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Article: Inhibition of

Mancini, Maria Vittoria / Damiani, Claudia / Short, Sarah M / Cappelli, Alessia / Ulissi, Ulisse / Capone, Aida / Serrao, Aurelio / Rossi, Paolo / Amici, Augusto / Kalogris, Cristina / Dimopoulos, George / Ricci, Irene / Favia, Guido

Pathogens (Basel, Switzerland)

2020 Volume 9, Issue 5

Abstract: Mosquitoes can transmit many infectious diseases, such as malaria, dengue, Zika, yellow fever, and lymphatic filariasis. Current mosquito control strategies are failing to reduce the severity of outbreaks that still cause high human morbidity and ... ...

Abstract	Mosquitoes can transmit many infectious diseases, such as malaria, dengue, Zika, yellow fever, and lymphatic filariasis. Current mosquito control strategies are failing to reduce the severity of outbreaks that still cause high human morbidity and mortality worldwide. Great expectations have been placed on genetic control methods. Among other methods, genetic modification of the bacteria colonizing different mosquito species and expressing anti-pathogen molecules may represent an innovative tool to combat mosquito-borne diseases. Nevertheless, this emerging approach, known as paratransgenesis, requires a detailed understanding of the mosquito microbiota and an accurate characterization of selected bacteria candidates. The acetic acid bacteria
Language	English
Publishing date	2020-05-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9050380
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Article ; Online: Inhibition of Asaia in Adult Mosquitoes Causes Male-Specific Mortality and Diverse Transcriptome Changes

Maria Vittoria Mancini / Claudia Damiani / Sarah M. Short / Alessia Cappelli / Ulisse Ulissi / Aida Capone / Aurelio Serrao / Paolo Rossi / Augusto Amici / Cristina Kalogris / George Dimopoulos / Irene Ricci / Guido Favia

Pathogens, Vol 9, Iss 380, p

2020 Volume 380

Abstract	Mosquitoes can transmit many infectious diseases, such as malaria, dengue, Zika, yellow fever, and lymphatic filariasis. Current mosquito control strategies are failing to reduce the severity of outbreaks that still cause high human morbidity and mortality worldwide. Great expectations have been placed on genetic control methods. Among other methods, genetic modification of the bacteria colonizing different mosquito species and expressing anti-pathogen molecules may represent an innovative tool to combat mosquito-borne diseases. Nevertheless, this emerging approach, known as paratransgenesis, requires a detailed understanding of the mosquito microbiota and an accurate characterization of selected bacteria candidates. The acetic acid bacteria Asaia is a promising candidate for paratransgenic approaches. We have previously reported that Asaia symbionts play a beneficial role in the normal development of Anopheles mosquito larvae, but no study has yet investigated the role(s) of Asaia in adult mosquito biology. Here we report evidence on how treatment with a highly specific anti- Asaia monoclonal antibody impacts the survival and physiology of adult Anopheles stephensi mosquitoes. Our findings offer useful insight on the role of Asaia in several physiological systems of adult mosquitoes, where the influence differs between males and females.
Keywords	Asaia ; Anopheles ; symbiont ; Medicine ; R
Subject code	590
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Dorsomorphin reverses the mesenchymal phenotype of breast cancer initiating cells by inhibition of bone morphogenetic protein signaling.

Garulli, Chiara / Kalogris, Cristina / Pietrella, Lucia / Bartolacci, Caterina / Andreani, Cristina / Falconi, Maurizio / Marchini, Cristina / Amici, Augusto

Cellular signalling

2013 Volume 26, Issue 2, Page(s) 352–362

Abstract: Increasing evidence supports the theory that tumor growth, homeostasis, and recurrence are dependent on a small subset of cells with stem cell properties, redefined cancer initiating cells (CICs) or cancer stem cells. Bone morphogenetic proteins (BMPs) ... ...

