Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides
•MMP sensitive RACPP-PLGC(Me)AG detects SCCA in an immune-competent carcinogen induced oral cancer mouse model.•RACPP-PLGC(Me)AG identifies cancer with excellent sensitivity and specificity.•RACPP-PLGC(Me)AG detects small cancerous lesions that are not visible by white light examination.•RACPP may b...
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| Veröffentlicht in: | Oral oncology 2017-08, Vol.71, p.156-162 |
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| creator | Hingorani, Dina V. Lemieux, Aaron J. Acevedo, Joseph R. Glasgow, Heather L. Kedarisetty, Suraj Whitney, Michael A. Molinolo, Alfredo A. Tsien, Roger Y. Nguyen, Quyen T. |
| description | •MMP sensitive RACPP-PLGC(Me)AG detects SCCA in an immune-competent carcinogen induced oral cancer mouse model.•RACPP-PLGC(Me)AG identifies cancer with excellent sensitivity and specificity.•RACPP-PLGC(Me)AG detects small cancerous lesions that are not visible by white light examination.•RACPP may be useful for intraoperative as well as non-invasive identification of cancer.
Ratiometric cell-penetrating-peptides (RACPP) are hairpin-shaped molecules that undergo cleavage by tumor-associated proteases resulting in measurable Cy5:Cy7 fluorescence ratiometric change to label cancer in vivo. We evaluated an MMP cleavable RACPP for use in the early detection of malignant lesions in a carcinogen-induced rodent tumor model.
Wild-type immune-competent mice were given 4-nitroquinoline-oxide (4NQO) for 16weeks. Oral cavities from live mice that had been intravenously administered MMP cleavable PLGC(Me)AG-RACPP were serially imaged from week 11 through week 21 using white-light reflectance and Cy5:Cy7 ratiometric fluorescence.
In an initial study we found that at week 21 nearly all mice (13/14) had oral cavity lesions, of which 90% were high-grade dysplasia or invasive carcinoma. These high-grade lesions were identifiable with white light reflectance and RACPP Cy5:Cy7 ratiometric fluorescence with similar detectability, Area Under Curve (AUC) for RACPP detection was 0.97 (95% Confidence interval (CI)=0.92–1.02, p |
| doi_str_mv | 10.1016/j.oraloncology.2017.06.009 |
| format | Article |
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Ratiometric cell-penetrating-peptides (RACPP) are hairpin-shaped molecules that undergo cleavage by tumor-associated proteases resulting in measurable Cy5:Cy7 fluorescence ratiometric change to label cancer in vivo. We evaluated an MMP cleavable RACPP for use in the early detection of malignant lesions in a carcinogen-induced rodent tumor model.
Wild-type immune-competent mice were given 4-nitroquinoline-oxide (4NQO) for 16weeks. Oral cavities from live mice that had been intravenously administered MMP cleavable PLGC(Me)AG-RACPP were serially imaged from week 11 through week 21 using white-light reflectance and Cy5:Cy7 ratiometric fluorescence.
In an initial study we found that at week 21 nearly all mice (13/14) had oral cavity lesions, of which 90% were high-grade dysplasia or invasive carcinoma. These high-grade lesions were identifiable with white light reflectance and RACPP Cy5:Cy7 ratiometric fluorescence with similar detectability, Area Under Curve (AUC) for RACPP detection was 0.97 (95% Confidence interval (CI)=0.92–1.02, p<0.001), sensitivity=89%, specificity=100%. In a follow up study, oral cavity lesions generated by 4NQO were imaged and histologically analyzed at weeks 16, 18 and 21. In this study we showed that RACPP-fluorescence detection positively identified 15 squamous cell carcinomas (in 6 separate mice) that were poorly visible or undetectable by white light reflectance.
