Regulation of Drug Sensitivity in Cultures of the Blast Stem Cells of Acute Myeloblastic Leukemia

2015 ◽  
pp. 137-147
Author(s):  
E. A. McCulloch
Keyword(s):  
Stem Cells ◽  
Drug Sensitivity ◽  
Acute Myeloblastic Leukemia

scholarly journals HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property in an NFκB-dependent way

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Wenxiang Wang ◽  
Yuxia Gao ◽  
Jing Hai ◽  
Jing Yang ◽  
Shufeng Duan
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Drug Sensitivity ◽  
Ovarian Cancer Cells ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Ovarian Cancer Stem Cells

Abstract Increasing evidence shows that cancer stem cells are responsible for drug resistance and relapse of tumors. In breast cancer, human epidermal growth factor receptor 2 (HER2) induces Herceptin resistance by inducing cancer stem cells. In the present study, we explored the effect of HER2 on cancer stem cells induction and drug sensitivity of ovarian cancer cell lines. First, we found that HER2 overexpression (HER2 OE) induced, while HER2 knockdown (HER2 KD) decreased CD44+/CD24− population. Consistently, HER2 expression was closely correlated with the sphere formation efficiency (SFE) of ovarian cancer cells. Second, we found that NFκB inhibition by specific inhibitor JSH23 or siRNA targetting subunit p65 dramatically impaired the induction of ovarian cancer stem cells by HER2, indicating that NFκB mediated HER2-induced ovarian cancer stem cells. Third, we found that HER2 KD significantly attenuated the tumorigenicity of ovarian cancer cells. Further, we found that HER2 inhibition increased drastically the sensitivity of ovarian cancer cells to doxorubicin (DOX) or paclitaxel (PTX). Finally, we examined the correlation between HER2 status and stem cell-related genes expression in human ovarian tumor tissues, and found that expressions of OCT4, COX2, and Nanog were higher in HER2 positive tumors than in HER2 negative tumors. Consistently, the 5-year tumor-free survival rate of HER2 positive patients was dramatically lower than HER2 negative patients. Taken together, our data indicate that HER2 decreases drug sensitivity of ovarian cancer cells via inducing stem cell-like property.

scholarly journals Sensitivity to 5-azacytidine of blast progenitors in acute myeloblastic leukemia

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 553-559 ◽  
Author(s):  
C Wang ◽  
EA McCulloch
Keyword(s):  
Stem Cells ◽  
Colony Formation ◽  
Acute Myeloblastic Leukemia ◽  
Survival Curves ◽  
Cellular Mechanisms ◽  
Self Renewal ◽  
Additional Advantage ◽  
Increased Sensitivity ◽  
The Difference ◽  
Preclinical Screening

Abstract In a previous study, we showed that the blast stem cells of acute myeloblastic leukemia (AML) were more sensitive to cytosine arabinoside (ara-C) when growing in suspension culture than during colony formation in methylcellulose. We suggested that the difference might be explained by considering the cellular mechanisms responsible for growth in suspension and colony formation. In the former, the clonogenic cells increase in number (self-renewal); in the latter, most of the divisions are terminal. The increased sensitivity to ara-C in suspension might then be attributed to its ability to inhibit self-renewal to a greater degree than cell division generally. A test of this hypothesis would be to compare the survival curves in suspension and in methylcellulose using a drug that spared or stimulated self-renewal. Such an agent is 5- azacytidine (5-aza) and has the additional advantage that its analogue, 6-azacytidine (6-aza) has no effect on self renewal. The data supported the hypothesis, since clonogenic AML blasts were much less sensitive to 5-aza in suspension than in methylcellulose. The effect of 6-aza, while qualitatively similar, was much less marked. Controls showed that the difference in survival curves could not be explained on a kinetic basis or by the secretion of growth factors by 5-aza-treated cells. We suggest that a comparison of the effects of drugs in suspension and in methylcellulose may be useful in preclinical screening of putative anti- AML compounds.