Abstract	Increasing evidence supports the theory that tumor growth, homeostasis, and recurrence are dependent on a small subset of cells with stem cell properties, redefined cancer initiating cells (CICs) or cancer stem cells. Bone morphogenetic proteins (BMPs) are involved in cell-fate specification during embryogenesis, in the maintenance of developmental potency in adult stem cells and may contribute to sustain CIC populations in breast carcinoma. Using the mouse A17 cell model previously related to mesenchymal cancer stem cells and displaying properties of CICs, we investigated the role of BMPs in the control of breast cancer cell plasticity. We showed that an autocrine activation of BMP signaling is crucial for the maintenance of mesenchymal stem cell phenotype and tumorigenic potential of A17 cells. Pharmacological inhibition of BMP signaling cascade by Dorsomorphin resulted in the acquisition of epithelial-like traits by A17 cells, including expression of Citokeratin-18 and E-cadherin, through downregulation of Snail and Slug transcriptional factors and Cyclooxygenase-2 (COX2) expression, and in the loss of their stem-features and self-renewal ability. This phenotypic switch compromised A17 cell motility, invasiveness and in vitro tumor growth. These results reveal that BMPs are key molecules at the crossroad between stemness and cancer.
MeSH term(s)	Animals ; Bone Morphogenetic Protein 4/pharmacology ; Bone Morphogenetic Protein Receptors, Type I/metabolism ; Bone Morphogenetic Protein Receptors, Type II/metabolism ; Bone Morphogenetic Proteins/metabolism ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Survival/drug effects ; Cyclooxygenase 2/genetics ; Cyclooxygenase 2/metabolism ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Gene Expression Regulation/drug effects ; Humans ; Inhibitor of Differentiation Protein 1/metabolism ; Mice ; Neoplastic Stem Cells/cytology ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Phenotype ; Pyrazoles/chemistry ; Pyrazoles/pharmacology ; Pyrimidines/chemistry ; Pyrimidines/pharmacology ; Signal Transduction/drug effects
Chemical Substances	Bmp4 protein, mouse ; Bone Morphogenetic Protein 4 ; Bone Morphogenetic Proteins ; Idb1 protein, mouse ; Inhibitor of Differentiation Protein 1 ; Pyrazoles ; Pyrimidines ; dorsomorphin (10K52CIC1Z) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Bmpr1a protein, mouse (EC 2.7.11.30) ; Bmpr2 protein, mouse (EC 2.7.11.30) ; Bone Morphogenetic Protein Receptors, Type I (EC 2.7.11.30) ; Bone Morphogenetic Protein Receptors, Type II (EC 2.7.11.30)
Language	English
Publishing date	2013-11-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2013.11.022
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Article: Inhibition of Asaia in Adult Mosquitoes Causes Male-Specific Mortality and Diverse Transcriptome Changes

Pathogens. 2020 May 15, v. 9, no. 5

2020

Abstract	Mosquitoes can transmit many infectious diseases, such as malaria, dengue, Zika, yellow fever, and lymphatic filariasis. Current mosquito control strategies are failing to reduce the severity of outbreaks that still cause high human morbidity and mortality worldwide. Great expectations have been placed on genetic control methods. Among other methods, genetic modification of the bacteria colonizing different mosquito species and expressing anti-pathogen molecules may represent an innovative tool to combat mosquito-borne diseases. Nevertheless, this emerging approach, known as paratransgenesis, requires a detailed understanding of the mosquito microbiota and an accurate characterization of selected bacteria candidates. The acetic acid bacteria Asaia is a promising candidate for paratransgenic approaches. We have previously reported that Asaia symbionts play a beneficial role in the normal development of Anopheles mosquito larvae, but no study has yet investigated the role(s) of Asaia in adult mosquito biology. Here we report evidence on how treatment with a highly specific anti-Asaia monoclonal antibody impacts the survival and physiology of adult Anopheles stephensi mosquitoes. Our findings offer useful insight on the role of Asaia in several physiological systems of adult mosquitoes, where the influence differs between males and females.
Keywords	Anopheles stephensi ; Asaia ; Bancroftian filariasis ; acetic acid bacteria ; control methods ; dengue ; females ; humans ; imagos ; insect larvae ; malaria ; males ; methodology ; monoclonal antibodies ; morbidity ; mortality ; mosquito control ; mosquito-borne diseases ; paratransgenesis ; pathogens ; symbionts ; transcriptome ; yellow fever
Language	English
Dates of publication	2020-0515
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9050380
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Article: Tailoring DNA Vaccines: Designing Strategies Against HER2-Positive Cancers.

Marchini, Cristina / Kalogris, Cristina / Garulli, Chiara / Pietrella, Lucia / Gabrielli, Federico / Curcio, Claudia / Quaglino, Elena / Cavallo, Federica / Amici, Augusto

Frontiers in oncology

2013 Volume 3, Page(s) 122

Abstract: The crucial role of HER2 in epithelial transformation and its selective overexpression on cancer tissues makes it an ideal target for cancer immunotherapies such as passive immunotherapy with Trastuzumab. There are, however, a number of concerns ... ...

