg /day) orally concomitant with BL administration. Sperm count, motility, and viability were investigated and chromatin quality and DNA integrity were also analyzed. Serum testosterone and MDA concentrations were measured as well. Results: BL caused decline significantly (pTayebeh amirshahi) PMID:24799882

Amirshahi, Tayebeh; Najafi, Gholamreza; Nejati, Vahid

2014-01-01

189

Protease activated receptor-1 deficiency diminishes bleomycin-induced skin fibrosis.  

Science.gov (United States)

Accumulating evidence shows that protease-activated receptor-1 (PAR-1) plays an important role in the development of fibrosis, including lung fibrosis. However, whether PAR-1 also plays a role in the development of skin fibrosis remains elusive. The aim of this study was to determine the role of PAR-1 in the development of skin fibrosis. To explore possible mechanisms by which PAR-1 could play a role, human dermal fibroblasts and keratinocytes were stimulated with specific PAR-1 agonists or antagonists. To investigate the role of PAR-1 in skin fibrosis, we subjected wild-type and PAR-1-deficient mice to a model of bleomycin-induced skin fibrosis. PAR-1 activation leads to increased proliferation and extra cellular matrix (ECM) production, but not migration of human dermal fibroblasts (HDF) in vitro. Moreover, transforming growth factor (TGF)-? production was increased in keratinocytes upon PAR-1 activation, but not in HDF. The loss of PAR-1 in vivo significantly attenuated bleomycin-induced skin fibrosis. The bleomycin-induced increase in dermal thickness and ECM production was reduced significantly in PAR-1-deficient mice compared with wild-type mice. Moreover, TGF-? expression and the number of proliferating fibroblasts were reduced in PAR-1-deficient mice although the difference did not reach statistical significance. This study demonstrates that PAR-1 contributes to the development of skin fibrosis and we suggest that PAR-1 potentiates the fibrotic response mainly by inducing fibroblast proliferation and ECM production. PMID:24842054

Duitman, Janwillem; Ruela-de-Sousa, Roberta R; Shi, Kun; De Boer, Onno J; Borensztajn, Keren S; Florquin, Sandrine; Peppelenbosch, Maikel P; Spek, C Arnold

2014-01-01

190

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.

Zuojun Xu

2012-07-01

191

Biological studies of samarium-153 bleomycin complex in human breast cancer murine xenografts for therapeutic applications  

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In this work, a potential therapeutic DNA targeting agent, {sup 153}Sm-bleomycin complex ({sup 153}Sm-BLM), was developed and the tumor accumulation studies were performed using single photon emission computed tomography (SPECT) and scarification studies. {sup 153}Sm-BLM was prepared at optimized conditions (room temperature, 4-8 h, 0.1 mg bleomycin for 740-3700 MBq {sup 153}SmCl{sub 3}, radiochemical purity over 98%, HPLC, specific activity = 55 TBq/mmol). {sup 153}Sm-BLM was administered into human breast cancer murine xenografts and the biodistribution and imaging studies were performed up to 48 h. {sup 153}Sm-BLM demonstrated superior tumor accumulation properties in contrast with the other radiolabeled bleomycins with tumor:blood ratios of 41, 72 and 182 at 4, 24 and 48 h, respectively, and tumor:muscle ratios of 23, 33 and > 1490 at 4, 24 and 48 h, respectively, while administered intravenously. The SPECT images also demonstrated the obvious tumor uptake at the chest region of the breast-tumor bearing mice. These initial experiments demonstrate significant accumulation of {sup 153}Sm-BLM in tumor tissues. (orig.)

Bahrami-Samani, A. [Faculty of Nuclear Engineering and Physics, Amirkabir Univ. of Tech., Tehran (Iran); Ghannadi-Maragheh, M. [Faculty of Nuclear Engineering and Physics, Amirkabir Univ. of Tech., Tehran (Iran); Radiopharmaceutical Research and Development Lab. (RRDL), Nuclear Science and Technology Research Inst. (NSTRI), Tehran (Iran); Jalilian, A.R.; Mazidi, M. [Radiopharmaceutical Research and Development Lab. (RRDL), Nuclear Science and Technology Research Inst. (NSTRI), Tehran (Iran)

2010-07-01

192

Protease Activated Receptor-1 Deficiency Diminishes Bleomycin-Induced Skin Fibrosis  

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Accumulating evidence shows that protease-activated receptor-1 (PAR-1) plays an important role in the development of fibrosis, including lung fibrosis. However, whether PAR-1 also plays a role in the development of skin fibrosis remains elusive. The aim of this study was to determine the role of PAR-1 in the development of skin fibrosis. To explore possible mechanisms by which PAR-1 could play a role, human dermal fibroblasts and keratinocytes were stimulated with specific PAR-1 agonists or antagonists. To investigate the role of PAR-1 in skin fibrosis, we subjected wild-type and PAR-1-deficient mice to a model of bleomycin-induced skin fibrosis. PAR-1 activation leads to increased proliferation and extra cellular matrix (ECM) production, but not migration of human dermal fibroblasts (HDF) in vitro. Moreover, transforming growth factor (TGF)-? production was increased in keratinocytes upon PAR-1 activation, but not in HDF. The loss of PAR-1 in vivo significantly attenuated bleomycin-induced skin fibrosis. The bleomycin-induced increase in dermal thickness and ECM production was reduced significantly in PAR-1-deficient mice compared with wild-type mice. Moreover, TGF-? expression and the number of proliferating fibroblasts were reduced in PAR-1-deficient mice although the difference did not reach statistical significance. This study demonstrates that PAR-1 contributes to the development of skin fibrosis and we suggest that PAR-1 potentiates the fibrotic response mainly by inducing fibroblast proliferation and ECM production. PMID:24842054

Duitman, JanWillem; Ruela-de-Sousa, Roberta R; Shi, Kun; de Boer, Onno J; Borensztajn, Keren S; Florquin, Sandrine; Peppelenbosch, Maikel P; Spek, C Arnold

2014-01-01

193

Biological studies of samarium-153 bleomycin complex in human breast cancer murine xenografts for therapeutic applications  

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In this work, a potential therapeutic DNA targeting agent, 153Sm-bleomycin complex (153Sm-BLM), was developed and the tumor accumulation studies were performed using single photon emission computed tomography (SPECT) and scarification studies. 153Sm-BLM was prepared at optimized conditions (room temperature, 4-8 h, 0.1 mg bleomycin for 740-3700 MBq 153SmCl3, radiochemical purity over 98%, HPLC, specific activity = 55 TBq/mmol). 153Sm-BLM was administered into human breast cancer murine xenografts and the biodistribution and imaging studies were performed up to 48 h. 153Sm-BLM demonstrated superior tumor accumulation properties in contrast with the other radiolabeled bleomycins with tumor:blood ratios of 41, 72 and 182 at 4, 24 and 48 h, respectively, and tumor:muscle ratios of 23, 33 and > 1490 at 4, 24 and 48 h, respectively, while administered intravenously. The SPECT images also demonstrated the obvious tumor uptake at the chest region of the breast-tumor bearing mice. These initial experiments demonstrate significant accumulation of 153Sm-BLM in tumor tissues. (orig.)

194

Controlled evaluation of combined radiation and bleomycin therapy for squamous cell carcinoma of the esophagus  

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In a controlled, randomized Eastern Cooperative Oncology Group (ECOG) study 77 evaluable patients with squamous cell carcinoma of the esophagus were treated with radiation therapy alone at a recommended dosage of 5000 to 6000 rad administered over five to six weeks in five or six fractions a week or with radiation given in combination with Bleomycin. Whereas the Bleomycin group experienced the additional toxicity of chemotherapy, Bleomycin did not contribute to therapeutic results in terms of either symptomatic pallation or survival. Further application of this approach by the methods we employed is not indicated. Overall treatment results were discouraging; the five year survival in this group of patients with regionally localized squamous cell carcinoma of the esophagus will not exceed 8%. In a non-randomized comparison, patients treated with 6000 rad did not show a therapeutic advantage over those treated with 5000 rad. Most favorable survival after treatment was seen in patients with lesions in the cervical esophagus and middle one-third of the thoracic esophagus. Least favorable survival was seen with lesions of the upper and lower one-third of the thoracic esophagus

195

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

2011-10-01

196

Esophageal cancer treated by low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta  

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Eight patients with esophageal cancer were treated by a new treatment schedule consisting of low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta. As monitored endoscopically, therapeutic responses were satisfactory : seven out of 8 patients have survived for a range of 3 to 20 months and still active at work or cancer-free. However, one patient suffered from a second malignancy of adenocarcinoma of the upper esophagus different from the initial squamous cell carcinoma at the lower esophagus which had successfully been treated 3 months before. The present therapeutic design aims at treatment of lymphatic spreads in the adjacent structures as well as the original tumor in the esophagus and submucosal invasions. It is basically a consecutive, multimodal integration of selective concentration of therapeutic effects (extensive radiotherapy, topical application of bleomycin polyacrylate pasta, lymphatic chasing with colloidal bleomycin, and spatial concentration of cisplatin as the result of radiation-induced inflammation), perpetuation of the repairable DNA damage, and biological amplifications (protection against esophageal perforation with polyacrylate coating, and specific cancer cell recruitment). Application of the present theraeputic design is being expanded to the treatment of cancer of other specific sites such as the head and neck tumors and rectal cancer with undeniable prospects. (author)

197

Esophageal cancer treated by low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta  

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Eight patients with esophageal cancer were treated by a new treatment schedule consisting of low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta. As monitored endoscopically, their therapeutic responses were satisfactory, and seven out of the eight survived for a range of 3 to 18 months and still active at work or ''cancer-free''. The seventh of the eight suffers from a second malignancy of adenocarcinoma of the cardia, different from the initial squamous cell carcinoma at the lower esophagus which had successfully been treated 3 months before. The present therapeutic design aims at treatment of lymphatic spreads in the adjacent structures as well as the original tumor in the esophagus and submucosal invasions. It is basically a consecutive, multimodal integration of selective concentration of therapeutic effects (extensive radiotherapy, topical application of bleomycin polyacrylate pasta, lymphatic chasing with colloidal bleomycin, and spatial concentration of cisplatin as the result of radiation-induced inflammations), perpetuation of the repairable DNA damage, and biological amplifications (protection against esophageal perforation with polyacrylate coating, and specific cancer cell recruitment). Application of the present therapeutic design is being expanded to treatment of cancer at other specific sites such as the head and neck tumors and rectal cancer with undeniable prospects. (author)

198

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.

C Fenoglio

2006-12-01

199

Bleomycin delivery by osmotic minipump: similarity to human scleroderma interstitial lung disease.  

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The interstitial lung diseases (ILD) include a large number of chronic, progressive, irreversible respiratory disorders involving pulmonary fibrosis, the most common of which are idiopathic pulmonary fibrosis and scleroderma lung disease (SSc ILD). Because bleomycin causes lung fibrosis when used in cancer chemotherapy, it is used to model human ILD in rodents. In most studies, bleomycin has been delivered directly into the lung by intratracheal or intraoral administration. Here we have compared the effects in mice of bleomycin delivered directly into the lungs (direct model) or systemically using osmotic minipumps (pump model) to determine which more closely resembles human ILD. The pump model is more similar to human SSc ILD in that: 1) lung injury/fibrosis is limited to the subpleural portion of the lung in the pump model and in SSc ILD, whereas the entire lung is affected in the direct model; 2) conversely, there is massive inflammation throughout the lung in the direct model, whereas inflammation is limited in the pump model and in SSc ILD; 3) hypertrophic type II alveolar epithelial cells are present at high levels in SSc ILD and in the pump model but not in the direct model; and 4) lung fibrosis is accompanied by dermal fibrosis. The pump model is also move convenient and humane than the direct model because there is less weight loss and mortality. PMID:24583879

Lee, Rebecca; Reese, Charles; Bonner, Michael; Tourkina, Elena; Hajdu, Zoltan; Riemer, Ellen C; Silver, Richard M; Visconti, Richard P; Hoffman, Stanley

2014-04-15

200

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.

Buhling Frank

2008-07-01

 
 
 
 
201

PCR-directed DNA sequencing of "nondeletion" HPRT-mutants induced by bleomycin in CHO K1-BH4 cells.  

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Bleomycin is one of the radiomimetic antibiotics which induces DNA double-strand breaks by highly specific free radical attack on deoxyribose moieties in DNA. Earlier, we have shown that bleomycin induces a high proportion of large deletions involving one or more exons in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in a Chinese hamster ovary (CHO) cell line CHO K1-BH4, in which no spontaneously occurring large deletions were detected by a polymerase chain reaction (PCR)-based deletion screening assay. Here we report the molecular nature of another class of mutants in which we did not observe any abnormal exon pattern. We refer to these mutants as the "nondeletion" type. Since bleomycin is a reactive oxygen species (ROS)-generating agent, we also studied whether the change of intracellular levels of ROS may affect the bleomycin-induced mutation spectra. We therefore also investigated the hprt mutation spectra induced by bleomycin with pretreatment by TRIEN (triethylenetetramine), a superoxide dismutase (SOD) inhibitor, and TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a SOD mimic. Analysis of these three bleomycin-induced "nondeletion" mutation spectra revealed that 5'-GTC-3' or 5'-GCC-3' sequences were the hot spots for single basepair deletions. Other types of mutation include abnormal cDNA or no cDNA amplification on the hprt locus. Due to the small sample size, we are unable to draw a definitive conclusion about the effects of TRIEN and TEMPOL on bleomycin-induced spectrum of "nondeletion" type hprt mutations. PMID:9814439

An, J; Trieff, N M; Hsie, A W

1998-01-01

202

New tumor imaging agent--111In-bleomycin complex. Comparison with 67Ga-citrate and 57Co-bleomycin in tumor-bearing animals  

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A new 111In-bleomycin complex (BLMC) has been found which has high affinity to tumor, does not bind to transferrin and is stable in vivo. Distribution in animals bearing glioma, hepatoma, or mammary adenocarcinoma at 48 hours showed: the ratios of tumor to blood, brain, heart, lung, liver, pancreas, stomach, and femur were 1.4-22.4 times as high for 111In-BLMC as for 67Ga-citrate. In mammary adenocarcinoma, 111In-BLMC bound more to viable and 57Co-Bleomycin (BLM) more to necrotic tumor. In viable tumor, the concentration of 111In-BLMC was similar to that of 57Co-BLM. The ratios of tumor to stomach and pancreas were higher, to blood, brain, muscle, heart, and femur were lower for 111In-BLMC than those for 57Co-BLM. The ratios of tumor to lung, liver, spleen, skin, and kidney were similar for the two compounds. Tumors were imaged more distinctly with the new 111In-BLMC and 57Co-BLM than with 67Ga-citrate. 111In-BLMC is promising for tumor imaging

203

Mechanism of reduction of bleomycin-Cu(II) by CO2- and oxidation of bleomycin-Cu(I) by H2O2 in the absence and presence of DNA  

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The reduction reaction of bleomycin-Cu(II) by CO2- has been studied by ? and pulse radiolysis at pH 7. The CO2-radical reduces bleomycin-Cu(II) at a rate of (6.7 +- 0.7) x 108 dm3 mol-1 s-1. In the presence of calf thymus DNA the rate of the reduction decreased as the concentration of DNA increased, indicating that the reduction reaction proceeds through free bleomycin-Cu(II). The stoichiometry and the kinetics of the oxidation of bleomycin-Cu(I) by H2O2 in the presence and absence of DNA have been studied. Our observations suggest that the OH radical is not produced during this reaction and the degradation of the drug occurs in the absence and presence of DNA. We assume that bleomycin-Cu(II) in the presence of a reducing agent and molecular oxygen or H2O2 does not cleave DNA since the oxidizing species, which are formed during the oxidation reaction by H2O2, attack the drug even in the presence of DNA. (author)

204

Changes of global terrestrial carbon budget and major drivers in recent 30 years simulated using the remote sensing driven BEPS model  

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The process-based Boreal Ecosystem Productivity Simulator (BEPS) model was employed in conjunction with spatially distributed leaf area index (LAI), land cover, soil, and climate data to simulate the carbon budget of global terrestrial ecosystems during the period from 1981 to 2008. The BEPS model was first calibrated and validated using gross primary productivity (GPP), net primary productivity (NPP), and net ecosystem productivity (NEP) measured in different ecosystems across the word. Then, four global simulations were conducted at daily time steps and a spatial resolution of 8 km to quantify the global terrestrial carbon budget and to identify the relative contributions of changes in climate, atmospheric CO2 concentration, and LAI to the global terrestrial carbon sink. The long term LAI data used to drive the model was generated through fusing Moderate Resolution Imaging Spectroradiometer (MODIS) and historical Advanced Very High Resolution Radiometer (AVHRR) data pixel by pixel. The meteorological fields were interpolated from the 0.5° global daily meteorological dataset produced by the land surface hydrological research group at Princeton University. The results show that the BEPS model was able to simulate carbon fluxes in different ecosystems. Simulated GPP, NPP, and NEP values and their temporal trends exhibited distinguishable spatial patterns. During the period from 1981 to 2008, global terrestrial ecosystems acted as a carbon sink. The averaged global totals of GPP NPP, and NEP were 122.70 Pg C yr-1, 56.89 Pg C yr-1, and 2.76 Pg C yr-1, respectively. The global totals of GPP and NPP increased greatly, at rates of 0.43 Pg C yr-2 (R2=0.728) and 0.26 Pg C yr-2 (R2=0.709), respectively. Global total NEP did not show an apparent increasing trend (R2= 0.036), averaged 2.26 Pg C yr-1, 3.21 Pg C yr-1, and 2.72 Pg C yr-1 for the periods from 1981 to 1989, from 1990 to 1999, and from 2000 to 2008, respectively. The magnitude and temporal trend of global terrestrial carbon budget were similar to the values recently reported by the Global Carbon Project. The obvious increases in global GPP and NPP were mainly driven by the enhancement of atmospheric CO2 fertilization. The change of LAI played the secondary role. Climate had a small negative impact on global terrestrial carbon sequestration. The relative importance of changes in climate, atmospheric CO2 concentration, and LAI in altering the temporal trend of carbon sequestration differed spatially. During the period from 2000 to 2008, terrestrial carbon sinks mainly existed in the northern region of South America, the western region of middle Africa, Southeast Asia, Southeast China, Southeast United States, and some regions of Eurasia.

Ju, W.; Chen, J.; Liu, R.; Liu, Y.

2013-12-01

205

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

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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.

206

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

1989-04-01

207

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

1987-10-01

208

Role of 57Co-bleomycin in the diagnosis of cervical cancer. Results of 4 years of investigations  

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57Co-bleomycin was applied in 64 patients with squamous carcinoma or precancerous conditions of the cervix. Clinical verification of these cases was compared with the results of scintigraphic examinations using 57Co-bleomycin. It was found that it was as useful to accept a low level of scintigraphy which did not exclude from further considerations lesions qualified as moderately intense malignant focus, since this increased the sensitivity of the method while its specificity was sufficient. The use of 57Co-bleomycin for assessing the extent of the malignant process in cervical carcinoma may be particularly important in less advanced cases of the disease determining the actual extent of the lesions and cases with allergy or with lymphatic vessels blockade making impossible lymphographic investigations. (author)

209

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

2009-03-01

210

Base substitutions, targeted single-base deletions, and chromosomal translocations induced by bleomycin in plateau-phase mammary epithelial cells.  

