WorldWideScience
1

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

OpenAIRE

Between July 1979 and December 1981, 43 patients with metastatic germ-cell tumours (36 testicular non-seminomas and 7 testicular seminomas) were treated with 2-6 cycles of bleomycin, etoposide and cis-platin (BEP). Forty (93%) are alive, 37 (86%) with no evidence of disease. Of 36 men with testicular non-seminoma 30 (83.3%) are alive and disease-free at 8-38 months (median 17.0 months). In the latter group 25/28 (89.3%) who had had no prior irradiation are alive and disease-free. Fourteen non...

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

1983-01-01

2

Effects of bleomycin, etoposide and cisplatin treatment on Leydig cell structure and transcription of steroidogenic enzymes in rat testis.  

Science.gov (United States)

Cytotoxic anticancer chemotherapy affects pituitary-testicular hormonal axis in humans and in animals. This study investigated the effects on Leydig cells of three cycles of bleomycin, etoposide and cisplatin (0.75, 7.5, and 1.5mg/kg, respectively; BEP) chemotherapy in rat testis. The chemotherapy has induced hyperplasia of and degenerative changes in Leydig cells at the end of BEP exposure, which remained so even after a recovery time of 63 days. The increased testicular oxidative stress at the end of the chemotherapy returned to normal level after the recovery time. The chemotherapy has stimulated the transcription of scavenger receptor class type-B1 (SCARB1), steroidogenic acute-regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (CYP11A1), CYP17A1, and inhibited that of 17?-hydroxysteroid dehydrogenase (HSD17B6) and CYP19A1 in association with increased cholesterol and decreased testosterone levels. Even after the recovery time, the chemotherapy still had inhibitory effects on the transcription of all of the above genes in addition to luteinizing hormone receptor and HSD3B1, but not on the StAR gene. The cholesterol and testosterone levels also did not show any significant differences with the control group. The decreased testosterone level at the end of chemotherapy was probably due to inhibition of HSD3B1 and HSD17B6 genes. In conclusion, clinically relevant dose-levels and treatment protocols of BEP chemotherapy adversely affect Leydig cell function. The BEP chemotherapy inhibits the transcription of steroidogenic enzymes and that these effects sustain over an extended period of time without returning to normal levels. PMID:25523482

Al-Bader, Maie; Kilarkaje, Narayana

2015-01-15

3

Basic Education and Policy Support (BEPS) Activity.  

Science.gov (United States)

The Basic Education and Policy Support (BEPS) Activity is a multi-year, worldwide, indefinite quantity contract by which the U.S. Agency for International Development (USAID) Global Bureau Center for Human Capacity (G/HCD) can work to achieve four objectives: (1) improve the quality, efficiency, access, and equity of education, particularly basic…

Creative Associates International, Inc., Washington, DC.

4

Cloning and structure of the BepI modification methylase.  

OpenAIRE

The gene coding for a CGCG specific DNA methylase has been cloned in E. coli from Brevibacterium epidermidis. The enzyme, named BepI methylase, is probably the cognate methylase of the FnuDII isoschizomer BepI endonuclease isolated from this strain. The expression of BepI methylase in E. coli is dependent on the orientation of the cloned fragment suggesting that the gene is transcribed from a promoter on the plasmid vector. No BepI endonuclease could be detected in the clones producing BepI m...

Kupper, D.; Zhou, J. G.; Venetianer, P.; Kiss, A.

1989-01-01

5

A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)  

OpenAIRE

Background: To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-prognosis germ-cell cancer (GCC).

Daugaard, G.; Skoneczna, I.; Aass, N.; Wit, R.; Santis, M.; Dumez, H.; Marreaud, S.; Collette, L.; Lluch, J. R. G.; Bokemeyer, C.; Schmoll, H. J.

2010-01-01

6

Beamed-Energy Propulsion (BEP) Study  

Science.gov (United States)

The scope of this study was to (1) review and analyze the state-of-art in beamed-energy propulsion (BEP) by identifying potential game-changing applications, (2) formulate a roadmap of technology development, and (3) identify key near-term technology demonstrations to rapidly advance elements of BEP technology to Technology Readiness Level (TRL) 6. The two major areas of interest were launching payloads and space propulsion. More generally, the study was requested and structured to address basic mission feasibility. The attraction of beamed-energy propulsion (BEP) is the potential for high specific impulse while removing the power-generation mass. The rapid advancements in high-energy beamed-power systems and optics over the past 20 years warranted a fresh look at the technology. For launching payloads, the study concluded that using BEP to propel vehicles into space is technically feasible if a commitment to develop new technologies and large investments can be made over long periods of time. From a commercial competitive standpoint, if an advantage of beamed energy for Earth-to-orbit (ETO) is to be found, it will rest with smaller, frequently launched payloads. For space propulsion, the study concluded that using beamed energy to propel vehicles from low Earth orbit to geosynchronous Earth orbit (LEO-GEO) and into deep space is definitely feasible and showed distinct advantages and greater potential over current propulsion technologies. However, this conclusion also assumes that upfront infrastructure investments and commitments to critical technologies will be made over long periods of time. The chief issue, similar to that for payloads, is high infrastructure costs.

George, Patrick; Beach, Raymond

2012-01-01

7

Bleomycin-induced flagellate dermatitis  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english A 29-year-old woman with stage IVB Hodgkin's lymphoma was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine. Two weeks after the first cycle was completed, she developed pruritic, linear erythematous lesions in a flagellate-like pattern on the trunk, neck and arms. After oral prednis [...] one therapy and cessation of bleomycin, the lesions started to recede.

Guilherme Devidé, Mota; Adriana Marques Damasco, Penna; Regina Cláudia, Soares; Otávio Carvalho Guimarães, Baiocchi.

2014-07-01

8

Energy consumption in commercial buildings: A comparison with BEPS budgets  

Science.gov (United States)

Metered energy consumption data were collected on existing commercial buildings to help establish the proposed building energy performance standards (BEPS). The search has identified 84 buildings whose metered energy consumption is equal to or less than that proposed for their BEPS budgets and another 7 buildings whose metered consumption is less than 20 percent above their BEPS budgets. The methodology used to identify the buildings and to collect their metered energy consumption data are described. The data are analyzed and summarized and conclusions are drawn.

1980-09-01

9

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

10

Treatment of Kaposi's sarcoma with bleomycin.  

Science.gov (United States)

Two cases of Kaposi's sarcome that responded to bleomycin therapy are reported herein. The first case, resistant to various treatments, responded remarkably well after 240 mg of bleomycin was administered over a thirteen month period. The second case had rapidly progressive untreated Kaposi's sarcoma of six months's duration; a prompt response was obtained to an initial course of 105 mg of bleomycin. PMID:83223

Kim, R; Guerrero, R C; Ho, R

1979-01-01

11

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

12

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.)

13

Vincristine, bleomycin, mitomycin C, cisplatin combination  

International Nuclear Information System (INIS)

During the past five years the EORTC Gynecological Cancer Cooperative Group (G.C.C.G.) performed several studies in patients with disseminated squamous cell carcinoma of the uterine cervix (SCCUC). The first trial protocol (55802) studies the efficacy and toxicity of a bleomycin-mitomycin C based regimen to which vincristine and cisplatin were added (VBMP). The overall response rate in 50 evaluable patients was 40% and median time to progression was 48 weeks and 32 weeks for patients with complete response (16%) and partial response respectively. Of interest was that the complete remission rate in patients with only distant metastases was 30% (for patients with only lung and/or lymph nodes metastases 40%) and some of these patients had long term disease-free survival. The toxicity of the VBMP regimen was acceptable to the patients

14

Pockets of opportunity: multicultural marketing strategies for BEP growth.  

Science.gov (United States)

Ranked among the 50 largest food service corporations in America, the Randolph-Sheppard Business Enterprise Program (BEP) represents a challenging and rewarding career opportunity for Americans who are legally blind. In recent years, however, the number of facilities and facility managers has declined. Multicultural consumers represent a major emerging growth market. The multicultural market is one of the most overlooked retail markets in the United States--and the one with the most buying power and growth potential. Multicultural marketing is among the least understood strategies available to facility managers, vocational rehabilitation counselors and BEP directors. Four major minority markets are discussed and marketing strategies are offered to help BEPs target and serve these unique consumers. PMID:12897395

Schaefer, Kelly

2003-01-01

15

Effects of the "Behavior Education Program" (BEP) on Office Discipline Referrals of Elementary School Students  

Science.gov (United States)

The "Behavior Education Program" (BEP; Crone et al., 2004) is a modified check-in, check-out intervention implemented with students who are at risk for more severe problem behaviors. The purpose of this study was to evaluate the effects of the BEP on problem behavior with 12 elementary school students. Results indicated that the BEP was…

Hawken, Leanne S.; Sandra MacLeod, K.; Rawlings, Linda

2007-01-01

16

Thermonuclear reaction rates of 9Be(p, ?)10B  

International Nuclear Information System (INIS)

An excitation function of the 9Be(p, ?)10B capture reaction has been measured over the proton energy range Ep=75 to 1800 keV using a 4? summing crystal. The data are dominated by three broad resonances including interference effects with the direct-capture process. Near temperatures of T9=0.8 the reaction rates are lower by a factor 4 compared to values given in a compilation, while at other temperatures the rates are similar. ((orig.))

17

Structure of ^8B through ^7Be+p scattering  

Science.gov (United States)

Cross sections for ^7Be+p elastic and inelastic scattering were measured at the HRIBF. Beams of ^7Be at 17 incident energies betweeen Ecm=0.5-3.4 MeV bombarded CH2 targets. Scattered protons were detected in a silicon-strip detector array covering ?cm=70^o-150^o. We have performed a multi-level R-matrix analysis of the combined cross sections (about 400 data points) to determine properties of states in ^8B. The inelastic scattering data provide evidence for positive-parity states that were previously unobserved but were predicted by theory. Results and implications will be discussed.

Blackmon, J. C.; Livesay, R. J.; Greife, U.; Bardayan, D. W.; Chae, K. Y.; Champagne, A. E.; Diebel, C.; Fitzgerald, R.; Johnson, M. S.; Jones, K. L.; Kozub, R. L.; Ma, Z.; Nesaraja, C. D.; Pain, S. D.; Sarazin, F.; Shriner, J. F., Jr.; Stracener, D. W.; Smith, M. S.; Thomas, J. S.; Visser, D. W.; Wrede, C.

2007-10-01

18

Bleomycin-detectable iron in brain tissue.  

Science.gov (United States)

The normal brain contains regions with high concentrations of iron, part of which appears to be in a low molecular mass chelatable form. Iron complexes with a molecular mass of below 10,000, were measured in ultrafiltrates of homogenized gerbil brains using the bleomycin assay, and were found to average 20.5 +/- 3.5 microM (n = 8). As expected, no bleomycin detectable iron was found in the plasma of these animals. No obvious difference in the tissue levels of bleomycin-detectable iron was recorded following ischaemia and reperfusion. This is probably due to the already abundant presence of iron in the brain and the likely release of iron from protected sites due to structural damage inherent in the preparative procedures used. PMID:1712743

Gutteridge, J M; Cao, W; Chevion, M

1991-01-01

19

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...

20

Excretion and organic distribution of 57Co-bleomycin emulsions  

International Nuclear Information System (INIS)

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

21

Marker Rescue from Bleomycin-Treated CHLAMYDOMONAS REINHARDI  

OpenAIRE

A new method has been developed for gene transfer in eukaryotic cells. Chlamydomonas reinhardi, a unicellular eukaryotic alga, was treated with a lethal dose of bleomycin, an agent that induces chromosome breakage. Bleomycin-treated cells were mated with untreated cells, and the mixture was plated onto selective agar medium. The progeny that arose contained the genetic markers from the untreated parent plus a subset of the genetic markers from the bleomycin-treated parent. Those markers deriv...

Hourcade, Dennis E.

1983-01-01

22

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

DEFF Research Database (Denmark)

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

Fronczek-Munter, Ture RØnved; Bligaard, Thomas

2008-01-01

23

An Investigation of the Impact of Function of Problem Behavior on Effectiveness of the Behavior Education Program (BEP)  

Science.gov (United States)

The Behavior Education Program (BEP) is a check-in, check-out intervention implemented with students who are at-risk for engaging in more severe problem behavior. Previous research with middle and elementary school students found that the BEP was more effective with students who had adult attention maintained problem behavior. The purposes of this…

Hawken, Leanne S.; O'Neill, Robert E.; MacLeod, K. Sandra

2011-01-01

24

BID-F1 and BID-F2 domains of Bartonella henselae effector protein BepF trigger together with BepC the formation of invasome structures.  

Science.gov (United States)

The gram-negative, zoonotic pathogen Bartonella henselae (Bhe) translocates seven distinct Bartonella effector proteins (Beps) via the VirB/VirD4 type IV secretion system (T4SS) into human cells, thereby interfering with host cell signaling [1], [2]. In particular, the effector protein BepG alone or the combination of effector proteins BepC and BepF trigger massive F-actin rearrangements that lead to the establishment of invasome structures eventually resulting in the internalization of entire Bhe aggregates [2], [3]. In this report, we investigate the molecular function of the effector protein BepF in the eukaryotic host cell. We show that the N-terminal [E/T]PLYAT tyrosine phosphorylation motifs of BepF get phosphorylated upon translocation but do not contribute to invasome-mediated Bhe uptake. In contrast, we found that two of the three BID domains of BepF are capable to trigger invasome formation together with BepC, while a mutation of the WxxxE motif of the BID-F1 domain inhibited its ability to contribute to the formation of invasome structures. Next, we show that BepF function during invasome formation can be replaced by the over-expression of constitutive-active Rho GTPases Rac1 or Cdc42. Finally we demonstrate that BID-F1 and BID-F2 domains promote the formation of filopodia-like extensions in NIH 3T3 and HeLa cells as well as membrane protrusions in HeLa cells, suggesting a role for BepF in Rac1 and Cdc42 activation during the process of invasome formation. PMID:22043280

Truttmann, Matthias C; Guye, Patrick; Dehio, Christoph

2011-01-01

25

Status of the solar reaction 7Be(p,?)8B  

International Nuclear Information System (INIS)

For decades the reaction 7Be(p,?)8B has been one of the major sources of uncertainties in estimating the 8B solar neutrino flux and has played a critical role in revealing the so-called 'Solar Neutrino Problem'. A summary of the current status of this reaction is given

26

The effects of Bleomycin A5 on infantile maxillofacial haemangioma  

Directory of Open Access Journals (Sweden)

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

27

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.)

28

Is the bithiazole moiety of bleomycin a classical intercalator?  

OpenAIRE

Bleomycin is a widespread anticancerous drug, the biological activity of which having been extensively studied. Its metal ion-chelating portion has been shown to cleave DNA whereas the role of the bithiazole moiety is still questionable. In order to elucidate this problem some 2', 4-disubstituted bithiazoles structurally related to the "tripeptide S" moiety of bleomycin were synthesized and their interaction with DNA was studied using delta Tm, fluorescence, EPR and viscometry techniques. The...

He?nichart, J. P.; Bernier, J. L.; Helbecque, N.; Houssin, R.

1985-01-01

29

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

30

Mitochondrial DNA damage by bleomycin induces AML cell death.  

Science.gov (United States)

Mitochondria contain multiple copies of their own 16.6 kb circular genome. To explore the impact of mitochondrial DNA (mtDNA) damage on mitochondrial (mt) function and viability of AML cells, we screened a panel of DNA damaging chemotherapeutic agents to identify drugs that could damage mtDNA. We identified bleomycin as an agent that damaged mtDNA in AML cells at concentrations that induced cell death. Bleomycin also induced mtDNA damage in primary AML samples. Consistent with the observed mtDNA damage, bleomycin reduced mt mass and basal oxygen consumption in AML cells. We also demonstrated that the observed mtDNA damage was functionally important for bleomycin-induced cell death. Finally, bleomycin delayed tumor growth in xenograft mouse models of AML and anti-leukemic concentrations of the drug induced mtDNA damage in AML cells preferentially over normal lung tissue. Taken together, mtDNA-targeted therapy may be an effective strategy to target AML cells and bleomycin could be useful in the treatment of this disease. PMID:25820141

Yeung, ManTek; Hurren, Rose; Nemr, Carine; Wang, Xiaoming; Hershenfeld, Samantha; Gronda, Marcela; Liyanage, Sanduni; Wu, Yan; Augustine, Jeevan; Lee, Eric A; Spagnuolo, Paul A; Southall, Noel; Chen, Catherine; Zheng, Wei; Jeyaraju, Danny V; Minden, Mark D; Laposa, Rebecca; Schimmer, Aaron D

2015-06-01

31

New charge exchange model of GEANT4 for $^{9}$Be(p, n)$^{9}$B reaction  

CERN Document Server

Taking ENDF/B-VII.1 differential cross section data as input, a new data-based charge exchange model of GEANT4 dedicated to the $^{9}$Be(p, n)$^{9}$B reaction is developed. The resulting model turns out to be in good agreement with the experimental data for the neutron yield spectrum, making significant improvement compared to other GEANT4 hadronic models.

Shin, Jae Won

2014-01-01

32

Study of the Be(p, n) and Be(d, n) source reactions  

International Nuclear Information System (INIS)

We have developed lithium glass detector arrays to measure the energy spectra of neutrons below 1 MeV. The use of a calibrated neutron source spectrum allows measurement of neutron spectra from 0.070 to 14 MeV. The angular distribution and the neutron energy spectra are reported for the Be(d, n) and Be(p, n) neutron source reactions. The applications of these reactions to Boron Neutron Capture Therapy (BNCT) and neutron radiography are discussed. (author)

33

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

34

The peroxidase activity of bleomycin-Fe3+ is associated with damage to biological components.  

Science.gov (United States)

In this study, bleomycin-Fe(3+) steadily oxidized tetramethylbenzidine (TMB) in the presence of peroxides. However, the ability of bleomycin-Fe(3+) to function as a peroxidase was extremely low compared with that of other peroxidases. A characteristic property of bleomycin-Fe(3+) different from that observed for other peroxidases is its ability to oxidize TMB at the similar rate at both a pH 5 and 8 in the presence of lipid hydroperoxide (LOOH). In the present experiments, hydroxyl radicals (HO•) were generated only when bleomycin-Fe(3+) was incubated with H2O2 at a pH of 5. No generation of HO• was observed during the incubation of bleomycin-Fe(3+) with LOOH. Meanwhile, bleomycin-Fe(3+) induced the formation of LOOH from linoleic acid and alcohol dehydrogenase was inactivated by bleomycin-Fe(3+) with peroxides. Thiobarbituric acid reactive substances were formed from DNA by bleomycin-Fe(3+) with H2O2, and strand breaks were caused by bleomycin-Fe(3+) with LOOH. The oxidative substrates for bleomycin-Fe(3+) blocked the damage to biological components induced by bleomycin-Fe(3+). These results suggest that compound I-like species contribute to the process of damage to biological components induced by bleomycin-Fe(3+). PMID:25359786

Miura, Toshiaki

2015-04-01

35

Combined bleomycin and radiotherapy in oral cancer  

International Nuclear Information System (INIS)

A clinical trial comparing bleomycin (BLM) plus radiation against radiation alone is reported. One hundred and fifty-seven previously untreated T3 and T4 and N0, N1 or N2 buccal squamous cell carcinomas were entered. Eighty-four of these received the combined therapy and 73 were controls. Cobalt-60 teletherapy using to opposing fields was employed. BLM was administered intra-arterially in 42 patients, intravenously in 22 patients and intramuscularly in 20 patients. The 73 controls received physiological saline as a placebo. Total clinical healing of the lesion within the volume of irradiation eight weeks after the end of radiotherapy was termed a favourable response. Anything else was a failure. Five-year recurrence-free rates and disease-free survival were also evaluated. The favourable response rate in the study group was 78.6% and in the control 19.1%. The corresponding recurrence-free rates and five-year survival rates were 71.8 and 17%, and 65.5 and 23.5% respectively. The main toxic features were acute mucositis, pneumonitis and dermatitis. (author)

36

Bleomycin and radiation-induced lung damage in mice  

International Nuclear Information System (INIS)

Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction. (author)

37

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.)

38

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, Antónia; Mota, Raquel; Paiva, Vera

2014-01-01

39

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

40

Acute respiratory failure induced by bleomycin and hyperoxia  

Energy Technology Data Exchange (ETDEWEB)

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% O/sub 2/ 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.

Goad, M.E.P.

1985-01-01

41

Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice  

OpenAIRE

The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.

Fujita, Masaki; Ye, Qing; Ouchi, Hiroshi; Harada, Eiji; Inoshima, Ichiro; Kuwano, Kazuyoshi; Nakanishi, Yoichi

2006-01-01

42

Interaction of radiation and bleomycin in intestinal crypt cells  

International Nuclear Information System (INIS)

Using the intestinal crypt cell system, the effects of bleomycin (BLM) with radiation have been determined. The LD/sub 50/60/ in LAF1 mice used was 167 units/kg and the MTD (LD01) was 100 units/kg. Survival of crypt cells was reduced to 40% of radiation alone when drug was given 3 hr after a dose of 1100 rad, but to less than 1% when the drug was given 2 hr before. When maximum tolerated doses (MTD) were given from -48 to +48 hr relative to a dose of 843 rad, the combination was much more effective when drug was given from -12 to -2 hr before irradiation, survival dropping from 100 to 5 cells per circumference. This increased cell kill could be due to synchrony, interference with repair of BLM damage, or other factors. A radiation survival curve determined 2 hr after drug administration had a slope similar to controls, but was shifted toward lower doses. The extrapolated D/sub q/ was 0 rad. A 3 hr split dose experiment yielded survival ratios of 6 for controls and 2 for mice given the MTD 2 hr before irradiation. There appears to be a marked interaction of bleomycin and radiation, with possible inhibition of repair of the radiation damage by bleomycin and possible inhibition of repair of the bleomycin damage by radiation

43

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

International Nuclear Information System (INIS)

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

44

Fungal Cell Wall Septation and Cytokinesis Are Inhibited by Bleomycins  

Science.gov (United States)

When the essential and distinctive cell walls of either pathogenic or nonpathogenic fungi break, cytoplasmic membranes rupture and fungi die. This fungicidal activity was discovered previously on nonproliferating Saccharomyces cerevisiae cells treated briefly with the oxidative tool and anticancer drug family of bleomycins. The present studies investigated effects of bleomycin on growing fungal organisms. These included the medically important Aspergillus fumigatus and Cryptococcus neoformans, as well as the emerging human pathogen and fungal model, S. cerevisiae. Bleomycin had its highest potency against A. fumigatus. Scanning electron microscopy and thin-section transmission electron microscopy were used to study morphological growth characteristics. Killing and growth inhibition were also measured. Long, thin, and segmented hyphae were observed when A. fumigatus was grown without bleomycin but were never observed when the mold was grown with the drug. Bleomycin arrested conidial germination, hyphal development, and the progression and completion of cell wall septation. Similarly, the drug inhibited the construction of yeast cell wall septa, preventing cytokinesis and progression in the cell division cycle of S. cerevisiae. Even when cytoplasms of mother and daughter cells separated, septation and cell division did not necessarily occur. Bizarre cell configurations, abnormally thickened cell walls at mother-daughter necks, abnormal polarized growth, large undivided cells, fragmented cells, and empty cell ghosts were also produced. This is the first report of a fungicidal agent that arrests fungal growth and development, septum formation, and cytokinesis and that also preferentially localizes to cell walls and alters isolated cell walls as well as intact cell walls on nongrowing cells. PMID:14506042

Moore, Carol W.; McKoy, Judith; Del Valle, Robert; Armstrong, Donald; Bernard, Edward M.; Katz, Norman; Gordon, Ronald E.

2003-01-01

45

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

OpenAIRE

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...

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

2012-01-01

46

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

OpenAIRE

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, respective...

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

2001-01-01

47

The Rise and Attenuation of the Basic Education Programme (BEP) in Botswana: A Global-Local Dialectic Approach  

Science.gov (United States)

Using a global-local dialectic approach, this paper traces the rise of the basic education programme in the 1980s and 1990s in Botswana and its subsequent attenuation in the 2000s. Amongst the local forces that led to the rise of BEP were Botswana's political project of nation-building; the country's dire human resources situation in the decades…

Tabulawa, Richard

2011-01-01

48

Passion fruit peel extract attenuates bleomycin-induced pulmonary fibrosis in mice.  

Science.gov (United States)

Idiopathic pulmonary fibrosis is a progressive fatal lung disease characterized by excessive collagen deposition, with no effective treatments. We investigated the efficacy of natural products with high anti-inflammatory activity, such as passion fruit peel extract (PFPE), in a mouse model of bleomycin-induced pulmonary fibrosis (PF). C57BL/6J mice were subjected to a single intratracheal instillation of bleomycin to induce PF. Daily PFPE treatment significantly reduced loss of body mass and mortality rate in mice compared with those treated with bleomycin. While bleomycin-induced PF resulted in elevated total numbers of inflammatory cells, macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage fluid on both days 7 and 21, PFPE administration significantly attenuated these phenomena compared with bleomycin group. On day 7, the decreased superoxide dismutase and myeloperoxidase activities observed in the bleomycin group were significantly restored with PFPE treatment. On day 21, enhanced hydroxyproline deposition in the bleomycin group was also suppressed by PFPE administration. PFPE treatment significantly attenuated extensive inflammatory cell infiltration and accumulation of collagen in lung tissue sections of bleomycin-induced mice on days 7 and 21, respectively. Our results indicate that administration of PFPE decreased bleomycin-induced PF because of anti-inflammatory and antioxidant activities. PMID:24933624

Chilakapati, Shanmuga Reddy; Serasanambati, Mamatha; Manikonda, Pavan Kumar; Chilakapati, Damodar Reddy; Watson, Ronald Ross

2014-08-01

49

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

50

Bleomycin Sclerotherapy for Severe Symptomatic and Persistent Pelvic Lymphocele  

OpenAIRE

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 sclerot...

Fernandes, Ana Sofia; Costa, Anto?nia; Mota, Raquel; Paiva, Vera

2014-01-01

51

Production of [103Pd]Bleomycin complex for targeted therapy  

International Nuclear Information System (INIS)

Due to the anticancer properties of bleomycin (BLM) complexes, production of [103Pd]bleomycin ([103Pd]BLM) was targeted. Palladium-103 (T1/2 16.96 d) was produced via the 103Rh(p,n)103Pd nuclear reaction using a natural rhodium target. Proton energy was 18 MeV with 200 ?A irradiation for 15 h (final activity 25.9 GBq of 103Pd2+, RCP > 95%, radionuclidic purity > 99%). 103Pd was separated from the irradiated target by anion exchange using a Dowex 1z8 (Cl-)/100-200 mesh resin in the form of Pd(NH3)2Cl2 in order to react with bleomycin to yield [103Pd]BLM. Chemical purity of the final product was in accordance to the accepted limits. [103Pd]BLM was prepared with a radiochemical yield of more than 98% at 80oC in 30 min. The labeling reaction was optimized for time, temperature and ligand concentration. Radiochemical purity of more than 99% was obtained using RTLC with specific activity of about 370 MBq/mmol. The stability of the tracer was checked in the final product and presence of human serum at up to 3 h. The complex was stable in human serum at 37 oC up to 2 h of incubation. Biodistribution studies using a SPECT system performed in normal rats in the first 2-3 h. (author)

52

Pulmonary epithelial permeability in rats with bleomycin-induced pneumonitis  

International Nuclear Information System (INIS)

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

53

Pulmonary epithelial permeability in rats with bleomycin-induced pneumonitis  

Energy Technology Data Exchange (ETDEWEB)

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

Anazawa, Yoshiki; Isawa, Toyoharu; Teshima, Takeo; Miki, Makoto; Motomiya, Masakichi (Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis and Cancer)

1992-07-01

54

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

55

Interactions among iron(II) bleomycin, Lewis bases, and DNA.  

OpenAIRE

The interaction of sulfur-containing ligands with complexes of Fe(II) bleomycin [Fe(II)Blm] was investigated by comparing DNA strand-scission activity with the structural characteristics of the complex. The bithiazole ring of excess Blm can form intermolecular complexes with Fe(II)Blm and with NO-Fe(II)Blm, and the bithiazole groups of CO-Fe(II)Blm interact with the metal center. This binding can be reversed by glutathione, CO-Fe(II)Blm binds to poly(dA-dT) . poly(dA-dT) via its bithiazole gr...

Antholine, W. E.; Petering, D. H.; Saryan, L. A.; Brown, C. E.

1981-01-01

56

The low-lying electronic states of BeP: a reliable and accurate quantum mechanical prediction  

International Nuclear Information System (INIS)

A very high level of theoretical treatment (complete active space self-consistent field CASSCF/MRCI/aug-cc-pV5Z) was used to characterize the spectroscopic properties of a manifold of quartet and doublet states of the species BeP, as yet experimentally unknown. Potential energy curves for 11 electronic states were obtained, as well as the associated vibrational energy levels, and a whole set of spectroscopic constants. Dipole moment functions and vibrationally averaged dipole moments were also evaluated. Similarities and differences between BeN and BeP were analysed along with the isovalent SiB species. The molecule BeP has a X 4?- ground state, with an equilibrium bond distance of 2.073 A, and a harmonic frequency of 516.2 cm-1; it is followed closely by the states 2? (Re = 2.081 A, ?e = 639.6 cm-1) and 2?- (Re = 2.074 A, ?e = 536.5 cm-1), at 502 and 1976 cm-1, respectively. The other quartets investigated, A 4? (Re = 1.991 A, ?e = 555.3 cm-1) and B 4?- (Re = 2.758 A, ?e = 292.2 cm-1) lie at 13 291 and 24 394 cm-1, respectively. The remaining doublets (2?, 2?+(2) and 2?(3)) all fall below 28 000 cm-1. Avoided crossings between the 2?+2?+ states and between the 2? states add an extra complexity to this manifold of states.

57

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

Directory of Open Access Journals (Sweden)

Full Text Available 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 wireless channels in femtocell propagation areas, this paper presents the performance of a promising candidate technology designed based on the state-of-the-art techniques. The performance of powerful space-time turbo codes (STTCs based on serial concatenation of quadratic interleaved codes (SC-QICs with the optimal and also suboptimal decoding algorithms, in conjunction with orthogonal space-time block codes (OSTBCs have been presented in this contribution for wireless multiple-input single-output (MISO, and multiple-input multiple-output (MIMO semi-femtocells.

Ardavan Rahimian

2013-01-01

58

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)

59

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)

60

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

Energy Technology Data Exchange (ETDEWEB)

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 [sup 99m]Tc-DTPA represents a useful mean of monitoring the functional status of the lung epithelial membrane during bleomycin treatment. (orig./MG).

Ugur, Oe.; Caner, B.; Ulutuncel, N.; Bekdik, C. (Hacettepe Univ., Ankara (Turkey). Dept. of Nuclear Medicine); Balbay, M.D.; Oezen, H.A.; Remzi, D. (Hacettepe Univ., Ankara (Turkey). Dept. of Urology)

1993-02-01

61

Long-term results of pleurodesis in malignant pleural effusions: Doxycycline vs Bleomycin  

Science.gov (United States)

Background: The aim of this study was to compare the response of doxycycline and bleomycin in pleurodesis of malignant pleural effusions. Materials and Methods: The radiologic and clinical responses of doxycycline and bleomycin in pleurodesis of malignant pleural effusions were compared in this randomized clinical trial. Forty-two patients were randomized to receive either bleomycin 45 mg or doxycycline 600 mg as the sclerotherapy agent. Chest X-rays were taken before and after intervention, 10 days and 2 months later to compare the radiologic response. Dyspnea and other side effects, before and after intervention, 10 days and 2 months later were recorded and compared. Chi-square test was applied to analyze the data. Results: The prevalence of dyspnea and its different severities, 10 days and 2 months after intervention were significantly different (P < 0.05) between the two groups. Analysis of pleural effusions revealed a significant difference (P < 0.05) between Doxycycline vs. Bleomycin 2 months after the intervention. Three months after pleurodesis, only one patient in bleomycin group needed pleural fluid drainage. Conclusion: Pleural effusions did not change with use of doxycycline and bleomycin in short time but long-term results of doxycycline sclerotherapy was better than bleomycin sclerotherapy in malignant pleural effusions that was supported by this study. However, additional studies with larger sample size are necessary to confirm the results. PMID:25221752

Rafiei, Rahmatollah; Yazdani, Behnam; Ranjbar, Sayed Milad; Torabi, Zahra; Asgary, Sedigheh; Najafi, Somayeh; Keshvari, Mahtab

2014-01-01

62

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

63

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)

64

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

65

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

International Nuclear Information System (INIS)

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

66

Complete Resolution of Cystic Hygroma with Single Session of Intralesional Bleomycin  

Directory of Open Access Journals (Sweden)

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

67

Bleomycin-detectable iron in the plasma of premature and full-term neonates.  

Science.gov (United States)

The bleomycin assay measures non-transferrin-bound iron, able to catalyze free radical reactions, in human plasma. No bleomycin-detectable iron is present in plasma from healthy adults. However, plasma from 3/15 premature babies was positive in this assay. Plasma from 52 apparently-healthy term babies was analyzed and 11 were positive in the bleomycin assay. Hence not only some premature but also some full-term apparently-healthy babies may be at risk of severe oxidative damage. PMID:1376697

Evans, P J; Evans, R; Kovar, I Z; Holton, A F; Halliwell, B

1992-06-01

68

Bleomycin-detectable iron in plasma from Plasmodium vinckei vinckei-infected mice.  

Science.gov (United States)

Plasma from mice heavily parasitized by Plasmodium vinckei vinckei was found to contain micromolar levels of iron as detected by the 'bleomycin assay' (slightly modified) of Gutteridge et al. [(1981) Biochem. J. 199, 263-265]. Uninfected mouse plasma contained little or no bleomycin-detectable iron. Plasma ultrafiltrate from infected mice contained no bleomycin-detectable iron, indicating that such iron was associated with the protein/macromolecule fraction. We speculate that this iron could catalyse reduction of peroxides in vivo and thus play a role in malaria pathology. PMID:2417884

Buffinton, G D; Cowden, W B; Hunt, N H; Clark, I A

1986-01-20

69

Efficacy of bleomycin in combination with hyperthermia in larynx cancer treatment  

International Nuclear Information System (INIS)

The efficacy of bleomycin in conservative treatment of 70 patients with larynx cancer was studied. All the patients were divided into three groups: the first group consisted of 20 patients, subjected to chemotherapy with bleomycin first and then radiotherapy; the second group consisted of 25 patients once subjected to chemotherapy, and the third group included 25 patients, subjected to chemotherapy added by local SHF hyperthermia. The comparison of the treatment results for all the groups has shown that application of bleomycin before radiotherapy turns out to be the most effective method in treatment of larynx cancer. Local hyperthermia combined with chemotherapy improves delayed results of treatment of larynx cancer. 1 tab

70

Antitumour activity and plasma kinetics of bleomycin by continuous and intermittent administration.  

OpenAIRE

We have studied the cytotoxicity of bleomycin (4--10 u/kg/day for 6 days) given by continuous i.p. infusion (using an osmotic minipump) compared to daily i.p. bolus administration, against P388 leukaemic spleen colony-forming-units(LCFU-S). Continuous i.p. bleomycin at 8 u/kg/day caused a 0.5 log greater reduction of LCFU-S than did an identical dose given by intermittent bolus administration. The infusion minipump provided constant bleomycin plasma levels of 0.62 +/- 0.03 mu/ml and a total p...

