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 1,099 records · Page 61Linked to original sources

PubMed2006

The stem cell factor/c-kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells.

BACKGROUND: The transmembrane protein c-kit is a receptor tyrosine kinase (KIT) and KIT is expressed in solid tumors and hematological malignancies such as gastrointestinal stromal tumor (GIST), small-cell lung cancer and chronic myelogenous leukemia (CML). KIT plays a critical role in cell proliferation and differentiation and represents a logical therapeutic target in GIST and CML. In pancreatic cancer, c-kit expression has been observed by immunohistochemical techniques. In this study, we examined the influence of c-kit expression on proliferation and invasion using five pancreatic cancer cell lines. In addition, the inhibitory effect of imatinib mesylate on stem cell factor (SCF)-induced proliferation and invasion was evaluated. Finally, we also analyzed KIT and SCF expression in pancreatic cancer tissues using immunohistochemistry and correlated the results with clinical features. RESULTS: RT-PCR revealed that two pancreatic cancer cell lines, PANC-1 and SW1990, expressed c-kit mRNA. By Western blot analysis, c-kit protein was also present in those lines. In KIT-positive pancreatic cancer cell lines, proliferation and invasion were significantly enhanced by addition of SCF. In contrast, SCF did not enhance proliferation and invasion in the three KIT-negative lines (BxPC-3, Capan-2 and MIA PaCa-2). 5 muM imatinib mesylate significantly inhibited SCF-enhanced proliferation to the same extent compared with the control. Similarly, SCF-enhanced invasive ability was significantly inhibited by 5 muM imatinib mesylate. KIT was expressed in 16 of 42 clinical specimens by immunohistochemistry, and KIT expression was significantly related to venous system invasion. Furthermore, patients expressing both KIT and SCF had a somewhat lower survival. CONCLUSION: Our results demonstrated that the SCF-KIT pathway enhanced the proliferation and invasiveness in KIT-positive pancreatic cancer cell lines and that the enhanced proliferation and invasion were inhibited by imatinib mesylate. We propose that inhibitors of c-kit tyrosine kinase receptor have the potential to slow the progression of KIT-positive pancreatic cancers.

Aged↗

PubMed2002

Early tandem high-dose ifosfamide, carboplatin, etoposide therapy with stem cell rescue for small-cell lung cancer: brief report on the results of a phase-I/II trial.

OBJECTIVE: High-dose therapy (HDT) for small-cell lung cancer is experimental. Late intensification HDT for chemosensitive disease can increase the number and quality of remissions and prolong relapse-free survival, but has not yet shown impact on overall survival. This is possibly due to resistant residual disease. To overcome the development of resistance, we have tested early intensification tandem HDT. METHODS: We performed a phase-I/II trial using 1 conventional cycle of ifosfamide, carboplatin, etoposide (ICE) plus granulocyte colony-stimulating factor for stem cell recruitment followed by 2 cycles of high-dose ICE with rescue by CD34+ cell-enriched peripheral blood mononuclear cells. Dose escalation was performed for the 2 high-dose ICE cycles. Radiotherapy for limited disease was according to standard protocols. RESULTS: 17 patients were entered: 2 female patients; 15 male patients; median age 53 (range 36-65) years; 2 patients with limited disease, and 15 patients with extensive disease. We treated 4 patients at dose level 1, 11 patients at level 2, and 2 patients at level 3. The maximum tolerable dose was at level 2 with neuropathy being dose-limiting. Overall, toxicity was < or = grade 2 for all patients up to dose level 2 with hematotoxicity being grade 4 for all patients. There were 15 partial remissions (88%), 1 no change (6%), and 1 progressive disease (6%). Median time to progression was 7.9 months. Overall survival was 12.9 months (median). CONCLUSIONS: Early intensification with this protocol is feasible. Although a comparatively good response rate and median time to progression have been observed in this group dominated by patients with extensive disease, overall survival is short and no substantial long-term survival was found.

Adult↗

PubMed2006

Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center.