Abstract	The crucial role of HER2 in epithelial transformation and its selective overexpression on cancer tissues makes it an ideal target for cancer immunotherapies such as passive immunotherapy with Trastuzumab. There are, however, a number of concerns regarding the use of monoclonal antibodies which include resistance, repeated treatments, considerable costs, and side effects that make active immunotherapies against HER2 desirable alternative approaches. The efficacy of anti-HER2 DNA vaccination has been widely demonstrated in transgenic cancer-prone mice, which recapitulate several features of human breast cancers. Nonetheless, the rational design of a cancer vaccine able to trigger a long-lasting immunity, and thus prevent tumor recurrence in patients, would require the understanding of how tolerance and immunosuppression regulate antitumor immune responses and, at the same time, the identification of the most immunogenic portions of the target protein. We herein retrace the findings that led to our most promising DNA vaccines that, by encoding human/rat chimeric forms of HER2, are able to circumvent peripheral tolerance. Preclinical data obtained with these chimeric DNA vaccines have provided the rationale for their use in an ongoing Phase I clinical trial (EudraCT 2011-001104-34).
Language	English
Publishing date	2013-05-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2013.00122
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Article ; Online: Wild celery (Smyrnium olusatrum L.) oil and isofuranodiene induce apoptosis in human colon carcinoma cells.

Quassinti, Luana / Maggi, Filippo / Barboni, Luciano / Ricciutelli, Massimo / Cortese, Manuela / Papa, Fabrizio / Garulli, Chiara / Kalogris, Cristina / Vittori, Sauro / Bramucci, Massimo

Fitoterapia

2014 Volume 97, Page(s) 133–141

Abstract: Smyrnium olusatrum (Apiaceae), well known as wild celery, is a biennal celery-scented plant used for many centuries as a vegetable, then abandoned after the introduction of celery. In the present work, the essential oil obtained from inflorescences and ... ...

Abstract	Smyrnium olusatrum (Apiaceae), well known as wild celery, is a biennal celery-scented plant used for many centuries as a vegetable, then abandoned after the introduction of celery. In the present work, the essential oil obtained from inflorescences and the amounts of its main constituents isofuranodiene, curzerene and germacrone were analyzed by GC as well as by HPLC because of their degradation (Cope rearrangement) occurring at high temperatures. The oil and the main constituents were assayed for cytotoxic activity on the human colon cancer cell line (HCT116) by MTT assay. Flower oil and isofuranodiene showed noteworthy activity on tumor cells with IC50 of 10.71 and 15.06 μg/ml, respectively. Analysis of the cytotoxic activity showed that wild celery oil and isofuranodiene are able to induce apoptosis in colon cancer cells in a time and concentration-dependent manner suggesting a potential role as models for the development of chemopreventive agents.
MeSH term(s)	Apiaceae/chemistry ; Apoptosis/drug effects ; Carcinoma/drug therapy ; Colonic Neoplasms/drug therapy ; DNA Fragmentation/drug effects ; Drug Screening Assays, Antitumor ; Furans/isolation & purification ; Furans/pharmacology ; Furans/therapeutic use ; HCT116 Cells ; Humans ; Microscopy, Fluorescence ; Oils, Volatile/chemistry ; Oils, Volatile/therapeutic use ; Phytotherapy ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use
Chemical Substances	Furans ; Oils, Volatile ; Plant Extracts ; isofuranodiene (57566-47-9)
Language	English
Publishing date	2014-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	412385-2
ISSN	1873-6971 ; 0367-326X
ISSN (online)	1873-6971
ISSN	0367-326X
DOI	10.1016/j.fitote.2014.06.004
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Article ; Online: Irreversible inhibition of Δ16HER2 is necessary to suppress Δ16HER2-positive breast carcinomas resistant to Lapatinib.

Tilio, Martina / Gambini, Valentina / Wang, Junbiao / Garulli, Chiara / Kalogris, Cristina / Andreani, Cristina / Bartolacci, Caterina / Elexpuru Zabaleta, Maria / Pietrella, Lucia / Hysi, Albana / Iezzi, Manuela / Belletti, Barbara / Orlando, Fiorenza / Provinciali, Mauro / Galeazzi, Roberta / Marchini, Cristina / Amici, Augusto

Cancer letters

2016 Volume 381, Issue 1, Page(s) 76–84

Abstract: HER2 tyrosine kinase receptor is a validated target in breast cancer therapy. However, increasing evidence points to a major role of Δ16HER2 splice variant commonly coexpressed with HER2 and identified as a clinically important HER2 molecular alteration ... ...

