Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone
Identifieur interne : 001061 ( PascalFrancis/Corpus ); précédent : 001060; suivant : 001062Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone
Auteurs : Daniel G. Branstetter ; Scott D. Nelson ; J. Carlos Manivel ; Jean-Yves Blay ; Sant Chawla ; David M. Thomas ; Susie Jun ; Ira JacobsSource :
- Clinical cancer research [ 1078-0432 ] ; 2012.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.
Notice en format standard (ISO 2709)
Pour connaître la documentation sur le format Inist Standard.
pA |
|
---|
Format Inist (serveur)
NO : | PASCAL 12-0354416 INIST |
---|---|
ET : | Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone |
AU : | BRANSTETTER (Daniel G.); NELSON (Scott D.); MANIVEL (J. Carlos); BLAY (Jean-Yves); CHAWLA (Sant); THOMAS (David M.); JUN (Susie); JACOBS (Ira) |
AF : | Amgen Inc/Seattle, Washington/Etats-Unis (1 aut.); University of California/Los Angeles, California/Etats-Unis (2 aut.); University of Minnesota/Minneapolis, Minnesota/Etats-Unis (3 aut.); University Claude Bernard Lyon I and Hôpital Edouard Heriot/Lyon/France (4 aut.); Sarcoma Oncology Center, Santa Monica/California/Etats-Unis (5 aut.); Peter MacCallum Cancer Centre, East Melbourne/Victoria/Australie (6 aut.); Amgen Inc., Thousand Oaks/California/Etats-Unis (7 aut., 8 aut.) |
DT : | Publication en série; Niveau analytique |
SO : | Clinical cancer research; ISSN 1078-0432; Coden CCREF4; Etats-Unis; Da. 2012; Vol. 18; No. 16; Pp. 4415-4424; Bibl. 50 ref. |
LA : | Anglais |
EA : | Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB. |
CC : | 002B02R; 002B15C |
FD : | Dénosumab; Tumeur maligne; Ostéogenèse; Homme; Malade; Tumeur osseuse à cellules géantes |
FG : | Cancer; Anticorps monoclonal; Pathologie du système ostéoarticulaire; Tumeur bénigne |
ED : | Denosumab; Malignant tumor; Osteogenesis; Human; Patient; Bone giant cell tumor |
EG : | Cancer; Monoclonal antibody; Diseases of the osteoarticular system; Benign neoplasm |
SD : | Denosumab; Tumor maligno; Osteogénesis; Hombre; Enfermo |
LO : | INIST-26073.354000504079990240 |
ID : | 12-0354416 |
Links to Exploration step
Pascal:12-0354416Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone</title>
<author><name sortKey="Branstetter, Daniel G" sort="Branstetter, Daniel G" uniqKey="Branstetter D" first="Daniel G." last="Branstetter">Daniel G. Branstetter</name>
<affiliation><inist:fA14 i1="01"><s1>Amgen Inc</s1>
<s2>Seattle, Washington</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Nelson, Scott D" sort="Nelson, Scott D" uniqKey="Nelson S" first="Scott D." last="Nelson">Scott D. Nelson</name>
<affiliation><inist:fA14 i1="02"><s1>University of California</s1>
<s2>Los Angeles, California</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Manivel, J Carlos" sort="Manivel, J Carlos" uniqKey="Manivel J" first="J. Carlos" last="Manivel">J. Carlos Manivel</name>
<affiliation><inist:fA14 i1="03"><s1>University of Minnesota</s1>
<s2>Minneapolis, Minnesota</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Blay, Jean Yves" sort="Blay, Jean Yves" uniqKey="Blay J" first="Jean-Yves" last="Blay">Jean-Yves Blay</name>
<affiliation><inist:fA14 i1="04"><s1>University Claude Bernard Lyon I and Hôpital Edouard Heriot</s1>
<s2>Lyon</s2>
<s3>FRA</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Chawla, Sant" sort="Chawla, Sant" uniqKey="Chawla S" first="Sant" last="Chawla">Sant Chawla</name>
<affiliation><inist:fA14 i1="05"><s1>Sarcoma Oncology Center, Santa Monica</s1>
<s2>California</s2>
<s3>USA</s3>
<sZ>5 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Thomas, David M" sort="Thomas, David M" uniqKey="Thomas D" first="David M." last="Thomas">David M. Thomas</name>
<affiliation><inist:fA14 i1="06"><s1>Peter MacCallum Cancer Centre, East Melbourne</s1>
<s2>Victoria</s2>
<s3>AUS</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Jun, Susie" sort="Jun, Susie" uniqKey="Jun S" first="Susie" last="Jun">Susie Jun</name>
<affiliation><inist:fA14 i1="07"><s1>Amgen Inc., Thousand Oaks</s1>
<s2>California</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Jacobs, Ira" sort="Jacobs, Ira" uniqKey="Jacobs I" first="Ira" last="Jacobs">Ira Jacobs</name>
<affiliation><inist:fA14 i1="07"><s1>Amgen Inc., Thousand Oaks</s1>
<s2>California</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">12-0354416</idno>
<date when="2012">2012</date>
<idno type="stanalyst">PASCAL 12-0354416 INIST</idno>
<idno type="RBID">Pascal:12-0354416</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">001061</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone</title>