Peng, Y. M.; Alberts, D. S.; Chen, H. S.; Mason, N.; Moon, T. E.

1980-01-01

71

Cellular localization of transforming growth factor-beta expression in bleomycin-induced pulmonary fibrosis.  

OpenAIRE

Bleomycin-induced pulmonary fibrosis is associated with increased lung transforming growth factor-beta (TGF-beta) gene expression, but cellular localization of the source of this expression has not been unequivocally established. In this study, lung fibrosis was induced in rats by endotracheal bleomycin injection on day 0 and, on selected days afterwards, lungs were harvested for in situ hybridization, immunohistochemical and histochemical analyses for TGF-beta 1 mRNA and protein expression, ...

Zhang, K.; Flanders, K. C.; Phan, S. H.

1995-01-01

72

Technetium-99m labeling by means of stannous pyrophosphate: application to bleomycin and red blood cells  

International Nuclear Information System (INIS)

A new technique of technetium labeling using stannous pyrophosphate instead of stannous chloride as reducing agent for pertechnetate has been applied to red blood cells and bleomycin. Results are so encouraging that this technique could be extended to other compounds capable of forming stable complexes with reduced technetium. No saline washes of red cells are necessary before or after the addition of pertechnetate. No purification step is performed after labeling of bleomycin. (U.S.)

73

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.

74

Cleavage of cellular and extracellular Saccharomyces cerevisiae DNA by bleomycin and phleomycin.  

Science.gov (United States)

Low-molecular-weight phleomycin (Mr approximately 1500-1600) is considerably less active on a per mol basis than structurally related bleomycin in degrading purified Saccharomyces cerevisiae DNA. Phleomycin also exhibits a substantially higher requirement than bleomycin for ferrous ions. However, phleomycin (0.13 to 3.3 x 10(-6) M) produced 7 to 350 times more breaks than bleomycin in prelabeled intracellular [2-14C]DNA and [6-3H]DNA and is considerably more cytotoxic than bleomycin. Phleomycin and bleomycin produced equivalent numbers of DNA breaks at equivalent, physiologically meaningful levels of survival, indicating that DNA breaks are related to lethal properties of the anticancer glycopeptides. Phleomycin degradation of extracellular DNA was only detectable at greater than or equal to 1.7 x 10(-4) M, approximately two orders of magnitude higher than the concentrations of phleomycin which yielded equivalent fragmentation of intracellular DNA, indicating that phleomycin causes substantially more degradation of intracellular DNA than extracellular DNA. In contrast, bleomycin (greater than or equal to 1.7 x 10(-5) M) degradation of purified DNA is quite extensive and considerably greater than the degradation of DNA in cells incubated with the same or higher concentrations of bleomycin. Neither phleomycin nor bleomycin cleaved extracellular DNA in the absence of ferrous ions, although both chemical analogues cleaved intracellular DNA without adding iron. Therefore, the requirement for metal ion in stimulating DNA degradation by the two structural families of glycopeptidic antibiotics is met by the cell itself. PMID:2479473

Moore, C W

1989-12-15

75

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

OpenAIRE

The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show fo...

Peng, Ruoqi; Sridhar, Sriram; Tyagi, Gaurav; Phillips, Jonathan E.; Garrido, Rosario; Harris, Paul; Burns, Lisa; Renteria, Lorena; Woods, John; Chen, Leena; Allard, John; Ravindran, Palanikumar; Bitter, Hans; Liang, Zhenmin; Hogaboam, Cory M.

2013-01-01

76

Dietary Flaxseed Oil Protects against Bleomycin-Induced Pulmonary Fibrosis in Rats  

OpenAIRE

Bleomycin, a widely used antineoplastic agent, has been associated with severe pulmonary toxicity, primarily fibrosis. Previous work has shown a reduction in bleomycin-induced lung pathology by long-chain omega-3 fatty acids. Treatment by short-chain omega-3 fatty acids, ?-linolenic acid, found in dietary flaxseed oil may also reduce lung fibrosis, as previously evidenced in the kidney. To test this hypothesis, 72 rats were divided between diets receiving either 15% (w/w) flaxseed oil or 15%...

Joshua Lawrenz; Betty Herndon; Afrin Kamal; Aaron Mehrer; Dim, Daniel C.; Cletus Baidoo; David Gasper; Jonathan Nitz; Agostino Molteni; Baybutt, Richard C.

2012-01-01

77

Molecular dynamics simulations exploring the interaction between DNA and metalated bleomycin  

OpenAIRE

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 ...

Eriksson, Leif A.; Palwai, Viraja R.

2011-01-01

78

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

Energy Technology Data Exchange (ETDEWEB)

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

79

The low-lying electronic states of BeP: a reliable and accurate quantum mechanical prediction  

Energy Technology Data Exchange (ETDEWEB)

A very high level of theoretical treatment (complete active space self-consistent field CASSCF/MRCI/aug-cc-pV5Z) was used to characterize the spectroscopic properties of a manifold of quartet and doublet states of the species BeP, as yet experimentally unknown. Potential energy curves for 11 electronic states were obtained, as well as the associated vibrational energy levels, and a whole set of spectroscopic constants. Dipole moment functions and vibrationally averaged dipole moments were also evaluated. Similarities and differences between BeN and BeP were analysed along with the isovalent SiB species. The molecule BeP has a X {sup 4}{Sigma}{sup -} ground state, with an equilibrium bond distance of 2.073 A, and a harmonic frequency of 516.2 cm{sup -1}; it is followed closely by the states {sup 2}PI (R{sub e} = 2.081 A, {omega}{sub e} = 639.6 cm{sup -1}) and {sup 2}{Sigma}{sup -} (R{sub e} = 2.074 A, {omega}{sub e} = 536.5 cm{sup -1}), at 502 and 1976 cm{sup -1}, respectively. The other quartets investigated, A {sup 4}PI (R{sub e} = 1.991 A, {omega}{sub e} = 555.3 cm{sup -1}) and B {sup 4}{Sigma}{sup -} (R{sub e} = 2.758 A, {omega}{sub e} = 292.2 cm{sup -1}) lie at 13 291 and 24 394 cm{sup -1}, respectively. The remaining doublets ({sup 2}{Delta}, {sup 2}{Sigma}{sup +}(2) and {sup 2}PI(3)) all fall below 28 000 cm{sup -1}. Avoided crossings between the {sup 2}{Sigma}{sup +} states and between the {sup 2}PI states add an extra complexity to this manifold of states.

Ornellas, Fernando R, E-mail: frornell@usp.b [Universidade de Sao Paulo, Instituto de Quimica, Departamento de Quimica Fundamental, Caixa Postal 26077, Sao Paulo, SP 05513-970 (Brazil)

2009-09-28

80

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

Directory of Open Access Journals (Sweden)

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

81

The Treatment of keloids and hypertrophic scars with intralesional bleomycin in skin of color.  

Science.gov (United States)

Intralesional injection with corticosteroid remains the mainstay of therapy for hypertrophic scars and keloids, however some lesions are unresponsive or may result in skin atrophy. Intralesional bleomycin injection is an alternative therapy that has been widely reported. In order to compare the effectiveness and safety of bleomycin for the treatment of keloids and hypertrophic scars in skin of color population, Fitzpatrick skin type III to V patients with keloids or hypertrophic scars were randomized into two groups. Group A was treated monthly with intralesional triamcinolone acetonide (10 mg/mL), while group B with intralesional bleomycin (1 mg/mL) for three consecutive months. Evaluation of the treatment was performed using "Patient and Observer Scar Assessment Scale" (POSAS), self-rated patient satisfaction score, photography, and ultrasonography. Two patients had their bleomycin blood levels monitored. Twenty-six patients with keloids or hypertrophic scars were recruited. The clinical improvement as assessed by the POSAS was not statistically significant. In terms of patients satisfaction score, one half of both groups reported a very good improvement. Photographic as well as ultrasonographic evaluation showed no difference between the two groups. Bleomycin was found to enter the blood circulation in a very small amount. The major side effect was hyperpigmentation. There was no skin atrophy detected in this study. Intralesional bleomycin is a safe and effective treatment for keloids and hypertrophic scars. The treatment is comparable to intralesional triamcinolone. Unfortunately, hyperpigmentation was the major side effect in darker skin type. PMID:25626920

Payapvipapong, Kittisak; Niumpradit, Nucha; Piriyanand, Chotinand; Buranaphalin, Sawanya; Nakakes, Artit

2015-03-01

82

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

Science.gov (United States)

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. PMID:22687607

Lee, Ye-Ji; Lee, Seung-Hae; Youn, Young-So; Choi, Ji-Yeon; Song, Keung-Sub; Cho, Min-Sun; Kang, Jihee Lee

2012-08-15

83

Bleomycin-induced flagellate erythema: A case report and review of the literature.  

Science.gov (United States)

Bleomycin has been used most commonly in the treatment of Hodgkin's lymphoma, certain germ cell tumors (GCT) and for the sclerosis of recurrent pleural effusions. Bleomycin toxicity predominantly affects the skin and lungs. Skin toxicity includes Raynaud's phenomenon, hyperkeratosis, nail-bed changes and palmoplantar desquamation. Flagellate erythema is an unusual rash occurring specifically during bleomycin use. In the present study, we report a case of bleomycin-induced flagellate erythema in a patient with GCT. A 42-year-old male was diagnosed with stage IIIB testicular cancer and treated with bleomycin, etoposide and cisplatin chemotherapy. After 10 days from the initiation of treatment, the patient subsequently developed a generalized pruritus and erythematous linear rash that was most prominent on the trunk, and upper and lower extremities. The patient was commenced on a short course of low-dose oral prednisolone, 20 mg daily, and antihistamine. Consequently, bleomycin was withheld from the patient's treatment regimen. The present study describes the case, along with a review of the associated literature. PMID:25009666

Lee, Hui-Young; Lim, Kyu-Hyoung; Ryu, Youngjoon; Song, Seo-Young

2014-08-01

84

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

85

The disaccharide moiety of bleomycin facilitates uptake by cancer cells.  

Science.gov (United States)

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

86

Modulation of bleomycin-induced pulmonary fibrosis in the BALB/c mouse by cyclophosphamide-sensitive T cells.  

OpenAIRE

Endotracheal bleomycin treatment is an effective inducer of pneumonitis and pulmonary fibrosis. Certain strains of mice, however, develop only minimal or no pulmonary fibrosis after treatment with bleomycin. The mechanism of unresponsiveness or low responsiveness in the BALB/c strain of mice is examined in this article. Pretreatment with cyclophosphamide (100 mg/kg) 2 days prior to bleomycin instillation significantly augmented the fibrotic response in these mice. Treatment by cyclophosphamid...

Schrier, D. J.; Phan, S. H.

1984-01-01

87

Transient iron overload with bleomycin detectable iron in the plasma of patients with adult respiratory distress syndrome.  

OpenAIRE

BACKGROUND--A retrospective study was conducted to evaluate iron status in plasma samples collected from five patients with the adult respiratory distress syndrome (ARDS) who had bleomycin detectable iron in at least one sample. Ten patients with ARDS with no evidence of bleomycin detectable iron and 10 healthy individuals served as controls. METHODS--Evidence of iron overload was established by measuring the percentage saturation of plasma transferrin. In each case the bleomycin assay for re...

Gutteridge, J. M.; Quinlan, G. J.; Evans, T. W.

1994-01-01

88

Differential expression of extracellular matrix remodeling genes in a murine model of bleomycin-induced pulmonary fibrosis.  

OpenAIRE

Exposure to the chemotherapeutic drug bleomycin leads to pulmonary fibrosis in humans and has been widely used in animal models of the disease. Using C57BL/6 bleomycin-sensitive mice, pulmonary fibrosis was induced by multiple intraperitoneal injections of the drug. An increase in the relative amounts of steady-state alpha1(I) procollagen, alpha1(III) procollagen, and fibronectin mRNA as well as histopathological evidence of fibrosis was observed. The effect of bleomycin on the expression of ...

Swiderski, R. E.; Dencoff, J. E.; Floerchinger, C. S.; Shapiro, S. D.; Hunninghake, G. W.

1998-01-01

89

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

International Nuclear Information System (INIS)

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

90

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

International Nuclear Information System (INIS)

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 at least in mouse kidney

91

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

International Nuclear Information System (INIS)

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)

92

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

Science.gov (United States)

The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGF? was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease. PMID:23565148

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

2013-01-01

93

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

Science.gov (United States)

The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGF? was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease. PMID:23565148

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

2013-01-01

94

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

International Nuclear Information System (INIS)

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

95

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

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Full Text Available

Background and Objectives: Silymarin, the active principle of Silybum marianum, has antifibrotic effects in hepatic fibrosis by several mechanisms. Since the pathogenesis of fibroproliferative diseases is similar, the effect of silymarin in bleomycin-induced pulmonary fibrosis was evaluated in this study.

Methods: Silymarin (50 mg/kg, i.p. was administered two days before the bleomycin instillation (3 U/kg and throughout the test interval in mice. After two weeks, lung tissues of mice were evaluated for fibrosis by biochemical measurement of collagen deposition and histological analysis of pathological lung changes. Data were evaluated by one-way ANOVA and Dunnett analysis. P<0.05 was considered as significant.

Results: Pretreatment with Silymarin significantly (P<0.05 prevented the increase in lung collagen content and also partially inhibited the histologic changes induced by bleomycin. The wet lung weight in silymarin group was similar to that of control group and significantly lower than bleomycin group (P<0.001.    

Conclusion: The results of this study indicate that silymarin may prevent the collagen deposition and inflammation and may be protective in fibrogenic effects of bleomycin on lung

L Safaeian

2012-05-01

96

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

International Nuclear Information System (INIS)

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)

97

Bleomycin-induced pulmonary endothelial cell injury: evidence for the role of iron-catalyzed toxic oxygen-derived species  

International Nuclear Information System (INIS)

Bleomycin, an effective cancer chemotherapeutic agent, is associated with serious pulmonary toxicity. As an in vitro model of bleomycin pulmonary toxicity, this study examined the ability of bleomycin to injure chromium 51-labeled bovine pulmonary artery endothelial (BPAE) cells in an 18-hour cytotoxicity assay. The data indicate that bleomycin-mediated injury to cultured BPAE cells can be quantified by 51Cr release, expressed as cytotoxic index (CI). Bleomycin-mediated injury to 51Cr-labeled BPAE cells (CI 19.4 +/- 1.6) could be significantly reduced by the iron chelator deferoxamine, 10(-3) mol/L (CI 7.5 +/- 1.1, P less than 0.001), but not by ethylenediaminetetraacetic acid, 10(-5) mol/L (CI 19.8 +/- 2.2). Similarly, bleomycin-mediated injury to BPAE cells (monitored by lactate dehydrogenase release) with a CI 27.1 +/- 4.8 could be reduced by 10(-3) mol/L deferoxamine to CI 10.5 +/- 2.6 (P less than 0.01). In contrast, hyperoxia (95% O2) accelerated bleomycin (1 to 100 mU/ml) toxicity to BPAE cells (P less than 0.01, all comparisons). This study suggests that bleomycin-induced injury of pulmonary endothelial cells may be dependent in part on two critical factors in the cellular environment: the availability of iron to the cell and the ambient O2 concentration

98

Bleomycin-induced pulmonary endothelial cell injury: evidence for the role of iron-catalyzed toxic oxygen-derived species  

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Bleomycin, an effective cancer chemotherapeutic agent, is associated with serious pulmonary toxicity. As an in vitro model of bleomycin pulmonary toxicity, this study examined the ability of bleomycin to injure chromium 51-labeled bovine pulmonary artery endothelial (BPAE) cells in an 18-hour cytotoxicity assay. The data indicate that bleomycin-mediated injury to cultured BPAE cells can be quantified by /sup 51/Cr release, expressed as cytotoxic index (CI). Bleomycin-mediated injury to /sup 51/Cr-labeled BPAE cells (CI 19.4 +/- 1.6) could be significantly reduced by the iron chelator deferoxamine, 10(-3) mol/L (CI 7.5 +/- 1.1, P less than 0.001), but not by ethylenediaminetetraacetic acid, 10(-5) mol/L (CI 19.8 +/- 2.2). Similarly, bleomycin-mediated injury to BPAE cells (monitored by lactate dehydrogenase release) with a CI 27.1 +/- 4.8 could be reduced by 10(-3) mol/L deferoxamine to CI 10.5 +/- 2.6 (P less than 0.01). In contrast, hyperoxia (95% O/sub 2/) accelerated bleomycin (1 to 100 mU/ml) toxicity to BPAE cells (P less than 0.01, all comparisons). This study suggests that bleomycin-induced injury of pulmonary endothelial cells may be dependent in part on two critical factors in the cellular environment: the availability of iron to the cell and the ambient O/sub 2/ concentration.

Martin, W.J. II; Kachel, D.L.

1987-08-01

99

Biological basis of combination therapy with radiation and bleomycin  

International Nuclear Information System (INIS)

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

100

Tanshinone ?A attenuates bleomycin-induced pulmonary fibrosis in rats.  

Science.gov (United States)

Idiopathic pulmonary fibrosis is a chronic and progressive fibrotic lung disorder with unknown etiology and a high mortality rate. Tanshinone ?A (Tan ?A) is a lipophilic diterpene extracted from the Chinese herb Salvia miltiorrhiza Bunge with diverse biological functions. The present study was conducted to evaluate the effects of Tan ?A on bleomycin (BLM)?induced pulmonary fibrosis in rats. Rats received an intraperitoneal injection of Tan ?A and normal rats were used as controls. Severe pulmonary edema, inflammation and fibrosis were observed in the BLM?treated rats and the counts of total cells, neutrophils and lymphocytes were significantly increased in the bronchoalveolar lavage fluids of those rats. These pathological changes were markedly attenuated by subsequent treatment with Tan ?A. In addition, BLM?induced increased expression of tumor necrosis factor??, interleukin (IL)?1?, IL?6, cyclooxygenase?2, prostaglandin E2, malondialdehyde, inducible nitric oxide synthase and nitric oxide in rats, which was also suppressed by Tan ?A injection. The present findings suggest therapeutic potential of Tan ?A for pulmonary fibrosis. PMID:25672255

He, Huanyu; Tang, Haiying; Gao, Lili; Wu, Yun; Feng, Zhiqiang; Lin, Hongli; Wu, Taihua

2015-06-01

101

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

International Nuclear Information System (INIS)

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

102

Determination of astrophysical 7Be(p, ?)8B reaction rates from the 7Li(d, p)8Li reaction  

Science.gov (United States)

The 7Be(p, ?)8B reaction plays a central role not only in the evaluation of solar neutrino fluxes but also in the evolution of the first stars. Study of this reaction requires the asymptotic normalization coefficient (ANC) for the virtual decay 8B g.s. ? 7Be + p. By using the charge symmetry relation, we obtain this proton ANC with the single neutron ANC of 8Li g.s. ?7Li + n, which is determined with the distorted wave Born approximation (DWBA) and adiabatic distorted wave approximation (ADWA) analysis of the 7Li(d, p)8Li angular distribution. The astrophysical S-factors and reaction rates of the direct capture process in the 7Be(p, ?)8B reaction are further deduced at energies of astrophysical relevance. The astrophysical S-factor at zero energy for direct capture, S 17(0), is derived to be (19.9 ± 3.5) eV b in good agreement with the most recent recommended value. The contributions of the 1+ and 3+ resonances to the S-factor and reaction rate are also evaluated. The present result demonstrates that the direct capture dominates the 7Be(p, ?)8B reaction in the whole temperature range. This work provides an independent examination to the current results of the 7Be(p, ?)8B reaction.

Du, XianChao; Guo, Bing; Li, ZhiHong; Pang, DanYang; Li, ErTao; Liu, WeiPing

2015-03-01

103

Coulomb Dissociation of 8B at 254 MeV/u for 7Be(p,?)8B  

Science.gov (United States)

The Coulomb dissociation of 8B into 7Be and a proton was measured at E(8B) = 254 MeV/u. The astrophysical S17-factors for the 7Be(p,?)8B reaction were extracted at Ecm = 0.25 - 2.78 MeV yielding the zero-energy S17-factor relevant to the solar neutrino problem to be S17(0) = 20.6 ± 1.2 ± 1.0 eV-b. Our results agree with the direct measurement results of Vaughn et al., Filippone et al., and Hammache et al. as well as the Coulomb dissociation results of Motobayashi et al. and Kikuchi et al. at E(8B) ? 50 MeV/u.

Iwasa, N.; Boué, F.; Surówka, G.; Sümmerer, K.; Baumann, T.; Blank, B.; Czajkowski, S.; Förster, A.; Gai, M.; Geissel, H.; Grosse, E.; Hellström, M.; Koczon, P.; Kohlmeyer, B.; Kulessa, R.; Laue, F.; Marchand, C.; Motobayashi, T.; Oeschler, H.; Ozawa, A.; Pravikoff, M. S.; Schwab, E.; Schwab, W.; Senger, P.; Speer, J.; Sturm, C.; Surowiec, A.; Teranishi, T.; Uhlig, F.; Wagner, A.; Walus, W.; Bertulani, C. A.

2003-04-01

104

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

International Nuclear Information System (INIS)

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

105

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

International Nuclear Information System (INIS)

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

106

Pulmonary complications of irradiation and bleomycin after radical surgery for esophageal cancer  

International Nuclear Information System (INIS)

From 1978 to 1980, 52 patients underwent radical surgery for esophageal cancer, and they given radiotherapy of 300-500 rads and/or 50-100 mg of bleomycin prophylatically during the postoperative period. Of the total cases, five patients developed acute interstitial pneumonitis. All cases were controlled successfully by the administration of prednisolone, but one patient died of a complication of systemic aspergillosis. Pneumonitis occurred during the early course of irradiation, i.e.two cases during irradiation and one cases three days after irradiation. Pneumonitis also occurred with a low dose of bleomycin (70 mg) in two cases. Clinical signs of radiation pneumonitis were more severe in cases of esophageal cancer than in cases of lung cancer and breast cancer as had been previously reported. These results suggest that surgery for esophageal cancer tends to sensitize the lung and leads to pulmonary complications after radiotherapy and chemotherapy employing bleomycin. (author)

107

Pulmonary complications of irradiation and bleomycin after radical surgery for esophageal cancer  

Energy Technology Data Exchange (ETDEWEB)

From 1978 to 1980, 52 patients underwent radical surgery for esophageal cancer, and they given radiotherapy of 300-500 rads and/or 50-100 mg of bleomycin prophylatically during the postoperative period. Of the total cases, five patients developed acute interstitial pneumonitis. All cases were controlled successfully by the administration of prednisolone, but one patient died of a complication of systemic aspergillosis. Pneumonitis occurred during the early course of irradiation, i.e. two cases during irradiation and one cases three days after irradiation. Pneumonitis also occurred with a low dose of bleomycin (70 mg) in two cases. Clinical signs of radiation pneumonitis were more severe in cases of esophageal cancer than in cases of lung cancer and breast cancer as had been previously reported. These results suggest that surgery for esophageal cancer tends to sensitize the lung and leads to pulmonary complications after radiotherapy and chemotherapy employing bleomycin.

Kitamura, Michihiko; Nishihira, Tetsuro; Tan, Masaki (Tohoku Univ., Sendai (Japan). School of Medicine)

1983-12-01

108

Antifibrotic effects of immobilized hyaluronidase in repeated bleomycin-induced lesions of the alveolar epithelium.  

Science.gov (United States)

Antifibrotic activity of testicular hyaluronidase, immobilized on polyethylenoxide and obtained by electron beam synthesis, was studied on the model of bleomycin injuries to the alveolar epithelium (irreversible pneumofibrosis) in C57Bl/6 mice and compared to the effect of testicular hyaluronidase. Intranasal therapy with immobilized and testicular hyaluronidases prevented the deposition of fibrotic mass in the parenchyma of "bleomycin" lungs. The effect of immobilized hyaluronidase was more pronounced than that of testicular hyaluronidase. The studied compounds were virtually inessential for infiltration of the alveolar interstitium and alveolar tracts by lymphocytes, macrophages, neutrophils, and plasma cells. Unchanged histoarchitectonics of bleomycin-damaged lungs in immobilized hyaluronidase therapy was due to suppression of the progenitor fibroblast cells (CD45(-)). PMID:24143378

Dygai, A M; Skurikhin, E G; Ermakova, N N; Reztsova, A M; Pershina, O V; Khmelevskaya, E S; Krupin, V A; Stepanova, I E; Reztsova, V M; Artamonov, A V; Bekarev, A A; Madonov, P G; Kinsht, D N

2013-08-01

109

Bleomycin-induced trans lipid formation in cell membranes and in liposome models.  

Science.gov (United States)

Cell cultures of NTera-2 cells incubated with bleomycin and liposomes as biomimetic models of cell membranes were used for examining some novel aspects of drug-metal induced reactivity with unsaturated lipids under oxidative conditions. In cell cultures, bleomycin was found for the first time to cause the formation of trans fatty acids. The chemical basis of this transformation was ascertained by liposome experiments, using bleomycin-iron complexes in the presence of thiol as a reducing agent that by incubation at 37 °C gave rise to the thiyl radical-catalysed double bond isomerisation of membrane phospholipids. The effect of oxygen and reagent concentrations on the reaction outcome was studied. An interesting scenario of free radical reactivity is proposed, which can be relevant for understanding the role of membrane lipids in antitumoral treatments and drug carrier interaction. PMID:25417813

Cort, Aysegul; Ozben, Tomris; Sansone, Anna; Barata-Vallejo, Sebastian; Chatgilialoglu, Chryssostomos; Ferreri, Carla

2015-01-28

110

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  

International Nuclear Information System (INIS)

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.)

111

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

112

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

International Nuclear Information System (INIS)

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 th 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

113

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  

Energy Technology Data Exchange (ETDEWEB)

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

114

Effects of radiotherapy combined with daily intramuscular injection of bleomycin for uterine cervical cancer  

International Nuclear Information System (INIS)

A total of 103 cases of cancer of the uterine cervix, untreated previously, were treated with radiotherapy combined with daily intramuscular injection of Bleomycin 30 minutes before irradiation (BR therapy) in 12 institutions. Result showed that especially in cases of stage III, BR therapy was superior in primary local control rate (89.6%), recurrence rate (20.8%) and crude 5-year survival rate (56.5%) to that of nationwide statistics. No severe side effects were found. It was concluded that external radiotherapy could control advanced cancers of uterine cervix combining with intramuscular injection of Bleomycin. (author)

115

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

OpenAIRE

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 metall...

NIKOS KATSAROS; IOANNIS BRATSOS; ATHANASIOS PAPAKYRIAKOU

2003-01-01

116

Irradiation facilitates the inhibitory effect of the heat shock protein 90 inhibitor NVP-BEP800 on the proliferation of malignant glioblastoma cells through attenuation of the upregulation of heat shock protein 70.  

Science.gov (United States)

The present study aimed to investigate the effect of NVP-BEP800, a novel heat shock protein (Hsp) 90 inhibitor of the 2-aminothieno[2,3-d]pyrimidine class, in combination with radiation on glioblastoma cells. T98G human glioblastoma cells were treated with dimethyl sulfoxide (DMSO), NVP-BEP800, NVP-BEP800 in combination with X-ray irradiation (10 Gy, 20 min), or X-ray irradiation only, and cultured for 40 h. Cell viability was measured upon completion of the treatments. In addition, apoptosis was measured and immunoblot analysis was performed to analyze the expression levels of cellular protein inhibitory ?B kinase ? (IKK?). The combined treatment with NVP-BEP800 and X-ray irradiation resulted in the synergistic destruction of malignant cells. Furthermore, NVP-BEP800 significantly induced apoptosis in the human glioblastoma cells. The immunoblot analysis data indicated that NVP-BEP800 markedly reduced the expression level of IKK?. The results also revealed that X-ray irradiation significantly attenuated the increase in the level of Hsp70 in cells treated with NVP-BEP800. Since elevated levels of Hsp70 are associated with drug resistance induced by Hsp90 inhibitors, the effects of X-ray irradiation on Hsp70 levels may be associated with the enhanced effect on cells of the presence of irradiation. The results of the current study suggest that irradiation enhances the inhibitory effect of NVP-BEP800 on the proliferation of malignant glioblastoma cells by downregulating the expression level of cellular signaling protein IKK? and attenuating the upregulation of Hsp70 that is induced by NVP-BEP800. PMID:25120620

Wu, Jianyue; Wang, Weimin; Shao, Qin; Xiao, Guomin; Cheng, Jun; Yuan, Yunpeng; Zhang, Mei

2014-09-01

117

T cell independence of bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

The role of T cells and cytokines in bleomycin (BLM)-induced fibrosis was evaluated in susceptible and resistant strains of normal and SCID mice. Histology and hydroxyproline analysis showed that BLM induced pulmonary fibrosis in C57BL/6 and (C57BL/6 x BALB/c)F1 mice, whereas BALB/c mice were resistant to the disease. To test whether lymphocytes were required for the induction of BLM-induced pulmonary fibrosis, SCID mice were injected intratracheally with BLM and evaluated for the development of pulmonary inflammation and fibrosis. Similar morphological changes and increases in hydroxyproline were observed in both C57BL/6 SCID and (C57BL/6 x CB.17)F1 SCID animals compared to those seen in wild-type C57BL/6 and (C57BL/6 x BALB/c)F1 mice. In contrast, CB.17 SCID mice, which are genetically similar to BALB/c mice, were resistant to disease induction. Analysis of the cellular infiltrate in BLM-treated C57Bl/6 SCID mice confirmed a lack of T cells in the lungs of SCID mice and demonstrated a pronounced accumulation of eosinophils in areas of developing pulmonary fibrosis. NK cells were significantly elevated in untreated SCID mice and did not increase further after BLM treatment. Analysis of selected cytokines 1 day after initiation of BLM-induced pulmonary fibrosis indicated that the levels of TNF-alpha and IFN-gamma appeared to segregate with fibrosis in both the SCID and wild-type mice. The data demonstrate that T cells are not required for the induction of fibrosis by BLM and suggest that responses by non-lymphoid cells may be sufficient for the induction of fibrosis. PMID:10088601

Helene, M; Lake-Bullock, V; Zhu, J; Hao, H; Cohen, D A; Kaplan, A M

1999-02-01

118

Irradiation facilitates the inhibitory effect of the heat shock protein 90 inhibitor NVP-BEP800 on the proliferation of malignant glioblastoma cells through attenuation of the upregulation of heat shock protein 70  

OpenAIRE

The present study aimed to investigate the effect of NVP-BEP800, a novel heat shock protein (Hsp) 90 inhibitor of the 2-aminothieno[2,3-d]pyrimidine class, in combination with radiation on glioblastoma cells. T98G human glioblastoma cells were treated with dimethyl sulfoxide (DMSO), NVP-BEP800, NVP-BEP800 in combination with X-ray irradiation (10 Gy, 20 min), or X-ray irradiation only, and cultured for 40 h. Cell viability was measured upon completion of the treatments. In addition, apoptosis...

Wu, Jianyue; Wang, Weimin; Shao, Qin; Xiao, Guomin; Cheng, Jun; Yuan, Yunpeng; Zhang, Mei

2014-01-01

119

Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats.  

Science.gov (United States)

Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N-acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol x kg(-1) x day(-1)) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257+/-323 and 3,200+/-192 microg x lung(-1) in vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor-alpha and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC-treated rats. These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N-acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model. PMID:14680076

Mata, M; Ruíz, A; Cerdá, M; Martinez-Losa, M; Cortijo, J; Santangelo, F; Serrano-Mollar, A; Llombart-Bosch, A; Morcillo, E J

2003-12-01

120

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

121

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

122

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

123

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

OpenAIRE

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.

Amirshahi, Tayebeh; Najafi, Gholamreza; Nejati, Vahid

2014-01-01

124

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

Energy Technology Data Exchange (ETDEWEB)

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.

Robson, C.N.; Harris, A.L.; Hickson, I.D.

1985-11-01

125

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

International Nuclear Information System (INIS)

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)

126

Preparation of phase I of clinical testing of kit for bleomycin labelling with 57Co  

International Nuclear Information System (INIS)

Experience is described gained in preclinical trials with a kit for bleomycin labelling with 57Co, of original manufacture. The 57Co-labelled bleomycin shows a positive tumor imaging potential. As against other labelled bleomycins described in the literature, it best meets the requirements of imaging tumors in the highest possible number of tissues and of good differentiation of tumors from the adjacent tissues. The three-component kit uses a phosphate buffer which makes it more suitable for i.v. administration and significantly increases bleomycin stability. The kit was found to show advantages over previously described radiopharmaceuticals of this type in that that it can quickly be reconstituted immediately prior to the application and that it is significantly cheaper to use, namely 140-fold cheaper than most other similar radiopharmaceuticals. Its disadvantage, i.e., the long half-life is balanced with a short biological half-life; within 24 hours following application 80 to 90% of the applied activity was found to be excreted from the organism. The short biological half-life is also beneficial for the patient in that the radiation load of the patient is 10 times lower than in the application of 67Ga. (L.O.)

127

Development of 153Sm-bleomycin as a possible therapeutic complex  

International Nuclear Information System (INIS)

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

128

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

International Nuclear Information System (INIS)

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

129

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

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

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

1982-08-01

130

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

131

Low-energy cross section of the 7Be(p,?)8B solar fusion reaction from the Coulomb dissociation of 8B  

International Nuclear Information System (INIS)

An exclusive measurement of the Coulomb breakup of 8B into 7Be+p at 254A MeV was used to infer the low-energy 7Be(p,?)8B cross section. The radioactive 8B beam was produced by projectile fragmentation of 350A MeV 12C and separated with the FRagment Separator (FRS) at Gesellschaft fuer Schwerionenforschung in Darmstadt, Germany. The Coulomb-breakup products were momentum-analyzed in the KaoS magnetic spectrometer; particular emphasis was placed on the angular correlations of the breakup particles. These correlations demonstrate clearly that E1 multipolarity dominates within the angular cuts selected for the analysis. The deduced astrophysical S17 factors exhibit good agreement with the most recent direct 7Be(p,?)8B measurements. By using the energy dependence of S17 according to the recently refined cluster model for 8B of P. Descouvemont [Phys. Rev. C 70, 065802 (2004)], we extract a zero-energy S factor of S17(0)=20.6±0.8(stat)±1.2(syst) eV b. These errors do not include the uncertainty of the theoretical model to extrapolate to zero relative energy, estimated by Descouvemont to be about 5%

132

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)

133

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

OpenAIRE

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 ...

Farahnaz Fatemi; Jamshid Najafian; Koroush Ahmadpour

2005-01-01

134

Rho-kinase inhibitor prevents bleomycin-induced injury in neonatal rats independent of effects on lung inflammation.  

