Effective removal of SCLC cells from human bone marrow. Use of four monoclonal antibodies and immunomagnetic beads

Myklebust, Arne T.; Pharo, Anne; Fodstad, Øystein

doi:10.1038/bjc.1993.246

Cited by 25 publications

(11 citation statements)

References 29 publications

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“…2,55 We have demonstrated in several studies a highly specific selection of carcinoma cells from BM mononuclear cells by the use of immunomagnetic beads coated with the MOC-31 monoclonal antibody. 7,8,10 The apparent conflicting data obtained from immunocytochemistry vs. the immunobead detection method may also depend on the notion that expression of cytokeratin antigens by breast carcinoma cells is occasionally lost during preparation of samples for the former analysis. 56 In the present study, we tested for possible expression of BM1 and BM4 by contaminating BM mesenchymal cells.…”

Section: Differential Display Analysis Of Immunoselected Breast Carcimentioning

confidence: 99%

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Differential display analysis of breast carcinoma cells enriched by immunomagnetic target cell selection: Gene expression profiles in bone marrow target cells

Ree

Engebraaten

Hovig

et al. 2001

Intl Journal of Cancer

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The red bone marrow (BM) is an important indicator organ of hematogenous micrometastatic spread of carcinomas. Characterization of biological properties specific for BM micrometastatic cells, however, is technically challenging due to the limited number of target cells usually available for the purpose. This report provides referrals to qualitative gene expression profiling of BM micrometastatic cells enriched by immunomagnetic selection. First, an experimental strategy was used to study regulatory mechanisms involved when BM micrometastatic cells colonize distant organs. The MA-11 cells, originating from BM micrometastases in a breast cancer patient clinically devoid of overt metastatic disease, were injected into immunodeficient rats. Metastatic MA-11 cells were subsequently immunoselected from the resulting in vivo lesions. The selected cell populations were compared to the injected cells by differential display analysis, and several genes possibly involved in tumor cell invasion and proliferation were confirmed as differentially expressed among the various MA-11 cell populations. A direct approach to qualitative gene expression profiling of BM micrometastatic cells was also explored. Carcinoma cells were immunoselected from BM and axillary lymph nodes obtained from breast cancer patients, and the isolated cell populations were compared by differential display analysis. Two candidate genes, identified as factors involved in cellular growth control, appeared as differentially expressed by the target cells from BM. Our study provides detailed information on how to combine an immunomagnetic selection procedure and differential display analysis to reveal gene expression profiles that may characterize BM micrometastatic cells. © 2002 Wiley-Liss, Inc. Key words: bone marrow; micrometastasis; breast cancer; immunomagnetic cell preparation; differential cloningClinical and experimental evidence suggests that epithelial tumor cells are able to disseminate to secondary organs at an early stage of primary tumor development. The red bone marrow (BM) compartment represents an important indicator organ of hematogenous micrometastatic spread of carcinomas. According to current concepts, however, disseminated tumor cells detected in the BM are not able to grow as distant metastatic lesions unless they possess certain biological characteristics, among which the ability of invasion into and proliferation within the target organ is considered highly significant. [1][2][3] The classical, experimental works on mechanisms of tumor metastasis demonstrated that only a small subset of cells within the parental population is capable of metastasizing 4 and that the cellular composition of secondary tumors differs from that of the primaries. 5 Subsequent reports introduced the concept of dynamic heterogeneity, which argues that although the metastatic phenotype is a genetically controlled trait, it is inherently unstable. 6 Indeed, cellular properties that are crucial for initiation of distant tumor growth may be obscured by the heterog...

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Section: Differential Display Analysis Of Immunoselected Breast Carcimentioning

confidence: 99%

“…2,[7][8][9][10][11][12] This rapid and simple procedure enables a sensitive and specific selection of the small number of target cells in BM aspirates and enrichment of tumor cells in tissue samples of clinical and experimental metastatic lesions.…”

mentioning

confidence: 99%

Differential display analysis of breast carcinoma cells enriched by immunomagnetic target cell selection: Gene expression profiles in bone marrow target cells

Ree

Engebraaten

Hovig

et al. 2001

Intl Journal of Cancer

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“…These patients with 'true LD' (i.e. with absence of immunoreactive tumour cells in BMA) may be suitable for novel therapeutic strategies, including high-dose chemotherapy, immunotherapy and targeted immunotherapy (Myklebust et al, 1993a(Myklebust et al, , 1993b. Further studies are in progress in our laboratory to confirm the role of immunocytochemistry of bone marrow among the prognostic factors already identified in large studies of SCLC patients.…”

