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Article: Small ruminant lentiviruses in goats in southern Italy: Serological evidence, risk factors and implementation of control programs

Cirone, Francesco / Aristide Maggiolino / Margie Cirilli / Alessio Sposato / Pasquale De Palo / Giacinto Ciappetta / Annamaria Pratelli

Veterinary microbiology. 2019 Jan., v. 228

2019

Abstract: Small ruminant lentiviruses (SRLVs) can drastically affect milk production in goat flocks and only an early detection can control and prevent their spread. Since SRLVs are responsible for persistent infections, antibody screening is the most valuable ... ...

Abstract	Small ruminant lentiviruses (SRLVs) can drastically affect milk production in goat flocks and only an early detection can control and prevent their spread. Since SRLVs are responsible for persistent infections, antibody screening is the most valuable tool to identify infected animals. ELISA is recommended as the election test both for its sensitivity and for its ability to detect low antibody titers, thus identifying infected animals earlier than agar gel immunodiffusion (AGID). In the present study, an investigation was conducted to assess the SRLV seroprevalence in goat flocks in southern Italy and a transversal comparative study was carried out through the analysis of the possible risk factors influencing SRLV spread. A total of 4800 sera from 1060 flocks were analyzed and overall seroprevalences of 18,64% and 51,69% at animal and herd levels, respectively, were observed. Both the region and the herd production systems were able to affect seroprevalence, differently from the herd size, probably because the mean number of goats per herd is low and the semi-intensive management is similar regardless of the dimensional class of each herd. In particular, meat producing herds showed the higher seroprevalence, as a result of the poor sanitation and low animal monitoring in comparison to milk producing herds, where animals are managed twice daily and the relationship between dams and kids is checked to guarantee an adequate quantitative/qualitative milk yield. In the absence of vaccines or effective treatments, health preventive management and seroepidemiological investigations are the only successful approach to restrict SRLV spread as observed in countries were official/voluntary control programs are carried out.
Keywords	Lentivirus ; agar ; antibodies ; antibody detection ; chronic diseases ; enzyme-linked immunosorbent assay ; flocks ; gels ; goats ; herd productivity ; herd size ; meat ; milk ; milk yield ; monitoring ; production technology ; risk factors ; sanitation ; screening ; seroprevalence ; vaccines ; Italy
Language	English
Dates of publication	2019-01
Size	p. 143-146.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	753154-0
ISSN	1873-2542 ; 0378-1135
ISSN (online)	1873-2542
ISSN	0378-1135
DOI	10.1016/j.vetmic.2018.11.023
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Subcutaneous versus transvenous implantable cardioverter defibrillators in children and young adults: A meta-analysis.

Vetta, Giampaolo / Parlavecchio, Antonio / Magnocavallo, Michele / Valente, Debora / Caminiti, Rodolfo / Polselli, Marco / Vetta, Francesco / Cirone, Donatello / Cauti, Filippo Maria / Crea, Pasquale / Rossi, Pietro / Chierchia, Gian Battista / Bianchi, Stefano / de Asmundis, Carlo / Natale, Andrea / Della Rocca, Domenico Giovanni

Pacing and clinical electrophysiology : PACE

2022 Volume 45, Issue 12, Page(s) 1409–1414

Abstract: Introduction: The implantable cardioverter defibrillator (ICD) has been demonstrated to successfully prevent sudden cardiac death (SCD) in children and young adults. A wide range of device-related complications/malfunctions have been described, which ... ...