Community respiratory viruses (CRVs) have been recognized as a potential cause of pneumonia and death among hematopoietic stem cell transplantation (HSCT) recipients and patients with hematologic malignancies. We reviewed the Microbiology Laboratory records dated from July 1, 2000, to June 30, 2002, to identify patients who had respiratory specimens positive for influenza, parainfluenza, respiratory syncytial virus, or picornavirus. We identified 343 infections among patients with underlying hematologic malignancies and HSCT. We collected data on type of disease, age, sex, type of infection, neutrophil and lymphocyte counts, therapy, and outcome. Influenza, parainfluenza, and respiratory syncytial virus accounted for most cases and were approximately equal in frequency. Most infections occurred predominantly among recipients of allogeneic transplants. Infection progressed to pneumonia in 119 patients (35%) and occurred with similar frequency for the 3 viruses. Patients at greatest risk for developing pneumonia included those with leukemia, those aged more than 65 years, and those with severe neutropenia or lymphopenia. Lack of respiratory syncytial virus-directed antiviral therapy (p=0.025) and age (p=0.042) were associated with development of respiratory syncytial virus pneumonia, and an absolute lymphocyte count<or=200 cells/mL (p=0.049) was associated with development of influenza pneumonia. The overall mortality rate for CRV pneumonia was 15%. The only independent predictor of fatal outcome was an absolute lymphocyte count<or=200 cells/mL (p=0.03) in patients with influenza pneumonia.HSCT recipients and patients with hematologic malignancies who develop upper respiratory infection due to CRVs should be considered for antiviral therapy of proven efficacy to reduce the risk of pneumonia and death.

Adolescent↗

PubMed1994

High-dose cyclophosphamide, thiotepa and hydroxyurea with autologous hematopoietic stem cell rescue: an effective consolidation chemotherapy regimen for early metastatic breast cancer.

Phase I and II trials have demonstrated that high-dose chemotherapy with autologous hematopoietic stem cell rescue is effective 'consolidation' chemotherapy for patients with responding metastatic breast cancer. In this study 26 women with metastatic breast cancer responding to lower dose combination chemotherapy were treated with 18 g/m2 of hydroxyurea added to the widely used combination of cyclophosphamide (CY) 6 g/m2 and thiotepa 600 mg/m2. Hematopoietic stem cell support was provided in the form of previously collected cryopreserved marrow or peripheral blood stem cells if there were malignant cells in the marrow. The patients ranged in age from 25 to 51 years with a median of 43 years. Three patients (12%) died of toxicity, one from Candida pneumonia and the other two from pulmonary and central nervous system bleeding secondary to platelet consumption associated with high fever and renal dysfunction, a syndrome we have seen with approximately the same frequency as a complication of other 'marrow transplant level' chemotherapy. The 1 and 2 year progression-free survivals are projected to be 42% and 27%, respectively. Patients in complete remission or with only residual radiographic abnormalities in bone prior to this therapy had 67% and 58% 1 and 2 year progression-free survival probabilities. High-dose hydroxyurea can safely be added to the CY and thiotepa combination.

Adult↗

PubMed2000

[Mobilization of Peripheral Blood Stem Cells with High Dose Cyclophosphamide Combination Chemotherapy and G-CSF in Breast Cancer Patients]

To evaluate the effect of mobilization of peripheral blood stem cells (PBSC) with high dose cyclophosphamide combination chemotherapy and G-CSF in breast cancer patients, a new mobilization protocol was designed on the basis of standard combination chemotherapy regimen, in which the dose of cyclophosphamide was raised to 2 to 4 times, and G-CSF began to be used at the dose of 150 micro g twice everyday when white blood cell (WBC) decreased below 1.0 x 10(9)/L. PBSC collection was performed while WBC increased over 5.0 x 10(9)/L during bone marrow recovering. The PBSC mobilization protocol was completed in 10 patients, the median nadir of WBC was 0.8 (0.4 - 1.0) x 10(9)/L, the median time of PBSC collection was 2 (2 - 4), the median number of collected CD34(+) cells was 6.43 (1.99 - 8.75) x 10(6)/kg. The results showed that the protocol, high dose cyclophosphamide combination chemotherapy, was an optimal PBSC mobilization regimen in breast cancer patients.

Journal Article↗

PubMed1998

Stroma-conditioned medium and sufficient prestimulation improve fibronectin fragment-mediated retroviral gene transfer into human primitive mobilized peripheral blood stem cells through effects on their recovery and transduction efficiency.

