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。 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：

An Optimized Primary Ovarian Cancer Xenograft Model
Mimics Patient’s Tumor Biology and Heterogeneity
Z Dobbin1, AA Katre1, A Ziebarth1, MM Shah1, AD Steg1,
RD Alvarez1, MG Conner2, CN Landen1
1Department of Obstetrics and Gynecology, Medical Scientist
Training Program, University of Alabama at Birmingham, AL;
2Department of Pathology, University of Alabama at
Birmingham, Birmingham, AL.
Background: Current xenograft and transgenic models of
ovarian cancer are predominantly homogeneous and inadequately
predict response to therapy in clinical trials. Use
of patients’ tumors may represent a better model for tumor
biology and offer potential to test personalized medical approaches,
but poor take rates and questions of recapitulation
of patients’ tumors have limited this approach. We have developed
a protocol for improved feasibility of such a model
and examined its similarity to the patient’s tumor.
Methods: Under institutional review board and Institutional
Animal Care and Use Committee approval, 23 metastatic
(omental) ovarian cancer samples were collected at the time of
tumor reductive surgery. Samples were implanted either
subcutaneously (SQ), intraperitoneally, in the mammary fat
pad, or in the subrenal capsule and monitored for tumor development.
Cohorts from 8 xenolines were treated with
combined carboplatin and paclitaxel chemotherapy or vehicle,
and response to therapy was compared between xenografts
and patients. Expression of tumor-initiating cell (TIC)
markers ALDH1, CD133, and CD44 was assessed by immunohistochemistry
in tumors from patients and treated and
untreated xenografts.
Results: At least one of the SQ implanted tumors developed
in 91.3% of xenografts, significantly higher than in the
mammary fat pad (63.6%), intraperitoneally implanted
(23.5%), or subrenal capsule (8%). Xenografts were similar in
expression of putative TICs compared to patients’ tumors
(ALDH, 17% vs 19%; CD44, 2.4% vs 5%; CD133, 10% vs
3%; P 9 0.05). The patients and the xenografts also have similar
responses to chemotherapy in that xenografts from patients with
a partial response to therapy responded more slowly than those
xenografts from patients achieving a complete response (45 vs
21 days, P = 0.004). Interestingly, xenografts that were treated
with chemotherapy were more densely composed of TICs, with
ALDH1 increasing to 36.1% from 16.2% (P = 0.002) and
CD133 increasing to 33.8% from 16.2% (P = 0.026).
Conclusions: Xenoline development can be achieved at a
high rate when tumors collected from metastatic sites
are implanted SQ. These xenografts are similar to patients’
tumors with regard to chemotherapy response and TIC expression
profiles. Our model may represent a more accurate
model for in vivo preclinical studies compared to current
models. As this xenograft model is developed directly from
patients’samples and the treated xenografts become enriched

in chemoresistant cells, this model represents a novel mechanism
to test patient-specific therapies.