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Results for “Cancer stemness”

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At least 649 records · Page 36Linked to original sources

PubMed2003

Economic analysis of conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer.

We performed an economic analysis of data from 180 women in a clinical trial of conventional-dose chemotherapy vs high-dose chemotherapy plus stem-cell transplantation for metastatic breast cancer responding to first-line chemotherapy. Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects' clinical trial records. Resources were valued using the Medicare Fee Schedule for inpatient costs at one academic medical center and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. Mean follow-up was 690 days in the transplantation group and 758 days in the conventional-dose chemotherapy group. Subjects in the transplantation group were hospitalized for more days (28.6 vs 17.8, P=0.0041) and incurred higher costs (US dollars 84055 vs US dollars 28169) than subjects receiving conventional-dose chemotherapy, with a mean difference of US dollars 55886 (95% CI, US dollars 47298-US dollars 63666). Sensitivity analyses resulted in cost differences between the treatment groups from US dollars 36528 to US dollars 75531. High-dose chemotherapy plus stem-cell transplantation resulted in substantial additional morbidity and costs at no improvement in survival. Neither the survival results nor the economic findings support the use of this procedure outside of the clinical trial setting.

Adult↗

PubMed1999

Autoaggression syndrome resembling acute graft-versus-host disease grade IV after autologous peripheral blood stem cell transplantation for breast cancer.

Acute graft-versus-host disease (aGVHD) after autologous progenitor cell transplantation has been associated with blood transfusion or cyclosporine. Mild aGVHD grades I-II, identified as autoaggression or engraftment syndrome, has recently been described in autologous progenitor transplantation. Here, we report the first case of pathologically documented grade IV aGVHD after autologous peripheral blood progenitor cell transplantation in a patient with breast cancer. The allogeneic origin was excluded by molecular techniques, and no cyclosporine or cytokines were administered.

Adult↗

PubMed2005

Platelet-mimicry of cancer cells: epiphenomenon with clinical significance.

Stem cell mimicry of cancer cells has been known for a long time and is considered to be responsible for ectopic gene expressions. The stem cell characteristics of tumor cells are shown to be involved in epithelial-mesenchymal transition and in the phenomenon of vascular mimicry. Certain cancer types acquire a geno-phenotype closely resembling the platelets and express several megakaryocytic genes (adhesion receptors alpha IIb beta 3, thrombin receptor and PECAM/CD 31 and/or platelet-type 12-LOX) able to activate the coagulation cascade or the platelets themselves. Here we define these potentials as platelet mimicry of cancer cells typical of pancreatic, breast, prostate, colorectal and urogenital cancers and melanoma. Data all support that platelet mimicry of certain cancer types is an important factor in their hematogenous dissemination and provides an attractive therapeutic target. Besides the long-available preclinical data, clinical trials have only recently provided evidence that targeting platelet mimicry of cancers is an efficient way to prevent tumor progression. The systematic discovery of the markers of platelet mimicry in various cancer types and their molecular targeting may provide new supportive therapeutic modalities for the management of the progressing disease.

Animals↗

PubMed2003

Small molecule regulation of phosphatase-dependent cell signaling pathways.

Small molecules provide exceptionally useful tools for probing signaling targets relevant for cancer and stem cell differentiation. In contrast to genetic approaches, the application of small molecules generally offers a graded and reversible disruption of a particular pathway. The vast array of theoretical chemical entities that exist in the chemical universe are now becoming available through the production and distribution of chemical libraries generated by both traditional and combinatorial methods, which are suitable for pharmacological use. Convenient and inexpensive cell-free and cell-based assays can be used to identify chemicals that exhibit desirable antisignaling properties. We illustrate a model of how agents targeted against signaling macromolecules involved in cancer, namely dual specificity protein phosphatases, can be identified.

Antineoplastic Agents↗

PubMed2007

Prostate cancer stem/progenitor cells: identification, characterization, and implications.

Several solid tumors have now been shown to contain stem cell-like cells called cancer stem cells (CSC). These cells, although generally rare, appear to be highly tumorigenic and may be the cells that drive tumor formation, maintain tumor homeostasis, and mediate tumor metastasis. In this Perspective, we first provide our insight on how a CSC should be defined. We then summarize our current knowledge of stem/progenitor cells in the normal human prostate (NHP), an organ highly susceptible to hyperproliferative diseases such as benign prostate hyperplasia (BPH) and prostate cancer (PCa). We further review the evidence that cultured PCa cells, xenograft prostate tumors, and patient tumors may contain stem/progenitor cells. Along with our discussion, we present several methodologies that can be potentially used to identify putative tumor-reinitiating CSC. Finally, we present a hypothetical model for the hierarchical organization of human PCa cells and discuss the implications of this model in helping understand prostate carcinogenesis and design novel diagnostic, prognostic, and therapeutic approaches.

