PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Cancer stemness”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 1,063 records · Page 59Linked to original sources
PubMed2006

Nucleostemin delays cellular senescence and negatively regulates TRF1 protein stability.

Nucleostemin (NS) encodes a nucleolar GTP-binding protein highly enriched in the stem cells and cancer cells. To determine its biological activity in vivo, we generated NS loss- and gain-of-function mouse models. The embryogenesis of homozygous NS-null (NS(-/-)) mice was aborted before the blastula stage. Although the growth and fertility of heterozygous NS-null (NS(+/-)) mice appeared normal, NS(+/-) mouse embryonic fibroblasts (MEFs) had fewer NS proteins, a lower population growth rate, and higher percentages of senescent cells from passage 5 (P5) to P7 than their wild-type littermates. Conversely, transgenic overexpression of NS could rescue the NS(-/-) embryo in a dose-dependent manner, increase the population growth rate, and reduce the senescent percentage of MEFs. Cell cycle analyses revealed increased pre-G1 percentages in the late-passage NS(+/-) MEF cultures compared to the wild-type cultures. We demonstrated that NS could interact with telomeric repeat-binding factor 1 (TRF1) and enhance the degradation but not the ubiquitination of the TRF1 protein, which negatively regulates telomere length and is essential for early embryogenesis. This work demonstrates the roles of NS in establishing early embryogenesis and delaying cellular senescence of MEFs and reveals a mechanism of a NS-regulated degradation of TRF1.

Animals↗
PubMed2005

Molecular target-based treatment of human cancer: summary of the 10th international conference on differentiation therapy.

The 10th International Conference on Differentiation Therapy was held between April 29 and May 3, 2004, in Shanghai, China. In the tradition of previous conferences from this series, which have been held biannually since the first meeting organized 20 years ago by Samuel Waxman and Giovanni Rossi in Sardinia, the organizers of the 10th International Conference on Differentiation Therapy aimed to gather basic and clinical cancer investigators in a setting of plenary sessions, workshops, and poster presentations to maximize the effective exchange of information and foster the establishment of collaborative interactions. Approximately 300 scientists attended the meeting with a mission to discuss targeted approaches to cancer treatment, which stem from our understanding of basic biological processes and the mechanisms of their deregulation during tumorigenesis.

Apoptosis↗
PubMed2006

Multiple controls regulate nucleostemin partitioning between nucleolus and nucleoplasm.

Nucleostemin plays an essential role in maintaining the continuous proliferation of stem cells and cancer cells. The movement of nucleostemin between the nucleolus and the nucleoplasm provides a dynamic way to partition the nucleostemin protein between these two compartments. Here, we show that nucleostemin contains two nucleolus-targeting regions, the basic and the GTP-binding domains, that exhibit a short and a long nucleolar retention time, respectively. In a GTP-unbound state, the nucleolus-targeting activity of nucleostemin is blocked by a mechanism that traps its intermediate domain in the nucleoplasm. A nucleostemin-interacting protein, RSL1D1, was identified that contains a ribosomal L1-domain. RSL1D1 co-resides with nucleostemin in the same subnucleolar compartment, unlike the B23 and fibrillarin, and displays a longer nucleolar residence time than nucleostemin. It interacts with both the basic and the GTP-binding domains of nucleostemin through a non-nucleolus-targeting region. Overexpression of the nucleolus-targeting domain of RSL1D1 alone disperses nucleolar nucleostemin. Loss of RSL1D1 expression reduces the compartmental size and amount of nucleostemin in the nucleolus. Our work reveals that the partitioning of nucleostemin employs complex mechanisms involving both nucleolar and nucleoplasmic components, and provides insight into the post-translational regulation of its activity.

Amino Acid Sequence↗
PubMed2002

[Preparation of the gene targeted knockout mice for human premature aging diseases, Werner syndrome, and Rothmund-Thomson syndrome caused by the mutation of DNA helicases].

The list of human RecQ helicase comprises RecQ1, BLM (Bloom syndrome), WRN (Werner syndrome), RTS (Rothmund-Thomson syndrome), and RecQ5. Of these, the defective BLM, WRN, and RTS helicases are responsible for distinct but overlapping clinical features suggesting premature aging and an enhanced risk of cancer, which apparently stems from chromosomal instability in the cells of tissues and organs where expression of the helicase genes are specified. In an effort to obtain an animal model for these diseases, we performed gene target experiments to generate the WRN and RTS knockout mice.

