10月13-16日,第14届国际妇科肿瘤学会双年会(IGCS 2012)在加拿大温哥华举行。IGCS 2012一如既往地为参会者奉上妇科肿瘤学领域最新研究进展,提供发布、讨论和争辩最新科学信息的良机。金宝搏网站登录技巧 对本届年会进行了专题报道(http://zt.cmt.com.cn/zt/igcs2012/index.html)。
10月13-16日,第14届国际妇科肿瘤学会双年会(IGCS 2012)在加拿大温哥华举行。IGCS 2012一如既往地为参会者奉上妇科肿瘤学领域最新研究进展,提供发布、讨论和争辩最新科学信息的良机。金宝搏网站登录技巧 对本届年会进行了专题报道(http://zt.cmt.com.cn/zt/igcs2012/index.html)。
研究摘要:
Molecular targeted ultrasound imaging of αvβ3-integrins
expressing microvessels in association with anti-NMP
antibodies detects ovarian cancer at early stage
A Barua1, T Qureshi1, P Bitterman1, JM Bahr2, S Basu3, J
Rotmensch,4 JA Abramowicz4
1Departments of Pharmacology, Pathology, and Obstetrics
and Gynecology, Rush University, Chicago, IL; 2Laboratory
of Animal Sciences, University of Illinois at Urbana-
Champaign (UIUC), Urbana-Champaign, IL; 3Department
of Preventive Medicine, Rush University, Chicago, IL; 4Department
of Obstetrics and Gynecology, Rush University,
Chicago, IL.
Background: Changes in nuclear morphology including
nuclear matrix proteins (NMPs) followed by tumor-associated
neoangiogenesis (TAN) are the 2 earlier events in malignant
transformation and progression of ovarian cancer (OVCA).
Anti-NMP antibodies are produced in response to NMPs
shed during malignant transformation. Expression of avb3-
integrins by TAN vessels is one of the features of ovarian
TAN. Anti-NMP antibodies and ovarian TAN may represent
markers of early-stage OVCA. Identification of patients at
early-stage OVCA is very difficult, and laying hens have
been shown to develop spontaneous OVCA with histopathology
similar to humans. The goal of this study was to examine
the feasibility of >vA3-integrinYtargeted transvaginal ultrasound
(TVUS) imaging and anti-NMP antibodies in detecting
OVCA at early stage.
Methods: Henswith (n = 50) or without (n = 20) serumanti-
NMP antibodies and without any TVUS-detectable ovarian
abnormality were selected for prospective monitoring by
avb3-integrinsYtargeted TVUS at 15 weeks’ interval up to
45 weeks. Hens were scanned before, during, and after injection
of targeted microbubbles at each interval. Preinjection
and postinjection images archived and analyzed off-line.
Hens were euthanized at diagnosis for OVCA or at the end
of the 45 weeks. Gross diagnosis was recorded at euthanasia.
Serum and tissues were processed for histology, immunohistochemistry
(smooth-muscle actin and >vA3 integrins), and
immunoblotting.
Results: Within 30 to 45 weeks of monitoring, 7 hens with
serum anti-NMP antibodies developed OVCA spontaneously.
>vA3-integrins targeted microbubbles enhanced the visualization
of ovarian tumors remarkably. Targeted microbubbleYbounded
areas appeared as a ring on the ovarian
surfaces of 5 hens on TVUS and suspected for OVCA.
Tumors were confirmed in all hens predicted to have OVCA
by targeted TVUS at euthanasia. In 4 hens, tumors were
limited to the ovaries (early stage); and in one hen, the tumor
metastasized to abdominal cavity. Targeted TVUS imaging
could not detect 2 hens with microscopic lesions without any
solid tumor mass. Thus, 7 of 50 hens had OVCA and targeted
microbubbles detected approximately 72% (5/7 hens). Serum
reacted against NMP antigens of various molecular weight from
malignant ovaries in immunoblotting. The frequency of TAN
vessels (smooth-muscle actin and >vA3-integrins expressing)
were significantly higher in OVCA hens than in normal hens
(P G 0.05).
Conclusions: Targeted imaging enhanced TVUS detection of
early-stage OVCA. Anti-NMP antibodies together with targeted
imaging may constitute an early detection test for
OVCA. The resultsmay form the foundation for a clinical study.
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