RACPP ratiometric fluorescence can be used to accurately detect carcinogen-induced carcinoma in immunocompetent mice that are poorly visible or undetectable by white light reflectance.</description><identifier>ISSN: 1368-8375</identifier><identifier>EISSN: 1879-0593</identifier><identifier>DOI: 10.1016/j.oraloncology.2017.06.009</identifier><identifier>PMID: 28688684</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>4-Nitroquinoline-1-oxide - toxicity ; Animals ; Carcinogen-induced head and neck squamous cell carcinoma ; Carcinogens - toxicity ; Carcinoma, Squamous Cell - chemically induced ; Carcinoma, Squamous Cell - diagnosis ; Cell-Penetrating Peptides - metabolism ; Disease Models, Animal ; Enzyme responsive ; Female ; Fluorescence ; In vivo ; Matrix metalloproteinase ; Mice ; Mice, Inbred C57BL ; Mouth Neoplasms - chemically induced ; Mouth Neoplasms - diagnosis ; Ratiometricfluorescence imaging ; Sensitivity and Specificity</subject><ispartof>Oral oncology, 2017-08, Vol.71, p.156-162</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-6cf4252bfc26a48c83ad5e6d59418d3bcee2a222643f3a966acaae717fe506f13</citedby><cites>FETCH-LOGICAL-c487t-6cf4252bfc26a48c83ad5e6d59418d3bcee2a222643f3a966acaae717fe506f13</cites><orcidid>0000-0001-6244-9135</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1368837517301616$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28688684$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hingorani, Dina V.</creatorcontrib><creatorcontrib>Lemieux, Aaron J.</creatorcontrib><creatorcontrib>Acevedo, Joseph R.</creatorcontrib><creatorcontrib>Glasgow, Heather L.</creatorcontrib><creatorcontrib>Kedarisetty, Suraj</creatorcontrib><creatorcontrib>Whitney, Michael A.</creatorcontrib><creatorcontrib>Molinolo, Alfredo A.</creatorcontrib><creatorcontrib>Tsien, Roger Y.</creatorcontrib><creatorcontrib>Nguyen, Quyen T.</creatorcontrib><title>Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides</title><title>Oral oncology</title><addtitle>Oral Oncol</addtitle><description>•MMP sensitive RACPP-PLGC(Me)AG detects SCCA in an immune-competent carcinogen induced oral cancer mouse model.•RACPP-PLGC(Me)AG identifies cancer with excellent sensitivity and specificity.•RACPP-PLGC(Me)AG detects small cancerous lesions that are not visible by white light examination.•RACPP may be useful for intraoperative as well as non-invasive identification of cancer.
Ratiometric cell-penetrating-peptides (RACPP) are hairpin-shaped molecules that undergo cleavage by tumor-associated proteases resulting in measurable Cy5:Cy7 fluorescence ratiometric change to label cancer in vivo. We evaluated an MMP cleavable RACPP for use in the early detection of malignant lesions in a carcinogen-induced rodent tumor model.
Wild-type immune-competent mice were given 4-nitroquinoline-oxide (4NQO) for 16weeks. Oral cavities from live mice that had been intravenously administered MMP cleavable PLGC(Me)AG-RACPP were serially imaged from week 11 through week 21 using white-light reflectance and Cy5:Cy7 ratiometric fluorescence.
In an initial study we found that at week 21 nearly all mice (13/14) had oral cavity lesions, of which 90% were high-grade dysplasia or invasive carcinoma. These high-grade lesions were identifiable with white light reflectance and RACPP Cy5:Cy7 ratiometric fluorescence with similar detectability, Area Under Curve (AUC) for RACPP detection was 0.97 (95% Confidence interval (CI)=0.92–1.02, p<0.001), sensitivity=89%, specificity=100%. In a follow up study, oral cavity lesions generated by 4NQO were imaged and histologically analyzed at weeks 16, 18 and 21. In this study we showed that RACPP-fluorescence detection positively identified 15 squamous cell carcinomas (in 6 separate mice) that were poorly visible or undetectable by white light reflectance.