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Previous work showed that treatment of plateau-phase Chinese hamster ovary cells with the radiomimetic double-strand cleaving agent bleomycin induced very small deletions as well as interchromosomal reciprocal translocations, both of which could be ascribed to errors in end joining of DNA double-strand breaks. In an attempt to assess the possible role of TP53 in suppressing such repair errors, bleomycin-induced mutagenesis at the HPRT locus was examined in immortalized 184B5 human mammary epithelial cells (TP53(+)), and in a TP53-defective derivative, 184B5-E6tfxc6. For both cell lines, the most frequent bleomycin-induced mutations were base substitutions, with no apparent targeting to major bleomycin lesions. However, both lines also sustained single-base deletions that were targeted to expected sites of double-strand breaks, suggesting that they arose by end-joining repair of the breaks. Surprisingly, only a few large deletions or rearrangements, and no interchromosomal events involving the HPRT locus were detected among the mutants. The results suggest that in both cell lines, errors in double-strand break repair resulting in heritable large deletions and rearrangements are rare. Spectral karyotyping of bleomycin-treated 184B5 cells showed that a significant number of translocations were present shortly after bleomycin exposure, but their frequency decreased upon continued culture of the cells. Thus, for these cells, the lack of induced interchromosomal rearrangements can be explained in part by selection against such events as the cells proliferate. PMID:12175310

Yu, Yin; Inamdar, Kedar V; Turner, Kristi; Jackson-Cook, Colleen K; Povirk, Lawrence F

2002-09-01

211

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

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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

212

Sensitivity to genotoxic effects of bleomycin of blood lymphocytes of people residing in villages of ChNPP exclusion zone  

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On purpose of comparative determination of cell repair system activity of people residing without permission in the villages of ChNPP exclusion zone and of Yahotyn district, Kiev region (control group) the chromosome sensitivity of peripheral blood lymphocytes to genotoxic effect of bleomycin in vitro was studied. Chromatid break frequency per cell was a criterium for the estimation. It was found a significantly higher sensitivity to bleomycin in ChNPP exclusion zone self-settlers' group due to cell reaction of people younger than 60. For the elderly people there was revealed no significant difference

213

Voip Protocols  

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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

2012-06-01

214

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

1997-03-01

215

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

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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

216

Cells of some cultured lymphoma lines are killed rapidly by X-rays and by bleomycin  

International Nuclear Information System (INIS)

In this report several cultured lines of mouse T and pre-B lymphoma cells have been identified which, like normal resting lymphocytes, show rapid cell death in interphase after 10 Gy X-irradiation. With 30 other lymphoid and non-lymphoid tumour lines, irradiation caused relatively delayed cell death with intervening mitotic activity. Differential rates of cell killing similar to those caused by irradiation of the two groups of cell lines were observed during exposure to the DNA-cleaving antibiotic bleomycin, implying that rapid death of lymphoid cells can be a cellular physiological response to damage. (author)

217

Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 ?M). Cell proliferation [...] was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of ?-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc mouse model, in part due to a reduction in ET-1.

Yinghua, Song; Lubing, Zhu; Ming, Li.

1350-13-01

218

Platinum complexes inhibit repair of potentially lethal damage following bleomycin treatment.  

Science.gov (United States)

The SCC-25 cell line is a well-established line derived from a human squamous carcinoma of the head and neck. The capacity of this cell line for recovery from potentially lethal damage following X-ray treatment has been documented. The survival curve of stationary phase SCC-25 cells exposed to various concentrations of bleomycin is biphasic with an initial sensitive phase and a less sensitive second phase as is common for many cell lines. Stationary phase SCC-25 cells were exposed to 100 mU ml-1 of bleomycin for 1 h. The drug was removed and the cells were allowed various periods to recover from potentially lethal damage. After 24 h, the SCC-25 cells showed a recovery ratio (R/R0) of 7.0 which corresponded to an immediate survival at a drug level of 27 mU ml-1, a dose 3.7-fold less than the exposure concentration of 100 mU ml-1. Over the course of the first 4 h following bleomycin exposure, 0.5 microM CDDP was a very effective inhibitor of potentially lethal damage repair, giving a R/R0 of 1.1 or nearly complete inhibition of recovery. Between 2 and 4 h the R/R0 was 1.6-1.8 with CDDP and 4.1-5.3 without CDDP indicating appreciable inhibition of recovery. Plant (10 microM) and Plato (10 microM) produced potentially lethal damage recovery inhibition patterns very similar to that of CDDP. After 1 h the recovery ratios in the presence of Plant and Plato were 1.1-1.3. Between 2 and 4 h, Plato and Plant gave recovery ratios of 1.8-2.3 and 1.6-1.9, respectively. NIPt and Pt(terpy) were examined at both 10 microM and 25 microM for their ability to inhibit potentially lethal damage recovery after bleomycin treatment. After 1 h, NIPt gave a recovery ratio of 1.3-1.4, and after 2-4 h the recovery ratio was 1.7-2.6. Pt(terpy) gave recovery ratios of 1.3-1.6 after 1 h and 1.5-1.8 after 24 h. PMID:2436643

Holden, S. A.; Teicher, B. A.; Boeheim, K.; Weichselbaum, R. R.; Ervin, T. J.

1987-01-01

219

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients  

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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...

Marlise Ladvocat Bartholomei-Santos; Edmundo José de Lucca

1997-01-01

220

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

Science.gov (United States)

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. PMID:23892034

Erdem, Arzum; Congur, Gulsah

2013-10-01

 
 
 
 
221

Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.  

LENUS (Irish Health Repository)

The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.

Quintyne, Keith Ian

2011-09-01

222

Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 ?M). Cell proliferation [...] was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of ?-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc mouse model, in part due to a reduction in ET-1.

Yinghua, Song; Lubing, Zhu; Ming, Li.

223

Kioto protocol  

International Nuclear Information System (INIS)

Atmospheric contamination by greenhouse gases is a global problem, and thus its solution requires global measures. Although the consequences of climate change are questioned and the foreseeable effects are not excessively serious, there are plenty of scientific reasons for all countries to make the necessary efforts to meet the objectives established by the Kyoto Protocol of reducing the six greenhouse gases over the period 2008-2012. Therefore, it seems essential that we understand the nature of the transformation that are occurring in the different systems, what changes they are causing and what costs they incur. Independently of its effectiveness and realism, the Kyoto Protocol is the first regulatory step in the direction of globalization in the environmental field. (Author)

224

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: English Abstract in english 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 a [...] im 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

MANUEL, OYARZÚN; NELSON, DUSSAUBAT; SERGIO, GONZÁLEZ.

225

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

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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.

Kazuyuki Tobe

2012-02-01

226

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.

Ferguson Mark WJ

2007-09-01

227

The Effect of Bleomycin to the Mitotic Index who were Exposed to Radiation Chronically  

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Full Text Available Beginning with the therapeutic dose and increasing three differentdoses and three different periods of time Bleomycin (Bleomycin 0.3 ?g/ml, 3?g/ml and 30 ?g/ml, 6, 24, 48 hours were added to blood which was beingcultured on 5 samples who were exposed to radiation chronically.The mitotic index in the lymphocyte culture was determined by means ofcounting 1000 cells from preparations belong to control and experimentgroups.The mitotic index was showed difference value to the differencebleomycin dose and the between difference samples. As the mitotic indexvalue (Per 1000 cell 10.86 for the control group, this value fall to 8.73 at0.3 ?g/ml, 5.0 at 3 ?g/ml and 3.93 at 30 ?g/ml. There were no significantdifferences between control group and 0.3 ?g/ml, 3 ?g/ml and 30 ?g/ml(P>0.05. An important fall was seen between control group and 3 ?g/mland 30 ?g/ml, 0.3 ?g/ml group and 3 ?g/ml, 30 ?g/ml (P<0.01.

Hilmi ?si

2004-01-01

228

Computer simulation of {sup 57}Fe bleomycin Auger effects in DNA  

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The antibiotic bleomycin binds to the DNA and induces double strand breaks (DSBs). To increase the cleavages, {sup 57}Fe is used to form a complex suitable for Moessbauer effect. The de-excitation of the resonant excited {sup 57}Fe nucleus releases Auger electrons and X rays. The goal of this work is to evaluate the increase in yield of DSBs due to the {sup 57}Fe, using Monte Carlo simulation methods. Particles spectra and the yields of single strand breaks (SSBs) and DSBs were calculated by considering direct events on DNA and reaction of all radical species generated in the radiolysis of its environment. The Auger spectrum shows a large number of electrons with energies below 100 eV, mainly responsible for direct damage, while another group around 600-700 eV is responsible for indirect damage effects. Bleomycin receives about one fourth of the energy deposited in DNA and an average of 0.65 DSBs per de-excitation is observed. (author)

Terrissol, M.; Pomplun, E.; Martin, C

2002-07-01

229

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

Directory of Open Access Journals (Sweden)

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

2005-01-01

230

Povidone-Iodine and Bleomycin in the Management of Malignant Pleural Effusion  

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Full Text Available "nMalignant pleural effusion is a common complication in certain malignancies. Pleurodesis is the best option most of the time. The purpose of this study was to compare the choice of belomycin with povidone-iodine, which is not only determined by the efficacy of the agent but also by its cost, accessibility, safety, ease of administration and the number of administrations to achieve a complete response. We performed a randomized clinical trial on 39 patients presenting with symptomatic malignant pleural effusion. Patients were selected and randomly assigned to undergo chemical pleurodesis with either bleomycin or povidone-iodine. Primary characteristics of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs. A complete response was obtained in 79% of belomycin group and 75% of povidone-iodine group which was not statistically significant. Patients on belomycin treatment had a significantly lower score for dyspnea in one month follow up. This was significant after controlling for age, pain score and dyspnea score after drainage, using general linear model. Due to similar effect and significant cost advantage between bleomycin and povidone-iodine, we conclude that povidone- iodine is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions.

Ali Asghar Alavi

2011-09-01

231

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.

Citro Gennaro

2008-11-01

232

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

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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

1995-06-01

233

Studies on malignant cancer with sup(99m)Tc-labelled bleomycin  

International Nuclear Information System (INIS)

Bleomycin (BLM), a group of the basic glycopeptide anti-biotics with antitumor properties that is produced by a strain Streptomyces verticillus, is a chemotherapeutic agent known to concentrate highly in tumor cells. Therefore, the potential value of BLM labelled with sup(99m)Tc as a tumor-seeking agent was studied in tissues of rats and mice bearing a Walker 256 carcinoma and Sarcoma 180 tumor cells. The optimal labelling procedure for BLM with sup(99m)Tc, using Sn(II) as the reductant are; pH value between 7.0 and 8.5 and Sn(II) concentration of 10-5 M. Bleomycin concentration has no influence and the chemical stability of the sup(99m)Tc complex is stable during 3 hours at room temperature. Under these condition, approximately 90% of labelling was investigated by thin layer chromatographic analysis. Various organs distribution were observed after intravenous administration of the sup(99m)-BLM into Walker 256 carcinoma and Sarcoma 180 tumor bearing rats and mice after 1 hr, 3 hrs and 5 hrs.The concentration of Walker 256 carcinoma and Sarcoma 180 tumor by sup(99m)Tc-BLM was 0.2% and 0.5%, respectively, administrated activity after an hour. Tumor uptake of sup(99m)Tc-BLM was concentrate slightly more than all organs except kidney and blood. (Author)

234

Contribution to the scintigraphic diagnosis of malignant endothoracic tumors by 57Co labeled bleomycin  

International Nuclear Information System (INIS)

The results of the exploration by 57Co bleomycin scintigraphy in 97 thoracic tumors are reported. The Bleo-57Co scintigraphy detects primary and secondary malignant tumors underevaluated by classical tests. In the thorax, the radioactive focus are easily detected on account of the light physiological uptake of the Bleo-57Co. It is particularly interesting in the mediastinal tumors where the picture is not covered by cardiovascular interference. Mediastinal, pleural and costal tumors have been explored. Pulmonary tumors give the best results, they fixe in 93% of the case. All the mediastinal tumors have capted the bleomycin but the uptake was very light even when the tumor was a large one. The exploration of pleural and costal tumors was less interesting. In conclusion, the Bleo-57Co scintigraphy, gives indications about the volume of the tumor and its spread in the organism. By this method, malignancy in a tumor can be diagnosed. It can be used to survey cancer patients which have been treated. Nevertheless the long half-life (270 days) and the lack of specificity of the Bleo-57Co for the malignant tumors, justify discussion about indications and the results of such an exploration

235

New 111In-bleomycin complex for combined radiotherapy and chemotherapy  

International Nuclear Information System (INIS)

Six days after tumor transplantation three daily intraperitoneal doses of 0.9% NaCl, bleomycin (BLM), or a new 111In-bleomycin complex (BLMC, 15 microCi/g body weight) were administered to glioma-bearing mice. After therapy, tumors in mice treated with 111In-BLMC were smaller than those treated with BLM. Sixteen days after the first injection tumor size for 111In-BLMC-treated mice was 560 (240-1,030) mm3, 1980 (1400-3290) mm3 for BLM (P less than 0.025), and 4830 (2580-9180) mm3 for NaCl (0.1 less than P less than 0.2). Thirteen days after tumor transplantation glioma-bearing mice received single intratumor injection of 0.9% NaCl, BLM, or 111In-BLMC (1.5 mCi, carried by 0.5 mg BLM/g tumor weight). The average tumor size for 111In-BLMC was smaller than that for BLM by a factor of 2.5-3.7. Host weights for these two groups were similar, and morphologic abnormalities were not found in kidney or liver

236

Human lung tumors: SPECT quantitation of differences in Co-57 bleomycin uptake.  

Science.gov (United States)

A newly developed single photon emission computed tomography (SPECT) method was used to measure noninvasively the concentration of labeled drugs in human lung tumors. The validity of the method was established by the high correlation (r = .92) between in vivo SPECT measurement of the concentration of glucoheptonate labeled with technetium-99m and in vitro measurement of the concentration of the drug in specimens of nine of the same tumors obtained at surgery. The in vivo concentration of intravenously injected bleomycin labeled with cobalt-57 was measured over time in 14 human lung tumors. Significant differences were found in the uptake of bleomycin by the tumors, even those with the same histologic characteristics, when the concentration over time, the tumor/blood ratio at 30 minutes, and the tumor cumulative concentration were measured in vivo. Since the drug concentration in the blood was not related to the concentration in the tumor (r = .54), uptake of chemotherapeutic drugs should be measured in each patient individually. PMID:2442794

Front, D; Israel, O; Iosilevsky, G; Even-Sapir, E; Frenkel, A; Peleg, H; Steiner, M; Kuten, A; Kolodny, G M

1987-10-01

237

A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross  

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Full Text Available Richard Gelinas1,3, Elissa J Chesler2, Daphne Vasconcelos1, Darla R Miller2, Yue Yuan3, Kai Wang3, David Galas1,31Battelle Memorial Institute, Columbus, OH; 2Oak Ridge National Laboratory, Oak Ridge, TN; 3Institute for Systems Biology, Seattle, WA, USAAbstract: The antineoplastic drug bleomycin leads to the side effect of pulmonary fibrosis in both humans and mice. We challenged genetically diverse inbred lines of mice from the Collaborative Cross with bleomycin to determine the heritability of this phenotype. Sibling pairs of mice from 40 lines were treated with bleomycin. Lung disease was assessed by scoring lung pathology and by measuring soluble collagen levels in lavage fluid. Serum micro ribonucleic acids (miRNAs were also measured. Inbred sibling pairs of animals demonstrated high coinheritance of the phenotypes of disease susceptibility or disease resistance. The plasma levels of one miRNA were clearly correlated in sibling mice. The results showed that, as in humans, the lines that comprise the Collaborative Cross exhibited wide genetic variation in response to this drug. This finding suggests that the genetically diverse Collaborative Cross animals may reveal drug effects that might be missed if a study were based on a conventional mouse strain.Keywords: collaborative cross, drug side effects, genetic diversity, disease susceptibility, disease resistance, bleomycin, lung disease

Gelinas R

2011-07-01

238

Scintigraphic investigations with 57Co-bleomycin and 67Ga-citrate in patients with malignant lymphomas  

International Nuclear Information System (INIS)

The purpose of this study was assessment of the diagnostic value of scintigraphy with 57Co-bleomycin in determining the pathological process in malignant lymphomas as compared with a similar usefulness of 67Ga-citrate which has been used for several years in the diagnosis of malignant lymphoma. The clinical material included 81 patients with the diagnosis of malignant processes of the reticulolymphatic system. 57Co-bleomycin and then 67Ga-citrate were given intravenously in doses of 55 MBq radioactivity. The sensitivity and specificity of the method were evaluated assessing scintigrams and clinical observations. Scintigraphic investigations with both these agents demonstrated a high usefulness of the method in assessing the extent of the malignant process in malignant lymphomas providing the clinicians with valuable information, frequently impossible to be obtained by other methods. The sensitivity of the method of 57Co-bleomycin was 75%, its specificity was good -83%. The sensitivity of the 67Ga-method was slightly lower - 70%, but its specificity was significantly less -72%. The superiority of 57Co-bleomycin over 67Ga-citrate was particularly evident in the detection of lesions in the region of the head, abdomen and pelvis. (author)

239

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

2008-01-01

240

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.

Borresen-Dale Anne-Lise

2011-04-01

 
 
 
 
241

Fic domain-catalyzed adenylylation: insight provided by the structural analysis of the type IV secretion system effector BepA.  

Science.gov (United States)

Numerous bacterial pathogens subvert cellular functions of eukaryotic host cells by the injection of effector proteins via dedicated secretion systems. The type IV secretion system (T4SS) effector protein BepA from Bartonella henselae is composed of an N-terminal Fic domain and a C-terminal Bartonella intracellular delivery domain, the latter being responsible for T4SS-mediated translocation into host cells. A proteolysis resistant fragment (residues 10-302) that includes the Fic domain shows autoadenylylation activity and adenylyl transfer onto Hela cell extract proteins as demonstrated by autoradiography on incubation with ?-[(32)P]-ATP. Its crystal structure, determined to 2.9-Å resolution by the SeMet-SAD method, exhibits the canonical Fic fold including the HPFxxGNGRxxR signature motif with several elaborations in loop regions and an additional ?-rich domain at the C-terminus. On crystal soaking with ATP/Mg(2+), additional electron density indicated the presence of a PP(i) /Mg(2+) moiety, the side product of the adenylylation reaction, in the anion binding nest of the signature motif. On the basis of this information and that of the recent structure of IbpA(Fic2) in complex with the eukaryotic target protein Cdc42, we present a detailed model for the ternary complex of Fic with the two substrates, ATP/Mg(2+) and target tyrosine. The model is consistent with an in-line nucleophilic attack of the deprotonated side-chain hydroxyl group onto the ?-phosphorus of the nucleotide to accomplish AMP transfer. Furthermore, a general, sequence-independent mechanism of target positioning through antiparallel ?-strand interactions between enzyme and target is suggested. PMID:21213248

Palanivelu, Dinesh V; Goepfert, Arnaud; Meury, Marcel; Guye, Patrick; Dehio, Christoph; Schirmer, Tilman

2011-03-01

242

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 SciELO Brazil | Language: English 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 curcumin [...] a na freqüência de aberrações cromossômicas induzidas pelo agente radiomimético bleomicina (BLM) foram investigados em células do ovário de hamster chinês (CHO). 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 aberr [...] ation frequencies induced by the radiomimetic agent bleomycin (BLM) were investigated in Chinese hamster ovary (CHO) cells. Three concentrations of each drug, turmeric (100, 250 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.

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

243

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 SciELO Brazil | Language: English 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 curcumin [...] a na freqüência de aberrações cromossômicas induzidas pelo agente radiomimético bleomicina (BLM) foram investigados em células do ovário de hamster chinês (CHO). 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 aberr [...] ation frequencies induced by the radiomimetic agent bleomycin (BLM) were investigated in Chinese hamster ovary (CHO) cells. Three concentrations of each drug, turmeric (100, 250 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.