Cell Differentiation↗

PubMed1993

Design of preparative regimens for stem cell transplantation in breast cancer.

We have evaluated tandem cycles of a tri-drug combination, termed CVP (cyclophosphamide, etoposide [VP-16], and cisplatin [Platinol]), at four levels in more than 300 patients with various types of tumors. Tandem CVP appears to be at least therapeutically equivalent to alternatives. A second potentially non-cross-resistant combination of mitoxantrone and thiotepa (MT), with or without etoposide, has been used in sequence following CVP to improve long-term, disease-free survival in patients who have multiple metastatic sites, who relapse shortly after adjuvant therapy, or who show other unfavorable clinical features. A combination of MT and etoposide (MVT) achieved an overall response rate of 61% in 32 patients with metastatic or refractory breast cancer. The etoposide was then eliminated to decrease the major toxicities of this regimen. MT was subsequently given to 37 evaluable patients prior to bone marrow infusion. The overall response rate was 48.5% Thirty patients with metastatic breast cancer were then treated with induction therapy, a cycle of CVP, and then a cycle of MT. Given the low complete remission (CR) rate to induction therapy in these patients, the CR rate achieved with CVP-MT was encouraging. Further studies are ongoing.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Buried alive: a novel approach to cancer treatment.

The heightened interest in the development of novel anti-cancer drugs that trigger apoptotic death in cancer cells stems from the fact that immediately upon execution of the death signal, the corpse is efficiently removed via specific recruitment of phagocytic cells. This prevents spilling of cellular contents and the associated inflammatory response, a likely scenario during necrotic death. Recent evidence has established that phagocytic removal of apoptotic cells is a function of ligand-receptor interaction, whereby the ligand(s) for the scavenger receptor(s) of phagocytic cells is/are specifically expressed on apoptosing cells. Therefore, by implication, enhancing this ligand-receptor interaction could be an alternate means for removing unwanted cells. Here we present a provocative hypothesis that circumvents the need for chemotherapy-induced apoptosis in cancer cells. According to our model, cancer cells need not die in order to be removed by scavenger cells, but could still be effectively phagocytosed provided the cell surface expression of specific molecules that strongly engage phagocytic cells is sufficiently enhanced. In other words, inducing the expression of "eat me" signals on cancer cells could be a novel approach to "bury alive" these unwanted cells without the untoward effects of chemotherapy-induced apoptosis.

Apoptosis↗

PubMed2001

Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer.

Because colorectal cancers (CRCs) frequently display APC mutation, inhibition of apoptosis, and increased expression of the antiapoptotic protein survivin, we hypothesized that APC mutation inhibits apoptosis by allowing constitutive survivin expression. Using HT-29 CRC cell lines having inducible wild-type APC (wt-APC) or transfected dominant-negative TCF-4, we show that wt-APC down-regulates survivin expression via APC/beta-catenin/TCF-4 signaling. Using normal colonic epithelium, we found survivin by immunostaining/reverse transcription-PCR to be preferentially expressed in the lower crypt (which inversely correlates with wt-APC's expression pattern). Thus, wt-APC, by progressively decreasing survivin and increasing apoptosis from crypt bottom to top, may limit the population size of stem cells and other proliferative cells in the lower crypt; mutant APC may allow expansion of these populations, thereby initiating tumorigenesis.

Adenomatous Polyposis Coli Protein↗

PubMedDate not supplied

Peripheral blood stem cell transplantation in breast cancer.

Over the past decade, peripheral blood progenitor cells (PBPCs) have replaced bone marrow as the major source of haematopoietic support. This transition from marrow to PBPCs is due to the fact that, for many clinical studies, a significantly faster rate of engraftment, particularly for platelets, has been demonstrated for patients who receive PBPC support when compared to similarly treated patients who are transplanted with bone marrow. The leukapheresis procedure itself, quality of PBPC graft, methods of PBPC mobilization, purging, and ex vivo expansion will be discussed in detail.

Breast Neoplasms↗

PubMedDate not supplied

End of life in pediatric oncology: how clinical practice leads to research.

In pediatric oncology nursing, and across practice disciplines in general, clinical research serves as the cornerstone for improving patient care. Historically, advances made in the care and cure of childhood cancer have stemmed directly from clinical research. The developments of new research questions are varied in their origin--some questions are based on previous work that leads logically to the next question, some are based on a clinical problem that requires more immediate attention, and then there are those that arise from an individual clinical experience. This last category provides clinicians with a poignant reason to search for answers on how to provide the most optimal care for all future patients. As the number of advanced practice nurses in pediatric oncology increases, there is the likelihood of an increased pursuit of clinical research. This article describes how one clinician's experience with dying children resulted in the pursuit of answers to clinical research questions. By reflecting on clinical practice and incorporating our practice in the development of research questions, we can improve the quality of care provided to all children with cancer.

