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At least 595 records · Page 33Linked to original sources
PubMed1995

High-dose carboplatin, thiotepa and cyclophosphamide (CTC) with peripheral blood stem cell support in the adjuvant therapy of high-risk breast cancer: a practical approach.

In 29 chemotherapy-naive patients with stage II-III breast cancer, peripheral blood stem cells (PBSCs) were mobilised following fluorouracil 500 mg m-2, epirubicin 90-120 mg m-2 and cyclophosphamide 500 mg m-2 (FEC) and granulocyte colony-stimulating factor (G-CSF; Filgrastim) 300 microgram s.c. daily. In all but one patient, mobilisation was successful, requiring three or fewer leucocytopheresis sessions in 26 patients; 28 patients subsequently underwent high-dose chemotherapy consisting of carboplatin 1600 mg m-2, thiotepa 480 mg m-2 and cyclophosphamide 6 g m-2 (CTC) followed by PBSC transplantation. Haemopoietic engraftment was rapid with a median time to neutrophils of 500 x 10(6) l(-1) of 9 days (range 8-10) in patients who received G-CSF after PBSC-transplantation; platelet transfusion independence was reached within a median of 10 days (range 7-16). Neutropenic fever occurred in 96% of patients. Gastrointestinal toxicity was substantial but reversible. Renal, neural or ototoxicity was not observed. Complications related to the central venous catheter were encountered in 64% of patients, with major vein thrombosis occurring in 18%. High-dose CTC-chemotherapy with PBSC-transplantation, harvested after mobilisation with FEC and G-CSF, is reasonably well tolerated without life-threatening toxicity and is a suitable high-dose strategy for the adjuvant treatment of breast cancer.

Adenocarcinoma↗
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↗
PubMed2001

Computer modeling implicates stem cell overproduction in colon cancer initiation.

On the basis of our investigation of the premalignant crypt phenotype in familial adenomatous polyposis patients, the hypothesis is developed that tumor initiation in the colon is caused by crypt stem cell overproduction. A novel kinetic model for the colonic crypt was used to investigate how the earliest tissue abnormality (altered crypt labeling index) arises in these patients who have a mutant APC genotype. Only an increase in crypt stem cell number, not changes in the rate of cell cycle proliferation, differentiation, or apoptosis of the non-stem cell population, simulated this abnormality. This suggests that APC regulates the number of stem cells in the colonic crypt and when the cells become mutant, an expansion of the crypt stem cell population results.

Adenomatous Polyposis Coli↗
PubMed1998

High-dose chemotherapy in patients with breast cancer: evaluation of infusing peripheral blood stem cells containing occult tumor cells.

The purpose of this study was to evaluate the frequency of detecting occult tumor cells in peripheral blood stem cell (PBSC) harvests and to determine the impact of infusing such cells on relapses after high-dose chemotherapy (HDC). Peripheral blood stem cell harvests from 223 patients with breast cancer were examined by an immunocytochemistry (ICC) method for detection of occult tumor cells, and infused after HDC without consideration of test results. Two hundred and four patients, 114 with stage II-III and 90 with stage IV disease who received only PBSC, that were tested by ICC were evaluated for time to relapse. Five hundred and eighty-one of 619 PBSC harvests (94%) from 223 patients were tested. Fifty-three of 581 harvests (9%), 8% from stage II-III and 10% from stage IV patients, were positive by ICC (P = 0.68). Forty-one of 223 patients (18%), 17/122 (14%) with stage II-III and 24/101 (24%) with stage IV disease, had positive harvests (P = 0.06). Eleven percent of patients who had 1-2 harvests tested were positive as compared to 32% of patients who had > or =3 PBSC harvests tested (P < 0.001). Nineteen patients who were infused with a mixture of ICC negative and untested PBSC harvests were excluded from analyses of relapse. The probabilities of relapse at 18 months for the 97 patients with stage II-III disease infused with ICC-negative and the 17 with ICC-positive PBSC were 0.19 and 0.13, respectively (P = 0.48). The probabilities of relapse at 18 months for patients achieving a CR or a CR in non-bone sites and improvement in bone lesions were 0.55 for the ICC-negative group (n = 30) and 0.45 for the ICC-positive group (n = 11) (P = 0.60). It was concluded that occult tumor cells were detected by ICC in PBSC harvests from a relatively small fraction of women with breast cancer, but were not associated with a significant increase in the probability of early relapse or progression when infused after HDC.

Adult↗
PubMed2000

High-dose ifosfamide and etoposide with filgrastim for stem cell mobilization in patients with advanced ovarian cancer.

