Log in

Relevant bibliographies by topics / Neoplastic Stem Cells / Journal articles

To see the other types of publications on this topic, follow the link: Neoplastic Stem Cells.

Journal articles on the topic 'Neoplastic Stem Cells'

Author: Grafiati

Published: 4 June 2021

Last updated: 30 July 2024

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'Neoplastic Stem Cells.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

McCracken, Melissa N., Benson M. George, Kevin S. Kao, Kristopher D. Marjon, Tal Raveh, and Irving L. Weissman. "Normal and Neoplastic Stem Cells." Cold Spring Harbor Symposia on Quantitative Biology 81 (2016): 1–9. http://dx.doi.org/10.1101/sqb.2016.81.030965.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Weissman, Irving. "Normal and neoplastic stem cells." Experimental Hematology 43, no. 9 (September 2015): S27. http://dx.doi.org/10.1016/j.exphem.2015.06.015.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Cherniack, E. Paul, Sahithi Chekuri, and Heather F. Lee. "Potential Non-neoplastic Applications for Polyphenols in Stem Cell Utilization." Current Drug Targets 20, no. 3 (January 25, 2019): 347–53. http://dx.doi.org/10.2174/1389450119666180731092453.

Full text

Abstract:

While polyphenols may have important effects on pluripotential stem cells that make them noteworthy as potential antineoplastic agents, their action on stem cells may portend other health benefits, such as treatments for cardiovascular and neurocognitive disorders. Resveratrol, the beststudied polyphenol, has been found to enable stem cells to differentiate into cardiomyocytes, neurons, osteocytes, and pancreatic beta cells, as well as facilitating augmentation of stem cell populations and protecting them from toxic injury. Curcumin protects mesenchymal stem cells from toxicity, and prevents them from facilitating chondrocytic hypertrophy. Quercetin enabled osteocytic and pancreatic beta cell differentiation, and protected neuronal stem cells from injury. Epigallocatechin gallate prevented damage to osteocyte precursors and averted differentiation into undesirable adipocytes. Genistein facilitated osteogenesis while preventing adipogenesis. Several other polyphenols, daidzein, caffeic and chlorogenic acid, kaempferol, and piceatannol, protect stems cells from reactive oxygen species and foster stem cells differentiation away from adipocytic and toward osteocytic lineages. Further research should better elucidate the pharmacokinetic profiles of each polyphenol, explore novel delivery systems, and expand investigation beyond rodent models to additional species.

APA, Harvard, Vancouver, ISO, and other styles

4

Laurenzana, Ilaria, Daniela Lamorte, Stefania Trino, Luciana De Luca, Concetta Ambrosino, Pietro Zoppoli, Vitalba Ruggieri, et al. "Extracellular Vesicles: A New Prospective in Crosstalk between Microenvironment and Stem Cells in Hematological Malignancies." Stem Cells International 2018 (May 27, 2018): 1–11. http://dx.doi.org/10.1155/2018/9863194.

Full text

Abstract:

The bone marrow (BM) microenvironment in hematological malignancies (HMs) comprises heterogeneous populations of neoplastic and nonneoplastic cells. Cancer stem cells (CSCs), neoplastic cells, hematopoietic stem cells (HSCs), and mesenchymal stromal/stem cells (MSCs) are all components of this microenvironment. CSCs are the HM initiators and are associated with neoplastic growth and drug resistance, while HSCs are able to reconstitute the entire hematopoietic system; finally, MSCs actively support hematopoiesis. In some HMs, CSCs and neoplastic cells compromise the normal development of HSCs and perturb BM-MSCs. In response, “reprogrammed” MSCs generate a favorable environment to support neoplastic cells. Extracellular vesicles (EVs) are an important cell-to-cell communication type in physiological and pathological conditions. In particular, in HMs, EV secretion participates to unidirectional and bidirectional interactions between neoplastic cells and BM cells. The transfer of EV molecular cargo triggers different responses in target cells; in particular, malignant EVs modify the BM environment in favor of neoplastic cells at the expense of normal HSCs, by interfering with antineoplastic immunity and participating in resistance to treatment. Here, we review the role of EVs in BM cell communication in physiological conditions and in HMs, focusing on the effects of BM niche EVs on HSCs and MSCs.

APA, Harvard, Vancouver, ISO, and other styles

5

Jandial, Rahul, Dawn J. Waters, and Mike Y. Chen. "Cancer Stem Cells Can Arise From Differentiated Neoplastic Cells." Neurosurgery 69, no. 2 (August 2011): N22. http://dx.doi.org/10.1227/01.neu.0000400017.39272.62.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Fan, Xing, and Charles G. Eberhart. "Medulloblastoma Stem Cells." Journal of Clinical Oncology 26, no. 17 (June 10, 2008): 2821–27. http://dx.doi.org/10.1200/jco.2007.15.2264.

Full text

Abstract:

Medulloblastoma and other embronal brain tumors are similar in appearance and differentiation potential to neural stem and progenitor cells. Expression studies performed using human tumor samples, as well as the analysis of murine transgenic models, suggest that both multipotent cerebellar stem cells and lineage-restricted progenitors of the external germinal layer can be transformed into medulloblastoma by genetic alterations. These molecular changes frequently involve constitutive activation of signaling pathways such as Wnt, Hedgehog, and Notch, which play a key role in non-neoplastic neural stem cells. Pharmacologic blockade of the Hedgehog and Notch pathways suppresses the growth of medulloblastoma in culture and in vivo and may prove effective in targeting the small cancer stem-cell subpopulation required for tumor initiation and long-term propagation.

APA, Harvard, Vancouver, ISO, and other styles

7

Schulenburg, Axel, Kira Brämswig, Harald Herrmann, Heidrun Karlic, Irina Mirkina, Rainer Hubmann, Sylvia Laffer, et al. "Neoplastic stem cells: Current concepts and clinical perspectives." Critical Reviews in Oncology/Hematology 76, no. 2 (November 2010): 79–98. http://dx.doi.org/10.1016/j.critrevonc.2010.01.001.

Full text

APA, Harvard, Vancouver, ISO, and other styles

8

Ruch, Randall. "Connexin43 Suppresses Lung Cancer Stem Cells." Cancers 11, no. 2 (February 2, 2019): 175. http://dx.doi.org/10.3390/cancers11020175.