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

1999-09-01

244

In vivo measurements of the fraction of dose of bleomycin labeled with cobalt 57 delivered to human tumors  

International Nuclear Information System (INIS)

Concentrations of bleomycin labeled with cobalt 57 (Co-bleo) over time were measured in vivo in 17 patients with 32 sites of lymphoma and 18 patients with lung tumors after administration of the same dose of bleomycin. There were marked variations in individual tumor drug concentrations even among tumors with the same histologic type, indicating that the tumor concentration of this drug in individuals cannot be predicted from the administered dose. Also, tumor concentration could not be predicted from the area under the concentration over time curve (AUC) of Co-bleo in the blood; there was no correlation (r = 0.53) between the AUC and the concentration in the tumor at any point in time between 30 minutes and 8 hours after injection. There was no significant difference in the percent of the injected dose per milliliter (%ID/ml) which was delivered to the tumor when low and high amounts of bleomycin were administered to the same patient. Also, a good correlation (r = 0.88) between the %ID/ml over time was found when injection of low and high doses of bleomycin were compared. The results indicate that using quantitative single photon emission computed tomography (SPECT) and a labeled tracer dose it is possible to predict what fraction of the dose of a chemotherapeutic drug will concentrate in an individual patient's tumor in vivo. They also show that, for bleomycin, escalation of dose will result in a proportional increase of tumor concentration. This increase depends on individual properties of tumors which can be measured quantitatively in vivo by SPECT and are expressed as percent of %ID/ml of tumor tissue

245

Targeting the hedgehog-glioma-associated oncogene homolog pathway inhibits bleomycin-induced lung fibrosis in mice.  

Science.gov (United States)

Idiopathic pulmonary fibrosis has been associated with the reactivation of developmental pathways, notably the Hedgehog-Glioma-associated oncogene homolog (GLI) pathway. In this study, we determined whether the Hedgehog pathway was activated in bleomycin-induced lung injury in mice, and whether targeting the Hedgehog-Gli pathway could decrease bleomycin-induced lung fibrosis. After intratracheal injection of bleomycin on Day 0, C57Bl6 mice received GDC-0449 (an inhibitor of Smoothened, the transducer of the pathway), or 2,2'-[[Dihydro-2-(4-pyridinyl)-1,3(2H,4H)-pyrimidinediyl]bis(methylene)]bis[N,N dimethylbenzenamine (GANT61; an inhibitor of GLI transcription factors in the nucleus), from Day 7 to Day 13. At Day 14, whole-lung homogenates were obtained for morphological analysis, assessment of cell apoptosis and proliferation, collagen quantification, and evaluation of profibrotic (transforming growth factor-?, connective tissue growth factor, plasminogen activator inhibitor 1, vascular endothelial growth factor-A) and proinflammatory mediators (IL-1?) expression. We showed that the Hedgehog pathway was activated in bleomycin-induced lung fibrosis on Day 14 after injury, with an increased lung expression of the ligand, Sonic Hedgehog, and with increased messenger RNA expression and nuclear localization of GLI1 and GLI2. Inhibition of Smoothened with GDC-0449 did not influence the development of bleomycin-induced lung fibrosis. By contrast, the inhibition of GLI activity with GANT61 decreased lung fibrosis and lung collagen accumulation, and promoted an antifibrotic and anti-inflammatory environment. Our results identify the hedgehog-Gli pathway as a profibrotic pathway in experimental fibrosis. Inhibition of the Hedgehog-Gli pathway at the level of GLI transcriptional activity could be a therapeutic option in fibrotic lung diseases. PMID:24450438

Moshai, Elika Farrokhi; Wémeau-Stervinou, Lidwine; Cigna, Natacha; Brayer, Stephanie; Sommé, Joëlle Marchal; Crestani, Bruno; Mailleux, Arnaud A

2014-07-01

246

Histology protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 to...

CarloAlberto Redi

2010-01-01

247

Cleanroom Protocol  

Science.gov (United States)

This is a description for a learning module from Maricopa Advanced Technology Education Center. This PDF describes the module; access may be purchased by visiting the MATEC website. The final module of MATEC's contamination curriculum develops your learners' skills in specific cleanroom protocols: wafer handling and transfer, area wipedowns, and area or equipment isolation. The instruction stresses that contaminants travel via many channels- air, people, process equipment, manufacturing process, wiping materials, wafer handling, electrostatic discharge, and chemicals. MATEC aims to make each learner acutely aware that minimizing contamination in the cleanroom requires his or her personal commitment. The module also discusses the automated systems used in modern and upcoming 300-mm fabs.

2012-12-21

248

Rejoining of double strand breaks in normal human and ataxia-telangiectasia fibroblasts after exposure to 60Co ?-rays, 241Am ?-particles or bleomycin  

International Nuclear Information System (INIS)

The rejoining of DNA double strand breaks (dsb) induced by 60Co ?-rays, 241Am ?-particles or bleomycin was measured by neutral filter elution. In agreement with their colony-forming ability, ataxia-telangiectasia cells (AT2BE) and normal fibroblasts exhibited similar dsb rejoining capacity following ?-irradiation, but showed marked differences in the rejoining kinetics of dsb induced by ?-rays or bleomycin. (author)

249

A yeast gene (BLH1) encodes a polypeptide with high homology to vertebrate bleomycin hydrolase, a family member of thiol proteinases  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We have purified bleomycin hydrolase from yeast (molecular mass 55 000 Da). Using protein sequence-derived degenerate oligonucleotide primers and amplification by polymerase chain reaction, the yeast gene BLH1 was isolated and characterized. The deduced amino acid sequence (483 amino acids) exhibits surprisingly high homology to vertebrate bleomycin hydrolase (43% identical residues and 22% conserved exchanges). It contains three blocks of sequences found conserved in other members of the thi...

Magdolen, Ulla; Mu?ller, Gu?nter; Magdolen, Viktor; Bandlow, Wolfhard

1993-01-01

250

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230.  

Science.gov (United States)

Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRI-assessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis. PMID:24727584

Egger, Christine; Gérard, Christelle; Vidotto, Nella; Accart, Nathalie; Cannet, Catherine; Dunbar, Andrew; Tigani, Bruno; Piaia, Alessandro; Jarai, Gabor; Jarman, Elizabeth; Schmid, Herbert A; Beckmann, Nicolau

2014-06-15

251

Rejoining of double strand breaks in normal human and ataxia-telangiectasia fibroblasts after exposure to 60Co gamma-rays, 241Am alpha-particles or bleomycin.  

Science.gov (United States)

The rejoining of DNA double strand breaks (dsb) induced by 60Co gamma-rays, 241Am alpha-particles or bleomycin was measured by neutral filter elution. In agreement with their colony-forming ability, ataxia-telangiectasia cells (AT2BE) and normal fibroblasts exhibited similar dsb rejoining capacity following alpha-irradiation, but showed marked differences in the rejoining kinetics of dsb induced by gamma-rays or bleomycin. PMID:2435666

Coquerelle, T M; Weibezahn, K F; Lücke-Huhle, C

1987-02-01

252

Pulmonary epithelial permeability in patients treated with bleomycin containing chemotherapy detected by technetium-99m diethylene triamine penta-acetic acid aerosol (99mTc-DTPA) scintigraphy  

International Nuclear Information System (INIS)

The purpose of this study was to evaluate pulmonary epithelial permeability using 99mTc-DTPA scintigraphy in patients treated with bleomycin-containing regimens. Twelve non-smoking chemotherapy-naive patients with no clinical or radiological evidence of pulmonary disease and treated with bleomycin-containing chemotherapy were tested with 99mTc-DTPA scintigraphy before the first cycle and every 3 weeks until the third month after the end of chemotherapy (total cumulative dose of bleomycin 347.9 mg). Pretreatment values (T1/2 74.93 minutes) of 99mTc-DTPA scintigraphy were significantly higher than those obtained after the total dose of bleomycin (T1/2 51.00 minutes) (p99mTc-DTPA values decreased as the bleomycin dose increased. We conclude that cumulative bleomycin doses are related to increased pulmonary epithelial permeability at a dose of 256.5 mg. However, whether this is related to clinical toxicity is uncertain and large, multi-center prospective studies are needed. (author)

253

DNA degradation by bleomycin: evidence for 2'R-proton abstraction and for C-O bond cleavage accompanying base propenal formation  

International Nuclear Information System (INIS)

Reaction of poly(dA-[2'S-3H]dU) with activated bleomycin yields [3H] uracil propenal that completely retains the tritium label. In contrast, the authors have previously shown that reaction of poly(dA-[2'R-3H]dU) with activated bleomycin affords unlabeled uracil propenal. They have also prepared both cis- and trans-thymine propenals by chemical synthesis and have observed that the trans isomer is the exclusive product of the bleomycin reaction. Moreover, the cis isomer was found to be stable to the conditions of bleomycin-induced DNA degradation. Taken together, these results establish that the formation of trans-uracil propenal occurs via an anti-elimination mechanism with the stereospecific abstraction of the 2R proton. The question of phosphodiester bond cleavage during base propenal formation has also been addressed by the analysis of the fate of oxygen-18 in poly(dA-[3'-18O]dT) upon reaction with activated bleomycin. The 5'-monophosphate oligonucleotide ends produced from thymine propenal formation have been converted to inorganic phosphate by the action of alkaline phosphatase, and the phosphate has been analyzed for 18O content by 31P NMR spectroscopy. The oxygen-18 is retained in the inorganic phosphate, establishing that the formation of thymine propenal by activated bleomycin proceeds with C-O bond cleavage at the 3-position

254

Crystal structure of DNA-bound Co(III)·bleomycin B[subscript 2]: Insights on intercalation and minor groove binding  

Energy Technology Data Exchange (ETDEWEB)

Bleomycins constitute a widely studied class of complex DNA cleaving natural products that are used to treat various cancers. Since their first isolation, the bleomycins have provided a paradigm for the development and discovery of additional DNA-cleaving chemotherapeutic agents. The bleomycins consist of a disaccharide-modified metal-binding domain connected to a bithiazole/C-terminal tail via a methylvalerate-Thr linker and induce DNA damage after oxygen activation through site-selective cleavage of duplex DNA at 5'-GT/C sites. Here, we present crystal structures of two different 5'-GT containing oligonucleotides in both the presence and absence of bound Co(III){center_dot}bleomycin B2. Several findings from our studies impact the current view of bleomycin binding to DNA. First, we report that the bithiazole intercalates in two distinct modes and can do so independently of well ordered minor groove binding of the metal binding/disaccharide domains. Second, the Co(III)-coordinating equatorial ligands in our structure include the imidazole, histidine amide, pyrimidine N1, and the secondary amine of the {beta} aminoalanine, whereas the primary amine acts as an axial ligand. Third, minor groove binding of Co(III){center_dot}bleomycin involves direct hydrogen bonding interactions of the metal binding domain and disaccharide with the DNA. Finally, modeling of a hydroperoxide ligand coordinated to Co(III) suggests that it is ideally positioned for initiation of C4'-H abstraction.

Goodwin, Kristie D.; Lewis, Mark A.; Long, Eric C.; Georgiadis, Millie M. (Indiana-Med); (IUPUI)

2008-07-21

255

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

Directory of Open Access Journals (Sweden)

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

2012-06-01

256

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese 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 d [...] eterminar 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. Abstract in english 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.

Marlise Ladvocat, Bartholomei-Santos; Edmundo José de, Lucca.

257

Angiotensin-converting enzyme: an indicator of bleomycin-induced pulmonary toxicity in humans?  

DEFF Research Database (Denmark)

In order to evaluate bleomycin-associated lung damage in humans, lung function parameters and serum levels of the endothelial-bound angiotensin-converting enzyme (ACE) were determined by serial measurements in 11 patients who were treated for testicular cancer. None developed clinical or radiological evidence of pulmonary damage. While the static and dynamic lung function parameters were unchanged, carbon monoxide diffusion capacity (DLCO) decreased significantly (P less than 0.01) during a total of 126 days of pulsed regimen, indicating damage to the alveolar-endothelial membrane. S-ACE was unchanged within each treatment course but increased significantly (P less than 0.05) from the initial value to the last treatment course. Two months after cessation of treatment S-ACE returned to pretreatment values. Although the changes were modest they might mirror treatment-associated endothelial damage.

SØrensen, Peter G; RØmer, F K

1984-01-01

258

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

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 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

2004-01-01

259

Labelling of bleomycin with technetium-99m for diagnosis in nuclear medicine  

International Nuclear Information System (INIS)

A study about the behavior of the labelling yield of an antineoplastic drug (bleomycin) with a short-leved radionuclide (99 sup(m) Tc), using An(II) as a reductor agent, is presented. Parameters like the pH in the labelling, influence of the reaction time and mass of tin on the labelling yield were analysed. To simplify the labelling,, a lyofilized kit of Sn(II)/BLM in evacuated vials was prepared. The quality control involving paper chromatography, sterility and 'in vivo' test was made. The 'in vivo' tests were made both in healthy rats and in those with tumorous tissues, under barbituric action. The biological distribution, the concentration time of the products in tumors, the excretion time and excretion via were studied by means of scintigraphy and scintiphotos. (Author)

260

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

International Nuclear Information System (INIS)

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.)

 
 
 
 
261

Scintigraphy with 67Ga-citrate and 3In-bleomycin in rectal cancer  

International Nuclear Information System (INIS)

Scintigraphy with 67Cs-citrate and 111In-bleomycin was performed in 26 patients with primary rectal cancer, 176 patients with suspected tumors, and in 34 patients without clinicoroentgenological signs of cancer recurrence. A focus of higher accumulation of these radionuclides in the rectal area was recorded in all 26 patients. Of 176 patients with symptoms of recurrence tumors were detected by means of ultrasonic and computed tomography of the small pelvis in 158 patients. False-positive results were marked in 18 (10.2%) patients with chronic infalmmatory processes at the site of the resected rectum, in anastomositis, and prostatic adenoma. In the control group of 34 patients false-positive results were marked in 8.8%. Positive scintigraphy used in combined diagnosis of rectal cancer recurrence holds promise

262

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese 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 d [...] eterminar 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. Abstract in english 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.

Marlise Ladvocat, Bartholomei-Santos; Edmundo José de, Lucca.

1997-03-01

263

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

Directory of Open Access Journals (Sweden)

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.

Inagaki Hirofumi

2006-01-01

264

The experimental study of intra-bronchus embolization of bleomycin-lipiodol emulsion in dogs  

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Objective: To investigate the possibility of using bleomycin-lipiodol emulsion (BLE) as an agent for functional pulmonary lobectomy. Methods: The bilateral lungs of sixteen healthy mongrel dogs were randomly divided into the Control group and the FPLT group. In FPLT group the target pulmonary, lobes were filled with BLE and then the target bronchi were occluded. In Control group the pulmonary lobes were done with nothing. The dogs were took X-ray films pre-procedure and post-procedure and then on 1st, 7th, 14th, 21st, and 28th day, respectively, some of them were sacrificed after procedure for histopathologieal examination. Results: Histopathologically in the early time the target pulmonary lobes were mainly inflammatory effusion. After seven days the alveoli collapsed, pulmonary interstitium widened and fibrous connective tissue proliferated. After twenty-eight days the target pulmonary lobes were atelectasis and entirely fibrosis. The fibrosis grade based on Ashcroft's semiquantitative grading system. The grade of pulmonary fibrosis was 0.66±0.06, 2.76±0.24, 4.70±0.22, 6.74±0.25 and 7.69±0.23 in FPLT group and 0.62±0.05, 0.63±0.10, 0.63±0.07, 0.62±011 and 0.63±0.10 in control group separately at 1st, 7th, 14th, 2lst and 28th day after procedure. There was significant difference in the corresponding period between the FPLT group and the control group (P<0.01) and between first day (0.66±0.06) and fourteenth day(40.66±0.06) and fourteenth day(4.70 ± 0.22) (P<0.01) and fourteenth day and twenty-eighth day (7.69±0.23) (P<0.01). Conclusion: Intra-bronchus embolization of bleomycin-lipiodol emulsion can result in atelectasis and fibrosis of the target pulmonary, lobes can achieve FPLT. (authors)

265

Conditioned medium from amniotic mesenchymal tissue cells reduces progression of bleomycin-induced lung fibrosis  

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Background and aims We have demonstrated recently that transplantation of placental membrane-derived cells reduces bleomycin-induced lung fibrosis in mice, despite a limited presence of transplanted cells in host lungs. Because placenta-derived cells are known to release factors with potential immunomodulatory and trophic activities, we hypothesized that transplanted cells may promote lung tissue repair via paracrine-acting molecules. To test this hypothesis, we examined whether administration of conditioned medium (CM) generated from human amniotic mesenchymal tissue cells (AMTC) was able to reduce lung fibrosis in this same animal model. Methods Bleomycin-challenged mice were either treated with AMTC-CM or control medium, or were left untreated (Bleo group). After 9 and 14 days, the distribution and severity of lung fibrosis were assessed histologically with a scoring system. Collagen deposition was also evaluated by quantitative image analysis. Results At day 14, lung fibrosis scores in AMTC-CM-treated mice were significantly lower (P<0.05) compared with mice of the Bleo group, in terms of fibrosis distribution [1.0 (interquartile range, IQR 0.9) versus 3.0 (IQR 1.8)], fibroblast proliferation [0.8 (IQR 0.4) versus 1.6 (IQR 1.0)], collagen deposition [1.4 (IQR 0.5) versus 2.0 (IQR 1.2)] and alveolar obliteration [2.3 (IQR 0.8) versus 3.2 (IQR 0.5)]. No differences were observed between mice of the Bleo group and mice treated with control medium. Quantitative analysis of collagen deposition confirmed these findings. Importantly, AMTC-CM treatment significantly reduced the fibrosis progression between the two observation time-points. Conclusions This pilot study supports the notion that AMTC exert anti-fibrotic effects through release of yet unknown soluble factors. PMID:21954836

Cargnoni, Anna; Ressel, Lorenzo; Rossi, Daniele; Poli, Alessandro; Arienti, Davide; Lombardi, Guerino; Parolini, Ornella

2012-01-01

266

Discovery in PET/CT of an acute pulmonary toxicity with rapidly fatal bleomycin; Decouverte en TEP/TDM d'une toxicite pulmonaire aigue a la bleomycine rapidement fatale  

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Purpose: we report the case of a patient treated by chemotherapy for a Hodgkin disease showing after treatment an important pulmonary uptake that appears bilateral and symmetric on PET in connection with an acute toxicity at the preclinical stage. Conclusions: an intense and diffuse pulmonary uptake of the {sup 18}F.D.G. during the chemotherapy, including particularly the bleomycin, can reveal an acute serious pulmonary toxicity and potentially deadly at the pre-symptomatic stage. (N.C.)

Le Dortz, L.; Ben Fredj, M.; Lenoir, L.; Bahri, H.; Devillers, A.; Garin, E. [Centre Eugene-Marquis, Service de medecine nucleaire, 35 - Rennes (France)

2010-07-01

267

Nucleobase-based barbiturates: their protective effect against DNA damage induced by bleomycin-iron, antioxidant, and lymphocyte transformation assay.  

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A number of nucleobase-based barbiturates have been synthesized by combination of nucleic acid bases and heterocyclic amines and barbituric acid derivatives through green and efficient multicomponent route and one pot reaction. This approach was accomplished efficiently using aqueous medium to give the corresponding products in high yield. The newly synthesized compounds were characterized by spectral analysis (FT-IR, (1)H NMR, (13)C NMR, HMBC, and UV spectroscopy) and elemental analysis. Representative of all synthesized compounds was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3 -TBA manifested the best protective effect against DNA damage induced by bleomycin. PMID:24900997

Dhorajiya, Bhaveshkumar D; Dholakiya, Bharatkumar Z; Ibrahim, Ahmed S; Badria, Farid A

2014-01-01

268

Determination of unbound technetium-99m (free technetium) in bleomycin-sup(99m)Tc preparations  

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Two forms of free technetium-99m exist in bleomycin-sup(99m)Tc preparations: Tc(7) and Tc reduced. For the sup(99m)Tc(7) determination the paper chromatography method was used with Whatman 1 paper and acetone: 30% acetic acid in proportion 7:3 as the developing solvent. The developing time was 2 hr, Rsub(f) for TcO4- is 0.9. For the sup(99m)Tc reduced forms determination the thin layer chromatography was elaborated with Sephadex G-25 superfine as the layer and 2.5N sodium chloride as the developing solvent. Developing time was 30 min. The sup(99m)Tc reduced stays on the start point, sup(99m)Tc(7) and bleomycin-sup(99m)Tc move from the start point to the distance of 2.0-3.5 cm and 4.5-7.0 cm respectively. (author)

269

Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions  

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Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium electroporation and electrochemotherapy.

