Dataset Information

Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients.

ABSTRACT:

Background

Cancer stem cells (CSCs) are epithelial tumor cells that express CD44(+)CD24(-/lo). CSCs can be further divided into those that have aldehyde dehydrogenase (ALDH) activity (Aldefluor(+)) and those that do not. We hypothesized that if CSCs are responsible for tumor dissemination, their presence in bone marrow (BM) would be prognostic in early stages of breast cancer (EBC) patients.

Patients and methods

BM aspirates were collected at the time of surgery from 108 patients with EBC. BM was analyzed for CSCs and ALDH activity by flow cytometry. Overall survival and disease-free survival (DFS) were calculated from the date of diagnosis and analyzed with Kaplan-Meier survival plots. Cox multivariate proportional hazards model was also carried out.

Results

Patients with CSCs in BM had a hazard ratio (HR) of 8.8 for DFS (P = 0.002); patients with Aldefluor(+) CSCs had a HR of 5.9 (P = 0.052) for DFS. All deceased patients (n = 7) had CSCs in BM. In multivariate analysis, the presence of CSCs in BM was a prognostic factor of DFS (HR = 15.8, P = 0.017).

Conclusions

The presence of BM metastasis is correlated with CSCs and these CSCs irrespective of ALDH activity are an independent adverse prognostic factor in EBC patients.

SUBMITTER: Giordano A

PROVIDER: S-EPMC3784333 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients.

Giordano A A Gao H H Cohen E N EN Anfossi S S Khoury J J Hess K K Krishnamurthy S S Tin S S Cristofanilli M M Hortobagyi G N GN Woodward W A WA Lucci A A Reuben J M JM

Annals of oncology : official journal of the European Society for Medical Oncology 20130624 10

<h4>Background</h4>Cancer stem cells (CSCs) are epithelial tumor cells that express CD44(+)CD24(-/lo). CSCs can be further divided into those that have aldehyde dehydrogenase (ALDH) activity (Aldefluor(+)) and those that do not. We hypothesized that if CSCs are responsible for tumor dissemination, their presence in bone marrow (BM) would be prognostic in early stages of breast cancer (EBC) patients.<h4>Patients and methods</h4>BM aspirates were collected at the time of surgery from 108 patients ...[more]

PMID: 23798614

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Project description:BackgroundPreclinical studies suggest that stem cells may be a valuable therapeutic tool in amyotrophic lateral sclerosis (ALS). As it has been demonstrated that there are molecular changes at the end-plate during the early stages of motorneuron degeneration in animal models, we hypothesize that the local effect of this stem cell delivery method could slow the progressive loss of motor units (MUs) in ALS patients.MethodsWe designed a Phase I/II clinical trial to study the safety of intramuscularly implanting autologous bone marrow mononuclear cells (BMMCs), including stem cells, in ALS patients and their possible effects on the MU of the tibialis anterior (TA) muscle. Twenty-two patients participated in a randomized, double-blind, placebo-controlled trial that consisted of a baseline visit followed by one intramuscular injection of BMNCs, follow-up visits at 30, 90, 180, and 360 days, and an additional year of clinical follow-up. In each patient, one TA muscle was injected with a single dose of BMMCs while the contralateral muscle was given a placebo; the sides were selected randomly. All visits included a complete EMG study of both TA muscles.ResultsOur results show that (1) the intramuscular injection of BMMCs is a safe procedure; (2) ALS patients show heterogeneities in the degree of TA injury; (3) a comparison of placebo-injected muscles with BMMC-injected muscles showed significant differences in only one parameter, the D50 index used to quantify the Compound Muscle Action Potential (CMAP) scan curve. This parameter was higher in the BMMC-injected TA muscle at both 90 days (placebo side: 29.55 ± 2.89, n = 20; experimental side: 39.25 ± 3.21, n = 20; p < 0.01) and 180 days (placebo side: 29.35 ± 3.29, n = 17; experimental side: 41.24 ± 3.34, n = 17; p < 0.01).ConclusionThis procedure had no effect on the TA muscle MU properties, with the exception of the D50 index. Finding differences in just this index supports the fact that it may be much more sensitive than other electrophysiological parameters when studying treatment effects. Given the low number of patients and their heterogeneity, these results justify exploring the efficacy of this procedure in further patients and other muscles, through Phase II trials.Clinical trial registrationwww.clinicaltrials.gov (identifier NCT02286011); EudraCT number 2011-004801-25.

Dataset Information

Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients.

Background

Patients and methods

Results

Conclusions

Publications

Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients.

Similar Datasets

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