Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cancer stem cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed1989

Isolation and storage of peripheral blood hematopoietic stem cells for autotransplantation into children with cancer.

Peripheral blood stem cells (PBSC) were collected for autotransplantation by a total of 46 continuous-flow leukaphereses in 17 children with various types of cancer in whom the stem-cell pool had been expanded by chemotherapy. As the cells collected by leukapheresis were contaminated with many visible cell clumps, platelets, and erythrocytes, they were separated from the platelet-rich plasma (PRP) by slow-speed centrifugation and fractionated on a discontinuous gradient of Percoll. All the hematopoietic progenitors (CFU-GM, CFU-GEMM) in the starting samples were recovered at the interface of 40% and 60% Percoll solutions largely free of other cellular components and with a substantial reduction in volume. The separation and freezing procedures could be completed within three hours after obtaining cells by leukapheresis. After their fractionation and storage, these PBSC were shown to be able to reconstitute normal hematopoiesis in ten children with poor prognosis leukemia or neuroblastoma for whom no HLA-compatible marrow donors were available and who had been subjected to marrow-ablative therapy. This separation procedure is simple, efficient, and readily available and can be used for children as a routine procedure for PBSC autotransplantation.

Adolescent↗
PubMed1998

Minimal Residual Cancer Detection in Hematopoietic Stem Cell Products and Its Prognostic Significance in Patients With Breast Cancer, Lymphoma, or Multiple Myeloma.

BACKGROUND: Despite the initial success of high-dose therapy and bone marrow transplant, the major reason for posttransplant failure is relapse of disease. Reinfusion of tumor cells may contribute to relapse in autologous stem cell transplants. We now have ultra-sensitive methods of tumor cell detection that can determine the presence of minimal residual cancer (MRC) in marrow and peripheral blood stem cells. METHODS: The author has conducted a critical review of the literature on this issue. Results: The factors that are associated with an increase in contamination of the graft include (1) the number of cycles of induction therapy, (2) the type of mobilization regimen used, (3) the presence of tumor cells in the marrow, and (4) the number of phereses. A number of studies show that the presence of occult breast cancer in the marrow and/or stem cell product predicts for a poor posttransplant clinical outcome. The presence of clonogenic breast cancer or lymphoma cells in the graft is also associated with a very poor outcome. Published data regarding contamination in graft and outcome for patients with myeloma are limited. CONCLUSIONS: Testing for minimal MRC in the oncology patient provides prognostic information that may be useful to the transplant physician.

Journal Article↗
PubMed2006

Targeting of CD44 eradicates human acute myeloid leukemic stem cells.

The long-term survival of patients with acute myeloid leukemia (AML) is dismally poor. A permanent cure of AML requires elimination of leukemic stem cells (LSCs), the only cell type capable of initiating and maintaining the leukemic clonal hierarchy. We report a therapeutic approach using an activating monoclonal antibody directed to the adhesion molecule CD44. In vivo administration of this antibody to nonobese diabetic-severe combined immune-deficient mice transplanted with human AML markedly reduced leukemic repopulation. Absence of leukemia in serially transplanted mice demonstrated that AML LSCs are directly targeted. Mechanisms underlying this eradication included interference with transport to stem cell-supportive microenvironmental niches and alteration of AML-LSC fate, identifying CD44 as a key regulator of AML LSCs. The finding that AML LSCs require interaction with a niche to maintain their stem cell properties provides a therapeutic strategy to eliminate quiescent AML LSCs and may be applicable to other types of cancer stem cells.

ADP-ribosyl Cyclase 1↗
PubMed2005

The role of LMO2 in development and in T cell leukemia after chromosomal translocation or retroviral insertion.

Chromosomal translocations are primary events in the development of leukemias, representing at least one genetic feature of the putative cancer stem cell. Studies of genes influenced by chromosomal translocations have yielded a vast amount of information about how cancer is initiated and maintained. In particular, acute leukemias have demonstrated that chromosomal translocations often involve transcription regulators that function by interacting with proteins and by controlling cell fate in the aberrant setting of the developing cancer cell. As a quintessential chromosomal translocation gene product, LMO2 has many properties that typify this class of molecule. In addition to its involvement in chromosomal translocations, the LMO2 gene was inadvertently activated in an X-SCID gene therapy trial by retroviral insertion. New molecular therapies targeted directly at the LMO2 protein could have major impact as adjuncts to existing therapies or as therapeutics in their own right. In this review, we outline the current knowledge about LMO2 and some possible routes to develop reagents that might be possible macromolecular drugs in the future.