Frandsen, Stine Krog; Gissel, Hanne

2013-01-01

270

Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores  

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Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPAR{gamma} agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

Jin, Gong Yong; Bok, Se Mi; Han, Young Min [Department of Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Chung, Myung Ja [Department of Pathology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Yoon, Kwon-Ha [Department of Radiology, Iksan Hospital, Iksan (Korea, Republic of); Kim, So Ri [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Yong Chul, E-mail: leeyc@jbnu.ac.kr [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of)

2012-08-15

271

Interaction of bleomycin, hyperthermia and a calmodulin inhibitor (trifluoperazine) in mouse tumour cells: I. In vitro cytotoxicity.  

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Evidence in the literature suggests that hyperthermia (HT) or inhibitors of calmodulin can increase the sensitivity of rodent cells to bleomycin (BLM) by interfering with DNA repair functions. In an attempt to explore methods of improving the efficacy of thermochemotherapy we have investigated the individual and combined effects of HT (44 degrees C) and the calmodulin inhibitor trifluoperazine (TFP, 30 micrograms ml-1) on early plateau phase monolayer cultures of mouse EMT6 tumour cells for s...

Mircheva, J.; Smith, P. J.; Bleehen, N. M.

1986-01-01

272

Bleomycin Hydrolase Is Regulated Biphasically in a Differentiation- and Cytokine-dependent Manner: RELEVANCE TO ATOPIC DERMATITIS  

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Loss-of-function mutation in the profilaggrin gene is a major risk factor for atopic dermatitis (AD). Previously, we showed that a neutral cysteine protease, bleomycin hydrolase (BH), has a role in generating natural moisturizing factors, and calpain I is an upstream protease in the filaggrin degradation pathway. Here, we investigated the transcriptional regulatory mechanisms of BH and the relevance of BH to AD. First, we cloned the 5?-flanking region of BH. Deletion analyses identified a c...

Kamata, Yayoi; Yamamoto, Mami; Kawakami, Fumitaka; Tsuboi, Ryoji; Takeda, Atsushi; Ishihara, Kazuhiko; Hibino, Toshihiko

2011-01-01

273

Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts  

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Abstract Background Lung fibrosis is characterized by fibroblast proliferation and the deposition of collagens. Curcumin, a polyphenol antioxidant from the spice tumeric, has been shown to effectively counteract fibroblast proliferation and reducing inflammation and fibrotic progression in animal models of bleomycin-induced lung injury. However, there is little mechanistic insight in the biological activity of curcumin. Here, we study the effects of curcumin on the expression...

Zhang Dongwei; Huang Chuangfang; Yang Changfu; Liu Renzuo J; Wang Jifeng; Niu Jianzhao; Brömme Dieter

2011-01-01

274

Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores  

International Nuclear Information System (INIS)

Peroxisome proliferator-activated receptor-? (PPAR?) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPAR? agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

275

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

2010-06-01

276

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

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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

277

Curcumin inhibits fibrosis-related effects in IPF fibroblasts and in mice following bleomycin-induced lung injury.  

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Idiopathic pulmonary fibrosis (IPF) is a progressive and typically fatal lung disease for which no effective therapy has been identified. The disease is characterized by excessive collagen deposition, possibly in response to dysregulated wound healing. Mediators normally involved in would healing induce proliferation of fibroblasts and their differentiation to myofibroblasts that actively secrete collagen. Curcumin, a polyphenolic compound from turmeric, has been shown to exert a variety of biological effects. Effects on IPF and associated cell types remain unclear, however. We accordingly tested the ability of curcumin to inhibit proliferation and differentiation to myofibroblasts by human lung fibroblasts, including those from IPF patients. To further examine the potential usefulness of curcumin in IPF, we examined its ability to reduce fibrosis in bleomycin-treated mice. We show that curcumin effectively reduces profibrotic effects in both normal and IPF fibroblasts in vitro and that this reduction is accompanied by inhibition of key steps in the transforming growth factor-? (TGF-?) signaling pathway. In vivo, oral curcumin treatment showed no effect on important measures of bleomycin-induced injury in mice, whereas intraperitoneal curcumin administration effectively inhibited inflammation and collagen deposition along with a trend toward improved survival. Intraperitoneal curcumin reduced fibrotic progression even when administered after the acute bleomycin-induced inflammation had subsided. These results encourage further research on alternative formulations and routes of administration for this potentially attractive IPF therapy. PMID:20061443

Smith, Monica R; Gangireddy, Srinivasa R; Narala, Venkata R; Hogaboam, Cory M; Standiford, Theodore J; Christensen, Paul J; Kondapi, Anand K; Reddy, Raju C

2010-05-01

278

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

2005-01-01

279

Evaluation of in vitro genotoxic activity of bleomycin and mitomycin C in human lymphocytes using the alkaline comet assay.  

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Although chemotherapy targets cancer tissue, it also damages the DNA of non-cancer cells. The aim of this study was to evaluate the in vitro genotoxic potential of therapeutic concentrations of bleomycin and mitomycin C, added alone or in combination to cultures of human peripheral lymphocytes. The levels of DNA damage and repair were assessed using the alkaline comet assay immediately after cell treatment as well as 24 and 48 hours following treatment. The results indicate that individual drugs and their combination induce a significant DNA damage to peripheral blood lymphocytes. Bleomycin alone induced the highest levels of primary DNA damage immediately after cell treatment. Although mitomycin C alone induced massive cross-linking and retarded DNA migration in resting cells, active proliferation and repair processes significantly increased DNA damage. Combined, they showed a synergetic effect, inducing complex patterns of DNA damage in peripheral blood lymphocytes and producing different types of lesions and a number of DNA alterations that directly or indirectly increased DNA migration. Our study has confirmed the sensitivity of the alkaline comet assay for assessing bleomycin and/or mitomycin C genotoxicity to human lymphocytes at concentration levels used in clinic. It has also demonstrated the utility of the alkaline comet assay as one of the primary screening methods for in vitro studies of drug-DNA interactions, especially in studying mechanisms of action of new drugs. PMID:15584551

Mili?, Mirta; Kopjar, Nevenka

2004-11-01

280

Place occupied by gallium 67 citrate and 57Co-bleomycine scintigraphy in the evaluation and supervision of cancers  

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This work attempts to situate 57Co-bleomycine and gallium67 citrate scintigraphy in pre-treatment evaluation and supervision of solid tumours or malignant lymphomas. The results given by these two radiopharmaceuticals are compared for a series of 136 patients and a bibliograhical survey covering more than 3.000 cases is compiled. The purpose of the study is to establish the diagnostic capacity of each of these two tumoral tracers, according to the nature and location of the lesions, and, on this basis, to try to estimate the position it occupies as well as its indications and limits. The following are dealt with successively: - the biological properties, development of labelling techniques and tumoral fixation mechanisms of 57Co-bleomycine and 67Ga citrate reviewed historically. - The physical and technological foundations of the scintigraphic methods used. - The results obtained with 57Co bleomycine and 67Ga citrate in patients carrying solid tumours and malignant lymphomas. In the discussion these two radiotracers are compared as a function of the histological nature and location of the lesions. Finally these two isotopic methods are situated with respect to other complementary examinations and from this their indications and limits are inferred

 
 
 
 
281

[Early results of the treatment of Hodgkin's disease in adults using the seven-drug cytostatic protocol].  

Science.gov (United States)

65 adult patients with Hodgkin's disease were treated acc. to multidrug protocol proposed by I. Koza et al. including doxorubicin, vincristine, vinblastine, bleomycin, procarbazine, lomustine and prednisone. 4 drugs (3 cytostatics and prednisone) including cycles were given repeatedly every 4 weeks. In the group of first line therapy (39 persons) 61.5% CR and 23% PR was obtained i.e. 84.5% therapeutic responses. The protocol used as salvage therapy resulted in 30% CR and 23% PR. Undesirable gastrointestinal effects were observed less commonly than after ABVD and CVPP schemes but myelosuppressive effect was more often seen and required attenuation of cytostatic drugs doses in the further cycles of therapy. The considered protocol seems to be a valuable one approaching to -but not achieving- the results of MOPP and ABVD schemes: is better tolerated because of elimination of strong emetic cytostatics (chlormethine and decarbazine) but late toxicity could be evaluable only after several years. PMID:1381821

Kotlarek-Haus, S; Gabry?, K; Wo?owiec, D; Kuliszkiewicz-Janus, M; Filip, A

1992-02-01

282

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

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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.

Ghofrani Hossein A

2010-05-01

283

A Investigation of the Bleomycin-Dna Interaction Using Perturbed Angular Correlations.  

Science.gov (United States)

Perturbed angular correlations (PAC) of the 173 keV-247 keV gamma-gamma cascade in the decay of ('111)In offers a sensitive new approach to probe biological molecules in aqueous solution. We have found that this method can be effectively utilized to study the interaction of anti -tumor drug molecules such as bleomycin, which chelate ('111)In('3+), with double helical DNA. For the small ('111)In-BLM complex, the time-integrated attenuation factor G(,2)(' )=(' )0.40, and when ('111)In-BLM is specifically bound to the large and sluggish DNA molecule, we have G(,2)(' )=(' )0.20 for ('111)In-BLM-DNA. Using these two extreme values as signatures of free and DNA-bound bleomycin fractions, we have studied the binding of BLM to various types of DNA. Binding curves for calf thymus DNA, and poly dA-dT are presented. The size of FLM binding site was determined to be 3.3 base pairs for calf thymus DNA, and 2.5 base pairs for poly dA-dT. These results and association constants compare well with results based on other biochemical methods, such as fluorescence quenching. A highly cooperative interaction of BLM with poly dA-dT was observed, but no evidence of cooperativity was seen in the case of calf thymus DNA. In addition, studies of salt-dependence of the binding revealed cooperative behavior in the case of poly dA-dT, and the covalently closed super-helical DNA of PM-2 bacteriophage, but not for calf thymus DNA. Soft modes of DNA under premelting conditions are suggested to be the likely reason for observed cooperativity in the case of poly dA-dT under the low Na('+) concentrations (<(, )10 mM) involved. In the case of calf thymus DNA, a thermodynamic analysis of ionic effects indicates that 1.2 counter ions are released per BLM molecule bound. Other studies revealed relatively weak binding of ('111)In-BLM to yeast RNA, and a likely conformational change in ('111)In -BLM brought about by the action of dethiothreitol.

Hallee, Gary John

284

Radiotherapy and bleomycin-containing chemotherapy in the treatment of advanced head and neck cancer: report of six patients and review of the literature  

International Nuclear Information System (INIS)

In an effort to improve the complete remission rate achievable with bleomycin and cisplatin, administered prior to radiotherapy in previously untreated patients with unresectable epidermoid carcinoma of the head and neck, we initiated a pilot study employing simultaneous chemotherapy and radiotherapy. Six patients were treated with bleomycin (B) 15 mg i.m. t.i.w. 30-60 minutes prior to radiotherapy (RT) treatment with conventional fractionation, 180-200 rad/fx, 5 fx/week. During interruptions in B + RT for healing of mucocutaneous reactions, patients received cisplatin 40 mg/mg m2 once weekly. Toxicity included severe mucositis within the radiation port in all patients, three episodes of infection, and significant myelosuppression in one patient. Transient mild serum creatinine elevation occurred in four patients. Three patients did not complete treatment because of severity of toxicity. Response was: primary--4/6CR, 1/6 PR; regional nodes--1/5 CR, 4/5 PR. Review of the literature of concurrent bleomycin and radiotherapy trials in head and neck cancer indicates that other investigators have encountered severe toxicity using bleomycin dose and radiation fractionation schedules similar to ours. Toxicity may be reduced when lower doses of concurrent bleomycin and/or alternative radiation fractionation schedules are employed. Although results of uncontrolled trials suggest a possible therapeutic advantage to treatment with the combination compared to radiotherapy alone, this has not clearly been established in the four randomized trials reviewed

285

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

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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

286

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)

287

Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis.  

Science.gov (United States)

Idiopathic pulmonary fibrosis has a poor prognosis and few efficacious treatments. The immunosuppressant cyclosporin A has been shown to inhibit tumour growth factor (TGF)-beta-induced collagen deposition in vitro, and is widely used in Japan as a potent antifibrotic agent. Tacrolimus (FK506) is another attractive immunosuppressant, which may be useful in the treatment of pulmonary fibrosis. The aim of the present study was to elucidate the antifibrotic effect of FK506. The inhibitory effect of FK506 on collagen synthesis in cultured lung fibroblastic cells, TIG-3-20, and its antifibrotic effect on bleomycin (BLM)-induced pulmonary fibrosis in mice was investigated. FK506 inhibited TGF-beta-induced collagen synthesis, and suppressed the expression of TGF-beta type I receptor (TbetaR-I) in TIG-3-20 cells. Consistent with the in vitro findings, FK506 treatment starting on day 6 attenuated BLM-induced pulmonary fibrosis, in part, via reduced TbetaR-I expression. FK506 treatment in the acute BLM injury phase unexpectedly increased pro-inflammatory cytokine levels in bronchoalveolar lavage fluid and enhanced lung injury, resulting in poor survival. In conclusion, the present results suggest that FK506 has a potent antifibrotic effect and may be useful for the treatment of pulmonary fibrosis, although its use in the acute inflammatory phase may exacerbate lung injury. PMID:16507844

Nagano, J; Iyonaga, K; Kawamura, K; Yamashita, A; Ichiyasu, H; Okamoto, T; Suga, M; Sasaki, Y; Kohrogi, H

2006-03-01

288

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 BLMgenic effect of BLM

289

Combined effects of local hyperthermia, bleomycin, and x-ray on Ehrlich ascites tumor in mice  

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The combined effects of local hyperthermia at 42.50C for 30 minutes (HTM), 1/10 LD50 Bleomycin iv(BLM) and 200 rad-irradiation (200 R) were studied in DDD strain male mice with Ehrlich ascites tumor. The objective was to acquire data on the optimum regimen for a combined administration of these 3 modalities. The treatments were carried out 10 days after the inoculation of 2 x 106 of the cells into the right hind-limb. HTM was applied by water bath heating. Concomitant application of the 3 modalities led to the best effect with a 80 % complete regression. A single modality produced no significant effect and a 30-50 % regression occurred when 2 modalities were combined. To assess the influence of timing and sequence, HTM was applied at 1,2,4 and 6 hours before, after or simultaneously with the combination of BLM and 200 R. A significant effect was obtained in case of simultaneous application of the 3 modalities and the effectiveness of HTM remained as long as the time interval between HTM and BLM plus 200 R was 2 hours. This enhancement disappeared in case of 4 hour intervals. (author)

290

Endothelial cells recruit macrophages and contribute to a fibrotic milieu in bleomycin lung injury.  

Science.gov (United States)

Systemic sclerosis (SSc) is a systemic autoimmune disease that causes inflammation, vasculopathy, and fibrosis of the skin and internal organs. One of the most severe complications of SSc involves the development of pulmonary fibrosis. Endothelial cell injury precedes the development of fibrosis, and is believed to be an initiating event. Therefore, we aimed to characterize the role of endothelial cells in the progression of pulmonary fibrosis, using a well-established bleomycin (BLM) model of pulmonary fibrosis. Endothelial cells were isolated by cell sorting, and the analysis of gene expression was performed with quantitative RT-PCR. Endothelial injury was induced between the first and second week, as shown by the elevated expression of the vascular injury markers matrix metallopeptidase-12 and von Willebrand factor. After injury, endothelial activation was indicated by the up-regulation of selectins, CCL chemokines, and inflammatory mediators, including complement anaphylatoxin receptors (C3aR and C5aR), oncostatin M, and leukemia inhibitory factor. The endothelial cell overexpression of fibrotic mediators, including connective tissue growth factor, plasminogen activator inhibitor-1, osteopontin, fibronectin, and fibroblast specific protein-1, was observed in the second and fourth weeks. This study suggests that endothelial cells actively contribute to the disease process via multiple mechanisms, including the recruitment of inflammatory cells and the establishment of a profibrotic environment during the development of BLM-induced pulmonary fibrosis. PMID:23885794

Leach, Heather G; Chrobak, Izabela; Han, Rong; Trojanowska, Maria

2013-12-01

291

Paracetamol Supplementation Does Not Alter The Antitumor Activity and Lung Toxicity of Bleomycin  

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Full Text Available Bleomycin (BLM is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Hyperpyrexia following injection of BLM was reported thus, paracetamol is sometimes administered with BLM as antipyretic drug. Actually, paracetamol was found to interfere with cytotoxicity of some drugs. This study was conducted to investigate the effect of paracetamol administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma (EAC cells. Paracetamol did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5-hydroxytryptamine (5-HT and increase in the contractility of tracheal smooth muscles induced by acetylcholine (ACh. The toxicity was also confirmed biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in reduced glutathione (GSH level. Pretreatment with paracetamol did not significantly change lipid peroxidation, GSH level, percent survival of rats or the response of pulmonary arterial rings and tracheal smooth muscles to 5-HT and ACh respectively. The results of the present study indicated that paracetamol neither modified the antitumor effect of BLM nor changed drug-induced lung toxicity.

Ghada M. Suddek

2014-01-01

292

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

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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.)

293

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

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Full Text Available SciELO Chile | Language: English 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 effec [...] t 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-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

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

294

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

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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. PMID:20414325

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

2010-08-01

295

Malformaciones linfáticas: tratamiento percutáneo con bleomicina / Lymphatic malformations: percutaneus treatment with bleomycin  

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Full Text Available SciELO Argentina | Language: Spanish Abstract in spanish Las malformaciones linfáticas son anomalías del desarrollo del sistema linfático que tienden a sufrir complicaciones en su evolución. En la última década, la terapia con agentes esclerosantes ha ido ganando popularidad sobre la cirugía, por su eficacia, sus menores complicaciones y sus excelentes re [...] sultados estéticos. Presentamos una serie de 24 pacientes tratados mediante esclerosis percutánea con bleomicina. Los resultados fueron excelentes (reducción de volumen ? 95% y asintomáticos) en 12 pacientes, buenos (reducción de volumen entre 50% y 95% y asintomáticos) en 5 pacientes, regulares (reducción de volumen Abstract in english Lymphatic malformations are developmental abnormalities of the lymphatic system, which tend to complicate during their evolution. In the last decade, therapy with sclerosing agents has gained popularity over surgery due to its effectiveness, fewer complications, and excellent cosmetic results. We pr [...] esent a series of 24 patients treated with percutaneous bleomycin injection. Results were excellent (volume reduction ? 95%, without symptoms) in 12 patients, good (volume reduction between 50% and 95%, without symptoms) in 5 patients, fair (volume reduction

José Luis, Cuervo; Eduardo, Galli; Guillermo, Eisele; Erica, Johannes; Alejandro, Fainboim; Silvia, Tonini; Walter, Joaquin; Bettina, Viola; Miguel, Nazar.