Mobilized peripheral blood stem cells (PBSC) are an attractive vehicle for cancer gene therapy. However these stem cells may have a reduced proliferative capacity due to previous cytotoxic chemotherapy treatment of the patient. In addition, primitive hematopoietic stem cells (HSC) from mobilized peripheral blood are almost exclusively quiescent, which makes it hard to induce proliferation in vitro and thus to improve stable transduction of introduced genes into a sufficiently large number of primitive stem cells. In this study CD34-selected mobilized PBSC from lymphoma and myeloma patients were used as target cells for retroviral-mediated gene transfer using a clinically relevant cell- and serum-free supernatant transduction protocol. We have investigated various parameters that may contribute to an improvement of the poor transduction efficiency of the primitive HSC, including prestimulation time, the use of the carboxy-terminal fibronectin fragment CH-296, as well as stromal cell line conditioned media. Retroviral supernatant transduction in combination with CH-296 increased significantly the gene transfer efficiency as compared to supernatant alone and made the use of polycations redundant. Gene transfer of primitive HSC (cobblestone area forming cell (CAFC) week 6) was specifically improved when this procedure was preceded by a 5-day pre-culture period as compared to a 2-day transduction procedure. However, irrespective of the numerical recovery, the CAFC week 6 after retroviral transduction produced less long-term culture colony-forming cells, suggesting a loss of individual stem cell quality. The addition of stroma-conditioned media during the pre-culture period did not affect the individual CAFC quality or transduction efficiency, but increased greatly the recovery of the total number of transduced and untransduced HSC leading to larger grafts containing higher numbers of transduced stem cells.

Animals↗

PubMed2002

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates.

Bone Neoplasms↗

PubMedDate not supplied

Selective elimination (purging) of contaminating malignant cells from hematopoietic stem cell autografts using recombinant adenovirus.

In this work we have explored the use of adenoviral vectors for the purging of cancer cells from hematopoietic stem cell (HSC) autografts. We showed that a recombinant adenovirus expressing the herpes simplex-1 thymidine kinase gene (AD-tk) plus ganciclovir (GCV) killed HELA cells more effectively than did GCV alone. HELA cells were then mixed with human HSCs and exposed to AD-tk/GCV. AD-tk/GCV reduced the number of HELA colonies to 4% of control values, with no detectable reduction in the hematopoietic progenitor, colony forming unit-granulocyte/monocyte (CFU-GM). Similar studies of the JB6 non-Hodgkins lymphoma cell line showed a reduction to 5% of controls; studies of MCF-7, a breast carcinoma cell line, showed a reduction to 30% of controls, with no CFU-GM toxicity. Thus, AD-tk mediated selective killing of contaminating tumor cells. We also evaluated a recombinant adenovirus encoding the tumor suppressor gene p53 (AD-p53). AD-p53 was able to selectively kill all three cell lines (reducing tumor colonies approximately 100-fold) without any toxicity to CFU-GM. Although both AD-tk/GCV and AD-p53 were effective in these experiments, AD-p53 seemed to be more potent. Adenoviral vectors show promise for selectively targeting cancer cells that contaminate HSC autografts.

Adenoviridae↗

PubMed2004

Micrometastatic bone marrow cells at diagnosis have no impact on survival of primary breast cancer patients with extensive axillary lymph node involvement treated with stem cell-supported high-dose chemotherapy.

BACKGROUND: To determine the impact of micrometastatic bone marrow cells (MMC) on survival in high-risk primary breast cancer (HRPBC) patients treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: Ninety-one HRPBC patients (73 patients with > or =10 involved axillary lymph nodes (ALN), 18 premenopausal women with > or =4 involved ALN) received one cycle (eight patients) or two cycles of HDCT and ASCT. Bone marrow aspiration was performed before systemic treatment to search for MMC using a cocktail of four monoclonal epithelial-specific antibodies (5D3, HEA125, BM7 and BM8). The influence of MMC and other prognostic factors on disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS) was analysed. RESULTS: In 23 of 91 patients (25%) we detected a median of three MMC (range, 1-43) among 10(6) mononuclear cells. With a median follow-up of 62 months (range, 10-117), the detection of MMC was not associated with DFS (P=0.929), DDFS (P=0.664) or OS (P=0.642). In multivariate analysis the strongest predictor was nodal ratio for DFS (P=0.012) and expression of p53 for OS (P <0.001). CONCLUSION: The detection of MMC at diagnosis has no impact on survival in HRPBC patients treated with HDCT and ASCT.

Adult↗

PubMed2006

Intensive multimodality therapy including paclitaxel and reduced-intensity allogeneic hematopoietic stem cell transplantation in the treatment of adrenal cancer with multiple metastases.

Adrenocortical carcinoma is a rare malignancy in adolescents and young adults. The prognosis of unresectable/metastatic adrenocortical carcinoma remains very poor because the rarity of the tumor has made it difficult to establish treatment guidelines, and diagnosis and the resultant treatment can be greatly delayed. We treated a 24-year-old woman who was diagnosed with adrenocortical carcinoma of the right adrenal gland which extended to the inferior vena cava. Although she underwent surgical resection of the extensive tumor as the primary treatment, the disease recurred in the lung and liver as multiple metastases shortly after surgery. She received intensive multimodality therapy, including chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP regimen), embolization of the feeding arteries, and proton irradiation for the liver mass. Finally, she underwent reduced-intensity allogeneic hematopoietic stem cell transplantation from an HLA 1-locus-mismatched sibling donor. A prolonged survival of 39 months after the onset of the disease was achieved. Although this experience is limited, we suggest that TIP chemotherapy was effective for adrenocortical carcinoma, and a graft-versus-tumor effect after reduced-intensity stem cell transplantation may have contributed to the prolonged survival.