Abstract	HER2 tyrosine kinase receptor is a validated target in breast cancer therapy. However, increasing evidence points to a major role of Δ16HER2 splice variant commonly coexpressed with HER2 and identified as a clinically important HER2 molecular alteration promoting aggressive metastatic breast cancer. Consistently, mice transgenic for the human Δ16HER2 isoform (Δ16HER2 mice) develop invasive mammary carcinomas with early onset and 100% penetrance. The present study provides preclinical evidence that Δ16HER2 expression confers de novo resistance to standard anti-HER2-therapies such as Lapatinib and acquired resistance to the selective Src inhibitor Saracatinib in breast cancer. Of note, Dacomitinib, an irreversible small molecule pan-HER inhibitor, was able to completely suppress Δ16HER2-driven breast carcinogenesis. Thus, only Dacomitinib may offer benefit in this molecularly defined patient subset by irreversibly inhibiting Δ16HER2 activation.
MeSH term(s)	Alternative Splicing ; Animals ; Benzodioxoles/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/enzymology ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Female ; Genetic Predisposition to Disease ; Humans ; Inhibitory Concentration 50 ; Mammary Neoplasms, Experimental/drug therapy ; Mammary Neoplasms, Experimental/enzymology ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/pathology ; Mice, Transgenic ; Phenotype ; Protein Isoforms ; Protein Kinase Inhibitors/pharmacology ; Quinazolines/pharmacology ; Quinazolinones/pharmacology ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Signal Transduction/drug effects ; Time Factors
Chemical Substances	Benzodioxoles ; PF 00299804 ; Protein Isoforms ; Protein Kinase Inhibitors ; Quinazolines ; Quinazolinones ; lapatinib (0VUA21238F) ; saracatinib (9KD24QGH76) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2016--10
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2016.07.028
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Article ; Online: Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition.

Kalogris, Cristina / Garulli, Chiara / Pietrella, Lucia / Gambini, Valentina / Pucciarelli, Stefania / Lucci, Cristiano / Tilio, Martina / Zabaleta, Maria Elexpuru / Bartolacci, Caterina / Andreani, Cristina / Giangrossi, Mara / Iezzi, Manuela / Belletti, Barbara / Marchini, Cristina / Amici, Augusto

Biochemical pharmacology

2014 Volume 90, Issue 3, Page(s) 226–234

Abstract: Basal-like breast cancer (BLBC) remains a great challenge because of its clinically aggressive nature and lack of effective targeted therapy. We analyzed the potential anti-neoplastic effects of sanguinarine, a natural benzophenanthridine alkaloid, ... ...

Abstract	Basal-like breast cancer (BLBC) remains a great challenge because of its clinically aggressive nature and lack of effective targeted therapy. We analyzed the potential anti-neoplastic effects of sanguinarine, a natural benzophenanthridine alkaloid, against BLBC cells. Sanguinarine treatment resulted in a reduction of cell migration, in a dose-dependent inhibition of cell viability and in the induction of cell death by apoptosis in both human (MDA-MB-231 cells) and mouse (A17 cells) in vitro models of BLBC. In vivo experiments demonstrated that oral administration of sanguinarine reduced the development and growth of A17 transplantable tumors in FVB syngeneic mice. Western blotting analysis revealed that suppression of BLBC growth by sanguinarine was correlated with a concurrent upregulation of p27 and downregulation of cyclin D1 and with the inhibition of STAT3 activation. In addition, we identified sanguinarine as a potent inhibitor of dihydrofolate reductase (DHFR), able to impair enzyme activity even in methotrexate resistant MDA-MB-231 cells. These results provide evidence that sanguinarine is a promising anticancer drug for the treatment of BLBC.
MeSH term(s)	Animals ; Antineoplastic Agents, Phytogenic/adverse effects ; Antineoplastic Agents, Phytogenic/pharmacology ; Antineoplastic Agents, Phytogenic/therapeutic use ; Apoptosis/drug effects ; Benzophenanthridines/adverse effects ; Benzophenanthridines/pharmacology ; Benzophenanthridines/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/enzymology ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Survival/drug effects ; Drug Resistance, Neoplasm ; Female ; Folic Acid Antagonists/adverse effects ; Folic Acid Antagonists/pharmacology ; Folic Acid Antagonists/therapeutic use ; Humans ; Isoquinolines/adverse effects ; Isoquinolines/pharmacology ; Isoquinolines/therapeutic use ; Methotrexate/pharmacology ; Mice ; Mice, Inbred Strains ; Necrosis ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/metabolism ; Neoplasm Transplantation ; Neoplasms, Basal Cell/drug therapy ; Neoplasms, Basal Cell/enzymology ; Neoplasms, Basal Cell/pathology ; Random Allocation ; Tetrahydrofolate Dehydrogenase/chemistry ; Tetrahydrofolate Dehydrogenase/metabolism ; Tumor Burden/drug effects
Chemical Substances	Antineoplastic Agents, Phytogenic ; Benzophenanthridines ; Folic Acid Antagonists ; Isoquinolines ; Neoplasm Proteins ; sanguinarine (AV9VK043SS) ; Tetrahydrofolate Dehydrogenase (EC 1.5.1.3) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2014-08-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2014.05.014
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Article ; Online: Identification of relevant conformational epitopes on the HER2 oncoprotein by using Large Fragment Phage Display (LFPD).

