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 415 records · Page 23Linked to original sources
PubMed1996

High-dose chemotherapy with stem-cell rescue for the treatment of breast cancer.

The use of high-dose chemotherapy with stem-cell rescue (HDC-SCR) in the treatment of breast cancer is reviewed. The rationale for HDC-SCR in breast cancer is based on the principles of dose response and dose intensity. After conventional-dose chemotherapy, hematopoietic progenitor cells are harvested from the bone marrow or peripheral blood. The patient then undergoes HDC-SCR. Peripheral-blood progenitor cells are becoming the preferred cells for hematopoietic rescue. Most clinical trails of HDC-SCR in metastatic breast cancer have resulted in high overall objective response rates (57-100%), with the highest rates occurring in patients with minimal residual disease or chemotherapy-sensitive disease at the time of high-dose treatment. Most protocols now include induction therapy before HDC-SCR; only patients who show sensitive disease proceed to high-dose therapy. In most studies published to date, the median duration of remission was less than one year from the time of high-dose therapy; however, 10-15% of patients achieved complete remissions lasting two or more years. Most patients relapse, however. Some studies have suggested value of HDC-SCR as consolidation therapy in the adjuvant setting for women at high risk of relapse. Short-term toxicities of HDC-SCR are manageable in experienced hands. Notable long-term adverse effects include leukemia, sterility, pulmonary toxicity, and hemolytic uremic syndrome. Unresolved issues include the utility of purging occult cancer cells from stem-cell-bearing specimens, the best preparative regimen, the implications of autologous graft-versus-host disease, the use of sequential cycles of high-dose chemotherapy, cost-effectiveness, and effectiveness compared with standard therapy. HDC-SCR appears to be a valid option for selected patients with metastatic breast cancer, and in the adjuvant setting for patients at high risk of recurrence. The cost-benefit profile remains to be defined in randomized trials.

Antineoplastic Agents↗
PubMed2006

Effect of stem cell turnover rates on protection against cancer and aging.

Tissue stem cells are responsible for replenishing and maintaining a population of cells which make up a functioning organ. They divide by asymmetric cell division where one daughter remains a stem cell while the other daughter becomes a transit cell, which divides a defined number of times and differentiates. A fully differentiated cell has a finite life-span. A tissue can be maintained by various strategies. Stem cells can divide often and differentiated cells die often (fast turnover). Alternatively, stem cells can divide infrequently, and the differentiated cells are long lived (slow turnover). Genetic alterations and mutations can interfere with tissue homoeostasis. Mutations can induce senescence and apoptosis, and this can result in a reduction of the number of functioning tissue cells which could correlate with tissue aging. Alternatively, mutations can result in the carcinogenic transformation of cells and the formation of a tumour. Using mathematical models, I find that the cellular turnover rate affects the ability of genetic alterations to induce aging and the development of cancer. If mutations occur as a result of errors during cell division, the model suggests that a low cellular turnover rate protects both against aging and the development of cancer. On the other hand, if mutations occur independent from cell division (e.g. if DNA is hit by damaging agents), I find that a high cellular turnover rate protects against aging, while it promotes the development of cancer. Implications for optimal tissue design are discussed.

Aging↗
PubMed2000

Chromosomal abnormalities in women with breast cancer after autologous stem cell transplantation are infrequent and may not predict development of therapy-related leukemia or myelodysplastic syndrome.

We determined prospectively the incidence of chromosomal abnormalities in patients with high-risk breast cancer (HRBC) after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), and correlated the cytogenetic abnormalities with the development of post-transplant myelodysplastic syndrome or acute myeloid leukemia (MDS/AML). From 1990 to 1999, 229 women with HRBC underwent ASCT. Cytogenetic analysis of bone marrow (BM) cells was performed 12-59 months after ASCT in 60 consecutive women uniformly treated with six courses of FAC/FEC followed by HDCT and ASCT. With a median follow-up of 36 months after ASCT, there were no cases of MDS/AML among the 229 patients. In the selected cohort of 60 patients, three (5%) showed clonal chromosomal abnormalities (two single trisomy X and one t(1;6)), whereas two additional patients showed non-clonal reciprocal translocations. Two of the patients with clonal aberrations had blood cytopenias as well as subtle dysplastic pictures in BM which were not classifiable as MDS according to the FAB criteria. Similar dysplastic features were also observed in four patients with normal karyotypes. All cytogenetic aberrations were transient and disappeared, except a +X detected by FISH in a residual cell population in one of the patients. Retrospective cytogenetic and FISH studies of samples obtained after six cycles of FAC/FEC and before transplant demonstrated no chromosomal abnormalities in any of the five patients with post-ASCT karyotypic changes. Early changes in karyotype detected in breast cancer patients following ASCT are transient and do not correlate with or predict development of MDS/AML. As these aberrations were not present before ASCT, they may be related to the HDCT regimen or transplant procedure rather than to the prior adjuvant therapy. Our results suggest that ASCT may be less likely to cause MDS or AML in breast cancer patients as compared to other malignancies. Bone Marrow Transplantation (2000) 25, 1203-1208.