Abstract	Introduction: The implantable cardioverter defibrillator (ICD) has been demonstrated to successfully prevent sudden cardiac death (SCD) in children and young adults. A wide range of device-related complications/malfunctions have been described, which depend on the intrinsic design of the defibrillation system (transvenous-implantable cardioverter defibrillator [TV-ICD] vs. subcutaneous-implantable cardioverter defibrillator [S-ICD]). Objective: To compare the device-related complications and inappropriate shocks with TV-ICD versus S-ICD. Methods and results: Electronic databases were queried for studies focusing on the prevention of SCD in children and young adults with TV-ICD or S-ICD. The effect size was estimated using a random-effect model as odds ratio (OR) and relative 95% confidence interval (CI). The primary endpoint was a composite of any device-related complications and inappropriate shocks. We identified a total of five studies including 236 patients (Group S-ICD: 76 patients; Group TV-ICD: 160 patients) with a mean follow-up time of 54.2 ± 24.9 months. S-ICD implantation contributed to a significant reduction in the risk of the primary endpoint of any device-related complications and inappropriate shocks (OR: 0.18; 95% CI: 0.05-0.73; p = .02). S-ICD was also associated with a significantly lower incidence of inappropriate shocks (OR: 0.28; 95% CI: 0.11-0.74; p = .01) and lead-related complications (OR: 0.18; 95% CI: 0.05-0.66; p = .01). A trend toward a higher risk of pocket complications (OR: 5.91; 95% CI: 0.98-35.63; p = .05) was recorded in patients with S-ICD. Conclusion: Children and young adults undergoing S-ICD implantation may have a lower risk of a composite of device-related complications and inappropriate shocks, compared to TV-ICD patients.
MeSH term(s)	Child ; Humans ; Social Group
Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Meta-Analysis ; Journal Article
ZDB-ID	424437-0
ISSN	1540-8159 ; 0147-8389
ISSN (online)	1540-8159
ISSN	0147-8389
DOI	10.1111/pace.14603
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Article ; Online: Small ruminant lentiviruses in goats in southern Italy: Serological evidence, risk factors and implementation of control programs.

Cirone, Francesco / Maggiolino, Aristide / Cirilli, Margie / Sposato, Alessio / De Palo, Pasquale / Ciappetta, Giacinto / Pratelli, Annamaria

Veterinary microbiology

2018 Volume 228, Page(s) 143–146

Abstract	Small ruminant lentiviruses (SRLVs) can drastically affect milk production in goat flocks and only an early detection can control and prevent their spread. Since SRLVs are responsible for persistent infections, antibody screening is the most valuable tool to identify infected animals. ELISA is recommended as the election test both for its sensitivity and for its ability to detect low antibody titers, thus identifying infected animals earlier than agar gel immunodiffusion (AGID). In the present study, an investigation was conducted to assess the SRLV seroprevalence in goat flocks in southern Italy and a transversal comparative study was carried out through the analysis of the possible risk factors influencing SRLV spread. A total of 4800 sera from 1060 flocks were analyzed and overall seroprevalences of 18,64% and 51,69% at animal and herd levels, respectively, were observed. Both the region and the herd production systems were able to affect seroprevalence, differently from the herd size, probably because the mean number of goats per herd is low and the semi-intensive management is similar regardless of the dimensional class of each herd. In particular, meat producing herds showed the higher seroprevalence, as a result of the poor sanitation and low animal monitoring in comparison to milk producing herds, where animals are managed twice daily and the relationship between dams and kids is checked to guarantee an adequate quantitative/qualitative milk yield. In the absence of vaccines or effective treatments, health preventive management and seroepidemiological investigations are the only successful approach to restrict SRLV spread as observed in countries were official/voluntary control programs are carried out.
MeSH term(s)	Animals ; Enzyme-Linked Immunosorbent Assay/veterinary ; Female ; Goat Diseases/epidemiology ; Goat Diseases/prevention & control ; Goat Diseases/virology ; Goats/virology ; Italy/epidemiology ; Lentivirus/immunology ; Lentivirus Infections/epidemiology ; Lentivirus Infections/prevention & control ; Lentivirus Infections/veterinary ; Lentivirus Infections/virology ; Milk/metabolism ; Risk Factors ; Ruminants ; Seroepidemiologic Studies
Language	English
Publishing date	2018-11-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	753154-0
ISSN	1873-2542 ; 0378-1135
ISSN (online)	1873-2542
ISSN	0378-1135
DOI	10.1016/j.vetmic.2018.11.023
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Article ; Online: Patient-derived xenografts reveal limits to PI3K/mTOR- and MEK-mediated inhibition of bladder cancer.

