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1. Robustness of the $0 -\pi $ transition against compositional and structural ageing in S/F/S heterostructures

Author

Loria, R., Meneghini, C., Torokhtii, K., Tortora, L., Pompeo, N., Cirillo, C., Attanasio, C., and Silva, E.

Subjects
Condensed Matter - Superconductivity
Abstract

We have studied the temperature induced $0 -\pi $ thermodynamic transition in Nb/PdNi/Nb Superconductor/Ferromagnetic/Superconductor (SFS) heterostructures by microwave measurements of the superfluid density. We have observed a shift in the transition temperature with the ageing of the heterostructures, suggesting that structural and/or chemical changes took place. Motivated by the electrodynamics findings, we have extensively studied the local structural properties of the samples by means of X-ray Absorption Spectroscopy (XAS) technique, and the compositional profile by Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). We found that the samples have indeed changed their properties, in particular for what concerns the interfaces and the composition of the ferromagnetic alloy layer. The structural and compositional data are consistent with the shift of the $0-\pi$ transition toward the behaviour of heterostructures with different F layers. An important emerging indication to the physics of SFS is the weak relevance of the ideality of the interfaces: even in aged samples, with less-than-ideal interfaces, the temperature-induced $0-\pi$ transition is still detectable albeit at a different critical F thickness., Comment: 11 pages, 9 figures, accepted for publication on Phys. Rev. B, http://journals.aps.org/prb/

Published
2015
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2. Superconducting and structural properties of Nb/PdNi/Nb trilayers

Author

Pompeo, N., Torokhtii, K., Meneghini, C., Mobilio, S., Loria, R., Cirillo, C., Ilyina, E. A., Attanasio, C., Sarti, S., and Silva, E.

Subjects
Condensed Matter - Superconductivity, Condensed Matter - Materials Science
Abstract

The superconducting and structural properties of S/F/S (Superconductor/Ferromagnet/Superconductor) heterostructures have been studied by means of microwave measurements (1-20 GHz) and x-ray absorption fine structure (XAFS) spectroscopy. Nb/PdNi/Nb trilayers have been studied as a function of F layer thicness. With respect to pure Nb, XAFS analysis shows that the heterostructures exhibit larger structural disorder in the S layers. Microwave measurements show evidence for a progressively weaker vortex pinning with increasing F thickness. However, no clear correlation is found with the local disorder in Nb: the weakest pinning is not in the most disordered trilayer. Therefore the structural disorder in the superconducting material cannot explain on its own the changes in vortex pinning. We argue that the F layer acts on the superconducting state itself. We propose possible explanations for the observed behavior., Comment: Submitted to J. Supercond. and Novel Magnetism

Published
2012

4. Experimental and cross-cultural evidence that parenthood and parental care motives increase social conservatism.

Author

Kerry, N, Al-Shawaf, L, Barbato, M, Batres, C, Blake, KR, Cha, Y, Chauvin, GV, Clifton, JDW, Fernandez, AM, Galbarczyk, A, Ghossainy, ME, Jang, D, Jasienska, G, Karasawa, M, Laustsen, L, Loria, R, Luberti, F, Moran, J, Pavlović, Z, Petersen, MB, Smith, AR, Žeželj, I, Murray, DR, Kerry, N, Al-Shawaf, L, Barbato, M, Batres, C, Blake, KR, Cha, Y, Chauvin, GV, Clifton, JDW, Fernandez, AM, Galbarczyk, A, Ghossainy, ME, Jang, D, Jasienska, G, Karasawa, M, Laustsen, L, Loria, R, Luberti, F, Moran, J, Pavlović, Z, Petersen, MB, Smith, AR, Žeželj, I, and Murray, DR

