Cancer stem cells: Models and concepts. Annu Rev Med ; Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Cancer Res ; Cancer stem cells: A review of potential clinical applications. Arch Pathol Lab Med ; A primitive hematopoietic cell is the target for the leukemic transformation in human philadelphia-positive acute lymphoblastic leukemia. Normal and leukemic hematopoiesis: Are leukemias a stem cell disorder or a reacquisition of stem cell characteristics?
A self-renewal program controls the expansion of genetically unstable cancer stem cells in pluripotent stem cell-derived tumors.
Cancer stem cell theory and emerging clinical application | RCSI Student Medical Journal
Stem Cells ; Cancer stem cells: Impact, heterogeneity, and uncertainty. Cancer Cell ; Tumor stroma and regulation of cancer development. Annu Rev Pathol ; Clarke MF, Fuller M. Stem cells and cancer: Two faces of eve.
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On Cancer: Stem Cell Biology
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Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol ; Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells.
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Oral Oncol ; Tumor growth need not be driven by rare cancer stem cells. Review: Biological relevance of disseminated tumor cells in cancer patients. Int J Cancer ; Dave B, Chang J. Treatment resistance in stem cells and breast cancer. J Mammary Gland Biol Neoplasia ; However, when I started as a cancer researcher at the Department of Zoophysiology in , the cancer survival rate was much worse. Thus, a lot has happened but there is still much to do. Today we know that a cancer is a clump of heterogeneous cells meaning that the cancer cells of a tumour are different. There seems to be different degrees of aggressiveness in the different cancer cells.
It has been hypothesized that the most aggressive cancer cells are resistant towards the chemotherapeutic drugs used today and also towards radiation. These very aggressive cells have been termed cancer stem cells CSCs because they have some properties that resemble them to normal stem cells, such as self-renewal and differentiation.
CSCs were first found in leukaemia and have subsequently been found in solid tumours of the breast, pancreas, ovary, prostate, ovaries and brain. A new generation of thinking in cancer treatment focuses on attacking the roots of cancer, the CSCs. Firstly, we are investigating the effect of new potential chemotherapeutic drugs on the CSC population of breast cancer cell lines but also of pancreas, ovarian and prostate cancer cell lines.
Together with Doc. Daniel Strand at the Center for Chemistry and Chemical Engineering, Department of Chemistry, Lund University, we are investigating the potency and selectivity of salinomycin and chemically modified salinomycin derivatives on CSCs. In another project together with Prof. PhD students are involved in all of these projects. Secondly, in the process of investigating the selectivity and potency of these compounds against CSCs we are also trying to understand the biology of CSCs by trying to deduce the mechanism of action of the compounds.
We are using different kinds of methods to study cell proliferation and cell cycle kinetics, differentiation and cell death of CSCs isolated using flow cytometry and magnetic bead separation. Flow cytometry is a method we use a lot in applications of cell identity and function. Western blot is used to elucidate molecular pathways involved in the responses. We are using a new microscopic technique called phase holographic imaging to characterize CSCs non-invasively.https://europeschool.com.ua/profiles/besyzasa/pajas-de-chicas.php
Cancer Stem Cells
As experimental model systems we use cells growing in culture. According to some views, much focus the past 50 years has been devoted to agents that de-bulk tumors but do not remove the source of the problem, not unlike pruning trees rather than eliminating their roots — the tree will grow back bigger and stronger than before.
Even early chemotherapeutics, as crude as nitrogen mustards, efficiently decrease tumor size. A common problem with such treatments is rapid and aggressive return of the disease, often in a form unresponsive to further treatment. A new generation of thinking in cancer treatment focuses on attacking the roots of cancer, the cancer stem cells CSCs.
CSCs are characterized by the ability of self-renewal, as well as the ability to spawn differentiated progeny non-CSCs. A consequence of this unresponsiveness, in part driven by resistance and drug uptake problems, is that chemotherapy imposes a strong selection for CSC survival. CSCs have been found across several cancer types including breast, pancreas, ovary, prostate cancer, and more recently leukemia. Small molecules selectively targeting CSCs constitute a hereto-unexploited opportunity for prevention of cancer recurrence and metastasis, and imply opportunities in widening the range of useful chemotherapeutic agents.
A report by Gupta, Weinberg and co-workers details the seminal find that salinomycin SA , selectively reduces the number of breast CSCs over control cells. Specifically, SA reduced the proportion of breast CSCs in mice, two orders of magnitude more efficiently than clinically used paclitaxel.
In , SA entered preliminary clinical trials. With its somewhat limited selectivity and an origin as a natural ionophore antibiotic, SA is unlikely to be an ideal candidate for clinical use in cancer treatment. We have therefore initiated an interdisciplinary program that aims to develop novel and superior structures for eradicating CSCs using a SA-informed approach. The synthesis driven approach that forms the basis for this proposal removes the limitation of studying only what is available or known SA and enables the study of unique designed structures SA analogs.
In a biological setting, the access to unique designed structures enables new ways of thinking about investigating the mechanisms through which SA selectively targets the CSC population. Skip to main content. Genetics of Sex Differences People Research projects Evolutionary diversification and the genetics of speciation Evolution of sex chromosomes Female-limited X-chromosome evolution in Drosophila Genotype-by-environment effects on sperm traits Intralocus sexual conflict in a hermaphrodite Genetics: Telomeres and Telomerase People Molecular genetics of telomeres and telomerase Life History and Functional Ecology People Research projects Body temperature regulation Effects of telomere dynamics and telomerase activity on life history tradeoffs Energetic adaptations in wintering passerines Immune function as a driver of variation in stopover ecology and behaviour Immune function as physiological mechanism of carry-over effects Incubation and embryo development Life history of owls Maternal effects Metabolic constraints on the evolution of life history strategies Partial migration in blue tits Should I stay or should I go?
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