Cirone, Pasquale / Andresen, Catharine J / Eswaraka, Jeetendra R / Lappin, Patrick B / Bagi, Cedo M

Cancer chemotherapy and pharmacology

2014 Volume 73, Issue 3, Page(s) 525–538

Abstract: Background: Metastatic bladder cancer is a serious condition with a 5-year survival rate of approximately 14 %, a rate that has remained unchanged for almost three decades. Thus, there is a profound need to identify the driving mutations for these ... ...

Abstract	Background: Metastatic bladder cancer is a serious condition with a 5-year survival rate of approximately 14 %, a rate that has remained unchanged for almost three decades. Thus, there is a profound need to identify the driving mutations for these aggressive tumors to better determine appropriate treatments. Mutational analyses of clinical samples suggest that mutations in either the phosphoinositide-3 kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) or RAS/MEK/ERK pathways drive bladder cancer progression, although it remains to be tested whether the inhibition of either (or both) of these pathways can arrest PI3K/mTOR- or Ras-driven proliferation. Methods: Herein, we used several bladder cancer cell lines to determine drug sensitivity according to genetic background and also studied mouse models of engrafted UM-UC-3 cells and patient-derived xenografts (PDXs) to test PI3K/mTOR and MEK inhibition in vivo. Results: Inhibition of these pathways utilizing PF-04691502, a PI3K and mTOR inhibitor, and PD-0325901, a MEK inhibitor, slowed the tumor growth of PDX models of bladder cancer. The growth inhibitory effect of combination therapy was similar to that of the clinical maximum dose of cisplatin; mechanistically, this appeared to predominantly occur via drug-induced cytostatic growth inhibition as well as diminished vascular endothelial growth factor secretion in the tumor models. Kinase arrays of tumors harvested after treatment demonstrated activated p53 and Axl as well as STAT1 and STAT3. Conclusion: Taken together, these results indicate that clinically relevant doses of PF-04691502 and PD-0325901 can suppress bladder tumor growth in PDX models, thus offering additional potential treatment options by a precision medicine approach.
MeSH term(s)	Aged, 80 and over ; Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Benzamides/administration & dosage ; Benzamides/pharmacology ; Diphenylamine/administration & dosage ; Diphenylamine/analogs & derivatives ; Diphenylamine/pharmacology ; Disease Models, Animal ; Female ; Humans ; MAP Kinase Kinase Kinases/antagonists & inhibitors ; MAP Kinase Kinase Kinases/genetics ; MAP Kinase Kinase Kinases/metabolism ; MAP Kinase Signaling System/drug effects ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/pharmacology ; Pyridones/administration & dosage ; Pyridones/pharmacology ; Pyrimidines/administration & dosage ; Pyrimidines/pharmacology ; Random Allocation ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Urinary Bladder Neoplasms/drug therapy ; Urinary Bladder Neoplasms/enzymology ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/pathology ; Xenograft Model Antitumor Assays/methods
Chemical Substances	2-amino-8-(4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido(2,3-d)pyrimidin-7(8H)-one ; Benzamides ; Phosphoinositide-3 Kinase Inhibitors ; Protein Kinase Inhibitors ; Pyridones ; Pyrimidines ; mirdametinib (86K0J5AK6M) ; Diphenylamine (9N3CBB0BIQ) ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; MAP Kinase Kinase Kinases (EC 2.7.11.25)
Language	English
Publishing date	2014-01-19
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	6820-2
ISSN	1432-0843 ; 0344-5704 ; 0943-9404
ISSN (online)	1432-0843
ISSN	0344-5704 ; 0943-9404
DOI	10.1007/s00280-014-2376-1
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Article: Immuno-isolation in cancer gene therapy.

Cirone, Pasquale / Potter, Murray / Hirte, Hal / Chang, Patricia

Current gene therapy

2006 Volume 6, Issue 2, Page(s) 181–191

Abstract: The implantation of genetically-modified non-autologous cells in immuno-protected microcapsules is an alternative to ex vivo gene therapy. Such cells delivering a recombinant therapeutic product are isolated from the host's immune system by being ... ...

