Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma

The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12–8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.

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Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma

Blood ◽

10.1182/blood.v77.8.1717.1717 ◽

1991 ◽

Vol 77 (8) ◽

pp. 1717-1722 ◽

Cited By ~ 340

Author(s):

RJ Berenson ◽

WI Bensinger ◽

RS Hill ◽

RG Andrews ◽

J Garcia-Lopez ◽

...

Keyword(s):

Breast Cancer ◽

Stage Iv ◽

In Vitro Assays ◽

Hematopoietic Progenitors ◽

Cd34 Antigen ◽

Stage Iv Breast Cancer ◽

Cd34 Cells ◽

Selection Of ◽

Marrow Cells

Abstract The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12–8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.

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BSCI-27. MELATONIN REDUCES MALIGNANCY OF BREAST CANCER BRAIN METASTATIC CELLS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.023 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i6-i6

Author(s):

Beatriz Fernandez Gil ◽

Katherine Rodriguez ◽

Paula Schiapparelli ◽

Carla Vazquez Ramos ◽

Germaine Escames ◽

...

Keyword(s):

Breast Cancer ◽

Stage Iv ◽

Metastatic Tumor ◽

Breast Cancer Cell Lines ◽

Small Subset ◽

Tumor Initiating Cells ◽

Stage Iv Breast Cancer ◽

Breast Cancer Brain Metastasis ◽

The Brain

Abstract Around fifteen to thirty percent of stage IV breast cancer metastasizes to the brain, severely decreasing the quality of life of these patients by causing neurological decline and eventually death. In metastatic cancers there is a small subset of cells in the primary tumor bulk called Metastatic Tumor Initiating Cells (MTICs) which are able to escape and produce a niche establishment at distal sites where they can quickly become resistant to surgery and radiation. Melatonin has shown an inhibitory role in the viability and invasiveness of breast cancer and in modulating the expression of proteins related to Breast Cancer Stem Cells (BCSCs). These findings suggest its potential anti-metastatic role in different breast cancer cell lines. In this study we aimed to evaluate the effects of melatonin treatment in vitro for breast cancer brain metastasis. The cell line MDA-BT was originally obtained from MDA-MB-231, passed through the rat’s heart and then isolated once engrafted as a tumor in the brain. After a dose response assay, cells were treated with melatonin at doses of 1500 and 3000 µM for 48hrs. Clonogenic assay, MTT, as well as a stem cell signature through RT-qPCR, including CD44, CD24 and ALDH1 markers, were performed to evaluate the malignancy of the MTICs. The results showed that melatonin at high doses impacts morphology, declines viability, reduces colony formation ability, and decreases stemness in MDA-BT cells. Therefore, our findings highlight melatonin as a relevant therapeutic candidate to target breast cancer brain metastases.

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Precursors of colony-forming cells in humans can be distinguished from colony-forming cells by expression of the CD33 and CD34 antigens and light scatter properties.

Journal of Experimental Medicine ◽

10.1084/jem.169.5.1721 ◽

1989 ◽

Vol 169 (5) ◽

pp. 1721-1731 ◽

Cited By ~ 240

Author(s):

R G Andrews ◽

J W Singer ◽

I D Bernstein

Keyword(s):

Light Scattering ◽

Stromal Cells ◽

Surface Antigens ◽

Marrow Stromal Cells ◽

Light Scatter ◽

Hematopoietic Progenitors ◽

Cell Surface Antigens ◽

Cd34 Cells ◽

Marrow Cells

We determined whether human marrow cells that directly form colonies in vitro could be distinguished from cells that generate or become CFC only after LTMC in the presence of irradiated marrow stromal cells. In previous studies, an anti-CD33 antibody, L4F3, and complement (C') were used to lyse nearly all CFC in marrow, and the remaining cells generated CFC in LTMC. In the present studies, marrow cells were treated with L4F3 + C' and the remaining CD33- cells were separated into CD34+ and CD34- populations and placed in LTMC. Only the CD34+ cells were found to generate significant numbers of CFC. To compare the CD33-CD34+ and CD33+CD34+ cells, we isolated each cell population using two-color FACS. Only LTMCs of the CD33-CD34+ cells generated CFC for greater than 5 wk. In contrast, cells that expressed both the CD33 and CD34 antigens, which contained most of the CFC, generated few CFC in LTMC. Fractionation of marrow cells based on right angle and forward light scattering suggested that precursors for CFC have low right angle and low forward light scattering properties. The CD33-CD34+ marrow cells were therefore further fractionated based on light scatter characteristics. Cells with low right angle and low forward light scatter formed few or no colonies on direct culture, yet generated greater numbers of CFC after 4 wk of LTMC than did cells with low right angle and high forward light scatter. Most (87-98%) CFC generated in the LTMCs that were initiated with CD33-CD34+ cells were found to express the CD33 antigen. Thus, hematopoietic progenitors with differing proliferative and differentiative potentials can be directly separated on the basis of their expression of CD33 and CD34 cell surface antigens and their light scatter properties.

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Discordant Results Obtained for Different Methods of HER-2/Neu Testing in Breast Cancer – A Question of Standardization, Automation and Timing

The International Journal of Biological Markers ◽

10.1177/172460080401900101 ◽

2004 ◽

Vol 19 (1) ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

D. Lüftner ◽

P. Henschke ◽

A. Kafka ◽

I. Anagnostopoulos ◽

K. Wiechen ◽

...

Keyword(s):

Breast Cancer ◽

Stage Iv ◽

Breast Cancer Patients ◽

Trastuzumab Therapy ◽

Number Of Patients ◽

Stage Iv Breast Cancer ◽

Tumor Load ◽

Her 2 ◽

Selection Of

Background HER-2/neu positivity is required for the selection of stage IV breast cancer patients for trastuzumab therapy. We compared the results of the recommended immunohistochemistry (IHC) evaluation with the automated ACIS™ IHC system and with fluorescence in situ hybridization (FISH). These HER-2/neu tissue results were correlated with the serum HER-2/neu (sHER-2/neu) levels at the time of metastatic spread. Patients and Methods A total of 61 IHC slides from 30 patients were stained using the HercepTest™. HER-2/neu gene amplification was determined using the Ventana™ FISH assay. sHER-2/neu levels were measured with the Oncogene Science” ELISA kit. The concordance of HER-2/neu results was determined using the concordance index Kappa (κ). Results The best concordance between any IHC and FISH was found for the automated ACIS system (88.5%, κ=0.68, category “good”). The comparison between the manual interpretations and the automated IHC was categorized as “very good” (95.1%, κ=0.85). The median sHER-2/neu level of FISH positive patients was significantly higher (67 ng/mL) than that of FISH negative patients (17 ng/mL, p=0.018). The increase in HER-2/neu positivity comparing tissue to stage IV serum was statistically significant (p=0.001). Conclusions The concordance between conventional IHC and computerized analysis was very good. The number of patients with stage IV breast cancer with an elevated sHER-2/neu level was much higher than HER-2/neu positivity in tissue. This discrepancy is only partially explained by the influence of tumor load. Patients with an elevated sHER-2/neu level and no tissue overexpression should be considered for retesting of tissue or a new biopsy.

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