Aging, Premature↗
PubMed2005

Optimization of the MB49 mouse bladder cancer model for adenoviral gene therapy.

Bladder cancer is regarded as a promising candidate for innovative therapies in the field of immune and gene therapy. In this paper, we present the subcutaneous, metastatic and a novel orthotopic model of murine MB49 bladder cancer in C57BL/6 mice. We further show the potential of using adenoviral vectors together with different transduction enhancers to augment in vivo gene delivery. Finally, we present candidate genes for tumour detection, therapy or targeting. The MB49 tumour grew rapidly in mice. The subcutaneous model allowed for tumour detection within a week and the possibility to monitor growth rate on a day-by-day basis. Injection of MB49 cells intravenously into the tail vein gave rise to lung metastases within 16 days, while instillation of tumour cells into pretreated bladders led to a survival time of 20-40 days. Adenoviral vectors can be used as a vehicle for gene transfer to the bladder. By far, the most potent transduction enhancer was Clorpactin, also known as oxychlorosene. Last, we show that MB49 cells express tumour-associated antigens like bladder cancer-4, prostate stem cell antigen and six-transmembrane epithelial antigen of the prostate. Given the possibility for efficient genetic modification of the bladder and the presence of known tumour antigens, the MB49 models can be used in innovative ways to explore immunogene therapy.

Adenoviridae↗
PubMed1983

Model for human carcinogenesis: action of environmental agents.

Current statistical prescriptions for low-dosage extrapolation of carcinogenic risk make no distinction between exposure to initiators and exposure to promoters despite the abundant data that these two classes of carcinogens have different modes of action. One reason for this is the lack of an appropriate model. In this paper, a model for carcinogenesis is presented which provides a framework for understanding the roles of "spontaneous" events, hereditary factors, and environmental agents in human carcinogenesis and for interpreting experimental carcinogenesis. This model incorporates two features: transition of target stem cells into cancer cells via an intermediate stage in two irreversible steps and growth and differentiation of normal target and intermediate cells. Cast in mathematical terms, the model can be fitted to age-specific incidence data on human cancers of both children and adults and can illuminate the relative importance of agents that affect transition rates, tissue growth and tissue differentiation. Within the context of the model, initiators act by affecting the transition rates, whereas promoters influence the kinetics of growth, especially of initiated cells. The model provides a good quantitative description of the epidemiology of carcinomas of the breast and of the lung. The data are consistent with the notion that hormones and cigarette smoke act as promoting agents in carcinoma of the breast and of the lung, respectively.

Age Factors↗
PubMed1997

Telomerase and telomere inhibitors in preclinical development.

Telomerase is an enzyme required by actively dividing cells to maintain the ends of chromosomes (telomeres). It is present in germline tissue, stem cells and cancer cells, but is repressed in somatic cells. Efforts are underway to exploit this selective expression of telomerase in cancer therapeutics. This review describes the status of telomerase research, which although at present predominantly preclinical, has the potential to enter clinical research.

Journal Article↗
PubMed1994

Antibody-targeted drugs for the therapy of cancer.

The advent of monoclonal antibodies has revitalised the concept of magic bullets and various agents (eg. drugs, toxins and isotopes) have been conjugated to monoclonal antibodies for selective delivery to tumours. Preclinical studies in mouse tumour models have been impressive and have lead to several clinical trials. These phase I trials have been less impressive. However, keeping in mind the aim of Phase I trials, the safety of using these conjugates in humans have been established. Several, major problems still remain to be overcome before these agents may be useful for the treatment of cancer. These problems stem from the nature of tumour vasculature, cytotoxic activity of the moiety linked to antibody and the targeted tumour antigen expressed on the cell surface. This review will deal with these various aspects described above and possible approaches to overcome these obstacles with a definite bias towards drug-monoclonal antibody conjugates. However, these concepts are equally applicable for improved targeting of other agents.

Animals↗
PubMed1995

Biological effects of power-frequency fields as they relate to carcinogenesis.