High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation has shown promise as treatment for recurrent or persistent epithelial ovarian cancer. We evaluated the stem cell mobilization regimen of high-dose ifosfamide plus etoposide in 32 patients with epithelial ovarian cancer, who had a positive second-look laparatomy or recurrent disease. Ifosfamide was given at 10 g/m2 by continuous i.v. from days 1 to 3. Etoposide was given at 150 mg/m2 every 12 h for six doses on days 1-3. Filgrastim was given at 10 microg/kg/d s.c. from day 5 until the completion of peripheral blood stem cell harvest. Fourteen of 32 patients had measurable or evaluable disease before mobilization therapy and were assessed for response. In nine (64%) of the 14 patients, treatment response was demonstrated, and these patients received a second cycle of mobilization therapy. The target CD34+ cell dose (>8 x 106 cells/kg) was achieved with a median of one apheresis (range 1-5). A median of 25.1 (range 8.0-122.5) x 106 CD34+ cells/kg body weight was collected. Non-hematologic toxicity was limited to grade 2 renal dysfunction in one patient and grade 2 hepatic dysfunction in three patients. In this patient group, high-dose ifosfamide plus etoposide with filgrastim support was well tolerated, lead to successful stem cell harvest and had antitumor activity.

Adult↗
PubMed1986

Concern about cancer in women undergoing elective gynaecological surgery.

Interviews were conducted with 63 women aged 18-75 shortly after their admission to hospital for routine non-cancer gynaecological surgery. Three groups were studied: major surgery, chiefly hysterectomy, carried out for benign conditions (n = 25); minor surgery such as dilatation and curettage (n = 29); fertility investigations and sterilisations (n = 9). Women were asked whether they worried if they were suffering from seven serious illnesses including heart disease, breast cancer and gynaecological cancer (cancer of the cervix, womb or ovaries). Significantly more women were concerned that they suffered from gynaecological cancer than any other illness. When asked why they were worried, over 85% of those expressing concern believed that their current gynaecological problem stemmed from cancer. Worry about gynaecological cancer was positively associated with psychiatric status and gynaecological knowledge, and negatively with satisfaction with treatment. A link with presenting clinical symptoms was also identified. This study revealed high levels of unwarranted distress in women undergoing routine surgery. Such fears may not be allayed, since surgeons and staff may not consider cancer to be relevant to the patient's clinical condition.

Adolescent↗
PubMed2006

Expression of Oct4, a stem cell marker, in the hamster pancreatic cancer model.

BACKGROUND: Oct4 has been shown to present a stem cell marker that is expressed in embryonic cells and in germ cell tumors. Recently, its expression in a few human tissues and cancer cells has been reported. Because in the hamster pancreatic cancer model most tumors develop from within islets presumably from stem cells, we investigated the expression of Oct4 in this model. METHODS: Two normal pancreases and 15 pancreatic cancers induced by N-nitrosobis(2-oxypropyl)amine (BOP) were processed for immunohistochemistry using a monoclonal Oct4 antibody at a concentration of 1:500. RESULTS: In the normal pancreas, Oct4 was expressed only in islet cells in a diffuse cytoplasmic pattern. No nuclear staining was found in any cells. In 14 of the pancreatic cancers, nuclear staining was detected in many cells or in small foci. Diffuse cytoplasmic but no nuclear staining was found in one tumor and a mixed Golgi type and nuclear staining in two cases. Nuclear staining was also identified in early intrainsular ductular and in Ca in situ lesions. CONCLUSIONS: BOP reactivates the Oct4 gene and can be considered an early tumor marker in this model.

Animals↗
PubMed1994

Dose intensive therapy with autologous blood stem cell transplantation in breast cancer.

BACKGROUND: Breast cancer is the commonest form of cancer in Australian women. Although approximately 50% of women with breast cancer achieve long term survival by current management methods, recurrent or metastatic disease is generally incurable. In addition, women with Stage II disease with > 10 positive axillary lymph nodes and also women with locally advanced disease (Stage III) have a poor survival even with adjuvant therapy. AIMS: To assess the toxicity and efficacy of high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation in women with both metastatic and poor prognosis primary breast cancer. METHODS: Twenty-eight women with either metastatic (15) or poor prognosis (13) primary breast cancer were enrolled in the study between November 1988 to January 1993. PBSC were harvested using high-dose cyclophosphamide (Cy) with or without granulocyte-colony stimulating factor (G-CSF) and a myeloablative regimen of Cy, melphalan and carboplatin (CMCp) was used in the transplantation phase. RESULTS: Optimum numbers of stem cells were harvested in 85% of patients. The use of five G/m2 Cy plus G-CSF resulted in better PBSC yields and a significant reduction in haematologic morbidity when compared to mobilisation with Cy alone. Twenty-two women underwent 23 PBSC transplants (PBSCT). There have been two early deaths due to sepsis. The predominant morbidities observed following high dose chemotherapy and transplantation have been nausea, mucositis and diarrhoea. The median number of days to discharge following infusion of PBSC was 15 (range 11-21). At a median follow up time of 1.1 years (range 0 months-3.6 years), 8/22 (36%) evaluable patients remain alive and disease free while 14/22 (64%) have relapsed or progressed or died. CONCLUSION: High-dose chemotherapy and autologous PBSCT is a potentially highly effective treatment of women with metastatic and poor prognosis primary breast cancer. Randomised studies are required to compare this form of therapy to more standard forms of treatment in breast cancer.