Full text

Abstract:

Alterations in gap junctions and their protein components, connexins, have been associated with neoplastic transformation and drug resistance, and more recently have been shown to play important roles in cancer stem cells (CSCs). However, there is less knowledge of connexins and gap junctions in lung CSCs. To address this, Connexin43 (Cx43), the major human lung epithelial gap junction protein, was expressed ectopically in poorly expressing National Cancer Institute-125 (NCI-H125) metastatic human lung adenocarcinoma cells, and phenotypic characteristics of malignant cells and abundance of CSCs were evaluated. The ectopic expression of Cx43 resulted in the formation of functional gap junctions; a more epithelial morphology; reduced proliferation, invasion, colony formation, tumorsphere formation, pluripotency marker expression, and percentage of aldehyde dehydrogenase (ALDH)-positive cells; and increased cisplatin sensitivity. Similarly, in NCI-H522 (human lung adenocarcinoma) and NCI-H661 (human lung large cell carcinoma) cell lines, which express Cx43 and functional gap junctions endogenously, the Cx43 content was lower in tumorspheres and ALDH-positive cells than in bulk cells. These results demonstrate that Cx43 can reverse several neoplastic characteristics and reduce the abundance of human lung CSCs.

APA, Harvard, Vancouver, ISO, and other styles

9

Xiao, Ying, Daniel T. Thoresen, Jonathan S. Williams, Chaochen Wang, James Perna, Ralitsa Petrova, and Isaac Brownell. "Neural Hedgehog signaling maintains stem cell renewal in the sensory touch dome epithelium." Proceedings of the National Academy of Sciences 112, no. 23 (May 26, 2015): 7195–200. http://dx.doi.org/10.1073/pnas.1504177112.

Full text

Abstract:

The touch dome is a highly patterned mechanosensory structure in the epidermis composed of specialized keratinocytes in juxtaposition with innervated Merkel cells. The touch dome epithelium is maintained by tissue-specific stem cells, but the signals that regulate the touch dome are not known. We identify touch dome stem cells that are unique among epidermal cells in their activated Hedgehog signaling and ability to maintain the touch dome as a distinct lineage compartment. Skin denervation reveals that renewal of touch dome stem cells requires a perineural microenvironment, and deleting Sonic hedgehog (Shh) in neurons or Smoothened in the epidermis demonstrates that Shh is an essential niche factor that maintains touch dome stem cells. Up-regulation of Hedgehog signaling results in neoplastic expansion of touch dome keratinocytes but no Merkel cell neoplasia. These findings demonstrate that nerve-derived Shh is a critical regulator of lineage-specific stem cells that maintain specialized sensory compartments in the epidermis.

APA, Harvard, Vancouver, ISO, and other styles

10

Bryukhovetskiy, I. S., A. S. Bryukhovetskiy, P. V. Mischenko, I. A. Merkulov, and Y. S. Khotimchenko. "STEM CELL THERAPY OF MALIGNANT BRAIN TUMORS: REALITY AND PROSPECTS." Journal of Clinical Practice 4, no. 4 (December 15, 2013): 45–54. http://dx.doi.org/10.17816/clinpract4445-54.

Full text

Abstract:

Modern methods for the treatment of malignant brain tumors are insufficiently effective. One reason for this is that the existing technologies and methods are focused on removing all neoplastic cellsfrom the body. Understanding the mechanisms of systemic migration of stem cells provides a new view on the role of this phenomenon in the development of malignant tumors. Migration and homing of normal stem cells, being originally the regulatory process, ensuring revascularization and remodeling of ischemic or traumatic injury of brain, play a role of the axial conductor of neoplastic process in carcinogenesis. The use of the phenomenon of migration and homing of stem cells in the tumor center for therapeutic purposes opens the possibility of overcoming the blood-brain barrier, reducing the toxicity of chemotherapy and increasing the radiation therapy efficiency, makes possible the directed influence on the hypoxic zone of the tumor, can directly affect to the key life processes of tumor stem cells. These arguments allow to consider the mechanisms of systemic migration and homing of stem cells to neoplastic foci as a fundamental theoretical platform for the creation of a fundamentally new class of anti-cancer, cell personalized medicines.

APA, Harvard, Vancouver, ISO, and other styles

11

Mikhail, Sameh, and Aiwu Ruth He. "Liver Cancer Stem Cells." International Journal of Hepatology 2011 (2011): 1–5. http://dx.doi.org/10.4061/2011/486954.

Full text

Abstract:

Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor properties susceptible to neoplastic transformation. Identification of specific cell surface markers for each of the liver cell types, production of corresponding monoclonal antibodies and cell sorting techniques have together revolutionized the characteristics of normal stem cells. In hepatocarcinogenesis, multiple signaling transduction pathways, important for stem cell proliferation and differentiations, are deregulated. Strategies are being developed to identify and characterize the liver cancer stem cells. Targeting liver cancer stem cells may bring hope to curing hepatocellular carcinoma.

APA, Harvard, Vancouver, ISO, and other styles

12

Weiler, V., P. Khalil, F. Schnabel, M. Siebeck, and R. Huss. "Adult stem cells in regenerating and neoplastic colon tissue." Pathology - Research and Practice 200, no. 4 (January 2004): 265. http://dx.doi.org/10.1016/s0344-0338(04)80447-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Huff, Carol Ann, and William Matsui. "Multiple Myeloma Cancer Stem Cells." Journal of Clinical Oncology 26, no. 17 (June 10, 2008): 2895–900. http://dx.doi.org/10.1200/jco.2007.15.8428.

Full text

Abstract:

Multiple myeloma is characterized by the clonal expansion of neoplastic plasma cells within the bone marrow, elevated serum immunoglobulin, and osteolytic bone disease. The disease is highly responsive to a wide variety of anticancer treatments including conventional cytotoxic chemotherapy, corticosteroids, radiation therapy, and a growing number of agents with novel mechanisms of action. However, few if any patients are cured with these modalities and relapse remains a critical issue. A better understanding of clonogenic multiple myleoma cells is essential to ultimately improving long-term outcomes, but the nature of the cells responsible for myeloma regrowth and disease relapse is unclear. We review evidence that functional heterogeneity exists in multiple myeloma and discuss potential strategies and clinical implications of the stem-cell model of cancer in this disease.

APA, Harvard, Vancouver, ISO, and other styles

14

Zhang, Daniel, Xin Wang, Yusha Sun, Donald O'Rourke, Guo-Li Ming, and Hongjun Song. "STEM-10. TEMPORAL MULTI-MODAL SINGLE-CELL ANALYSES REVEAL DYNAMIC INTERACTIONS BETWEEN GLIOBLASTOMA AND CAR-T CELLS AND IMMUNOLOGIC MODULATORS OF CANCER STEM CELL STATE." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii33. http://dx.doi.org/10.1093/neuonc/noac209.127.