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Bleomycin-induced lung injury is characterized in the neonatal rat by inflammation dominated by neutrophils and macrophages, inhibited distal airway and vascular development, and pulmonary hypertension, similar to human infants with severe bronchopulmonary dysplasia. Rho-kinase (ROCK) is known to mediate lung injury in adult animals via stimulatory effects on inflammation. We therefore hypothesized that inhibition of ROCK may ameliorate bleomycin-induced lung injury in the neonatal rat. Pups received daily intraperitoneal bleomycin or saline from Postnatal Days 1 through 14 with or without Y-27632, a ROCK inhibitor. Treatment with Y-27632 prevented bleomycin-induced pulmonary hypertension, as evidenced by normalized pulmonary vascular resistance, decreased right-ventricular hypertrophy, and attenuated remodeling of pulmonary resistance arteries. Bleomycin-induced changes in distal lung architecture, including septal thinning, inhibited alveolarization, and decreased numbers of peripheral arteries and capillaries, were partially or completely normalized by Y-27632. Treatment with Y-27632 or a CXCR2 antagonist, SB265610, also abrogated tissue neutrophil influx, while having no effect on macrophages. However, treatment with SB265610 did not prevent bleomycin-induced lung injury. Lung content of angiostatic thrombospondin-1 (TSP1) was increased significantly in the lungs of bleomycin-exposed animals, and was completely attenuated by treatment with Y-27632. Thrombin-stimulated TSP1 production by primary cultured rat pulmonary artery endothelial cells was also attenuated by Y-27632. Taken together, our findings suggest a preventive effect of Y-27632 on bleomycin-mediated injury by a mechanism unrelated to inflammatory cells. Our data suggest that improvements in lung morphology may have been related to indirect stimulatory effects on angiogenesis via down-regulation of TSP1. PMID:23947621

Lee, Alvin H; Dhaliwal, Rupinder; Kantores, Crystal; Ivanovska, Julijana; Gosal, Kiran; McNamara, Patrick J; Letarte, Michelle; Jankov, Robert P

2014-01-01

135

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.

136

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 bleomycinellular sensitivity to bleomycin

137

Transient iron-overload with bleomycin-detectable iron present during cardiopulmonary bypass surgery.  

Science.gov (United States)

Extracorporeal circulation of blood during cardiopulmonary bypass surgery exposes cells to non-physiological surfaces and shear stress which can activate several regulatory cascades, and neutrophils to release superoxide and hydrogen peroxide. Shear stresses generated by pumps and suction systems cause lysis of red blood cells and the release of haemoglobin. Together the release of reactive forms of oxygen and haemoglobin can lead to the appearance of low molecular mass chelatable iron (bleomycin-detectable iron). All patients undergoing open heart surgery appear to release iron to plasma transferrin, increasing its iron saturation. In 13% of patients, however, the transferrin became fully iron-saturated, and by the end of open-heart surgery we could detect bleomycin-chelatable iron in the plasma. Saturation of transferrin with iron eliminates its iron-binding antioxidant properties, which can result in a stimulation of iron-dependent radical damage to selected detector molecules. PMID:7522839

Pepper, J R; Mumby, S; Gutteridge, J M

1994-08-01

138

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

139

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

140

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

OpenAIRE

Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs) coated with polyacrylic acid (PAA) as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR). The load...

Yue Xu; Yi Lin; Lin Zhuang; Jiong Lin; Jiahong Lv; Qin Huang; Jiadong Sun

2013-01-01

141

Further insights into the mechanism of the reaction of activated bleomycin with DNA  

OpenAIRE

Bleomycin (BLM) is a glycopeptide anticancer drug that effectively carries out single- and double-stranded DNA cleavage. Activated BLM (ABLM), a low-spin ferric-hydroperoxide, BLM–FeIII–OOH, is the last intermediate detected before DNA cleavage. We have previously shown through experiments and DFT calculations that both ABLM decay and reaction with H atom donors proceed via direct H atom abstraction. However, the rate of ABLM decay had been previously found, based on indirect methods, to ...

Chow, Marina S.; Liu, Lei V.; Solomon, Edward I.

2008-01-01

142

Mice Lacking Neutrophil Elastase Are Resistant to Bleomycin-Induced Pulmonary Fibrosis  

OpenAIRE

Neutrophil elastase is a serine protease stored in the azurophilic granules of leukocytes. It has been implicated in the pathology of several lung diseases and is generally presumed to contribute to the tissue destruction and extracellular matrix damage associated with these conditions. To delineate the role of neutrophil elastase in pulmonary inflammation and fibrosis, neutrophil elastase-null mice were intratracheally instilled with bleomycin. In neutrophil elastase-null mice, biochemical a...

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

2007-01-01

143

Phase-directed therapy: TSG-6 targeted to early inflammation improves bleomycin-injured lungs  

OpenAIRE

Previous reports demonstrated that bleomycin-induced injury of lungs in mice can be improved by the administration of murine multipotent adult stem/progenitor cells (MSCs) from the bone marrow. Recently some of the beneficial effects of MSCs have been explained by the cells being activated by signals from injured tissues to express the inflammation modulating protein TNF-?-stimulated gene/protein 6 (TSG-6). In this study, we elected to test the hypothesis that targeting the early phase of bl...

Foskett, Andrea M.; Bazhanov, Nikolay; Ti, Xinyu; Tiblow, April; Bartosh, Thomas J.; Prockop, Darwin J.

2013-01-01

144

Phase-directed therapy: TSG-6 targeted to early inflammation improves bleomycin-injured lungs.  

Science.gov (United States)

Previous reports demonstrated that bleomycin-induced injury of lungs in mice can be improved by the administration of murine multipotent adult stem/progenitor cells (MSCs) from the bone marrow. Recently some of the beneficial effects of MSCs have been explained by the cells being activated by signals from injured tissues to express the inflammation modulating protein TNF-?-stimulated gene/protein 6 (TSG-6). In this study, we elected to test the hypothesis that targeting the early phase of bleomycin-induced lung injury with systemic TSG-6 administration may produce therapeutic effects such as preventing the deterioration of lung function and increasing survival by modulation of the inflammatory cascade. Lung injury in C57Bl/6J mice was induced by intratracheal administration of bleomycin. Mice then received intravenous injections of TSG-6 or sham controls. Pulse oximetry was used to monitor changes in lung function. Cell infiltration was evaluated by flow cytometry, cytokine expression was measured by ELISA assays, and lungs were assessed for histological attributes. The results demonstrated that intravenous infusion of TSG-6 during the early inflammatory phase decreased cellular infiltration into alveolar spaces. Most importantly, it improved both the subsequent decrease in arterial oxygen saturation levels and the survival of the mice. These findings demonstrated that the beneficial effects of TSG-6 in a model of bleomycin-induced lung injury are largely explained by the protein modulating the early inflammatory phase. Similar phase-directed strategy with TSG-6 or other therapeutic factors that MSCs produce may be useful for other lung diseases and diseases of other organs. PMID:24242012

Foskett, Andrea M; Bazhanov, Nikolay; Ti, Xinyu; Tiblow, April; Bartosh, Thomas J; Prockop, Darwin J

2014-01-01

145

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

OpenAIRE

"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 ...

Han, Khin Ei; Okada, Shigeru

1995-01-01

146

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

147

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

148

Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases  

OpenAIRE

BACKGROUND: Electrochemotherapy (ECT) combines chemotherapy and electroporation to increase drug uptake. Its role in cutaneous melanoma metastasis treatment is not well defined; indeed, few studies have been reported, without complete follow-up data. AIM: To prospectively evaluate clinical activity and tolerability of ECT with i.v. bleomycin, and to analyze the response increase associated to repeated sessions, in the largest series of cutaneous melanoma metastases reported to date (n = 233)....

Bernengo, Maria Grazia; Osella Abate, Simona; Savoia, Paola; Quaglino, Pietro

2008-01-01

149

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 caneems to be effective on advanced oral cancers because the local tumor control rate increased markedly. (author)

150

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

International Nuclear Information System (INIS)

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

151

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

International Nuclear Information System (INIS)

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 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. (paper)

152

Unusual treatment of Kasabach-Merritt syndrome secondary to hepatic hemangioma: embolization with bleomycin.  

Science.gov (United States)

Kasabach-Merritt syndrome (KMS) is a rare complication of cavernous hemangiomas characterized with anemia, thrombocytopenia, and consumption coagulopathy. This syndrome usually develops due to superficial soft tissue hemangiomas in infancy and childhood. KMS developing secondarily to hepatic hemangioma is very rare. In this report, we aimed to present the treatment of KMS developing secondarily to giant cavernous hemangioma of the liver with transarterial chemoembolization using bleomycin. PMID:25471004

Bozkaya, Halil; Cinar, Celal; Unalp, Omer Vedat; Parildar, Mustafa; Oran, Ismail

2014-12-01

153

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

OpenAIRE

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 a...

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

2006-01-01

154

Intralesional bleomycin sclerotherapy: an effective treatment of cystic hygroma in children  

International Nuclear Information System (INIS)

Objective: To study the outcome of intralesional sclerotherapy with injection Bleomycin in cystic hygroma in children. Study Design: A case series. Place and Duration of Study: The department of Pediatric Surgery at Military Hospital, Rawalpindi, Pakistan from Jan 2011 to Dec 2012. Patients and Methods: All patients with peripheral cystic hygroma (CH) presenting to us, were enrolled in the study. The cyst was aspirated in the operation theater under sedation. Injection bleomycin 0.5 mg /kg diluted in 10-15 cc of distilled water was injected in the cyst at multiple sites. Injection was repeated after every month depending upon the response. Results: A total of 30 patients reported to the department with superficial cystic hygroma, 12 were males (40%) and 18 were females (60%), age ranged from 15 days to 8 years. Cervico-facial was the most common site. Results were assessed in terms of excellent (complete resolution), good (> 50% reduction in size) and poor (< 50% reduction in size). In 2 patients, complete resolution was achieved after maximum seven shots of intra-lesional bleomycin injections (IBI), while 18/30 (60%) resolved after single dose. Twenty seven patients (90%) resolved completely, 2 (6.6%) had good response, 1 (3.3%) showed poor response. Minor complications were noted which were treated by ymptomatic treatment. No major side effects or recurrence were noted in maximum 2 years follow up. (author)

155

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

Energy Technology Data Exchange (ETDEWEB)

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

156

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

International Nuclear Information System (INIS)

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.)

157

CC-chemokine receptor 2 required for bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

MCP-1, which signals via the CC chemokine receptor 2 (CCR2), is induced in lung fibrosis that is accompanied by mononuclear cell recruitment and activation of lung fibroblasts. To evaluate the role of CCR2 in lung fibrosis, CCR2 knockout (ko) mice were used in a model of bleomycin-induced lung fibrosis. Wild type (wt) and ko mice were injected endotracheally with bleomycin to induce lung injury and fibrosis, and then analyzed for degree of lung fibrosis and cytokine expression. The results showed significantly reduced fibrosis in ko mice as evidenced by decreased lung type I collagen gene expression and hydroxyproline content relative to those in wt mice. Lung TNF-alpha and TGF-beta1 expression was significantly lower in ko vs. wt mice, while MCP-1 expression was unaffected. Interestingly, lung alpha-smooth muscle actin (alpha-SMA) expression, a marker for myofibroblast differentiation, was also decreased in ko mice, which was confirmed by analysis of isolated lung fibroblasts. Fibroblasts from ko mice exhibited decreased responsiveness to TGF-beta1 induced alpha-SMA expression, which was associated with reduced expression of TGF-beta receptor II (TbetaRII) and Smad3. These findings suggest that CCR2 signaling plays a key role in bleomycin-induced pulmonary fibrosis by regulating fibrogenic cytokine expression and fibroblast responsiveness to TGF-beta. PMID:14609568

Gharaee-Kermani, Mehrnaz; McCullumsmith, Robert E; Charo, Israel F; Kunkel, Steven L; Phan, Sem H

2003-12-21

158

Intralesional bleomycin injection in management of low flow vascular malformations in children.  

Science.gov (United States)

Low flow vascular malformations are challenging to manage, particularly with their propensity to grow, and can lead to severe disfigurement and dysfunction. Traditional surgical excision is fraught with tedious dissection and complications, particularly in the head and neck region. Trends toward less invasive techniques, such as intralesional sclerotherapy, are proving to be successful independent treatments or adjuncts in management in low flow vascular malformations. This study was a retrospective case note review, over an 8-year period, reporting the outcomes of 32 children (mean = 5.8 years, range = 5 months-11.5 years) with radiologically confirmed low flow vascular malformations, treated with serial intralesional bleomycin injection (IBI) therapy. Patient demographics, lesion characteristics, imaging findings, treatment course, radiological and clinical response to treatment were recorded. An overall 91% (n = 29) response rate was achieved, with 28% obtaining complete resolution for low flow vascular malformations. Lesions were sub-categorized into venous malformation, including mixed venous-capillary (n = 27) or lymphatic malformation (LM) (n = 5). Twenty-seven of 32 children experienced no complications. Local complications included superficial skin infection (n = 2), skin necrosis (n = 1), hyperpigmentation, and minor contour deformity. There was no recurrence and no systemic side-effects to bleomycin. Mean follow-up was 38 months (range = 6-95 months). In conclusion, serial intralesional bleomycin injections can be effective and also safe in a paediatric population for the successful management of symptomatic or disfiguring low flow vascular malformations. PMID:25204206

Mohan, Anita T; Adams, Saleigh; Adams, Kevin; Hudson, Donald A

2015-04-01

159

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

International Nuclear Information System (INIS)

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

160

Increase in bleomycin-detectable iron in ischaemia/reperfusion injury to rat kidneys.  

Science.gov (United States)

Iron has been shown to be important in ischaemic, immune and toxic forms of tissue injury in various organs. Although it is generally accepted that iron participates in the generation of powerful oxidant species (e.g. hydroxyl radicals) there has not been any direct evidence that iron capable of catalysing free-radical reactions is increased in tissues in these models of injury. In the present study we demonstrate that ischaemia/reperfusion injury to the kidney results in no significant change in total, nonhaem or ferritin iron levels, but there is a marked and specific increase in bleomycin-detectable iron (capable of catalysing free-radical reactions) in the kidney. The increase in bleomycin-detectable iron is observed only after reperfusion but not during the ischaemic period. In a separate study we demonstrate that despite a drastic reduction in the iron content in the kidney, as a result of feeding an iron-deficient diet, there is a similar and a marked increase in the bleomycin-detectable iron in kidneys accompanied by a lack of protection against ischaemia/reperfusion injury. PMID:7683877

Baliga, R; Ueda, N; Shah, S V

1993-05-01

161

Bleomycin-dependent damage to the bases in DNA is a minor side reaction.  

Science.gov (United States)

The antitumor antibiotic bleomycin degrades DNA in the presence of ferric ions and H2O2 or in the presence of ferric ions, oxygen, and ascorbic acid. When DNA degradation is measured as formation of base propenals by the thiobarbituric acid assay, it is not inhibited by superoxide dismutase and scavengers of the hydroxyl radical or by catalase (except that catalase inhibits in the bleomycin/ferric ion/H2O2 system by removing H2O2). Using the technique of gas chromatography/mass spectrometry with selected-ion monitoring, we show that DNA degradation is accompanied by formation of small amounts of modified DNA bases. The products formed are identical with those generated when hydroxyl radicals react with DNA bases. Base modification is significantly inhibited by catalase and partially inhibited by scavengers of the hydroxyl radical and by superoxide dismutase. We suggest that the bleomycin-oxo-iron ion complex that cleaves the DNA to form base propenals can decompose in a minor side reaction to generate hydroxyl radical, which accounts for the base modification in DNA. However, hydroxyl radical makes no detectable contribution to the base propenal formation. PMID:1705818

Gajewski, E; Aruoma, O I; Dizdaroglu, M; Halliwell, B

1991-03-01

162

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

International Nuclear Information System (INIS)

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)

163

Degradation of DNA and structure-activity relationship between bleomycins A2 and B2 in the absence of DNA repair  

International Nuclear Information System (INIS)

The contribution of DNA repair to the net number of DNA breaks produced during chemical degradation of DNA was determined by using temperature-sensitive mutant cells deficient in ATP-dependent DNA ligase. In a very sensitive assay for determining lesions introduced into Saccharomyces cerevisiae DNAs, 2-14C- and 6-3H-prelabeled DNAs from ligase-proficient and ligase-deficient cells were sedimented together through precalibrated, isokinetic alkaline sucrose gradients. DNA ligation was slower after chemical degradation of DNA by bleomycin than after ? irradiation. DNA breaks increased approximately linearly with drug concentrations, and were approximately equivalent for ligase-proficient and ligase-deficient cells. These results were unexpected because ligase-deficient, but not ligase-proficient, cells lacked the capacity to eliminate DNA breaks produced by bleomycin. The results indicated that DNA repair did not occur during the chemical degradation of DNA under the experimental conditions. Bleomycin B2 produced considerably more DNA breaks than bleomycin A2 over a range of concentrations in ligase-proficient cells, which tolerated higher numbers of DNA breaks in general than ligase-deficient cells. The chemical analogues are structurally identical except for their cationic C-terminal amine. The actual number of DNA breaks produced by bleomycin A2 or bleomycin B2, and not the concentration of bleomycin A and not the concentration of bleomycin A2 or bleomycin B2 per se, determined the amount of cell killing. DNA repair is critical in quantitating DNA breaks produced by chemicals, but was ruled out as a factor in the higher DNA breakage by bleomycin B2 than bleomycin A2

164

A windowless hydrogen gas target for the measurement of {sup 7}Be(p, {gamma}){sup 8}B with the recoil separator ERNA  

Energy Technology Data Exchange (ETDEWEB)

A new measurement of the cross section of {sup 7}Be(p, {gamma}){sup 8}B will be done in inverted kinematics with the recoil separator ERNA at the CIRCE laboratory in Caserta, Italy. The {sup 8}B recoils will be produced in a windowless hydrogen gas target. We report here on the construction and characterization of the gas cell. In detail we describe measurements for target density, the profile determination via the {sup 7}Li(p, p'){sup 7}Li{sup *} reaction as well as the role and performance of a gaseous post-stripper. (orig.)

Schuermann, D.; Di Leva, A.; Imbriani, G.; Romano, M. [Sezione di Napoli, INFN, Napoli (Italy); Universita Federico II, Dipartimento di Scienze Fisiche, I-80126 (Italy); Gialanella, L.; De Cesare, M.; De Cesare, N.; D' Onofrio, A; Terrasi, F. [Sezione di Napoli, INFN, Napoli (Italy); Seconda Universita di Napoli, Dipartimento di Matematica e Fisica, Caserta (Italy); Romoli, M. [Sezione di Napoli, INFN, Napoli (Italy)

2013-06-15

165

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

Directory of Open Access Journals (Sweden)

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

166

Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs.  

Science.gov (United States)

Arginase is an enzyme that limits substrate l-arginine bioavailability for the production of nitric oxide by the nitric oxide synthases and produces l-ornithine, which is a precursor for collagen formation and tissue remodeling. We studied the pulmonary vascular effects of arginase inhibition in an established model of repeated systemic bleomycin sulfate administration in neonatal rats that results in pulmonary hypertension and lung injury mimicking the characteristics typical of bronchopulmonary dysplasia. We report that arginase expression is increased in the lungs of bleomycin-exposed neonatal rats and that treatment with the arginase inhibitor amino-2-borono-6-hexanoic acid prevented the bleomycin-induced development of pulmonary hypertension and deposition of collagen. Arginase inhibition resulted in increased l-arginine and l-arginine bioavailability and increased pulmonary nitric oxide production. Arginase inhibition also normalized the expression of inducible nitric oxide synthase, and reduced bleomycin-induced nitrative stress while having no effect on bleomycin-induced inflammation. Our data suggest that arginase is a promising target for therapeutic interventions in neonates aimed at preventing lung vascular remodeling and pulmonary hypertension. PMID:25595650

Grasemann, Hartmut; Dhaliwal, Rupinder; Ivanovska, Julijana; Kantores, Crystal; McNamara, Patrick J; Scott, Jeremy A; Belik, Jaques; Jankov, Robert P

2015-03-15

167

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

International Nuclear Information System (INIS)

The combined interest of thermography and sup(99m)Tc bleomycin scintigraphy in the differential diagnosis of a cold thyroid nodule was evaluated in 86 patients. In all cases a histological examination was performed. Of the 30 malignant nodules (clinically suspect and solitary nodules) 21 (70%) showed concentrations of sup(99m)Tc bleomycin while only 7 of the 12 solitary malignant nodules did so. Among the 54 benign nodules the false positive rate was 54%. Thermography was positive in 26 (87%) of the 30 malignant nodules and in only 8 (67%) of the 12 solitary malignant nodules. For the 54 benign nodules the false positive rate was 72%. The combined results of the study do not provide any improvement in diagnostic accuracy. Thus it can be said that applications of sup(99m)Tc bleomycin and thermography in the diagnosis of solitary hypofixiant nodules are of limited value

168

A spatially explicit hydro-ecological modeling framework (BEPS-TerrainLab V2.0): Model description and test in a boreal ecosystem in Eastern North America  

Science.gov (United States)

SummaryA spatially explicit, process-based hydro-ecological model, BEPS-TerrainLab V2.0, was developed to improve the representation of ecophysiological, hydro-ecological and biogeochemical processes of boreal ecosystems in a tightly coupled manner. Several processes unique to boreal ecosystems were implemented including the sub-surface lateral water fluxes, stratification of vegetation into distinct layers for explicit ecophysiological representation, inclusion of novel spatial upscaling strategies and biogeochemical processes. To account for preferential water fluxes common in humid boreal ecosystems, a novel scheme was introduced based on laboratory analyses. Leaf-scale ecophysiological processes were upscaled to canopy-scale by explicitly considering leaf physiological conditions as affected by light and water stress. The modified model was tested with 2 years of continuous measurements taken at the Eastern Old Black Spruce Site of the Fluxnet-Canada Research Network located in a humid boreal watershed in eastern Canada. Comparison of the simulated and measured ET, water-table depth (WTD), volumetric soil water content (VSWC) and gross primary productivity (GPP) revealed that BEPS-TerrainLab V2.0 simulates hydro-ecological processes with reasonable accuracy. The model was able to explain 83% of the ET, 92% of the GPP variability and 72% of the WTD dynamics. The model suggests that in humid ecosystems such as eastern North American boreal watersheds, topographically driven sub-surface baseflow is the main mechanism of soil water partitioning which significantly affects the local-scale hydrological conditions.

Govind, Ajit; Chen, Jing Ming; Margolis, Hank; Ju, Weimin; Sonnentag, Oliver; Giasson, Marc-André

2009-04-01

169

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

170

Effects of Matrine on JAK-STAT Signaling Transduction Pathways in Bleomycin-Induced Pulmonary Fibrosis  

OpenAIRE

The current study aims to investigate the effects of matrine on the JAK-STAT signaling transduction pathways in bleomycin (BLM)-induced pulmonary fibrosis (PF) and to explore its action mechanism. A total of 72 male C57BL/6 mice were randomized into the control, model, and treatment groups. PF models were established by instilling BLM intratracheally. The treatment group was given daily matrine through gastric lavage. Six mice were sacrificed in each group at 3, 7, 14, and 28 days. The lung t...

Ma, Xiuqin; Chen, Ruhua; Liu, Xiufang; Xie, Jin; Si, Keyun; Duan, Lirong

2013-01-01

171

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

172

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)

173

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

174

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

International Nuclear Information System (INIS)

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

175

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

International Nuclear Information System (INIS)

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

176

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

177

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

178

Conjugated bleomycin A5-DTPA and its labelling with 153Sm  

International Nuclear Information System (INIS)

Bleomycin A5(BLMA5) is conjugated with cyclic DTPA anhydride and labelled with 153Sm. The conditions of conjugation and labelling are investigated. The possible composition of BLMA5-DTPA is analyzed by measurement and computation. The results show that bleomycin A5 can conjugate with DTPA anhydride easily when the mole ratio of cDTPAA to BLMA5 is more than 10 in weak basic media, and the conjugating yield is more than 80%; A molecule of BLMA5 conjugate with 2 molecule of cDTPAA when the mole ratio of cDTPAA to BLMA5 is not less than 15, and the conjugative positions is on 2 different N atoms. The results of labeling experiments indicate that the labeling yield of 153Sm-DTPAA-BLMA5 is 98% at pH7 - 9 and room temperature for 30 min when the mole ratio of DTPA-BLMA5 to 153Sm is more than 8. 153Sm-BLMA5-DTPA is stable and the radiochemical purity is more than 96% at room temperature for 6 days

179

Minimally Invasive Treatment of Giant Haemangiomas of the Liver: Embolisation With Bleomycin  

International Nuclear Information System (INIS)

PurposeThe management of patients with giant haemangioma of the liver remains controversial. Although the usual treatment method for symptomatic giant haemangioma is surgery, the classical paradigm of operative resection remains. In this study, we evaluated the symptomatic improvement and size-reduction effect of embolisation with bleomycin mixed with lipiodol for the treatment of symptomatic giant hepatic haemangioma.MethodsThis study included 26 patients [21 female, five male; age 41–65 years (mean 49.83 ± 1.53)] with symptomatic giant haemangioma unfit for surgery and treated with selective embolisation by bleomycin mixed with lipiodol. The patients were followed-up (mean 7.4 ± 0.81 months) clinically and using imaging methods. Statistical analysis was performed using SPSS version 16.0, and p 3 (range 3.39–1559 cm3) before intervention and 244.43 ± 54.38 cm3 (range 94–967 cm3) after intervention. No mortality or morbidity related to the treatment was identified. Symptomatic improvement was observed in all patients, and significant volume reduction was achieved (p = 0.001).ConclusionThe morbidity of surgical treatment in patients with giant liver hemangioma were similar to those obtained in patients followed-up without treatment. Therefore, follow-up without treatment is preferred in most patients. Thus, minimally invasive embolisation is an alternative and effective treatment for giant symptomatic haemangioma of the liver

180

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

181

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

Science.gov (United States)

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 mus 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. PMID:18980687

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

2008-01-01

182

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

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"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 iron does not preclude the presence of free iron in the serum. PMID:7545860

Han, K E; Okada, S

1995-06-01

183

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

184

Enhanced killing of human small cell lung cancer by hyperthermia and indium-111-bleomycin complex  

International Nuclear Information System (INIS)

Indium-111-bleomycin complex (111In-BLMC) is a radiopharmaceutical agent that produces tumor regression in mouse glioma in vivo and kills human small cell lung cancer (SCLC) cells in vitro. The interaction between hyperthermia and 111In-BLMC against human SCLC (N417) cells was studied for bleomycin (BLM) (15 micrograms/ml) or 111In-BLMC (40-50 microCi carried by 15 micrograms BLM/ml) for 5 min or 1.5, 2, or 4 hr at 37 degrees C or 43 degrees C exposures. Cell survival was determined by colony formation in soft agarose. There was a synergistic effect for 111In-BLMC and hyperthermia for cell killing. At 37 degrees C, the percent survival of N417 cells for BLM alone was 25.9%, and for 111In-BLMC it was 13.2%; at 43 degrees C, survival was 5.3% for BLM alone and 1.2% for 111In-BLMC by a 4 hr treatment. Effectiveness was greater when 111In-BLMC was combined with hyperthermia

185

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

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

MANUEL OYARZÚN

2005-01-01

186

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.

187

Further characterizations of bleomycin-sensitive (blm) mutants of Saccharomyces cerevisiae with implications for a radiomimetic model.  

OpenAIRE

Direct selection for 12 mutations (blm) conferring hypersensitivities to lethal effects of bleomycins in Saccharomyces cerevisiae resulted in mutants exhibiting cross-hypersensitivity to ionizing radiation and hydrogen peroxide. Remaining mutations did not confer cross-hypersensitivity to radiation. All blm mutations were recessive, except codominant blm3-1, and were assigned to seven complementation groups.

Moore, C. W.

1991-01-01

188

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

189

A Comparison of Effects of ABVD and ChlVPP Chemotherapeutic Protocols for Hodgkin's Disease on Rats’ Epididiymal and Testicular Tissues  

OpenAIRE

The goal of this study was to determine the effects of ABVD and ChlVPP chemotherapeutic protocols for Hodgkin's disease on the structure of testis and epididymis of male rat. After determining tolerance dose of drugs in pilot study, 24 male rats were divided to four groups: ABVD (doxorubicin, bleomycine, vinblastin, dacarbazine) group, ChlVPP (chlorambucil, vinblastin, procarbazine, prednisolone) group and two control groups one for each treatment group. One half of the lethal dose for 50% of...

Zare, S.; Mohammad Gholizad, L.; Eyshi Oskooii, A.; Nejati, V.

2010-01-01

190

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

191

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

192

Lysophosphatidic Acid Receptor–2 Deficiency Confers Protection against Bleomycin-Induced Lung Injury and Fibrosis in Mice  

Science.gov (United States)

Idiopathic pulmonary fibrosis is a devastating disease characterized by alveolar epithelial cell injury, the accumulation of fibroblasts/myofibroblasts, and the deposition of extracellular matrix proteins. Lysophosphatidic acid (LPA) signaling through its G protein–coupled receptors is critical for its various biological functions. Recently, LPA and LPA receptor 1 were implicated in lung fibrogenesis. However, the role of other LPA receptors in fibrosis remains unclear. Here, we use a bleomycin-induced pulmonary fibrosis model to investigate the roles of LPA2 in pulmonary fibrogenesis. In the present study, we found that LPA2 knockout (Lpar2?/?) mice were protected against bleomycin-induced lung injury, fibrosis, and mortality, compared with wild-type control mice. Furthermore, LPA2 deficiency attenuated the bleomycin-induced expression of fibronectin (FN), ?–smooth muscle actin (?-SMA), and collagen in lung tissue, as well as levels of IL-6, transforming growth factor–? (TGF-?), and total protein in bronchoalveolar lavage fluid. In human lung fibroblasts, the knockdown of LPA2 attenuated the LPA-induced expression of TGF-?1 and the differentiation of lung fibroblasts to myofibroblasts, resulting in the decreased expression of FN, ?-SMA, and collagen, as well as decreased activation of extracellular regulated kinase 1/2, Akt, Smad3, and p38 mitogen-activated protein kinase. Moreover, the knockdown of LPA2 with small interfering RNA also mitigated the TGF-?1–induced differentiation of lung fibroblasts. In addition, LPA2 deficiency significantly attenuated the bleomycin-induced apoptosis of alveolar and bronchial epithelial cells in the mouse lung. Together, our data indicate that the knockdown of LPA2 attenuated bleomycin-induced lung injury and pulmonary fibrosis, and this may be related to an inhibition of the LPA-induced expression of TGF-? and the activation and differentiation of fibroblasts. PMID:23808384

Huang, Long Shuang; Fu, Panfeng; Patel, Priya; Harijith, Anantha; Sun, Tianjiao; Zhao, Yutong; Garcia, Joe G. N.; Chun, Jerold

2013-01-01

193

Bleomycin-detectable iron in knee-joint synovial fluid from arthritic patients and its relationship to the extracellular antioxidant activities of caeruloplasmin, transferrin and lactoferrin.  

Science.gov (United States)

Some 40% of knee-joint synovial fluids from arthritic patients show the presence of bleomycin-detectable iron. This is released from a protein component of the fluid to bleomycin at acidic pH values. Patients whose fluids release iron have lower contents of transferrin, lactoferrin and caeruloplasmin than do patients whose fluids do not release iron to bleomycin. These proteins are important extracellular antioxidants, and measured antioxidant activities are extremely low in the iron-releasing fluids. The propensity of some fluids to release iron at low pH values, characteristic of the microenvironment beneath adherent macrophages, coupled with their decreased antioxidant protection against iron-stimulated oxygen-radical damage, might explain previously reported correlations between clinical disease severity, lipid peroxide content and the presence of bleomycin-detectable iron [Rowley, Gutteridge, Blake, Farr & Halliwell (1984) Clin. Sci. 66, 691-695]. PMID:2444216

Gutteridge, J M

1987-07-15

194

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)

195

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

196

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

197

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

International Nuclear Information System (INIS)

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

198

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

199

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)

200

Cyclotron production of carrier-free cobalt-55, a new positron-emitting label for bleomycin  

International Nuclear Information System (INIS)

A method for producing carrier-free 55Co (18.5 h) by proton bombardment of natural iron targets is presented. 55Co is formed primarily by means of the 56Fe (p, 2n)55Co reaction. Thin-target and thick-target yields as well as cross-section calculations are given in the 15-MeV to 40-MeV proton-energy range. Half-life measurements indicate a value of 18.5 h for 55Co. Chemical purification of the 55Co from the iron target is described 56Co, 52Mn, and 54Mn were found as radionuclidic impurities in the final preparation. The 55Co solution contains less than 0.5 ?g/ml of iron contamination. Synthesis of 55Co-bleomycin results in better than 99% labelling yield. (author)

201

Effects of conformation radiotherapy combined with daily intramuscular injection of bleomycin for uterine cervical cancer  

International Nuclear Information System (INIS)

During the period 1970-1978, 112 fresh cervical cancer patients were treated with conformation radiotherapy (60Co ?-ray). Since 1973, 2mg of Bleomycin was injected intramuscularly about 30 minutes before the irradiation in 30 cases of them (i.e. BR-therapy). The comparative prognosis for each treatment method was investigated and the following results were obtained. 1) In Stage II and III cases the incidence of the local recurrence was reduced from 32.6% with conformation radiotherapy alone to 16.7% by BR-therapy. 2) The 5 year crude survival rate for Stage III patients was 31.8% in the former group and 50.0% in the latter group. This evidence supports the view that BR-therapy is an effective treatment for the carcinoma of the cervix. (author)

202

Chromosome aberrations by a new /sup 111/In-Bleomycin complex  

International Nuclear Information System (INIS)

A new /sup 111/In-Bleomycin Complex (/sup 111/In-BLMC) was prepared and was effective for tumor imaging and therapy in mouse glioma and for killing human small cell lung cancer (SCLC) cells. Human SCLC cells (N417 or H526, NCI) were exposed to 0.9% NaCl, BLM (10-20 ?g/ml) or /sup 111/In-BLMC (24-50 ?Ci carried by 10-20 ?g BLM/ml) at 370C for 60 min. Cells were washed with fresh medium, treated with colcemid, hypotonic solution and fixer. Slides were stained with Giemsa solution and Q-binding stain. The karyotpe of the cells was analyzed. Experimental data is given. The results indicate that the /sup 111/In-BLMC causes chromosome damage which contributes to the tumor cell killing. The radiation dose from Auger electrons is small but concentrated and greatly increased chromosomal effects over that caused by BLM alone

203

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)

204

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

205

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

206

Minimally Invasive Treatment of Giant Haemangiomas of the Liver: Embolisation With Bleomycin  

Energy Technology Data Exchange (ETDEWEB)

PurposeThe management of patients with giant haemangioma of the liver remains controversial. Although the usual treatment method for symptomatic giant haemangioma is surgery, the classical paradigm of operative resection remains. In this study, we evaluated the symptomatic improvement and size-reduction effect of embolisation with bleomycin mixed with lipiodol for the treatment of symptomatic giant hepatic haemangioma.MethodsThis study included 26 patients [21 female, five male; age 41–65 years (mean 49.83 ± 1.53)] with symptomatic giant haemangioma unfit for surgery and treated with selective embolisation by bleomycin mixed with lipiodol. The patients were followed-up (mean 7.4 ± 0.81 months) clinically and using imaging methods. Statistical analysis was performed using SPSS version 16.0, and p < 0.05 was considered to indicate statistical significance.ResultsEmbolisation of 32 lesions in 26 patients was performed. The mean volume of the haemangiomas was 446.28 ± 88 cm{sup 3} (range 3.39–1559 cm{sup 3}) before intervention and 244.43 ± 54.38 cm{sup 3} (range 94–967 cm{sup 3}) after intervention. No mortality or morbidity related to the treatment was identified. Symptomatic improvement was observed in all patients, and significant volume reduction was achieved (p = 0.001).ConclusionThe morbidity of surgical treatment in patients with giant liver hemangioma were similar to those obtained in patients followed-up without treatment. Therefore, follow-up without treatment is preferred in most patients. Thus, minimally invasive embolisation is an alternative and effective treatment for giant symptomatic haemangioma of the liver.