296

Preparation of sup(99m)Tc-bleomycin with electrogenerated tin(II) ions  

International Nuclear Information System (INIS)

Some parameters influencing the efficiency of labelling bleomycin (BLM) with sup(99m)Tc using tin electrodes for electrolytic production of tin(II) ions were investigated. The results showed clearly the superiority of tin electrodes for labelling BLM with sup(99m)Tc in comparison with Zn electrodes. The alteration of the primary properties of BLM is negligible. The optimal procedure for the labelling of BLM is as follows. Into a vessel (15-20 cm3) containing the corresponding amount of BLM in saline, and the desired amount of sup(99m)TcO4- eluate in 0.9% NaCl, 0.5 ml 0.5 M HCl is added and diluted with saline to 10 ml. The electrolysis is performed using tin electrodes with a current density of about 6 mA/cm2 for 10 to 20 s with stirring, which is prolonged after electrolysis for a few minutes. After filtration through a 0.22 ?m Millipore filter, the labelled compound can be used for clinical applications. For analytical control of labelled BLM, gel filtration on Sephadex G-25 with UV and radioactivity detection can be recommended. From the results obtained, it has been concluded that gel filtration on Sephadex G-25 can give applicable information about the quality of this radiopharmaceutical. (T.G.)

297

Vesnarinone Represses the Fibrotic Changes in Murine Lung Injury Induced by Bleomycin  

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Full Text Available We investigated the potential usefulness of vesnarinone, a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM-induced pulmonary fibrosis. Mice were fed a control diet (n=42, or a diet containing low (n=42 or high (n=42 dose of vesnarinone. Dietary intake of vesnarinone minimized the BLM toxicity as reflected by significant decreases in numbers of inflammatory cells, KC, and soluble TNF receptors in the bronchoalveolar lavage fluid. A quantitative evaluation of histology demonstrated significantly mild lung parenchymal lesions in BLM-treated mice fed with diet containing high dose of vesnarinone than in the control diet group. Consistent with the histopathology, hydroxyproline levels in lung tissue from BLM-treated mice fed with diet containing vesnarinone were significantly lower than that from mice fed with control diet. We concluded that vesnarinone inhibits BLM-induced pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in the early phase.

Minoru Inage, Hidenori Nakamura, Hiroshi Saito, Shuichi Abe, Toshihiko Hino, Noriaki Takabatake, Kyoko Terashita, Manabu Ogura, Shuichi Kato, Tetsumi Hosokawa, Makoto Sata, Hitonobu Tomoike

2009-01-01

298

Malformaciones linfáticas: tratamiento percutáneo con bleomicina / Lymphatic malformations: percutaneus treatment with bleomycin  

Scientific Electronic Library Online (English)

Full Text Available SciELO Argentina | Language: Spanish Abstract in spanish Las malformaciones linfáticas son anomalías del desarrollo del sistema linfático que tienden a sufrir complicaciones en su evolución. En la última década, la terapia con agentes esclerosantes ha ido ganando popularidad sobre la cirugía, por su eficacia, sus menores complicaciones y sus excelentes re [...] sultados estéticos. Presentamos una serie de 24 pacientes tratados mediante esclerosis percutánea con bleomicina. Los resultados fueron excelentes (reducción de volumen ? 95% y asintomáticos) en 12 pacientes, buenos (reducción de volumen entre 50% y 95% y asintomáticos) en 5 pacientes, regulares (reducción de volumen Abstract in english Lymphatic malformations are developmental abnormalities of the lymphatic system, which tend to complicate during their evolution. In the last decade, therapy with sclerosing agents has gained popularity over surgery due to its effectiveness, fewer complications, and excellent cosmetic results. We pr [...] esent a series of 24 patients treated with percutaneous bleomycin injection. Results were excellent (volume reduction ? 95%, without symptoms) in 12 patients, good (volume reduction between 50% and 95%, without symptoms) in 5 patients, fair (volume reduction

José Luis, Cuervo; Eduardo, Galli; Guillermo, Eisele; Erica, Johannes; Alejandro, Fainboim; Silvia, Tonini; Walter, Joaquin; Bettina, Viola; Miguel, Nazar.

2011-10-01

299

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

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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.

Matsunaga Hirofumi

2011-10-01

300

Diagnostic value of female genital malignant tumors by using 111In-bleomycin scintigraphy  

International Nuclear Information System (INIS)

In order to know if it is possible to objectively decide the extent of infiltration of female genital malignant tumors into parametrium by using 111In-bleomycin scintigraphy, a fundamental and clinical investigation was made. The radiochemical purity and stability of 111In-BLM were comparatively unchangeable. When this complex was kept at room temperature for a week, there was not more than 2% of the free 111In. As to blood clearance, when the blood radioactivity of 111In-BLM 5 minutes after the injection was counted as 100%, about 80% of the radioactivity was cleared from the blood in 48 hours. Over 50% of the radioactivity was excreted into the urine in 48 hours. Of 29 cases of female genital malignant tumors, 23 cases (79%) showed positive images. Therefore 111In-BLM was found to be one of the suitable radiopharmaceuticals for the diagnosis of female genital malignant tumors. 111In-BLM scintigraphy was of great use for deciding the extent of the invasion of carcinoma cervicis uteri into parametrium and for the search of metastasis. (author)

 
 
 
 
301

Angular distribution for 7Be(d,n)8B reaction at Ec.m. = 8.3 MeV and the astrophysical S17(0) factor for 7Be(p, ?)8B reaction  

International Nuclear Information System (INIS)

The differential cross section for 7Be(d, n)8B reaction at Ec.m. 8.3 MeV has been measured by using a 7Be radioactive beam. The reaction cross section was determined to be 28 +- 3 mb. The astrophysical S17(0) factor for the 7Be(p, ?)8B reaction was derived to be 24 +- 5 eVb through the asymptotic normalization constant of 8B extracted from the experimental data. This results is found to be consistent with a previous value obtained from the same reaction at Ec.m. = 5.8 MeV, implying the energy independence of this indirect method within the uncertainty

302

Measurement of the angular distribution for the 7Be(d,n)8B reaction and determination of the astrophysical S factor for the 7Be(p,?)8B reaction  

International Nuclear Information System (INIS)

The differential cross section for the 7Be(d,n)8B reaction at Ec.m=5.8 MeV has been measured using a 7Be beam produced by the radioactive nuclear beam facility at the China Institute of Atomic Energy. The 8B ions were detected in full geometry with a two dimensional position sensitive ?E-E counter telescope. The reaction cross section was determined to be 58±8 mb. The angular distribution data were analyzed with a distorted-wave Born approximation calculation. The astrophysical S17(0) factor for the 7Be(p,?)8B reaction was derived to be 27.4±4.4 eV b through the asymptotic normalization constant extracted from the experimental data. (orig.)

303

Cultured mouse SR-1 cells exposed to low dose of gamma-rays become less susceptible to the induction of mutagenesis by radiation as well as bleomycin.  

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The effect of pre-exposure of cultured mouse SR-1 cells to a low dose of gamma-rays on the induction of mutations at the hprt locus by subsequent high dose radiation or bleomycin was studied. When cells were pre-exposed to 0.01 Gy gamma-rays, the induction of mutations by a 3 Gy gamma-ray dose given 18 or 24 h later was significantly reduced as compared with those which did not receive the low dose pre-exposure. When cells were challenged with 5 or 10 micrograms/ml bleomycin for 12 h, which can produce double-strand breaks in DNA, instead of 3 Gy gamma-rays, a similar mutagenetic adaptive response was observed. We conclude that this resistance to radiation- or bleomycin-induced mutation is attributed to the induction of a DNA double-strand break repair mechanism. PMID:7681929

Zhou, P K; Liu, X Y; Sun, W Z; Zhang, Y P; Wei, K

1993-03-01

304

Cultured mouse SR-1 cells exposed to low dose of ?-rays become less susceptible to the induction of mutagenesis by radiation as well as bleomycin  

International Nuclear Information System (INIS)

The effect of pre-exposure of cultured mouse SR-1 cells to a low dose of ?-rays on the induction of mutations at the hprt locus by subsequent high dose radiation or bleomycin was studied. When cells were pre-exposed to 0.01 Gy ?-rays, the induction of mutations by a 3 Gy ?-ray dose given 18 or 24 h later was significantly reduced as compared with those which did not receive the low dose pre-exposure. When cells were challenged with 5 or 10 ?g/ml bleomycin for 12 h, which can produce double strand breaks in DNA, instead of 3 Gy ?-rays, a similar mutagenetic adaptive response was observed. The authors conclude that this resistance to radiation- or bleomycin-induced mutation is attributed to the induction of a DNA double-strand break repair mechanism. (Author)

305

The combined effect of bleomycin and irradiation on mouse lip mucosa. 2. Influence on the accumulation and repair of sublethal damage during fractionated irradiation  

International Nuclear Information System (INIS)

The effect on the mouse lip mucosa of different fractionated irradiation schedules with and without bleomycin was investigated. Lowering the fraction size resulted in a progressive increase of both the dose modification factors (DMF) and the absolute dose reduction (ADR), i.e. from 1.19 and 2.8 Gy respectively for single doses to 1.86 and 21.5 Gy respectively for 20 fractions. The mechanisms involved are most probably a direct cell kill by bleomycin, together with a reduced capacity to accumulate and/or to repair sublethal damage, although the influence of redistribution in the cell cycle during bleomycin infusion can not be excluded. Such large differences in the interaction between chemotherapy and irradiation as a function of the fractionation schedule could lead to a significant underestimate of response if data from single dose or 2-fraction experiments are extrapolated to regimens used in clinical practice. (Auth.)

306

Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats  

International Nuclear Information System (INIS)

Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The present study was designed to assess the potential antifibrotic effect of thymoquinone (TQ) and whether TQ can attenuate the severity of oxidative stress and inflammatory response during bleomycin-induced pulmonary fibrosis. Male Wister rats were treated intraperitoneally with either bleomycin (15 mg/kg, 3 times a week for 4 weeks) and/or thymoquinone (5 mg/kg/day, 1 week before and until the end of the experiment). Bleomycin significantly increased lung weight and the levels of Lactate dehydrogenase, total leucocytic count, total protein and mucin in bronchoalveolar lavage and these effects were significantly ameliorated by TQ treatment. As markers of oxidative stress, bleomycin caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease in the antioxidant enzyme activity of superoxide dismutase and glutathione transferase. TQ treatment restored these markers toward normal values. TQ also counteracted emphysema in air alveoli, inflammatory cell infiltration, lymphoid hyperplastic cells activation surrounding the bronchioles and the over expression of activated form of nuclear factor kappa-B (NF-B) in lung tissue that was induced by bleomycin. Fibrosis was assessed by measuring hydroxyproline content, which increased markedly in the bleomycin group and significantly reduced by concurrent treatment with TQ. Furthermore, histopathological examination confirmed the antifibrotic effect of TQ. Collectively these findings indicate that TQ has potential antifibrotic effect beside its antioxidant activity that could be through NF-?B inhibition.

307

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

2008-01-01

308

Investigation of the interacorporcal decay, elimination rate and diagnostic confidence of 57Co-bleomycine in patients with the uterine cervix cancer  

International Nuclear Information System (INIS)

In 20 women with diagnosed squamous carcinoma of the uterine cervix the 57Co-Bleomycine was used for the estimation of the intracorporeal decay, elimination rate and neoplasmic tissue storage of the complex. Whole body scanner ''Scan modus'' type and gamma chamber were used. A rapid elimination of the examined complex with urine was noted, the blood concentration was significantly higher (p57Co-Bleomycine) can be applied as diagnostic means in cases of uterine squamous carcinoma and in its metastases. (author)

309

Comparative study of fixation of Co57 labelled bleomycin, labelled gallium citrate and Hg197 labelled mercury chloride, benign or malignant pulmonary lesions  

International Nuclear Information System (INIS)

Over the last ten years, numerous labelled molecules have been used in lung diseases, in order to attempt definite localisation of primary or secondary carcinoma. Three of these substances are now used: cobalt 57-labelled bleomycin, Hg197Cl2 and Ga67 citrate. A study of 34 patient with malignant or tuberculous lung disease with definite diagnosis, permitted demonstration of the fact that the highest uptake, or the best images, were obtained with labelled bleomycin. However, the long period of Co57 limits its indications in young subjects and, in these cases, HgCl2 is indicated

310

Prevention of Bleomycin-Induced Lung Inflammation and Fibrosis in Mice by Naproxen and JNJ7777120 Treatment.  

Science.gov (United States)

Pulmonary fibrosis, a progressive and lethal lung disease characterized by inflammation and accumulation of extracellular matrix components, is a major therapeutic challenge for which new therapeutic strategies are warranted. Cyclooxygenase (COX) inhibitors have been previously utilized to reduce inflammation. Histamine H4 receptor (H4R), largely expressed in hematopoietic cells, has been identified as a novel target for inflammatory and immune disorders. The aim of this study was to evaluate the effect of JNJ7777120 (1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine), a selective H4R antagonist, and naproxen, a well known nonsteroidal anti-inflammatory drug, and their combination in a murine model of bleomycin-induced fibrosis. Bleomycin (0.05 IU) was instilled intratracheally to C57BL/6 mice, which were then treated by micro-osmotic pump with vehicle, JNJ7777120 (40 mg/kg b.wt.), naproxen (21 mg/kg b.wt.), or a combination of both. Airway resistance to inflation, an index of lung stiffness, was assessed, and lung specimens were processed for inflammation, oxidative stress, and fibrosis markers. Both drugs alone were able to reduce the airway resistance to inflation induced by bleomycin and the inflammatory response by decreasing COX-2 and myeloperoxidase expression and activity and thiobarbituric acid-reactive substance and 8-hydroxy-2'-deoxyguanosine production. Lung fibrosis was inhibited, as demonstrated by the reduction of tissue levels of transforming growth factor-?, collagen deposition, relative goblet cell number, and smooth muscle layer thickness. Our results demonstrate that both JNJ7777120 and naproxen exert an anti-inflammatory and antifibrotic effect that is increased by their combination, which could be an effective therapeutic strategy in the treatment of pulmonary fibrosis. PMID:25185215

Rosa, Arianna Carolina; Pini, Alessandro; Lucarini, Laura; Lanzi, Cecilia; Veglia, Eleonora; Thurmond, Robin L; Stark, Holger; Masini, Emanuela

2014-11-01

311

Chromosomal aberrations in the peripheral lymphocytes of cancer patients treated with high-energy electrons and bleomycin  

International Nuclear Information System (INIS)

5 patients with inoperable bronchogenic carcinomas on a weekly therapy with a low dose of bleomycin (BL) plus irradiation with high-energy electrons, were analysed cytogenetically by cultivating peripheral lymphocytes taken immediately before the BL treatments and some hours before the irradiations. For the induction of dicentric chromosomes, linear dose-effect relationships were found: 3 of the patients responded with similar dose-effect relationships. The other 2 were different: they were not comparable with those 3 or with each other. These results were unexpected because all 5 patients received similar types of treatment. (orig.)

312

Local injection of OK-432 and Mitomycin C into vulvar cancer responding poorly to Bleomycin and linac irradiation  

International Nuclear Information System (INIS)

In one case of vulvar carcinoma (T2N0M0) in which a radical surgery appeared unfeasible, linac radiation and intratumoral injection of Bleomycin were performed as the primary treatment. These treatments, however, failed to achieve regression of the tumor, and the therapeutic effect was rated as ''no change''. The primary treatment was therefore, discontinued, and intratumoral injections of OK-432 and Mitomycin C were tried as the secondary treatment. Following the administration, the tumor mass disappeared, and, on histological examination, there were no findings suggestive of malignancy (complete response). (author)

313

Quantitative PCR Protocol  

Science.gov (United States)

This protocol describes how to genotype mice using Quantitative Polymerase Chain Reaction (PCR). The protocol focuses specifically on Ts65Dn mice, but can be used as a basis for genotyping ohter strains.

The Jackson Laboratory (The Jackson Laboratory)

2012-01-06

314

A Short DNA Sequence Confers Strong Bleomycin Binding to Hairpin DNAs.  

Science.gov (United States)

Bleomycins A5 and B2 were used to study the structural features in hairpin DNAs conducive to strong BLM-DNA interaction. Two members of a 10-hairpin DNA library previously found to bind most tightly to these BLMs were subsequently noted to share the sequence 5'-ACGC (complementary strand sequence 5'-GCGT). Each underwent double-strand cleavage at five sites within, or near, an eight base pair region of the DNA duplex which had been randomized to create the original library. A new hairpin DNA library was selected based on affinity for immobilized Fe(III)·BLM A5. Two of the 30 newly identified DNAs also contained the sequence 5'-ACGC/5'-GCGT. These DNAs bound to the Fe(II)·BLMs more tightly than any DNA characterized previously. Surface plasmon resonance confirmed tight Fe(III)·BLM B2 binding and gave an excellent fit for a 1:1 binding model, implying the absence of significant secondary binding sites. Fe(II)·BLM A5 was used to assess sites of double-strand DNA cleavage. Both hairpin DNAs underwent double-strand cleavage at five sites within or near the original randomized eight base region. For DNA 12, four of the five double-strand cleavages involved independent single-strand cleavage reactions; DNA 13 underwent double-strand DNA cleavage by independent single-strand cleavages at all five sites. DNA 14, which bound Fe·BLM poorly, was converted to a strong binder (DNA 15) by insertion of the sequence 5'-ACGC/5'-GCGT. These findings reinforce the idea that tighter DNA binding by Fe·BLM leads to increased double-strand cleavage by a novel mechanism and identify a specific DNA motif conducive to strong BLM binding and cleavage. PMID:25188011

Tang, Chenhong; Paul, Ananya; Alam, Mohammad P; Roy, Basab; Wilson, W David; Hecht, Sidney M

2014-10-01

315

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

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Full Text Available 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-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<0.001 for all. While LD simvastatin had no effect on cytokine levels, HD significantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05 and TGF-?1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05. Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the high dose caused partial improvement in profibrotic cytokine levels.

Baykal Tulek

2012-01-01

316

Response of mouse tongue epithelium to single doses of bleomycin and radiation  

International Nuclear Information System (INIS)

Both bleomycin (BLM) and local X-irradiation (25 kV) induce denudation in the tongue epithelium of the C3H-Neuherberg mouse in a dose-dependent manner. In the present study the effect of BLM alone and of combined single doses of drug and radiation were studied using the incidence of epithelial denudation as the end-point. In 'time-line' experiments, 8 mg/kg BLM were given before or after graded doses of X-rays. BLM treatment required a reduction of the radiation dose (ED50) from 15 Gy to 5-7 Gy, independent of sequence or time interval. In contrast, the time course of the response was clearly dependent on the treatment interval. Latency decreased when the drug was injected less than 2 h before irradiation with minimum latency observed at 30 min. Isobologram analysis of experiments with varying combinations of X-rays and BLM demonstrated that small drug doses were relatively more effective than larger doses, suggesting an upward concavity of the BLM dose-effective curve in vivo, i.e. a 'negative shoulder' of the curve in the low dose region. In contrast to the response to X-rays alone, which has a constant latent time to ulcer of 10 days, the latency in combined treatment was clearly shortened with increasing drug dose and at high doses eventually approximated the epithelial turnover time of 5 days. The data suggest that BLM both as a single agent and in combination with X-rays reduced the probability of abortive divisions and through this effect shortened tisions and through this effect shortened the latent time to epithelial denudation. (author)

317

The effects of combined treatment with radiation and bleomycin on the primary oral carcinoma  

International Nuclear Information System (INIS)

Eighty-two previously untreated patients with squamous cell carcinoma arising from the oral mucosa were treated by concurrent combined treatment with 22.5 Gy of radiation and 110 mg of bleomycin or 55 mg of peplomycin at our department from 1976 to 1985. Therapeutic effects were examined clinically and histologically, and the role as a preoperative treatment was discussed. Moreover, a statistical analysis was performed to determine the factors related to the histological effects. 1. The ratio of complete response was 42.7 % and the ratio of partial response was 89.0 %. 2. 59 patients had subsequent treatment with surgery. Step sections were prepared from surgically resected specimens and examined microscopically. 1) According to Shimosato's classification of histological effects, 19 belonged to Grade III/IV, 15 to IIb, 13 to IIa and 12 to I/0. 2) In 7 of 15 Grade IIb patients, residual survival cancer cells were not observed at the margin of the area previously occupied by tumor at the beginning of treatment. Accordingly, 44.1 % (7 with IIb and 19 with III/IV) of 59 patients may be controlled by the more conservative surgery. 3. 18 patients with CR received additional combined therapy alone without any further treatment. Local control rate of these patients was 66.7 %. Therefore, 31 patients (these 12 patients and 19 of Grade III/IV) could be controlled by this therapy alone. 4. The histological effects significantly depended on the following factors of tumors; size, on the following factors of tumors; size, growth pattern, and degree of histologic differentiation. 82.2 % of 73 patients could be classified into good effective group or poor group accurately by the quantification theory Type II of Hayashi. It is considered that this method is useful for predicting the effects of this combined treatment. (author) 57 refs

318

Potentiation of the mutagenicity and recombinagenicity of bleomycin in yeast by unconventional intercalating agents.  