Abstract

Differences in attitudes on social issues such as abortion, immigration and sex are hugely divisive, and understanding their origins is among the most important tasks facing human behavioural sciences. Despite the clear psychological importance of parenthood and the motivation to provide care for children, researchers have only recently begun investigating their influence on social and political attitudes. Because socially conservative values ostensibly prioritize safety, stability and family values, we hypothesized that being more invested in parental care might make socially conservative policies more appealing. Studies 1 (preregistered; n = 376) and 2 (n = 1924) find novel evidence of conditional experimental effects of a parenthood prime, such that people who engaged strongly with a childcare manipulation showed an increase in social conservatism. Studies 3 (n = 2610, novel data from 10 countries) and 4 (n = 426 444, World Values Survey data) find evidence that both parenthood and parental care motivation are associated with increased social conservatism around the globe. Further, most of the positive association globally between age and social conservatism is accounted for by parenthood. These findings support the hypothesis that parenthood and parental care motivation increase social conservatism.

Published
2022

5. Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study

Author

Bon, G, Pizzuti, L, Laquintana, V, Loria, R, Porru, M, Marchio, C, Krasniqi, E, Barba, M, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Barchiesi, G, Mazzotta, M, Marinelli, D, Tomao, S, Marchetti, P, Valerio, M, Mirabelli, R, Russo, A, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Giotta, F, Garufi, C, Cazzaniga, M, Del Medico, P, Roselli, M, Sanguineti, G, Sperduti, I, Sapino, A, De Maria, R, Leonetti, C, Di Leo, A, Ciliberto, G, Falcioni, R, Vici, P, Bon G., Pizzuti L., Laquintana V., Loria R., Porru M., Marchio C., Krasniqi E., Barba M., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Barchiesi G., Mazzotta M., Marinelli D., Tomao S., Marchetti P., Valerio M. R., Mirabelli R., Russo A., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Giotta F., Garufi C., Cazzaniga M., Del Medico P., Roselli M., Sanguineti G., Sperduti I., Sapino A., De Maria R., Leonetti C., Di Leo A., Ciliberto G., Falcioni R., Vici P., Bon, G, Pizzuti, L, Laquintana, V, Loria, R, Porru, M, Marchio, C, Krasniqi, E, Barba, M, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Barchiesi, G, Mazzotta, M, Marinelli, D, Tomao, S, Marchetti, P, Valerio, M, Mirabelli, R, Russo, A, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Giotta, F, Garufi, C, Cazzaniga, M, Del Medico, P, Roselli, M, Sanguineti, G, Sperduti, I, Sapino, A, De Maria, R, Leonetti, C, Di Leo, A, Ciliberto, G, Falcioni, R, Vici, P, Bon G., Pizzuti L., Laquintana V., Loria R., Porru M., Marchio C., Krasniqi E., Barba M., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Barchiesi G., Mazzotta M., Marinelli D., Tomao S., Marchetti P., Valerio M. R., Mirabelli R., Russo A., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Giotta F., Garufi C., Cazzaniga M., Del Medico P., Roselli M., Sanguineti G., Sperduti I., Sapino A., De Maria R., Leonetti C., Di Leo A., Ciliberto G., Falcioni R., and Vici P.

Abstract

Background: HER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to different drugs sequences including pertuzumab and T-DM1 in HER2 positive cell lines. Methods: The biology of HER2 was investigated in vitro through sequential exposure of resistant HER2 + breast cancer cell lines to trastuzumab, pertuzumab, and their combination. In vitro experiments were paralleled by the analysis of data from 555 HER2 + ABC patients treated with T-DM1 and evaluation of T-DM1 efficacy in the 371 patients who received it in second line. Survival estimates were graphically displayed in Kaplan Meier curves, compared by log rank test and, when possibile, confirmed in multivariate models. Results: We herein show evidence of lower activity of T-DM1 in two HER2+ breast cancer cell lines resistant to trastuzumab+pertuzumab, as compared to trastuzumab-resistant cells. Lower T-DM1 efficacy was associated with a marked reduction of HER2 expression on the cell membrane and its nuclear translocation. HER2 downregulation at the membrane level was confirmed in biopsies of four trastuzumab/pertuzumab-pretreated patients. Among the 371 patients treated with second-line T-DM1, median overall survival (mOS) from diagnosis of advanced disease and median progression-free survival to second-line treatment (mPFS2) were 52 and 6 months in 177 patients who received trastuzumab/pertuzumab in f