Bozkaya, Halil, E-mail: halilbozkaya@yahoo.com; Cinar, Celal, E-mail: celalcinar@hotmail.com [Ege University, Division of Interventional Radiology, Department of Radiology, School of Medicine (Turkey); Besir, Fahri Halit, E-mail: drfhbesir@gmail.com [Duzce University, Department of Radiology, School of Medicine (Turkey); Par?ldar, Mustafa, E-mail: mparildar@yahoo.com; Oran, Ismail, E-mail: ismailoran@gmail.com [Ege University, Division of Interventional Radiology, Department of Radiology, School of Medicine (Turkey)

2013-04-12

207

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

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

Inagaki Hirofumi

2006-01-01

208

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

Science.gov (United States)

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

209

Measurement of the efficient cross section of the reaction 7Be(p, ?)8B at low energies and implications in the problem of solar neutrinos  

International Nuclear Information System (INIS)

The 8B produced inside the sun through the reaction 7Be(p,?)8B is the main, and even unique, source of high energy neutrinos detected in most solar neutrino detection experiments, except with Gallex and Sage. These experiments have all measured a neutrinos flux lower than the one predicted by solar models. Several explanations have been proposed to explain this deficit, but all require a precise knowledge of the efficient cross-section of the reaction 7Be(p,?)8B, because the neutrinos flux of 8B is directly proportional to this reaction. The direct measurement of this cross section for the solar energy is impossible because of its low value (about 1 femto-barn). In order to get round this problem, the cross sections are measured at higher energy and extrapolated to the solar energy using a theoretical energy dependence. The 6 previous experimental determinations of the efficient cross section were shared in two distinct groups with differences of about 30% which leads to an uncertainty of the same order on the high energy neutrinos flux. The re-measurement of the cross section of this reaction with a better precision is thus of prime importance. A direct measurement of the cross section in the energy range comprised between 0.35 and 1.4 MeV (cm) has been performed first. These experiments have permitted the precise measurement of each parameter involved in the determination of the cross section. Then, measurements of the cross section have been carried out with the PAPAP accelerator at 185.8, 134.7 and 111.7 keV, the lowest mass center energy never reached before. The results are in excellent agreement with those obtained at higher energies. The value obtained by extrapolation of these data for the astrophysical factor S17(0) is 19.21.3 EV-B, which leads to a significant reduction of the uncertainty on the high energy neutrinos flux of 8B. (J.S.)

210

Lung fibroblast alpha-smooth muscle actin expression and contractile phenotype in bleomycin-induced pulmonary fibrosis.  

OpenAIRE

The emergence of the myofibroblast phenotype (characterized by alpha-smooth muscle actin expression) in wound healing and in tissues undergoing fibrosis is thought to be responsible for the increased contractility of the affected tissues. In bleomycin-induced pulmonary fibrosis, the myofibroblast is also responsible for the observed increase in collagen gene expression. To evaluate further these phenotypic changes in lung fibroblasts, contractile and other phenotypic properties of fibroblasts...

Zhang, H. Y.; Gharaee-kermani, M.; Zhang, K.; Karmiol, S.; Phan, S. H.

1996-01-01

211

A Novel Mechanism for CCR4 in the Regulation of Macrophage Activation in Bleomycin-Induced Pulmonary Fibrosis  

OpenAIRE

Macrophage polarization into M1 or M2 phenotypes dictates the nature, duration, and severity of an inflammatory response. The objective of this study was to examine the role of CC chemokine receptor 4 (CCR4) in macrophage polarization during pulmonary oxidative injury in wild-type [WT (CCR4+/+)] and CCR4-deficient (CCR4?/?) mice. Intrapulmonary administration of bleomycin sulfate provoked lethal inflammatory and fibrotic responses in WT (CCR4+/+) mice, but such responses were absent in CC...

Trujillo, Glenda; O’connor, Erica C.; Kunkel, Steven L.; Hogaboam, Cory M.

2008-01-01

212

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

Energy Technology Data Exchange (ETDEWEB)

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

213

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.

214

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

Science.gov (United States)

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. PMID:21296518

Jin, Gong Yong; Bok, Se Mi; Han, Young Min; Chung, Myung Ja; Yoon, Kwon-Ha; Kim, So Ri; Lee, Yong Chul

2012-08-01

215

Effect of Polyunsaturated Fatty Acids and Their Metabolites on Bleomycin-Induced Cytotoxic Action on Human Neuroblastoma Cells In Vitro  

Science.gov (United States)

In the present study, we noted that bleomycin induced growth inhibitory action was augmented by all the polyunsaturated fatty acids (PUFAs) tested on human neuroblastoma IMR-32 (0.5×104 cells/100 µl of IMR) cells (EPA> DHA> ALA?=?GLA?=?AA> DGLA?=?LA: ?60, 40, 30, 10–20% respectively) at the maximum doses used. Of all the prostaglandins (PGE1, PGE2, PGF2?, and PGI2) and leukotrienes (LTD4 and LTE4) tested; PGE1, PGE2 and LTD4 inhibited the growth of IMR-32 cells to a significant degree at the highest doses used. Lipoxin A4 (LXA4), 19,20-dihydroxydocosapentaenoate (19, 20 DiHDPA) and 10(S),17(S)-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid (protectin: 10(S),17(S)DiHDoHE), metabolites of DHA, significantly inhibited the growth of IMR-32 cells. Pre-treatment with AA, GLA, DGLA and EPA and simultaneous treatment with all PUFAs used in the study augmented growth inhibitory action of bleomycin. Surprisingly, both indomethacin and nordihydroguaiaretic acid (NDGA) at 60 and 20 µg/ml respectively enhanced the growth of IMR-32 cells even in the presence of bleomycin. AA enhanced oxidant stress in IMR-32 cells as evidenced by an increase in lipid peroxides, superoxide dismutase levels and glutathione peroxidase activity. These results suggest that PUFAs suppress growth of human neuroblastoma cells, augment growth inhibitory action of bleomycin by enhancing formation of lipid peroxides and altering the status of anti-oxidants and, in all probability, increase the formation of lipoxins, resolvins and protectins from their respective precursors that possess growth inhibitory actions. PMID:25536345

Polavarapu, Sailaja; Mani, Arul M.; Gundala, Naveen K. V.; Hari, Anasuya D.; Bathina, Siresha; Das, Undurti N.

2014-01-01

216

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

OpenAIRE

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 ...

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

2011-01-01

217

A MicroCT-Based Method for the Measurement of Pulmonary Compliance in Healthy and Bleomycin-Exposed Mice  

OpenAIRE

Micro-computed tomography (microCT) is being increasingly used to examine small animal models of pulmonary injury. We have developed a microCT technique suitable for the determination of pulmonary compliance in injured mice. Lung volumes in normal mice were radiographically determined at end-inspiration and end-expiration and pulmonary compliance was calculated at two timepoints 2 weeks apart, while a second group of mice were given bleomycin and imaged 3 weeks following drug administration. ...

Shofer, Scott; Badea, Cristian; Auerbach, Scott; Schwartz, David A.; Johnson, G. Allan

2007-01-01

218

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

International Nuclear Information System (INIS)

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

219

The hypersensitivity of the Chinese hamster ovary variant BL-10 to bleomycin killing is due to a lack of glutathione S-transferase-alpha activity.  

Science.gov (United States)

As a means to understand the fundamental mechanisms of bleomycin cell killing, we previously isolated 19 bleomycin-sensitive mutants which represent at least six genetically distinct complementation groups (T.D. Stamato, B. Peters, P. Patil, N. Denko, R. Weinstein, and A. Giaccia. Cancer Res., 47: 1588-1592, 1987). One class of mutants represented by the cell line BL-10 displays only hypersensitivity to killing by bleomycin in both acute (16 h) and chronic treatments but no sensitivity to killing by other DNA-damaging agents. Complementation studies between this mutant and human fibroblasts suggested that the human gene which corrects the defect of BL-10 rested on human chromosome 6. It has been reported that the gene for human glutathione S-transferase (GST) alpha also resides on chromosome 6. Measurements of selenium-independent peroxidase (alpha-GST + glutathione peroxidase) activity in wild-type Chinese hamster ovary (CHO) cells, using cumene hydrogen peroxide as a substrate, gave a value of 112 nmol of glutathione oxidized/min/mg protein compared with 88.1 nmol of glutathione oxidized/min/mg protein for BL-10. Measurement of the selenium-dependent peroxidase activity, using H2O2 as a substrate, resulted in 65.9 nmol of reduced glutathione oxidized/min/mg protein in CHO and 81.5 nmol of reduced glutathione oxidized/min/mg protein for BL-10. In other words, BL-10 cells did not exhibit a difference in their ability to metabolize both substrates in contrast to CHO cells. This indicates that BL-10 possesses little alpha-GST activity. Transfection of BL-10 cells with a mammalian expression vector containing the alpha-GST gene increases the survival of BL-10 to bleomycin and does not increase the bleomycin resistance of two other bleomycin mutants which lie in different genetic complementation groups. These data strongly implicate a role for alpha-GST in the resistance of cells to bleomycin. PMID:1714344

Giaccia, A J; Lewis, A D; Denko, N C; Cholon, A; Evans, J W; Waldren, C A; Stamato, T D; Brown, J M

1991-08-15

220

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

International Nuclear Information System (INIS)

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

221

BeP2: a tetrahedral structure of type order-disorder which obeys a coordination rule for short-range order  

International Nuclear Information System (INIS)

Single-crystal studies on BeP2 indicate that this compound possesses an OD structure. The substructure has a tetragonal unit cell with: a = 3.546 A, c = 15.01 A, Z = 4, space group: I41/amd. The final R factor has a value of 0.033. The atom sites in this substructure correspond to the sites of diamond if the latter is described with a tetragonal cell, where a = (2/sup 1/2//a/sub diamond/ and c = 3a/sub diamond/. A short-range order governs the occupation of these sites with Be and P atoms. Each Be has four tetrahedral P neighbors and every P has two Be and two P neighbors. Consideration of the maxima on the diffuse streaks between the sharp reflectins of the substructure leads to an intermediate unit cell with a = 7.09 A and c = 30.02 A. Coordination considerations allow a structure proposal to be formulated for this intermediate structure which is triclinic but pseudotetragonal. The true unit cell is also pseudotetragonal with a = 7.09 A and c = N . 15.01 A, where N is a large integer

222

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

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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 radiotheraith the combination compared to radiotherapy alone, this has not clearly been established in the four randomized trials reviewed

223

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

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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 m/sup 2/ 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.

Forastiere, A.A.; Uikram, B.; Spiro, R.H.; Wittes, R.E.

1981-10-01

224

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

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Twenty four patients with squamous carcinoma of the head and neck and advanced regional (N2/sub -/3) disease were treated. The regimen consisted of 3 cycles, each of 28 days. Cyclophosphamide (I gm/m2 I.V.) were given on day 1, bleomycin (15 ? I.M.) on days 2, 4, 9 and 11, and ionizing radiation (60Co, 180 rad/fraction) days 1-5, and 8-12. No therapy was given on days 13-28. After three cycles of therapy, 13 patients had a complete response; following further therapy (surgery, interstitial or extenal beam radiation), 16 patients were free of disease. However, remissions were not durable and 11/16 patients recurred loco-regionally with a median time to recurrence of 5 months; most (7/11) also developed distant metastases. These patients have biologically aggressive disease and may have a worse prognosis than patients who are Stage IV based on a T4 primary lesion only

225

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

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

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

1982-01-01

226

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

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

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

1982-01-01

227

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

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

Tagami Atsuro

2008-05-01

228

Sclerosing cholangitis secondary to bleomycin-iodinated embolization for liver hemangioma.  

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Sclerosing cholangitis (SC) is a rarely reported morbidity secondary to transcatheter arterial chemoembolization (TACE) with bleomycin-iodinated oil (BIO) for liver cavernous hemangioma (LCH). This report retrospectively evaluated the diagnostic and therapeutic course of a patient with LDH who presented obstructive jaundice 6 years after TACE with BIO. Preoperative imaging identified a suspected malignant biliary stricture located at the convergence of the left and right hepatic ducts. Operative exploration demonstrated a full-thickness sclerosis of the hilar bile duct with right hepatic duct stricture and right lobe atrophy. Radical hepatic hilar resection with right-side hemihepatectomy and Roux-en-Y hepaticojejunostomy was performed because hilar cancer could not be excluded on frozen biopsy. Pathological results showed chronic pyogenic inflammation of the common and right hepatic ducts with SC in the portal area. Secondary SC is a long-term complication that may occur in LCH patients after TACE with BIO and must be differentiated from hilar malignancy. Hepatic duct plasty is a definitive but technically challenging treatment modality for secondary SC. PMID:25516686

Jin, Shuo; Shi, Xiao-Ju; Sun, Xiao-Dong; Wang, Si-Yuan; Wang, Guang-Yi

2014-12-14

229

Cytotoxic activity, tumor accumulation, and tissue distribution of ruthenium-103-labeled bleomycin  

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Bleomycin (BLM) was labeled with gamma-emitting 103Ru. Yields of 103Ru-labeled BLM as high as 50.6% were attained. 103Ru-labeled BLM was stable in vitro and the 103ru label was not displaced by large excesses of Cu (II) and Co (II) or Fe (III). Chromatography of the urine following 103Ru-labeled BLM injection indicated no in vivo decomposition. Pharmacokinetic studies in healthy inbred SD and tumor-bearing inbred BUF rats demonstrated tumor accumulations, tissue distributions, and clearance nearly identical with those reported for 3H-labeled BLM. Cytotoxicity studies on a WI-L2 human B-cell line showed that BLM labeled with nonradioactive Ru retained 100% of the activity demonstrated by native BLM. Thus BLM may be labeled with isotopes of Ru to form stable complexes by a simple, rapid reaction without loss of its chemotherapeutic properties or variations in its in vivo distribution. BLM labeled with the proper Ru isotope should prove useful as a gamma-emitting tracer for BLM or a beta-emitting compound capable of providing combination chemotherapy and radiotherapy of tumors

230

Presence of bleomycin-detectable free iron in the alveolar system of preterm infants.  

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Chronic lung disease (CLD) is a major cause of long term morbidity in preterm infants. Reactive oxygen species (ROS) play an important role in the pathogenesis of CLD. We show that a high percentage (63 to 83%) of the investigated bronchoalveolar secretions (BAS) of neonates contain bleomycin-detectable free iron concentrations (0. 04-0.124 nmol/micrograms SC, median range). Beside the presence of redox-active iron several iron-binding proteins like transferrin, ferritin and lactoferrin were determined in BAS. Comparison of protein distribution within the first three days of life showed slight differences between the group of preterm infants who developed CLD and the neonates who recovered from RDS. Because of the existence of free iron we suggest a higher risk of hydroxyl radical formation in the alveolar space. In an artificial system with addition of iron and hydrogen peroxide we were able to demonstrate OH-radical production in BAS by electron paramagnetic resonance (EPR). OH-radical formation by H2O2 and iron in buffer solution was slightly enhanced in the presence of BAS, indicating the absence of OH-radical-scavengers in BAS. PMID:10092536

Gerber, C E; Bruchelt, G; Stegmann, H; Schweinsberg, F; Speer, C P

1999-04-01

231

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

232

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.

233

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

International Nuclear Information System (INIS)

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

234

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)

235

Intratumoral injection of 5-fluorouracil and bleomycin for inoperable cancer in the cardioesophageal region  

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The methods and results of combined therapy (drugs+radiation+intratumoral injection of 5-fluorouracil and chemoimmunotherapy+intratumoral injection of blemycin) were compared with the standard procedure (chemotherapy+radiation) for treating inoperable cancer in the cardioesophageal region. The study group included 47 patients aged 32-79. Tumors were inoperable due to considerable expansion in 32 and remote metastases in 15 patients. The single dose of 5-flyorouracil injected into tumor via a fibroendoscope at the start of chemoradiation treatment ranged 750-1000 mg (course dose of the drug - 2.75-4.25 g, total focal dose of radiation - 24-36 Gy). The single intratumoral dose of bleomycin injected prior to total polychemotherapy (vinblastin, ftorafur, cyclophosphamide) was 10-15 mg. In the control group receiving standard combined therapy, the total focal dose was 60-62 Gy and course dose of 5-fluorouracil - 5-7 g. Objective improvement was observed in 63.6% matched by a mean survival time of 14.6 months after combined therapy given in conjunction with supporting chemoimmunotherapy. This showed an improvement on the results of standard combination therapy which were 58.3% and 9.3 months, respectively

236

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

237

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.

238

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

239

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)

240

The copper chelator tetrathiomolybdate regressed bleomycin-induced pulmonary fibrosis in mice, by reducing lysyl oxidase expressions.  

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Pulmonary fibrosis (PF) is characterized by an increase in the number of fibroblasts and an accumulation of collagen fibers in the extracellular matrix (ECM). The members of the copper-dependent lysyl oxidase (LOX) enzyme family regulate the collagen accumulation in the ECM. Tetrathiomolybdate (TM) is a copper chelator. The present study reported the effect of TM on the expression of LOX proteins (LOX, LOXL1, and LOXL2), collagen digestion enzymes (MMP2 and MMP8), and TIMP1 (a collagenase inhibitor) in PF. The PF in mice was induced by intratracheal bleomycin instillation. Adult mice were divided into four groups: mice dissected after 21 days of the first bleomycin (0.08 mg/kg, single dose) treatment (I) and their controls (II), and mice treated with TM for 1 week (1.2 mg/day/mice for the first 4 days and 0.9 mg/day/mice for the last 3 days) after 14 days of the first bleomycin instillation and dissected in the 21st day of the experiment (III) and their controls (IV). Mice in groups III and IV were fed a low-copper (2 mg/kg) diet during the last 7 days of the experiment. The fibrosis score in the lung was determined under a microscope. The expressions of collagen-I, LOX, MMP, and TIMP1 proteins were analyzed by Western blotting in the lung. Mice lungs with fibrosis were characterized by an overexpression of collagen-I, LOX, MMP, and TIMP1 proteins in addition to an accumulation of collagen fibers. TM treatments significantly regressed the overexpression of these proteins in the fibrotic mice lung. In conclusion, TM treatments can be used for the regression of PF, by decreasing collagen-I protein expression and accumulation. PMID:25349139

Ovet, Hale; Oztay, Fusun

2014-12-01

241

Fibrosis, Vascular Activation, and Immune Abnormalities Resembling Systemic Sclerosis in Bleomycin-Treated Fli-1–Haploinsufficient Mice  

Science.gov (United States)

Objective Fli-1, a potential predisposing factor for systemic sclerosis (SSc), is constitutively down-regulated in the lesional skin of patients with SSc by an epigenetic mechanism. To investigate the impact of Fli-1 deficiency on the induction of an SSc phenotype in various cell types, we generated bleomycin-induced skin fibrosis in Fli-1+/? mice and investigated the molecular mechanisms underlying its phenotypic alterations. Methods Messenger RNA (mRNA) levels and protein expression of target molecules were examined by quantitative reverse transcription–polymerase chain reaction and immunostaining. Transforming growth factor ? (TGF?) bioassay was used to evaluate the activation of latent TGF?. The binding of Fli-1 to the target gene promoters was assessed with chromatin immunoprecipitation. Results Bleomycin induced more severe dermal fibrosis in Fli-1+/? mice than in wild-type mice. Fli-1 haploinsufficiency activated dermal fibroblasts via the up-regulation of ?v?3 and ?v?5 integrins and activation of latent TGF?. Dermal fibrosis in Fli-1+/? mice was also attributable to endothelial-to-mesenchymal transition, which is directly induced by Fli-1 deficiency and amplified by bleomycin. Th2/Th17-skewed inflammation and increased infiltration of mast cells and macrophages were seen, partly due to the altered expression of cell adhesion molecules in endothelial cells as well as the induction of the skin chemokines. Fli-1+/? mouse macrophages preferentially differentiated into an M2 phenotype upon stimulation with interleukin-4 (IL-4) or IL-13. Conclusion Our findings provide strong evidence for the fundamental role of Fli-1 deficiency in inducing SSc-like phenotypic alterations in dermal fibroblasts, endothelial cells, and macrophages in a manner consistent with human disease. PMID:25385187

Taniguchi, Takashi; Asano, Yoshihide; Akamata, Kaname; Noda, Shinji; Takahashi, Takehiro; Ichimura, Yohei; Toyama, Tetsuo; Trojanowska, Maria; Sato, Shinichi

2015-01-01

242

Accumulation of low molecular weight (bleomycin detecable) iron in bone marrow cells of rats after benzene exposure  

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An accumulation of low molecular weight (LMW) bleomycin detectable iron in the bone marrow was observed after administration of benzene (IP 0.5 ml/kg, daily) for 5 and 10 days in female albino rats. However, this LMW iron was not detectable in the bone marrow of rats from the control group. Studies of bone marrow fractionation showed that the maximum accumulation of this LMW iron was in the mitochondrial fraction. An increase in the activity of superoxide dismutase and lipid peroxidation was also noticed in the benzene exposed groups. (orig.).

Pandya, K.P.; Rao, G.S.; Khan, S.; Krishnamurthy, R. (Industrial Toxicology Research Centre, Lucknow (India))

1990-06-01

243

Accumulation of low molecular weight (bleomycin detectable) iron in bone marrow cells of rats after benzene exposure.  

Science.gov (United States)

An accumulation of low molecular weight (LMW) bleomycin detectable iron in the bone marrow was observed after administration of benzene (IP 0.5 ml/kg, daily) for 5 and 10 days in female albino rats. However, this LMW iron was not detectable in the bone marrow of rats from the control group. Studies of bone marrow fractionation showed that the maximum accumulation of this LMW iron was in the mitochondrial fraction. An increase in the activity of superoxide dismutase and lipid peroxidation was also noticed in the benzene exposed groups. PMID:1696804

Pandya, K P; Rao, G S; Khan, S; Krishnamurthy, R

1990-01-01

244

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.)

245

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

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

Ricardo Aurino Pinho

2009-09-01

246

Bleomycin sulphate loaded nanostructured lipid particles augment oral bioavailability, cytotoxicity and apoptosis in cervical cancer cells.  

Science.gov (United States)

In present investigation, bleomycin sulphate loaded nanostructured lipid particles (BLM-NLPs) were constructed to enhance the oral bioavailability by overwhelming the first pass hepatic metabolism. The particles size and nanoencapsulation efficiency of BLM-NLPs were measured to be 17.4±5.4nm and 45.3±3.4%, respectively. Our studies indicated that the drug was molecularly dispersed in the lipid nanocoacervates, with amorphous geometry, without altering the chemical structure, as ascertained by spectral studies. The nanoformulation, BLM-NLPs was analyzed for dissolution testing, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cell line, HeLa cells. BLM-NLPs released the drug with first order kinetic in simulated intestinal fluid (pH?6.8±0.1), characterized by initial burst and followed by slow release. Further, an enhanced cytotoxicity (?5.6 fold lower IC50), improved intracellular concentration (?4.38 fold) and greater degree of apoptosis was induced by BLM-NLPs in HeLa cells, as compared to BLM alone. Moreover, BLM-NLPs also showed dose-dependent internalization, as evinced by cellular uptake study. The in vivo study indicated a significantly (P<0.0001) smaller elimination rate constant (KE), volume of distribution (Vd) and clearance rate (CLTotal) for BLM-NLPs, as compared to BLM solution in post-oral administrations. This clearly depicts the retention and stability of tailored nanoformulation in intestinal absorption pathway. In addition, our nanoformulation, BLM-NLPs documented significantly (P<0.0001)?3.4 fold (66.20±2.57%) higher bioavailability than BLM solution (19.56±0.79%). In conclusion, our in vitro and in vivo results warrant the safety, efficacy and potency of tailored nanoformulation in clinical settings. PMID:24732397

Saini, Jyoti; Bansal, Vikas; Chandra, Ankush; Madan, Jitender; Jain, Upendra Kumar; Chandra, Ramesh; Jain, Sarvesh Malviya

2014-06-01

247

Rikkunshito ameliorates cachexia associated with bleomycin-induced lung fibrosis in mice by stimulating ghrelin secretion.  

Science.gov (United States)

Cachexia is a frequent complication in patients with respiratory failure, such as lung fibrosis, and it is a determining factor for functional capacity, health status, and mortality. Reductions in body weight and skeletal muscle mass are key features of cachexia that are resistant to current therapies. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment for patients with gastrointestinal symptoms and known to stimulate ghrelin secretion. By using bleomycin (BLM)-induced lung fibrosis mice in this study, we tested our hypothesis that RKT administration could ameliorate pulmonary cachexia. After BLM administration, mice were provided with either RKT or distilled water on a daily basis. Compared with the BLM-injected mice, the RKT-treated mice had smaller reductions of food intake and body weight. Skeletal muscle weights were retained in the RKT-treated mice, in conjunction with reduced expressions of MuRF-1 and atrogin-1 in the lysates of skeletal muscle found in lung fibrosis. Rikkunshito administration restored the plasma concentrations of ghrelin in BLM-injected mice. The anticachectic efficacies of RKT administration in BLM-injected mice were canceled by the concurrent treatment of a ghrelin receptor antagonist. Rikkunshito administration did not decrease the degree of loss of body weight or food intake reduction in either ghrelin-deficient mice or growth hormone secretagogue receptor-deficient mice. Our results indicate that RKT administration exerts protective effects on pulmonary cachexia by ameliorating skeletal muscle wasting and food intake reduction as mediated by the ghrelin system and, thus, highlight RKT as a potential therapeutic agent for the management of lung fibrosis. PMID:25270999

Tsubouchi, Hironobu; Yanagi, Shigehisa; Miura, Ayako; Mogami, Sachiko; Yamada, Chihiro; Iizuka, Seiichi; Hattori, Tomohisa; Nakazato, Masamitsu

2014-10-01

248

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

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Full Text Available Abstract Background C-C chemokine receptor (CCR7 is a regulator of dendritic cell and T cell migration, and its role in tissue wound healing has been investigated in various disease models. We have previously demonstrated that CCR7 and its ligand, chemokine (C-C motif ligand (CCL21, modulates wound repair in pulmonary fibrosis (PF but the mechanism of this is unknown. The objective of this study was to investigate whether the absence of CCR7 protects against bleomycin (BLM-induced PF. CCR7-/- mice failed to mount a fibrotic pulmonary response as assessed by histologic collagen staining and quantification by hydroxyproline. We hypothesized that the prominent characteristics of CCR7-/- mice, including elevated levels of cytokine and chemokine mediators and the presence of bronchus-associated lymphoid tissue (BALT might be relevant to the protective phenotype. Results Pulmonary fibrosis was induced in CCR7+/+ and CCR7-/- mice via a single intratracheal injection of BLM. We found that the lung cytokine/chemokine milieu associated with the absence of CCR7 correlated with an increase in BALT, and might be attributable to regulatory T cell (Treg homeostasis and trafficking within the lungs and lymph nodes. In response to BLM challenge, CCR7-/- mice exhibited an early, steady increase in lung CD4+ T cells and increased CD4+ CD25+ FoxP3+ Tregs in the lungs 21 days after challenge. These findings are consistent with increased lung expression of interleukin-2 and indoleamine 2,3-dioxygenase in CCR7-/- mice, which promote Treg expansion. Conclusions Our study demonstrates that the protective phenotype associated with BLM-treated CCR7-/- mice correlates with the presence of BALT and the anchoring of Tregs in the lungs of CCR7-/- mice. These data provide novel evidence to support the further investigation of CCR7-mediated Treg trafficking in the modulation of BLM-induced PF.

Trujillo Glenda

2010-09-01

249

Proteomic analysis of altered extracellular matrix turnover in bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

Fibrotic disease is characterized by the pathological accumulation of extracellular matrix (ECM) proteins. Surprisingly, very little is known about the synthesis and degradation rates of the many proteins and proteoglycans that constitute healthy or pathological extracellular matrix. A comprehensive understanding of altered ECM protein synthesis and degradation during the onset and progression of fibrotic disease would be immensely valuable. We have developed a dynamic proteomics platform that quantifies the fractional synthesis rates of large numbers of proteins via stable isotope labeling and LC/MS-based mass isotopomer analysis. Here, we present the first broad analysis of ECM protein kinetics during the onset of experimental pulmonary fibrosis. Mice were labeled with heavy water for up to 21 days following the induction of lung fibrosis with bleomycin. Lung tissue was subjected to sequential protein extraction to fractionate cellular, guanidine-soluble ECM proteins and residual insoluble ECM proteins. Fractional synthesis rates were calculated for 34 ECM proteins or protein subunits, including collagens, proteoglycans, and microfibrillar proteins. Overall, fractional synthesis rates of guanidine-soluble ECM proteins were faster than those of insoluble ECM proteins, suggesting that the insoluble fraction reflected older, more mature matrix components. This was confirmed through the quantitation of pyridinoline cross-links in each protein fraction. In fibrotic lung tissue, there was a significant increase in the fractional synthesis of unique sets of matrix proteins during early (pre-1 week) and late (post-1 week) fibrotic response. Furthermore, we isolated fast turnover subpopulations of several ECM proteins (e.g. type I collagen) based on guanidine solubility, allowing for accelerated detection of increased synthesis of typically slow-turnover protein populations. This establishes the presence of multiple kinetic pools of pulmonary collagen in vivo with altered turnover rates during evolving fibrosis. These data demonstrate the utility of dynamic proteomics in analyzing changes in ECM protein turnover associated with the onset and progression of fibrotic disease. PMID:24741116

Decaris, Martin L; Gatmaitan, Michelle; FlorCruz, Simplicia; Luo, Flora; Li, Kelvin; Holmes, William E; Hellerstein, Marc K; Turner, Scott M; Emson, Claire L

2014-07-01

250

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

251

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

International Nuclear Information System (INIS)

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

252

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

253

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

254

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

255

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

International Nuclear Information System (INIS)

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-HT3 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 (10-5 mol/l) had no effect on the survival of irradiated cells. Granisetron (10-5 mol/l) significantly potentiated cytoxocity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10-7 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-HT3 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.)

256

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)

257

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

OpenAIRE

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

258

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

259

Javvin: Protocol Dictionary  

Science.gov (United States)

The Javvin Company offers this online Network Protocol Suite Directory and Index. A network protocol is made up of "a formal set of rules, conventions and data structure that governs how computers exchange information over a network." This compiled online database is handy given that these protocols are defined by various organizations and technology vendors. The database organizes the protocols according to their key functions or their origin/sponsors, but the listing can be viewed alphanumerically by protocol name. The website also provides information on Javvin's products. Visitors can get a free a protocol network map poster by contributing to the protocol dictionary.

260

Analysing layered security protocols  

OpenAIRE

Many security protocols are built as the composition of an application-layer protocol and a secure transport protocol, such as TLS. There are many approaches to proving the correctness of such protocols. One popular approach is verification by abstraction, in which the correctness of the application-layer protocol is proven under the assumption that the transport layer satisfies certain properties, such as confidentiality. Following this approach, we adapt the strand spaces model in order to ...

Gibson-robinson, Thomas; Lowe, Gavin

2013-01-01

261

A young male with shortness of breath  

Directory of Open Access Journals (Sweden)

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

262

Clinical studies with In-111 BLEDTA, a tumor-imaging conjugate of bleomycin with a bifunctional chelating agent  

International Nuclear Information System (INIS)

Indium-111 BLEDTA, a bleomycin analog containing an EDTA group, was used for tumor imaging in 110 patients with cancer. Scans with In-111 BLEDTA agreed with biopsy results in 75 of 95 patients (79% accuracy). A positive scan was obtained in 71 of 88 patients with a positive biopsy (81% sensitivity). In 21 of 95 patients (22%), the scan revealed tumor sites that had not been detected. The main limitation of visualization was the size of the tumor (1.5--2.0 cm diameter was the smallest size seen). Background radioactivity in the liver, spleen, and bone marrow also made tumor detection in these areas more difficult. The cause of this background, and of false-positive uptake in sites of inflammation, is correlated with specific radiolabeling of polymorphonuclear leukocytes by In-111 BLEDTA. Means of eliminating this background are discussed

263

Pulmonary changes at computed tomography in patients with testicular carcinoma treated with cis-platinum, vinblastine and bleomycin  

International Nuclear Information System (INIS)

Computed tomography was performed before and after CVB therapy (cis-platinum, vinblastine, bleomycin) in 42 patients with metastatic testicular carcinoma. Twenty-one of these (3 symptomatic, 18 asymptomatic) developed subpleural pulmonary abnormalities which were streaky or reticular in 7, homogeneous with a broad base against pleura in 3 and had a mixed pattern in 11 patients. Histologic examination was obtained in 3 patients and showed fibrosis with no tumor tissue. Twelve patients with marked CVB induced abnormalities underwent repeat CT within 6 to 24 weeks. Changes disappeared spontaneously in 7, diminished in 3 and increased in 2 of these. Further conventional chest radiography of the latter two revealed complete regression of changes. Pulmonary lesions induced by CVB therapy should be kept in mind at follow-up so that an erroneous diagnosis of tumor progression is not made. (orig.)

264

Distribution of 67Ga-Bleomycin complex in normal rats and comparison with 67Ga-Cl3  

International Nuclear Information System (INIS)

67Ga- chloride was prepared in Cyclotron Department of Nuclear Research Center of Agriculture and Medicine, then Bleomycin was labeled with 67Ga-Chloride according to the general procedure, but some factors were modified. Distribution of 67 Ca-Bleomycin and 67 Ga-Chloride in 12 tissue of normal rats was studied 1,2, 4, 24 and 48 hours after injection, percent of injection dose per gram of tissue (%ID/g. tissue) in all of 12 normal rats for 67 Ga-Cl3 was lesser than 67Ga-Bl 1,2 and 4 hours after injection, About 67Ga-Bl %ID/g, tissues for bladder was high, because it goes out of body by urine, and there was a high %ID/g, tissue in lung after 1, 2 and 4 hours. About 67GaCl3 likes 67Ga-Bl there was a high %ID/g tissue for bladder, after that was high %ID/g tissue in lung and kidney, too. Also 48 hours after injection, clearance of 67Ga-Bl from blood was 2.64 times that of 67Ga-Cl3 in normal rats and the clearance of 607Ga-Bl in blood from 1 hour till 48 hours after injection to the clearance of 67GaCl3 in blood for above times is about 7 times. They can be reasons that 67Ga does not isolated from 67Ga-Bl complex and not attach to plasma proteins

265

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.

266

Increased bleomycin-induced chromosome damage in lymphocytes of patients with common variable immunodeficiency indicates an involvement of chromosomal instability in their cancer predisposition.  

Science.gov (United States)

To study mutagen-induced chromosome instability in cancer disposition, late S and G2 lymphocytes of 15 patients with common variable immunodeficiency and 14 healthy controls were exposed to bleomycin in vitro. The groups did not differ in the frequency of spontaneous chromosome aberrations. In bleomycin-treated samples we found higher numbers of break events per cell and increased frequency of cells with aberrations compared to the control group. A slightly reduced breakage of chromosome group D was noted in patients. These results support the hypothesis that a higher incidence of cancer in patients with genetically determined immunodeficiencies may be explained by an increased mutagen-induced chromosome instability in at least some of them. PMID:2473834

Vorechovsky, I; Munzarova, M; Lokaj, J

1989-01-01

267

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

268

Transport Protocol Throughput Fairness  

OpenAIRE

Interest continues to grow in alternative transport protocols to the Transmission Control Protocol (TCP). These alternatives include protocols designed to give greater efficiency in high-speed, high-delay environments (so-called high-speed TCP variants), and protocols that provide congestion control without reliability. For the former category, along with the deployed base of ‘vanilla’ TCP – TCP NewReno – the TCP variants BIC and CUBIC are widely used within Linux: for the latter cate...

