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n engl j med 359;25 www.nejm.org december 18, 2008
Motesanib Diphosphate in Progressive Differentiated
To the Editor: Sherman et al. (July 3 issue)1
highlight the importance of selecting patients for
alternative therapies, such as motesanib diphos-
phate, in the treatment of progressive differenti-
ated thyroid carcinomas. Although radiographic
findings are useful criteria for predicting a re-
sponse to motesanib, they can be supplemented
by the microscopical findings — in particular,
growth pattern, necrosis, and desmoplastic reac-
tion — which have been correlated with progres-
sion prediction.2 The genotypic alterations de-
scribed in follicular-cell neoplasms control the
mitogen-activated protein (MAP) kinase pathway
and proliferation. Was any correlation found with
proliferation markers? Which radiographic crite-
ria were used to define progression in metastatic
neoplasms? As for tumor progression, it normal-
ly refers to the acquisition of invasive capabilities
in intraepithelial lesions or metastatic potential
in invasive cancers.3
Salvador J. Diaz-Cano, M.D., Ph.D.
King’s College Hospital
London SE5 9RS, United Kingdom
Sherman SI, Wirth LJ, Droz JP, et al. Motesanib diphosphate
in progressive differentiated thyroid cancer. N Engl J Med 2008;
Arif S, Patel J, Blanes A, Diaz-Cano SJ. Cytoarchitectural and
kinetic features in the histological evaluation of follicular thy-
roid neoplasms. Histopathology 2007;50:750-63.
Diaz-Cano SJ. General morphological and biological fea-
tures of neoplasms: integration of molecular findings. Histopa-
The author replies: We agree with Diaz-Cano
that careful selection of patients for treatment with
investigational therapies for differentiated thyroid
cancer is essential. As is standard in cancer-thera-
py trials, in our trial progression was defined by
application of the Response Evaluation Criteria in
Solid Tumors (RECIST) for determination of both
eligibility and response.1 The microscopical fea-
tures referenced by Diaz-Cano may certainly be
valuable in characterizing follicular neoplasms but
have not yet been established as predictors of re-
sponses to therapy. Future studies of molecularly
targeted therapies in thyroid cancer may well ben-
efit from serial assessment of cellular responses
to treatment, including proliferation markers and
signaling intermediates, as he suggests.
Steven I. Sherman, M.D.
University of Texas M.D. Anderson Cancer Center
Houston, TX 77230-1402
for the Motesanib Thyroid Cancer Study Group
Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines
to evaluate the response to treatment in solid tumors: European
Organization for Research and Treatment of Cancer, National
Cancer Institute of the United States, National Cancer Institute
of Canada. J Natl Cancer Inst 2000;92:205-16.
Platelets and the Vascular Wall
To the Editor: In their review of the importance
of platelets in maintaining the integrity of the vas-
cular wall, Nachman and Rafii (Sept. 18 issue)1
provide evidence that maintenance of the endo-
thelial barrier depends on a reciprocal communi-
cation between endothelial cells and platelets and
the formation of zipper structures at adherens
junctions. A protein that is central in the activa-
tion status of platelets and endothelial zipper struc-
tures is vasodilator-stimulated phosphoprotein
(VASP). VASP is crucial for the polymerization of
the actin cytoskeleton and is intimately linked to
several proteins forming adherens junctions, such
as α-catenin. Endothelial cells deficient in VASP
are leaky, and platelets lacking VASP demonstrate
severe abnormalities in the platelet interaction with
the endothelium.2,3 Therefore, we wonder what the
authors think about the role of VASP in the cross-
talk between platelets and endothelial cells.
Valbona Mirakaj, M.D.
David Köhler, Ph.D.
Peter Rosenberger, M.D., Ph.D.
University Hospital Tübingen
72076 Tübingen, Germany
The New England Journal of Medicine
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