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Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors.

ABSTRACT: Bone marrow is a major homing site for circulating epithelial tumor cells. The present study was aimed to assess the proliferative capacity of occult metastatic cells in bone marrow of patients with operable solid tumors especially with regard to their clinical outcome. We obtained bone marrow aspirates from 153 patients with carcinomas of the prostate (n = 46), breast (n = 45), colon (n = 33), and kidney (n = 29). Most of the patients (87%) had primary disease with no clinical signs of overt metastases [tumor-node-metastasis (TNM)-stage UICC (Union Internationale Contre le Cancer) I-III]. After bone marrow was cultured for 21-102 days under special cell culture conditions, viable epithelial cells were detected by cytokeratin staining in 124 patients (81%). The cultured epithelial cells harbored Ki-ras2 mutations and numerical chromosomal aberrations. The highest median number of expanded tumor cells was observed in prostate cancer (2,619 per flask). There was a significant positive correlation between the number of expanded tumor cells and the UICC-stage of the patients (P = 0.03) or the presence of overt metastases (P = 0.04). Moreover, a strong expansion of tumor cells was correlated to an increased rate of cancer-related deaths (P = 0.007) and a reduced survival of the patients (P = 0.006). In conclusion, the majority of cancer patients have viable tumor cells in their bone marrow at primary tumor diagnosis, and the proliferative potential of these cells determines the clinical outcome.

SUBMITTER: Solakoglu O

PROVIDER: S-EPMC122350 | biostudies-literature | 2002 Feb

REPOSITORIES: biostudies-literature

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Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors.

Solakoglu Oender O Maierhofer Christine C Lahr Georgia G Breit Elisabeth E Scheunemann Peter P Heumos Isabella I Pichlmeier Uwe U Schlimok Gunter G Oberneder Ralph R Kollermann Manfred W MW Kollermann Jens J Speicher Michael R MR Pantel Klaus K

Proceedings of the National Academy of Sciences of the United States of America 20020201 4

Bone marrow is a major homing site for circulating epithelial tumor cells. The present study was aimed to assess the proliferative capacity of occult metastatic cells in bone marrow of patients with operable solid tumors especially with regard to their clinical outcome. We obtained bone marrow aspirates from 153 patients with carcinomas of the prostate (n = 46), breast (n = 45), colon (n = 33), and kidney (n = 29). Most of the patients (87%) had primary disease with no clinical signs of overt me ...[more]

PMID: 11854519

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Project description:The distribution of nanomedicines inside solid tumors is often restricted to perivascular areas, leaving most distal tumor cells out of reach. This partly explains modest patient benefit of many nanomedicines compared to their free-form counterparts. The objective for this study is to develop a mathematical model to quantitatively analyze this phenomenon and the influencing factors to such perivascular distribution and seek for effective strategies to alleviate this. A spatial tumor distribution model was firstly constructed to mimic the geometrical structure of tumor vessels and the surrounding tumor cells. This tumor model was further integrated with a systemic pharmacokinetics model for nanoparticles. A variety of factors on the tumor spatial distributions of nanomedicines were considered in the model. With the model, we quantified the effect of these influencing factors on tumor delivery efficacy (ID %), the magnitude of heterogeneous distribution (H index), and the effect of enhanced permeability and retention (EPR). In particularly, we compared the spatial distributions of the nanoparticles and the free payloads insides tumors. The model predicted high degrees of distributional heterogeneity for both nanoparticles and free payloads. The degree of heterogeneity and the influencing factors for free payloads were markedly different from those for nanoparticles. We found that nanoparticle diffusion coefficient was the most effective factor in reducing the nanoparticle H index but exerted moderate influence on the free payloads H index. The most effective factor in reducing the H index of free payload was payload diffusion coefficient. The factors that improved free payload distribution were closely associated with higher drug efficacy. In contrast, the factors that improved nanoparticle spatial distributions did not always confer improved anti-tumor efficacy of the delivered drug. These findings highlight the importance of assessing the heterogeneous free payload distribution in tumors for the development of effective nanomedicines.

Dataset Information

Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors.

Publications

Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors.

Similar Datasets

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