Adult↗
PubMed1995

Blood stem cell transplantation and gene therapy of cancer.

Based on the concept of circulating hematopoietic stem cells with indefinite self-renewal capacity that gives rise to all three cell lineages, peripheral blood progenitor cells (PBPCs) have widely replaced the use of bone marrow (BM) progenitors for autologous transplantation purposes in patients with malignant hematological disorders and selected solid tumors. Ex vivo purification of normal CD34+ cell subsets contained in the patient's apheresis product possibly eliminates clonogenic tumor cells, but also serves as a target cell population for gene transduction. Genetic tagging of PBPC autografts has proven that: 1) NEOR gene expression is sustained for more than 18 months and 2) clonogenic tumor cells contaminating the autograft contribute to relapse. A second generation of gene transduction studies includes new treatment strategies such as the induction of chemoprotection (multidrug resistance gene-1), chemotherapy sensitization (p53), cancer vaccination and genetic chemosensitization. Most recently allogeneic PBPC transplantation has successfully been introduced with the intention of improving the graft-versus-leukemia effect without inducing a higher incidence or more severe graft-versus-host disease (GVHD) than what is expected after BM transplantation. Introducing the herpes virus thymidine kinase cDNA into activated donor T cells makes them susceptible to gangciclovir, thus allowing the in vivo inactivation of GVHD-inducing T cells. With the close interaction of molecular genetics and clinical oncology/hematology, genetic engineering of stem cell grafts will lead into a new stage of stem cell transplantation technology.

Genetic Therapy↗
PubMed2004

Nonmyeloablative allogeneic stem cell transplantation for patients with unresectable pancreatic cancer.

OBJECTIVES: To clarify whether nonmyeloablative allogeneic stem cell transplantation (NST) can produce the graft versus tumor (GVT) effect in patients with pancreatic cancer. METHODS: A pilot trial of NST was conducted in 5 patients with unresectable pancreatic cancer. Preparative conditioning consisted of administration of 60 mg/kg cyclophosphamide on days 6 and 7 before transplantation, followed by 25 mg fludarabine per square meter of body surface on each of the last 5 days prior to transplantation. Cyclosporine was started 4 days before transplantation. Peripheral blood stem cells from the patients' HLA-identical siblings were transfused into the patients. RESULTS: Complete donor T-cell chimerism in peripheral blood was obtained in 4 patients on day 15 after transplantation. NST resulted in tumor reduction in 2 patients as determined by CT, decreasing levels of tumor markers in 2 patients, pain relief in 2 patients, and a decrease in pleural fluid in 1 patient. Two patients developed acute graft versus host disease (GVHD) of grade II or III and 2 had chronic GVHD involving skin and/or liver. Administration of immunosuppressive drugs for the treatment of GVHD resulted in the elevation of tumor marker levels. CONCLUSION: These findings are the first to suggest that NST induces a GVT effect on pancreatic cancer.

Adult↗
PubMed2006

Embryonic stem cells: a great hope for a new era of medicine.

Current stem-cell research has the potential to lead to new approaches for the treatment of cardiovascular, neurodegenerative and musculoskeletal diseases, as well as diabetes and cancer. Stem-cell-based approaches could be employed in cell-replacement therapy or in drug treatments that encourage adult stem cells to migrate and activate at a site of injury or disease. For such therapeutic approaches to be successful, a greater understanding of the signaling pathways that determine the diverse developmental fates of these cells is needed. From a drug-discovery perspective, efforts are being deployed in developing cell-based assays to screen for small molecules that can modulate stem-cell fate. Such compounds will provide new insights into stem-cell biology, and may ultimately contribute to effective disease treatments.

Animals↗
PubMed2006

Utilizing quantitative polymerase chain reaction to evaluate prostate stem cell antigen as a tumor marker in pancreatic cancer.

