Micrometastases of Bone Marrow in Localized Prostate Cancer: Correlation With Established Risk Factors

Weckermann, Dorothea; Müller, Peter E.; Wawroschek, Friedhelm; Krawczak, Gunnar; Riethmüller, Gert; Schlimok, Günter

doi:10.1200/jco.1999.17.11.3438

Cited by 46 publications

(32 citation statements)

References 18 publications

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“…38 In BM from PCa patients without overt metastases, the presence of CK-positive DTCs has been shown to be related to an unfavorable outcome. 6 However, cytokeratins are no tumor-specific markers, and human epithelial antigen, prostatespecific transcripts (e.g., PSA mRNA) or tumor-associated MAGE transcripts have therefore also been used as markers for DTCs. 4,45,46 Although these transcripts are usually not amplified from normal BM cells, they are not expressed by all prostate cancer cells and can occur in non-tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…The antibody is well evaluated and has already been applied for BM analysis to obtain clinical relevant information on patients with different solid tumor types including PCa. [3][4][5][6][7][8] Out of 57 PCa patients, we were able to investigate BM from 55 patients, and detected DTCs in 12 (22%) samples. A representative example of a CK-positive cell in the BM of a PCa patient is shown in Figure 5.…”

Section: Relationship Of the Detected Lohs In Bm Plasma And Tumor Tismentioning

confidence: 99%

“…1 Thus, several groups (including ours) have developed sensitive methods and were able to detect disseminated tumor cells (DTCs) in BM of 20-30% of PCa patients at the time of primary surgery years before the onset of overt metastases. [4][5][6][7][8] In particular, enrichment techniques and immunocytochemical assays based on monoclonal antibodies specific for epithelial cytokeratins (CK) allow now the detection of single DTCs in BM of patients with solid epithelial tumors including PCa. 2 Initiation and progression of PCa is accompanied by a multistep process with numerous genetic aberrations.…”

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Detection of tumor‐specific DNA in blood and bone marrow plasma from patients with prostate cancer

Schwarzenbach

Chun

Lange

et al. 2007

Intl Journal of Cancer

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Tumor tissues, blood plasma and bone marrow (BM) aspirates of 57 prostate cancer patients (PCa) without clinical signs of overt metastases were assessed for LOH (loss of heterozygosity) by a PCRbased fluorescence microsatellite analysis, using a panel of 15 markers. Additionally, micrometastatic tumor cells in BM were monitored by an immunocytological cytokeratin assay. In total, 25 (44%), 32 (56%) and 41 (72%) of the patients had at least 1 LOH in their blood, BM and tumor samples, respectively. Among the informative cases, the frequency of LOH was highest in blood plasma for the markers D8S360 (18%) and D10S1765 (15%), and in BM plasma for THRB (24%) and D8S137 (22%). Comparison of blood plasma and BM with tumors showed discrepant results in 35% and 45% of patients, respectively. Whereas all LOHs at THRB in BM plasma were also detected in the autologous tumor tissues, LOHs at D6S474 and D11S898 in BM were not retrieved in the tumors. The comparison with established risk factors showed a correlation of borderline significance for LOH at D9S1748 in the BM aspirates (p 5 0.055) and a significant correlation in the tumor samples (p 5 0.004) with increasing pathologic Gleason scores. Interestingly, 22% of the PCa patients harbored tumor cells in their BM and tended (p 5 0.065) to have more frequent LOH (16%) in BM plasma compared to patients without tumor cells (9%). These data demonstrate, for the first time, the presence of free tumor-specific DNA in blood and BM of PCa patients and suggest a possible relationship to BM micrometastasis. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Relationship Of the Detected Lohs In Bm Plasma And Tumor Tismentioning

confidence: 99%

mentioning

confidence: 99%

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Detection of tumor‐specific DNA in blood and bone marrow plasma from patients with prostate cancer

Schwarzenbach

Chun

Lange

et al. 2007

Intl Journal of Cancer

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“…In one study of approximately 154 patients with localized disease who underwent serial biopsies, 25% of patients had CK 18 + cells in the marrow, but had an identical rate of biochemical relapse to those who did not, at a median follow-up period of 32 months [5]. The presence of such cells also appears to be unrelated to Gleason score, pretreatment PSA level, and other standard prognostic criteria [6]. Nonetheless, the prognostic value of micrometastatic disease is unclear because outcome can vary according to the antibody used to detect these cells [7].…”

Section: Introductionmentioning

confidence: 99%

“…Nonetheless, the prognostic value of micrometastatic disease is unclear because outcome can vary according to the antibody used to detect these cells [7]. Moreover, it is unclear whether, biologically, all micrometastases have the capacity to progress to overt metastases [4,6]. Thus, the question is raised whether the cells that populate the marrow in patients with advanced disease arise from cells found in early stages, or whether the marrow is repopulated with aggressive, resistant cells later in the disease course.…”

Section: Introductionmentioning

confidence: 99%

Clinical Approaches to Osseous Metastases in Prostate Cancer

Morris

Scher

2003

The Oncologist

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Background. Prostate cancer is unique among solid tumors in its proclivity to metastasize primarily to bone. Osseous metastases pose a formidable health threat to patients with metastatic disease, putting them at risk for pain, marrow crowding, fracture, and other sequelae. Treatments directed against bone disease have the potential both to palliate pain and to increase survival.Conclusions. A number of agents exist that have the potential to palliate the effects of osseous metastases and should be routinely applied in the clinical care of

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A Simple Protocol to Stabilize Gold Nanoparticles using Amphiphilic Block Copolymers: Stability Studies and Viable Cellular Uptake

Rahme¹,

Vicendo²,

Ayela³

et al. 2009

Chemistry A European J

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Di- and triblock non-ionic copolymers based on poly(ethylene oxide) and poly(propylene oxide) were studied for the stabilization of nanoparticles in water at high ionic strength. The effect of the molecular architecture (di- vs. triblock) of these amphiphilic copolymers was investigated by using gold nanoparticles (AuNPs) as probes for colloidal stability. The results demonstrate that both di- and triblock copolymers can provide long term stability, and that in both cases AuNPs are individually embedded within globules of polymers. However, in the case of diblock copolymers, the colloidal stability was related to the formation of micelles, in contrast with the case of triblock copolymers, which were previously shown to provide good stability even at concentrations at which micelles do not form. Quartz crystal microbalance (QCM) experiments showed that the presence of the hydrophobic block in the structure of the polymer is important to ensure quantitative adsorption upon a gold surface and to limit desorption. We demonstrate that with an appropriate choice of polymer, the polymer/AuNP hybrids can also undergo filtration and freeze-drying without noticeable aggregation, which can be very convenient for further applications. Finally, preliminary studies of the cytotoxicity effect on fibroblast cells show that the polymer/AuNP hybrids were not cytotoxic. TEM micrographs on ultrathin sections of cells after incubation with the colloidal solutions show that the nanoparticles were internalized into the cells, conserving their initial size and shape.

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Micrometastases of Bone Marrow in Localized Prostate Cancer: Correlation With Established Risk Factors

Abstract: We assume the presence of epithelial cells in bone marrow to be an independent parameter, the clinical importance of which must be substantiated by further studies.

Cited by 46 publications

References 18 publications

Detection of tumor‐specific DNA in blood and bone marrow plasma from patients with prostate cancer

Detection of tumor‐specific DNA in blood and bone marrow plasma from patients with prostate cancer

Clinical Approaches to Osseous Metastases in Prostate Cancer

A Simple Protocol to Stabilize Gold Nanoparticles using Amphiphilic Block Copolymers: Stability Studies and Viable Cellular Uptake

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