Adaptor Proteins, Signal Transducing↗
PubMed1980

Feedback in cancer.

The theory presented regards cancer as a systemic disease initiated by carcinogens, and neoplasia as the organism's main defence against it. Carcinogens are assumed to destroy a vital substance "A" which is replenished by a second, "B", produced by neoplastic stem cells. Cancer progression is manifested by a gradual deterioration of the "A" producing machinery accompanied by a compensatory proliferation of neoplastic "B" producing stem cells whose size is therefore closely regulated so as to meet the organism's demands. Any stem cell pool reduction leading to a loss of "A" or "B" is followed by a proliferation of the remaining stem cells to replenish the loss. Such may be observed in chronic lymphoblastic leukemia maintaining a nearly constant elevated peripheral lymphoblast count. Following selective lymphoblast destruction the count is rapidly replenished to its pretreatment level. The same mechanism is assumed to explain the detrimental effect of some surgical interventions on cancer patients. Neoplastic progression is postulated to a obey a "stem cell conservation" principle which when violated is followed either by a stem cell replenishment or aggrevates the patient's conditions. This conservation law introduces a new definition of carcinogenesis: Any process reducing the "A" or "B" producing machinery is regarded as a carcinogen. A definition embracing, surgical extirpation of normal or neoplastic stem cells or cell destruction by irradiation, chemotherapy or chemical carcinogens.

Carcinogens↗
PubMed1990

[Peripheral blood stem cell autografts in pediatric cancer].

Harvest of peripheral blood stem cells (PBSC) for autografts is a safe, reliable procedure with low morbidity in children with cancer, and cryopreserved PBSC are useful in reducing cytopenia following marrow-ablative chemotherapy. The colony forming unit granulocyte/macrophage (CFU-GM) content of the thawed grafts is an important determinant of hematopoietic recovery after PBSC autografts. The possible value of high-dose chemotherapy without total body irradiation and PBSCT compared to intensified chemotherapy in the treatment of children with very high-risk lymphoid malignant disorders was reported.

Adolescent↗
PubMed2005

Why therapeutic response may not prolong the life of a cancer patient: selection for oncogenic resistance.

Most cancers do not respond to chemotherapy. Disappointedly, even objective clinical responses to anticancer therapy often do not translate into improvements in overall survival. To explain the response-survival paradox, it has been pointed out that effective therapy is ineffective against cancer stem cells, which replenish the tumor (causing relapse). In contrast, I discuss that, according to this scenario, patient survival will be prolonged at least by the duration of remission. Furthermore, stem-cell-based relapses will be sensitive to the initial therapy, and in theory cancer could be controlled indefinitely. To explain the paradox, I discuss that effective therapy selects for resistance among proliferating cancer cells. Importantly, mechanisms of resistance can be divided into nononcogenic (e.g., drug transporters and mutation in drug-targets) and oncogenic (e.g., apoptosis avoidance and cell cycle dysregulation). Oncogenic resistance is associated with highly aggressive cancer phenotype and, therefore, there is no increase in overall survival. I further suggest that (a) therapeutic response is a prerequisite for successful therapy, (b) resistance can be exploited for therapeutic advantage, (c) each response can be translated into increased survival, and (e) in slow growing tumors, cancer can be stopped without tumor shrinkage. Therapy will control cancer if it can selectively suppress proliferating cancer cells and will improve survival as long as acquired resistance can be exploited.

Cell Proliferation↗
PubMed2005

PTEN negatively regulates neural stem cell self-renewal by modulating G0-G1 cell cycle entry.