Published
2020

8. Involvement of a cytochrome P450 monooxygenase in thaxtomin A biosynthesis by Streptomyces acidiscabies

Author

Healy, F.G., Krasnoff, S.B., Wach, M., Gibson, D.M., and Loria, R.

Subjects
Bacteria, Phytopathogenic -- Research, Cyclic compounds -- Physiological aspects, Cytochrome P-450 -- Physiological aspects, Microbiological synthesis -- Research, Biological sciences
Abstract

The P450 monooxygenase homolog, txtC, encodes a cytochrome P450-type monooxygenase that is involved in the postcyclization hydroxylation of the cyclic dipeptide, thaxtomin A. Results show that Escherichia coli produced TxtC possesses spectral properties similar to the spectra of cytochrome P-450-type hemoproteins.

Published
2002

9. Horizontal transfer of the plant virulence gene, nec1, and flanking sequences among genetically distinct Streptomyces strains in the Diastatochromogenes cluster

Author

Bukhalid, R. A., Takeuchi, T., Labeda, D., and Loria, R.

Subjects
Microbiological research -- Analysis, Plants -- Genetic aspects, Virulence (Microbiology) -- Genetic aspects, Streptomyces -- Genetic aspects, Pathogenic microorganisms -- Genetic aspects, Biological sciences
Abstract

Research has been conducted on the pathogenicity island which carries virulence gene nec1 and flanking sequences among Streptomyces strains in the Diastatochromogenes cluster. The horizontal transfer of this pathogenicity island has been investigated and the results indicate that plant-pathogenic Streptomyces strains are genetically distinct from those of S. scabiei.

Published
2002

11. Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study

Author

Bon, G., Pizzuti, L., Laquintana, V., Loria, R., Porru, M., Marchio, C., Krasniqi, E., Barba, M., Maugeri-Sacca, M., Gamucci, T., Berardi, R., Livi, L., Ficorella, C., Natoli, C., Cortesi, E., Generali, D., La Verde, N., Cassano, Alessandra, Bria, Emilio, Moscetti, L., Michelotti, A., Adamo, V., Zamagni, C., Tonini, G., Barchiesi, G., Mazzotta, M., Marinelli, D., Tomao, S., Marchetti, P., Valerio, M. R., Mirabelli, R., Russo, A., Fabbri, M. A., D'Ostilio, N., Veltri, E., Corsi, D., Garrone, O., Paris, I., Sarobba, G., Giotta, F., Garufi, C., Cazzaniga, M., Del Medico, P., Roselli, M., Sanguineti, G., Sperduti, I., Sapino, A., De Maria Marchiano, Ruggero, Leonetti, C., Di Leo, A., Ciliberto, G., Falcioni, R., Vici, P., Cassano A. (ORCID:0000-0002-3311-7163), Bria E. (ORCID:0000-0002-2333-704X), De Maria R. (ORCID:0000-0003-2255-0583), Bon, G., Pizzuti, L., Laquintana, V., Loria, R., Porru, M., Marchio, C., Krasniqi, E., Barba, M., Maugeri-Sacca, M., Gamucci, T., Berardi, R., Livi, L., Ficorella, C., Natoli, C., Cortesi, E., Generali, D., La Verde, N., Cassano, Alessandra, Bria, Emilio, Moscetti, L., Michelotti, A., Adamo, V., Zamagni, C., Tonini, G., Barchiesi, G., Mazzotta, M., Marinelli, D., Tomao, S., Marchetti, P., Valerio, M. R., Mirabelli, R., Russo, A., Fabbri, M. A., D'Ostilio, N., Veltri, E., Corsi, D., Garrone, O., Paris, I., Sarobba, G., Giotta, F., Garufi, C., Cazzaniga, M., Del Medico, P., Roselli, M., Sanguineti, G., Sperduti, I., Sapino, A., De Maria Marchiano, Ruggero, Leonetti, C., Di Leo, A., Ciliberto, G., Falcioni, R., Vici, P., Cassano A. (ORCID:0000-0002-3311-7163), Bria E. (ORCID:0000-0002-2333-704X), and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Background: HER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to different drugs sequences including pertuzumab and T-DM1 in HER2 positive cell lines. Methods: The biology of HER2 was investigated in vitro through sequential exposure of resistant HER2 + breast cancer cell lines to trastuzumab, pertuzumab, and their combination. In vitro experiments were paralleled by the analysis of data from 555 HER2 + ABC patients treated with T-DM1 and evaluation of T-DM1 efficacy in the 371 patients who received it in second line. Survival estimates were graphically displayed in Kaplan Meier curves, compared by log rank test and, when possibile, confirmed in multivariate models. Results: We herein show evidence of lower activity of T-DM1 in two HER2+ breast cancer cell lines resistant to trastuzumab+pertuzumab, as compared to trastuzumab-resistant cells. Lower T-DM1 efficacy was associated with a marked reduction of HER2 expression on the cell membrane and its nuclear translocation. HER2 downregulation at the membrane level was confirmed in biopsies of four trastuzumab/pertuzumab-pretreated patients. Among the 371 patients treated with second-line T-DM1, median overall survival (mOS) from diagnosis of advanced disease and median progression-free survival to second-line treatment (mPFS2) were 52 and 6 months in 177 patients who received trastuzumab/pertuzumab in f