Science.gov (United States)

Interactions between bleomycin (BLM) and conventional or unconventional intercalating agents were analyzed in an assay for mitotic gene conversion at the trp5 locus and reversion of the ilv1-92 allele in Saccharomyces cerevisiae strain D7. BLM is a potent recombinagen and mutagen in the assay. Various chemicals modulate the genetic activity of BLM, producing either antimutagenic effects or enhanced genotoxicity. Effects of cationic amino compounds include enhancement of BLM activity by aminoacridines and protection against BLM by aliphatic amines. The potentiation of BLM is similar to findings in a micronucleus-based BLM amplification assay in Chinese hamster V79 cells. In this study, the amplification of BLM activity was explored in yeast using known intercalators, compounds structurally related to known intercalators, and unconventional intercalators that were identified on the basis of computer modeling or results in the Chinese hamster BLM amplification assay. As shown in previous studies, the classical intercalator 9-aminoacridine (9AA) caused dose-dependent enhancement of BLM activity. Other compounds found to enhance the induction of mitotic recombination and point mutations in strain D7 were chlorpromazine, chloroquine, mefloquine, tamoxifen, diphenhydramine, benzophenone, and 3-hydroxybenzophenone. The increased activity was detectable by cotreatment of yeast with BLM and the modulator compound in growth medium or by separate interaction of the intercalator with DNA followed by BLM treatment of nongrowing cells in buffer. The data support the interpretation drawn from micronucleus assays in mammalian cells that BLM enhancement results from DNA intercalation and may be useful in detecting noncovalent interactions with DNA. Environ. PMID:20839230

Hoffmann, George R; Laterza, Amanda M; Sylvia, Katelyn E; Tartaglione, Jason P

2011-03-01

319

Preventive effect of chrysin on bleomycin-induced lung fibrosis in rats.  

Science.gov (United States)

The aim of the current study is determination of protective effect of chrysin (CRS), a natural flavonoid, on cell injury produced by lung fibrosis induced with bleomycin (BLC) in rats. Twenty-eight female rats were assigned to four groups as follows: control group, CRS group; 50 mg/kg CRS was continued orally for 14 days, BLC group; a single intratracheal injection of BLC (2.5 mg/kg body weight in 0.25 ml phosphate buffered saline), BLC?+?CRS group; 50 mg/kg CRS was administered 1 day before the intratracheal BLC injection and continued for 14 days orally. All animals were sacrificed at day 14th after BLC administration. The semiquantitative assessment of histopathological consisting of lung inflammation and collagen deposition, tissue levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reducted glutathione (GSH) were measured. BLC provoked histological changes consisting of alveolar congestion, increase connective tissue, infiltration, and the thickness of alveolar wall were detected significantly when compared to the control group (p???0.0001). CRS supplementation significantly restored these histological damages (p???0.0001). The level of tissue TBARS was increased with BLC (p?TBARS was significantly reversed by CRS administration. Also, BLC administration reduced tissue activities of SOD, GPx, CAT, and GSH in the lung tissue compared to control group (p?

Kilic, Talat; Ciftci, Osman; Cetin, Asli; Kahraman, Hasan

2014-12-01

320

Bleomycin hydrolase and hyperhomocysteinemia modulate the expression of mouse proteins involved in liver homeostasis.  

Science.gov (United States)

The liver is the major contributor to homocysteine (Hcy) metabolism and fatty liver disease is associated with hyperhomocysteinemia. Bleomycin hydrolase (Blmh) is an aminohydrolase that also participates in Hcy metabolism by hydrolyzing Hcy-thiolactone. To gain insight into hepatic functions of Blmh, we analyzed the liver proteome of Blmh(-/-) and Blmh(+/+) mice in the absence and presence of diet-induced (high methionine) hyperhomocysteinemia using 2D IEF/SDS-PAGE gel electrophoresis and MALDI-TOF mass spectrometry. We identified eleven liver proteins whose expression was significantly altered as a result of the Blmh gene inactivation. The differential expression (Blmh(-/-) vs. Blmh(+/+)) of four liver proteins was lower, of two proteins was higher, and was further modified in mice fed with a hyperhomocysteinemic high-Met diet. The down-regulated proteins are involved in lipoprotein metabolism (ApoA1, ApoE), antigen processing (Psme1), energy metabolism (Atp5h, Gamt), methylglyoxal detoxification (Glo1), oxidative stress response (Sod1), and inactivation of catecholamine neurotransmitters (Comt). The two up-regulated proteins are involved in nitric oxide generation (Ddah1) and xenobiotic detoxification (Sult1c1). We also found that livers of Blmh(-/-) mice expressed a novel variant of glyoxalase domain-containing protein 4 (Glod4) by a post-transcriptional mechanism. Our findings suggest that Blmh interacts with diverse cellular processes-from lipoprotein metabolism, nitric oxide regulation, antigen processing, and energy metabolism to detoxification and antioxidant defenses-that are essential for liver homeostasis and that modulation of these interactions by hyperhomocysteinemia underlies the involvement of Hcy in fatty liver disease. PMID:24633403

Suszy?ska-Zajczyk, Joanna; Wróblewski, Jacek; Utyro, Olga; Luczak, Magdalena; Marczak, Lukasz; Jakubowski, Hieronim

2014-06-01

 
 
 
 
321

Point- To- Point Protocol  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 res...

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

2012-01-01

322

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

323

Adaptation of TURN protocol to SIP protocol  

Directory of Open Access Journals (Sweden)

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.

Mokhtar Keche

2010-01-01

324

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

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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

2010-04-01

325

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

326

The Effect of Bleomycin to the Satellite Association who were Exposed to Radiation (X-Ray Chronically  

Directory of Open Access Journals (Sweden)

Full Text Available Beginning with the therapeutic dose and increasing three differentdoses and three different periods of time Bleomycin (Bleomycin 0.3 ?g/ml, 3?g/ml and 30 ?g/ml, 6,24, 48 hours were added to blood which was beingcultured on 5 samples who were exposed to radiation (x-ray chronically.The satellite association was evaluated in 2639 metaphases frompreparations belong to control and experiment groups.The satellite association was showed difference value to the differencebleomycin dose and the between difference samples. As the satelliteassociation 31.7% for the control group, this value fall to 30.9% at 0.3?g/ml, 27.2% at 3 ?g/ml and 19.7% at 30 ?g/ml. Statistically; there were nosignificant differences between in the 6 hour control group and dose groups(P>0.05. There were significant differences between in the 24 hour controlgroup and 30 ?g/ml dose groups (P<0.05. There were significantdifferences between in the 48 hour control group and 3 ?g/ml and 30 ?g/mldose groups (P<0.01.

Hilmi ?si

2004-01-01

327

SD rats response to the cyclophosphamide and bleomycin administration by means of the chromosomal aberration assay in bone marrow.  

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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.

Luis Alfredo Rosario Fernández

2010-03-01

328

Interaction of the antiemetics ondansetron and granisetron with the cytotoxicity induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in vitro  

Energy Technology Data Exchange (ETDEWEB)

At cancer treatment, the use of antiemetics are often needed due to induction of nausea and vomiting. Some antiemetics have been shown to interact with the direct cytotoxic effects. The newly developed antiemetics have, so far as we know, not been studied in this respect. In the present study, the effects of the 5-HT{sub 3} receptor antagonists ondansetron and granisetron were evaluated on the cytotoxicity, induced by irradiation, bleomycin, epirubicin, estramustine, and cisplatin using fibroblasts (V79) and lung cancer cells (P31) in vitro. Ondansetron or granisetron (10{sup -5} mol/l) had no effect on the survival of irradiated cells. Granisetron (10{sup -5} mol/l) significantly potentiated cytoxocity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10{sup -7} mol/l) on the cytotoxic effect of 25 mg/l bleomycin, and estramustine (80 mg/l) seemed additive to lung cancer cells. Ondansetron was non-interactive with the cytotoxicity induced by any of the anti-cancer drugs. Although the encountered observation with an enhancing effect of granisetron on the epirubicin-induced cytotoxicity is seen in a specific experimental situation in vitro, the fact that 5-HT{sub 3} receptor antagonists are routinely used during cancer treatment indicate that attention should be given to a possible interaction with the antineoplastic action of cancer treatment. (orig.).

Behnam Motlagh, P. [Dept. of Oncology, Umeaa Univ. Hospital (Sweden); Henriksson, R. [Dept. of Oncology, Umeaa Univ. Hospital (Sweden); Grankvist, K. [Dept. of Clinical Chemistry, Umeaa Univ. Hospital (Sweden)

1995-12-31

329

Modeling Transport Layer Protocols  

Science.gov (United States)

In a layered communication architecture, transport layer protocols handle the data exchange between processes on different hosts over potentially lossy communication channels. Typically, transport layer protocols are either connection-oriented or are based on the transmission of individual datagrams. Well known transport protocols are the connection-oriented Transmission Control Protocol (TCP) [372] and the User Datagram Protocol (UDP) [370] as well as the Stream Control Transmission Protocol (SCTP) [340] and DCCP, the Datagram Congestion Control Protocol [259]. In this chapter, we focus on the modeling process of the transport layer. While we mostly use TCP and UDP as a base of comparison from this point, we emphasize that the methodologies discussed further on are conferrable to virtually any transport layer in any layered communication architecture.

Sasnauskas, Raimondas; Weingaertner, Elias

330

Assessment of preferential cleavage of an actively transcribed retroviral hybrid gene in murine cells by deoxyribonuclease I, bleomycin, neocarzinostatin, or ionizing radiation  

International Nuclear Information System (INIS)

Preferential cleavage induced by bleomycin, neocarzinostatin, or ionizing radiation in a transcribed cellular gene was evaluated through comparisons with deoxyribonuclease I. The glucocorticoid-inducible LTL gene previously described served as the specific DNA target. A Southern blot analysis was used to specifically assess cleavage of the LTL gene in nuclei isolated from cells either treated or untreated with the synthetic glucocorticoid dexamethasone. Hypersensitivity of the gene to bleomycin or neocarzinostatin, which paralleled deoxyribonuclease I hypersensitivity, was evident only in nuclei isolated from dexamethasone-treated cells. Like deoxyribonuclease I, sites of dexamethasone-inducible drug hypersensitivity were coincident with the binding region for the glucocorticoid receptor found within the regulatory sequences of the LTL gene. In contrast, no hypersensitivity to ionizing radiation was evident. Although bleomycin and neocarzinostatin showed qualitatively similar preferences for the threshold LTL gene, quantitative evaluations of damage to total cellular DNA by filter elution showed that the relative specificity of bleomycin for the hypersensitive region was much less than that of either deoxyribonuclease I or neocarzinostatin

331

Intratumoral 57Co-bleomycin administration in carcinomas of the oral cavity. Experiments in the xenogeneic nude mouse and clinical pilot study  

International Nuclear Information System (INIS)

Experiments concerning the kinetics and biodistribution of 57Co-bleomycin in three different lines of the squamous cell carcinoma of the oral cavity in a nude-mouse model yielded a more than tenfold higher concentration after single intratumoral application of an aqueous solution of 57Co-labelled bleomycin in spite of a remarkable drain of radioactivity in the tumor up to 48 hours post application, compared to intravenous injection. The distribution of the radiopharmaceutical within the tumor was determining by autoradiography. The xenografts were removed and cut (5 ?m) 1, 5, 24, and 28 hours after bleomycin administration, respectively. The preparations were covered with an autoradiographic film and exposed for about three weeks. Thereafter an inhomogenous distribution of the radioactive nuclide was produced within the tumor, and a particularly high activity concentration could be demonstrated in the necrotic tumor areas. The results obtained from the animal experiments have been corroborated by a pilot study consisting of bleomycin application in 9 patients with a carcinoma of the oral mucosa. (author)

332

The valence state of technetium-99 in its complexes with bleomycin, 1-hydroxy-ethylidene-1,1-diphosphonate and human serum albumin  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The valence state of technetium-99 in its complexes with bleomycin, 1-hydroxy-ethylidene-1,1-diphosphonate and human serum albumin was determined by titration of 99TcO4? with Sn(II) in the presence of these complexing agents. Both direct titration, and addition of an excess of Sn(II) and back-titration with iodine was employed.

Korteland, J.; Dekker, B. G.; Ligny, C. L.

1980-01-01

333

Atorvastatin Attenuates Bleomycin-Induced Pulmonary Fibrosis via Suppressing iNOS Expression and the CTGF (CCN2/ERK Signaling Pathway  

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Full Text Available Pulmonary fibrosis is a progressive and fatal lung disorder with high mortality rate. To date, despite the fact that extensive research trials are ongoing, pulmonary fibrosis continues to have a poor response to available medical therapy. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known for its broad pharmacological activities, remains a remedy against multiple diseases. The present study investigated the antifibrotic potential of atorvastatin against bleomycin-induced lung fibrosis and to further explore the possible underlying mechanisms. Our results showed that atorvastatin administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. Atorvastatin reduced malondialdehyde (MDA level and lung indices. Atorvastatin also markedly decreased the expression of inducible nitric oxide synthase (iNOS in lung tissues and, thus, prevented nitric oxide (NO release in response to bleomycin challenge. Furthermore, atorvastatin exhibited target down-regulation of connective tissue growth factor (CTGF (CCN2 and phosphorylation extracellular regulated protein kinases (p-ERK expression. Taken together, atorvastatin significantly ameliorated bleomycin-induced pulmonary fibrosis in rats, via the inhibition of iNOS expression and the CTGF (CCN2/ERK signaling pathway. The present study provides evidence that atorvastatin may be a potential therapeutic reagent for the treatment of lung fibrosis.

Bo Zhu

2013-12-01

334

Comparison of 67Ga-citrate, 111In-bleomycin and 99sup(m)Tc-citrate in the evaluation of pulmonary lesions  

International Nuclear Information System (INIS)

A total of 128 patients were examined using three tumor localizing agents, 99sup(m)Tc-citrate, 111In-bleomycin and 67Ga-citrate. All these patients had clinical symptoms of pulmonary disease and chest X-rays. Twenty-two patients were excluded from the original number. Of the 106 remaining patients, 14 were benign cases and 92 malignant. A scan with a ?-camera was performed 3 to 4 h following an intravenous injection of 15 mCi of 99sup(m)Tc-citrate. Upon completion of this examination, the patient was given 2.5 mCi of 67Ga-citrate and 72 h later, scans were obtained using a 5 in. rectilinear scanner. Fifteen days later 2.5 mCi of 111In-bleomycin was given and a similar examination to that of gallium was performed. In evaluating benign lesions, 99sup(m)Tc-citrate gave no false positive results, while 111In-bleomycin gave 5% and 67Ga-citrate 20%. In the case of malignant lesions, 67Ga-citrate gave 79% true positive diagnoses, 111In-bleomycin 65% and 99sup(m)Tc-citrate (of 57 evaluated patients) 46%. (orig.)

335

position statement on gypsum protocol  

...this position statement A quality protocol setting out end-of-waste...protocols.htm. As the quality protocol (QP) is voluntary, the purpose...the requirements of the quality protocol; • recycled gypsum that does not...

336

Evaluación de implantes de norgestomet reutilizados en protocolos de sincronización del estro en vacas Brahman / Evaluation of reused norgestomet implants in estrus synchronization protocols in Brahman cows  

Scientific Electronic Library Online (English)

Full Text Available SciELO Colombia | Language: Spanish Abstract in spanish Objetivo. Evaluar las concentraciones de progesterona, la manifestación de estro y las tasas de preñez en vacas Bos indicus sometidas a varios protocolos de sincronización del estro con un implante de norgestomet usado previamente. Materiales y métodos. Sesenta vacas recibieron un implante auricular [...] de norgestomet reutilizado y fueron distribuidas en uno de cuatro protocolos: (1) benzoato de estradiol (BE) + progesterona (P4) + prostaglandina F2? (PG) (BE+P4+PG); (2) valerato de estradiol (VE) + norgestomet (NG) (VE+NG); (3) el mismo protocolo BE+P4+PG, asociado con 400 UI de gonadotropina coriónica equina (eCG) (BE+P4+PG+eCG); (4) el mismo protocolo VE+NG, asociado con 400 UI de eCG (VE+NG+eCG). El implante fue removido el día 9, con inseminación artificial (IA) 12 horas después de la detección del estro. La preñez fue diagnosticada 45 días después de la IA. Las muestras de sangre fueron tomadas los días 0, 4 y 9 (después de colocar el implante) para el análisis de progesterona por RIA. Resultados. En el día 4, las concentraciones de progesterona fueron menores en vacas tratadas con BE+P4+PG (0.90 ± 0.73 ng/ml; p0.05). Conclusiones. Los implantes de norgestomet reutilizados fueron eficaces para sincronizar el estro y alcanzar tasas de preñez adecuadas en vacas Brahman. Abstract in english Objective. To evaluate progesterone concentrations, occurrence of estrus and pregnancy rates in Bos indicus cows submitted to several estrous synchronization protocols with previously used Norgestomet implants. Materials and methods. Sixty cows were given a reused Norgestomet ear implant on Day 0 an [...] d were assigned to receive one of four protocols: (PROT 1) estradiol benzoate (EB) + progesterone (P4) + prostaglandin F2? (PG) (EB+P4+PG); (PROT 2) estradiol valerate (EV) + norgestomet (NG) (EV+NG); (PROT 3) same as EB+P4+PG protocol, plus a 400 UI equine chorionic gonadotropin (eCG) (EB+P4+PG+eCG); (PROT 4) same as EV+NG protocol, plus a 400 UI eCG (EV+NG+eCG). The implant was removed on Day 9, with artificial insemination (AI) 12 h after detection of estrus. Pregnancy was diagnosed 45 d after AI. Blood samples were collected on Day 0, 4 and 9 (after ear implant was placed), for progesterone analysis by RIA. Results. On day 4, progesterone concentrations were lower in cows treated with EB+P4+PG (0.90 ± 0.73 ng/ml; p0.05). Conclusions. Reusing Norgestomet implants was effective for synchronizing estrus and promote satisfactory pregnancy rates in Brahman cows.

Luis, Uribe-Velásquez; Adriana, Correa-Orozco; Lina, Cuartas-Betancurth; Diego, Villamizar-Ramirez; Santiago, Ángel-Botero.