Previous studies have demonstrated that a small subpopulation of brain tumor cells share key characteristics with neural stem/progenitor cells in terms of phenotype and behavior. These findings suggest that brain tumors might contain "cancer stem cells" that are critical for tumor growth. However, the molecular pathways governing such stem cell-like behavior remain largely elusive. Our previous study suggests that the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene, one of the most frequently mutated genes in glioblastomas, restricts neural stem/progenitor cell proliferation in vivo. In the present study, we sought to determine the role of PTEN in long-term maintenance of stem cell-like properties, cell cycle entry and progression, and growth factor dependence and gene expression. Our results demonstrate an enhanced self-renewal capacity and G(0)-G(1) cell cycle entry and decreased growth factor dependency of Pten null neural/stem progenitor cells. Therefore, loss of PTEN leads to cell physiological changes, which collectively are sufficient to increase the pool of self-renewing neural stem cells and promote their escape from the homeostatic mechanisms of proliferation control.

Animals↗
PubMed2004

26th Annual San Antonio Breast Cancer Symposium, San Antonio, Texas, USA, 3-6 December 2003: update on preclinical and translational research.

The San Antonio Breast Cancer Symposium is the largest annual meeting devoted solely to breast cancer research. The late William L McGuire's vision for this meeting was to stimulate 'translational research', many years before this term became popular. In this way, the San Antonio Breast Cancer Symposium represents a forum in which basic and clinical researchers present their research side by side. Each year sees the continued evolution of our understanding of the basic mechanisms of breast cancer initiation and progression, and the clinical application of this knowledge. Major topics of discussion at the symposium this year were the cell cycle, new evolving concepts of estrogen receptor action, breast cancer stem cells, new predictive and prognostic markers (including microarray studies), and continued exploration of the mechanisms of drug resistance. This report will summarize preclinical and translational highlights from the meeting.

Breast Neoplasms↗
PubMed1996

Telomerase is activated in the prostate and seminal vesicles of the castrated rat.

Telomeres, the repetitive non-coding DNA sequences found at the ends of all eukaryotic chromosomes, shorten with each cell division. It has been proposed that telomere shortening may be the counting element of a mitotic clock that keeps track of cell divisions; with shortening to a critical length acting as a senescence signal underlying cellular aging. The enzyme telomerase functions to maintain telomere length, thus allowing unlimited cell division, and has been associated with cellular immortalization and cancer. Stem cells have large, perhaps unlimited, replicative capacities. Since these cells are potentially immortal, we reasoned that they might posses active telomerase. We therefore assayed for telomerase activity in the stem cell enriched pools of the androgen-depleted sex accessory tissues in the castrated male rat. Following castration, the ventral prostate and seminal vesicles of the rat involute, losing approximately 90% of their cells by 21 days. These residual glands persist, and are enriched for stem cells, being capable of fully regenerating these glands if testosterone is re-introduced into the animal. We assayed telomerase activity in extracts from normal, involuted, and regenerating ventral prostate and seminal vesicles. Normal glands were found to be telomerase negative, whereas telomerase activity appeared as these glands involuted following castration. Conversely, telomerase activity disappeared during testosterone-induced regeneration of these residual glands. These results provide strong evidence for the ability of androgen to negatively-regulate telomerase activity in stem cell populations of the rat ventral prostate and seminal vesicles. and represent the first in vivo model system for the modulation of telomerase activity.

Animals↗
PubMed2025

SNORA47 affects stemness and chemotherapy sensitivity via EBF3/RPL11/c-Myc axis in luminal A breast cancer.

Chemotherapy sensitivity is an important factor that restricts the prognosis of breast cancer, and breast cancer stem cells (BCSCs) are the root cause of chemotherapy sensitivity. SNORA47, a member of the small nucleolar RNAs, has not been documented in the context of breast cancer, although it has been reported in lung cancer. In this study, high SNORA47 expression was linked to unfavorable survival outcomes among patients with Luminal A breast cancer in The Cancer Genome Atlas (TCGA). Among Luminal A patients, an elevated expression of SNORA47 correlated with high TNM stage (P = 0.049). SNORA47 was strongly associated with breast cancer stemness phenotype and tumor sensitivity in vivo and in vitro. Our findings demonstrated that SNORA47, through its interaction with early B-cell factor 3(EBF3), facilitated the translocation of ribosomal protein L11(RPL11), which as a modulator that subsequently regulates the expression levels of the oncogene c-Myc. These discoveries provided novel insights into the molecular mechanisms of breast cancer progression and suggested potential therapeutic targets for overcoming drug sensitivity by disrupting the SNORA47-EBF3-RPL11 axis.