There is a widespread public perception that exposure to electricity is linked to cancer. The public concern stems largely from epidemiological studies which appear to show a relationship between cancer incidence and exposure to power-frequency electromagnetic fields. This review will discuss the biophysics of power-frequency electromagnetic fields as it relates to biological effects, summarize the current state of the cancer epidemiology, and then concentrate on the laboratory studies that are relevant to addressing the possibility that power-frequency fields are carcinogenic. Review of the epidemiological evidence shows that the association between exposure to power-frequency fields and cancer is weak and inconsistent, and generally fails to show a dose-response relationship. The laboratory studies of power-frequency fields show little evidence of the type of effects on cells or animals that point towards power-frequency fields causing or contributing to cancer. Finally, from what is known about the biophysics of power-frequency fields, there is no reason to even suspect that they would cause or contribute to cancer. Application of "Hill's criteria" to epidemiological and laboratory studies shows that the evidence for a causal association between exposure to power-frequency fields and the incidence of cancer is weak.

Animals↗
PubMed2001

Human bone marrow transplant rejection is associated with telomere cleavage.

Telomeres that guard chromosomes are shortened with each cell division because of replication-dependent sequence loss at both termini. The gradual erosion of telomeric length has been directly related to the process of aging in vivo. Recently we have reported, in murine and human cancer cells treated with different apoptogens, cleavage and extrusion of telomeric DNA prior to cell death on one hand and an amplification of telomeric DNA in metastatic epithelial malignancies of different histopathologic origin on the other. This study tested our hypothesis that telomere cleavage is linked to transplant rejection in cancer patients receiving stem cells either from bone marrow (BM) or umbilical cord blood transfusion. Telomere integrity and mitotic catastrophe were studied by cytogenetic and molecular fluorescence in situ hybridization (FISH) techniques in two BM samples taken from a male stem cell transplant recipient diagnosed with aplastic anemia. The first BM sample, which was aspirated 27 days after transplant, was mitotically active. Only one of 50 metaphases showed a chromatid break. Every cell karyotyped was of male origin with 46, XY chromosome constitution. The second BM sample aspirated 52 days after transplant gave no metaphases and most interphase cells appeared dead. FISH preparations of the second BM sample showed cleavage and drastic reduction of telomeric DNA at the time the patient was rejecting the transplant. In contrast, the first BM sample had shown no indication of cleavage of the telomeric DNA, although the percentage of telomeric area was smaller than in the control. The replicative stress imposed on the stem cells engrafted may result in an accelerated aging effect, possibly due to the erosion of telomeric DNA. We, therefore, conclude that BM rejection could be directly associated with the cleavage, clustering, and extrusion of telomeric DNA in the donor cells.

Adolescent↗
PubMed1994

Psychological support at night. A pilot study.

In-depth interviews with a sample of 10 nurses working permanent night duty in a British regional oncology and radiotherapy hospital reported that a significant part of their job involved psychological support for those patients who were awake and experiencing stress. The respondents explained that this psychological work was often disregarded and/or went unrecognized by the nursing staff on day duty, an attitude that could jeopardize the continuity of care of cancer patients. The findings stem from the author's doctoral dissertation concerning the role of the cancer nurse in relation to stress and the person with cancer, and they lay the foundation for further studies into the nature of the nurse's support role of cancer patients at night and in different health-care settings.

Canada↗
PubMed1997

Cytokine therapy for hematological malignancies.

Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, we have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines in this review. IFN-a is one of most useful and wide-ranging antitumor agents in hematological malignancies. The most striking effects have been studies in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients, and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the most appropriate category of treatment is difficult to determine in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase the dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been conducted to sensitize leukemic cells by CSFs, making them more susceptible to chemotherapy; but no convincing evidence has been obtained.

Antineoplastic Agents↗
PubMed1998

[Telomerase activity and telomere length as diagnostic tumor marker for ovarian tumors].

Telomerase activity was detected in germ cells, stem cells and cancer cells. In tumors of the ovary, an organ that contains germ cells, the authors examined availability to detect telomerase activity. Telomerase activity of malignant tumors was extremely high compared with that of normal ovaries and benign tumors. Strength and frequency of telomerase activity in malignant tumors was significant different from that in benign tumors. Telomere length tended to be smaller for malignant tumors of advanced stage, but no significant relationship between telomere length and telomerase activity and tumor stage could be recognized. Telomerase activity may be a useful marker for the diagnosis of ovarian tumors.

Biomarkers, Tumor↗
PubMed2001

Quality of life issues among women undergoing high-dose chemotherapy for breast cancer.