Full text

Abstract:

Abstract CAR-T cell therapy is a promising new immunotherapy for a number of difficult-to-treat cancers, however, it has yet to yield broad success in glioblastoma (GBM). In particular, tumor heterogeneity presents a major therapeutic challenge, and a detailed understanding of the complex interplay between different neoplastic, non-neoplastic, and CAR-T cells is critical for developing better treatments. Using a patient-derived GBM organoid model of CAR-T cell therapy, we performed single-cell multi-omics to examine the longitudinal dynamics of the adaptive tumor response, changes in cell states, and evolution of cell-to-cell interaction networks. We find that all tumor cell types - neoplastic and non-neoplastic - respond to CAR-T cell activity, and they generate to an initially anti-tumor, but subsequently pro-tumor and immune-inhibitory microenvironment, which is accompanied by eventual CAR-T cell dysfunction and exhaustion. Unexpectedly, CAR-T cell activity also leads to attenuation of glioma stem-like states in both antigen-positive and antigen-negative neoplastic cells and reduces their proliferation via diffusible factors, of which IFNɣ is required but not sufficient. These findings are supported by analyses in patient samples from CAR-T cell therapy clinical trials, and they are consistent across both de novo and recurrent tumors with different somatic mutational landscapes. Our study unravels how the complex heterogeneity of GBM interacts with CAR-T cell therapy, and we identify previously unappreciated possibilities to affect antigen-negative neoplastic cells in ways that may be further augmented for enhanced therapeutic efficacy.

APA, Harvard, Vancouver, ISO, and other styles

15

Weissman, Irving. "Evolution of normal and neoplastic tissue stem cells: progress after Robert Hooke." Philosophical Transactions of the Royal Society B: Biological Sciences 370, no. 1680 (October 19, 2015): 20140364. http://dx.doi.org/10.1098/rstb.2014.0364.

Full text

Abstract:

The appearance of stem cells coincides with the transition from single-celled organisms to metazoans. Stem cells are capable of self-renewal as well as differentiation. Each tissue is maintained by self-renewing tissue-specific stem cells. The accumulation of mutations that lead to preleukaemia are in the blood-forming stem cell, while the transition to leukaemia stem cells occurs in the clone at a progenitor stage. All leukaemia and cancer cells escape being removed by scavenger macrophages by expressing the 'don't eat me' signal CD47. Blocking antibodies to CD47 are therapeutics for all cancers, and are currently being tested in clinical trials in the US and UK.

APA, Harvard, Vancouver, ISO, and other styles

16

Dingwall, Steve, Jung Bok Lee, Borhane Guezguez, Aline Fiebig, Jamie McNicol, Douglas Boreham, Tony J. Collins, and Mick Bhatia. "Neoplastic human embryonic stem cells as a model of radiation resistance of human cancer stem cells." Oncotarget 6, no. 26 (June 13, 2015): 22258–69. http://dx.doi.org/10.18632/oncotarget.4165.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Abd Elmageed, Zakaria Y., Yijun Yang, Raju Thomas, Manish Ranjan, Debasis Mondal, Krzysztof Moroz, Zhide Fang, et al. "Neoplastic Reprogramming of Patient-Derived Adipose Stem Cells by Prostate Cancer Cell-Associated Exosomes." STEM CELLS 32, no. 4 (March 17, 2014): 983–97. http://dx.doi.org/10.1002/stem.1619.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Sica, Gigliola. "Stem Cells and Tissue Engineering Techniques." Urologia Journal 80, no. 1 (January 2013): 11–19. http://dx.doi.org/10.5301/ru.2013.10762.

Full text

Abstract:

The therapeutic use of stem cells and tissue engineering techniques are emerging in urology. Here, stem cell types, their differentiating potential and fundamental characteristics are illustrated. The cancer stem cell hypothesis is reported with reference to the role played by stem cells in the origin, development and progression of neoplastic lesions. In addition, recent reports of results obtained with stem cells alone or seeded in scaffolds to overcome problems of damaged urinary tract tissue are summarized. Among others, the application of these biotechnologies in urinary bladder, and urethra are delineated. Nevertheless, apart from the ethical concerns raised from the use of embryonic stem cells, a lot of questions need to be solved concerning the biology of stem cells before their widespread use in clinical trials. Further investigation is also required in tissue engineering utilizing animal models.

APA, Harvard, Vancouver, ISO, and other styles

19

Lambert, Arthur W., and Robert A. Weinberg. "Linking EMT programmes to normal and neoplastic epithelial stem cells." Nature Reviews Cancer 21, no. 5 (February 5, 2021): 325–38. http://dx.doi.org/10.1038/s41568-021-00332-6.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Eaves, C., C. Udomsakdi, J. Cashman, M. Barnett, and A. Eaves. "The Biology of Normal and Neoplastic Stem Cells in CML." Leukemia & Lymphoma 11, sup1 (January 1993): 245–53. http://dx.doi.org/10.3109/10428199309047894.

Full text

APA, Harvard, Vancouver, ISO, and other styles

21

Li, Ren, Niansong Qian, Kaishan Tao, Nan You, Xinchuan Wang, and Kefeng Dou. "MicroRNAs involved in neoplastic transformation of liver cancer stem cells." Journal of Experimental & Clinical Cancer Research 29, no. 1 (2010): 169. http://dx.doi.org/10.1186/1756-9966-29-169.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Valent, Peter, Dominique Bonnet, Stefan Wöhrer, Michael Andreeff, Mhairi Copland, Christine Chomienne, and Connie Eaves. "Heterogeneity of Neoplastic Stem Cells: Theoretical, Functional, and Clinical Implications." Cancer Research 73, no. 3 (January 23, 2013): 1037–45. http://dx.doi.org/10.1158/0008-5472.can-12-3678.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Schulenburg, Axel, Herbert Ulrich-Pur, Dietmar Thurnher, Boban Erovic, Stefan Florian, Wolfgang R. Sperr, Peter Kalhs, et al. "Neoplastic stem cells: A novel therapeutic target in clinical oncology." Cancer 107, no. 10 (2006): 2512–20. http://dx.doi.org/10.1002/cncr.22277.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Weissman, Irving L. "The E. Donnall Thomas Lecture: Normal and Neoplastic Stem Cells." Biology of Blood and Marrow Transplantation 14, no. 8 (August 2008): 849–58. http://dx.doi.org/10.1016/j.bbmt.2008.05.003.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Martins, Filipe Correia, Maria Filomena Botelho, António Manuel Cabrita, Maria Isabel Torgal, and Carlos Freire De Oliveira. "Cancer and deregulation of stem cells pathways." Oncology Reviews 2, no. 4 (December 18, 2011): 199. http://dx.doi.org/10.4081/oncol.2008.199.