Adult↗
PubMedDate not supplied

Screening for infectious foci in breast cancer patients prior to high-dose chemotherapy and stem cell transplantation.

UNLABELLED: Cancer patients treated with high-dose chemotherapy (HDC) followed by peripheral stem cell transplantation are at risk for infections during neutropenia. Our standard policy was to screen for potential infectious foci prior to HDC. Screening for infectious foci consisted of chest and sinus roentgenograms and a visit to the ear-nose-throat surgeon (ENT surgeon) and the dentist. The purpose of this study was to evaluate this approach. Between 1993 and 2000, 73 breast cancer patients received HDC. RESULTS: All chest roentgenograms were normal. ENT screening yielded in three (symptomatic) patients a potential infectious focus. In 32 patients (44%) a potential dental infectious focus was diagnosed and treated. During neutropenia after HDC clinical infections occurred in 15 patients (21%). In only 5 patients (7%) the infection focus was probably the upper respiratory tract. CONCLUSION: Potential ENT infectious foci were infrequent and all were symptomatic. Potential dental infectious foci were seen quite often; whether they would have had clinical impact if left untreated remains speculative.

Adult↗
PubMed2000

Typhlitis complicating autologous blood stem cell transplantation for breast cancer.

Three cases of typhlitis occurring during autologous blood stem cell transplantation (ABSCT) for metastatic breast cancer are described. Typhlitis is a rare complication of neutropenia and has uncommonly been reported in the autologous transplant setting. Although it has been most commonly described in children with leukemia, typhlitis has increasingly been reported in adult leukemias and in association with neutropenia secondary to chemotherapy for a number of solid tumors. Only five previous cases of typhlitis in the setting of ABSCT have been described. Whereas diarrhea and fever are common toxicities associated with high-dose chemotherapy, it is likely that many cases of typhlitis go unrecognized. Bone Marrow Transplantation (2000) 25, 321-326.

Adult↗
PubMed2005

Prostate stem cell antigen is overexpressed in prostate cancer metastases.

PURPOSE: Prostate stem cell antigen (PSCA) is expressed by a majority of prostate cancers and is a promising therapeutic target. PSCA protein and mRNA expression was examined in prostate cancer bone, lymph node, and visceral metastases to assess the potential of PSCA as an immunotherapeutic target in advanced prostate cancer. EXPERIMENTAL DESIGN: Immunohistochemical analysis of PSCA protein expression and quantitative mRNA expression analysis of PSCA was done on clinical specimens of prostate cancer bone, lymph node, and visceral metastases. PSCA protein and mRNA expression levels were quantified and compared between available matched pairs of bone and lymph node or visceral metastases. RESULTS: Bone metastases stained with higher intensity of PSCA compared with lymph node or liver metastases in seven of eight (87.5%) matched pairs (P = 0.035). PSCA mRNA expression was equal or greater than that of LAPC-9, a PSCA expressing xenograft, in 12 of 24 (50%) cases of prostate cancer metastases and was significantly correlated with PSCA protein expression (sigma = 0.84, P = 0.0019). Overall, PSCA protein expression was detected in 41 of 47 (87.2%), four of six (66.7%), and two of three (66.7%) cases of bone, lymph node, and liver metastases, respectively. Mean PSCA staining intensity was significantly higher in prostate cancer bone metastases compared with lymph node metastases (2.0 +/- 0.02 versus 0.83 +/- 0.31, P = 0.014). CONCLUSIONS: Prostate cancer metastases express PSCA. However, greater PSCA staining intensity and level of PSCA mRNA expression was associated with bone metastases compared with lymph node metastases. This study suggests that PSCA is a promising tumor marker and potential therapeutic target for patients with metastatic prostate cancer.

Antigens, Neoplasm↗
PubMed2026

EZH1/2 inhibition selectively targets SMARCA4/2 co-deficient lung cancer cells by suppressing stemness and proliferation.