High-dose chemotherapy with autologous stem cell support for the treatment of breast cancer can have a profound effect on patients' quality of life (QOL). This article reviews findings from studies assessing QOL before, during, and after high-dose chemotherapy. The impact of high-dose therapy on overall QOL and specific aspects of QOL including physical functioning, symptoms, psychosocial/emotional and cognitive functioning, sexual functioning, and role functioning is considered. High-dose chemotherapy with stem cell transplant results in largely transient impairment of overall QOL and physical functioning, with subsequent improvement to baseline or better over time. Despite these encouraging global QOL findings, many patients continue to suffer considerable symptoms and concerns attributable to their transplant long after completion of the therapy. Additional research in this area is needed to optimize QOL for patients receiving high-dose chemotherapy.

Journal Article↗
PubMed2000

High-dose chemotherapy and stem cell transplantation for patients with stage IV breast cancer without clinically evident disease: correlation of CD34+ selection to clinical outcome.

Forty-five patients with metastatic breast cancer without clinically evident disease were treated with thiotepa 750 mg/m2, mitoxantrone 40 mg/m2 and carboplatin 1000 mg/m2 followed by stem cell transplantation to determine the safety and efficacy of CD34+ selection of peripheral blood stem cells. Of these, 15 patients' (group I) stem cells were processed through Baxter Isolex 300 device for CD34+ selection, whereas 30 patients (group II) received unmanipulated stem cells. Toxicity, progression-free survival and survival were compared between these two groups. There was no difference in transfusion requirements, white cell count and platelet recovery and non-hematologic toxicity between the two groups. The survival of patients in group I was 27 months compared to 38 months in group II (P = 0.8). The progression-free survival was 12 months and 13.5 months for group I and group II patients, respectively (P = 0.6). Our results indicate that while there is no adverse effect, there is also no significant advantage of CD34+ selection in terms of progression-free survival and survival in patients with metastatic breast cancer without clinically evident disease. Bone Marrow Transplantation (2000).

Adult↗
PubMed1999

High-Dose Chemotherapy with Autologous Stem Cell Rescue as a Treatment Modality for Breast Cancer.

Retrospective analyses of clinical trials as well as several prospective randomized clinical trials designed to evaluate dose intensity have emphasized the importance of intensive chemotherapy in determining outcomes in breast cancer treatment. One strategy that can deliver a large increment in dose intensity is high-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT), since it overcomes myelosuppression, a major dose-limiting toxicity of most chemotherapy regimens. Phase II data from HDC-ASCT trials have indicated improved complete remission rates and longer remission duration when compared to historical conventional-dose chemotherapy regimens. With declining treatment-related mortality (TRM) through improvements in supportive care and innovations in stem cell collection procedures, exploration of HDC-ASCT in prospective randomized trials has been made possible. Several prospective randomized trials have completed accrual and early results are now available, while other studies are still ongoing. Unfortunately the trial designs are quite varied, the characteristics of patients differ from study to study, the early data provide conflicting results, and the follow-up is quite short, making firm conclusions impossible at present. Of note, the comparison arms in several of the studies are performing better than historical nontransplant treatments, perhaps a result of an intermediate dose intensity employed in the nontransplant arm of these trials. These data suggest that dose intensity, whether supported by stem cells or hematopoietic growth factors, may be quite important in optimizing treatment outcomes, affirming earlier concepts of the importance of dose intensity. Further follow-up of the current clinical trials and analyses of ongoing studies not yet reported are necessary before firm conclusions are possible as to the optimal strategy of using dose intensity in the management of breast cancer.

Journal Article↗
PubMed1993

Phase II pilot study of high-dose busulfan and CY followed by autologous BM or peripheral blood stem cell transplantation in patients with advanced chemosensitive breast cancer.

The combination of busulfan and CY ('BU-CY') has been widely employed as a conditioning regimen for patients undergoing BMT for hematologic malignancies. However, little information is available regarding the utility of BU-CY in treating patients with advanced breast cancer. Fifteen patients with heavily pretreated Stage IIIB or Stage IV chemosensitive breast cancer were treated with busulfan (16 mg/kg) and CY (6000 mg/m2) followed by rescue with autologous BM or autologous peripheral blood stem cells. Toxicity and engraftment parameters were similar to those observed in patients receiving BU-CY for other indications. The overall response rate was 87%, with 53% of patients achieving CR. The median progression-free survival was 164 days, and the median overall survival was 292 days. We conclude that BU-CY is able to induce remissions in a high percentage of patients with heavily pretreated advanced breast cancer. However, remissions are brief, and alternative strategies for patient selection and/or management will be necessary to improve on these results.

Adenocarcinoma↗