Published
2020

17. H19-Dependent Transcriptional Regulation of beta 3 and beta 4 Integrins Upon Estrogen and Hypoxia Favors Metastatic Potential in Prostate Cancer

Author

Bacci, Lorenza, Aiello, A, Ripoli, Cristian, Loria, R, Pugliese, D, Pierconti, Francesco, Rotili, D, Strigari, L, Pinto, Francesco, Bassi, Pierfrancesco, Mai, A, Grassi, Claudio, Pontecorvi, Alfredo, Falcioni, R, Farsetti, A, Nanni, Simona, Bacci, L, Ripoli, C (ORCID:0000-0002-5315-0163), Pierconti, F (ORCID:0000-0003-0951-4131), Pinto, F, Bassi, PF (ORCID:0000-0002-4313-8427), Grassi, C (ORCID:0000-0001-7253-1685), Pontecorvi, A (ORCID:0000-0003-0570-6865), Nanni, S (ORCID:0000-0002-3320-1584), Bacci, Lorenza, Aiello, A, Ripoli, Cristian, Loria, R, Pugliese, D, Pierconti, Francesco, Rotili, D, Strigari, L, Pinto, Francesco, Bassi, Pierfrancesco, Mai, A, Grassi, Claudio, Pontecorvi, Alfredo, Falcioni, R, Farsetti, A, Nanni, Simona, Bacci, L, Ripoli, C (ORCID:0000-0002-5315-0163), Pierconti, F (ORCID:0000-0003-0951-4131), Pinto, F, Bassi, PF (ORCID:0000-0002-4313-8427), Grassi, C (ORCID:0000-0001-7253-1685), Pontecorvi, A (ORCID:0000-0003-0570-6865), and Nanni, S (ORCID:0000-0002-3320-1584)