SMARCA4-deficient thoracic malignancies comprise biologically heterogeneous tumors, ranging from conventional non-small cell lung cancer with SMARCA4 alterations to thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT), an aggressive entity frequently associated with concomitant SMARCA2 loss. However, the extent to which SMARCA4-deficient lung cancer cell lines recapitulate SMARCA4-UT-like biology remains incompletely defined. Here, we characterized lung cancer cell lines across distinct SMARCA4 and SMARCA2 states and identified a subgroup with SMARCA4/2 co-deficiency that exhibited reduced expression of epithelial lineage markers and transcriptional similarity to SMARCA4-UT and other SWI/SNF-deficient malignancies. The EZH1/2 inhibitor HM97662 selectively suppressed growth in SMARCA4/2-deficient cells, with limited effects in SMARCA2-proficient cells. EZH1/2 inhibition broadly reduced H3K27me3 and induced derepression of PRC2 targets regardless of drug sensitivity. However, its biological effects were most pronounced in SMARCA4/2-deficient cells, where it promoted apoptosis, reduced stemness marker expression, attenuated the SMARCA4-UT-associated transcriptional signature, and suppressed proliferative and mTORC1-related programs. Chromatin accessibility analysis further revealed cell-line-specific patterns of accessibility loss, with reduced accessibility at stemness-associated transcription factor motif-enriched regions coupled with transcriptional repression of nearby genes in SMARCA4/2-deficient cells. These findings support dual EZH1/2 inhibition as a potential therapeutic vulnerability in SMARCA4/2-deficient, SMARCA4-UT-like lung cancer cells.

Humans↗
PubMed1987

An improved human tumor stem cell assay in ovarian cancer.

To evaluate the effect of improved growth rates of ovarian cancers in the human tumor stem cell assay and its value in predicting clinical chemotherapy response, we studied 59 assays in 54 patients. A total of 81.6% of solid specimens and 85.7% of ascites specimens were successfully cultured and yielded an overall growth rate of 82.9%. Simultaneous primary and metastatic cultures were concordant for chemosensitivity in 80% (n = 16). The patients were evaluated for previous chemotherapy, residual volume of tumor, histologic type, and grade, and these were not statistically different between clinical responders and nonresponders. In vivo-in vitro correlations were made in 27 patients and yielded a predictive response of 13% and predictive resistance of 86% at 70% colony inhibition and 31% and 71% at 50% colony inhibition. Improved growth rates therefore did not result in better predictive correlations. The reported experience in ovarian cancer is summarized and the current status of the human tumor stem cell assay is reviewed.

Colony-Forming Units Assay↗
PubMed1996

Hematopoietic potential of IL-2-cultured peripheral blood stem cells from breast cancer patients.

Patients receiving autologous transplants for various malignancies generally experience an increased incidence of relapse compared with patients receiving unmanipulated allogeneic transplants. We initiated a protocol for IL-2 activation of peripheral blood stem cells (PBSC) for induction of in vitro and in vivo autologous graft-versus-tumor (GVT) activity in patients with breast cancer. In this study we analyzed the effects of 24 h of IL-2 incubation on the hematopoietic potential of PBSC from these patients. Cells collected by leukapheresis were first cryopreserved and stored in liquid nitrogen, then thawed rapidly and incubated with IL-2 in a serum-free system for 24 h, with samples analyzed before and after incubation. Although there was a significant drop in mononuclear cells (MNC) (from 4.5 to 3.7 x 10(8)/kg) and CD34+ cells (from 12.3 to 7.5 x 10(6)/kg) after 24 h in culture, there was no significant change in colony-forming units (CFU) (from 12.5 to 11.5 x 10(5)/kg). Time to engraftment (neutrophils: < 0.5 x 10(9)/l; platelets: > 20 x 10(9)/l) was comparable to a cohort of similar patients receiving non-cultured PBSC transplants. These results indicate that mobilized frozen/thawed PBSC which have been cultured in IL-2 for 24 h retain adequate potential for hematopoietic reconsistution in this group of patients.

Breast Neoplasms↗
PubMed1996

Selection and expansion of peripheral blood CD34+ cells in autologous stem cell transplantation for breast cancer.