Full text

Abstract:

Stem cells may have an important etiological role in cancer. Their classic regulatory pathways are deregulated in tumors, strengthening the stem cell theory of cancer. In this manuscript, we review Wnt, Notch and Hedhehog pathways, describing which of their factors may be responsible for the neoplastic development. Furthermore, we classify these elements as oncogenes or tumor suppressor genes, demonstrating their mutation implications in cancer. The activation of these pathways is associated with the expression of certain genes which maintain proliferation and apoptosis inhibition. Further work should be carried out in the future in order to control tumor development by controlling these signaling cascades.

APA, Harvard, Vancouver, ISO, and other styles

26

Lochter, André. "Plasticity of mammary epithelia during normal development and neoplastic progression." Biochemistry and Cell Biology 76, no. 6 (December 1, 1998): 997–1008. http://dx.doi.org/10.1139/o99-010.

Full text

Abstract:

The functional unit of the mammary gland is the epithelium. It consists of luminal epithelial cells and myoepithelial cells that are generated from self-renewing stem and progenitor cells. The latter two cell types are scattered throughout the mammary epithelium and are concentrated in specialized structures, the end buds. In transplantation studies the pluripotency of mammary stem cells has been confirmed by demonstrating that they can regenerate a complete mammary gland. The ability of mammary epithelial cells to produce an elaborate ductal system during puberty and to differentiate into milk-producing alveoli during pregnancy is not only influenced by their genetic make-up, but is also governed by local molecular signals. Recent studies suggest that the transdifferentiation of epithelial cells into tumor cells is under microenvironmental control, despite the prominence of genetic mutations in breast cancer. Consequently, disturbances of tissue homeostasis can alter mammary gland development or result in preneoplastic and neoplastic pathologies. The plasticity of mammary epithelia is not limited to the entry of cells into differentiation and transdifferentiation pathways, but extends to their ability to regain facets of their preceding stage of functionality. Deciphering the molecular cues that determine cell plasticity is prerequisite for establishing a unifying concept of mammary gland development and breast tumor progression.Key words: branching morphogenesis, lactogenic differentiation, stem cells, epithelial-to-mesenchymal transition, cancer.

APA, Harvard, Vancouver, ISO, and other styles

27

Galindo-Vega, Aaron, Vilma Maldonado-Lagunas, Irma B. Mitre-Aguilar, and Jorge Melendez-Zajgla. "Tumor Microenvironment Role in Pancreatic Cancer Stem Cells." Cells 12, no. 12 (June 6, 2023): 1560. http://dx.doi.org/10.3390/cells12121560.

Full text

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a majority of patients presenting with unresectable or metastatic disease, resulting in a poor 5-year survival rate. This, in turn, is due to a highly complex tumor microenvironment and the presence of cancer stem cells, both of which induce therapy resistance and tumor relapse. Therefore, understanding and targeting the tumor microenvironment and cancer stem cells may be key strategies for designing effective PDAC therapies. In the present review, we summarized recent advances in the role of tumor microenvironment in pancreatic neoplastic progression.

APA, Harvard, Vancouver, ISO, and other styles

28

Hirth, Carlos Gustavo, Adriele Machado dos Santos, João Batista Gadelha de Cerqueira, Francisco Vagnaldo Fechine Jamacaru, Maria do Perpétuo Socorro Saldanha da Cunha, and Conceição Aparecida Dornelas. "PanCD44 Immunohistochemical Evaluation in Prostatectomies from Patients with Adenocarcinoma." BioMed Research International 2018 (2018): 1–7. http://dx.doi.org/10.1155/2018/2061268.

Full text

Abstract:

Introduction. CD44 has been proposed as a prognostic marker and a stem cell marker but studies in patients with prostate cancer have yielded inconsistent results. Patients and Methods. Patients submitted to radical prostatectomy between 2008 and 2013 at a university hospital were followed with biannual serum PSA tests to determine the biochemical recurrence (BR). Archived paraffin blocks with neoplastic and nonneoplastic tissue were evaluated immunohistochemically for a panCD44 and MYC. Results. Sixty-nine patients completed follow-up and were included. CD44 positivity was observed in inflammatory cells (42%), nonneoplastic epithelium (39.7%), and neoplastic tissue (12.3%). In nonneoplastic tissues staining was observed in basal and luminal cells with the morphology of terminally differentiated cells. In neoplastic tissues, CD44 negativity was correlated with higher Gleason scores (Rho = −0.204; p=0.042) and higher preoperative serum PSA levels when evaluated continuously (p=0.029). CD44 expression was not associated with tumor stage (p=0.668), surgical margin status (p=0.471), or BR (p=0.346), nor was there any association between CD44 and MYC expression in neoplastic tissue (p=1.0). Conclusion. In the bulk of cells, the minority of cancer stem cells would not be detected by immunohistochemistry using panCD44. As a prognostic marker, its expression was weakly correlated with Gleason score and preoperative PSA level, but not with surgical margin status, tumor stage, or BR.

APA, Harvard, Vancouver, ISO, and other styles

29

Ruan, Yongsheng, Hye Na Kim, Heather Ogana, and Yong-Mi Kim. "Wnt Signaling in Leukemia and Its Bone Marrow Microenvironment." International Journal of Molecular Sciences 21, no. 17 (August 28, 2020): 6247. http://dx.doi.org/10.3390/ijms21176247.

Full text

Abstract:

Leukemia is an aggressive hematologic neoplastic disease. Therapy-resistant leukemic stem cells (LSCs) may contribute to the relapse of the disease. LSCs are thought to be protected in the leukemia microenvironment, mainly consisting of mesenchymal stem/stromal cells (MSC), endothelial cells, and osteoblasts. Canonical and noncanonical Wnt pathways play a critical role in the maintenance of normal hematopoietic stem cells (HSC) and LSCs. In this review, we summarize recent findings on the role of Wnt signaling in leukemia and its microenvironment and provide information on the currently available strategies for targeting Wnt signaling.

APA, Harvard, Vancouver, ISO, and other styles

30

Cesselli, Daniela, Antonio Paolo Beltrami, Alessandra Poz, Stefania Marzinotto, Elisa Comisso, Natascha Bergamin, Evgenia Bourkoula, et al. "Role of Tumor Associated Fibroblasts in Human Liver Regeneration, Cirrhosis, and Cancer." International Journal of Hepatology 2011 (2011): 1–15. http://dx.doi.org/10.4061/2011/120925.