Saleem Bhatti; Martin Bateman

2009-01-01

269

Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-0-tetradecanoylphorbol 13-acetate  

International Nuclear Information System (INIS)

We have shown that oncogenic transformation induced by x-rays or bleomycin and the enhancement of transformation by phorbol esters (TPA) can be inhibited by superoxide dismutase (SOD). SOD catalyzes the conversion of the superoxide radical (02-) to H2O2 plus O2, and H2O2 is removed by catalase. The present results suggest that SOD plays an inhibitory role in oncogenic transformation by inhibiting promotion. 33 references, 2 figures, 2 tables

270

Oxidation of the sugar moiety of DNA by ionizing radiation or bleomycin could induce the formation of a cluster DNA lesion  

OpenAIRE

Bleomycin, a radiomimetic drug currently used in human cancer therapy, is a well known carcinogen. Its toxicity is mostly attributed to its potentiality to induce DNA double strand breaks likely arising from the formation of two vicinal DNA strand breaks, initiated by C4-hydrogen abstraction on the 2-deoxyribose moiety. In this work we demonstrate that such a hydrogen abstraction reaction is able to induce the formation of a clustered DNA lesion, involving a 3? strand break together with a ...

Regulus, Peggy; Duroux, Benoit; Bayle, Pierre-alain; Favier, Alain; Cadet, Jean; Ravanat, Jean-luc

2007-01-01

271

Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.  

OpenAIRE

Using short-term cultures of hamster embryo cells, we have examined the effects of the free-radical scavenger superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and the enzyme catalase (hydrogen-peroxide:hydrogenperoxide oxidoreductase, EC 1.11.1.6) on x-ray- and bleomycin-induced transformation and on the enhancement of radiogenic transformation by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). We find that superoxide dismutase inhibits (i) transformatio...

Borek, C.; Troll, W.

1983-01-01

272

BET bromodomain proteins mediate downstream signaling events following growth factor stimulation in human lung fibroblasts and are involved in bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

Epigenetic alterations, such as histone acetylation, regulate the signaling outcomes and phenotypic responses of fibroblasts after growth factor stimulation. The bromodomain and extra-terminal domain-containing proteins (Brd) bind to acetylated histone residues, resulting in recruitment of components of the transcriptional machinery and subsequent gene transcription. Given the central importance of fibroblasts in tissue fibrosis, this study sought to determine the role of Brd proteins in human lung fibroblasts (LFs) after growth factor stimulation and in the murine bleomycin model of lung fibrosis. Using small interfering RNA against human Brd2 and Brd4 and pharmacologic Brd inhibitors, this study found that Brd2 and Brd4 are essential in mediating the phenotypic responses of LFs downstream of multiple growth factor pathways. Growth factor stimulation of LFs causes increased histone acetylation, association of Brd4 with growth factor-responsive genes, and enhanced transcription of these genes that could be attenuated with pharmacologic Brd inhibitors. Of note, lung fibrosis induced after intratracheal bleomycin challenge in mice could be prevented by pretreatment of animals with pharmacologic inhibitors of Brd proteins. This study is the first demonstration of a role for Brd2 and Brd4 proteins in mediating the responses of LFs after growth factor stimulation and in driving the induction of lung fibrosis in mice in response to bleomycin challenge. PMID:23115324

Tang, Xiaoyan; Peng, Ruoqi; Ren, Yonglin; Apparsundaram, Subramanium; Deguzman, Jeremy; Bauer, Carla M; Hoffman, Ann F; Hamilton, Shannon; Liang, Zhenmin; Zeng, Hang; Fuentes, Maria E; Demartino, Julie A; Kitson, Christopher; Stevenson, Christopher S; Budd, David C

2013-01-01

273

Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-O-tetradecanoylphorbol 13-acetate  

International Nuclear Information System (INIS)

Using short-term cultures of hamster embryo cells, we have examined the effects of the free-radical scavenger superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and the enzyme catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase, EC 1.11.1.6) on x-ray-and bleomycin-induced transformation and on the enhancement of radiogenic transformation by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). We find that superoxide dismutase inhibits (i) transformation induced by x-ray and bleomycin and (ii) promotional action of TPA in vitro. The results suggest that the oncogenic action of x-rays and bleomycin and the enhancement of oncogenic transformation by TPA are mediated in part by free radicals. The findings also suggest that superoxide dismutase can serve as an inhibitor of oncogenesis and that its actions, as seen in this in vitro system, are most predominantly on inhibiting late events in the progression of cellular transformation--those associated with promotion

274

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

275

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

276

Killing of human lung cancer cells using a new ( sup 111 In)bleomycin complex ( sup 111 In)BLMC  

Energy Technology Data Exchange (ETDEWEB)

The ability of a ({sup 111}In)bleomycin complex (({sup 111}In)BLMC) to kill five cell lines of human lung cancer (small cell lung cancer) was investigated. Cells were exposed to either 0.9% NaCl, ({sup 111}In)Cl3, BLM, ({sup 111}In)BLMC, nonradioactive InCl3, or In-BLMC for 60 minutes, plated in soft agarose, and assessed for colony formation. ({sup 111}In)BLMC (40-200 microCi carried by 15-25 micrograms BLM/ml) was more cytotoxic than BLM (15-25 micrograms BLM/ml) by a factor of 1.6-5.3 for five cell lines. The percent survival of N417 cells was 28.4 for ({sup 111}In)BLMC (40 microCi/15 micrograms BLM/ml) and 54.3 for BLM (15 micrograms/ml); 1.9 for ({sup 111}In)BLMC (200 microCi/25 micrograms BLM/ml), and 10.0 for BLM (25 micrograms/ml). {sup 111}InCl3 (200 microCi/ml) and nonradioactive InCl3 failed to inhibit colony formation. The new ({sup 111}In)BLMC may be useful for therapy of some lung cancer patients.

Hou, D.Y.; Hamburger, A.W.; Beach, J.L.; Maruyama, Y. (Univ. of Maryland Cancer Center, Baltimore (USA))

1989-01-01

277

Killing of human lung cancer cells using a new [111In]bleomycin complex [111In]BLMC  

International Nuclear Information System (INIS)

The ability of a [111In]bleomycin complex [(111In]BLMC) to kill five cell lines of human lung cancer (small cell lung cancer) was investigated. Cells were exposed to either 0.9% NaCl, [111In]Cl3, BLM, [111In]BLMC, nonradioactive InCl3, or In-BLMC for 60 minutes, plated in soft agarose, and assessed for colony formation. [111In]BLMC (40-200 microCi carried by 15-25 micrograms BLM/ml) was more cytotoxic than BLM (15-25 micrograms BLM/ml) by a factor of 1.6-5.3 for five cell lines. The percent survival of N417 cells was 28.4 for [111In]BLMC (40 microCi/15 micrograms BLM/ml) and 54.3 for BLM (15 micrograms/ml); 1.9 for [111In]BLMC (200 microCi/25 micrograms BLM/ml), and 10.0 for BLM (25 micrograms/ml). 111InCl3 (200 microCi/ml) and nonradioactive InCl3 failed to inhibit colony formation. The new [111In]BLMC may be useful for therapy of some lung cancer patients

278

Killing of human lung cancer cells using a new [111In]bleomycin complex [111In]BLMC.  

Science.gov (United States)

The ability of a [111In]bleomycin complex [( 111In]BLMC) to kill five cell lines of human lung cancer (small cell lung cancer) was investigated. Cells were exposed to either 0.9% NaCl, [111In]Cl3, BLM, [111In]BLMC, nonradioactive InCl3, or In-BLMC for 60 minutes, plated in soft agarose, and assessed for colony formation. [111In]BLMC (40-200 microCi carried by 15-25 micrograms BLM/ml) was more cytotoxic than BLM (15-25 micrograms BLM/ml) by a factor of 1.6-5.3 for five cell lines. The percent survival of N417 cells was 28.4 for [111In]BLMC (40 microCi/15 micrograms BLM/ml) and 54.3 for BLM (15 micrograms/ml); 1.9 for [111In]BLMC (200 microCi/25 micrograms BLM/ml), and 10.0 for BLM (25 micrograms/ml). 111InCl3 (200 microCi/ml) and nonradioactive InCl3 failed to inhibit colony formation. The new [111In]BLMC may be useful for therapy of some lung cancer patients. PMID:2483533

Hou, D Y; Hamburger, A W; Beach, J L; Maruyama, Y

1989-01-01

279

Long-acting human serum albumin-thioredoxin fusion protein suppresses bleomycin-induced pulmonary fibrosis progression.  

Science.gov (United States)

Idiopathic pulmonary fibrosis (IPF) is thought to involve inflammatory cells and reactive oxygen species (ROS), such as superoxide anion radical (O2(·-)). There is currently no effective treatment of IPF. We previously developed a human serum albumin (HSA)-thioredoxin 1 (Trx) fusion protein (HSA-Trx) designed to overcome the unfavorable pharmacokinetic and short pharmacological properties of Trx, an antioxidative and anti-inflammatory protein. In this study, we examined the therapeutic effect of HSA-Trx on an IPF animal model of bleomycin (BLM)-induced pulmonary fibrosis. A pharmacokinetic study of HSA-Trx or Trx in BLM mice showed that the plasma retention and lung distribution of Trxc was markedly improved by fusion with HSA. A weekly intravenous administration of HSA-Trx, but not Trx, ameliorated BLM-induced fibrosis, as evidenced by a histopathological analysis and pulmonary hydroxyproline levels. HSA-Trx suppressed active-transforming growth factor (TGF)-? levels in the lung and inhibited the increase of inflammatory cells in bronchoalveolar lavage fluid, pulmonary inflammatory cytokines, and oxidative stress markers. An in vitro EPR experiment using phosphate-buffered saline-stimulated neutrophils confirmed the O2(·-) scavenging ability of HSA-Trx. Furthermore, post-treatment of HSA-Trx had a suppressive effect against BLM-induced fibrosis. These results suggest that HSA-Trx has potential as a novel therapeutic agent for IPF, because of its long-acting antioxidative and anti-inflammatory modulation effects. PMID:23442250

Tanaka, Ryota; Watanabe, Hiroshi; Kodama, Azusa; Chuang, Victor Tuan Giam; Ishima, Yu; Hamasaki, Keisuke; Tanaka, Ken-ichiro; Mizushima, Tohru; Otagiri, Masaki; Maruyama, Toru

2013-05-01

280

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.

281

Bleomycin-induced changes of lung epithelial permeability in rats and the effects of glucocorticosteroid on it  

International Nuclear Information System (INIS)

Purpose: To observe changes of lung epithelial permeability (LEP) and effects of glucocorti-costeroid (GC) on it in bleomycin (BM)-induced pulmonary fibrosis rats. Methods: Fifty-eight adult male Wistar rats were divided into control group and experimental group (subdivided into 7 day, 14 day non-treated groups and 7 day, 14 day GC-treated groups). The rat pulmonary fibrosis was induced by a single intratracheal installations of BM. LEP was measured by inhalation of 99mTc-DTPA aerosol. Results: Seven days after injection of GC, alkaline phosphatase (AKP) in broncho-alveolar lavage fluid (BALF) and LEP of GC-treated group were lower than those of non-treated group, but in comparison with those of control group, they are still higher; LEP has a positive correlation with AKP in BALF. Conclusions: This study suggests: 1) at early stage, GC can reduce LEP of BM-induced pulmonary fibrosis; 2) the severer the damage of lung epithelium is, the higher LEP increases; and LEP can be used as a sensitive and noninvasive index for detecting lung epithelial damage

282

Tumor necrosis factor-alpha processing inhibitor-1 inhibits skin fibrosis in a bleomycin-induced murine model of scleroderma.  

Science.gov (United States)

Elevated serum concentration of soluble tumor necrosis factor receptor p55 (sTNFRp55) is known to correlate with the severity of systemic sclerosis (SSc). However, it has not been verified whether this increase contributes to the pathogenesis of SSc. In this study, we found that sTNFRp55 also is increased in the bleomycin (BLM)-induced murine model of SSc. Therefore, we examined the effect of tumor necrosis factor-alpha processing inhibitor-1 (TAPI-1), the inhibitor of TNFRp55 sheddase, in this model. TAPI-1 was administered weekly to mice with skin fibrosis induced by daily BLM injections. TAPI-1 significantly suppressed BLM-induced skin thickness and the number of myofibroblasts. It also inhibited the increase of serum sTNFRp55 after 3 weeks of BLM injections. The mRNA expression of collagen type I alpha1, transforming growth factor-beta1 and alpha smooth muscle actin were decreased by TAPI-1 administration. Taken together, these findings indicate that targeting the TNFalpha converting enzyme might be a new type of therapy for patients with SSc. PMID:19758314

Terao, Mika; Murota, Hiroyuki; Kitaba, Shun; Katayama, Ichiro

2010-01-01

283

Effects of poly(ADP-ribose) polymerase inhibition on cell death and chromosome damage induced by VP16 and bleomycin.  

Science.gov (United States)

Poly(ADP-ribose) polymerase (PARP) is a DNA-binding protein involved in cellular response to various genotoxic agents. To understand the role of PARP in the mechanisms which lead from specific DNA damage to cell death, we studied the effects of PARP inhibition in human lymphoblasts damaged with bleomycin (BLM) and VP16. These agents can induce DNA breakage but through different mechanisms, enabling the study of the different effects of PARP in inducing apoptosis in damaged cells. We demonstrate that in lymphoblasts VP16 treatment induces apoptosis to a greater extent than BLM treatment, and that PARP inhibition reduces VP16-induced apoptosis whereas it has no effect on BLM-induced apoptosis. After VP16 treatment with PARP inhibition, a reduction in the depletion of the proliferative compartment and a G2/M phase arrest are observed. Therefore, the increase in cell viability and the reduction in chromosome damage may both be the result of a prolonged DNA repair time. Hence, PARP appears to play a significant role in VP16-induced apoptosis and not in BLM-induced apoptosis. Since apoptosis is important in tumor treatment these findings might be useful when considering the combined employment of PARP inhibition with antineoplastic drugs. PMID:9707099

D'Agnano, I; Antonelli, A; Bucci, B; Marcucci, L; Petrinelli, P; Ambra, R; Zupi, G; Elli, R

1998-01-01

284

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

285

Bleomycin-detectable iron and phenanthroline-detectable copper in the cerebrospinal fluid of patients with neuronal ceroid-lipofuscinoses.  

Science.gov (United States)

The neuronal ceroid-lipofuscinoses (NCLs) are a group of recessively inherited neurodegenerative lysosomal storage diseases, the pathogenesis of which is unknown. In the present study, we have measured iron and cooper in cerebrospinal fluids (CSF) using methods that detect these metals in a "loosely bound" form, complexable to the chelators bleomycin and 1,10-phenanthroline. We studied 25 children with NCL, 21 children with encephalopathy of some other type, and 5 control children without neurological complications. The CSF concentrations of loosely bound iron at neutral pH values and of loosely bound copper did not correlate with the clinical diagnosis of the patients, nor did they parallel degenerative symptoms in NCL, such as mental impairment, visual loss, motor handicap, and epilepsy. However, the concentrations of loosely bound iron and copper increased significantly with the age of the patient; this is a novel finding and may represent increasing tissue destruction with age. Our present findings do not support a major role for primary iron toxicity in the development of neuronal degeneration. To investigate any secondary pathological role for malplaced transition metals, further research is required. PMID:2464355

Heiskala, H; Gutteridge, J M; Westermarck, T; Alanen, T; Santavuori, P

1988-01-01

286

The effect of octreotide, an analog of somatostatin, on bleomycin-induced interstitial pulmonary fibrosis in rats.  

Science.gov (United States)

In this study, octreotide (OCT), a synthetic somatostatin analog, was tested for its beneficial effects in the prevention of interstitial pulmonary fibrosis (IPF) induced by bleomycin (BLM) in rats by histological examination and by evaluating tissue OH-proline levels. Thirty male Wistar rats were divided randomly into three groups: group I: intratracheal (i.t.) BLM (7.5 mg/kg, single dose) + saline solution [0.9% NaCl, subcutaneously (s.c.), once-daily for 7 days]; group II: i.t. BLM (7.5 mg/kg, single dose) + OCT acetate (82.5 µg/kg, s.c., once-daily for 7 days); and the control group. At the end of the 7 days, lung tissues were excised and examined by histopathological methods. Levels of tissue hydroxyproline (OH-proline) were determined. BLM administration resulted in prominent histopathologic findings, such as diffuse alveolar damage and interstitial pulmonary fibrosis, as well as a significant increase in OH-proline level, as compared to controls. OCT application explicitly attenuated the histopathologic changes to a significant extent. OCT decreased paranchymal fibrosis and structural deformities in BLM-induced lung fibrosis. These results suggest that OCT administration to rats with BLM-induced IPF has a protective effect. Further studies are necessary to reveal the molecular mechanism(s) of OCT-induced protective effect. PMID:22946449

Tug, Tuncer; Kara, Haki; Karaoglu, Aziz; Karatas, Fikret; Turgut, Nergiz Hacer; Ayan, Erhan; Boran, Cetin; Tug, Esra

2013-04-01

287

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

288

A new 111In-bleomycin complex for tumor imaging: preparation, stability, and distribution in glioma-bearing mice  

International Nuclear Information System (INIS)

A new 111In-bleomycin complex (111In-BLMC) is here reported. Its radiochemical purity was 99% by thin-layer chromatography (TLC) (Rf 0.65) and in 5% agarose gel electrophoresis in 0.02 M NaHCO3 it migrated toward the anode. Autoradiographs of TLC and gel electrophoresis plates showed no change on storage for 3 weeks. Urine and plasma from untreated or glioma-bearing mice after injection of 111In-BLMC were analyzed by TLC and gel electrophoresis. Results indicated stability in vivo, nonbinding to transferrin, affinity to viable tumor, and excretion faster than 111In-BLM-B2, 111In-BLM, or 57Co-BLM. Tissue distributions 24 hr after injection of radiopharmaceutical showed activity ratios of tumor to blood, muscle, and brain of 13.1, 12.4, and 81.6, respectively, which were significantly higher than those for previously prepared 111In-BLM-B2 or 111In-BLM (except for brain, 0.05 less than P less than 0.1). The new 111In-BLM complex may be useful in clinical imaging and for combining radionuclide radiotherapy and chemotherapy

289

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)

290

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

291

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.)

292

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

293

Neoadjuvant chemotherapy with bleomycin, ifosfamide and nedaplatin (NAC-BIN) followed by radiotherapy in locoregionally advanced uterine cervical cancer  

Energy Technology Data Exchange (ETDEWEB)

Twelve patients with locoregionally advanced uterine cervical cancer (IIIB: 10, IVA: 2) were treated with neoadjuvant chemotherapy consisting of bleomycin, ifosfamide, and nedaplatin (NAC-BIN) and full dose radical radiotherapy. NAC-BIN achieved one complete response and seven partial responses, for a response rate of 67%. Hematologic toxicity was the most common side effect. Five experienced grade 3{<=}leukopenia, and three had grade 3{<=}anemia. With the mean follow-up of 25 months (range: 9-52 months), nine of 12 patients developed recurrence. Eight had pelvic recurrence alone, and one had both pelvic recurrence and distant metastases. The 2-year pelvic control rate, disease-free survival rate (DFS), and absolute survival rate (AS) were 25%, 25%, and 42%, respectively. The 2-year DFS and AS for patients who responded well to NAC-BIN (CR+PR) was 38% and 63%, whereas for those with a poor response (NC) were 0%. From these results, we consider that preoperative NAC-BIN should not be indicated for patients with unresectable stage (stage III{<=}) uterine cervical cancer, because poor responders must subsequently be treated with definitive radiotherapy and may suffer poor prognosis. (author)

Toita, Takafumi; Ogawa, Kazuhiko; Kakinohana, Yasumasa; Adachi, Genki; Nishikuramori, Yukiko; Murayama, Sadayuki [Ryukyus Univ., Nishihara, Okinawa (Japan). School of Medicine

2000-06-01

294

Neoadjuvant chemotherapy with bleomycin, ifosfamide and nedaplatin (NAC-BIN) followed by radiotherapy in locoregionally advanced uterine cervical cancer  

International Nuclear Information System (INIS)

Twelve patients with locoregionally advanced uterine cervical cancer (IIIB: 10, IVA: 2) were treated with neoadjuvant chemotherapy consisting of bleomycin, ifosfamide, and nedaplatin (NAC-BIN) and full dose radical radiotherapy. NAC-BIN achieved one complete response and seven partial responses, for a response rate of 67%. Hematologic toxicity was the most common side effect. Five experienced grade 3?leukopenia, and three had grade 3?anemia. With the mean follow-up of 25 months (range: 9-52 months), nine of 12 patients developed recurrence. Eight had pelvic recurrence alone, and one had both pelvic recurrence and distant metastases. The 2-year pelvic control rate, disease-free survival rate (DFS), and absolute survival rate (AS) were 25%, 25%, and 42%, respectively. The 2-year DFS and AS for patients who responded well to NAC-BIN (CR+PR) was 38% and 63%, whereas for those with a poor response (NC) were 0%. From these results, we consider that preoperative NAC-BIN should not be indicated for patients with unresectable stage (stage III?) uterine cervical cancer, because poor responders must subsequently be treated with definitive radiotherapy and may suffer poor prognosis. (author)

295

Energy Efficient MAC Protocols  

OpenAIRE

This paper presents a survey of energy efficiency of Medium Access Control (MAC) protocols for Wireless Body Area Sensor Networks (WBASNs). We highlight the features of MAC protocols along with their advantages and limitations in context of WBASNs. Comparison of Low Power Listening (LPL), Scheduled Contention and Time Division Multiple Access (TDMA) is also elaborated. MAC protocols with respect to different approaches and techniques which are used for energy minimization, t...

Hayat, S.; Javaid, N.; Khan, Z. A.; Shareef, A.; Mahmood, A.; Bouk, S. H.

2012-01-01

296

Security of RFID protocols  

OpenAIRE

Radio-frequency identification (RFID) is a technology that uses radio waves to exchange data between RFID readers and tags. The low manufacturing costs and small size and the lack of need of a power source make RFID tags useful in many applications, but also impose a strong need for secure RFID protocols. The first part of this thesis considers the analysis of untraceability of RFID protocols. We start by designing a formal syntax and semantics for security protocols. We define untraceab...

Deursen, Ton

2011-01-01

297

Protocols for Distributed Management  

OpenAIRE

We survey approaches to distributed management and highlight an architecture thatis especially suited for distributed management in a large network. We then discuss indetail two fundamental classes of protocols that execute within such an architecture.The rst is the class of Echo protocols, which can be used for distributed polling, globalstate estimation, resource discovery, and distributed conguration. The second classis that of GAP protocols, whose main application is continuous real-time ...

Stadler, Rolf

2012-01-01

298

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

299

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

300

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

301

Effect of apurinic/apyrimidinic endonucleases and polyamines on DNA treated with bleomycin and neocarzinostatin: specific formation and cleavage of closely opposed lesions in complementary strands  

International Nuclear Information System (INIS)

Bleomycin and neocarzinostatin induce modified apurinic/apyrimidinic (AP) sites by oxidation of the sugar moiety in DNA. In order to quantitatively assess the susceptibility of these lesions to repair endonucleases, drug-treated 3H-labeled colE1 DNA was mixed with 14C-labeled heat-depurinated DNA, and endonuclease-susceptible sites in the mixture were titrated with various AP endonucleases or with polyamines. Single- and double-strand breaks were quantitated by determining the fractions of supercoiled, nicked circular, and linear molecules. Exonuclease III and endonucleases III and IV of Escherichia coli, indicating cleavage of drug-induced AP sites. Bleomycin-induced AP sites were much more sensitive to cleavage by putrescine than heat-induced sites. Treatment with putrescine or very high concentrations of endonuclease III also increased the number of double-strand breaks in bleomycin-treated DNA, suggesting a minor class of lesion consisting of an AP site accompanied by a closely opposed break in the complementary strand. These complex lesions were resistant to cleavage by endonuclease IV. These results suggest that virtually all neocarzinostatin-induced AP sites are accompanied by a closely opposed strand break. Several characteristics of the putative AP site/strand break lesions induced by neocarzinostatin suggest that they may correspond to certain AP-like lesions which were previously detected on DNA sequencing gels as endonuclease IV susceA sequencing gels as endonuclease IV susceptible sites and which have been strongly implicated in neocarzinostatin-induced mutagenesis

302

Delivery of antifibroblast agents as adjuncts to filtration surgery. Part I--Periocular clearance of cobalt-57 bleomycin in experimental drug delivery: pilot study in the rabbit  

International Nuclear Information System (INIS)

Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (57Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity

303

Absence of O6-alkylguanine-DNA alkyltransferase induction in chick embryo liver and brain following X-irradiation or treatment with bleomycin  

International Nuclear Information System (INIS)

The presence of O6-alkylguanine-DNA alkyltransferase (AT) in liver and brain of chick embryos, chicks and hens was demonstrated. An induction of AT activity has only been found in the liver of chicks and hens 48 h after X-irradiation. The administration of methylmethanesulphonate to the chick embryo resulted 3-24 hr later in strong inhibition of AT activity accompanied by DNA alkylation. Under the same conditions, X-irradiation, dimethylnitrosamine and bleomycin exhibited no effect. The results are compared with those obtained in mouse, rat and human foetal tissues. (author)

304

Clinical results of sup(99m)Tc labelled bleomycin scintigraphy in various malignant and benign diseases  

International Nuclear Information System (INIS)

Scintigraphy after sup(99m)Tc bleomycin (BLM) administration was performed on 390 patients suspected of having malignancy. In most of the cases scintigraphy after 67Ga citrate (Ga) administration was performed simultaneously. These results were analyzed according to the location of the lesion, clinical diagnosis, histological findings, size of the lesion and effect of treatment. In 239 malignant cases, BLM scintigraphy gave 193 (81%) positive results, while Ga scintigraphy gave 114 positives in the 176 examinations (65%). BLM scintigraphy was found favorable for tumors located close to the body surface, and excellent results were obtained in tumors of the thyroid, breast, extremities and face, while poor results were found in tumors of the abdominal and pelvic regions and in malignant lymphomas. On the other hand, Ga scintigraphy gave useful information on malignant lymphomas but poor accumulation was observed generally in adenocarcinomas. Such different characters of the two scintigraphy were consistent in metastatic lesions and in follow-up studies after various treatments. In 126 cases with various benign diseases, BLM gave 21 false positives (17%), but Ga scintigraphy gave 35 positives in 77 cases (45%). Of note was that BLM gave 23% positives in 53 cases with inflammatory and granulomatous changes, while Ga gave a high 73% figure in these cases. In 25 various brain lesions, BLM scintigraphy gave better results than sup(99m)Tc pertechnetate scintigraphythan sup(99m)Tc pertechnetate scintigraphy in metastatic brain tumors and tumors located in the brain basis or the occipital region. In conclusion, BLM scintigraphy was considered much more reliable than Ga scintigraphy in differentiating malignant from benign diseases. However, the two materials were also found to have different characters and they were considered rather compensatory to each other. Therefore, the selection of suitable material or parallel study by both materials was considered to be commendable. (author)

305

Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast  

International Nuclear Information System (INIS)

The effects of amines on the induction of mitotic gene conversion by bleomycin (BLM) were studied at the trp5 locus in Saccharomyces cerevisiae strain D7. BLM induces double-strand breaks in DNA and is a potent recombinagen in this assay. The polyamine spermidine causes concentration-dependent protection against the genotoxicity of BLM, reducing the convertant frequency by over 90% under the most protective conditions. Spermine, diethylenetriamine, ethylenediamine, putrescine, and ethylamine were also antigenotoxic in combined treatments with BLM. There was a general correspondence between the protective effect and the number of amino groups, suggesting that more strongly cationic amines tend to be stronger antirecombinagens. Electrostatic association of the amines with DNA probably hinders BLM access to the 4' position of deoxyribose where it generates a free radical. Other amines interact with BLM differently from these unbranched aliphatic amines. The aminothiol cysteamine inhibits the genotoxicity of BLM under hypoxic conditions but increases it under euoxic conditions. In contrast, pargyline potentiates the genotoxicity of BLM under hypoxic conditions but not under euoxic conditions. The antirecombinagenic effect of cysteamine apparently involves DNA binding and depletion of oxygen needed for BLM activity, whereas its potentiation of BLM entails its serving as an electron source for the activation of BLM. Pargyline may enhance BLM indirectly by preventing the dephance BLM indirectly by preventing the depletion of oxygen by monoamine and polyamine oxidase. The planar 9-aminoacridine weakly induces gene conversion in strain D7, but it is strongly synergistic with BLM. Enhancement of BLM activity by this compound and by the related nitroacridine Entozon is apparently mediated by intercalation of the acridine ring system into DNA. Thus, the influence of amines on the genotoxicity of BLM in yeast encompasses antigenotoxic, potentiating, and synergistic interactions. The underlying mechanisms involve noncovalent association with DNA, altered BLM access to DNA, and modulation of physiological conditions

306

111Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy  

International Nuclear Information System (INIS)

Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung region of interest (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuaa suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis

307

Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin  

International Nuclear Information System (INIS)

Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 oC. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in tf mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells

308

Protective effects of 1-[(aminopropyl)amino] ethanethiol against bleomycin and nitrogen mustard-induced mutagenicity in V79 cells  

International Nuclear Information System (INIS)

The effects of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR1065) on bleomycin (BLM) and nitrogen mustard- (HN2) induced cytotoxicity, DNA damage, and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster cells were examined. The antimutagenic effect of WR1065 on cis-diamminedichloroplatinum (cis-DDP) and radiation- (XRT) induced HGPRT mutations was also evaluated for comparative purposes. Cell survival and mutagenesis were assayed after a 30-min exposure of WR1065 (4 mM) to the cells and a subsequent 30-min exposure to therapy agents. WR1065 effectively protected against both effects. The induction of mutants corrected for background by BLM, HN2, cis-DDP or XRT was linear in all cases. Mutation frequencies without WR1065 were 78 x 10-6 per unit BLM; 66 x 10-7 per ?g HN2; 25 x 10-7 per ?g cis-DDP; and 87 10-7 per Gy of XRT. With WR1065 these frequencies were reduced to 37 x 10-6 per unit BLM; 40 x 10-7 per ?g HN2; 1 x 10-7 per ?g cis-DDP; and 44 x 10-7 per Gy of XRT. Mutation protection factors (MPF), a ratio of the corresponding slopes of the mutation induction curves, with and without WR1065, were BLM, MPF = 2.8; HN2, MPF = 3.4; cis-DDP, MPF = 7.1; and XRT, MPF = 5.1. WR1065 protected against the formation of single-strand-breaks (SSB) in DNA by BLM or HN2, as assayed by the method of alkaline elution. WR1065 did not induce SSB in control cells. The ability of radioprotectors to reduce the mutagenic effects of agents used in radiation and chemotherapy may be an important additional benefit for consideration in their use in the treatment of human cancer. 18 refs., 6 figs., 1 tab

309

A sensitive fluorescence turn-on assay of bleomycin and nuclease using WS2 nanosheet as an effective sensing platform.  

Science.gov (United States)

As an important antitumor drug, bleomycin (BLM) is widely used in the treatment of a variety of cancers. In addition, nucleases play a crucial role in DNA replication, recombination and repair which are associated with cancer development. Thus, the development of BLM and nuclease detection methods is of great significance in cancer therapy and related biological mechanism research. Here, a WS2 nanosheet-based turn-on fluorescent sensing platform for simple, fast and sensitive detection of BLM and nuclease was reported. WS2 nanosheet exhibits different affinity toward ssDNA with different length and excellent fluorescence quenching ability. A fluorescein (FAM)-labeled long ssDNA could be adsorbed on the surface of WS2 nanosheet and the fluorescence was therefore quenched. In the presence of BLM·Fe(II) or S1 nuclease (a ssDNA-specific nuclease which was used as a model enzyme), an irreversible scission of long ssDNA was underwent through the BLM-induced oxidation cleavage or S1 nuclease-induced enzymatic hydrolysis. Short FAM-linked oligonucleotide fragments which could not be adsorbed on the nanosheet surface were then produced, resulting in a weak fluorescence quenching after mixing WS2 nanosheets. Thus, the fluorescence signal was restored. The proposed sensor displays a wide linear range and a high sensitivity with a detection limit of 0.3 nM for BLM and 0.01 U mL(-1) for S1 nuclease. It also exhibits a good performance in complex biological samples. This method not only provides a strategy for BLM or S1 nuclease assay but also offers a potential application in biomedical and clinical study. PMID:25732696

Qin, Yingfeng; Ma, Yefei; Jin, Xue; Zhang, Liangliang; Ye, Gaojie; Zhao, Shulin

2015-03-25

310

Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast  

Energy Technology Data Exchange (ETDEWEB)

The effects of amines on the induction of mitotic gene conversion by bleomycin (BLM) were studied at the trp5 locus in Saccharomyces cerevisiae strain D7. BLM induces double-strand breaks in DNA and is a potent recombinagen in this assay. The polyamine spermidine causes concentration-dependent protection against the genotoxicity of BLM, reducing the convertant frequency by over 90% under the most protective conditions. Spermine, diethylenetriamine, ethylenediamine, putrescine, and ethylamine were also antigenotoxic in combined treatments with BLM. There was a general correspondence between the protective effect and the number of amino groups, suggesting that more strongly cationic amines tend to be stronger antirecombinagens. Electrostatic association of the amines with DNA probably hinders BLM access to the 4' position of deoxyribose where it generates a free radical. Other amines interact with BLM differently from these unbranched aliphatic amines. The aminothiol cysteamine inhibits the genotoxicity of BLM under hypoxic conditions but increases it under euoxic conditions. In contrast, pargyline potentiates the genotoxicity of BLM under hypoxic conditions but not under euoxic conditions. The antirecombinagenic effect of cysteamine apparently involves DNA binding and depletion of oxygen needed for BLM activity, whereas its potentiation of BLM entails its serving as an electron source for the activation of BLM. Pargyline may enhance BLM indirectly by preventing the depletion of oxygen by monoamine and polyamine oxidase. The planar 9-aminoacridine weakly induces gene conversion in strain D7, but it is strongly synergistic with BLM. Enhancement of BLM activity by this compound and by the related nitroacridine Entozon is apparently mediated by intercalation of the acridine ring system into DNA. Thus, the influence of amines on the genotoxicity of BLM in yeast encompasses antigenotoxic, potentiating, and synergistic interactions. The underlying mechanisms involve noncovalent association with DNA, altered BLM access to DNA, and modulation of physiological conditions.

Hoffmann, George R. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)], E-mail: ghoffmann@holycross.edu; Gessner, Gabrielle S.; Hughes, Jennifer F.; Ronan, Matthew V.; Sylvia, Katelyn E.; Willett, Christine J. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)

2007-10-01

311

Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast.  