Abstract

Estrogen and hypoxia promote an aggressive phenotype in prostate cancer (PCa), driving transcription of progression-associated genes. Here, we molecularly dissect the contribution of long non-coding RNA H19 to PCa metastatic potential under combined stimuli, a topic largely uncovered. The effects of estrogen and hypoxia on H19 and cell adhesion molecules' expression were investigated in PCa cells and PCa-derived organotypic slice cultures (OSCs) by qPCR and Western blot. The molecular mechanism was addressed by chromatin immunoprecipitations, overexpression, and silencing assays. PCa cells' metastatic potential was analyzed by in vitro cell-cell adhesion, motility test, and trans-well invasion assay. We found that combined treatment caused a significant H19 down-regulation as compared with hypoxia. In turn, H19 acts as a transcriptional repressor of cell adhesion molecules, as revealed by up-regulation of both beta 3 and beta 4 integrins and E-cadherin upon H19 silencing or combined treatment. Importantly, H19 down-regulation and beta integrins induction were also observed in treated OSCs. Combined treatment increased both cell motility and invasion of PCa cells. Lastly, reduction of beta integrins and invasion was achieved through epigenetic modulation of H19-dependent transcription. Our study revealed that estrogen and hypoxia transcriptionally regulate, via H19, cell adhesion molecules redirecting metastatic dissemination from EMT to a beta integrin-mediated invasion.

Published
2019

18. HMGA1 is a new biomarker of liposarcoma progression

Author

Loria, R., primary, Laquintana, V., additional, Bon, G., additional, Trisciuoglio, D., additional, Covello, R., additional, Amoreo, C.A., additional, Ferraresi, V., additional, Zoccali, C., additional, D'Incalci, M., additional, Biagini, R., additional, and Falcioni, R., additional

Published
2017
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21. Microwave properties of Nb/PdNi/Nb trilayers and Nb thin films

Author

Silva E., POMPEO, NICOLA, Loria R., Ilyina E. A., Cirillo C., Attanasio C., Sarti S., MENEGHINI, CARLO, TOROKHTII, KOSTIANTYN, Silva, E., Pompeo, Nicola, Torokhtii, Kostiantyn, Loria, R., Ilyina, E. A., Cirillo, C., Attanasio, C., Sarti, S., and Meneghini, Carlo

Published
2010

22. Robustness of the $0 -��$ transition against compositional and structural ageing in S/F/S heterostructures

Author

Loria, R., Meneghini, C., Torokhtii, K., Tortora, L., Pompeo, N., Cirillo, C., Attanasio, C., and Silva, E.

Subjects
Superconductivity (cond-mat.supr-con), FOS: Physical sciences
Abstract

We have studied the temperature induced $0 -��$ thermodynamic transition in Nb/PdNi/Nb Superconductor/Ferromagnetic/Superconductor (SFS) heterostructures by microwave measurements of the superfluid density. We have observed a shift in the transition temperature with the ageing of the heterostructures, suggesting that structural and/or chemical changes took place. Motivated by the electrodynamics findings, we have extensively studied the local structural properties of the samples by means of X-ray Absorption Spectroscopy (XAS) technique, and the compositional profile by Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). We found that the samples have indeed changed their properties, in particular for what concerns the interfaces and the composition of the ferromagnetic alloy layer. The structural and compositional data are consistent with the shift of the $0-��$ transition toward the behaviour of heterostructures with different F layers. An important emerging indication to the physics of SFS is the weak relevance of the ideality of the interfaces: even in aged samples, with less-than-ideal interfaces, the temperature-induced $0-��$ transition is still detectable albeit at a different critical F thickness., 11 pages, 9 figures, accepted for publication on Phys. Rev. B, http://journals.aps.org/prb/

Published
2015
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30. Cytochrome P450-catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis

Author

Barry, S.M., Kers, J.A., Johnson, E.G., Song, L., Aston, P.R., Patel, B., Krasnoff, S.B., Crane, B.R., Gibson, D.M., Loria, R., Challis, G.L., and Publica

Abstract

Thaxtomin phytotoxins produced by plant-pathogenic Streptomyces species contain a nitro group that is essential for phytotoxicity. The N,N-dimethyldiketopiperazine core of thaxtomins is assembled from L-phenylalanine and L-4-nitrotryptophan by a nonribosomal peptide synthetase, and nitric oxide synthase-generated NO is incorporated into the nitro group, but the biosynthesis of the nonproteinogenic amino acid L-4-nitrotryptophan is unclear. Here we report that TxtE, a unique cytochrome P450, catalyzes L-tryptophan nitration using NO and O 2.

