Association of stem cell marker CD133 expression with dissemination of glioblastomas

Satō, Atsushi; Sakurada, Kaori; Kumabe, Toshihiro; Sasajima, Toshio; Beppu, Teruhiko; Asano, Kenichiro; Ohkuma, Hiroki; Mizoi, Kazuo; Tominaga, Teiji; Kitanaka, Chifumi; Kayama, Takamasa

doi:10.1007/s10143-010-0239-8

Cited by 32 publications

(25 citation statements)

References 44 publications

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“…2D and E), which was also suggested in the report by Sato et al 34 According to previous reports, glioma stem cells with high CD133 expression are resistant to chemoradiotherapy 18,35 and grow as floating cells. 36 Thus, these cells may survive the initial treatment and may be able to propagate through CSF, resulting in distant recurrence.…”

Section: Discussionsupporting

confidence: 59%

The expression status of CD133 is associated with the pattern and timing of primary glioblastoma recurrence

et al. 2013

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Background. Glioblastoma carries a poor prognosis primarily because of its high rate of recurrence. The ability to predict the recurrence pattern and timing would be highly useful for determining effective treatment strategies. We examined the correlation between prognostic factors and the pattern of recurrence in patients with primary glioblastoma. In particular, we examined whether there was a correlation between the expression of CD133 and glioblastoma recurrence. Methods. We retrospectively analyzed 112 patients with primary glioblastoma. The timing and pattern (local or distant) of the initial recurrence were obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by Western blots and immunohistochemistry, clinical (age, sex, KPS, Ki67 labeling index, surgery, ventricular entry) and genetic (IDH1, 7p, 9p, 10q, MGMT) factors. Results. Of the 112 patients, 99 suffered recurrence. The first recurrence was local in 77 patients and distant in 22 patients. Among the factors to predict the pattern of recurrence, CD133 expression was significantly higher in distant than in local recurrence. Of the factors to predict the timing of recurrence, high CD133 expression was associated with shorter time to distant recurrence in both univariate and multivariate analyses (P ¼ .0011 and P ¼ .038, respectively). Conclusions. The expression of CD133 may be a predictor of the pattern and timing of recurrence of primary glioblastoma.Keywords: glioblastoma, CD133, distant recurrence, local recurrence, stem cells. P rimary glioblastoma, classified as grade IV tumor by the World Health Organization (WHO), is the most malignant tumor of the human central nervous system.1 Despite aggressive treatment, the median survival of patients with these tumors is 12.5 -15 months.2,3 During their clinical course, almost all patients suffer a posttreatment recurrence. Therefore, to improve the prognosis, the pattern and timing of tumor recurrence must be better understood.Advances in surgical treatments such as 5-aminolevulinic acid fluorescence-guided surgery, 4 intraoperative MRI, 5 and functional mapping 6 have enabled maximal resection of these tumors without eliciting severe morbidity. Postoperative treatment with temozolomide and radiation to achieve local tumor control also improves the prognosis slightly.7 Despite good control of the initial lesion, some patients suffer tumor recurrence at a distant location. 8 -12 The reported rate of postoperative distant recurrence including dissemination ranges from 8% to 43.6%. 9,11 -13 To predict and address the clinical course of patients with glioblastoma, we must acquire a better understanding of factors involved in the pattern and timing of not only local but also distant tumor recurrence. Detailed analysis of these factors may make prophylactic treatment for recurrences possible. However, there are few studies on such clinical and molecular features.Here, we conducted a retrospective study to identify the factors associated with distant and lo...