Abstract	The implantation of genetically-modified non-autologous cells in immuno-protected microcapsules is an alternative to ex vivo gene therapy. Such cells delivering a recombinant therapeutic product are isolated from the host's immune system by being encapsulated within permselective microcapsules. This approach has been successful in pre-clinical animal studies involving delivery of hormone or enzymes to treat dwarfism, lysosomal storage disease, or hemophilia B. Recently, this platform technology has shown promise in the treatment for more complex diseases such as cancer. One of the earliest strategy was to augment the chemotherapeutic effect of a prodrug by implanting encapsulated cells that can metabolise prodrugs into cytotoxic products in close proximity to the cancer cells. More recent approaches include enhancing tumor cell death through immunotherapy, or suppressing tumor cell proliferation through anti-angiogenesis. These can be achieved by delivering single molecules of cytokines or angiostatin, respectively, by implanting microencapsulated cells engineered to secrete these recombinant products. Recent refinements of these approaches include genetic fusion of cytokines or angiostatin to additional functional groups with tumor targeting or tumor cell killing properties, thus enhancing the potency of the recombinant products. Furthermore, a COMBO strategy of implanting microencapsulated cells to deliver multiple products targeted to diverse pathways in tumor suppression also showed much promise. This review will summarise the application of microencapsulation of genetically-modified cells to cancer treatment in animal models, the efficacy of such approaches, and how these studies have led to better understanding of the biology of cancer treatment. The flexibility of this modular system involving molecular engineering, cellular genetic modification, and polymer chemistry provides potentially a huge range of application modalities, and a tremendous multi-disciplinary challenge for the future.
MeSH term(s)	Animals ; Capsules ; Disease Models, Animal ; Drug Delivery Systems ; Genetic Therapy/methods ; Humans ; Immunotherapy/methods ; Models, Biological ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/therapy
Chemical Substances	Capsules
Language	English
Publishing date	2006-03-28
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2146187-9
ISSN	1566-5232
ISSN	1566-5232
DOI	10.2174/156652306776359513
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Zs.A 5883: Show issues

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Article: A multiprong approach to cancer gene therapy by coencapsulated cells.

Cirone, Pasquale / Shen, Feng / Chang, Patricia L

Cancer gene therapy

2005 Volume 12, Issue 4, Page(s) 369–380

Abstract: Immune-isolation of nonautologous cells with microencapsulation protects these cells from graft rejection, thus allowing the same recombinant therapeutic cell line to be implanted in different recipients. This approach was successful in treating HER2/neu- ...

Abstract	Immune-isolation of nonautologous cells with microencapsulation protects these cells from graft rejection, thus allowing the same recombinant therapeutic cell line to be implanted in different recipients. This approach was successful in treating HER2/neu-expressing tumors in mice by delivering an interleukin-2 fusion protein (sFvIL-2), or angiostatin. However, treatment with interleukin-2 led to profuse inflammation, while angiostatin delivery did not result in long-term tumor suppression, in part due to endothelial cell-independent neovascularization (vascular mimicry). We hypothesize that coencapsulating the two producer cells in the same microcapsules may enhance the efficacy and ameliorate the above side effects. Hence, B16-F0/neu tumor-bearing mice were implanted with sFvIL-2- and angiostatin-secreting cells coencapsulated in the same alginate-poly-L-lysine-alginate microcapsules. However, this protocol only produced an incremental but not synergistic improvement, as measured with greater tumor suppression and improved survival. Compared to the single sFvIL-2 treatment, the coencapsulation protocol showed improved efficacy associated with: mobilization of sFvIL-2 from the spleen; a higher level of cytokine delivery systemically and to the tumors; increased tumor and tumor-associated endothelial cell apoptosis; and a reduced host inflammatory response. However, compared to the single angiostatin treatment, the efficacy was reduced, primarily due to a "bystander" effect in which the angiostatin-secreting cells suffered similar transgene silencing as the coencapsulated cytokine-secreting cells. Nevertheless, the level of "vascular mimicry" of the single angiostatin treatment was significantly reduced. Hence, while there was no synergy in efficacy, an incremental improvement and some reduction in undesirable side effects of inflammation and vascular mimicry were achieved over the single treatments.
MeSH term(s)	Alginates/chemistry ; Angiostatins/genetics ; Angiostatins/metabolism ; Animals ; Cell Line ; Cell Line, Tumor ; Cell Survival ; Cells, Cultured ; Cytokines/metabolism ; Endothelium, Vascular/cytology ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Transfer Techniques ; Genetic Therapy/methods ; Humans ; Immunohistochemistry ; Inflammation ; Interleukin-2/genetics ; Lymph Nodes/metabolism ; Melanoma, Experimental/therapy ; Mice ; Mice, Inbred C57BL ; Necrosis ; Neoplasms/therapy ; Neoplasms, Experimental/therapy ; Neovascularization, Pathologic ; Polylysine/genetics ; Recombinant Fusion Proteins/metabolism ; Spleen/metabolism ; Time Factors ; Transgenes ; Umbilical Veins/cytology ; von Willebrand Factor/metabolism
Chemical Substances	Alginates ; Cytokines ; Interleukin-2 ; Recombinant Fusion Proteins ; von Willebrand Factor ; Polylysine (25104-18-1) ; Angiostatins (86090-08-6)
Language	English
Publishing date	2005-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1212513-1
ISSN	0929-1903
ISSN	0929-1903
DOI	10.1038/sj.cgt.7700786
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Zs.A 4125: Show issues