BACKGROUND: Real-time quantitative polymerase chain reaction (qPCR) may prove to be a sensitive technique by which to evaluate potential tumor markers in pancreatic cancer. METHODS: The prostate stem cell antigen (PSCA) gene was identified as a marker highly expressed in pancreatic adenocarcinoma and not normal pancreas. RNA from pancreatic and nonpancreatic cancer cell lines as well as tissue and blood from pancreatic cancer and control patients was reverse-transcribed and PSCA quantified by qPCR. RESULTS: Individual operator experience affects the results of qPCR, with significantly different copy numbers at experiment numbers 5, 15, and 40. Five of six pancreatic cell lines had PSCA/actin ratios 10-fold greater than nonpancreatic cancer lines. Mean PSCA expression in pancreatic tumor tissue was significantly higher (P < 0.05, Student's t-test) than in the tissue of benign pancreatic processes. The close correlation of PSCA/actin copy number with number of tumor cells in the blood was demonstrated by regression analysis (r = 0.768, P = 0.0001). PSCA copy number was significantly higher in the blood of patients with metastatic pancreatic cancer than in that of normal patients (P < 0.05, Student's t-test). CONCLUSIONS: Such trends suggest that PSCA may prove to be a valuable pancreatic cancer tumor marker. More generally, the technique of qPCR is shown to provide a sensitive method of evaluating markers in cancer patients.

Adenocarcinoma↗
PubMed1993

Immunological reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation for advanced ovarian cancer.

We evaluated the immunological reconstitution of patients who underwent high-dose chemotherapy and autologous blood stem cell transplantation (ABSCT) for advanced ovarian cancer. Sixty days after transplantation a complete reconstitution of lymphocytes and of the CD3, CD4, CD8, CD19, and CD16/56 subsets was observed in this series. A significant increase in the count of interleukin-2 receptor expressing lymphocyte (CD25) was found on day +60 after transplantation compared to that obtained at diagnosis and before transplantation. A significantly higher lymphokine-activated killer (LAK) precursor activity was seen on day +60 compared to the values obtained at diagnosis and before transplantation while natural killer activity did not show any significant variation. We conclude that ABSCT gives prompt and complete immunohaematopoietic reconstitution after high-dose treatment. Moreover, our data support the feasibility of interleukin-2/LAK therapy as consolidative therapy after ABSCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

UKCCSG study of accelerated radiotherapy for pediatric brain stem gliomas. United Kingdom Childhood Cancer Study Group.

PURPOSE: Between 1991 and 1994, the United Kingdom Childhood Cancer Study Group (UKCCSG) conducted a multicenter study to assess the efficiency and tolerability of accelerated radiotherapy in children with a diagnosis of poor-prognosis brain stem glioma. METHODS AND MATERIALS: Patients eligible for study were those aged 3-16 years with tumors arising in the pons, medulla, or midbrain, not previously treated with radiotherapy or chemotherapy. Histologic confirmation was not mandatory, but computed tomography or magnetic resonance imaging and clinical findings had to be typical, and patients were selected with short prediagnosis symptom history (<3 months), cranial nerve palsies or long tract signs, and intrinsic diffuse lesions on scanning. The treatment dose was 48.6 Gy in 27 fractions, increased to 50.4 Gy in 28 fractions in January 1992, delivered twice daily (except weekends) with an interfraction interval of at least 8 h. Between January 1991 and July 1994, 28 available patients were recruited: 15 boys and 13 girls with ages ranging between 3 and 13 years (median 6). RESULTS: After treatment, neurologic improvement sustained for a period of at least 6 weeks without steroids was reported in 13 children (46%). On central review of postradiotherapy imaging, 50% of children showed evidence of partial response, but none exhibited a complete response. A further six patients (22%) had stable disease. The median survival time was 37 weeks (8.5 months); 1-year survival was 32%, and 2-year survival 11%. The pattern of relapse was local in all 26 patients who died of their disease; 1 patient had evidence of leptomeningeal seeding. Acute radiation morbidity was minimal, with only three patients (11%) exhibiting mild toxicity. No evidence of radiation-induced necrosis was found radiologically or histologically at postmortem. Ability to withdraw steroids following radiotherapy was the single most important prognostic variable in our study. CONCLUSION: The results of this study are comparable to previous outcomes of studies with conventional and hyperfractionated radiotherapy in poor-prognosis brain stem glioma. The fractionation regimen was shown to be tolerable with an acceptable morbidity profile. However, further research is required to improve the poor prognosis of these unfortunate children.

Adolescent↗