RACPP ratiometric fluorescence can be used to accurately detect carcinogen-induced carcinoma in immunocompetent mice that are poorly visible or undetectable by white light reflectance.</description><subject>4-Nitroquinoline-1-oxide - toxicity</subject><subject>Animals</subject><subject>Carcinogen-induced head and neck squamous cell carcinoma</subject><subject>Carcinogens - toxicity</subject><subject>Carcinoma, Squamous Cell - chemically induced</subject><subject>Carcinoma, Squamous Cell - diagnosis</subject><subject>Cell-Penetrating Peptides - metabolism</subject><subject>Disease Models, Animal</subject><subject>Enzyme responsive</subject><subject>Female</subject><subject>Fluorescence</subject><subject>In vivo</subject><subject>Matrix metalloproteinase</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mouth Neoplasms - chemically induced</subject><subject>Mouth Neoplasms - diagnosis</subject><subject>Ratiometricfluorescence imaging</subject><subject>Sensitivity and Specificity</subject><issn>1368-8375</issn><issn>1879-0593</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUduKFDEQDaK4F_0FCb53b5LupNM-CLKuF1jwRZ9DdVI9ZuhOxnTPwPyE32wN4y7rmxCo6zlVqcPYWylqKaS52da5wJSTz1PeHGslZFcLUwvRP2OX0nZ9JXTfPCe_MbayTacv2NWybIUQWmrxkl0oayy99pL9voMyHXnAFf0ac-J55MuvPcx5v3CP08Q9FB9TnoHH9BBsMFEU9h4DP-1C-eSx8JIDppXPZCY-HHkB4pxxLdFzIP4DrDBMeCbeYaIKdaQN-bs1BlxesRcjTAu-_muv2Y9Pd99vv1T33z5_vf1wX_nWdmtl_NgqrYbRKwOt9baBoNEE3bfShmbwiAqUUqZtxgZ6Y8ADYCe7EbUwo2yu2fsz724_zBg8bU3fcLsSZyhHlyG6fysp_nSbfHBad9r2lgjenQl8yctScHzESuFOKrmte6qSO6nkhHGkEoHfPJ3-CH2QhRo-nhuQbnCIWNziI9KJQyykkws5_s-cP1NxsYI</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Hingorani, Dina V.</creator><creator>Lemieux, Aaron J.</creator><creator>Acevedo, Joseph R.</creator><creator>Glasgow, Heather L.</creator><creator>Kedarisetty, Suraj</creator><creator>Whitney, Michael A.</creator><creator>Molinolo, Alfredo A.</creator><creator>Tsien, Roger Y.</creator><creator>Nguyen, Quyen T.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6244-9135</orcidid></search><sort><creationdate>20170801</creationdate><title>Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides</title><author>Hingorani, Dina V. ; Lemieux, Aaron J. ; Acevedo, Joseph R. ; Glasgow, Heather L. ; Kedarisetty, Suraj ; Whitney, Michael A. ; Molinolo, Alfredo A. ; Tsien, Roger Y. ; Nguyen, Quyen T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-6cf4252bfc26a48c83ad5e6d59418d3bcee2a222643f3a966acaae717fe506f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>4-Nitroquinoline-1-oxide - toxicity</topic><topic>Animals</topic><topic>Carcinogen-induced head and neck squamous cell carcinoma</topic><topic>Carcinogens - toxicity</topic><topic>Carcinoma, Squamous Cell - chemically induced</topic><topic>Carcinoma, Squamous Cell - diagnosis</topic><topic>Cell-Penetrating Peptides - metabolism</topic><topic>Disease Models, Animal</topic><topic>Enzyme responsive</topic><topic>Female</topic><topic>Fluorescence</topic><topic>In vivo</topic><topic>Matrix metalloproteinase</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mouth Neoplasms - chemically induced</topic><topic>Mouth Neoplasms - diagnosis</topic><topic>Ratiometricfluorescence imaging</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hingorani, Dina V.</creatorcontrib><creatorcontrib>Lemieux, Aaron J.</creatorcontrib><creatorcontrib>Acevedo, Joseph R.</creatorcontrib><creatorcontrib>Glasgow, Heather L.</creatorcontrib><creatorcontrib>Kedarisetty, Suraj</creatorcontrib><creatorcontrib>Whitney, Michael A.</creatorcontrib><creatorcontrib>Molinolo, Alfredo A.