Section: Discussionmentioning

confidence: 88%

“…Moreover, most staging protocols include BM assessment through morphological screening of mono-or bilateral core biopsies, aspiration clots or smears from iliac crests (Abrams et al, 1998). Many studies have addressed the detection of SCLC cells in bone marrow aspirates (BMA) by immunocytochemistry (Frew et al, 1986;Berendsen et al, 1988;Hay et al, 1988;Moss et al, 1988;Trillet et al, 1989;Leonard et al, 1990;Beiske et al, 1992;Skov et al, 1992;Myklebust et al, 1993aMyklebust et al, , 1993b, but the clinical relevance of this approach is still debated. Furthermore, few reports have investigated the relationship between BM involvement and prognosis (Leonard et al, 1990;Bucher et al, 1994;Pasini et al, 1994bPasini et al, , 1995Pasini et al, , 1998, but no study has systematically assessed the effects of treatment on marrow contamination in sequential BMA.…”

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confidence: 99%

Immunocytochemical assessment of bone marrow aspirates for monitoring response to chemotherapy in small-cell lung cancer patients

Pelosi

Pasini

Ottensmeier³

et al. 1999

Br J Cancer

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Summary Recent reports have suggested that tumour cell immunodetection in bone marrow of small-cell lung cancer patients is by far more frequent than found cytohistologically and may have clinical relevance. This study evaluates primarily the efficacy of chemotherapy as method of in vivo purging, but also the relationship of marrow involvement with survival. A total of 112 bone marrow aspirates from 30 chemo-naïve patients were stained twice using anti-NCAM antibodies, first at diagnosis and then after chemotherapy (24 patients) or at disease progression (six patients). Marrow contamination was associated with lower survival (P = 0.002), and was also detected in 7/17 patients conventionally staged as having limited disease. At multivariate analysis, marrow involvement was an independent factor of unfavourable prognosis (P = 0.033). The amount of tumour contamination, before and after chemotherapy, remained unchanged also in responders and even in the subset of patients with apparent limited disease. Following chemotherapy, bone marrow became tumour negative only in 25% of initially positive responders and in none of non-responders. Our results indicate that (i) chemotherapy is not effective in purging bone marrow even in chemo-responsive patients and (ii) a subset of patients with limited disease and negative bone marrow aspirates might have a more favourable prognosis.

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“…Patients with solid tumors such as lung cancer [23], breast cancer [8], testicular cancer [36], or neuroblastoma [21] are increasingly being treated by this procedure. Patients suffering from leukemia undergo ABMT/PBSCT in some cases [37,39], especially if no sibling or unrelated donor with sufficient histocompatibility is available for allogeneic bone marrow transplantation [10].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the composition of bone marrow prior to and following autologous BMT and PBSCT by magnetic resonance

Schick

Einsele

Weiss

et al. 1996

Annals of Hematology

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Lumbar bone marrow was assessed by means of magnetic resonance (MR) in 23 examinations of eight patients who underwent autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT). Various imaging and spectroscopic techniques were applied for measurements carried out prior to conditioning for ABMT/PBSCT and in the course of reconstitution and correlated with clinical and blood chemistry data in these patients. The signal intensity from lumbar bone marrow was determined in T1-weighted and water- and fat-selective MR images. The distribution of the magnetic field was demonstrated by a field-mapping method. Localized proton spectroscopy was performed from volume elements of 2 ml located in the central region of vertebral bodies in order to evaluate the fraction of the water signals, the transverse relaxation times T2 of the signals from water and lipids, and the line widths of the spectral signals. Regions of bone marrow after inflammatory conditions or intensive irradiation are shown to be not involved in marrow reconstitution. Additional information about marrow composition was obtained by the magnetic field mapping and by the line widths in the spectra. Considerable alterations of the amount of paramagnetic hemosiderin were revealed following transplantation. Patients with low water signal and strong local inhomogeneities of the magnetic field in the marrow prior to transplantation had a delayed hematopoietic reconstitution compared with the patients lacking these MR features.

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Effective removal of SCLC cells from human bone marrow. Use of four monoclonal antibodies and immunomagnetic beads

Cited by 25 publications

References 29 publications

Differential display analysis of breast carcinoma cells enriched by immunomagnetic target cell selection: Gene expression profiles in bone marrow target cells

Differential display analysis of breast carcinoma cells enriched by immunomagnetic target cell selection: Gene expression profiles in bone marrow target cells

Immunocytochemical assessment of bone marrow aspirates for monitoring response to chemotherapy in small-cell lung cancer patients

Assessment of the composition of bone marrow prior to and following autologous BMT and PBSCT by magnetic resonance

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