Science.gov (United States)

The effects of amines on the induction of mitotic gene conversion by bleomycin (BLM) were studied at the trp5 locus in Saccharomyces cerevisiae strain D7. BLM induces double-strand breaks in DNA and is a potent recombinagen in this assay. The polyamine spermidine causes concentration-dependent protection against the genotoxicity of BLM, reducing the convertant frequency by over 90% under the most protective conditions. Spermine, diethylenetriamine, ethylenediamine, putrescine, and ethylamine were also antigenotoxic in combined treatments with BLM. There was a general correspondence between the protective effect and the number of amino groups, suggesting that more strongly cationic amines tend to be stronger antirecombinagens. Electrostatic association of the amines with DNA probably hinders BLM access to the 4' position of deoxyribose where it generates a free radical. Other amines interact with BLM differently from these unbranched aliphatic amines. The aminothiol cysteamine inhibits the genotoxicity of BLM under hypoxic conditions but increases it under euoxic conditions. In contrast, pargyline potentiates the genotoxicity of BLM under hypoxic conditions but not under euoxic conditions. The antirecombinagenic effect of cysteamine apparently involves DNA binding and depletion of oxygen needed for BLM activity, whereas its potentiation of BLM entails its serving as an electron source for the activation of BLM. Pargyline may enhance BLM indirectly by preventing the depletion of oxygen by monoamine and polyamine oxidase. The planar 9-aminoacridine weakly induces gene conversion in strain D7, but it is strongly synergistic with BLM. Enhancement of BLM activity by this compound and by the related nitroacridine Entozon is apparently mediated by intercalation of the acridine ring system into DNA. Thus, the influence of amines on the genotoxicity of BLM in yeast encompasses antigenotoxic, potentiating, and synergistic interactions. The underlying mechanisms involve noncovalent association with DNA, altered BLM access to DNA, and modulation of physiological conditions. PMID:17428504

Hoffmann, George R; Gessner, Gabrielle S; Hughes, Jennifer F; Ronan, Matthew V; Sylvia, Katelyn E; Willett, Christine J

2007-10-01

312

Protocol Fuel Mix reporting  

International Nuclear Information System (INIS)

The protocol in this document describes a method for an Electricity Distribution Company (EDC) to account for the fuel mix of electricity that it delivers to its customers, based on the best available information. Own production, purchase and sale of electricity, and certificates trading are taken into account. In chapter 2 the actual protocol is outlined. In the appendixes additional (supporting) information is given: (A) Dutch Standard Fuel Mix, 2000; (B) Calculation of the Dutch Standard fuel mix; (C) Procedures to estimate and benchmark the fuel mix; (D) Quality management; (E) External verification; (F) Recommendation for further development of the protocol; (G) Reporting examples

313

Playing With Population Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Population protocols have been introduced as a model of sensor networks consisting of very limited mobile agents with no control over their own movement: A collection of anonymous agents, modeled by finite automata, interact in pairs according to some rules. Predicates on the initial configurations that can be computed by such protocols have been characterized under several hypotheses. We discuss here whether and when the rules of interactions between agents can be seen as a game from game theory. We do so by discussing several basic protocols.

Xavier Koegler

2009-06-01

314

Quantum deniable authentication protocol  

Science.gov (United States)

The proposed quantum identity authentication schemes only involved authentication between two communicators, but communications with deniability capability are often desired in electronic applications such as online negotiation and electronic voting. In this paper, we proposed a quantum deniable authentication protocol. According to the property of unitary transformation and quantum one-way function, this protocol can provide that only the specified receiver can identify the true source of a given message and the specified receiver cannot prove the source of the message to a third party by a transcript simulation algorithm. Moreover, the quantum key distribution and quantum encryption algorithm guarantee the unconditional security of this scheme. Security analysis results show that this protocol satisfies the basic security requirements of deniable authentication protocol such as completeness and deniability and can withstand the forgery attack, impersonation attack, inter-resend attack.

Shi, Wei-Min; Zhou, Yi-Hua; Yang, Yu-Guang

2014-07-01

315

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

316

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.

317

Deletions at short direct repeats and base substitutions are characteristic mutations for bleomycin-induced double- and single-strand breaks, respectively, in a human shuttle vector system  

Science.gov (United States)

Using the radiomimetic drug, bleomycin, we have determined the mutagenic potential of DNA strand breaks in the shuttle vector pZ189 in human fibroblasts. The bleomycin treatment conditions used produce strand breaks with 3'-phosphoglycolate termini as > 95% of the detectable dose-dependent lesions. Breaks with this end group represent 50% of the strand break damage produced by ionizing radiation. We report that such strand breaks are mutagenic lesions. The type of mutation produced is largely determined by the type of strand break on the plasmid (i.e. single versus double). Mutagenesis studies with purified DNA forms showed that nicked plasmids (i.e. those containing single-strand breaks) predominantly produce base substitutions, the majority of which are multiples, which presumably originate from error-prone polymerase activity at strand break sites. In contrast, repair of linear plasmids (i.e. those containing double-strand breaks) mainly results in deletions at short direct repeat sequences, indicating the involvement of illegitimate recombination. The data characterize the nature of mutations produced by single- and double-strand breaks in human cells, and suggests that deletions at direct repeats may be a 'signature' mutation for the processing of DNA double-strand breaks.

Dar, M. E.; Jorgensen, T. J.

1995-01-01

318

Measurement of cross-linked elastin synthesis in bleomycin-induced pulmonary fibrosis using a highly sensitive assay for desmosine and isodesmosine  

International Nuclear Information System (INIS)

Cross-linked elastin synthesis was measured in the intratracheal bleomycin model of interstitial pulmonary fibrosis by incorporation of 14C-lysine into the elastin-specific crosslinks, desmosine and isodesmosine. Detection of the labeled crosslinks was facilitated by development of a highly sensitive assay utilizing thin-layer electrophoresis. The results indicate that crosslinked elastin synthesis is significantly elevated from controls (p less than 0.05) at 1 to 3 weeks after exposure to bleomycin and returns to normal by 5 weeks. The increases in labeled elastin synthesis are not directly related to changes in either total lung protein synthesis or the pool size of the 14C-lysine. In comparison with collagen and glycosaminoglycan synthesis in this model of lung injury, maximal increases in cross-linked elastin formation occur later, but overlap with the elevated synthesis of these other connective tissue components. The marked increase from normal in cross-linked elastin synthesis in this model suggests that this tissue component is an important part of the fibrotic response of the pulmonary parenchyma and may play a role in the observed alterations in lung structure and function

319

Analysis of the dose-response relationships of chromosomal aberrations after irradiation and bleomycin exposure of different human lymphocyte fractions in vitro  

International Nuclear Information System (INIS)

Cytogenetic analyses could be carried out on whole blood and pure T-cell cultures and also on cells of the 'buffy-coat'. In pure B-cell cultures even after 96 hours no mitogenic stimulation could be achieved. Parameters of radiosensitivity and bleomycin sensitivity were dicentric chromosomes, for which the dose-response relationships were calculated. Chromosomal investigations on the 'buffy-coat' cells did not provide indications referring to a varying radiosensitivity compared to whole blood cultures. In pure T-cell cultures T-lymphocytes, which had been separated after whole blood irradiation exposure, showed lower aberration rates than lymphocytes, which had been cultured after whole blood irradiation without previous separation. In the case of bleomycin exposure the treatment of previously separated leucocytes and T-lymphocytes respectively, led to lower aberration rates than the treatment before separation. Therefore it is apparently not necessary for a cytogenetic dosimetry or mutagenicity to depart from the whole blood culture method. (orig./MG)

320

Treatment of advanced refractory lymphomas with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (the BBVDD regimen). An ECOG pilot study.  

Science.gov (United States)

Forty-four patients with relapsed, refractory malignant lymphomas (12 Hodgkin's disease, 32 non-Hodgkin's lymphoma) were treated with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (BBVDD regimen). Patients had failed at least one, and frequently two, chemotherapy regimens before admission to the study. Of the patients with Hodgkin's disease, 2 (17%) achieved complete response (CR), and 3 (25%) attained a partial response (PR) for an overall response rate (CR + PR) of 42%. Among the patients with non-Hodgkin's lymphoma there were 6 CR (19%) and 12 PR (37%), for an overall response rate of 56%. Median durations of response ranged from 2.5 months for nodular non-Hodgkin's lymphoma in PR to 28.5 + months for Hodgkin's disease in CR. In these heavily pretreated patients, the incidence of toxic effects was grade 3 (48%), grade 4 (23%), grade 5 (2%). The one death (grade 5 toxicity) was attributed to pulmonary impairment due to bleomycin. BBVDD is a moderately effective regimen for the palliation of patients with refractory lymphomas and merits further study. PMID:1720279

Spiers, A S; Weens, J H; Rowe, J M; Smith, T J; Horton, J; Gordon, L I; Glick, J H

1991-12-01

321

Optimal Protocols for Nonlocality Distillation  

CERN Document Server

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

Hoyer, Peter

2010-01-01

322

Boswellic acids extract attenuates pulmonary fibrosis induced by bleomycin and oxidative stress from gamma irradiation in rats  

Science.gov (United States)

Background Interstitial pulmonary fibrosis is characterized by an altered cellular composition of the alveolar region with excessive deposition of collagen. Lung inflammation is also common in pulmonary fibrosis. This study aims to test the inhibition of 5-lipooxygenase (5-LOX) by boswellic acid (BA) extract in an experimental model of pulmonary fibrosis using bleomycin (BL). Methods Boswellic acid extract (1 g/kg) was force-fed to rats seven days prior to administration of BL or gamma irradiation or both. BL (0.15 U/rat) in 25 ?l of 0.9% normal saline (NS) or 0.9% NS alone was administered intratracheally. Rats were exposed to two fractionated doses of gamma irradiation (0.5 Gy/dose/week) with a gamma cell-40 (Cesium-137 irradiation units, Canada) during the last two weeks of the experiment. BA was administered during BL or irradiation treatment or both. After the animals were sacrificed, bronchoalveolar lavage was performed; lungs were weighed and processed separately for biochemical and histological studies. Results In rats treated with BL, levels of transforming growth factor-?1 (TGF-?1) and tumor necrosis factor-? (TNF-?) were significantly elevated (P = 0.05 and P = 0.005). Hydroxyproline was highly and extensively expressed. Immunoreactive compounds were abundantly expressed, represented in the levels of macrophages infiltrate, accumulation of eosinophils and neutrophils in the lung as well as the aggregation of fibroblasts in the fibrotic area. The levels of lipoxygenase enzyme activity were significantly increased (P = 0.005). Antioxidant activities measured in BL-treated rats deteriorated, coupled with the elevation of both levels of plasma lipid peroxide (LP) content and bronchoalveolar lavage lactate dehydrogenase activity. BA-treated rats had reduced number of macrophages, (P = 0.01), neutrophils in bronchoalveolar lavage (P = 0.01) and protein (P = 0.0001). Moreover, the hydroxyproline content was significantly lowered in BA-treated rats (P = 0.005). BA extract inhibited the TGF-ß induced fibrosis (P = 0.01) and 5-LOX activity levels (P = 0.005). Histologically, BA reduced the number of infiltrating cells, ameliorated the destruction of lung architecture and attenuated lung fibrosis. Conclusion BA attenuates the BL-induced injury response in rats, such as collagen accumulation, airway dysfunction and injury. This study suggests that the blocking of 5-LOX may prevent the progression of fibrosis. PMID:21961991

2011-01-01

323

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

324

Quarantine and protocol  

Science.gov (United States)

The purpose of the Orbiting Quarantine Facility is to provide maximum protection of the terrestrial biosphere by ensuring that the returned Martian samples are safe to bring to Earth. The protocol designed to detect the presence of biologically active agents in the Martian soil is described. The protocol determines one of two things about the sample: (1) that it is free from nonterrestrial life forms and can be sent to a terrestrial containment facility where extensive chemical, biochemical, geological, and physical investigations can be conducted; or (2) that it exhibits "biological effects" of the type that dictate second order testing. The quarantine protocol is designed to be conducted on a small portion of the returned sample, leaving the bulk of the sample undisturbed for study on Earth.

1981-01-01

325

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

326

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

327

Simple wavelength assignment protocol  

Science.gov (United States)

IP routers can be coupled with wavelength-selective optical cross- connects to support existing Internet infrastructure in a wavelength division multiplexing (WDM) optical network. Because optical wavelength routing is transparent to IP, packets can bypass traditional forwarding and pass directly through the optical cross-connect, resulting in very high throughput and low delay routing. This approach shares features with label switching, but wavelengths are much more scarce resource than labels. Because optical switches have larger switching times than electronic switches, and wavelength conversions are expensive, wavelength label swapping is not easily done. Wavelength label assignments must consider these limitations to be practical in an optical environment. The performance of an instance of this approach, called Packet over Wavelengths (POW) has been simulated and studied. A new signaling protocol, Simple Wavelength Assignment Protocol (SWAP) is devised to be POW signaling protocol. SWAP takes into account the optical device limitations, and is designed to minimize wavelength conversion, utilize wavelengths with the merging of flows, and reduce the reconfiguration of optical switches. SWAP, to our knowledge, is the first approach to combine signaling and wavelength assignment in an on- line protocol. This paper describes high level SWAP design challenges, decision, and overhead.

Suryaputra, Stephen; Touch, Joseph D.; Bannister, Joseph A.

2000-10-01

328

DNA repair protocols  

DEFF Research Database (Denmark)

In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly successful Methods in Molecular Biology? series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, DNA Repair Protocols, Third Edition provides expert guidance for DNA repair, recombination, and replication.

Bjergbæk, Lotte

2012-01-01

329

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

330

Model Additional Protocol  

International Nuclear Information System (INIS)

Since the end of the cold war a series of events has changed the circumstances and requirements of the safeguards system. The discovery of a clandestine nuclear weapons program in Iraq, the continuing difficulty in verifying the initial report of Democratic People's Republic of Korea upon entry into force of their safeguards agreement, and the decision of the South African Government to give up its nuclear weapons program and join the Treaty on the Non-Proliferation of Nuclear Weapons have all played a role in an ambitious effort by IAEA Member States and the Secretariat to strengthen the safeguards system. A major milestone in this effort was reached in May 1997 when the IAEA Board of Governors approved a Model Protocol Additional to Safeguards Agreements. The Model Additional Protocol was negotiated over a period of less than a year by an open-ended committee of the Board involving some 70 Member States and two regional inspectorates. The IAEA is now in the process of negotiating additional protocols, State by State, and implementing them. These additional protocols will provide the IAEA with rights of access to information about all activities related to the use of nuclear material in States with comprehensive safeguards agreements and greatly expanded physical access for IAEA inspectors to confirm or verify this information. In conjunction with this, the IAEA is working on the integration of these measures with those provided for in comprehensive safeguards agreemded for in comprehensive safeguards agreements, with a view to maximizing the effectiveness and efficiency, within available resources, the implementation of safeguards. Details concerning the Model Additional Protocol are given. (author)

331

Combined chemotherapy and radiotherapy in diffuse large cell immunoblastic lymphoma: a phase II study of CHOP/bleomycin/methotrexate alternating with ifosfamide/methotrexate/etoposide  

Energy Technology Data Exchange (ETDEWEB)

The clinical outcome of 23 patients with high grade diffuse large cell immunoblastic lymphoma (Working Formulation, category H) treated by an intensive shortened schedule regimen of chemotherapy is described. Alternating cycles of cyclophosphamide, doxorubicin, vincristine, bleomycin and prednisolone, and ifosfamide, etoposide and methotrexate were given over an 18-week (range 16.0-20.8) period. External beam radiotherapy was administered as consolation therapy to sites of original bulky disease in 17 patients. Treatment was well tolerated, though there were two toxic deaths. A 90% response rate was obtained. Sixteen of 18 patients followed for a minimum of 36 months are alive and in complete remission, representing a disease free survival of 69.5%; two further patients are alive following autologous bone marrow transplant. The 3-year disease free survival was 73% ({+-}9%) and the overall 3-year survival 78% ({+-}9%). (author).

Rodriguez, J.M.; Khan, A.A. [Al-Hada Armed Forces Hospital, Al-Taif (Saudi Arabia)

1995-12-01

332

Homogeneous preparations of 3'-phosphoglycolate-terminated oligodeoxynucleotides from bleomycin-treated DNA as verified by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.  

Science.gov (United States)

Single- and double-strand breaks bearing 3'-phosphoglycolate termini are among the most frequent lesions formed in DNA by ionizing radiation and other oxidative mutagens. In order to obtain homogeneous preparations of defined 3'-phosphoglycolate substrates for repair studies, 5'-(32)P-end-labeled partial duplex DNAs were treated with bleomycin, and individual cleavage products were isolated from polyacrylamide gels. The fragments were then treated with alkaline phosphatase and further purified by reverse-phase HPLC. Electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry of the purified oligomers produced molecular ions of the expected masses, with no detectable contaminants. Gas-phase sequencing by tandem mass spectrometry of these single species yielded the expected sequence ions and confirmed the presence of phosphoglycolate on the 3'-terminal fragments only. The fragments could be relabeled with polynucleotide kinase to yield highly purified, high-specific-activity substrates for repair studies. PMID:11161322

Chen, S; Hannis, J C; Flora, J W; Muddiman, D C; Charles, K; Yu, Y; Povirk, L F

2001-02-15

333

Combined chemotherapy and radiotherapy in diffuse large cell immunoblastic lymphoma: a phase II study of CHOP/bleomycin/methotrexate alternating with ifosfamide/methotrexate/etoposide  

International Nuclear Information System (INIS)

The clinical outcome of 23 patients with high grade diffuse large cell immunoblastic lymphoma (Working Formulation, category H) treated by an intensive shortened schedule regimen of chemotherapy is described. Alternating cycles of cyclophosphamide, doxorubicin, vincristine, bleomycin and prednisolone, and ifosfamide, etoposide and methotrexate were given over an 18-week (range 16.0-20.8) period. External beam radiotherapy was administered as consolation therapy to sites of original bulky disease in 17 patients. Treatment was well tolerated, though there were two toxic deaths. A 90% response rate was obtained. Sixteen of 18 patients followed for a minimum of 36 months are alive and in complete remission, representing a disease free survival of 69.5%; two further patients are alive following autologous bone marrow transplant. The 3-year disease free survival was 73% (±9%) and the overall 3-year survival 78% (±9%). (author)

334

Successful treatment of multiple basaliomas with bleomycin-based electrochemotherapy: a case series of three patients with Gorlin-Goltz syndrome.  

Science.gov (United States)

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring. PMID:22565566

Kis, Erika; Baltás, Eszter; Kinyó, Agnes; Varga, Erika; Nagy, Nikoletta; Gyulai, Rolland; Kemény, Lajos; Oláh, Judit

2012-11-01

335

Phase I/II trial of carboplatin dose escalation in combination chemotherapy with etoposide, bleomycin and GM-CSF support for poor prognosis nonseminomatous germ cell tumors patients  

International Nuclear Information System (INIS)

To determine the maximum tolerated dose (MTD), and therapeutic efficacy of carboplatin (CBDCA) in combination with etoposide and bleomycin (CEB) as initial chemotherapy for poor prognosis germ cell tumors, a CBDCA dose escalation supported with GM-CSF had been performed. Twenty four untreated patients were treated with CBDCA 400 mg/m2 on day 1, etoposide 100 mg/m2 on days 1 to 5 and bleomycin 30 mg on days 1,3, 5. Four cycles were scheduled at 21-day interval. The first cohort of 6 patients received only initial chemotherapy regimen. In the subsequent cohorts of six patients, the CBDCA dose was increased by 100 mg?m2. A fixed dose and schedule of GM-CSF at 5 ?g/kg subcutaneously was given on days 6 though 15. Myelosuppression, with neutropenic fever and hemorrhages, was the dose-limiting toxicity at the 600 mg/m2 dose level. The recommended dose of CBDCA is 500 mg/m2. Overall complete response (CR) rate was 71% and with median follow up of 25 (16-34) months, 58% of patients are alive and have no evidence of disease (NED). A higher number of CR was achieved with CBDCA dose higher than 400 mg/m2 compared with CBDCA dose of 400 mg/m2 (92 vs. 50%, p=0.03), as well as a higher proportion of patients who alive and with NED (75 vs. 42%, p=0.1). Despite GM-CSF support, the MTD of CBDCA could not be increased beyond 500 mg/m2 (50% of the dose escalation of the dose escalation), due to sevetion of the dose escalation), due to severe myelosuppression. The treatment outcomes obtained with CEB in our study are no better than the standard cisplatin-based chemotherapy. Further studies of this regimen, where CBDCA dose should be calculated according to to the patients glomerular filtration rate are warranted. (author)

336

Growth Differentiation Factor 15 (GDF-15) Plasma Levels Increase during Bleomycin- and Cisplatin-Based Treatment of Testicular Cancer Patients and Relate to Endothelial Damage  

Science.gov (United States)

Introduction Chemotherapy-related endothelial damage contributes to the early development of cardiovascular morbidity in testicular cancer patients. We aimed to identify relevant mechanisms of and search for candidate biomarkers for this endothelial damage. Methods Human micro-vascular endothelial cells (HMEC-1) were exposed to bleomycin or cisplatin with untreated samples as control. 18k cDNA microarrays were used. Gene expression differences were analysed at single gene level and in gene sets clustered in biological pathways and validated by qRT-PCR. Protein levels of a candidate biomarker were measured in testicular cancer patient plasma before, during and after bleomycin-etoposide-cisplatin chemotherapy, and related to endothelial damage biomarkers (von Willebrand Factor (vWF), high-sensitivity C-Reactive Protein (hsCRP)). Results Microarray data identified several genes with highly differential expression; e.g. Growth Differentiation Factor 15 (GDF-15), Activating Transcription Factor 3 (ATF3) and Amphiregulin (AREG). Pathway analysis revealed strong associations with ‘p53’ and ‘Diabetes Mellitus’ gene sets. Based on known function, we measured GDF-15 protein levels in 41 testicular patients during clinical follow-up. Pre-chemotherapy GDF-15 levels equalled controls. Throughout chemotherapy GDF-15, vWF and hsCRP levels increased, and were correlated at different time-points. Conclusion An unbiased approach in a preclinical model revealed genes related to chemotherapy-induced endothelial damage, like GDF-15. The increases in plasma GDF-15 levels in testicular cancer patients during chemotherapy and its association with vWF and hsCRP suggest that GDF-15 is a potentially useful biomarker related to endothelial damage. PMID:25590623

Altena, Renske; Fehrmann, Rudolf S. N.; Boer, Hink; de Vries, Elisabeth G. E.; Meijer, Coby; Gietema, Jourik A.

2015-01-01

337

Preventive effects of Citrus reticulata essential oil on bleomycin-induced pulmonary fibrosis in rats and the mechanism  

Directory of Open Access Journals (Sweden)

Full Text Available OBJECTIVE: To investigate the effects of essential oil of Citrus reticulata (EOCR on proliferation of human embryonic lung fibroblasts (HELFs, and to explore its protective effects on bleomycin (BLM-induced lung fibrosis in rats.METHODS: Routinely cultured HELFs during the logarithmic phase of growth were divided into control and treated groups, and applied for evaluation of inhibitory activity using methylthiazol tetrazolium (MTT assay. A rat model of BLM-induced pulmonary fibrosis was used for the evaluation of antifibrotic effect of EOCR. Forty-two Sprague-Dawley rats were randomly divided into normal group, model group, prednisone group and different doses of EOCR groups. BLM was intratracheally instilled into all the rats except those in the normal group, and EOCR was orally given to BLM-treated rats at doses of 25, 50, 100 and 200 mg/kg once per day for four weeks. The rats in the normal group were intratracheally administered the same volume of saline. On the 28th day, rats were sacrificed under anesthesia, and the serum and lung tissues were collected. Superoxide dismutase (SOD activities and malondialdehyde (MDA contents in serum and lung tissues were analyzed with corresponding kits; type ? collagen (Col ? content in lung tissues was evaluated with enzyme-linked immunosorbent assay; pulmonary fibrosis was assessed by lung histology; protein and mRNA expressions of connective tissue growth factor (CTGF in lung tissues were measured with immunohistochemical and in situ hybridization semiquantitative image analyses, respectively.RESULTS: The EOCR at different concentrations displayed inhibitory activity on proliferation of HELFs. In in vivo experiment, the weight gain of the rats in groups treated with EOCR at doses of 50, 100 and 200 mg/kg per day was significantly higher than those in the model group at the 7th, 14th, 21st and 28th day (P?0.05 or P?0.01. The scores of alveolitis and pulmonary fibrosis in the groups treated with EOCR at doses of 100 and 200 mg/kg per day were significantly lower than those in the model group (P?0.01; the SOD levels in serum and pulmonary tissues of the EOCR (50, 100 and 200 mg/kg groups were markedly increased compared with the model group (P?0.01 , while the MDA levels in both serum and pulmonary tissues were markedly reduced (P?0.05; the Col ? level in pulmonary tissues of the EOCR (100 and 200 mg/kg per day groups were markedly lower than that of the model group (P?0.01; the protein and mRNA expressions of CTGF in the groups treated with EOCR at doses of 100 and 200 mg/kg per day were down-regulated compared with the model group (P?0.01.CONCLUSION: The results indicate that EOCR has preventive effects on BLM-induced pulmonary fibrosis in rats. The mechanism may be via adjusting the unbalance of oxidation and antioxidation, down-regulating CTGF protein and mRNA expressions, and reducing collagen deposition and fibrosis.

Xian-mei Zhou

2012-02-01

338

Synchronizing internet protocol security (SIPSec)  

CERN Document Server

Synchronizing Internet Protocol Security (SIPSec) focuses on the combination of theoretical investigation and practical implementation, which provides an in-depth understanding of the Internet Protocol Security (IPSec) framework. The standard internet protocol is completely unprotected, allowing hosts to inspect or modify data in transit. This volume identifies the security problems facing internet communication protocols along with the risks associated with internet connections. It also includes an investigative case study regarding the vulnerabilities that impair IPSec and proposes a SIPSec

Shoniregun, Charles A

2007-01-01

339

Generalized Teleportation Protocol  

CERN Document Server

A generalized teleportation protocol (GTP) for N qubits is presented, where the teleportation channels are non-maximally entangled and all the free parameters of the protocol are considered: Alice's measurement basis, her sets of acceptable results, and Bob's unitary operations. The full range of Fidelity (F) of the teleported state and the Probability of Success (P_{suc}) to obtain a given fidelity are achieved by changing these free parameters. A channel capacity bound is found, where one can determine how to divide it between F and P_{suc}. A one qubit formulation is presented and then expanded to N qubits. A proposed experimental setup that implements the GTP is given using linear optics.

Gordon, G; Gordon, Goren; Rigolin, Gustavo

2005-01-01

340

The Biosafety Protocol  

Science.gov (United States)

On January 20, international negotiators resumed talks in Montreal to finalize a Biosafety Protocol that "seeks to reduce potential risks from the transboundary movement of living modified organisms (LMOs) and address potential threats to biodiversity" from products modified by genetic engineering. The Protocol is being negotiated under the UN Convention on Biological Diversity that was adopted at the Rio Earth Summit in 1992, and upon acceptance, it would regulate trade and movement of genetically engineered products. At this new site, provided by the US State Department (an advocate of biotechnology), users will find a variety of resources related to the Montreal talks and biosafety. These include the full text of the 1992 Convention on Biological Diversity (CBD) (also in French in Spanish), updated fact sheets, a biotechnology glossary and news stories, biosafety links, summary points on the negotiations, and press releases.

341

Diplomacy and Diplomatic Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available The present study aims to observe relationships and determining factors between diplomacyand diplomatic protocol as outlined by historical and contextual analyses. The approach is very dynamic,provided that concepts are able to show their richness, antiquity and polyvalence at the level of connotations,semantics, grammatical and social syntax. The fact that this information is up to date determines anattitude of appreciation and a state of positive contamination.

Lect. Ph.D Oana Iucu

2008-12-01

342

Blind Cognitive MAC Protocols  

OpenAIRE

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-pri...

Mehanna, Omar; Sultan, Ahmed; Gamal, Hesham El

2008-01-01

343

Multiparticle entanglement purification protocols  

Science.gov (United States)

Purification schemes for multiparticle entangled states cannot be treated as straightforward extensions of those two-particle ones because of the lack of symmetry they possess. We propose purification protocols for a wide range of mixed entangled states of many particles. These are useful for understanding entanglement, and could be of practical significance in multiuser cryptographic schemes or distributed quantum computation and communication. We show that operating locally on multiparticle entangled states directly is more efficient than relying on two-particle purification.

Murao, M.; Plenio, M. B.; Popescu, S.; Vedral, V.; Knight, P. L.

1998-06-01

344

Mars Communication Protocols  

Science.gov (United States)

Over the next decade, international plans and commitments are underway to develop an infrastructure at Mars to support future exploration of the red planet. The purpose of this infrastructure is to provide reliable global communication and navigation coverage for on-approach, landed, roving, and in-flight assets at Mars. The claim is that this infrastructure will: 1) eliminate the need of these assets to carry Direct to Earth (DTE) communications equipment, 2) significantly increase data return and connectivity, 3) enable small mission exploration of Mars without DTE equipment, 4) provide precision navigation i.e., 10 to 100m position resolution, 5) supply timing reference accurate to 10ms. This paper in particular focuses on two CCSDS recommendations for that infrastructure: CCSDS Proximity-1 Space Link Protocol and CCSDS File Delivery Protocol (CFDP). A key aspect of Mars exploration will be the ability of future missions to interoperate. These protocols establish a framework for interoperability by providing standard communication, navigation, and timing services. In addition, these services include strategies to recover gracefully from communication interruptions and interference while ensuring backward compatibility with previous missions from previous phases of exploration.

Kazz, G. J.; Greenberg, E.

2000-01-01

345

Communication complexity protocols for qutrits  

International Nuclear Information System (INIS)

Consider a function where its entries are distributed among many parties. Suppose each party is allowed to send only a limited amount of information to a referee. The referee can use a classical protocol to compute the value of the global function. Is there a quantum protocol improving the results of all classical protocols? In a recent work Brukner et al. showed the deep connection between such problems and the theory of Bell inequalities. Here we generalize the theory to trits. There, the best classical protocol fails whereas the quantum protocol yields the correct answer

346

A simple, highly sensitive and improved method for the measurement of bleomycin-detectable iron: the 'catalytic iron index' and its value in the assessment of iron status in haemochromatosis.  

Science.gov (United States)

In the presence of ferrous ions (Fe(2+)), the anti-tumour agent bleomycin will induce DNA degradation. Degradation of DNA into substances detectable by the thiobarbituric acid test has been used previously for the detection of iron in a form that is capable of catalysing the formation of the potentially harmful hydroxyl free radical. In the present paper, we describe the application of the ethidium-binding assay of DNA damage to the measurement of bleomycin-detectable iron, comparing its performance with the conventional method in the assessment of iron standard solutions and plasma samples from haemochromatosis patients. The ethidium-binding assay proved to be more responsive than the thiobarbituric acid test in the detection of DNA damage induced by very low concentrations of iron, but became saturated at higher iron concentrations. Agreement between the two versions of the assay in the identification of plasma samples containing bleomycin-detectable iron was good, but agreement on the actual concentrations of such iron in the positive samples was poor. This discrepancy is believed to be due to interference with the thiobarbituric acid assay by plasma. Consequently, it was not possible to obtain reliable estimates of free iron concentrations in plasma when using the conventional version of the bleomycin assay. We have devised a parameter of iron status called the catalytic iron index. For healthy, non-haemochromatotic individuals, the mean value of this parameter was found to be 0.81 (range 0.78-0.84; n=20). Elevated values were observed in some plasma samples from haemochromatosis patients, but these showed no correlation with serum ferritin levels. In contrast, correlations were seen with both serum iron and transferrin saturation levels, but only when these were above the normal range. PMID:11222109

Burkitt, M J; Milne, L; Raafat, A

2001-03-01

347

Influência do biofármaco DNA-hsp65 na lesão pulmonar induzida por bleomicina / Influence of a DNA-hsp65 vaccine on bleomycin-induced lung injury  

Scientific Electronic Library Online (English)

Full Text Available OBJETIVO: Avaliar a influência do biofármaco DNA-hsp65 em um modelo de distúrbio fibrosante pulmonar experimental. MÉTODOS: Foram estudados 120 camundongos machos C57BL/6, divididos em quatro grupos: grupo SS, animais tratados com salina (placebo) e injetados com salina intratraqueal (IT); grupo SB, [...] tratados com salina (placebo) e injetados com bleomicina IT; grupo PB, tratados com plasmídeo, sem gene bacteriano, e injetados com bleomicina IT; e grupo BB, tratados com DNA-hsp65 e injetados com bleomicina IT. A bleomicina foi injetada 15 dias após a última imunização, e os animais sacrificados seis semanas após o uso da droga IT. O pulmão esquerdo retirado foi utilizado para análise morfológica, e o pulmão direito para dosagens de hidroxiprolina. RESULTADOS: A proporção de camundongos que apresentaram morte não-programada depois de 48 h da injeção IT foi maior no grupo SB em comparação ao grupo SS (57,7% vs. 11,1%). A área percentual média de interstício septal foi maior nos grupos SB e PB (53,1 ± 8,6% e 53,6 ± 9,3%, respectivamente) em comparação aos grupos SS e BB (32,9 ± 2,7% e 34,3 ± 6,1%, respectivamente). Os grupos SB, PB e BB mostraram aumentos nos valores médios da área de interstício septal corada por picrosirius em comparação ao grupo SS (SS: 2,0 ± 1,4%; SB: 8,2 ± 4,9%; PB: 7,2 ± 4,2%; e BB:6,6±4,1%).O conteúdo pulmonar de hidroxiprolina no grupo SS foi inferior ao dos demais grupos (SS: 104,9 ± 20,9 pg/pulmão; SB: 160,4 ±47,8 pg/pulmão; PB:170,0 ± 72,0 pg/pulmão; e BB: 162,5 ± 39,7 pg/pulmão). CONCLUSÕES: A imunização com o biofármaco DNA-hsp65 interferiu na deposição de matriz não-colágena em um modelo de lesão pulmonar induzida por bleomicina. Abstract in english OBJECTIVE: To evaluate the effects of immunization with a DNA-hsp65 vaccine in an experimental model of pulmonary fibrosis. METHODS: A total of 120 male C57BL/6 mice were distributed into four groups: SS, injected with saline (placebo) and then receiving intratracheal (IT) instillation of saline; SB [...] , injected with saline (placebo) and then receiving IT instillation of bleomycin; PB, treated with plasmid only, without bacterial genome, and then receiving IT instillation of bleomycin; and BB, treated with the vaccine and then receiving IT instillation of bleomycin. Bleomycin was instilled 15 days after the last immunization, and the animals were killed six weeks thereafter. The left and right lungs were removed, the former for morphological analysis and the latter for hydroxyproline measurements. RESULTS: The proportion of deaths within the first 48 h after the IT instillation (deaths attributed to the surgical procedure) was higher in the SB group than in the SS group (57.7% vs. 11.1%). The mean area of pulmonary interstitial septa was greater in the SB and PB groups (53.1 ± 8.6% and 53.6±9.3%, respectively) than in the SS and BB groups (32.9 ± 2.7% and 34.3 ± 6.1%, respectively). The mean area of interstitial septa stained by picrosirius was greater in the SB, PB and BB groups than in the SS group (8.2 ± 4.9%, 7.2 ± 4.2% and 6.6 ± 4.1%, respectively, vs. 2.0±1.4%). The total hydroxyproline content in the lung was significantly lower in the SS group (104.9 ± 20.9 pg/lung) than in the other groups (SB: 160.4 ± 47.8 pg/lung; PB: 170.0 ± 72.0 pg/lung; and BB: 162.5 ± 39.7 pg/lung). CONCLUSIONS: Immunization with the DNA-hsp65 vaccine reduced the deposition of noncollagen matrix in a model of bleomycin-induced lung lesion.