</creatorcontrib><creatorcontrib>Tsien, Roger Y.</creatorcontrib><creatorcontrib>Nguyen, Quyen T.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oral oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hingorani, Dina V.</au><au>Lemieux, Aaron J.</au><au>Acevedo, Joseph R.</au><au>Glasgow, Heather L.</au><au>Kedarisetty, Suraj</au><au>Whitney, Michael A.</au><au>Molinolo, Alfredo A.</au><au>Tsien, Roger Y.</au><au>Nguyen, Quyen T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides</atitle><jtitle>Oral oncology</jtitle><addtitle>Oral Oncol</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>71</volume><spage>156</spage><epage>162</epage><pages>156-162</pages><issn>1368-8375</issn><eissn>1879-0593</eissn><abstract>•MMP sensitive RACPP-PLGC(Me)AG detects SCCA in an immune-competent carcinogen induced oral cancer mouse model.•RACPP-PLGC(Me)AG identifies cancer with excellent sensitivity and specificity.•RACPP-PLGC(Me)AG detects small cancerous lesions that are not visible by white light examination.•RACPP may be useful for intraoperative as well as non-invasive identification of cancer.
Ratiometric cell-penetrating-peptides (RACPP) are hairpin-shaped molecules that undergo cleavage by tumor-associated proteases resulting in measurable Cy5:Cy7 fluorescence ratiometric change to label cancer in vivo. We evaluated an MMP cleavable RACPP for use in the early detection of malignant lesions in a carcinogen-induced rodent tumor model.
Wild-type immune-competent mice were given 4-nitroquinoline-oxide (4NQO) for 16weeks. Oral cavities from live mice that had been intravenously administered MMP cleavable PLGC(Me)AG-RACPP were serially imaged from week 11 through week 21 using white-light reflectance and Cy5:Cy7 ratiometric fluorescence.
In an initial study we found that at week 21 nearly all mice (13/14) had oral cavity lesions, of which 90% were high-grade dysplasia or invasive carcinoma. These high-grade lesions were identifiable with white light reflectance and RACPP Cy5:Cy7 ratiometric fluorescence with similar detectability, Area Under Curve (AUC) for RACPP detection was 0.97 (95% Confidence interval (CI)=0.92–1.02, p<0.001), sensitivity=89%, specificity=100%. In a follow up study, oral cavity lesions generated by 4NQO were imaged and histologically analyzed at weeks 16, 18 and 21. In this study we showed that RACPP-fluorescence detection positively identified 15 squamous cell carcinomas (in 6 separate mice) that were poorly visible or undetectable by white light reflectance.
RACPP ratiometric fluorescence can be used to accurately detect carcinogen-induced carcinoma in immunocompetent mice that are poorly visible or undetectable by white light reflectance.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28688684</pmid><doi>10.1016/j.oraloncology.2017.06.009</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-6244-9135</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 4-Nitroquinoline-1-oxide - toxicity Animals Carcinogen-induced head and neck squamous cell carcinoma Carcinogens - toxicity Carcinoma, Squamous Cell - chemically induced Carcinoma, Squamous Cell - diagnosis Cell-Penetrating Peptides - metabolism Disease Models, Animal Enzyme responsive Female Fluorescence In vivo Matrix metalloproteinase Mice Mice, Inbred C57BL Mouth Neoplasms - chemically induced Mouth Neoplasms - diagnosis Ratiometricfluorescence imaging Sensitivity and Specificity |
| title | Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides |
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