Full text

Abstract:

Tumor associated fibroblasts (TAFs) are considered a microenvironmental element critical for tumor growth and progression. Experimental studies suggest that their origin could be from mesenchymal stem cells (MSCs) derived from the bone marrow. However, the role played by TAFs in cirrhosis, hepatocellular carcinoma development, and progression is largely unknown, andin vitrohuman models are missing. This paper for the first time demonstrates that (1) human neoplastic livers possess a population of multipotent adult stem cells (MASCs) with properties of TAFs; (2) a population of MASC-derived TAFs is already present in cirrhotic, not yet neoplastic, livers; (3) MASCs isolated from nonneoplastic and noncirrhotic liver scan acquire a TAF phenotype when grown in a medium conditioned by tumor cell lines, supporting the notion that TAF could originate from resident primitive cells (MASCs), possibly through a paracrine mechanism.

APA, Harvard, Vancouver, ISO, and other styles

31

Zhang, Meili, Li Cheng, Yuyan Jia, Guang Liu, Cuiping Li, Shuhui Song, Allan Bradley, and Yue Huang. "Aneuploid embryonic stem cells exhibit impaired differentiation and increased neoplastic potential." EMBO Journal 35, no. 21 (August 24, 2016): 2285–300. http://dx.doi.org/10.15252/embj.201593103.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Werbowetski-Ogilvie, Tamra E., Marc Bossé, Morag Stewart, Angelique Schnerch, Veronica Ramos-Mejia, Anne Rouleau, Tracy Wynder, et al. "Characterization of human embryonic stem cells with features of neoplastic progression." Nature Biotechnology 27, no. 1 (January 2009): 91–97. http://dx.doi.org/10.1038/nbt.1516.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Kaur, R., L. Liang, and T. Werbowetski-Ogilvie. "PS1 - 158 The Role of LIN28A in Neoplastic Transformation of Human Embryonic Stem Cells (hESCs)." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 43, S4 (October 2016): S10. http://dx.doi.org/10.1017/cjn.2016.356.

Full text

Abstract:

Human embryonic stem cells (hESCs) are known for their indefinite self-renewal ability and pluripotent nature. However, during long-term culture, normal hESCs can undergo neoplastic transformation and acquire enhanced self-renewal ability and aberrant differentiation potential. These transformed-hESCs (trans-hESCs) exhibit high expression of the pluripotent gene, LIN28A. LIN28A, an RNA binding protein, is known: for its role in self-renewal of hESCs, as a reprogramming factor for generating induced-pluripotent stem cells and as a potent oncogene in several poorly differentiated, highly malignant human cancers. Despite its multiple functions, how LIN28A contributes to neoplastic transformation of normal hESCs is poorly understood. Our preliminary data demonstrate that following LIN28A knockdown, trans-hESCs display normal hESCs morphology consisting of both pluripotent colony cells surrounded by more differentiated fibroblast-like cells. Neural precursors derived from LIN28A knockdown trans-hESCs also revert back to a state of normal cell morphology and growth. Further analyses revealed that the expression levels of stage-specific embryonic antigen (SSEA3), OCT3/4 and NANOG decreases and are comparable to that observed in normal hESCs following LIN28A downregulation. Expression of miRNA targets of LIN28A such as let7i and mir125b was increased to levels seen in normal hESCs. These preliminary results indicate that LIN28A is a major contributing factor to neoplastic transformation of hESCs and that this process can be reversed by cellular “reprogramming”. This study will enhance our understanding of role of LIN28A in the transformation process in various human cancers thus, underscoring the value of hESCs and their neoplastic-derivatives as cellular and molecular model for studying tumor progression.

APA, Harvard, Vancouver, ISO, and other styles

34

Eisenwort, Gregor, Barbara Peter, Katharina Blatt, Sabine Cerny-Reiterer, Gregor Hoermann, Irina Sadovnik, Martin Bilban, et al. "Identification of a Neoplastic Stem Cell in Human Mast Cell Leukemia." Blood 124, no. 21 (December 6, 2014): 817. http://dx.doi.org/10.1182/blood.v124.21.817.817.

Full text

Abstract:

Abstract Leukemic stem cells (LSCs) have recently been identified as an important target of therapy in various human leukemias and related blood cell disorders. Systemic mastocytosis (SM) is a rare hematologic neoplasm characterized by abnormal growth and accumulation of mast cells (MCs) in various organ systems, including the bone marrow (BM). Whereas patients with indolent SM (ISM) have a normal life-expectancy, patients with more advanced forms of SM have a poor prognosis. In these patients, neoplastic MCs are usually resistant against conventional drugs and various targeted drugs. MC leukemia (MCL) is the rare leukemic variant of advanced SM, defined by a rapidly devastating expansion of immature MCs in various hematopoietic organs and a poor prognosis with short survival times. Although MCL is considered a stem cell disease, little is known about the origin and phenotype of MCL-initiating LSCs. We examined the phenotypic and functional characteristics of putative LSCs in patients with aggressive SM (ASM, n=12) and MCL (n=6). Putative LSCs were identified and characterized phenotypically by flow cytometry. Highly enriched, sorted LSCs were injected into NOD-SCID-IL-2Rγ-/- mice exhibiting a 220 amino acid isoform of human membrane-bound hSCF (NSGSCF). We found that disease-initiating and propagating LSCs reside within a CD34+ fraction of the MCL clone. Whereas cell fractions containing CD34+ cells as well as highly enriched CD34+ cells produced engraftment in NSGSCF mice with a MCL-like disease (43-77% human MCL cells in mouse BM after 10-22 weeks), no substantial engraftment was produced by MC-rich but stem cell-depleted, KIT+/CD34─ cell fractions obtained from the same patients (<1% engraftment in mouse BM). In dilution experiments, engraftment of CD34+ cells was documented down to a minimum of 50 cells per mouse. The identity of engrafting MCL cells was confirmed by morphology, phenotyping and molecular studies demonstrating the presence of KIT mutations that were initially detected in the primary MCL samples used. Moreover, we were able to confirm long-term engraftment by successful serial transplantations into secondary recipient mice. In consecutive experiments, we were able to show that CD45+/CD34+/CD38─ cells also produce leukemic engraftment in NSGSCF mice. As assessed by flow cytometry, these CD34+/CD38─ MCL LSCs were found to express several stem cells markers, including aminopeptidase-N (CD13), leukosialin (CD43), Pgp-1 (CD44), the IL-3R alpha-chain (CD123), AC133 (CD133) and CXCR4 (CD184). In addition, in most patients examined, MCL LSCs were found to display IL-1RAP, a surface antigen that is otherwise expressed in CML LSCs but is not expressed in normal stem cells. In addition, MCL LSCs were found to express various cell surface targets, including CD33 and CD52. By contrast, MCL LSCs did not express CD2, CD25, CD26 and CLL-1. The more mature progenitor cell fractions (CD34+/CD38+) were found to stain positive for CD13, CD33, CD43, CD44, CD90, CD117, CD123, CD133 and CD184. Mature clonal MCs expressed a similar phenotype, including molecular markers and targets, such as CD13, CD30 CD33, CD52 and CD184. In patients with ISM and aggressive SM (ASM), the CD34+/CD38─ stem cells exhibited a similar surface marker profile compared to MCL, but expressed lower levels of CD133 and did not express IL-1RAP. In the validation phase of our study, we examined the effects of target-specific antibodies. As assessed by flow cytometry, the CD52-targeting antibody alemtuzumab was found to induce complement-dependent lysis of CD34+ and CD34+/CD38─ cells in all MCL samples analysed. Furthermore, pre-incubation of MCL cells with alemtuzumab prior to injection into NSGSCF mice resulted in a significantly reduced engraftment (2.7±4.1%) after 22 weeks. In conclusion, our data show that the MCL clone originates from a primitive hematopoietic stem cell that co-expresses CD34, CD123, CD133 and IL-1RAP but lacks CD25 and CD26. In addition, our data show that MCL LSC express a number of clinically relevant surface targets, including CD33, CD52 and CD117 (KIT). These observations may facilitate LSC detection and isolation in MCL and may lead to the development of novel LSC-eradicating treatment concepts in this highly aggressive and drug-resistant form of leukemia. Disclosures Valent: Novartis: Consultancy, Honoraria, Research Funding.