Adriana Ignacio de, Padua; Célio Lopes, Silva; Simone Gusmão, Ramos; Lúcia Helena, Faccioli; José Antônio Baddini, Martinez.

2008-11-01

348

Sincalide - the final protocol  

International Nuclear Information System (INIS)

Full text: HIDA biliary studies examine the gallbladder (GB) to give a percentage ejection fraction (EF). Porcine CCK was an accepted agent for stimulating the GB prior to being withdrawn in the UK from 1998. Sincalide (a synthetic CCK) was the suggested replacement. We have tried many administration regimes in an attempt to get results comparable with our established CCK protocols. Dose concentration and length of infusion times have been studied. Initially a dose of 10 ngm/kg/min given over 2 minutes (manufacturer's recommended dose) was used. This gave falsely low ejection fractions. The dose was reduced to 3 ngm/kg/min over 3 minutes as it was felt the higher dose may be causing constriction of the sphincter of Oddi. This gave a slight improvement with 22 % of patients having normal EF (>35 %). The length of infusion was extended to 15 minutes and the dose concentration reduced again to 0.6 ngm/kg/min. 62 % of patients had a normal EF. However, on many of the curves the gallbladder was still contracting on completion of the 15 minute infusion and began to refill immediately after stopping Sincalide. A further change of protocol was indicated. The infusion time was extended to 30 minutes and the dose concentration per minute kept the same. Imaging began at 30 minutes post HIDA injection and continued for a total of 50 minutes. Sincalide infusion began at 35 minutes if a GB was visualized. This protocol has been performed on 17 patients. 53 % of these had a normal result (comparable with a normal rate of 40 % previously established with CCK) with a mean EF of 60 %. The mean EF of patients with abnormal studies was 15 %. Curves showed a plateau by 30 minutes in 94 % of patients indicating that gallbladder contraction was complete. No normal range is available so results were compared with ultrasound (US). All patients who had an abnormal US scan also had abnormal HIDA results. Three patients had a normal US scan and abnormal HIDA study. These are currently undergoing further investigations. We conclude that 0.6 ngm/kg/minute Sincalide infused over 30 minutes is a satisfactory replacement for CCK and is the protocol we recommend for HIDA studies. (author)

349

Synthesizing a protocol converter from executable protocol traces  

Science.gov (United States)

Communicating finite state machines (CFSM's) with FIFO (first in, first out) queues are used to model a protocol converter. A protocol conversion algorithm is developed and presented for the CSFM model of the protocols A and B. A converter H for protocols A = (A0, A1) and B = (B0, B1) is viewed as a black box such that H is between sender A0 and receiver B1. This gives a resulting protocol X = (A0, H, B1). The conversion algorithm requires a specification of the message relationships between the messages of protocols A and B. It is assumed that protocols A and B have the required progress properties. The algorithm includes a search for related messages from the two protocols in an FIFO from a composite space formed by a Cartesian cross-product of state spaces A1 and B0. The search produces finite-length traces which are combined to form a state machine H, which is examined for freedom from unspecified receptions, deadlocks, and livelocks. A protocol conversion example demonstrates the applicability of the algorithm.

Rajagopal, Murali; Miller, Raymond E.

1991-01-01

350

Stream Control Transmission Protocol Steganography  

CERN Document Server

Stream Control Transmission Protocol (SCTP) is a new transport layer protocol that is due to replace TCP (Transmission Control Protocol) and UDP (User Datagram Protocol) protocols in future IP networks. Currently, it is implemented in such operating systems like BSD, Linux, HP-UX or Sun Solaris. It is also supported in Cisco network devices operating system (Cisco IOS) and may be used in Windows. This paper describes potential steganographic methods that may be applied to SCTP and may pose a threat to network security. Proposed methods utilize new, characteristic SCTP features like multi-homing and multistreaming. Identified new threats and suggested countermeasures may be used as a supplement to RFC 5062, which describes security attacks in SCTP protocol and can induce further standard modifications.

Fraczek, Wojciech; Szczypiorski, Krzysztof

2010-01-01

351

Security and SCADA protocols  

International Nuclear Information System (INIS)

Supervisory control and data acquisition (SCADA) networks have replaced discrete wiring for many industrial processes, and the efficiency of the network alternative suggests a trend toward more SCADA networks in the future. This paper broadly considers SCADA to include distributed control systems (DCS) and digital control systems. These networks offer many advantages, but they also introduce potential vulnerabilities that can be exploited by adversaries. Inter-connectivity exposes SCADA networks to many of the same threats that face the public internet and many of the established defenses therefore show promise if adapted to the SCADA differences. This paper provides an overview of security issues in SCADA networks and ongoing efforts to improve the security of these networks. Initially, a few samples from the range of threats to SCADA network security are offered. Next, attention is focused on security assessment of SCADA communication protocols. Three challenges must be addressed to strengthen SCADA networks. Access control mechanisms need to be introduced or strengthened, improvements are needed inside of the network to enhance security and network monitoring, and SCADA security management improvements and policies are needed. This paper discusses each of these challenges. This paper uses the Profibus protocol as an example to illustrate some of the vulnerabilities that arise within SCADA networks. The example Profibus security assessment establishes a network moderity assessment establishes a network model and an attacker model before proceeding to a list of example attacks. (authors)

352

[Computerized clinical protocol for occlusion].  

Science.gov (United States)

In making a protocol it is necessary that all members of the team who are going to collect information have the same unity of criterion about the different variables that compose it. The drawing up of this document is as much or more necessary than the protocol itself. In this work we all data collected in the protocol and we give the explanations of each concept. PMID:3078632

Salsench, J; Ferrer, J; Nogueras, J

1988-11-01

353

Biomodelos para la inducción de micronúcleos en células de la médula ósea por ciclofosfamida y bleomicina / Biomodels for micronucleis induction on bone marrow cells by cyclophosphamide and bleomycin  

Scientific Electronic Library Online (English)

Full Text Available En este trabajo se evaluó la línea de ratones Balb/c, de ambos sexos, como biomodelo en la inducción de micronúcleos en células de la médula ósea por ciclofosfamida y bleomicina. Se formaron cinco grupos experimentales/sexo: al primero se le administró NaCl al 0,9%, al segundo y al tercero ciclofosf [...] amida y al cuarto y quinto bleomicina. Todos los medicamentos fueron suministrados por vía intraperitoneal, con diseños de tratamientos diferentes y dosis de 50 mg/kg en los tres primeros grupos y de 20 mg/kg en los dos últimos. Se obtuvo como resultado una mayor inducción de micronúcleos en eritrocitos policromáticos y un mayor índice de citotoxicidad por el uso de la ciclofosfamida, administrada en dos ocasiones antes del sacrificio, con intervalos de 24 horas entre ambas administraciones. Esto constituyó, bajo nuestras condiciones experimentales, el mejor diseño para inducir un número considerable de micronúcleos en células de la médula ósea de ratones, siendo estos resultados útiles para evaluar drogas con efecto antigenotóxico y pudiera servir también como control positivo en estudios de mutagénesis o genotoxicidad. Abstract in english Balb/c mice of both sexes were evaluated as biomodel in the induction of micronucleis in bone marrow cells by cyclophosphamide and bleomycin. They were divided into five experimental groups per sex. The first one was administered with NaCl 0.9% by intraperitoneal (i.p) route, the second and third gr [...] oups 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 20 mg/kg doses. This resulted in a higher micronucleis induction of polychromatic erythrocytes and in a higher citotoxicity index with the use of cyclophosphamide administered twice before the sacrifice, with a 24-hours interval between administrations. According to our experimental conditions, this is the best design to induce a considerable number of micronucleis in bone marrow cells of mice, being useful in experimental designs to evaluate drugs with antigenotoxic effect. In addition, it implies its use according to the best found experimental design as positive control in mutagenesis and genotoxicity studies.

Daniel Francisco, Arencibia; Alexis, Vidal; Luis Alfredo, Rosario; Yolanda Emilia, Suárez; Livan, Delgado.

2011-04-01

354

Very low dose and dose-rate X-ray induced adaptive response in human lymphocytes at various cell cycle stages against bleomycin induced chromatid aberrations  

International Nuclear Information System (INIS)

Complete text of publication follows. Objective: To study the adaptive response induced by very low doses of X-rays at very low dose rate in human lymphocytes at different cell cycle stages followed by a challenge dose of bleomycin sulphate at G2 phase. Materials and Methods: Human peripheral blood lymphocytes before (G0) and after PHA stimulation (G1 and G2) were exposed to 1 and 5 cGy X-rays generated by a fluoroscopy unit with a dose rate of 5.56 mGy/min and challenged with 5 ?g/ml bleomycin sulphate (BLM) 48 hours after culture initiation. Mitotic cells were arrested at metaphase by addition of colcemid in cultures 1.5 h before harvesting. Harvesting and slide preparation was performed using standard method. 100 well spread metaphases were analyzed for the presence of chromatid type aberrations for each sample. Results: Results obtained indicate that there is a linear relationship between the dose of BLM and chromatid aberrations below 5 ?g/ml (R=0.93, p<0.0001). The results also show that pretreatment of lymphocytes with low dose X-rays at G0, G1 and G2 phases of the cell cycle significantly reduced the sensitivity of lymphocytes to the clastogenic effects of BLM in G2. Much lower frequencies of chromatid aberrations were observed in X-ray irradiated lymphocytes following BLM treatment (p<0.05). The magnitudes of adaptation induced at different phases of the cell cycle were not significantly different. Furthermore, there was no a significant difference in the mwas no a significant difference in the magnitude of adaptive response induced by either 1 or 5 cGy X-rays. Conclusion: These observations might indicate that resistance of pre-exposure of lymphocytes to very low doses of X-rays protects them from clastogenic effects of BLM. This effect might be due to initial DNA damage induced in these cells leading to provocation of an active DNA repair mechanism independent of cell cycle stage.

355

Protocols for Scholarly Communication  

CERN Document Server

CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should naturally guide authors towards OA publication and CERN wants to help reach a full...

Pepe, Alberto; Pepe, Alberto; Yeomans, Joanne

2007-01-01

356

Publishing protocols for partnered research.  

Science.gov (United States)

Published scientific protocols are advocated as a means of controlling bias in research reporting. Indeed, many journals require a study protocol with manuscript submission. However, publishing protocols of partnered research (PPR) can be challenging in light of the research model's dynamic nature, especially as no current reporting standards exist. Nevertheless, as these protocols become more prevalent, a priori documentation of methods in partnered research studies becomes increasingly important. Using as illustration a suite of studies aimed at improving coordination and communication in the primary care setting, we sought to identify challenges in publishing PPR relative to traditional designs, present alternative solutions to PPR publication, and propose an initial checklist of content to be included in protocols of partnered research. Challenges to publishing PPR include reporting details of research components intended to be co-created with operational partners, changes to sampling and entry strategy, and alignment of scientific and operational goals. Proposed solutions include emulating reporting standards of qualitative research, participatory action research, and adaptive trial designs, as well as embracing technological tools that facilitate publishing adaptive protocols, with version histories that are able to be updated as major protocol changes occur. Finally, we present a proposed checklist of reporting elements for partnered research protocols. PMID:25355092

Hysong, Sylvia J; Woodard, LeChauncy; Garvin, Jennifer H; Murawsky, Jeffrey; Petersen, Laura A

2014-12-01

357

Message Broadcasting Protocols in VANET  

Directory of Open Access Journals (Sweden)

Full Text Available Vehicular Ad hoc Networks (VANET is one of the most challenging research areas in the field of mobile ad hoc networks. In this research, we propose a comparison between the emergency message broadcasting protocols and identifying the Pros and cons of each protocol.

Ghassan Samara

2012-01-01

358

Message Broadcasting Protocols in VANET  

OpenAIRE

Vehicular Ad hoc Networks (VANET) is one of the most challenging research areas in the field of mobile ad hoc networks. In this research, we propose a comparison between the emergency message broadcasting protocols and identifying the Pros and cons of each protocol.

Ghassan Samara; Ali Alsalihy, Wafaa A. H.

2012-01-01

359

Enhancer- A Time Commit Protocol  

OpenAIRE

This paper contains content with theinvestigating the performance implications of providingtransaction atomicity for a deadline real timeapplications operating on distributed data. Consideringall the commit protocols and discussing all phases of thecommit protocols and examine their working modelover different aspects of distributed database.Implementing distributed real time databasesystem(DRTDBS) content which must be design on alllevel of database architecture to support timelyexecution of...

Himanshu Dubey, Aman Kr Srivastava

2012-01-01

360

A Streaming Protocol for Memcached  

Directory of Open Access Journals (Sweden)

Full Text Available Memcached is a general-purpose distributed memory caching system that was originally developed by Danga Interactive for Live Journal but is now used by many other sites and It is thought to be one of the most effective solutions to speed up dynamic database-driven websites by caching data and objects in RAM to reduce the number of times that an external data source must be read. Memcached system uses a client-server architecture, it provides its standard memcached protocol to support any types of programming languages. The memcached protocol is simple and very efficient, while it doesn’t support big data objects very well. In this study, the memcached systems were firstly illustrated and then a detailed introduction was provided for the memcached protocol and then the issues of the stock protocol were specified. After that, a new streaming protocol was illustrated which was well designed for big data objects and could be easily integrated into original memcached protocols. Finally, some experiments were done to evaluate the new streaming protocol and finally the new protocol was proved to be very efficient for big data objects storage and it explored new application fields for memcached.

W. Li

2012-01-01

361

Preparation, distribution, stability and tumour imaging properties of [62Zn] bleomycin complex in normal and tumour-bearing mice as a molecular pet generator  

International Nuclear Information System (INIS)

PET is a powerful imaging technique with many advantages over single photon imaging. Nowadays, several positron emitter radioisotopes and their radio-labeled complexes have been developed for imaging. 62Zn/62Cu positron generator system has been widely proposed as a source of perfusion tracers (Green, 1987 and Green et al, 1988). In this study we have developed a 62Zn/62Cu-bleomycin tracer system as a biological generator for PET. The radiochemical separation of the 62Zinc (Neirinckx 1977) from natural copper target (electroplated over Ni layer) was carried out with a method described by (Green et al, 1990 and Okazawa et al, 1994) with slight modification. After dissolving of the irradiated target, solution was heated under a flow of nitrogen to dry up until a precipitate was formed. The precipitate was rinsed 2 times by distilled water (10 ml) and a portion of 2N HCl was added and mixed gently. The solution was pumped through a column 10x100mm filled with BioRad AG-1X8 resin and preconditioned with 2N HCl. For the elution of 62Zn in anion exchange resin, 0.005 N HCl was adopted instead of water used by (Green et al, 1990, Qaim 2001), because [62Zn] chloride form is suitable for the BLM labeling The samples were taken for the gamma spectroscopy analysis, using HPGe Canberra detector, in each steps. [62Zn]Zinc chloride (0.25-2.5 mCi) dissolved in acidic media obtained above (0.5-2 med in acidic media obtained above (0.5-2 ml) was transferred to a 2 ml-vial and pH was adjusted using HCl 1M and/or NaOH 1M (pH=1-7). The mixture was evaporated by slight warming, under a nitrogen flow. A mixture of BLM (0.25-2.5 mg,) in normal saline (0.1 mL) was then added. This mixture was heated at different temperatures (25, 50, 80 and 100 deg. C). The mixture was cooled in an ice bath and rapidly sent for use. The active solution was checked for radiochemical purity by polymer-backed silica gel layer using a mixture of ammonium acetate 10%-methanol as the mobile phase. These analyses were carried out every 30 min after labeling step. The final solution was then passed through a 0.22 m filter and pH adjusted to 5-7 by the addition of sodium acetate (1M) buffer. Pyrogen test was performed using a commercial LAL kit. Stability of [62Zn]BLM complex in final product and human/mice serum in vitro. A sample of [62Zn]BLM (0.5 mCi) was kept at room temperature for 48 hrs while checked by RTLC at various time intervals (2, 4, 8, 12 and 24). A micropipette sample (50 mL) was taken from the shaking mixture and the ratio of free radiozinc to [62Zn]BLM was checked by radio thin layer chromatography (eluent: 10% NH4OAc and methanol 1:1). The patterns for [62Zn]ZnCl2 and [62Zn]BLM were not changed in 24 hrs. Animal studies: Fibrosarcoma cells (about 104) of were injected SC to the dorsal area of Balb C mice weighing 20-25 g. After 14 days the tumour weighed 0.7 g and was not grossly necrotic. The distribution of [62Zn]-ZnCl2 and [62Zn]-BLM among tissues were determined for untreated mice and for mice with fibrosarcoma. A volume (0.1 ml) of final [62Zn]-BLM solution containing 20-40 uCi radioactivity (6 mg bleomycin in 50 mL) was injected into the dorsal tail vein. The total amout of radioactivity injected into each mouse was measured by counting the 1-ml syringe before and after injection in a radiometer with a fixed geometry. The animals were sacrificed by ether asyxphycation at selected times after injection, the tissues weighed and their specific activities determined with a gamma-ray scintillation as percentage of injected dose per gram of tissues (data not shown here) No unlabelled and/or labeled by-products were observed upon RTLC analysis of the final preparations. In contrast to other labeled bleomycins, [62Zn]bleomycin, has a lower half life causing less undesirable irradiation and it also benefits from PET radiopharmacutical advantages. Its rather higher half-life in contrast to other PET radioisotopes and high chemical stability of radiopharmaceutical form makes it a suitable possible PET tracer for use in neighborhood PET centers. [62Zn]-BLM

362

Influence of chlorpromazine, bleomycin and WR-2721 singly or in combination on the formation of radiation-induced micronuclei in mice bone marrow  

International Nuclear Information System (INIS)

Female BALB/c mice were divided into 8 groups according to the treatment they received viz. 1. DDW (double distilled water), 2. chlorpromazine (CPZ) 10 mg/kg body-weight, 3. CPZ 15 mg/kg body-weight, 4. bleomycin (BLM), 5. WR-2721, 6. CPZ (10 mg)+WR-2721, 7. CPZ (15 mg)+WR-2721, 8. BLM+WR-2721. After 30 min of drug/s administration the animals were exposed to either 0 or 4 Gy of 60Co g-radiation. The animals were killed at 24 h post-irradiation by cervical dislocation and the micronuclei were prepared according to the method described by Jagetia. The administration of CPZ (10 or 15 mg) alone increased the frequency of micronuclei significantly when compared to the DDW treatment. The exposure of mice with 4 Gy resulted in a significant increase in the frequency of micronuclei compared to the concurrent control groups. The frequency of micronuclei increased significantly in CPZ (15 mg) and BLM+irradiated groups. However, treatment with WR-2721 before irradiation reduced the frequency of micronuclei by approximately 50% of the DDW+irradiated group. A further reduction in the frequency of micronuclei was observed when WR-2721 was combined with CPZ (10 and 15 mg) before irradiation. A combination of BLM with WR-2721 also resulted in a nonsignificant reduction in the frequency of micronuclei. (orig.)

363

Comparison of computed tomography and 57Co-bleomycin scintigraphy in staging the mediastinal lymph nodes of patients with non-small-cell lung cancer  

International Nuclear Information System (INIS)

The value of computed tomography (CT) and of 57Co-bleomycin scintigraphy (57Co-BLM) in staging the mediastinal lymph nodes was compared in 28 patients suffering from non-small-cell lung cancer. The results were assessed against the pathological findings obtained during thoracotomy or mediastinoscopy. CT staging of the mediastinum had a sensitivity of 75%, a specificity of 80%, an accuracy of 79%, a positive predictive index of 60% and a negative predictive index of 89%. 57Co-BLM scintigraphic staging had a sensitivity of 43%, a specificity of 94%, and accuracy of 80%, a positive predictive index of 75% and a negative predictive index of 81%. In this small series these differences were not statistically significant; it thus appears that CT and 57Co-BLM are of equal value in staging the mediastinum. Mediastinoscopy is not contributory in case of a negative CT or 57Co-BLM. A positive CT or 57Co-BLM, however, indicates the need for histological verification of the mediastinal findings. (orig.)

364

[VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, predonisolone, bleomycin) therapy in elderly patients with aggressive non-Hodgkin lymphoma--a study of efficacy and safety, final report].  

Science.gov (United States)

We experienced the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, predonisolone, bleomycin) combination regimen for the treatment of elderly patients with aggressive non-Hodgkin lymphoma (NHL) in a multicenter study by 6 collaborative institutions. Patients were previously untreated > or = 60 years of age and received prophylactic G-CSF. Twenty patients entered this trial, and all of them were evaluated for feasibility, toxicity, and efficacy. The complete remission rate was 75.0%, with a 100% overall response rate; overall survival (OS) rate at 3 years was 79.1% (median follow up 761.5 days), with a 60.7% progression-free 3-year survival (PFS) rate (median follow-up 600.0 days). Our trial was promising and well-tolerated. According to IPI, high/high-intermediate risk was associated with significantly worse OS and PFS than low/low-intermediate risk (2-year OS: 51.8% versus 100.0%, p=0.0118; 2-year PFS: 33.3% versus 80.0%, p=0.0125). Grade 3/4 infections occurred in 3 patients, but no patients experienced it with predonisolone reduced. PMID:15675580

Ishii, Kazuyoshi; Yamamoto, Yoshihisa; Shigeki, Takashi; Kitayama, Hitoshi; Hayashi, Kunio; Hirose, Asao; Ohta, Tadanobu; Mugitani, Atsuko; Fujino, Hiroko; Yagi, Toshiya; Hirai, Manabu; Teshima, Hirofumi; Katsurada, Tatsuya; Urase, Fumiaki; Kitajima, Hiroyuki

2005-01-01

365

Pretreatment with UV light renders the chromatin in human fibroblasts more susceptible to the DNA-damaging agents bleomycin, gamma radiation and 8-methoxypsoralen  

International Nuclear Information System (INIS)

Confluent human fibroblast cultures were pretreated with either 254 nm UV light (UV) or methyl methanesulphonate (MMS), incubated at 370C and subsequently challenged on ice with bleomycin (BLM), gamma-radiation or 8-methoxy-psoralen (MOP). The resulting number of challenge-induced DNA damages (measured as DNA strand breaks or cross-links) were compared with the numbers induced in similarly challenged but non-pretreated control cells. It was found that the timing of the subsequent challenge of cells pretreated with UV did significantly affect the amount of induced DNA damage. When the challenging agents were administered after a 10-20 min incubation period following UV pretreatment, the amount of induced DNA damage was increased 50% over control cells. In contrast, the timing of the subsequent challenge of cells pretreated with MMS has no influence on the level of challenge-induced damage. It is hypothesized that UV-irradiated chromatin undergoes a time-dependent decondensation that renders it more susceptible to the induction of strand breaks and cross-links by BLM, gamma-radiation and MOP. A possible role for chromatin decondensation in UV-induced excision repair is discussed. (author)

366

"RAPID AND SIMULTANEOUS DETERMINATION OF ADRIAMYCIN, BLEOMYCIN, VINBLASTINE AND DACARBAZINE IN PLASMA OF HODGKIN'S LYMPHOMA PATIENTS BY A REVERSED PHASE HPLC METHOD"  

Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: English Abstract in english The RP-HPLC analytical method with UV detection at 230nm with ODS Hypersil C18 column (250mm x 4.6mm, 5µ particle size) was developed for simultaneous determination of Adriamycin, Bleomycin, Vinblastine and Dacarbazine in plasma of lymphoma patients using mobile phase composition of 300 volumes Acet [...] onitrile and 700 volumes 0.05M Disodium Hydrogen Phosphate containing 0.5ml TEA and pH of the mobiles phase was maintained at 3.7 with 2M Phosphoric acid at a flow rate of 0.75ml/minute with linearity ranges of 0.05-50, 0.06-50, 0.075-50 and 0.09-50 µg/ml respectively with LOD and LOQ of 0.020, 0.050; 0.045, 0.060; 0.060, 0.075 and 0.040, 0.090 respectively. % recovery of DOX, BLM, VBL and DTIC were 99.24, 99.23, 99.08 and 99.09 respectively.

MUHAMMAD, ZUBAIR MALIK; MAHMOOD, AHMAD; SALEH, MUAHAMMAD.

1674-16-01

367

21 CFR 312.30 - Protocol amendments.  

Science.gov (United States)

...has submitted the protocol to FDA for its review; and (2) the protocol has been approved by the Institutional Review Board (IRB) with responsibility...Changes in a protocol. (1) A sponsor...of the study. Examples of changes...

2010-04-01

368

Internet Protocol Television (IPTV  

Directory of Open Access Journals (Sweden)

Full Text Available IPTV is one of the mostly used technology of Internet and IP application. IPTV is a service for the delivery of broadcast TV, movies on demand and other interactive multimedia services over a secure, end-to-end operator managed broadband IP data network with desired QoS to the public with a broadband Internet connection. IPTV system may also include Internet services such as Web access and VoIP where it may be called Triple Play and is typically supplied by a broadband operator using the same infrastructure. IPTV is not the Internet Video that simply allows users to watch videos, like movie previews and web-cams, over the Internet in a best effort fashion. IPTV technology offers revenue-generating opportunities for the telecom and cable service providers. For traditional telephone service providers, Triple Play is delivered using a combination of optical fiber and Digital Subscriber Line (DSL technologies to its residential base. IPTV is a system where a digital television service is delivered by using Internet Protocol over a network infrastructure, which may include delivery by a broadband connection. A general definition of IPTV is television content that, instead of being delivered through traditional broadcast and cable formats, is received by the viewer through the technologies used for computer networks. In this paper I am trying to discuss this topic as my knowledge, including what is IPTV, how it works, its advantages and its applications

Lokesh Mittal

2012-09-01

369

Protocols for Scholarly Communication  

Science.gov (United States)

CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should guide authors naturally towards OA publication, and CERN wants to help reach a full open access publishing environment for the particle physics community and related sciences in the next few years.

Pepe, A.; Yeomans, J.

2007-10-01

370

The HPA photon protocol and proposed electron protocol  

International Nuclear Information System (INIS)

The Hospital Physicists Association (HPA) photon dosimetry protocol has been produced and was published in 1983. Revised values of some components of Csub(lambda) and refinements introduced into the theory in the last few years have enabled new Csub(lambda) values to be produced. The proposed HPA electron protocol is at present in draft form and will be published shortly. Both protocels are discussed. (Auth.)

371

Prehospital thrombolysis in acute myocardial infarction: the Belgian eminase prehospital study (BEPS). BEPS Collaborative Group.  

Science.gov (United States)

Interest in early thrombolysis has prompted a study on the feasibility and time course of prehospital thrombolysis in patients with acute myocardial infarction (AMI) in six centres in Belgium. Patients with clinically suspected AMI and with typical ECG changes presenting within 4 h after onset of pain were treated with 30 units of Anisoylated Plasminogen Streptokinase Activator Complex (APSAC, eminase) intravenously by a mobile intensive care unit (MICU). Sixty-two patients were included in the study and an AMI was confirmed in 60. The mean time (+/- 1 SD) from onset of pain to injection of APSAC was 95 +/- 47 min and the mean estimated time gain, calculated as the time difference between the arrival of the MICU at home and the arrival of the MICU at the emergency department, was 50 +/- 17 min. In the prehospital period four patients developed ventricular fibrillation and one cardiogenic shock. During hospital stay severe complications were observed in four patients. Two events were fatal, one diffuse haemorrhage and one septal rupture; two events were non fatal, one feasible and that an estimated time gain of 50 min can be obtained. Potential risks and benefits remain to be demonstrated in a large controlled clinical trial. PMID:1936009

1991-09-01

372

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

B6.Cg-Tg(S100b-v-erbB)4496Waw Cdkn2atm1Rdp/Nci PCR Protocol Strain: B6.Cg-Tg(S100b-v-erbB)4496Waw Cdkn2atm1Rdp/Nci Strain Code: 01XD3 Protocol Number: 1 Introductory Comment: Primers:  E001 :   5'-cTc AcA GcA ATc TcA AAG cTc ccc -3'  E002 :   5'-AGc

373

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

C3.Cg-Tg(RIP1-Tag2)2Dh/Nci PCR Protocol Strain: C3.Cg-Tg(RIP1-Tag2)2Dh/Nci Strain Code: 01XD6 Protocol Number: 1 Introductory Comment: Primers:  T018 :   5'-GGA cAA Acc AcA AcT AGA ATG cAG -3'  T020 :   5'-cAc cGG AGA ATG GGA AGc cGA A -3'  T019 :

374

SNOMED CT® Encoded Cancer Protocols  

OpenAIRE

SNOMED Clinical Terms® (SNOMED CT®) is being used to encode the Cancer Protocols published by the College of American Pathologists (CAP). As of January 1, 2004, one of the standards set for approved cancer programs by the American College of Surgeons Commission on Cancer will be that at least 90% of surgical pathology reports contain all essential data elements identified in the CAP Cancer Protocols.

Berkum, Monique M.

2003-01-01

375

Multilevel Security Protocol using RFID  

OpenAIRE

Though RFID provides automatic object identification, yet it is vulnerable to various security threats that put consumer and organization privacy at stake. In this work, we have considered some existing security protocols of RFID system and analyzed the possible security threats at each level. We have modified those parts of protocol that have security loopholes and thus finally proposed a modified four-level security model that has the potential to provide fortification against security threats

Syed Faiazuddin; Venkat Rao, S.; Ramana Rao, S. C. V.; Sainatha Rao, M. V.; Sathish Kumar, P.

2011-01-01

376

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

B6.129S6-Nf1tm1Fcr/Nci PCR Protocol Strain: B6.129S6-Nf1tm1Fcr/Nci Strain Code: 01XF3 Protocol Number: 1 Introductory Comment: Primers:  N010 :   5'-GTA TTG AAT TGA AGc Acc TTT GTT TGG -3'  N012 :   5'-cTG ccc AAG GcT ccc ccA G -3'  N011 :   5'-GcG

377

Secure E-payment Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available The vast spreading of information in the last decade has led to greatdevelopment in e-commerce. For instance, e-trade and e-bank are two mainInternet services that implement e-transaction from anyplace in the world. Thishelps merchant and bank to ease the financial transaction process and to giveuser friendly services at any time. However, the cost of workers andcommunications falls down considerably while the cost of trusted authority andprotecting information is increased. E-payment is now one of the most centralresearch areas in e-commerce, mainly regarding online and offline paymentscenarios. In this paper, we will discuss an important e-payment protocol namelyKim and Lee scheme examine its advantages and delimitations, whichencourages the author to develop more efficient scheme that keeping allcharacteristics intact without concession of the security robustness of theprotocol. The suggest protocol employs the idea of public key encryption schemeusing the thought of hash chain. We will compare the proposed protocol with Kimand Lee protocol and demonstrate that the proposed protocol offers moresecurity and efficiency, which makes the protocol workable for real worldservices.

Sattar J Aboud

2009-11-01

378

A Comparison of Effects of ABVD and ChlVPP Chemotherapeutic Protocols for Hodgkin's Disease on Rats’ Epididiymal and Testicular Tissues  

Directory of Open Access Journals (Sweden)

Full Text Available The goal of this study was to determine the effects of ABVD and ChlVPP chemotherapeutic protocols for Hodgkin's disease on the structure of testis and epididymis of male rat. After determining tolerance dose of drugs in pilot study, 24 male rats were divided to four groups: ABVD (doxorubicin, bleomycine, vinblastin, dacarbazine group, ChlVPP (chlorambucil, vinblastin, procarbazine, prednisolone group and two control groups one for each treatment group. One half of the lethal dose for 50% of population (LD50 was used for treatment of animals in each protocol. Testes and epididymis tissues were examined for structural changes and serum testosterone level was measured by Lission (chemiluminescence method. Body weight, testis and epididymis weights, in treated rats were significantly less than their control groups specifically in ABVD group was less than ChlVPP group. Decreasing of mean diameter of seminiferous tubules, height of spermatogenic cells and diameter of epididymis in caput, corpus and cauda in ABVD group were significantly more than ChlVPP and control group. The serum testosterone level in ABVD group was significantly less than ChlVPP and control group. According to this study results, the ChlVPP had fewer impairment effects than ABVD on testis and epididymis tissue in tolerance doses on male rats' reproductive system. More clinical trial studies are suggested on Hodgkin's patients. With equal treatment effectiveness, it will be better to use the most reliable and safe treatment especially in young patients.

S. Zare

2010-01-01

379

A comparison of effects of ABVD and ChlVPP chemotherapeutic protocols for Hodgkin's disease on rats' epididiymal and testicular tissues.  