Biomedical Research↗

PubMed2005

[Viral infections in pediatric cancer patients].

Children with cancer or stem cell transplantation (SCT) are at considerable risk to develop life threatening viral infections. Due to both underlying disease and immunosuppressive therapy lymphocyte number and function are low and the cellular immunity against viral infections is restricted or missing. As immunosuppressive treatment regimens and mismatched or T-cell-depleted stem cell products are being used increasingly, viral infections will become an even greater problem in the future. PCR-based methods have become an indispensable tool for early recognition, preemptive therapy, and monitoring therapeutic responses by qualitative and quantitative approaches. Assays are now available that allow for parallel screening of the 16 most common viral agents. Responses to antiviral therapy are often limited in immunocompromised patients and mainly depend on the time of their initiation. Most antiviral agents have a toxicity profile that may become clinically relevant and curtail antiviral therapy. New options for treatment are therefore warranted. For the next future, these may include the transfer of specific T-cells and other immunotherapeutic approaches. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Hematology/Oncology (GPOH) and the German Society for Pediatric Infectious Diseases (DGPI) for diagnosis and treatment of viral infections in children with cancer or post HSCT. They are based on the results of clinical trials, case series and expert opinions using the evidence criteria set forth by the Infectious Diseases Society of America (IDSA).

Adolescent↗

PubMed2021

ERBB3 overexpression due to miR-205 inactivation confers sensitivity to FGF, metabolic activation, and liability to ERBB3 targeting in glioblastoma.

In glioblastoma (GBM), the most frequent and lethal brain tumor, therapies suppressing recurrently altered signaling pathways failed to extend survival. However, in patient subsets, specific genetic lesions can confer sensitivity to targeted agents. By exploiting an integrated model based on patient-derived stem-like cells, faithfully recapitulating the original GBMs in vitro and in vivo, here, we identify a human GBM subset (∼9% of all GBMs) characterized by ERBB3 overexpression and nuclear accumulation. ERBB3 overexpression is driven by inheritable promoter methylation or post-transcriptional silencing of the oncosuppressor miR-205 and sustains the malignant phenotype. Overexpressed ERBB3 behaves as a specific signaling platform for fibroblast growth factor receptor (FGFR), driving PI3K/AKT/mTOR pathway hyperactivation, and overall metabolic upregulation. As a result, ERBB3 inhibition by specific antibodies is lethal for GBM stem-like cells and xenotransplants. These findings highlight a subset of patients eligible for ERBB3-targeted therapy.

Antibodies↗

PubMed1993

Peripheral blood stem cell transplantation for breast cancer patients with bone marrow metastases using GM-CSF priming.

Twenty-seven patients with metastastic breast cancer to the bone marrow underwent successful collection of peripheral blood progenitor cells (PBPC) following GM-CSF cytokine priming and were engrafted following courses of high-dose chemotherapy. Myeloid engraftment was observed in a median of 12 days, with a range of 8-29 days. The cell dose infused correlated, although weakly, with days to engraftment, although assays of CFU-GM and CD34+ cells did not, suggesting refinement in such assays is needed. The failure to observe complete remission of the tumor suggests alternative chemotherapy regimens should be investigated.

Adult↗

PubMed2000

Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia Bone Marrow Transplant Group.

BACKGROUND: We conducted a randomized trial in which we compared high-dose chemotherapy plus hematopoietic stem-cell rescue with a prolonged course of monthly conventional-dose chemotherapy in women with metastatic breast cancer. METHODS: Women 18 to 60 years of age who had metastatic breast cancer received four to six cycles of standard combination chemotherapy. Patients who had a complete or partial response to induction chemotherapy were then randomly assigned to receive either a single course of high doses of carboplatin, thiotepa, and cyclophosphamide plus transplantation of autologous hematopoietic stem cells or up to 24 cycles of cyclophosphamide, methotrexate, and fluorouracil in conventional doses. The primary end point was survival. RESULTS: The median follow-up was 37 months. Of 553 patients who enrolled in the study, 58 had a complete response to induction chemotherapy and 252 had a partial response. Of these, 110 patients were assigned to receive high-dose chemotherapy plus hematopoietic stem cells and 89 were assigned to receive conventional-dose chemotherapy. In an intention-to-treat analysis, we found no significant difference in survival overall at three years between the two treatment groups (32 percent in the transplantation group and 38 percent in the conventional-chemotherapy group). There was no significant difference between the two treatments in the median time to progression of the disease (9.6 months for high-dose chemotherapy plus hematopoietic stem cells and 9.0 months for conventional-dose chemotherapy). CONCLUSIONS: As compared with maintenance chemotherapy in conventional doses, high-dose chemotherapy plus autologous stem-cell transplantation soon after the induction of a complete or partial remission with conventional-dose chemotherapy does not improve survival in women with metastatic breast cancer.