APA, Harvard, Vancouver, ISO, and other styles

35

Melzer, Catharina, Juliane von der Ohe, and Ralf Hass. "In Vitro Fusion of Normal and Neoplastic Breast Epithelial Cells with Human Mesenchymal Stroma/Stem Cells Partially Involves Tumor Necrosis Factor Receptor Signaling." STEM CELLS 36, no. 7 (March 28, 2018): 977–89. http://dx.doi.org/10.1002/stem.2819.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Sangkhae, Veena, S. Leah Etheridge, Kenneth Kaushansky, and Ian S. Hitchcock. "The thrombopoietin receptor, MPL, is critical for development of a JAK2V617F-induced myeloproliferative neoplasm." Blood 124, no. 26 (December 18, 2014): 3956–63. http://dx.doi.org/10.1182/blood-2014-07-587238.

Full text

Abstract:

Key Points MPL is essential for the development of JAK2V617F-positive myeloproliferative neoplasms in vivo. Ablation or reduction of Mpl significantly reduces the pool of neoplastic hematopoietic stem cells.

APA, Harvard, Vancouver, ISO, and other styles

37

Bubin, Roman, Romans Uljanovs, and Ilze Strumfa. "Cancer Stem Cells in Pancreatic Ductal Adenocarcinoma." International Journal of Molecular Sciences 24, no. 8 (April 10, 2023): 7030. http://dx.doi.org/10.3390/ijms24087030.

Full text

Abstract:

The first discovery of cancer stem cells (CSCs) in leukaemia triggered active research on stemness in neoplastic tissues. CSCs represent a subpopulation of malignant cells, defined by unique properties: a dedifferentiated state, self-renewal, pluripotency, an inherent resistance to chemo- and radiotherapy, the presence of certain epigenetic alterations, as well as a higher tumorigenicity in comparison with the general population of cancer cells. A combination of these features highlights CSCs as a high-priority target during cancer treatment. The presence of CSCs has been confirmed in multiple malignancies, including pancreatic ductal adenocarcinoma, an entity that is well known for its dismal prognosis. As the aggressive course of pancreatic carcinoma is partly attributable to treatment resistance, CSCs could contribute to adverse outcomes. The aim of this review is to summarize the current information regarding the markers and molecular features of CSCs in pancreatic ductal adenocarcinoma and the therapeutic options to remove them.

APA, Harvard, Vancouver, ISO, and other styles

38

Salvi, Pooja S., and Robert A. Cowles. "Butyrate and the Intestinal Epithelium: Modulation of Proliferation and Inflammation in Homeostasis and Disease." Cells 10, no. 7 (July 14, 2021): 1775. http://dx.doi.org/10.3390/cells10071775.

Full text

Abstract:

The microbial metabolite butyrate serves as a link between the intestinal microbiome and epithelium. The monocarboxylate transporters MCT1 and SMCT1 are the predominant means of butyrate transport from the intestinal lumen to epithelial cytoplasm, where the molecule undergoes rapid β-oxidation to generate cellular fuel. However, not all epithelial cells metabolize butyrate equally. Undifferentiated colonocytes, including neoplastic cells and intestinal stem cells at the epithelial crypt base preferentially utilize glucose over butyrate for cellular fuel. This divergent metabolic conditioning is central to the phenomenon known as “butyrate paradox”, in which butyrate induces contradictory effects on epithelial proliferation in undifferentiated and differentiated colonocytes. There is evidence that accumulation of butyrate in epithelial cells results in histone modification and altered transcriptional activation that halts cell cycle progression. This manifests in the apparent protective effect of butyrate against colonic neoplasia. A corollary to this process is butyrate-induced inhibition of intestinal stem cells. Yet, emerging research has illustrated that the evolution of the crypt, along with butyrate-producing bacteria in the intestine, serve to protect crypt base stem cells from butyrate’s anti-proliferative effects. Butyrate also regulates epithelial inflammation and tolerance to antigens, through production of anti-inflammatory cytokines and induction of tolerogenic dendritic cells. The role of butyrate in the pathogenesis and treatment of intestinal neoplasia, inflammatory bowel disease and malabsorptive states is evolving, and holds promise for the potential translation of butyrate’s cellular function into clinical therapies.

APA, Harvard, Vancouver, ISO, and other styles

39

Ehtesham, Moneeb, Charles B. Stevenson, and Reid C. Thompson. "Stem cell therapies for malignant glioma." Neurosurgical Focus 19, no. 3 (September 2005): 1–11. http://dx.doi.org/10.3171/foc.2005.19.3.6.