Cytopenia after high-dose chemotherapy and autologous stem cell reinfusion is a major cause of morbidity. Ex vivo cultured expansion and differentiation of CD34+ peripheral blood progenitor cells (PBPC) to neutrophil precursors may shorten the neutropenic period further. We explored the use of these ex vivo cultured PBPCs in nine patients with metastatic breast cancer. All underwent PBPC mobilization with cyclophosphamide, VP-16, and G-CSF. Subsequently, they underwent four to five apheresis procedures. One apheresis product from each patient was prepared using the Isolex 300 Magnetic Cell Separation System (Baxter Immunotherapy, Irvine, CA) to obtain CD34+ cells. These cells were then cultured in gas permeable bags containing serum-free X-VIVO 10 (BioWhittaker, Walkersville, MD) medium supplemented with 1% human serum albumin and 100 ng/mL PIXY321. At day 12 of culture the mean fold expansion was 26x with a range of 6 to 64x. One patient's cells did not expand because of a technical difficulty. The final cell product contained an average of 29.3% CD15+ neutrophil precursors with a range of 18.5% to 48.1%. The patients underwent high-dose chemotherapy with cyclophosphamide, carboplatin, and thiotepa. On day 0, the cryopreserved PBPCs were reinfused and on day +1 the 12-day cultured cells were washed, resuspended, and reinfused into eight of nine patients. One patient was not infused with cultured cells. The mean number of cultured cells reinfused was 44.6 x 10(6) cells/kg with a range of 0.8 to 156.6 x 10(6) cells/kg. No toxicity was observed after reinfusion. The eight patients have recovered absolute neutrophil counts > 500/microL on a median of 8 days (range 8 to 10 days); the median platelet transfusion independence occurred on day 10 (range 8 to 12 days) and platelet counts > 50,000/microL were achieved by day 12 (range 9 to 14) for the seven patients whose platelet counts could be determined. Expanded CD34+ selected PBPC can be obtained and safely reinfused into patients.

Adult↗
PubMed2003

Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia.

All of the different types of stomach epithelial cells are known to be derived from a single progenitor cell in each gland. Similarly, cancers develop from single cells, based on data from clonality analysis in C3H/HeN<-->BALB/c chimeric mice. Using gastric and intestinal epithelial cell markers, intestinal metaplasia (IM) can be divided into two major types: a gastric and intestinal (GI) mixed type, and a solely intestinal (I) type. Ectopic expression of Cdx genes and down-regulation of Sox2 in isolated single GI mixed IM glands suggests abnormal differentiation of stem cells that can produce both gastric (G) and I type cells. Similarly, phenotypic expression of gastric cancer cells of each histological type can be clearly classified into G and I type epithelial cells. The heterogeneity of phenotypic expression of gastric cancer cells in individual cancers is assumed to reflect this intrinsic potential for differentiation in two directions. Gastric cancers at early stages, independent of the histological type, mainly consist of G type cells, and phenotypic shift from G to I type expression is clearly observed with progression. The data thus suggest IM may not be a preneoplastic change in gastric carcinoma, but rather that cells of the I type may appear independently in the gastric mucosa in IM and in gastric cancers. Intestinalization of gastric mucosa and cancer cells may represent a kind of homeotic transformation. Whether disturbance of the regulation of Sox2 and Cdx genes may be of importance to the biological behavior of gastric cancers should therefore be clarified in future studies.

Animals↗
PubMed2000

Graft-versus-tumour effect in non-small-cell lung cancer after allogeneic peripheral blood stem cell transplantation.

Clinical evidence of a graft-vs.-tumour effect in solid tumours after haematopoietic stem cell transplantation is lacking. We report for the first time a complete and durable regression of a stage IB non-small-cell lung carcinoma in a patient who had received an allogeneic peripheral blood haematopoietic stem cell transplant for acute myeloblastic leukaemia in first complete remission. Disappearance of the tumour coincided with development of graft-vs. -host disease. This suggests that simultaneous generation of cytotoxic T lymphocytes against lung carcinoma cells could have been responsible for the regression. This unique clinical observation broadens the possibility of using allogeneic haematopoietic stem cell transplantation in treating neoplasias lacking significant sensitivity to chemotherapy.

Biopsy↗
PubMed2007

OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer.