Adrenal Gland Neoplasms↗

PubMedDate not supplied

Developmental aspects of early pancreatic cancer.

The specific cell of origin responsible for generating pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma remains unknown. During development, epithelial stem cells within embryonic pancreatic epithelium give riseto mature acinar, ductal, and islet elements. Emerging evidence suggests that cells with precursor potential also exist within adult pancreas, resulting in significant developmental plasticity among both endocrine and exocrine cell types. In this review, the contribution of developmental plasticity in initiating pancreatic metaplasia and neoplasia is considered, and evidence supporting a role for epithelial stem cells in pancreatic cancer is discussed.

Carcinoma, Pancreatic Ductal↗

PubMed2006

Breast cancer-specific mRNA transcripts presence in peripheral blood after adjuvant chemotherapy predicts poor survival among high-risk breast cancer patients treated with high-dose chemotherapy with peripheral blood stem cell support.

PURPOSE: To study the prognostic significance of the presence of breast cancer-specific mRNA transcripts in peripheral blood (PB), defined by serial analysis of gene expression, in high-risk breast cancer (HRBC) patients undergoing high-dose chemotherapy after receiving adjuvant chemotherapy. METHODS: From 1994 to 2000, 84 HRBC patients (median age, 44 years; > 10 nodes; 74%) received adjuvant chemotherapy (fluorouracil, epirubicin, and cyclophosphamide for six cycles [83%] or doxorubicin and cyclophosphamide followed by paclitaxel) before undergoing one course of cyclophosphamide plus thiotepa plus carboplatin (STAMP V). Radiotherapy or hormone therapy was administered whenever indicated. Aliquots of apheresis-mononuclear blood cells were frozen from each patient. mRNA was isolated using an automatic nucleic acid extractor based on the magnetic beads technology; reverse transcription was performed using random hexamers. Cytokeratin 19, HER-2, P1B, PS2, and EGP2 transcripts were quantified to B-glucuronidase by real-time polymerase chain reaction (RT-PCR) using a linear DNA probe marked with a quencher and reporter fluorophores used in RT-PCR. Presence of PB micrometastases, estrogen receptor and progesterone receptor status, tumor size, age, tumor grade, number of nodes affected, and treatment with paclitaxel were included in the statistical analysis. RESULTS: Median follow-up was 68.3 months (range, 6 months to 103 months). Forty-seven relapses (56%) and 35 deaths (41.7%) were registered. Both tumor size and presence of micrometastases reached statistical significance according to the Cox multivariate model. Relapse hazard ratio (HR) for those patients with PB micrometastases was 269% (P = .006); death HR, 300% (P = .011). Time relapse was 53 months longer for patients without micrometastases: 31.3 v 84.2 months (P = .021). CONCLUSION: PB micrometastases presence after adjuvant chemotherapy predicts both relapse and death more powerful than classical factors in HRBC patients undergoing high-dose chemotherapy. Micrometastases search using a gene panel appears to be a more accurate procedure than classical approaches involving only one or two genes.

Adult↗

PubMed2004

Regimen-related toxicity following reduced-intensity stem-cell transplantation (RIST): comparison between Seattle criteria and National Cancer Center Common Toxicity Criteria (NCI-CTC) version 2.0.

Acute regimen-related toxicity (RRT) is minimal in reduced-intensity stem-cell transplantation (RIST). However, the Seattle RRT grading (Bearman et al), developed in the context of conventional-intensity transplantation, is frequently applied to RIST. We compared the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0 with the Seattle criteria after RIST in 86 patients. RRT within 30 days of transplant graded by both sets of criteria were significantly associated with the outcome confirming the predictive value of both the systems. A total of 15 patients died of disease progression, and 12 of transplant-related mortality: RRT (n = 2), graft-versus-host disease (GVHD) (n = 7), infection (n = 1), and others (n = 2). GVHD-related deaths primarily resulted from infections after steroid treatment (n = 6) and bronchiolitis obliterans (n = 1). This study shows that NCI-CTC is appropriate in toxicity evaluation of RIST, and that its application to RIST enables a toxicity comparison between RIST and other types of cancer treatments. Since GVHD is a significant problem in RIST, modifications are required to evaluate immunological complications following RIST.