<author><name sortKey="Branstetter, Daniel G" sort="Branstetter, Daniel G" uniqKey="Branstetter D" first="Daniel G." last="Branstetter">Daniel G. Branstetter</name>
<affiliation><inist:fA14 i1="01"><s1>Amgen Inc</s1>
<s2>Seattle, Washington</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Nelson, Scott D" sort="Nelson, Scott D" uniqKey="Nelson S" first="Scott D." last="Nelson">Scott D. Nelson</name>
<affiliation><inist:fA14 i1="02"><s1>University of California</s1>
<s2>Los Angeles, California</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Manivel, J Carlos" sort="Manivel, J Carlos" uniqKey="Manivel J" first="J. Carlos" last="Manivel">J. Carlos Manivel</name>
<affiliation><inist:fA14 i1="03"><s1>University of Minnesota</s1>
<s2>Minneapolis, Minnesota</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Blay, Jean Yves" sort="Blay, Jean Yves" uniqKey="Blay J" first="Jean-Yves" last="Blay">Jean-Yves Blay</name>
<affiliation><inist:fA14 i1="04"><s1>University Claude Bernard Lyon I and Hôpital Edouard Heriot</s1>
<s2>Lyon</s2>
<s3>FRA</s3>
<sZ>4 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Chawla, Sant" sort="Chawla, Sant" uniqKey="Chawla S" first="Sant" last="Chawla">Sant Chawla</name>
<affiliation><inist:fA14 i1="05"><s1>Sarcoma Oncology Center, Santa Monica</s1>
<s2>California</s2>
<s3>USA</s3>
<sZ>5 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Thomas, David M" sort="Thomas, David M" uniqKey="Thomas D" first="David M." last="Thomas">David M. Thomas</name>
<affiliation><inist:fA14 i1="06"><s1>Peter MacCallum Cancer Centre, East Melbourne</s1>
<s2>Victoria</s2>
<s3>AUS</s3>
<sZ>6 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Jun, Susie" sort="Jun, Susie" uniqKey="Jun S" first="Susie" last="Jun">Susie Jun</name>
<affiliation><inist:fA14 i1="07"><s1>Amgen Inc., Thousand Oaks</s1>
<s2>California</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Jacobs, Ira" sort="Jacobs, Ira" uniqKey="Jacobs I" first="Ira" last="Jacobs">Ira Jacobs</name>
<affiliation><inist:fA14 i1="07"><s1>Amgen Inc., Thousand Oaks</s1>
<s2>California</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Clinical cancer research</title>
<title level="j" type="abbreviated">Clin. cancer res.</title>
<idno type="ISSN">1078-0432</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Clinical cancer research</title>
<title level="j" type="abbreviated">Clin. cancer res.</title>
<idno type="ISSN">1078-0432</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Bone giant cell tumor</term>
<term>Denosumab</term>
<term>Human</term>
<term>Malignant tumor</term>
<term>Osteogenesis</term>
<term>Patient</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Dénosumab</term>
<term>Tumeur maligne</term>
<term>Ostéogenèse</term>
<term>Homme</term>
<term>Malade</term>
<term>Tumeur osseuse à cellules géantes</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>1078-0432</s0>
</fA01>
<fA02 i1="01"><s0>CCREF4</s0>
</fA02>
<fA03 i2="1"><s0>Clin. cancer res.</s0>
</fA03>
<fA05><s2>18</s2>
</fA05>
<fA06><s2>16</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>BRANSTETTER (Daniel G.)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>NELSON (Scott D.)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>MANIVEL (J. Carlos)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>BLAY (Jean-Yves)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>CHAWLA (Sant)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>THOMAS (David M.)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>JUN (Susie)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>JACOBS (Ira)</s1>
</fA11>
<fA14 i1="01"><s1>Amgen Inc</s1>
<s2>Seattle, Washington</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>University of California</s1>
<s2>Los Angeles, California</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>University of Minnesota</s1>
<s2>Minneapolis, Minnesota</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>University Claude Bernard Lyon I and Hôpital Edouard Heriot</s1>
<s2>Lyon</s2>
<s3>FRA</s3>
<sZ>4 aut.</sZ>
</fA14>
<fA14 i1="05"><s1>Sarcoma Oncology Center, Santa Monica</s1>
<s2>California</s2>
<s3>USA</s3>
<sZ>5 aut.</sZ>
</fA14>
<fA14 i1="06"><s1>Peter MacCallum Cancer Centre, East Melbourne</s1>
<s2>Victoria</s2>
<s3>AUS</s3>
<sZ>6 aut.</sZ>
</fA14>
<fA14 i1="07"><s1>Amgen Inc., Thousand Oaks</s1>
<s2>California</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</fA14>
<fA20><s1>4415-4424</s1>
</fA20>
<fA21><s1>2012</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>26073</s2>