scholarly journals Intratumoral Heterogeneity and Longitudinal Changes in Gene Expression Predict Differential Drug Sensitivity in Newly Diagnosed and Recurrent Glioblastoma

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 520 ◽  
Author(s):  
Ella L. Kim ◽  
Maxim Sorokin ◽  
Sven Rainer Kantelhardt ◽  
Darius Kalasauskas ◽  
Bettina Sprang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Drug Sensitivity ◽  
Recurrent Glioblastoma ◽  
Intratumor Heterogeneity ◽  
Glioma Stem Cells ◽  
Newly Diagnosed ◽  
Glioblastoma Stem Cells ◽  
Longitudinal Changes ◽  
Glioblastoma Recurrence

Background: Inevitable recurrence after radiochemotherapy is the major problem in the treatment of glioblastoma, the most prevalent type of adult brain malignancy. Glioblastomas are notorious for a high degree of intratumor heterogeneity manifest through a diversity of cell types and molecular patterns. The current paradigm of understanding glioblastoma recurrence is that cytotoxic therapy fails to target effectively glioma stem cells. Recent advances indicate that therapy-driven molecular evolution is a fundamental trait associated with glioblastoma recurrence. There is a growing body of evidence indicating that intratumor heterogeneity, longitudinal changes in molecular biomarkers and specific impacts of glioma stem cells need to be taken into consideration in order to increase the accuracy of molecular diagnostics still relying on readouts obtained from a single tumor specimen. Methods: This study integrates a multisampling strategy, longitudinal approach and complementary transcriptomic investigations in order to identify transcriptomic traits of recurrent glioblastoma in whole-tissue specimens of glioblastoma or glioblastoma stem cells. In this study, 128 tissue samples of 44 tumors including 23 first diagnosed, 19 recurrent and 2 secondary recurrent glioblastomas were analyzed along with 27 primary cultures of glioblastoma stem cells by RNA sequencing. A novel algorithm was used to quantify longitudinal changes in pathway activities and model efficacy of anti-cancer drugs based on gene expression data. Results: Our study reveals that intratumor heterogeneity of gene expression patterns is a fundamental characteristic of not only newly diagnosed but also recurrent glioblastomas. Evidence is provided that glioblastoma stem cells recapitulate intratumor heterogeneity, longitudinal transcriptomic changes and drug sensitivity patterns associated with the state of recurrence. Conclusions: Our results provide a transcriptional rationale for the lack of significant therapeutic benefit from temozolomide in patients with recurrent glioblastoma. Our findings imply that the spectrum of potentially effective drugs is likely to differ between newly diagnosed and recurrent glioblastomas and underscore the merits of glioblastoma stem cells as prognostic models for identifying alternative drugs and predicting drug response in recurrent glioblastoma. With the majority of recurrent glioblastomas being inoperable, glioblastoma stem cell models provide the means of compensating for the limited availability of recurrent glioblastoma specimens.

Roles of miRNAs in breast cancer stem cells, drug sensitivity, and spontaneous metastases in orthotopic human-in-mouse models.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 1082-1082 ◽  
Author(s):  
H. Liu ◽  
J. Bockhorn ◽  
R. Dalton ◽  
M. E. Dolan ◽  
C. M. Perou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Mouse Models ◽  
Drug Sensitivity ◽  
Breast Cancer Stem Cells

scholarly journals The heritable nature of clonal characteristics in acute myeloblastic leukemia

Blood ◽  
1981 ◽  
Vol 58 (1) ◽  
pp. 105-109
Author(s):  
EA McCulloch ◽  
RN Buick ◽  
JE Curtis ◽  
HA Messner ◽  
JS Senn
Keyword(s):  
Cytosine Arabinoside ◽  
Drug Sensitivity ◽  
Blast Cell ◽  
Acute Myeloblastic Leukemia ◽  
Chemotherapeutic Drugs ◽  
Self Renewal

Marked patient-to-patient variation is observed when blood or marrow from AML patients is examined using colony methods in culture. Concentrations of the progenitors of colonies change with time during the course of the disease. We asked whether blast progenitor properties were more stable. We measured blast cell self-renewal and drug sensitivity (adriamycin and cytosine arabinoside) repeatedly in the courses of seven AML patients. These properties were found to be stable or slowly evolving. We conclude that capacity for renewal and sensitivities to certain chemotherapeutic drugs are heritable characteristics in leukemic clones.