Graft vs Host Disease↗

PubMed2004

Towards an integrated model for breast cancer etiology: the crucial role of the number of mammary tissue-specific stem cells.

Perinatal events and conditions, notably birth weight, are associated with breast cancer risk in offspring, and correlates of mammary gland mass are predictors of breast cancer risk. These findings may be interpreted as indicating that high levels of estrogens and components of the insulin-like growth factor system during pregnancy favour the generation of mammary tissue-specific stem cells, and that the number of these cells, which is positively associated with mammary gland mass, is an important determinant of breast cancer risk. Perinatal events and conditions may also affect risk for other malignancies, but the evidence in the case of breast cancer is prominent, possibly because estrogens and the insulin-like growth factor system are both involved in breast cancer etiology and affect birth weight.

Breast↗

PubMed1994

Tumour stem cells: the biological concept and its application in cancer treatment.

Experiments in different transplantable mouse tumours suggest that a proportion ranging from 0.1% to 100% of all tumour cells in these different tumours meet the functional definition criteria of tumour stem cells, i.e. regrowth of the tumour proceeded by clonal expansion from a single cell with unlimited proliferative potential. It is concluded that the proliferative organization of many or most human tumours may resemble that of the tissue of origin with a small proportion of stem cells and the majority of transit cells, both proliferating or resting. Cell loss and accelerated repopulation are due to regulated changes in the symmetry constraint of stem cell divisions.

Animals↗

PubMed2004

Overview of melanoma vaccines and promising approaches.

It is difficult to envision anything better than melanoma vaccines to exemplify the effectiveness of modern biotechnology in developing biologically rational therapeutics. Melanoma vaccines can reproducibly induce cytotoxic T lymphocyte (CTL) responses better than any other anticancer therapy. Anticancer vaccines have been labeled by some as ineffective for the simple reason that they only rarely lead to cancer regression. This oxymoron stems from the naïve expectation that CTLs are all that is needed to reject cancer. Little is known about requirements for CTL localization and effector function within the tumor microenvironment. In the future, more attention should be given to events downstream of immunization (afferent arm of immune response) to identify combination therapies likely to facilitate localization and activation of CTL at the receiving end (efferent arm).

Antigens, Neoplasm↗

PubMed1997

Cycles of dose-intensive chemotherapy with peripheral stem cell support in persistent or recurrent platinum-sensitive ovarian cancer.

OBJECTIVE: The objective was to determine the toxicity and surgically documented response rate of sequential high-dose chemotherapy with peripheral stem cell support in patients with persistent or recurrent cisplatin-sensitive ovarian cancer. METHODS: Fourteen patients (average age, 45 years) were treated with cyclophosphamide (4.5 g/m2), followed by granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral stem cell harvests. The subsequent regimen prescribed three courses of carboplatin (1 g/m2) and cyclophosphamide (1.5 g/m2 with 2-mercaptoethanesulfonate) every 2 weeks with stem cell support. This was followed by three courses of paclitaxel at 250 mg/m2 every 2 weeks with G-CSF support only. Six patients were entered on the basis of a positive second-look laparotomy and 8 patients had a first recurrence after at least a 6-month disease-free interval. RESULTS: Fourteen patients were entered and 12 patients completed all planned courses of therapy (mean time, 13 weeks). Normal hematopoiesis was reestablished after each cycle. Hospitalization for neutropenic fever occurred in 11/93 cycles (11.8%). Thirteen patients required blood transfusions and in 12 patients platelet transfusions were given. One patient had grade 3 neurotoxicity. An initial elevated CA 125 returned to normal in 7/8 patients (88%) and 71% of patients with measurable disease responded to therapy. There were 2 pathologic complete responders (PCR), making the PCR rate 2/14 or 14% (0-35%). CONCLUSION: Although this regimen was well tolerated and clinical response rates were high, the surgically documented response rate was not clearly superior to conventional salvage regimens in platinum-sensitive patients.

Adult↗

PubMed1999

Detection of circulating testicular cancer cells in peripheral blood.

Patients who receive peripheral blood stem cell transplants are at risk of developing cancer recurrence due to the presence of malignant cells in the transplants. We investigated a sensitive method to detect malignant cells in the peripheral blood and peripheral blood stem cells of patients with testicular cancer using nested, reverse transcription-polymerase chain reaction (RT-PCR) to measure alpha-fetoprotein gene expression. Using this technique, a single cancer cell could be detected in 10(6) peripheral blood mononuclear cells. This is the first report of an attempt to detect circulating malignant cells in the peripheral blood of patients with testicular cancer by nested RT-PCR.

Actins↗