Humans↗
PubMed2026

Interplay between DNA and RNA methylation shapes cancer cell plasticity.

Cellular plasticity refers to the ability of healthy cells to shift between phenotypic states and modify their characteristics to maintain tissue homeostasis and integrity. In the tumor context, cancer stem cells (CSCs) exploit this flexibility to withstand stress, facilitate tumor dissemination, and evade therapeutic interventions. Epigenetic regulation, particularly DNA methylation at CpG sites, is recognized as a well-known driver of tumor plasticity by repressing differentiation programs through modulation of chromatin accessibility. More recently, RNA modifications (epitranscriptomics) have emerged as crucial post-transcriptional regulators of gene expression that shape RNA fate and function. Among these, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), and N7-methylguanosine (m7G) contribute to the regulation of cell identity by modulating stemness-differentiation balance, stress adaptation, and epithelial-to-mesenchymal transition (EMT). Notably, dysregulation of both DNA and RNA methylation signatures is frequently observed in tumors, suggesting potential functional interactions between these regulatory layers. Emerging evidence indicates that DNA CpG methylation and RNA methylation pathways may cooperate to influence stemness, survival, and EMT-associated signaling, thereby supporting CSCs' plasticity. Although the molecular mechanisms underlying this crosstalk remain incompletely understood, accumulating studies suggest that DNA and RNA methylation could converge within interconnected regulatory networks that contribute to the control of cancer cell identity. A deeper understanding of these interactions may uncover novel vulnerabilities for targeting tumor plasticity. In this review, we summarize the current knowledge on the interplay between DNA and RNA methylation in regulating tumor plasticity, highlighting emerging mechanistic insights, functional interactions, and potential implications for future epigenetic and epitranscriptomic therapeutic strategies.

Humans↗
PubMed2002

Cancerous genetic peculiarities non-responsible for cancer development.

Certain genetic peculiarities recently identified in cancer cells have generally been regarded as the abnormalities responsible for cancer development. However, these abnormalities may also be found in maturable cancer cells and are not limited only to the non-maturable type. As previously described by the authors, cancer tissue consists of two types of cancerous cells: maturable and non-maturable. The development of cancer may be dependent only on the non-maturable cancerous stem cells, not on the maturable type. Since the non-maturable cell may be solely responsible for carcinogenesis, the relevant genetic peculiarities that are also found in the maturable cancer cells should not be regarded as the abnormalities responsible for carcinogenesis.

Cell Division↗
PubMed2006

Usefulness of predictive tests for cancer treatment.

This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future. At least six lines of research have recently emerged as potential contributors to changes in clinical practice. Abundant pre-clinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Low levels predict cisplatin sensitivity and antimicrotubule drug resistance, and the opposite occurs with high levels. Secondly, single nucleotide polymorphisms in the ERCC1 gene influence survival and toxicity with cisplatin-based chemotherapy. The main core of recent research has centered on EGFR mutations and gene copy numbers. For the first time, EGFR mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas, with a threefold increase in time to progression and survival in patients receiving EGFR tyrosine kinase inhibitors. In contrast, K-ras mutations confer a negative effect in these patients. Evidence has also been accumulated on the crosstalk between estrogen and EGFR receptor pathways, paving the way for clinical trials of EGFR tyrosine kinase inhibitors plus aromatase inhibitors. microRNAs control the expression of cognate target genes, and downregulation of Dicer has been shown to be a strong predictor of relapse in surgically resected non-small-cell lung cancer patients. Finally, overexpression of the Wingless-type (Wnt) genes and methylation of Wnt antagonists like WIF and secreted frizzled related proteins have been documented in non-small-cell lung cancer and are believed to be an important mechanism of cancer stem cell maintenance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

The neurobiology of neurooncology.