OCT-4 (also known as POU5F1) is a key regulator of self-renewal in embryonic stem cells. Regarding the new cancer stem cell concept, the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of tumor behavior, such as tumor recurrence or resistance to therapies. Although OCT-4 has been introduced as a molecular marker for germ cell tumors, little is known about its expression in somatic cancers. Here, we have investigated the potential expression of OCT-4 in bladder cancer. We used semiquantitative RT-PCR to examine the expression of OCT-4 in 32 tumors, 13 apparently nontumor tissues taken from the margin of tumors and 9 normal urothelial tissues. The expression of OCT-4 at protein level was further determined by Western blotting and immunohistochemical (IHC) analysis. OCT-4 expression was detected in almost all examined tumors (31/32), but at much lower level (p<0.001) in some nonneoplastic samples (6/22). A significantly strong correlation of 0.6 has been observed between OCT-4 expression and the presence of tumors (p<0.001). Western blot analysis further confirmed the expression of OCT-4 in tumor biopsies. According to IHC results, OCT-4 is primarily localized in the nuclei of tumor cells, with no or low immunoreactivity in nontumor cells. Our study demonstrated, for the first time, the expression of OCT-4 in bladder cancer and a further clue to the involvement of embryonic genes in carcinogenesis.

Biomarkers, Tumor↗
PubMed2005

[Study on the mechanisms of imatinib-resistance of cancer stem-like cells in K562/Vp16 cell line].

OBJECTIVE: To elucidate the mechanisms of imatinib resistance involved in some chronic myeloid leukemia (CML) cells overexpressing P-glycoprotein (P-gp). METHODS: Generation of resistant K562 cell line K562/Vp16 overexpressing P-gp was achieved by exposure of K562 cells to stepwise increase of concentrations of Vp16. A small set of side population (SP) with the characteristics of stem cells being capable of efflux fluorescent dye Hoechst 33342 in the cell line was isolated by flow cytometry. The mechanisms involved in K562/Vp16 SP cells resistant to imatinib were studied. RESULTS: The levels of BCR/ABL and ABL proteins in K562 cells were similar to those in K562/Vp16 non-SP and K562/Vp16 SP cells. The 170 KDa P-gp was detected in K562/Vp16 and K562/Vp16 SP cells at similar levels but not in K562 cells. Compared with K562/Vp16 non-SP cells, K562/Vp16 SP cells were more resistant to imatinib, which could hardly be reversed by many multidrug resistance inhibitors. In addition, in vivo study showed that the malignancy of K562/Vp16 cells was largely attributed to the SP cells. CONCLUSIONS: Bcr/Abl gene amplification and multidrug-resistant gene 1 (mdr1) overexpression might not be an important clinical mechanism in the diversity of resistance to imatinib treatment, and the development of drug resistance by leukemia cells may be at least partly due to a rare SP of tumor stem-like cells which drives leukemia occurrence and maintenance. These SP cells might be targeted for effective cancer therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Purging of contaminating breast cancer cells from hematopoietic stem cell grafts by adenoviral GAL-TEK gene therapy and magnetic antibody cell separation.

The presence of contaminating tumor cells in autologous bone marrow or peripheral blood stem cell (PB-SC) preparations increase the likelihood of relapse in women receiving transplants for metastatic breast cancer. We describe a new technique for purging breast cancer cells (BCCs) that combines two independent strategies: (a) the specific enrichment of CD34+ progenitor stem cells by magnetic antibody cell separation (MACS), and then (b) infection of the contaminating BCCs with a recombinant adGAL-TEK marker/suicide gene adenovirus (ad-v), followed by the addition of ganciclovir (GCV). Infection with this ad-v results in three to four times greater expression of ad-v-delivered reporter gene in BCCs than in CD34+ cells. In addition -2 h, -low multiplicity of infection (50:1) adGAL-TEK infections of BCC lines (MCF-7 and BT474) eradicated >99% of BCCs after 72 h of exposure to 20 microM GCV. However, exposure to both adenovirus and GCV at the MOIs and doses used had little effect on hematopoietic stem cells to form colonies in colony-forming unit assays. adGAL-TEK infection in our model system (10(3)-10(5) BCCs added into 10(7) HSCs) also resulted in the 3 to 5 log eradication of clonogenic BCCs after the addition of GCV. MACS enrichment/purification of CD34+ cells from PB-SC contaminated with 2 x 10(6) to 5 x 10(7) BCCs followed by adGAL-TEK infection and GCV addition resulted in 5-7-log depletion of clonogenic BCCs as well as enrichment of CD34+ progenitor cells to >98%, with the recovery of >70% of hematopoietic stem cells. This adenoviral purging system is so robust that poor MACS purification, resulting in 1.5-log depletion of BCCs, still permits excellent ad-v infection and BCC killing.

Adenoviridae↗