Gabrielli, Federico / Salvi, Roberto / Garulli, Chiara / Kalogris, Cristina / Arima, Serena / Tardella, Luca / Monaci, Paolo / Pupa, Serenella M / Tagliabue, Elda / Montani, Maura / Quaglino, Elena / Stramucci, Lorenzo / Curcio, Claudia / Marchini, Cristina / Amici, Augusto

PloS one

2013 Volume 8, Issue 3, Page(s) e58358

Abstract: We developed a new phage-display based approach, the Large Fragment Phage Display (LFPD), that can be used for mapping conformational epitopes on target molecules of immunological interest. LFPD uses a simplified and more effective phage-display approach ...

Abstract	We developed a new phage-display based approach, the Large Fragment Phage Display (LFPD), that can be used for mapping conformational epitopes on target molecules of immunological interest. LFPD uses a simplified and more effective phage-display approach in which only a limited set of larger fragments (about 100 aa in length) are expressed on the phage surface. Using the human HER2 oncoprotein as a target, we identified novel B-cell conformational epitopes. The same homologous epitopes were also detected in rat HER2 and all corresponded to the epitopes predicted by computational analysis (PEPITO software), showing that LFPD gives reproducible and accurate results. Interestingly, these newly identified HER2 epitopes seem to be crucial for an effective immune response against HER2-overexpressing breast cancers and might help discriminating between metastatic breast cancer and early breast cancer patients. Overall, the results obtained in this study demonstrated the utility of LFPD and its potential application to the detection of conformational epitopes on many other molecules of interest, as well as, the development of new and potentially more effective B-cell conformational epitopes based vaccines.
MeSH term(s)	Animals ; BALB 3T3 Cells ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics ; Breast Neoplasms/immunology ; Breast Neoplasms/pathology ; Epitopes, B-Lymphocyte/chemistry ; Epitopes, B-Lymphocyte/genetics ; Epitopes, B-Lymphocyte/immunology ; Female ; Humans ; Mice ; Neoplasm Metastasis ; Peptide Library ; Protein Structure, Tertiary ; Rats ; Receptor, ErbB-2/chemistry ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/immunology
Chemical Substances	Epitopes, B-Lymphocyte ; Peptide Library ; ERBB2 protein, human (EC 2.7.10.1) ; Erbb2 protein, rat (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2013-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0058358
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Article ; Online: Identification of relevant conformational epitopes on the HER2 oncoprotein by using Large Fragment Phage Display (LFPD).

Federico Gabrielli / Roberto Salvi / Chiara Garulli / Cristina Kalogris / Serena Arima / Luca Tardella / Paolo Monaci / Serenella M Pupa / Elda Tagliabue / Maura Montani / Elena Quaglino / Lorenzo Stramucci / Claudia Curcio / Cristina Marchini / Augusto Amici

PLoS ONE, Vol 8, Iss 3, p e

2013 Volume 58358

Abstract	We developed a new phage-display based approach, the Large Fragment Phage Display (LFPD), that can be used for mapping conformational epitopes on target molecules of immunological interest. LFPD uses a simplified and more effective phage-display approach in which only a limited set of larger fragments (about 100 aa in length) are expressed on the phage surface. Using the human HER2 oncoprotein as a target, we identified novel B-cell conformational epitopes. The same homologous epitopes were also detected in rat HER2 and all corresponded to the epitopes predicted by computational analysis (PEPITO software), showing that LFPD gives reproducible and accurate results. Interestingly, these newly identified HER2 epitopes seem to be crucial for an effective immune response against HER2-overexpressing breast cancers and might help discriminating between metastatic breast cancer and early breast cancer patients. Overall, the results obtained in this study demonstrated the utility of LFPD and its potential application to the detection of conformational epitopes on many other molecules of interest, as well as, the development of new and potentially more effective B-cell conformational epitopes based vaccines.
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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