The histological classification of brain tumors currently is based on the morphological appearance and protein expression patterns that reflect specific cell types within the central nervous system. Recent studies have suggested that the cells of origin for brain tumors may persist in the fully formed tumors, and that these "cancer stem cells" might represent the relevant cellular targets for anticancer therapy. In this regard, insights into the developmental neurobiology of brain tumors has significant impact on our understanding of the molecular and cellular pathogenesis of these devastating cancers, as well as the development of new strategies for treating brain tumors.

Astrocytoma↗
PubMed2006

The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis.

Proper response of normal stem cells (NSC) to motomorphogens and chemoattractants plays a pivotal role in organ development and renewal/regeneration of damaged tissues. Similar chemoattractants may also regulate metastasis of cancer stem cells (CSC). Growing experimental evidence indicates that both NSC and CSC express G-protein-coupled seven-transmembrane span receptor CXCR4 and respond to its specific ligand alpha-chemokine stromal derived factor-1 (SDF-1), which is expressed by stroma cells from different tissues. In addition, a population of very small embryonic-like (VSEL) stem cells that express CXCR4 and respond robustly to an SDF-1 gradient was recently identified in adult tissues. VSELs express several markers of embryonic and primordial germ cells. It is proposed that these cells are deposited early in the development as a dormant pool of embryonic/pluripotent NSC. Expression of both CXCR4 and SDF-1 is upregulated in response to tissue hypoxia and damage signal attracting circulating NSC and CSC. Thus, pharmacological modulation of the SDF-1-CXCR4 axis may lead to the development of new therapeutic strategies to enhance mobilization of CXCR4+ NSC and their homing to damaged organs as well as inhibition of the metastasis of CXCR4+ cancer cells.

Animals↗
PubMed1998

Bayesian optimal design in population models for haematologic data.

We introduce a population model to design optimal apheresis schedules to collect blood stem cells from cancer patients. Blood stem cells are collected prior to the patient undergoing high-dose chemoradiotherapy and are returned after this treatment to enable reconstitution of the white blood cell components. Maximizing the number of cells collected in as few apheresis as possible is desirable. We use a longitudinal data model with random effects to describe profiles of individual patients. A hierarchical prior model introduces common mean profiles for patients undergoing different treatments. We find the optimal apheresis schedule for a new patient by minimizing an expected loss over the posterior predictive distribution of the patient's predicted CD34 profile. We implement estimation of the model and solution of the optimal design problem by a simulation approach, which allows us to accommodate arbitrary shapes for the profiles and realistic loss functions that include relative penalties for the number of scheduled stem cell collections and for collecting fewer than a specified target quantity of total collected stem cells.

Antigens, CD34↗
PubMed2001

Bispecific single-chain antibodies as effective tools for eliminating epithelial cancer cells from human stem cell preparations by redirected cell cytotoxicity.

High-dose chemotherapy (HDC) with autologous bone marrow or peripheral stem cell transplantation is discussed as one option to treat the extensive stage of a variety of tumors. Effective methods to eliminate contaminating tumor cells from human bone marrow or stem cell grafts may improve the outcome of the patients. We investigated 3 recombinant bispecific single-chain antibodies (bscAbs) directed against 17-1A (EpCAM), c-erbB-2 (HER-2/neu) and LeY on the one and CD3 on the other binding site for their ability to induce lysis of epithelial tumor cells by retargeting autochthonous T lymphocytes present in bone marrow mononuclear cells (BMMC) and in peripheral stem cell mononuclear cells (PSMC). The bscAbs showed remarkable specific lysis of different epithelial tumor cell lines with BMMCs as well as with PSMCs as effector cells. Investigation of the alpha 17-1A-alpha CD3 bscAb revealed a significant correlation between the percentage of CD3(+) cells present in the BMMCs and the rate of lysis as well as the absence of detrimental effects on the viability of hematopoietic progenitor cells as determined by colony-forming unit assays (CFUs). Our results indicate that recombinant bispecific single-chain antibodies could be new tools for purging of human bone marrow and peripheral stem cell grafts from contaminating epithelial cancer cells for patients receiving autologous stem cell transplantation after HDC.

Antibodies, Bispecific↗