Published
2012

41. The National Plant Diagnostic Network

Author

Stack, J., primary, Cardwell, K., additional, Hammerschmidt, R., additional, Byrne, J., additional, Loria, R., additional, Snover-Clift, K., additional, Baldwin, W., additional, Wisler, G., additional, Beck, H., additional, Bostock, R., additional, Thomas, C., additional, and Luke, E., additional

Published
2006
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49. Protective Effects of DHEA and AED against Viral, Bacterial and Parasitic Infections.

Author

Loria, R. M. and Ben-Nathan, D.

Subjects
*MICROORGANISMS, *IMMUNITY, *VETERINARY therapeutics, *DNA viruses, *CYCLOPENTAPHENANTHRENE
Abstract

The use of agents that can boost host immunity to combat infections may be of considerable benefit in the treatment of animals' infectious outbreaks and complement the available modes of various treatments. This report deals with the role of beta androstenes as agents that up-regulate host immune response to a level that enables the host to resist lethal infection by viruses, bacteria, and parasites. The agents reviewed consist of a specific subgroup of androstene steroids that increase the levels of the TH1 cytokines such as, IL-2, IL- 3, and IFNγ. Similarly to hydrocortisone, they suppress inflammation, but do not suppress immunity and function in the maintenance of the TH1/TH2 balance and immune homeostasis. We report that DHEA, and AED up-regulate immune resistance and protect the host from lethal infection by RNA and DNA viruses, Gram positive and Gram negative bacteria, parasitic infections, and stress mediated immune suppression. These agents provide a unique new avenue for the control, mitigation, and prevention of animal diseases by viral, bacterial and parasitic infections. Moreover, immune up-regulation may have a significant role in limiting antibiotic resistant and stress mediated infection. [ABSTRACT FROM AUTHOR]

Published
2011

50. Beta androstenediol mitigates the damage of 1 GeV/n Fe ion particle radiation to the hematopoietic system.

Author

Loria R, Beckman M, Contaifer D, Tamariz F, Gibb D, Thompson L, Guida P, Loria, Roger, Beckman, Mathew, Contaifer, Daniel, Tamariz, Francisco, Gibb, David, Thompson, Laura, and Guida, Peter

Abstract

Space exploration is associated with exposure to 1-3 Gy solar particle radiation and galactic cosmic radiation that could increase cancer rates. Effective nontoxic countermeasures to high linear energy transfer (LET) radiation exposure are highly desirable but currently not available. The aim was to determine whether a single subcutaneous injection of androstenediol (Δ(5) androsten-3β, 17β-diol [AED]) could mitigate and restore the mouse hematopoetic system from the radiation-mediated injury of 3 Gy whole-body high LET (56)Fe(26+) exposure. The findings show that postradiation AED treatment has an overall positive and significant beneficial effect to restore the levels of hematopoeitic elements (p<0.001). Androstenediol treatment significantly increased monocyte levels at days 4, 7, and 14 and, similarly, increased red blood cell, hemoglobin, and platelet counts. Flow cytometry analysis 14 days after radiation and AED treatment demonstrated an increase (p<0.05) in bone marrow cells counts. Ex vivo osteoclastogenesis studies show that AED treatment is necessary and advantageous for the development and restoration of osteoclastogenesis after radiation exposure. These findings clearly show that androstenediol functions as a countermeasure to remedy hematopoeitic injury mediated by high LET iron ion radiation. Presently, no other agent has been shown to have such properties. [ABSTRACT FROM AUTHOR]

Published
2011
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