2013-01-01

337

Biosynthesis of collagen crosslinks. III. In vivo labeling and stability of lung collagen in rats with bleomycin-induced pulmonary fibrosis  

International Nuclear Information System (INIS)

Rats were injected intraperitoneally with 1 mCi (each) of [3H]lysine at Day 11 of neonatal life to label their lung collagen. Five weeks later, half of the animals were given an intratracheal injection of 1.5 U of bleomycin sulfate via a tracheostomy; control animals received saline intratracheally by the same technique. Age-matched groups of control and bleomycin-treated rats were killed, and their lung collagen was analyzed at zero (control animals only), 1, 2, 4, 6, and 10 wk after bleomycin administration, a time course appropriate for development of pulmonary fibrosis in this animal model. We measured radioactivity in hydroxylysine and in the difunctional collagen crosslinks hydroxylysinonorleucine and dihydroxylysinonorleucine at each time point. No evidence of breakdown of this pool of mature, preformed collagen was observed in lungs of either the control or the bleomycin-treated rats. We also measured the total lung content of hydroxypyridinium, a trifunctional collagen crosslink, by its intrinsic fluorescence. There was no evidence of collagen degradation in lungs of either group of rats by this criterion either. We conclude that there is no biochemically detectable turnover of mature lung collagen, defined as that pool of lung collagen that is obligatorily extracellular (i.e., crosslinked and containing labeled hydroxylysine from an injection of precursor 5 to 15 wk earlier), in either normal rat lungs or lungs of rats made fibrotic with bleomycin. Statistical analysis of the data suggests that our methodology was sensitive and precise enough to have detected turnover of less than 0.5% of lung collagen per day, some 20-fold less than estimates of lung collagen turnover that have been suggested to be occurring in vivo by others using different techniques and presumably studying different pools of lung collagen

338

Long-term treatment with fasudil improves bleomycin-induced pulmonary fibrosis and pulmonary hypertension via inhibition of Smad2/3 phosphorylation.  

Science.gov (United States)

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. PMID:23928001

Bei, Yihua; Hua-Huy, Thông; Duong-Quy, Sy; Nguyen, Viet-Ha; Chen, Weihua; Nicco, Carole; Batteux, Frédéric; Dinh-Xuan, Anh Tuan

2013-12-01

339

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English 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 compar [...] ados 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. 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 bleo [...] mycin 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.

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

340

siRNA against plasminogen activator inhibitor-1 ameliorates bleomycin-induced lung fibrosis in rats  

Science.gov (United States)

Aim: Plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. The present study was undertaken to examine the effects on pulmonary fibrosis of silencing PAI-1 expression with small interfering RNA (siRNA) and to assess the possible underlying mechanisms. Methods: Male Wistar rats were subjected to intratracheal injection of bleomycin (BLM, 5 mg/kg, 0.2 mL) to induce pulmonary fibrosis. Histopathological changes of lung tissue were examined with HE or Masson's trichrome staining. The expression levels of ?-smooth muscle actin (?-SMA), collagen type-I and type-III, caspase-3, as well as p-ERK1/2 and PI3K/Akt in the lung tissue were evaluated using imunohistochemistry and Western blot analyses. The fibroblasts isolated from BLM-induced fibrotic lung tissue were cultured and transfected with pcDNA-PAI-1 or PAI-1siRNA. The expression level of PAI-1 in the fibroblasts was measured using real time RT-PCR and Western blot analysis. The fibroblast proliferation was evaluated using MTT assay. Results: Intratracheal injection of PAI-1-siRNA (7.5 nmoL/0.2 mL) significantly alleviated alveolitis and collagen deposition, reduced the expression of PAI-1, ?-SMA, collagen type-I and collagen type-III, and increased the expression of caspase-3 in BLM-induced fibrotic lung tissue. In consistence with the in vivo results, the proliferation of the cultured fibroblasts from BLM-induced fibrotic lung tissue was inhibited by transfection with PAI-1-siRNA, and accelerated by overexpression of PAI-1 by transfection with pcDNA-PAI-1. The expression of caspase-3 was increased as a result of PAI-1 siRNA transfection, and decreased after transfection with pcDNA-PAI-1. In addition, the levels of p-ERK1/2 and PI3K/Akt in the fibrogenic lung tissue were reduced after treatment with PAI-1siRNA. Conclusion: The data demonstrate that PAI-1 siRNA inhibits alveolitis and pulmonary fibrosis in BLM-treated rats via inhibiting the proliferation and promoting the apoptosis of fibroblasts. Suppression ERK and AKT signalling pathways might have at least partly contributed to this process. Targeting PAI-1 is a promising therapeutic strategy for pulmonary fibrosis. PMID:22659625

Zhang, Yan-ping; Li, Wen-bin; Wang, Wei-li; Liu, Jian; Song, Shu-xia; Bai, Lin-lin; Hu, Yu-yan; Yuan, Ya-dong; Zhang, Min

2012-01-01

 
 
 
 
341

Attenuation of bleomycin-induced lung injury and oxidative stress by N-acetylcysteine plus deferoxamine.  

Science.gov (United States)

Reactive oxygen species (ROS) play an important role in the pathogenesis of pulmonary injury and antioxidant therapy may be useful with impaired oxidative defense mechanism. This study examines the effect of N-acetylcysteine (NAC) and deferoxamine (DFX) on inflammatory indicators and oxidative stress in the lungs of mice exposed to bleomycin (BLM). The animals received endotracheally a single dose of BLM (2.5 U/kg body weight dissolved in 0.25 ml of 0.9% NaCl) or saline (0.9% NaCl) and were divided into eight groups (n=8): saline; BLM; saline+NAC; BLM+NAC; saline+DFX; BLM+DFX; saline+NAC+DFX; BLM+NAC+DFX. Treatments with NAC (20mg/kg) or DFX (30 mg/kg) were administered for 60 days after BLM exposure. Lactate dehydrogenase (LDH) activity and total cell count, neutrophil and protein concentration were determined in the bronchoalveolar lavage fluid (BALF). Lipid peroxidation thiobarbituric acid-reactive species (TBARS), oxidative protein damage (carbonyl contents), and catalase and superoxide dismutase activities were determined in the lung tissue. BLM administration resulted in lung lesion as determinated lung histology, which is almost completely prevented by NAC plus DFX. The results of total cell counts and neutrophils and LDH increased after BLM exposure and were reduced with NAC. DFX and NAC plus DFX also caused a significant decrease of LDH activity. The increased malondialdehyde equivalents and carbonyl contents in lung tissue produced by BLM were also prevented by NAC plus DFX. However, the isolated use of NAC increased lipid peroxidation. SOD activity increased after BLM exposure only in the group treated with DFX and catalase activity not was altered in the presence of BLM. Data presented here indicates that the isolated use of NAC had limited effects on BLM-induced pulmonary oxidative stress in mice. The use of DFX improves the defense response and in association with NAC may be a good alternative in the treatment or prevention of diseases that have ROS and iron involved in their pathogenesis. PMID:17904883

Teixeira, Kelly C; Soares, Fernanda S; Rocha, Luís G C; Silveira, Paulo C L; Silva, Luciano A; Valença, Samuel S; Dal Pizzol, Felipe; Streck, Emilio L; Pinho, Ricardo A

2008-01-01

342

Point- To- Point Protocol  

Directory of Open Access Journals (Sweden)

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,

2012-11-01

343

Rejoining of double strand breaks in normal human and ataxia-telangiectasia fibroblasts after exposure to /sup 60/Co. gamma. -rays, /sup 241/Am. cap alpha. -particles or bleomycin  

Energy Technology Data Exchange (ETDEWEB)

The rejoining of DNA double strand breaks (dsb) induced by /sup 60/Co ..gamma..-rays, /sup 241/Am ..cap alpha..-particles or bleomycin was measured by neutral filter elution. In agreement with their colony-forming ability, ataxia-telangiectasia cells (AT2BE) and normal fibroblasts exhibited similar dsb rejoining capacity following ..cap alpha..-irradiation, but showed marked differences in the rejoining kinetics of dsb induced by ..gamma..-rays or bleomycin.

Coquerelle, T.M.; Luecke-Huhle, C.; Weibezahn, K.F.

1987-02-01

344

Cooperative Hybrid ARQ Protocols: Unified Frameworks for Protocol Analysis  

CERN Document Server

Cooperative hybrid-ARQ (HARQ) protocols, which can exploit the spatial and temporal diversities, have been widely studied. The efficiency of cooperative HARQ protocols is higher than that of cooperative protocols, because retransmissions are only performed when necessary. We classify cooperative HARQ protocols as three decode-and-forward based HARQ (DF-HARQ) protocols and two amplified-and-forward based (AF-HARQ) protocols. To compare these protocols and obtain the optimum parameters, two unified frameworks are developed for protocol analysis. Using the frameworks, we can evaluate and compare the maximum throughput and outage probabilities according to the SNR, the relay location, and the delay constraint for the protocols.

Byun, Ilmu

2008-01-01

345

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

346

Dexamethasone attenuates bleomycin-induced lung fibrosis in mice through TGF-?, Smad3 and JAK-STAT pathway  

Science.gov (United States)

In order to find the possible mechanism of Dexamethasone (Dex) during curing fibrosis, the bleomycin (BLM)-induced mice model was used. After fibrosis were induced by BLM, histopathological evaluation and RT-PCR were employed to detect the expression of TGF-?1, Smad3 and STAT1. It was found that BLM promoted the development of inflammation, leading to severe pulmonary fibrosis with the increasing of TGF-?1, Smad3 and STAT1. After Dex treatment, the expression of TGF-?1, Smad3 and STAT1 showed a little higher with alleviation of the fibrosis. Thus it is concluded that there is a possible pathway of mouse pulmonary fibrosis model through TGF-?, Smad3 and JAK-STAT pathway. PMID:25356121

Shi, Keyun; Jiang, Jianzhong; Ma, Tieliang; Xie, Jing; Duan, Lirong; Chen, Ruhua; Song, Ping; Yu, Zhixin; Liu, Chao; Zhu, Qin; Zheng, Jinxu

2014-01-01

347

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.

Turgay Budak

2004-01-01

348

The use of bleomycin labelled with sup(99m)Tc in the diagnosis of neoplasms of the visual system  

International Nuclear Information System (INIS)

The authors report their preliminary experiences in the following case: choroid malignant melanoma, retinoblastoma, metastatic carcinoma of the iris and retina, and pseudotumour of the orbit. Significant differences were found in accumulation of BLEO sup(99m)Tc between the healthy eye and the eye with malignant melanoma and retinoblastoma, and metastatic carcinoma of the iris. In the investigations with the use of sodium pertechnate such differences were found only in retinoblastoma. In orbital pseudotumour and in metastatic retinal tumour no differences in radioactivity levels were found between the orbits after treatment with cytostatic drugs. Differences were demonstrated between radioactivity distributions in scintigrams of both orbits in cases of very small neoplasms. The method with bleomycin labelled with sup(99m)Tc used for diagnostic purposes was found to be very useful. (author)

349

Coded Splitting Tree Protocols  

DEFF Research Database (Denmark)

This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main design problem is determining the order of splitting, which enables successful decoding as early as possible. Evaluations show that the proposed protocol provides considerable gains over the standard tree splitting protocol applying SIC. The improvement comes at the expense of an increased feedback and receiver complexity.

SØrensen, Jesper Hemming; Stefanovic, Cedomir

2013-01-01

350

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

2005-11-01

351

77 FR 1917 - Madrid Protocol  

Science.gov (United States)

...Office Madrid Protocol ACTION: Proposed...certification marks. Individuals and businesses that use or...USPTO). The Protocol Relating to...the Madrid Protocol. The USPTO...Affected Public: Individuals or households; businesses or...

2012-01-12

352

Linear Logical Voting Protocols  

DEFF Research Database (Denmark)

Current approaches to electronic implementations of voting protocols involve translating legal text to source code of an imperative programming language. Because the gap between legal text and source code is very large, it is difficult to trust that the program meets its legal specification. In response, we promote linear logic as a high-level language for both specifying and implementing voting protocols. Our linear logical specifications of the single-winner first-past-the-post (SW- FPTP) and single transferable vote (STV) protocols demonstrate that this approach leads to concise implementations that closely correspond to their legal specification, thereby increasing trust.

DeYoung, Henry; Schürmann, Carsten

2012-01-01

353

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)

354

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.

355

Timed Analysis of Security Protocols  

CERN Document Server

We propose a method for engineering security protocols that are aware of timing aspects. We study a simplified version of the well-known Needham Schroeder protocol and the complete Yahalom protocol, where timing information allows the study of different attack scenarios. We model check the protocols using UPPAAL. Further, a taxonomy is obtained by studying and categorising protocols from the well known Clark Jacob library and the Security Protocol Open Repository (SPORE) library. Finally, we present some new challenges and threats that arise when considering time in the analysis, by providing a novel protocol that uses time challenges and exposing a timing attack over an implementation of an existing security protocol.

Corin, R; Hartel, P H; Mader, A

2005-01-01

356

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  

Scientific Electronic Library Online (English)

Full Text Available SciELO Spain | Language: Spanish Abstract in spanish 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 de [...] l 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. Abstract in english 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.

357

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

2012-12-01

358

Spin-Labelled 1-Ethyl-1-Nitrosourea Prevents Doxorubicin and Bleomycin-Induced Oxidative Stress in Lungs, Hearts and Kidneys of Tumour-Bearing Mice  

Directory of Open Access Journals (Sweden)

Full Text Available This study was carried out to determine the possible protective effect of 1-ethyl-3-[4-(2, 2, 6, 6-tetramethylpiperidine-1-oxyl]-1-nitrosourea (SLENU, recently synthesised in our laboratory on doxorubicin and bleomycin-induced oxidative toxicity in C57 black tumour-bearing mice. Specifically, alterations in some biomarkers of oxidative stress, such as lipid peroxidation products measured as malondialdehyde (MDA levels and activities of the antioxidant enzymes, superoxide dismutase (SOD and catalase (CAT, were studied in lung, heart and kidney homogenates isolated from C57 black tumor-bearing mice after i.p. treatment with solutions of DOX (60 mg/kg and BLM (60 mg/kg. The same biomarkers were also measured after i.p. pretreatment of mice with SLENU (100 mg/kg. After treatment with doxorubicin, heart and kidney homogenates of mice had significantly higher productions of lipid peroxidation compared to lung homogenates. It was accompanied by increased activity of the antioxidant defence enzyme superoxide dismutase and decreased activity of catalase. Bleomycin-induced oxidative stress was confirmed by significantly higher production of lipid peroxidation in lungs compared to heart homogenates, elevation of the anti-oxidant activity of superoxide dismutase and decreased activity of catalase enzymes. After pre-treatment of the mice with SLENU, the levels of all studied oxidative stress biomarkers were significantly improved in comparison with those of the mice treated alone with either bleomycin, or doxorubicin. The present results and those from a previously demonstrated superoxide scavenging activities (SSA of the nitrosourea SLENU have enabled us to explain the protective effect of the spin-labelled nitrosourea on doxorubicin and bleomycin-induced oxidative stress by scavenging of  O2- and increased NO release.

Veselina G. Gadjeva

2014-08-01

359

Freshwater Macroinvertebrates Protocol  

Science.gov (United States)

This activity guides students through sampling, identification and counting of macroinvertebrates sampled in a GLOBE hydrology study site, and understand how the taxa composition found in the sample can be an indicator of water quality and ecosystem health. The resource includes 8 field and laboratory protocols. This resource is a protocol within the Hydrology chapter of the GLOBE Teacher's Guide. GLOBE (Global Learning and Observation to Benefit the Environment) is a worldwide, hands-on, K-12 school-based science education program.

360

USA-USSR protocol  

CERN Document Server

On 30 November the USA Atomic Energy Commission and the USSR State Committee for the Utilization of Atomic Energy signed, in Washington, a protocol 'on carrying out of joint projects in the field of high energy physics at the accelerators of the National Accelerator Laboratory (Batavia) and the Institute for High Energy Physics (Serpukhov)'. The protocol will be in force for five years and can be extended by mutual agreement.

1970-01-01

 
 
 
 
361

Appraisal of efficacy and safety of intralesional injection of high concentration of bleomycin a5 for treatment of huge macrocystic lymphatic malformations in cervical region.  

Science.gov (United States)

The objective of this study was to investigate the therapeutic effects and safety of intralesional injection of high concentration of bleomycin A5 for huge (more than 5 cm in diameter) macrocystic lymphatic malformations (LMs) in the cervical region. Thirty-two patients with huge macrocystic LMs were treated with percutaneous injection of bleomycin A5 in our department between 2006 and 2011. Among them, 13 patients had unilateral submandibular lesions, and 19 patients had lesions in anterior cervical regions. The age of patients ranged from 10 months to 29 years (mean age, 11.4 y). The concentration of the drug was as high as 2.7 mg/mL (8 mg/3 mL) with an addition of dexamethasone. The mean sessions of injection were 1.6 (1-3 sessions). Repeated injection interval was 4 to 6 weeks. The follow-up period was 6 months to 4 years after the last treatment, and the mean follow-up time was 18 months. The results were evaluated based on clinical examination and Doppler ultrasonography scan. The clinical follow-up showed excellent response in 28 of the 32 patients, whereas 4 of the 32 patients also had a satisfactory response. No serious complications were encountered. Intralesional injection of high concentration of bleomycin A5 was an effective and safe treatment of huge macrocystic LMs in the cervical region and can obtain satisfactory results esthetically and functionally without surgery. PMID:25119414

Xu, Da-Peng; Zhai, Qin-Kai; Cheng, Chen; Gong, He; Wang, Hong-Wei; Wang, Xu-Kai

2014-09-01

362

Unconditionally Secure Protocols  

DEFF Research Database (Denmark)

This thesis contains research on the theory of secure multi-party computation (MPC). Especially information theoretically (as opposed to computationally) secure protocols. It contains results from two main lines of work. One line on Information Theoretically Secure Oblivious RAMS (covered in Chapter 3 and 4), and how they are used to speed up secure computation. An Oblivious RAM is a construction for a client with a small O(1) internal memory to store N pieces of data on a server while revealing nothing more than the size of the memory N, and the number of accesses. This specifically includes hiding the access pattern. We construct an oblivious RAM that hides the client’s access pattern with information theoretic security with an amortized log3 N query overhead. And how to employ a second server that is guaranteed not to conspire with the first to improve the overhead to log2 N, while also avoiding the bottleneck of sorting networks. And we show how to utilize this construction for four-playerMPC. Another line of work (covered in Chapter 2) has results about the power of correlated randomness; meaning in a preprocessing phase the participants in a MPC protocol receive samples from some joint distribution to aid them implement the secure computation. Especially we look at the communication complexity of protocols in this model, and perfectly secure protocols. We show general protocols for any finite functionality with statistical security and optimal communication complexity (but exponential amount of preprocessing). And for two-player functionalities where only one player receives output (sender-receiver functionalities) with perfect security. We also show protocols for some specific sender-receiver tasks with both optimal communication and small preprocessing. We show lower bounds on the amount of communication and show the impossibility of general perfect protocols when both parties receive output. Also we show how to use the sender-receiver protocols with perfect security given correlated randomness to construct secure protocols in the plain model with perfect correctness.

Meldgaard, Sigurd Torkel

2013-01-01

363

Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Lung fibrosis is characterized by fibroblast proliferation and the deposition of collagens. Curcumin, a polyphenol antioxidant from the spice tumeric, has been shown to effectively counteract fibroblast proliferation and reducing inflammation and fibrotic progression in animal models of bleomycin-induced lung injury. However, there is little mechanistic insight in the biological activity of curcumin. Here, we study the effects of curcumin on the expression and activity of cathepsins which have been implicated in the development of fibrotic lung diseases. Methods We investigated the effects of curcumin administration to bleomycin stimulated C57BL/6 mice and human fetal lung fibroblasts (HFL-1 on the expression of cathepsins K and L which have been implicated in matrix degradation, TGF-?1 modulation, and apoptosis. Lung tissues were evaluated for their contents of cathepsins K and L, collagen, and TGF-?1. HFL-1 cells were used to investigate the effects of curcumin and cathepsin inhibition on cell proliferation, migration, apoptosis, and the expression of cathepsins K and L and TGF-?1. Results Collagen deposition in lungs was decreased by 17-28% after curcumin treatment which was accompanied by increased expression levels of cathepsins L (25%-39% and K (41%-76% and a 30% decrease in TGF-?1 expression. Moreover, Tunel staining of lung tissue revealed a 33-41% increase in apoptotic cells after curcumin treatment. These in vivo data correlated well with data obtained from the human fibroblast line, HFL-1. Here, cathepsin K and L expression increased 190% and 240%, respectively, in the presence of curcumin and the expression of TGF-?1 decreased by 34%. Furthermore, curcumin significantly decreased cell proliferation and migration and increased the expression of surrogate markers of apoptosis. In contrast, these curcumin effects were partly reversed by a potent cathepsin inhibitor. Conclusion This study demonstrates that curcumin increases the expression of cathepsins K and L in lung which an effect on lung fibroblast cell behavior such as proliferation, migration and apoptosis rates and on the expression of TGF-?1 in mouse lung and HFL-1 cells. These results suggest that cathepsin-inducing drugs such as curcumin may be beneficial in the treatment of lung fibrosis.