DICER1 gene and miRNA dysregulation in mesenchymal stem cells of patients with myelodysplastic syndrome and acute myeloblastic leukemia

2017 ◽  
Vol 63 ◽  
pp. 62-71 ◽  
Author(s):  
Hakan Ozdogan ◽  
Bala Gur Dedeoglu ◽  
Yasemin Oztemur Islakoglu ◽  
Alp Aydos ◽  
Sevil Kose ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Myelodysplastic Syndrome ◽  
Acute Myeloblastic Leukemia

Ovarian cancer stem cells (OCSCs): Therapy for advanced chemoresistant ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16542-e16542
Author(s):  
Prattusha Sengupta ◽  
Sudeshna Gangopadhyay ◽  
Saubhik Sengupta ◽  
Ujjal Kanti Ray ◽  
Ashis Mukhopadhyay
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Drug Sensitivity ◽  
Ex Vivo ◽  
Cancer Site ◽  
Chemotherapeutic Drugs ◽  
Ovarian Cancer Stem Cells

e16542 Background: Invasive and mesenchymal property of Ovarian Cancer Stem Cells (OCSCs)with CD44+/CD133+has made them promising target for targeted treatment. Chemotherapy treatment uses medicine to weaken and destroy cancer cells in body, including cells at original cancer site and any cancer cells that may have spread to another part of body. Chemotherapeutic drugs for advanced chemo-resistant ovarian cancer are yet to be well defined. Combination of drugs is also not fully known. Our objective is to define chemotherapeutic drugs and its action in OCSC which is the major reason for chemo resistance in case of advanced chemo-resistant ovarian cancer patients. Methods: A total of twenty biopsy proven advanced chemo-resistant ovarian cancer patients in the age group of 22-36 years were selected randomly and tested for CD44/CD133 via flow cytometry. Isolated OCSCs were cultured for ex vivo drug sensitivity towards platinum, anthracyclin, docetaxel, rapamycin, sunitinib, sorafenib and gefitinib. Correlation was drawn between cell differentiations, % of stem cells and drug response. Accordingly chemotherapy was designed for a particular patient. Results: We detected OCSCs in 90% of cases. Among positive samples ex vivo drug sensitivity was seen in 4(20%) to rapamycin, 1(5%) to sunitinib, 1(5%) to sorafenib, 1(5%) to gefitinib, 3(15%) to platinum, 1(5%) to anthracyclin, 1(5%) to docetaxel and rest showed no sensitivity to any drug. Conclusions: Thus primary aim to target OCSCs at onset of tumors in ovarian cancer patients to control metastasis and relapse of disease was somewhat obtained. Most interestingly, we found that the chemotherapeutic drugs which were less prescribed for ovarian cancer showed greater sensitivity in comparison to the widely used ones. We like to do animal model study followed by phase I, II and III human clinical trial to establish our hypothesis for better management of chemo-resistant ovarian cancer.

A rapid assay for drug sensitivity of glioblastoma stem cells

2007 ◽  
Vol 358 (3) ◽  
pp. 908-913 ◽  
Author(s):  
Hilah Gal ◽  
Arik Makovitzki ◽  
Ninette Amariglio ◽  
Gideon Rechavi ◽  
Zvi Ram ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Sensitivity ◽  
Glioblastoma Stem Cells ◽  
Rapid Assay
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