Adolescent↗

PubMed2005

High-dose chemotherapy and autologous stem cell rescue for metastatic breast cancer: superior survival for tandem compared with single transplants.

During 1990-1999, we treated 60 patients with breast cancer who had distant metastases with high-dose chemotherapy and autologous stem cell rescue (HDC) after they had responded to induction chemotherapy. HDC regimens were MiTepa (60 mg/m2 mitoxantrone by continuous intravenous infusion over 3 days plus 300 mg/m2 thiotepa intravenously over 2 hours daily x 3 days) and ICE (12 g/m2 ifosfamide, 1800 mg/m2 carboplatin, 2 g/m2 etoposide; all 3 by continuous intravenous over 4 days). At a median follow up >8 years, the median failure-free survival (FFS) was 13.9 months, median overall survival (OS) 29.1 months, 5-year FFS 12%s and 5-year OS 25%. Thirty-three patients underwent tandem (T) transplants; 27 underwent a single (S) HDC. Median ages for these 2 groups were 45 and 48 years; bone and liver metastases were more prevalent in the T cohort, whereas lung metastases were more prevalent in the S cohort. At a median follow up of 6.5 years for the S group and >9 years for the T group, there were 52 deaths. FFS was better for T: median 15.7 versus 7.7 months (p2 = 0.010) as was OS: median 32.7 versus 17.7 months, 2-year survival 68% versus 41%, and 5-year survival 32% versus 15% (p2 = 0.010). As a group, patients with distant metastatic breast cancer who underwent tandem transplants had a better posttransplant survival than patients who underwent a single HDC.

Adult↗

PubMed2004

Modulation of cellular differentiation and cell fate for cancer therapy.

Dysregulation of fundamental processes in developmental biology such as stem cell differentiation and proliferation may be the basis of many neoplastic diseases. Cancer stem cells have recently been identified in a number of malignancies, including leukemia and breast tumors. Drugs that affect differentiation, such as retinoic acid, have found therapeutic niches for the treatment of various forms of leukemia. As new understanding of stem cell biology and its role in cancer emerges, the development and application of drugs that target stem cell differentiation and cell fate will provide new therapeutic modalities for the management and treatment of malignant diseases.

Animals↗

PubMed2000

High CD34 cell doses do not worsen regimen-related toxicity or early mortality after autologous blood stem cell transplantation for breast cancer.

BACKGROUND: Some transplant-related complications, such as the engraftment syndrome, are thought to be mediated by cytokines released during expansion of hematopoietic progenitors at the time of neutrophil recovery. Since there is an inverse correlation between CD34(+) cell dose and time to neutrophil recovery, we sought to determine if peritransplant toxicity and early mortality were adversely affected by high CD34(+) cell doses. METHODS: The study group included 186 women with breast cancer who received high-dose cyclophosphamide, carmustine, thiotepa and an autologous PBSC transplant. The median CD34(+) cell dose was 5.9 x 10(6)/kg (1.0-154.7 x 10(6)/kg). Patients were categorized by CD34(+) cell dose (1.0-3.5, 3.6-5.9, 6.0-19.9, and 20.0-154.7 x 10(6)/kg) for assessment of outcomes. RESULTS: Grades 2-4 mucositis occurred in 49%, cardiac toxicity in 7%, pulmonary toxicity in 5%, cystitis in 4%, diarrhea in 3%, renal toxicity in 1%, and central nervous system toxicity in 1%. A Grade 2-4 regimen-related toxicity occurred in 109 patients (59%) and Grade 3-4 in eight patients (4%). Overall survival was 100% at Day 30, 96% at Day 90, and 89% at 1 year. Treatment-related mortality was 3.8%. In multivariate analyses that included prior chemotherapy, disease status, visceral metastases, prior chest radiation and age, CD34(+) cell dose group was not an independent risk factor for Grade 2-4 mucositis, Grade 2-4 maximum toxicity, Grade > or =3 cumulative toxicity, 90 day survival or 1 year survival. DISCUSSION: We conclude that CD34(+) cell doses >20 x 10(6)/kg do not affect transplant outcome in a negative or positive fashion.

Adult↗

PubMed2006

Asymmetric and symmetric stem-cell divisions in development and cancer.

Much has been made of the idea that asymmetric cell division is a defining characteristic of stem cells that enables them to simultaneously perpetuate themselves (self-renew) and generate differentiated progeny. Yet many stem cells can divide symmetrically, particularly when they are expanding in number during development or after injury. Thus, asymmetric division is not necessary for stem-cell identity but rather is a tool that stem cells can use to maintain appropriate numbers of progeny. The facultative use of symmetric or asymmetric divisions by stem cells may be a key adaptation that is crucial for adult regenerative capacity.

Animals↗