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Article ; Online: Activation of the planar cell polarity formin DAAM1 leads to inhibition of endothelial cell proliferation, migration, and angiogenesis.

Ju, Rong / Cirone, Pasquale / Lin, Shengda / Griesbach, Hilary / Slusarski, Diane C / Crews, Craig M

Proceedings of the National Academy of Sciences of the United States of America

2010 Volume 107, Issue 15, Page(s) 6906–6911

Abstract: The Wnt/planar cell polarity (PCP) pathway regulates directed cell movement during development and was recently found to play a critical role in endothelial cell proliferation and angiogenesis [Zhang Y, et al. (2006) Chem Biol 13:1001-1009; Masckauchan ... ...

Abstract	The Wnt/planar cell polarity (PCP) pathway regulates directed cell movement during development and was recently found to play a critical role in endothelial cell proliferation and angiogenesis [Zhang Y, et al. (2006) Chem Biol 13:1001-1009; Masckauchan TN, et al. (2006) Mol Biol Cell 17:5163-5172]. However, the mechanisms by which PCP signaling components regulate angiogenesis remain unknown. We report that expression of a constitutively active C-terminal domain of Dishevelled-associated activator of morphogenesis 1 (DAAM1) selectively inhibited endothelial cell proliferation. Moreover, this activated construct suppressed endothelial cell migration and the ability to form coordinated networks in vivo and in vitro. Although constitutively active DAAM1 (CDAAM1) induced both actin polymerization and microtubule (MT) stabilization, the stabilization of MTs alone was sufficient to inhibit endothelial cell growth selectively. Inhibition of actin polymerization alone by jasplakinolide treatment failed to reproduce the inhibitory effects of CDAAM1. These results indicate that DAAM1 regulates endothelial cell growth through MT stabilization in a cell type-selective manner and suggest that PCP signaling plays a pivotal role in angiogenesis by regulating MT stabilization.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Cell Line ; Cell Movement ; Cell Polarity/genetics ; Cell Proliferation ; Dogs ; Gene Expression Regulation ; Green Fluorescent Proteins/metabolism ; Humans ; Microfilament Proteins ; Models, Biological ; Neovascularization, Pathologic ; Signal Transduction ; Zebrafish ; rho GTP-Binding Proteins
Chemical Substances	Adaptor Proteins, Signal Transducing ; DAAM1 protein, human ; Microfilament Proteins ; Green Fluorescent Proteins (147336-22-9) ; rho GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2010-03-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1001075107
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Article: Antiangiogenic cancer therapy with microencapsulated cells.

Cirone, Pasquale / Bourgeois, Jacqueline M / Chang, Patricia L

Human gene therapy

2003 Volume 14, Issue 11, Page(s) 1065–1077

Abstract: Inhibition of angiogenesis has led to tumor suppression in several cancer models. Although administering purified recombinant antiangiogenic product is effective, alternative approaches through genetic manipulation may be more cost-effective. We propose ... ...