Full text

Abstract:

The prognosis for patients with malignant glioma, which is the most common primary intracranial neoplasm, remains dismal despite significant progress in neurooncological therapies and technology. This is largely due to the inability of current treatment strategies to address the highly invasive nature of this disease. Malignant glial cells often disseminate throughout the brain, making it exceedingly difficult to target and treat all intracranial neoplastic foci, with the result that tumor recurrence is inevitable despite aggressive surgery and adjuvant radiotherapy and/or chemotherapy. The use of neural stem cells (NSCs) as delivery vehicles for tumor-toxic molecules represents the first experimental strategy aimed specifically at targeting disseminated tumor pockets. Investigators have demonstrated that NSCs possess robust tropism for infiltrating tumor cells, and that they can be used to deliver therapeutic agents directly to tumor satellites, with significant therapeutic benefit. With the aim of developing these findings into a clinically viable technology that would not be hindered by ethical and tissue rejection–related concerns, the use of adult tissue–derived stem cells has recently been explored. These technologies represent important progress in the development of a treatment strategy that can specifically target disseminated neoplastic pockets within the brain. Despite encouraging results in preclinical models, however, there are significant impediments that must be overcome prior to clinical implementation of this strategy. Key among these are an inadequate understanding of the specific tropic mechanisms that govern NSC migration toward invasive tumor, and the need to refine the processes used to generate tumor-tropic stem cells from adult tissues so that this can be accomplished in a clinically practicable fashion. Despite these limitations, the use of stem cell therapies for brain tumors holds significant promise and may emerge as an important therapeutic modality for patients with malignant glioma.

APA, Harvard, Vancouver, ISO, and other styles

40

Werbowetski-Ogilvie, Tamra E., Ludivine Coudière Morrison, Aline Fiebig-Comyn, and Mickie Bhatia. "In Vivo Generation of Neural Tumors from Neoplastic Pluripotent Stem Cells Models Early Human Pediatric Brain Tumor Formation." STEM CELLS 30, no. 3 (February 14, 2012): 392–404. http://dx.doi.org/10.1002/stem.1017.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Dainiak, Nicholas. "Practical and theoretical issues in 1993 concerning radiation effects on the growth of normal and neoplastic hematopoietic cells." STEM CELLS 15, S1 (June 4, 2009): 75–85. http://dx.doi.org/10.1002/stem.5530150712.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Szymonik, Julia, Kamila Wala, Tomasz Górnicki, Jolanta Saczko, Bartosz Pencakowski, and Julita Kulbacka. "The Impact of Iron Chelators on the Biology of Cancer Stem Cells." International Journal of Molecular Sciences 23, no. 1 (December 22, 2021): 89. http://dx.doi.org/10.3390/ijms23010089.

Full text

Abstract:

Neoplastic diseases are still a major medical challenge, requiring a constant search for new therapeutic options. A serious problem of many cancers is resistance to anticancer drugs and disease progression in metastases or local recurrence. These characteristics of cancer cells may be related to the specific properties of cancer stem cells (CSC). CSCs are involved in inhibiting cells’ maturation, which is essential for maintaining their self-renewal capacity and pluripotency. They show increased expression of transcription factor proteins, which were defined as stemness-related markers. This group of proteins includes OCT4, SOX2, KLF4, Nanog, and SALL4. It has been noticed that the metabolism of cancer cells is changed, and the demand for iron is significantly increased. Iron chelators have been proven to have antitumor activity and influence the expression of stemness-related markers, thus reducing chemoresistance and the risk of tumor cell progression. This prompts further investigation of these agents as promising anticancer novel drugs. The article presents the characteristics of stemness markers and their influence on the development and course of neoplastic disease. Available iron chelators were also described, and their effects on cancer cells and expression of stemness-related markers were analyzed.

APA, Harvard, Vancouver, ISO, and other styles

43

Catlin, Sandra N., Peter Guttorp, and Janis L. Abkowitz. "The kinetics of clonal dominance in myeloproliferative disorders." Blood 106, no. 8 (October 15, 2005): 2688–92. http://dx.doi.org/10.1182/blood-2005-03-1240.

Full text

Abstract:

AbstractTo study clonal evolution in myeloproliferative disorders, we used stochastic models of hematopoiesis for mouse and cat, species for which the in vivo kinetics of hematopoietic stem cells (HSCs) have been experimentally defined. We determined the consequence if 1 HSC became able to survive without the support of a microenvironmental niche while the rest of its behavior did not change. Neoplastic cells persisted and dominated hematopoiesis in 14% of mice and 17% of cats, requiring mean times of 2.5 ± 0.5 and 7.0 ± 1.2 years, respectively (n = 1000 simulations/species). In both species, when the number of neoplastic HSCs exceeded 0.5% of all HSCs, clonal dominance was inevitable. Our results can explain the absence of clonal myeloproliferative disorders in mice (lifetime, 2 years), are consistent with clinical observations in cats, and provide insight into the progression of chronic myelogenous leukemia (CML) in humans. They also demonstrate that competition for microenvironmental support can lead to the suppression of normal hematopoiesis as neoplasia evolves. Toxic or immunologic suppression of normal HSCs is not required.

APA, Harvard, Vancouver, ISO, and other styles

44

Matsumoto, Yasushi, Toshiro Fukui, Shunsuke Horitani, Yuji Tanimura, Ryo Suzuki, Takashi Tomiyama, Yusuke Honzawa, Tomomitsu Tahara, Kazuichi Okazaki, and Makoto Naganuma. "A Short-Term Model of Colitis-Associated Colorectal Cancer That Suggests Initial Tumor Development and the Characteristics of Cancer Stem Cells." International Journal of Molecular Sciences 24, no. 14 (July 20, 2023): 11697. http://dx.doi.org/10.3390/ijms241411697.

Full text

Abstract:

The mechanisms underlying the transition from colitis-associated inflammation to carcinogenesis and the cell origin of cancer formation are still unclear. The azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model reproduces human colitis-associated colorectal cancer. To elucidate the mechanisms of cancer development and dynamics of the linker threonine-phosphorylated Smad2/3 (pSmad2/3L-Thr)-positive cells, we explored the early stages of colitis-associated colorectal cancer in AOM/DSS mice. The AOM/DSS mice were sacrificed at 4 to 6 weeks following AOM administration. To analyze the initial lesions, immunofluorescence staining for the following markers was performed: β-catenin, Ki67, CDK4, Sox9, Bmi1, cyclin D1, and pSmad2/3L-Thr. Micro-neoplastic lesions were flat and unrecognizable, and the uni-cryptal ones were either open to the surfaces or hidden within the mucosae. These neoplastic cells overexpressed β-catenin, Sox9, Ki67, and Cyclin D1 and had large basophilic nuclei in the immature atypical cells. In both the lesions, pSmad2/3L-Thr-positive cells were scattered and showed immunohistochemical co-localization with β-catenin, CDK4, and Bmi1 but never with Ki67. More β-catenin-positive neoplastic cells of both lesions were detected at the top compared to the base or center of the mucosae. We confirmed initial lesions in the colitis-associated colorectal cancer model mice and observed results that suggest that pSmad2/3L-Thr is a biomarker for tissue stem cells and cancer stem cells.