<s5>354000504079990240</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2012 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>50 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>12-0354416</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Clinical cancer research</s0>
</fA64>
<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02R</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002B15C</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Dénosumab</s0>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Denosumab</s0>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Denosumab</s0>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Tumeur maligne</s0>
<s2>NM</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Malignant tumor</s0>
<s2>NM</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Tumor maligno</s0>
<s2>NM</s2>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Ostéogenèse</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Osteogenesis</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Osteogénesis</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Homme</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Human</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Hombre</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Malade</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Patient</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Enfermo</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Tumeur osseuse à cellules géantes</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Bone giant cell tumor</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Cáncer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Anticorps monoclonal</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Monoclonal antibody</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Anticuerpo monoclonal</s0>
<s5>37</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Pathologie du système ostéoarticulaire</s0>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Diseases of the osteoarticular system</s0>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Sistema osteoarticular patología</s0>
<s5>38</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Tumeur bénigne</s0>
<s5>39</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Benign neoplasm</s0>
<s5>39</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Tumor benigno</s0>
<s5>39</s5>
</fC07>
<fN21><s1>275</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
<server><NO>PASCAL 12-0354416 INIST</NO>
<ET>Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone</ET>
<AU>BRANSTETTER (Daniel G.); NELSON (Scott D.); MANIVEL (J. Carlos); BLAY (Jean-Yves); CHAWLA (Sant); THOMAS (David M.); JUN (Susie); JACOBS (Ira)</AU>
<AF>Amgen Inc/Seattle, Washington/Etats-Unis (1 aut.); University of California/Los Angeles, California/Etats-Unis (2 aut.); University of Minnesota/Minneapolis, Minnesota/Etats-Unis (3 aut.); University Claude Bernard Lyon I and Hôpital Edouard Heriot/Lyon/France (4 aut.); Sarcoma Oncology Center, Santa Monica/California/Etats-Unis (5 aut.); Peter MacCallum Cancer Centre, East Melbourne/Victoria/Australie (6 aut.); Amgen Inc., Thousand Oaks/California/Etats-Unis (7 aut., 8 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Clinical cancer research; ISSN 1078-0432; Coden CCREF4; Etats-Unis; Da. 2012; Vol. 18; No. 16; Pp. 4415-4424; Bibl. 50 ref.</SO>
<LA>Anglais</LA>
<EA>Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB. Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL. Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells. Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.</EA>
<CC>002B02R; 002B15C</CC>
<FD>Dénosumab; Tumeur maligne; Ostéogenèse; Homme; Malade; Tumeur osseuse à cellules géantes</FD>
<FG>Cancer; Anticorps monoclonal; Pathologie du système ostéoarticulaire; Tumeur bénigne</FG>
<ED>Denosumab; Malignant tumor; Osteogenesis; Human; Patient; Bone giant cell tumor</ED>
<EG>Cancer; Monoclonal antibody; Diseases of the osteoarticular system; Benign neoplasm</EG>
<SD>Denosumab; Tumor maligno; Osteogénesis; Hombre; Enfermo</SD>
<LO>INIST-26073.354000504079990240</LO>
<ID>12-0354416</ID>
</server>
</inist>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/PascalFrancis/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001061 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PascalFrancis/Corpus/biblio.hfd -nk 001061 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Asie |area= AustralieFrV1 |flux= PascalFrancis |étape= Corpus |type= RBID |clé= Pascal:12-0354416 |texte= Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone }}
![]() | This area was generated with Dilib version V0.6.33. | ![]() |