Science.gov (United States)

The goal of this study was to determine the effects of ABVD and ChlVPP chemotherapeutic protocols for Hodgkin's disease on the structure of testis and epididymis of male rat. After determining tolerance dose of drugs in pilot study, 24 male rats were divided to four groups: ABVD (doxorubicin, bleomycine, vinblastin, dacarbazine) group, ChlVPP (chlorambucil, vinblastin, procarbazine, prednisolone) group and two control groups one for each treatment group. One half of the lethal dose for 50% of population (LD50) was used for treatment of animals in each protocol. Testes and epididymis tissues were examined for structural changes and serum testosterone level was measured by Lission (chemiluminescence method). Body weight, testis and epididymis weights, in treated rats were significantly less than their control groups specifically in ABVD group was less than ChlVPP group. Decreasing of mean diameter of seminiferous tubules, height of spermatogenic cells and diameter of epididymis in caput, corpus and cauda in ABVD group were significantly more than ChlVPP and control group. The serum testosterone level in ABVD group was significantly less than ChlVPP and control group. According to this study results, the ChlVPP had fewer impairment effects than ABVD on testis and epididymis tissue in tolerance doses on male rats' reproductive system. More clinical trial studies are suggested on Hodgkin's patients. With equal treatment effectiveness, it will be better to use the most reliable and safe treatment especially in young patients. PMID:23350161

Oskooii, A Eyshi; Gholizad, L Mohammad; Zare, S; Nejati, V

2010-09-15

380

Induced radiation resistance by a long term culture of low dose bleomycin and cis-diamminedichloroplatinum (II) in seven head and neck squamous cell carcinoma cell lines  

International Nuclear Information System (INIS)

Chemotherapeutic (bleomycin (BLM) and cis-diamminedichloroplatinum (II) (CDDP)) and radiation (X-ray) intrinsic resistance, as well as BLM and CDDP induced chemo- and X-ray resistance were examined among seven human head and neck originated squamous cell carcinoma cell lines. Cell survival was determined by colony forming assay. A positive relationship between BLM and X-ray intrinsic resistance but not between CDDP and X-ray resistance was observed. A long term (24 weeks) culture by low dose BLM (0.2 ?g/ml) and low dose CDDP (0.1 ?g/ml) treatments were performed if those treatments induce BLM and CDDP resistance and also X-ray resistance. The BLM long term culture resulted in more resistance in 1 cell line which is relatively intrinsic sensitive to BLM. The CDDP long term culture resulted in more resistance to CDDP in 6 out of 7 cell lines. Furthermore, the BLM long term culture induced more X-ray resistance in 1 out of 7 cell lines, and the CDDP long term culture induced more X-ray resistance in 6 out of 7 cell lines, indicating that the long term culture of BLM and CDDP may cause the resistance to both chemotherapeutics and X-ray. Interesting, SCC-61 cell line which is the most sensitive to X-rays, induced the most resistance to X-rays by both the BLM and CDDP long term culture. These results suggest that X-ray resistance could be induced by either a BLM type or a CDDP type, of which the mechanisms of cell killing are different. (author)ent. (author)

381

Monoclonal antibodies technology. Protocols  

International Nuclear Information System (INIS)

Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 ?g/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x107 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x107 spleen cells to 1x106 myeloma cells (ratio 10:1). Centrifuge the mixture of cells at 300g for 10 minutes. While the cells are centrifuging, set aside 30 ml of serum-free RPMI 1640 in another 50-ml tube. Prepare the 50% PEG and place the timer in the hood. 6. Remove all the supernatant from the cell pellet. Overlay the pellet of cells with 0.5 ml of 50% PEG with a Pasteur pipet during 1 minute. Then add 5 ml of serum-free RPMI 1640 during 3 minutes. At the end of 3 minutes, add during a minute 15 ml of the same medium. 7. Centrifuge at 250g for 10 minutes. Gently resuspend the fused cells at a concentration of 5 x104 cells/ml, in a RPMI medium containing serum at 20%, HAT (selective growth) and antibiotics. 8. Distribute the cell suspension into 96-well-flat-bottom-tissue-culture plates add 0.2 ml per well. Incubate the plates at 37 deg. C in 5% CO2. Three to 4 days in HAT medium is sufficient for arresting the proliferation of unfused myeloma cells. Screening and establishing a Hybridorna line. The screening could be perform using different immunoassay alternatives (ELISA, RIA, etc). The principal requisite is have been developed a reproducible method before to make the fusion. These method could be improve using the serum of mice immunized as sample. Approximately 1 week after the fusion, colonies of hybrid cells will be ready to screen. During the screening, samples of tissue culture media are removed from wells that have growing hybridomas and are tested for the presence of the desired antibodies. Successful fusions will produce between 2000 and 5000 hybridomas colonies. Depending on the fusion, individual wells will become ready to screening over 2 to 6 day period. Typically, the first wells could be ready to screen in day 7 or 8, and most of the wells will need to be screened within the next 4 or 5 days. When you detected a possible positive clone, you could transfer hybrids of interest to 24-plates adding 1 ml of HAT medium (RPMI 1640) supplemented with serum at 20%. Cryopreserve each culture of cells when they have reached at least 3/4 confluency, 2 ampules/cell culture. Save the supernatants for further studies. Re

382

Hybrid broadcasting protocol for video on demand  

Science.gov (United States)

Broadcasting protocols can improve the efficiency of video on demand services by reducing the bandwidth required to transmit videos that are simultaneously watched by many viewers. It has been recently shown that broadcasting protocols using a very large number of very low bandwidth streams for each video required less total bandwidth than protocols using a few high-bandwidth streams shared by all videos. We present a hybrid broadcasting protocol that combines the advantages of these two classes of protocols. Our pagoda broadcasting protocol uses only a small number of high-bandwidth streams and requires only slightly more bandwidth than the best extant protocols to achieve a given maximum waiting time.

Paris, Jehan-Francois; Carter, Steven W.; Long, Darrell D. E.

1998-12-01

383

SILC-A Secured Internet Chat Protocol  

OpenAIRE

The Secure Internet Live Conferencing (SILC) protocol, a new generation chat protocol provides full featured conferencing services, compared to any other chat protocol. Its main interesting point is security which has been described all through the paper. We have studied how encryption and authentication of the messages in the network achieves security. The security has been the primary goal of the SILC protocol and the protocol has been designed from the day one security in mind. In this pap...

ANINDITA SINHA; SAUGATA SINHA

2013-01-01

384

New Spacewire Protocols and Tools  

Science.gov (United States)

SpaceWire is now being used on many spacecraft for payload data-handling applications. Several new protocols have recently been published enhancing the level of standardization that SpaceWire offers. For example, the SpaceWire Remote Memory Access Protocol (RMAP) provides a means of reading or writing to memory in a remote node over a SpaceWire network, and is already being used on several missions. Additional protocols are being developed including SpaceWire-D, which aims to support control applications running over SpaceWire that need deterministic data transfer. This paper introduces the latest set of protocols designed to operate over SpaceWire and describes SpaceWire-D in some detail. STAR-Dundee has developed and extended its range of test and development equipment to support the new protocols running over SpaceWire. This new range of test equipment from STAR-Dundee, which provides comprehensive evaluation, development and test capabilities, is described.

Parkes, S.; Mills, S.; McClements, C.; Mason, A.; McKechnie, P.; Scott, P.; Yu, B.; Roberts, D.

2010-08-01

385

Cyclooxygenase-2 deficiency results in a loss of the anti-proliferative response to transforming growth factor-beta in human fibrotic lung fibroblasts and promotes bleomycin-induced pulmonary fibrosis in mice.  

Science.gov (United States)

Prostaglandin E(2) (PGE(2)) inhibits fibroblast proliferation and collagen production. Its synthesis by fibroblasts is induced by profibrotic mediators including transforming growth factor (TGF)-beta(1). However, in patients with pulmonary fibrosis, PGE(2) levels are decreased. In this study we examined the effect of TGF-beta(1) on PGE(2) synthesis, proliferation, collagen production, and cyclooxygenase (COX) mRNA levels in fibroblasts derived from fibrotic and nonfibrotic human lung. In addition, we examined the effect of bleomycin-induced pulmonary fibrosis in COX-2-deficient mice. We demonstrate that basal and TGF-beta(1)-induced PGE(2) synthesis is limited in fibroblasts from fibrotic lung. Functionally, this correlates with a loss of the anti-proliferative response to TGF-beta(1). This failure to induce PGE(2) synthesis is because of an inability to up-regulate COX-2 mRNA levels in these fibroblasts. Furthermore, mice deficient in COX-2 exhibit an enhanced response to bleomycin. We conclude that a decreased capacity to up-regulate COX-2 expression and COX-2-derived PGE(2) synthesis in the presence of increasing levels of profibrotic mediators such as TGF-beta(1) may lead to unopposed fibroblast proliferation and collagen synthesis and contribute to the pathogenesis of pulmonary fibrosis. PMID:11290559

Keerthisingam, C B; Jenkins, R G; Harrison, N K; Hernandez-Rodriguez, N A; Booth, H; Laurent, G J; Hart, S L; Foster, M L; McAnulty, R J

2001-04-01

386

Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars / Resultados de uma combinacao de bleomicina e triamcinolone acetonide no tratamento de queloides e cicatrizes hipertroficas  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese Enquanto normalmente o tratamento de queloides e cicatrizes hipertróficas mostra resultados moderados, o tratamento com bleomicina revelou resultados mais promissores. Este estudo foi dividido em duas partes. Na primeira parte, o objetivo foi mostrar os resultados da utilização de uma combinação de [...] bleomicina e acetonido de triancinolona por cm2 (BAT). Na segunda parte, o objetivo foi determinar a resposta aos dois medicamentos em queloides grandes, que foram divididos em quadrados de 1 cm2, tratando cada quadrado com a dose utilizada anteriormente. Na primeira parte do estudo, a resposta clínica de 37 queloides de 0,3 to 1,8 cm2 tratados com BAT foi monitorada por um período de 1 a 2 anos. Injeções de 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona foram aplicadas a cada 3 meses. Na segunda parte do estudo, revisamos a resposta clínica em 6 pacientes com queloides grandes. A dose mensal administrada nunca excedeu 3 UI de bleomicina. O primeiro estudo mostrou que 36 queloides (97,29%) amoleceram após a primeira dose. No segundo estudo, 5 mostraram diferentes respostas (a resposta foi completa nos quatro queloides menores). O queloide maior necessitou de 9 doses para apresentar melhora de 70%. Concluindo, o tratamento combinado com 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona por cm2foi considerado um procedimento aceitável para o tratamento de queloides. Os melhores resultados foram obtidos em queloides com mais de 1 cm2 ou divididos em áreas de 1cm2. Estudos mais amplos deveriam ser realizados, para confirmar esses resultados. Abstract in english While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per [...] cm2 (BTA). In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29%) softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids). The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..

Francisco Miguel, Camacho-Martinez; Elena Rodriguez, Rey; Francisco Camacho, Serrano; Adriana, Wagner.

2013-06-01

387

Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars Resultados de uma combinação de bleomicina e triamcinolone acetonide no tratamento de quelóides e cicatrizes hipertróficas  

Directory of Open Access Journals (Sweden)

Full Text Available While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per cm2 (BTA. In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29% softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids. The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..Enquanto normalmente o tratamento de queloides e cicatrizes hipertróficas mostra resultados moderados, o tratamento com bleomicina revelou resultados mais promissores. Este estudo foi dividido em duas partes. Na primeira parte, o objetivo foi mostrar os resultados da utilização de uma combinação de bleomicina e acetonido de triancinolona por cm2 (BAT. Na segunda parte, o objetivo foi determinar a resposta aos dois medicamentos em queloides grandes, que foram divididos em quadrados de 1 cm2, tratando cada quadrado com a dose utilizada anteriormente. Na primeira parte do estudo, a resposta clínica de 37 queloides de 0,3 to 1,8 cm2 tratados com BAT foi monitorada por um período de 1 a 2 anos. Injeções de 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona foram aplicadas a cada 3 meses. Na segunda parte do estudo, revisamos a resposta clínica em 6 pacientes com queloides grandes. A dose mensal administrada nunca excedeu 3 UI de bleomicina. O primeiro estudo mostrou que 36 queloides (97,29% amoleceram após a primeira dose. No segundo estudo, 5 mostraram diferentes respostas (a resposta foi completa nos quatro queloides menores. O queloide maior necessitou de 9 doses para apresentar melhora de 70%. Concluindo, o tratamento combinado com 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona por cm2foi considerado um procedimento aceitável para o tratamento de queloides. Os melhores resultados foram obtidos em queloides com mais de 1 cm2 ou divididos em áreas de 1cm2. Estudos mais amplos deveriam ser realizados, para confirmar esses resultados.

Francisco Miguel Camacho-Martínez

2013-06-01

388

Cryptographic Protocols: : Theory and Implementation  

DEFF Research Database (Denmark)

The art of keeping messages secret is ancient. It must have been invented only shortly after the invention of the messages themselves. Merchants and generals have always had a need to exchange critical messages while keeping them secret from the prying eyes of competitors or the enemy. Classical cryptography was thus concerned with message confidentiality and integrity. Modern cryptography cover a much wider range of subjects including the area of secure multiparty computation, which will be the main topic of this dissertation. Our first contribution is a new protocol for secure comparison, presented in Chapter 2. Comparisons play a key role in many systems such as online auctions and benchmarks — it is not unreasonable to say that when parties come together for a multiparty computation, it is because they want to make decisions that depend on private information. Decisions depend on comparisons. We have implemented the comparison protocol in Java and benchmarks show that is it highly competitive and practical. The biggest contribution of this dissertation is a general framework for secure multiparty computation. Instead of making new ad hoc implementations for each protocol, we want a single and extensible framework. We call this framework VIFF, short for Virtual Ideal Functionality Framework. VIFF implements a UC functionality for general multiparty computation on asynchronous networks. We give a formal definition of the functionality in Chapter 3. There we also describe how we implemented the functionality with a variant of the classic BGW protocol. The protocol is secure against a semi-honest adversary. In Chapter 4 we describe a new protocol for VIFF that is secure against malicious adversaries. The protocol guarantees termination if the adversary allows a preprocessing phase to terminate, in which no information is released. The communication complexity of this protocol is the same as that of a passively secure solution up to a constant factor. It is secure against an adaptive and active adversary corrupting less than n=3 players. Following the presentation of VIFF, we turn to a more theoretical subject. Chapter 5 investigates the notion of a covert adversary — an adversary type that intuitively lies in between semi-honest and malicious adversaries. The main idea is that we accept that a cheating adversary may succeed with a given probability, which need not be negligible. The reasoning is that in many real-world cases, a large probability of being caught is sufficient to prevent the adversary from trying to cheat. We show how to compile a passively secure protocol for honest majority into a protocol that is secure against covert attacks, again for honest majority. The transformed protocol catches cheating with probability 1/4 . Though we present no implementation of this compiler, we believe it will be very efficient and practical to implement using, say, VIFF. The cost of the modified protocol is essentially twice that of the original plus an overhead that only depends on the number of inputs. We round off this dissertation with Chapter 6. There we return to the practical side of things and consider how users of online collaboration tools and network storage services place considerable trust in their providers. We presents a novel approach for protecting data integrity in revision control systems hosted by an untrusted provider. It guarantees atomic read and write operations on the shared data when the service is correct and preserves fork-linearizability when the service is faulty. A prototype has been implemented on top of the Subversion revision control system; benchmarks show that the approach is practical.

Geisler, Martin Joakim Bittel

2010-01-01

389

The Geneva Protocol of 1925  

International Nuclear Information System (INIS)

This paper reports that when President Gerald Ford signed the instruments of ratification for the Geneva Protocol of 1925 on January 22, 1975, a tortured, half-century-long chapter in U.S. arms control policy was brought to a close. Fifty years earlier, at the Geneva Conference for the Control of the International Trade in Arms, Munitions and Implements of War, the United States had played a key role in drafting and reaching agreement on the Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases and of Bacteriological Methods of Warfare. The protocol, signed by thirty nations, including the United States, on June 17, 1925, prohibits the use in war of asphyxiating, poisonous or other gases, and of all analogous liquids, materials or devices as well as the use of bacteriological methods of warfare

390

Sequential Rationality in Cryptographic Protocols  

CERN Document Server

Much of the literature on rational cryptography focuses on analyzing the strategic properties of cryptographic protocols. However, due to the presence of computationally-bounded players and the asymptotic nature of cryptographic security, a definition of sequential rationality for this setting has thus far eluded researchers. We propose a new framework for overcoming these obstacles, and provide the first definitions of computational solution concepts that guarantee sequential rationality. We argue that natural computational variants of subgame perfection are too strong for cryptographic protocols. As an alternative, we introduce a weakening called threat-free Nash equilibrium that is more permissive but still eliminates the undesirable ``empty threats'' of non-sequential solution concepts. To demonstrate the applicability of our framework, we revisit the problem of implementing a mediator for correlated equilibria (Dodis-Halevi-Rabin, Crypto'00), and propose a variant of their protocol that is sequentially r...

Gradwohl, Ronen; Rosen, Alon

2010-01-01

391

Cryptographic Protocols under Quantum Attacks  

CERN Document Server

The realm of this thesis is cryptographic protocol theory in the quantum world. We study the security of quantum and classical protocols against adversaries that are assumed to exploit quantum effects to their advantage. Security in the quantum world means that quantum computation does not jeopardize the assumption, underlying the protocol construction. But moreover, we encounter additional setbacks in the security proofs, which are mostly due to the fact that some well-known classical proof techniques are forbidden by certain properties of a quantum environment. Interestingly, we can exploit some of the very same properties to the benefit of quantum cryptography. Thus, this work lies right at the heart of the conflict between highly potential effects but likewise rather demanding conditions in the quantum world.

Lunemann, Carolin

2011-01-01

392

Developing protocols for obstetric emergencies.  

Science.gov (United States)

There is potential for important steps to be missed in emergency situations, even in the presence of many health care team members. Developing a clear plan of response for common emergencies can ensure that no tasks are redundant or omitted, and can create a more controlled environment that promotes positive health outcomes. A multidisciplinary team was assembled in a large community hospital to create protocols that would help ensure optimum care and continuity of practice in cases of postpartum hemorrhage, shoulder dystocia, emergency cesarean surgical birth, eclamptic seizure and maternal code. Assignment of team roles and responsibilities led to the evolution of standardized protocols for each emergency situation. PMID:25316538

Roth, Cheryl K; Parfitt, Sheryl E; Hering, Sandra L; Dent, Sarah A

2014-01-01

393

Agreement reached on Kyoto Protocol  

Science.gov (United States)

Environment ministers from 178 nations meeting in Bonn, Germany, reached a broad political agreement July 23 on the rules for the Kyoto Protocol on climate change. The agreement, which came despite United States opposition to the treaty, keeps the protocol alive and on track for potential final approval later this year by the signatories.Japanese Prime Minister Junichiro Koizumi, who indicated he prefers U.S. participation, said he was basically pleased with the outcome of the negotiations. “I welcome the basic agreement on ‘core elements’ which has been consequently reached,’ he said.

Showstack, Randy

394

Heterogeneous planning for homogeneous protocols  

International Nuclear Information System (INIS)

Clinical trials often require homogeneous treatment plans. Many institutions, however, have begun using heterogeneous plans. Is it possible to satisfy the requirements of such a protocol while achieving the superior accuracy of heterogeneous treatment planning? At the University of Texas M. D. Anderson Cancer Center, we currently use conformal treatment planning with heterogeneities for thoracic cancers. This paper describes a procedure that has been developed to satisfy the requirements of a homogeneous protocol, such as RTOG 98-01 (A Phase III Study of Amifostine mucosal protection), while maintaining accuracy in treatment planning

395

The Kyoto protocol development; La viabilite du protocole de Kyoto  

Energy Technology Data Exchange (ETDEWEB)

From the author R. Cooper point of view the Kyoto Protocol is a flawed concept. The reasons for dropping Kyoto are presented in this paper insisting that rejecting Kyoto not means to imply that global climate change is not a serious problem. After a presentation of the US policy facing the Climatic Change, some concluding propositions are proposed. (A.L.B.)

Cooper, R. [Harvard Univ., Barrow, AK (United States); Guesneris, R. [College de France, 75 - Paris (France)

2002-04-01

396

Detection of epithelial to mesenchymal transition in airways of a bleomycin induced pulmonary fibrosis model derived from an ?-smooth muscle actin-Cre transgenic mouse  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Epithelial to mesenchymal transition (EMT in alveolar epithelial cells (AECs has been widely observed in patients suffering interstitial pulmonary fibrosis. In vitro studies have also demonstrated that AECs could convert into myofibroblasts following exposure to TGF-?1. In this study, we examined whether EMT occurs in bleomycin (BLM induced pulmonary fibrosis, and the involvement of bronchial epithelial cells (BECs in the EMT. Using an ?-smooth muscle actin-Cre transgenic mouse (?-SMA-Cre/R26R strain, we labelled myofibroblasts in vivo. We also performed a phenotypic analysis of human BEC lines during TGF-?1 stimulation in vitro. Methods We generated the ?-SMA-Cre mouse strain by pronuclear microinjection with a Cre recombinase cDNA driven by the mouse ?-smooth muscle actin (?-SMA promoter. ?-SMA-Cre mice were crossed with the Cre-dependent LacZ expressing strain R26R to produce the double transgenic strain ?-SMA-Cre/R26R. ?-galactosidase (?gal staining, ?-SMA and smooth muscle myosin heavy chains immunostaining were carried out simultaneously to confirm the specificity of expression of the transgenic reporter within smooth muscle cells (SMCs under physiological conditions. BLM-induced peribronchial fibrosis in ?-SMA-Cre/R26R mice was examined by pulmonary ?gal staining and ?-SMA immunofluorescence staining. To confirm in vivo observations of BECs undergoing EMT, we stimulated human BEC line 16HBE with TGF-?1 and examined the localization of the myofibroblast markers ?-SMA and F-actin, and the epithelial marker E-cadherin by immunofluorescence. Results ?gal staining in organs of healthy ?-SMA-Cre/R26R mice corresponded with the distribution of SMCs, as confirmed by ?-SMA and SM-MHC immunostaining. BLM-treated mice showed significantly enhanced ?gal staining in subepithelial areas in bronchi, terminal bronchioles and walls of pulmonary vessels. Some AECs in certain peribronchial areas or even a small subset of BECs were also positively stained, as confirmed by ?-SMA immunostaining. In vitro, addition of TGF-?1 to 16HBE cells could also stimulate the expression of ?-SMA and F-actin, while E-cadherin was decreased, consistent with an EMT. Conclusion We observed airway EMT in BLM-induced peribronchial fibrosis mice. BECs, like AECs, have the capacity to undergo EMT and to contribute to mesenchymal expansion in pulmonary fibrosis.

Yang Xiao

2007-01-01

397

Nitric oxide inhibition decreases bleomycin-detectable iron in spleen, bone marrow cells and heart but not in liver in exercise rats.  

Science.gov (United States)

The possible role of nitric oxide on the exercise-induced changes in bleomycin-detectable iron (BDI) in the liver, spleen, bone marrow cells and heart was investigated. Female Sprague-Dawley rats were randomly assigned to four groups: S1 (Sedentary), S2 (Sedentary + L-NAME [N-nitro-L-arginine methyl ester]), E1 (Exercise) and E2 (Exercise + L-NAME). Animals in the E1 and E2 swam for 2 h/day for 3 months. L-NAME in the drinking water (1 mg/ml) was administrated to rats in the S2 and E2 groups for the same period. At the end of the 3rd month, nitrite and nitrate (NOx), BDI and non-heme iron (NHI) contents in the liver, spleen, bone marrow cells and heart were measured. The ratio of BDI/NHI was calculated. The exercise induced a significant increase in NOx and BDI contents and/or BDI/NHI ratio in the spleen, bone morrow cells and heart. Treatment with L-NAME, an inhibitor of NOS, led to a significant decrease in NOx and an increase in BDI levels and BDI/NHI ratios in these tissues. The correlative analysis showed that there is significantly positive correlation between NOx levels and BDI contents and/or BDI/NHI ratios in the spleen, bone marrow cells and heart. These results suggest that the increased nitric oxide might be one of the reasons leading to the increased BDI levels in these tissues in the exercised rats. In contrast to the above tissues, in the liver, exercise led to a significant decrease rather than increase in BDI levels and BDI/NHI ratios with a significant increase in NOx contents. Treatment with L-NAME led to a significant increase in BDI levels and BDI/NHI ratios and a decrease in NOx contents in the tissue. These findings plus the results reported by others imply that nitric oxide might have an inhibitory effect on BDI in the liver. PMID:15228083

Xiao, De Sheng; Ho, Kwok Ping; Qian, Zhong Ming

2004-05-01

398

Superposition Attacks on Cryptographic Protocols  

DEFF Research Database (Denmark)

Attacks on classical cryptographic protocols are usually modeled by allowing an adversary to ask queries from an oracle. Security is then defined by requiring that as long as the queries satisfy some constraint, there is some problem the adversary cannot solve, such as compute a certain piece of information. In this paper, we introduce a fundamentally new model of quantum attacks on classical cryptographic protocols, where the adversary is allowed to ask several classical queries in quantum superposition. This is a strictly stronger attack than the standard one, and we consider the security of several primitives in this model. We show that a secret-sharing scheme that is secure with threshold $t$ in the standard model is secure against superposition attacks if and only if the threshold is lowered to $t/2$. We use this result to give zero-knowledge proofs for all of NP in the common reference string model. While our protocol is classical, it is sound against a cheating unbounded quantum prover and computational zero-knowledge even if the verifier is allowed a superposition attack. Finally, we consider multiparty computation and show that for the most general type of attack, simulation based security is not possible. However, putting a natural constraint on the adversary, we show a non-trivial example of a protocol that can indeed be simulated.

Damgård, Ivan Bjerre; Funder, Jakob LØvstad

2011-01-01

399

Bundle Security Protocol for ION  

Science.gov (United States)

This software implements bundle authentication, conforming to the Delay-Tolerant Networking (DTN) Internet Draft on Bundle Security Protocol (BSP), for the Interplanetary Overlay Network (ION) implementation of DTN. This is the only implementation of BSP that is integrated with ION.

Burleigh, Scott C.; Birrane, Edward J.; Krupiarz, Christopher

2011-01-01

400

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

These mice carry a floxed allele of Nf1 with LoxP site in introns 30 and 32. The strategy of the genotyping protocol is to detect the Neo cassette by primers NF02 and NF03. An internal control is included in the reaction using primer NF02 and NF01.

401

DSTC Layering Protocols in Wireless Cooperative Networks  

CERN Document Server

In adhoc wireless relay networks, layers of relays are used to communicate from a source to a destination to achieve better reliability. In this paper, we consider five protocols derived from an earlier proposed protocol, where the relays do a simple processing before transmitting and as a result achieve distributed space-time code. Four of the protocols discussed utilize more complicated relaying schemes than simple layered protocols proposed in earlier literature. We have analyzed the effectiveness of these protocols in various power loss configurations among the paths. Optimum power allocation of the total power among various transmissions have been found by reasonable fine search for all the protocols. Bit error rate plots are compared under optimum power allocation for these protocols. From the simulation results, we draw some guidelines as to which protocol is good for what kind of environment.

Elamvazhuthi, P S; Dey, B K

2008-01-01

402

Authenticated Key Agreement Protocols: A Comparative Study  

Directory of Open Access Journals (Sweden)

Full Text Available One of the most important and challenging cryptographic primitives in Public Key Cryptography is Key Agreement Protocol where two or more parties share secret values and establish the session key. Many authors have proposed key agreement protocols. In this article, we have viewed some authenticated Key Agreement Protocols and presented a comparative study. We have also described the design principle, security requirement and various attacks on Key Agreement Protocol.

Areej Omar Baalghusun

2014-12-01

403

Automatic Verification of Security Protocols Using Approximations  

OpenAIRE

Security protocols are widely used in open modern networks to ensure safe communications. It is now recognized that formal analysis can provide the level of assurance required by both developers and users of the protocols. Unfortunately it is generally undecidable to certify whether a protocol is safe or not. However the automatic verification of security protocols can be attempted using abstraction-based approximation. For this purpose, tree automata approximations were introduced by Genet a...

Boichut, Yohan; He?am, Pierre-cyrille; Kouchnarenko, Olga

2005-01-01

404

Static Validation of a Voting Protocol  

DEFF Research Database (Denmark)

The desired security properties of electronic voting protocols include verifiability, accuracy, democracy and fairness. In this paper we use a static program analysis tool to validate these properties for one of the classical voting protocols under appropriate assumptions. The protocol is formalised in an extension of the LySa process calculus with blinding signatures. The analysis, which is fully automatic, pinpoints previously undiscovered flaws related to verifiability and accuracy and we suggest modifications of the protocol needed for validating these properties.

Nielsen, Christoffer Rosenkilde; Andersen, Esben Heltoft

2005-01-01

405

Rapid-purification protocols for optical homodyning  

OpenAIRE

We present a number of rapid-purification feedback protocols for optical homodyne detection of a single optical qubit. We derive first a protocol that speeds up the rate of increase of the average purity of the system, and find that like the equivalent protocol for a non-disspative measurement, this generates a deterministic evolution for the purity in the limit of strong feedback. We also consider two analogues of the Wiseman-Ralph rapid-purification protocol in this settin...

Chiruvelli, Aravind; Jacobs, Kurt

2007-01-01

406

Using Ovsynch protocol versus Cosynch protocol in dairy cows  

Directory of Open Access Journals (Sweden)

Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 As a research on the reproductive physiology and endocrinology surrounding the estrous cycle in dairy cattle has been compiled, several estrous synchronization programs have been developed for use with dairy cows. These include several programs that facilitate the mass breeding of all animals at a predetermined time (timed-AI rather than the detection of estrus. We studied on 15 dary cows which were synchronized by Ovsynch and Cosynch programs. The estrus response for cows in Ovsynch protocol was of 63%. Pregnancy per insemination at 60 days was of 25%. Estrus response for cow in Cosynch protocol was of 57%. Pregnancy per insemination at 60 days was of 57%. Synchronization of ovulation using Ovsynch protocols can provide an effective way to manage reproduction in lactating dairy cows by eliminating the need for estrus detection. These are really efficient management programs for TAI of dairy cows that are able to reduce both the labour costs and the extra handling to daily estrus detection and AI. 

Ion Valeriu Caraba

2013-10-01

407

Multipartite purification protocols: upper and optimal bounds  

OpenAIRE

A method for producing an upper bound for all multipartite purification protocols is devised, based on knowing the optimal protocol for purifying bipartite states. When applied to a range of noise models, both local and correlated, the optimality of certain protocols can be demonstrated for a variety of graph and valence bond states.

Kay, Alastair; Pachos, Jiannis K.

2006-01-01

408

Multipartite purification protocols: Upper and optimal bounds  

International Nuclear Information System (INIS)

A method for producing an upper bound for all multipartite purification protocols is devised, based on knowing the optimal protocol for purifying bipartite states. When applied to a range of noise models, both local and correlated, the optimality of certain protocols can be demonstrated for a variety of graph and valence bond states

409

Neonatal euthanasia: The Groningen Protocol.  

Science.gov (United States)

For the past thirty years, voluntary euthanasia and physician-assisted suicide of adult patients have been common practice in the Netherlands. Neonatal euthanasia was recently legalized in the Netherlands and the Groningen Protocol (GP) was developed to regulate the practice. Supporters claim compliance with the GP criteria makes neonatal euthanasia ethically permissible. An examination of the criteria used by the Protocol to justify the euthanasia of seriously ill neonates reveals the criteria are not based on firm moral principles. The taking of the life of a seriously ill person is not the solution to the pain and suffering of the dying process. It is the role of the medical professional to care for the ailing patient with love and compassion, always preserving the person's dignity. Neonatal euthanasia is not ethically permissible. PMID:25473136

Vizcarrondo, Felipe E

2014-11-01

410

Chapter 14: Chiller Evaluation Protocol  

Energy Technology Data Exchange (ETDEWEB)

This protocol defines a chiller measure as a project that directly impacts equipment within the boundary of a chiller plant. A chiller plant encompasses a chiller--or multiple chillers--and associated auxiliary equipment. This protocol primarily covers electric-driven chillers and chiller plants. It does not include thermal energy storage and absorption chillers fired by natural gas or steam, although a similar methodology may be applicable to these chilled water system components. Chillers provide mechanical cooling for commercial, institutional, multiunit residential, and industrial facilities. Cooling may be required for facility heating, ventilation, and air conditioning systems or for process cooling loads (e.g., data centers, manufacturing process cooling). The vapor compression cycle, or refrigeration cycle, cools water in the chilled water loop by absorbing heat and rejecting it to either a condensing water loop (water cooled chillers) or to the ambient air (air-cooled chillers).

Tiessen, A.

2014-09-01

411

Cost estimation of Kyoto Protocol  

International Nuclear Information System (INIS)

This article proposes a reflection on important aspects in the costs determination performance of Kyoto Protocol. The evaluation of the main models evidence possible impacts on the economies. A key role in the determination of the cost is represented by the relative hypothesis to emission trading and the projects CDM-JI and from the political capacity at the cost negative or equal to zero

412

A Bier block implementation protocol.  

Science.gov (United States)

The Bier block procedure has been in use for over 100 years, but only recently has received renewed attention. As emergency departments look for ways to maximize efficiency, the use of the Bier block has been recognized as effective and fast with minimal adverse effects. This article summarizes a proposed protocol for the implementation of both pre- and posthospitalization Bier blocks by healthcare providers. PMID:24706243

Stancil, Stewart A

2014-01-01

413

Power Control Protocols in VANET  

OpenAIRE

Vehicular Ad hoc Networks (VANET) is one of the most challenging research area in the field of the Mobile Ad hoc Network (MANET), Power control is a critical issue in VANETwhere is should be managed carefully to help the channel to have high performance. In this paper a comparative study in the published protocols in the field of safety message dynamic power control will be presented and evaluated.

Samara, Ghassan; Salem, Amer O. Abu; Alhmiedat, Tareq

2013-01-01

414

Petri Nets in Cryptographic Protocols  

DEFF Research Database (Denmark)

A process language for security protocols is presented together with a semantics in terms of sets of events. The denotation of process is a set of events, and as each event specifies a set of pre and postconditions, this denotation can be viewed as a Petri net. By means of an example we illustrate how the Petri-net semantics can be used to prove security properties.

Crazzolara, Federico; Winskel, Glynn

2001-01-01

415

Dynamic Computation of Population Protocols  

OpenAIRE

Population protocols provide theoretical foundations for mobile tiny device networks in which global behavior emerges from a set of simple interactions between anonymous agents. The works in this area mostly focus on studying the computational power of the model. Results hold as long as a fair scheduler, which governs the interactions between nodes, ensures that all reachable system states may eventually happen. This paper studies for the first time the impact of the agents' mobility model on...

Bertier, Marin; Busnel, Yann; Kermarrec, Anne-marie

2010-01-01

416

Multiple protocol fluorometer and method  

Science.gov (United States)

A multiple protocol fluorometer measures photosynthetic parameters of phytoplankton and higher plants using actively stimulated fluorescence protocols. The measured parameters include spectrally-resolved functional and optical absorption cross sections of PSII, extent of energy transfer between reaction centers of PSII, F.sub.0 (minimal), F.sub.m (maximal) and F.sub.v (variable) components of PSII fluorescence, photochemical and non-photochemical quenching, size of the plastoquinone (PQ) pool, and the kinetics of electron transport between Q.sub.a and PQ pool and between PQ pool and PSI. The multiple protocol fluorometer, in one embodiment, is equipped with an excitation source having a controlled spectral output range between 420 nm and 555 nm and capable of generating flashlets having a duration of 0.125-32 .mu.s, an interval between 0.5 .mu.s and 2 seconds, and peak optical power of up to 2 W/cm.sup.2. The excitation source is also capable of generating, simultaneous with the flashlets, a controlled continuous, background illumination.

Kolber, Zbigniew S. (Shoreham, NY); Falkowski, Paul G. (Stony Brook, NY)

2000-09-19

417

Developing protocols for advanced and consultant practice  

International Nuclear Information System (INIS)

Radiographers engaged in advanced and consultant roles are advised to base their work within an agreed framework of practice, commonly known as a protocol. A protocol is an agreed and documented system which outlines how certain categories of patients are to be managed, and by whom. Whilst many variations in the terminology and layout of protocols may cause confusion, scrutiny of a range of protocols from different clinical centres suggests that they often adopt a similar approach to their content. This article explores the vital 'ingredients' that make up a protocol for advanced practice, highlighting a range of good practice to minimise the risks to both the radiographer and patient

418

Analysing ZigBee Key Establishment Protocols  

CERN Document Server

In this report, we present our approach for protocol analysis together with a real example where we find an important flow in a contemporary wireless sensor network security protocol. We start by modelling protocols using a specific process algebraic formalism called LySa process calculus. We then apply an analysis based on a special program analysis technique called control flow analysis. We apply this technique to the ZigBee-2007 End-to-End Application Key Establishment Protocol and with the help of the analysis discover an unknown flaw. Finally we suggest a fix for the protocol, and verify that the fix works by using the same technique.

Yüksel, Ender

2012-01-01

419

Bleomycin, methotrexate and vincristine before irradiation of stage III and IV laryngeal and pharyngeal squamous cell carcinoma. A study initiated by the Danish Society of Head and Neck Cancer  

DEFF Research Database (Denmark)

Primary treatment with bleomycin, methotrexate and vincristine for two weeks followed by curatively intended 60Co irradiation was administered to 153 patients consecutively referred to the three main treatment centres in Denmark over more than a two-year period. Seventy-one laryngeal and 82 pharyngeal squamous cell carcinomas were evaluated. According to the TNM classification (UICC) 76 patients had stage III and 77 patients stage IV disease. The immediate response (complete + partial) to chemotherapy was 20 per cent. Judging from frequency of local recurrence, metastases as well as survival the treatment results were not obviously improved. A high frequency of complications was observed after this combination of chemotherapy and irradiation, and it was often impossible to fulfil the irradiation to the planned dose in appropriate time.

Hansen, H S; Rygård, J

2013-01-01