Zhang Dongwei

2011-11-01

364

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

2010-03-01

365

Blind Cognitive MAC Protocols  

CERN Document Server

We consider the design of cognitive Medium Access Control (MAC) protocols enabling an unlicensed (secondary) transmitter-receiver pair to communicate over the idle periods of a set of licensed channels, i.e., the primary network. The objective is to maximize data throughput while maintaining the synchronization between secondary users and avoiding interference with licensed (primary) users. No statistical information about the primary traffic is assumed to be available a-priori to the secondary user. We investigate two distinct sensing scenarios. In the first, the secondary transmitter is capable of sensing all the primary channels, whereas it senses one channel only in the second scenario. In both cases, we propose MAC protocols that efficiently learn the statistics of the primary traffic online. Our simulation results demonstrate that the proposed blind protocols asymptotically achieve the throughput obtained when prior knowledge of primary traffic statistics is available.

Mehanna, Omar; Gamal, Hesham El

2008-01-01

366

Symmetric cryptographic protocols  

CERN Document Server

This book focuses on protocols and constructions that make good use of symmetric pseudo random functions (PRF) like block ciphers and hash functions - the building blocks for symmetric cryptography. Readers will benefit from detailed discussion of several strategies for utilizing symmetric PRFs. Coverage includes various key distribution strategies for unicast, broadcast and multicast security, and strategies for constructing efficient digests of dynamic databases using binary hash trees.   •        Provides detailed coverage of symmetric key protocols •        Describes various applications of symmetric building blocks •        Includes strategies for constructing compact and efficient digests of dynamic databases

Ramkumar, Mahalingam

2014-01-01

367

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.

Reiner Dojen

2009-10-01

368

Evaluation of Bleomycin-induced chromosome aberrations under simulated microgravity conditions in human lymphocytes using "FISH" techniques  

Science.gov (United States)

In the present investigation we report the effects of simulated microgravity conditions (clinostat) on the induction of chromosomal aberrations in human lymphocytes in vitro by ®Bleomycin. Chromosomal aberrations have been analysed by means of fluorescent in situ hybridisation (FISH) and chromosome-specific composite DNA probes (chromosome painting). The results obtained show that, under simulated microgravity conditions, the levels of both symmetrical and asymmetrical (dicentrics, rings), the number of cells bearing "complex" aberrations and hence the total numbers of aberrations were significantly elevated at any of the dose-levels assayed, compared to the parallel treatments performed as 1g control ("ground"). Furthermore, the ratio symmetrical:asymmetrical translocations was markedly elevated under simulated microgravity conditions, compared to the findings usually observed under "normal" 1g conditions. On these bases, we are much inclined to believe that simulated microgravity, rather than limiting the resealing of DNA double strand breaks (DSB's) induced by genotoxic agents is influencing in terms of enhancement the misrejoining of DSB's which is actually responsible for the fixation of the original lesions to DNA into chromosomal aberrations. In addition, the possible different misrepair processes leading to the formation of symmetrical and asymmetrical translocations might be differentially influenced by microgravity being the symmetrical translocations significantly more represented.

Mosesso, P.; Schuber, M.; Seibt, D.; Schatz, A.; Fosci, A.; Fonti, E.; Palitti, F.

369

Experimental studies on the radiation-modifying effect of bleomycin in malignant and normal mouse tissue in vivo  

DEFF Research Database (Denmark)

The interaction between bleomycin (BLM) and radiation was studied in a C3H mammary carcinoma and its surrounding normal skin. In the skin, single and fractionated doses of sequential treatment with BLM (25 mg/kg) 24 hours prior to radiation therapy did not influence the response to irradiation, whereas simultaneous treatment with BLM given 15 minutes before radiation therapy enhanced the reaction to irradiation by a factor of 1.2 or 1.4 following treatment with one fraction or five fractions, respectively. The tumor response to irradiation was not influenced by a single sequential treatment, but five daily fractions of radiation therapy following five daily dose fractions of BLM increased the radiation dose needed to control 50% of the tumors, probably because the tumors continued to grow during the BLM treatment. Simultaneous treatment enhanced the response to irradiation by a factor of 1.2 after both single-dose and fractionated therapy. Based on these data it was concluded that none of the combined treatment schedules were able to produce a better therapeutic effect than radiation therapy alone. Furthermore, mortality due to lung fibrosis in mice treated with BLM indicated the marked toxicity of the drug. This toxicity was most pronounced after fractionated treatment and when radiation therapy and BLM were given simultaneously.

Molin, J; SØgaard, P E

1981-01-01

370

Potentiation of the bleomycin, arabinofuranosylcytosine and adriamycin-caused inhibition of DNA synthesis in lymphocytes by bestatin in vitro.  

Science.gov (United States)

Combinations of 1-beta-D-arabinofuranosylcytosine (araC), bleomycin (BLM) or adriamycin (ADM) with the dipeptide bestatin do not result in an enhanced in vitro cytotoxicity in the macrophage-free L5178y mouse lymphoma cell system. However, in macrophage-containing murine spleen lymphocytes bestatin causes a potentiating effect of the cytostatic drugs araC, BLM and ADM with respect to their potencies to inhibit DNA synthesis. In the presence of 1 microgram bestatin/ml, the ED50 concentrations causing a 50% reduction of [3H]dThd incorporation were significantly lowered; 4.3-fold in the studies with araC and BLM, and 1.8-fold in the experiments with ADM. Bestatin, given alone, displays a stimulating effect on [3H]dThd incorporation into macrophage-containing lymphocyte cultures within the concentration range 0.1-10 micrograms/ml. In contrast to the bestatin-stimulated lymphocytes, ConA-stimulated as well as LPS-stimulated lymphocytes do not show a higher sensitivity to the selected drugs inhibiting DNA synthesis. These data should encourage the practical use of bestatin in combination with araC, BLM or ADM in cancer treatment. PMID:2416570

Leyhausen, G; Schröder, H C; Schuster, D K; Maidhof, A; Umezawa, H; Müller, W E

1985-11-01

371

Melatonin Inhibits Endoplasmic Reticulum Stress and Epithelial-Mesenchymal Transition during Bleomycin-Induced Pulmonary Fibrosis in Mice  

Science.gov (United States)

Several reports indicate that melatonin alleviates bleomycin (BLM)-induced pulmonary fibrosis in rodent animals. Nevertheless, the exact mechanism remains obscure. The present study investigated the effects of melatonin on endoplasmic reticulum (ER) stress and epithelial-mesenchymal transition (EMT) during BLM-induced lung fibrosis. For the induction of pulmonary fibrosis, mice were intratracheally injected with a single dose of BLM (5.0 mg/kg). Some mice were intraperitoneally injected with melatonin (5 mg/kg) daily for a period of 3 wk. Twenty-one days after BLM injection, lung fibrosis was evaluated. As expected, melatonin significantly alleviated BLM-induced pulmonary fibrosis, as evidenced by Sirius red staining. Moreover, melatonin significantly attenuated BLM-induced EMT to myofibroblasts, as determined by its repression of ?-SMA expression. Further analysis showed that melatonin markedly attenuated BLM-induced GRP78 up-regulation and elevation of the cleaved ATF6 in the lungs. Moreover, melatonin obviously attenuated BLM-induced activation of pulmonary eIF2?, a downstream target of the PERK pathway. Finally, melatonin repressed BLM-induced pulmonary IRE1? phosphorylation. Correspondingly, melatonin inhibited BLM-induced activation of XBP-1 and JNK, two downstream targets of the IRE1 pathway. Taken together, these results suggest that melatonin alleviates ER stress and ER stress-mediated EMT in the process of BLM-induced pulmonary fibrosis. PMID:24818755

Zhao, Hui; Wu, Qing-Qing; Cao, Lin-Feng; Qing, Hou-Ying; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Liu, Rong-Ru; Xu, De-Xiang

2014-01-01

372

Bleomycin - induced DNA damage and DNA repair in chicken embryo cells as compared to X-irradiation  

International Nuclear Information System (INIS)

Following in vitro- and in ovo-exposure of chicken embryo cells, the level of bleomycin (BM) - induced damage was evaluated by using DNA synthesis, nucleoid sedimentation (SED), and viscometry of alkaline cell lysates (VISC). This damage was compared to X-irradiation, using 5.9-378 nM BM in vitro, 1.5-116 ?g BM/egg in ovo, and 2-32 Gy, respectively, in vitro as well as in ovo. With respect to BM, the most notable result is the increase in DNA synthesis and VISC at the lowest concentrations of the drug. A decrease in both parameters was observed at high BM concentrations and following exposure to X-rays, concomitantly with an increase in SED. Regarding the radiomimetic drug BM and X-rays, different modes of DNA damage and DNA repair are suggested by previous investigations and the present results. Therefore, further evidence is presented, that the chicken embryo can act as a simple, rapid and inexpensive test system to characterize the biological effects of many nucleo- and/or cytotoxic agents. (orig.)

373

N-acetylcysteine amide, a thiol antioxidant, prevents bleomycin-induced toxicity in human alveolar basal epithelial cells (A549).  

Science.gov (United States)

Bleomycin (BLM), a glycopeptide antibiotic from Streptomyces verticillus, is an effective antineoplastic drug. However, its clinical use is restricted due to the wide range of associated toxicities, especially pulmonary toxicity. Oxidative stress has been implicated as an important factor in the development of BLM-induced pulmonary toxicity. Previous studies have indicated disruption of thiol-redox status in lungs (lung epithelial cells) upon BLM treatment. Therefore, this study focused on (1) investigating the oxidative effects of BLM on lung epithelial cells (A549) and (2) elucidating whether a well-known thiol antioxidant, N-acetylcysteine amide (NACA), provides any protection against BLM-induced toxicity. Oxidative stress parameters, such as glutathione (GSH), malondialdehyde (MDA), and antioxidant enzyme activities were altered upon BLM treatment. Loss of mitochondrial membrane potential (??m), as assessed by fluorescence microscopy, indicated that cytotoxicity is possibly mediated through mitochondrial dysfunction. Pretreatment with NACA reversed the oxidative effects of BLM. NACA decreased the reactive oxygen species (ROS) and MDA levels and restored the intracellular GSH levels. Our data showed that BLM induced A549 cell death by a mechanism involving oxidative stress and mitochondrial dysfunction. NACA had a protective role against BLM-induced toxicity by inhibiting lipid peroxidation, scavenging ROS, and preserving intracellular GSH and ??m. NACA can potentially be developed into a promising adjunctive therapeutic option for patients undergoing chemotherapy with BLM. PMID:23805793

Tobwala, S; Fan, W; Stoeger, T; Ercal, N

2013-09-01

374

Topics in free radical-mediated DNA damage: purines and damage amplification - superoxic reactions - bleomycin, the incomplete radiomimetic  

International Nuclear Information System (INIS)

Only a small percentage of the DNA damage set by ionizing radiation in the living cell manifests itself as lethal. It is now increasingly accepted that clustered lesions may constitute the kind of damage that the repair enzymes cannot adequately deal with. The question is raised as to whether damage amplification reactions (radical transfer reactions) may contribute to these clustered lesions, and examples of such damage amplification reactions are given. In one example a purine is involved. With 2'-deoxy adenosine and 2'-deoxy guanosine it is shown that these purine nucleosides undergo unexpected radical reactions. Evidence for the radical transfer from the purine to the sugar moiety is provided by the formation of the 5'-aldehydes. These products have been assayed with 2-thiobarbituric acid (TBA), a reagent commonly applied to the detection of malonaldehyde. TBA-reactive material has also been assayed in ?-irradiated DNA, about one-third of this is free malonaldehyde, while the major part of the TBA-reactive material remains bound to the DNA. In contrast, bleomycin-treated DNA yields practically no free malonaldehyde, and the major TBA-reactive products are identified as the thymine and adenine base propenals. (Author)

375

Experimental studies on the radiation-modifying effect of bleomycin in malignant and normal mouse tissue in vivo  

International Nuclear Information System (INIS)

The interaction between bleomycin (BLM) and radiation was studied in a C3H mammary carcinoma and its surrounding normal skin. In the skin, single and fractionated doses of sequential treatment with BLM (25 mg/kg) 24 hours prior to radiation therapy did not influence the response to irradiation, whereas simultaneous treatment with BLM given 15 minutes before radiation therapy enhanced the reaction to irradiation by a factor of 1.2 or 1.4 following treatment with one fraction or five fractions, respectively. The tumor response to irradiation was not influenced by a single sequential treatment, but five daily fractions of radiation therapy following five daily dose fractions of BLM increased the radiation dose needed to control 50% of the tumors, probably because the tumors continued to grow during the BLM treatment. Simultaneous treatment enhanced the response to irradiation by a factor of 1.2 after both single-dose and fractionated therapy. Based on these data it was concluded that none of the combined treatment schedules were able to produce a better therapeutic effect than radiation therapy alone. Furthermore, mortality due to lung fibrosis in mice treated with BLM indicated the marked toxicity of the drug. This toxicity was most pronounced after fractionated treatment and when radiation therapy and BLM were given simultaneously

376

Enhancement of the recombinagenic and mutagenic activities of bleomycin in yeast by intercalation of acridine compounds into DNA.  

Science.gov (United States)

Strain D7 of Saccharomyces cerevisiae was used to measure the induction by bleomycin (BLM) of mitotic recombination at the trp5 locus and point mutations at ilv1 in the presence and absence of acridine compounds. BLM is a potent mutagen and recombinagen in the D7 assay. The acridines vary, some being mutagenic or recombinagenic and others not. Combined treatments were used to distinguish whether a genetically inactive acridine has no effect on the genetic activity of BLM or modulates its action. When an acridine is itself genetically active, combined treatments were used to determine whether its effects are additive with those of BLM or whether there is interaction between the two compounds. Acridine compounds that share the ability to intercalate between the base pairs of DNA but differ in their mutagenic specificity owing to the presence of different substituent groups were analysed. Clear potentiation and synergistic interactions were detected in combined treatments with BLM and aminoacridines, nitroacridines or an acridine mustard. Potentiation and synergy were also observed in sequential exposures in which the yeast were grown in the presence of acridine compounds and then treated with BLM in the absence of free acridine. The results are consistent with an increase in BLM susceptibility conferred by acridine intercalation. It is likely that the intercalating agents increase the access of BLM to the minor groove of DNA, where it abstracts a hydrogen from the 4' position of deoxyribose, creating a free radical that is processed into strand breaks. PMID:19406902

Hoffmann, George R; Ronan, Matthew V; Sylvia, Katelyn E; Tartaglione, Jason P

2009-07-01

377

Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina  

International Nuclear Information System (INIS)

Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (p 0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (p < 0.05). Therefore, our data suggest that chronic exposure of aircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals

378

The effect of extremely low frequency electromagnetic fields on the chromosomal instability in bleomycin treated fibroblast cells  

Energy Technology Data Exchange (ETDEWEB)

In order to determine the effect of Extremely Low Frequency ElectroMagnetic Fields (ELF-EMF) on the frequency of MicroNuclei (MN), aneuploidy and chromosomal rearrangement induced by BLeoMycin (BLM) in human fibroblast cells, a 60 Hz ELF-EMF of 0.8 mT field strength was applied either alone or with BLM throughout the culture period and a micronucleus-centromere assay was performed. Our results indicate that the frequencies of MN, aneuploidy and chromosomal rearrangement induced by BLM increased in a dose-dependent manner. The exposure of cells to 0.8 mT ELF-EMF followed by BLM exposure for 3 hours led to significant increases in the frequencies of MN and aneuploidy compared to BLM treatment for 3 hours alone (p<0.05), but no significant difference was observed between field exposed and sham exposed control cells. The obtained results suggest that low density ELF-EMF could act as enhancer of the initiation process of BLM rather than as an initiator of mutagenic effects in human fibroblast.

Cho, Yoon Hee; Kim, Yang Jee; Lee, Joong Won; Kim, Gye Eun; Chung, Hai Won [Seoul National University, Seoul (Korea, Republic of)

2008-12-15

379

The effect of extremely low frequency electromagnetic fields on the chromosomal instability in bleomycin treated fibroblast cells  

International Nuclear Information System (INIS)

In order to determine the effect of Extremely Low Frequency ElectroMagnetic Fields (ELF-EMF) on the frequency of MicroNuclei (MN), aneuploidy and chromosomal rearrangement induced by BLeoMycin (BLM) in human fibroblast cells, a 60 Hz ELF-EMF of 0.8 mT field strength was applied either alone or with BLM throughout the culture period and a micronucleus-centromere assay was performed. Our results indicate that the frequencies of MN, aneuploidy and chromosomal rearrangement induced by BLM increased in a dose-dependent manner. The exposure of cells to 0.8 mT ELF-EMF followed by BLM exposure for 3 hours led to significant increases in the frequencies of MN and aneuploidy compared to BLM treatment for 3 hours alone (p<0.05), but no significant difference was observed between field exposed and sham exposed control cells. The obtained results suggest that low density ELF-EMF could act as enhancer of the initiation process of BLM rather than as an initiator of mutagenic effects in human fibroblast

380

X-ray-sensitive mutants of mouse mammary carcinoma cells are hypersensitive to bleomycin and hydrogen peroxide  

International Nuclear Information System (INIS)

Radiation-sensitive mutants, SX9 and SX10, were isolated from mouse mammary carcinoma FM3A cells. The mutant SX9 complemented another radiation-sensitive strain M10 of mouse leukemia L5178Y cells, but SX10 did not. SX9 and SX10 cells were more sensitive than the wild-type cells to the lethal effects of bleomycin. The frequency of X-ray-induced mutations to 6-thioguanine resistance was much higher in SX9 cells than in the wild-type cells in the dose range up to 1 Gy, although the induced mutant frequencies were not very different between these two cell strains when compared at equivalent survival. SX9, SX10 and M10 cells were found to be far more sensitive than the respective wild-type cells to hydrogen peroxide inactivation, but the levels of catalase activity were similar among these cell strains. These mutants should be useful for cloning and identifying the human genes responsible for radiation sensitivity. (author)

 
 
 
 
381

Free flap monitoring protocol.  

Science.gov (United States)

In microsurgery, the successful salvage of free tissue transfer is dependent on the rapid decision to return to the operating room. Therefore, a free flap monitoring protocol is presented, including checking color, temperature, capillary return, and signal from a handheld Doppler ultrasonograph in an intraoperatively marked skin area directly over the pedicle. PMID:20613605

Kruse, Astrid L; Luebbers, Heinz T; Grätz, Klaus W; Obwegeser, Joachim A

2010-07-01

382

Metal Protocol Taskforce Minutes  

2. Minutes of the previous meeting and actions. 2.1. The Chair asked for any \\comments on the previous minutes. None were received ... Based on the \\tonnages delivered by the different steel protocols the taskforce ... Any other \\business. 5.1.

383

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

384

Security Protocol Design: A Case Study Using Key Distribution Protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 th...

Reiner Dojen; Tom Coffey; Anca Jurcut; Robert Gyorodi

2009-01-01

385

Composite Protocols and Networking Services  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Active Networking is concerned with the rapid definition and deployment of innovative, but reliable and robust, networking services. Towards this end we have developed a composite protocol and networking services architecture that encourages re-use of protocol functions, is well defined, and facilitates automatic checking of interfaces and protocol component properties. The architecture has been used to implement common Internet protocols and services. We will report on this work at the works...

Minden, Gary

2005-01-01

386