APA, Harvard, Vancouver, ISO, and other styles

45

Arock, Michel, François-Xavier Mahon, and Peter Valent. "Characterization and targeting of neoplastic stem cells in Ph+chronic myeloid leukemia." International Journal of Hematologic Oncology 4, no. 4 (September 2015): 151–65. http://dx.doi.org/10.2217/ijh.15.16.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Zhu, Liqin, Paul Gibson, D. Spencer Currle, Yiai Tong, Robert J. Richardson, Ildar T. Bayazitov, Helen Poppleton, Stanislav Zakharenko, David W. Ellison, and Richard J. Gilbertson. "Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation." Nature 457, no. 7229 (December 17, 2008): 603–7. http://dx.doi.org/10.1038/nature07589.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Valent, Peter, Irina Sadovnik, Gregor Eisenwort, Harald Herrmann, Karin Bauer, Niklas Mueller, Wolfgang R. Sperr, Daniel Wicklein, and Udo Schumacher. "Redistribution, homing and organ-invasion of neoplastic stem cells in myeloid neoplasms." Seminars in Cancer Biology 60 (February 2020): 191–201. http://dx.doi.org/10.1016/j.semcancer.2019.07.025.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

Yamamoto, Yusuke, Gang Ning, Brooke E. Howitt, Karishma Mehra, Lingyan Wu, Xia Wang, Yue Hong, et al. "In vitroandin vivocorrelates of physiological and neoplastic human Fallopian tube stem cells." Journal of Pathology 238, no. 4 (January 9, 2016): 519–30. http://dx.doi.org/10.1002/path.4649.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Hoermann, Gregor, Katharina Blatt, Harald Herrmann, Sabine Cerny-Reiterer, Leonhard Müllauer, Peter Valent, and Matthias Mayerhofer. "Identification of Campath-1 Antigen (CD52) As a Novel Therapeutic Target in Advanced Systemic Mastocytosis." Blood 120, no. 21 (November 16, 2012): 2866. http://dx.doi.org/10.1182/blood.v120.21.2866.2866.

Full text

Abstract:

Abstract Abstract 2866 Systemic mastocytosis (SM) is a neoplasm of mast cells (MC) and MC progenitor cells. The clinical picture in SM ranges from an indolent course to highly aggressive cases with short survival time. In a majority of all patients with SM, the KIT mutation D816V is detectable. In addition, activating RAS mutations have recently been identified in patients with advanced SM. So far, no curative therapy for advanced SM is available. To identify molecular targets in neoplastic MC, we have generated novel human MC lines by lentiviral immortalization of cord blood-derived MC progenitors with RAS G12V, SV40 large T antigen, and hTERT. These cell lines, designated MCPV1 through MCPV4, display a morphology and ultrastructure resembling immature MC progenitors. MCPV cells also express a number of MC differentiation antigens, such as KIT and tryptase, and produce an aggressive MC disease when injected into NOD-SCID IL-2RG−/− (NSG) mice. As assessed by flow cytometry, MCPV cells were found to express a number of different surface antigens, including CD13, CD30, CD33, CD44, CD52, CD54, CD63, and CD95. In consecutive analyses, we studied the cell surface target CD52, also known as CAMPATH-1 antigen. As assessed by FACS, CD52 was found to be expressed on primary neoplastic MC in patients with aggressive SM (ASM, n=3), whereas in all patients with indolent SM (ISM, n=6), neoplastic MC stained negative or only slightly positive for CD52. Normal MC stained negative for CD52 in these experiments. Expression of CD52 in neoplastic MC was also demonstrable by immunohistochemical staining of bone marrow biopsy sections. We then asked whether the putative stem cells in ISM and ASM would express CD52. Indeed, in all patients examined, including cases with ISM and ASM, the immature CD34+/CD38- cells were found to express CD52. Next, we studied the regulation of expression of CD52 in neoplastic MC. Since activating RAS mutants have been described to be expressed in neoplastic MC in patients with advanced SM, we asked whether oncogenic RAS would promote expression of CD52 in MC. Indeed, lentiviral-mediated expression of activated RAS mutants was found to upregulate mRNA expression and to promote surface expression of CD52 in the human MC line HMC-1 as well as in various other myeloid cell lines. To validate CD52 as a potential target in neoplastic MC, we applied the CD52-targeting drug alemtuzumab. In these experiments, alemtuzumab exerted only minimal direct effects on viability of MCPV cells after IgG-mediated crosslinking. However, incubation of MCPV cells with alemtuzumab induced rapid and dose-dependent cell death via complement-dependent cytotoxicity (Figure 1). Furthermore, alemtuzumab was found to induce complement-dependent cytotoxicity in CD52+ primary neoplastic MC obtained from patients with advanced SM (n=2). In conclusion, we have established a new powerful model for studying the biology of advanced SM. Moreover, our study has identified CD52 as a novel promising therapeutic target in neoplastic MC and MC progenitor cells. Whether targeting of neoplastic (stem) cells in advanced SM using alemtuzumab will improve therapy by eradicating malignant cells remains to be determined in clinical trials. Figure 1. Alemtuzumab induces complement-dependent cytotoxicity in MCPV cells. MCPV cells were incubated with alemtuzmab and human serum as a source of complement (black bars). Heat-inactivation of the serum (white bars) abolished the cytotoxic effect. Figure 1. Alemtuzumab induces complement-dependent cytotoxicity in MCPV cells. MCPV cells were incubated with alemtuzmab and human serum as a source of complement (black bars). Heat-inactivation of the serum (white bars) abolished the cytotoxic effect. Disclosures: Valent: Phadia: Research Funding.

APA, Harvard, Vancouver, ISO, and other styles

50

Zhou, Yan, Thomas J. Kipps, and Suping Zhang. "Wnt5a Signaling in Normal and Cancer Stem Cells." Stem Cells International 2017 (2017): 1–6. http://dx.doi.org/10.1155/2017/5295286.

Full text

Abstract:

Wnt5a is involved in activating several noncanonical Wnt signaling pathways, which can inhibit or activate canonical Wnt/β-catenin signaling pathway in a receptor context-dependent manner. Wnt5a signaling is critical for regulating normal developmental processes, including stem cell self-renewal, proliferation, differentiation, migration, adhesion, and polarity. Moreover, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a signaling in regulating normal and cancer stem cell self-renewal, cancer cell proliferation, migration, and invasion. In this article, we review recent findings regarding the molecular mechanisms and roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or neoplastic breast or ovary, highlighting that Wnt5a may have different effects on target cells depending on the surface receptors expressed by the target cell.

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!