Abstract	Inhibition of angiogenesis has led to tumor suppression in several cancer models. Although administering purified recombinant antiangiogenic product is effective, alternative approaches through genetic manipulation may be more cost-effective. We propose to implant nonautologous recombinant cells secreting angiostatin for systemic delivery of angiostatin in cancer treatment. These cells are protected from graft rejection in alginate microcapsules to function as "micro-organs" to deliver angiostatin in vivo. This approach was tested by implanting encapsulated mouse myoblast C2C12 cells genetically modified to secrete angiostatin into mice bearing solid tumor. Angiostatin was detected in sera of the treated mice. Efficacy was demonstrated by suppression of palpable tumor growth and improved survival. At autopsy, angiostatin localized to residual tumors and high levels of angiostatic activity were detected in tumor extracts. Tumor tissues showed increased apoptosis and necrosis compared with those from untreated or mock-treated mice. Immunohistochemical staining against von Willebrand factor, an endothelial cell marker, showed that within tumors from the treated mice, the neovasculature was poorly defined by endothelial cells, many of which were undergoing apoptosis. However, the tumors eventually developed neovasculature independent of endothelial cells. Such vascular mimicry would account for the lack of long-term efficacy despite persistent angiostatin delivery. In conclusion, implantation with nonautologous microencapsulated cells is feasible for systemic delivery of angiostatin, resulting in localization of angiostatin to tumors and targeted apoptosis of the endothelial cells. Clinical efficacy was demonstrated by suppression of tumor growth and extension of life span. Although the potential of this cell-based approach for angiostatin-mediated cancer therapy is confirmed, long-term efficacy must take into account the possible escape by some tumors from angiogenesis inhibition.
MeSH term(s)	Alginates/chemistry ; Angiogenesis Inhibitors ; Angiostatins ; Animals ; Apoptosis ; Cell Line ; Cell Transplantation/methods ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Female ; Genetic Engineering ; Graft Rejection/prevention & control ; Immunohistochemistry ; Injections, Intraperitoneal ; Mice ; Mice, Inbred C57BL ; Myoblasts/metabolism ; Myoblasts/transplantation ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Neoplasms, Experimental/therapy ; Peptide Fragments/genetics ; Plasminogen/genetics ; Polylysine/analogs & derivatives ; Polylysine/chemistry ; Tumor Cells, Cultured ; von Willebrand Factor/analysis ; von Willebrand Factor/immunology
Chemical Substances	Alginates ; Angiogenesis Inhibitors ; Peptide Fragments ; alginate-polylysine-alginate ; von Willebrand Factor ; Polylysine (25104-18-1) ; Angiostatins (86090-08-6) ; Plasminogen (9001-91-6)
Language	English
Publishing date	2003-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/104303403322124783
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Zs.A 2988: Show issues

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Article ; Online: A role for planar cell polarity signaling in angiogenesis.

Cirone, Pasquale / Lin, Shengda / Griesbach, Hilary L / Zhang, Yi / Slusarski, Diane C / Crews, Craig M

Angiogenesis

2008 Volume 11, Issue 4, Page(s) 347–360

Abstract: The planar cell polarity (PCP) pathway is a highly conserved signaling cascade that coordinates both epithelial and axonal morphogenic movements during development. Angiogenesis also involves the growth and migration of polarized cells, although the ... ...