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Section: Discussionsupporting

confidence: 59%

The expression status of CD133 is associated with the pattern and timing of primary glioblastoma recurrence

et al. 2013

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“…The latter allows targeting of zones with high cell density [23], whereas targeting with perfusion-weighted MRI relates to greater malignant vascularity. Perfusion MRI mapping may be more useful than PET, given that neoangiogenesis is the strongest predictive factor for glial tumors [14,24,25,26]. In the present study, targeting based on perfusion-weighted MRI corresponded to contrast enhancement data for 10 of the 11 glial tumors.…”

Section: Discussionmentioning

confidence: 81%

Perfusion MRI as a Neurosurgical Tool for Improved Targeting in Stereotactic Tumor Biopsies

Lefranc

Monet²,

Desenclos³

et al. 2012

Stereotact Funct Neurosurg

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Objective: Stereotactic biopsies are subject to sampling errors (essentially due to target selection). The presence of contrast enhancement is not a reliable marker of malignancy. The goal of the present study was to determine whether perfusion-weighted imaging can improve target selection in stereotactic biopsies. Methods: We studied 21 consecutive stereotactic biopsies between June 2009 and March 2010. Perfusion-weighted magnetic resonance imaging (MRI) was integrated into our neuronavigator. Perfusion-weighted imaging was used as an adjunct to conventional MRI data for target determination. Conventional MRI alone was used to determine the trajectory. Results: We found a linear correlation between regional cerebral blood volume (rCBV) and vessel density (number of vessels per mm²; R = 0.64; p < 0.001). Perfusion-weighted imaging facilitated target determination in 11 cases (52.4%), all of which were histopathologically diagnosed as glial tumors. For glial tumors, which presented with contrast enhancement, perfusion-weighted imaging identified a more precisely delimited target in 9 cases, a different target in 1 case, and exactly the same target in 1 other case. In all cases, perfusion-selected sampling provided information on cellular features and tumor grading. rCBV was significantly associated with grading (p < 0.01), endothelial proliferation (p < 0.01), and vessel density (p < 0.01). For lesions with rCBV values ≤1, perfusion-weighted MRI did not help to determine the target but was useful for surgical management. Conclusions: For stereotactic biopsies, targeting based on perfusion-weighted imaging is a feasible method for reducing the sampling error and improving target selection in the histopathological diagnosis of tumors with high rCBVs.

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“…These authors determined that these CD133 + cells were glioblastoma stem cells, and also identified a more aggressive subtype of the disease (21) , insofar as these cells are highly resistant to radiation and chemotherapy procedures (16) . Other studies have also suggested that the expression of the marker CD133 + could be a molecular indicator of glioblastoma spreading (16,22) , which justifies its prognostic value (23) and the recent demand for drugs that act against this subset of cells (CD133 + ) in order to inhibit or retard the proliferation of highly invasive gliomas (24) .…”

Section: Discussionmentioning

confidence: 99%

Isolation, cultivation and characterization of CD133+ stem cells from human glioblastoma

Pavon

Marti

Sibov

et al. 2012

Einstein (São Paulo)

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Objective: To establish the method of isolation and culture of human glioblastoma neurospheres, and the purification of their stem cells, followed by the process of obtaining tumor subspheres, immunophenotypically characterizing this clonogenic set. Methods: Through the processing of glioblastoma samples (n=3), the following strategy of action was adopted: (i) establish primary culture of glioblastoma; (ii) isolation and culture of tumor neurospheres; (iii) purify cells that initiate tumors (CD133 + ) by magnetic separation system (MACS); (iv) obtain tumor subspheres; (v) study the expression of the markers nestin, CD133, and GFAP. Results: The study successfully described the process of isolation and culture of glioblastoma subspheres, which consist of a number of clonogenic cells immunophenotypically characterized as neural, which are able to initiate tumor formation. Conclusion: These findings may contribute to a better understanding of the process of gliomagenesis.

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Association of stem cell marker CD133 expression with dissemination of glioblastomas

Cited by 32 publications

References 44 publications

The expression status of CD133 is associated with the pattern and timing of primary glioblastoma recurrence

The expression status of CD133 is associated with the pattern and timing of primary glioblastoma recurrence

Perfusion MRI as a Neurosurgical Tool for Improved Targeting in Stereotactic Tumor Biopsies

Isolation, cultivation and characterization of CD133+ stem cells from human glioblastoma

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