Abstract	The planar cell polarity (PCP) pathway is a highly conserved signaling cascade that coordinates both epithelial and axonal morphogenic movements during development. Angiogenesis also involves the growth and migration of polarized cells, although the mechanisms underlying their intercellular communication are poorly understood. Here, using cell culture assays, we demonstrate that inhibition of PCP signaling disrupts endothelial cell growth, polarity, and migration, all of which can be rescued through downstream activation of this pathway by expression of either Daam-1, Diversin or Inversin. Silencing of either Dvl2 or Prickle suppressed endothelial cell proliferation. Moreover, loss of p53 rescues endothelial cell growth arrest but not the migration inhibition caused by PCP disruption. In addition, we show that the zebrafish Wnt5 mutant (pipetail (ppt)), which has impaired PCP signaling, displays vascular developmental defects. These findings reveal a potential role for PCP signaling in the coordinated assembly of endothelial cells into vascular structures and have important implications for vascular remodeling in development and disease.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Animals ; Blood Vessels/abnormalities ; Blood Vessels/drug effects ; Caveolin 1/metabolism ; Cell Line ; Cell Movement/drug effects ; Cell Polarity/drug effects ; Cell Proliferation/drug effects ; Cyclohexanes/pharmacology ; Dishevelled Proteins ; Endothelial Cells/cytology ; Endothelial Cells/drug effects ; Humans ; Mice ; Models, Animal ; Mutation/genetics ; Neovascularization, Physiologic/drug effects ; O-(Chloroacetylcarbamoyl)fumagillol ; Phosphoproteins/genetics ; Sesquiterpenes/pharmacology ; Signal Transduction/drug effects ; Tumor Suppressor Protein p53/metabolism ; Wnt Proteins/metabolism ; Zebrafish ; beta Catenin/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Caveolin 1 ; Cyclohexanes ; DVL2 protein, human ; Dishevelled Proteins ; Dvl2 protein, mouse ; Phosphoproteins ; Sesquiterpenes ; Tumor Suppressor Protein p53 ; Wnt Proteins ; beta Catenin ; O-(Chloroacetylcarbamoyl)fumagillol (X47GR46481)
Language	English
Publishing date	2008-09-17
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1484717-6
ISSN	1573-7209 ; 0969-6970
ISSN (online)	1573-7209
ISSN	0969-6970
DOI	10.1007/s10456-008-9116-2
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Article: Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells.

Cirone, Pasquale / Bourgeois, Jacqueline M / Shen, Feng / Chang, Patricia L

Human gene therapy

2004 Volume 15, Issue 10, Page(s) 945–959

Abstract: An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft ...

Abstract	An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to pass by diffusion. This strategy was applied to the treatment of cancer with some success by delivering either interleukin 2 or angiostatin. However, as cancer is a complex, multifactorial disease, a multipronged approach is now being developed to attack tumorigenesis via multiple pathways in order to improve treatment efficacy. A combination of immunotherapy with angiostatic therapy was investigated by treating B16-F0/neu melanoma-bearing mice with intraperitoneally implanted, microencapsulated mouse myoblasts (C2C12) genetically modified to deliver angiostatin and an interleukin 2 fusion protein (sFvIL-2). The combination treatment resulted in improved survival, delayed tumor growth, and increased histological indices of antitumor activity (apoptosis and necrosis). In addition to improved efficacy, the combination treatment also ameliorated some of the undesirable side effects from the individual treatments that have led to the previous failure of the single treatments, for example, inflammatory response to IL-2 or vascular mimicry due to angiostatin. In conclusion, the combination of immuno- and antiangiogenic therapies delivered by immunoisolated cells was superior to individual treatments for antitumorigenesis activity, not only because of their known mechanisms of action but also because of unexpected protection against the adverse side effects of the single treatments. Thus, the concept of a "cocktail" strategy, with microencapsulation delivering multiple antitumor recombinant molecules to improve efficacy, is validated.
MeSH term(s)	Angiogenesis Inhibitors/pharmacology ; Angiostatins/chemistry ; Angiostatins/genetics ; Angiostatins/metabolism ; Animals ; Apoptosis ; Cell Line ; Cell Survival ; Cytokines/metabolism ; Drug Compounding ; Endothelium, Vascular/cytology ; Enzyme-Linked Immunosorbent Assay ; Genetic Therapy/methods ; Immunohistochemistry ; Immunotherapy/methods ; Interleukin-2/genetics ; Interleukin-2/metabolism ; Lymphocyte Activation ; Melanoma, Experimental/therapy ; Mice ; Mice, Inbred C57BL ; Necrosis ; Neoplasms/genetics ; Neoplasms/therapy ; Recombinant Proteins/chemistry ; Spleen/metabolism ; T-Lymphocytes/metabolism ; T-Lymphocytes, Cytotoxic/metabolism ; Time Factors ; Transgenes ; von Willebrand Factor/metabolism
Chemical Substances	Angiogenesis Inhibitors ; Cytokines ; Interleukin-2 ; Recombinant Proteins ; von Willebrand Factor ; Angiostatins (86090-08-6)
Language	English
Publishing date	2004-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/hum.2004.15.945
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