Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:High-dose chemotherapy with stem-cell rescue for the treatment of breast cancer. 869 12

The interval between courses of chemotherapy have classically been kept to a minimum in order to maximize dose intensity. Certain clinical observations suggest that longer intervals, particularly in the high-dose setting, may be more effective. This is based in part on the evidence that resistance is reversible over time and that the interval should be sufficient to allow for such a reversal. Clinical evidence for such reversibility include the following. In metastatic breast cancer, double or double high-dose stem cell rescue (HD-SCR) studies involving a minimal interval, have not, at least as yet, been shown to be superior to single HD-SCR. In Hodgkin's disease, response after relapse correlates directly with duration of time to relapse. In a comparative study of metastatic breast cancer, early HD-SCR preceded by daunorubicin induction was inferior to delayed HD-SCR. The latter was not preceded by induction chemotherapy. In a comparative study of childhood ALL, patients randomized to delayed (4 month interval) intensification had a significantly superior survival as compared to patients randomized to immediate (1 month interval) intensification. Taken together, these clinical observations indicate that resistance is reversible and that optimization of the interval must take this into account. Cytokinetic modeling of those clinical studies also found that delayed HD-SCR could result in a superior effect. Cytokinetic models of minimal residual tumor which were also examined included the Skipper exponential model, the Norton-Simon model which emphasizes the Gompertzian effect, the clonal evolution model, and the Retsky-Demisheli model which derives from a bimodal relapse pattern above. Biological and clinical data have resulted in a clinical protocol in the CALGB wherein patients with metastatic breast cancer are randomly allocated to (1) a single HD-SCR arm; (2) a double HD-SCR with a 5-week interval; and (3) a double HD-SCR arm with a 16 week interval.
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PMID:The interval between courses of high-dose chemotherapy with stem cell rescue: therapeutic hypotheses. 1055 51

Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. Vascular endothelial growth factor-C (VEGF-C) and VEGF-A are involved in lymphangiogenesis and angiogenesis. To inhibit metastasis, combination therapy with vector-based small interfering RNA (siRNA) against VEGF-C and/or VEGF-A was conducted on murine metastatic mammary cancer. Syngeneic, inoculated, metastatic mammary cancers received direct intratumoral injection of plasmid siRNA vector targeting VEGF-C (psiRNA-VEGF-C), VEGF-A (psiRNA-VEGF-A), both VEGF-C and VEGF-A (both psiRNA-VEGF-C and psiRNA-VEGF-A vectors injected, referred to as the psiRNA-VEGF-C+A group) or a scrambled sequence (psiRNA-SCR) as control, once a week for 8 weeks. Gene electrotransfer was performed on the tumors after each injection. Tumor volume was significantly lower in the psiRNA-VEGF-A and the psiRNA-VEGF-C+A groups throughout the study. Lymph node metastasis was significantly less frequent in all therapeutic groups, whereas the multiplicity of lung metastases was significantly lower in the psiRNA-VEGF-C+A group only. All siRNA therapeutic groups showed a significant reduction in the number of dilated lymphatic vessels containing intraluminal cancer cells and microvessel density. Our data suggest that specific silencing of the VEGF-C or VEGF-A gene alone can inhibit lymph node metastasis. However, combination siRNA therapy targeting both VEGF-C and VEGF-A inhibits both lymph node and lung metastasis, rendering this combined therapy more beneficial than either alone. The observed anti-metastatic activity of siRNA-expressing vectors targeting VEGF-C or VEGF-A may be of high clinical significance in the treatment of metastatic breast cancer.
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PMID:Combination therapy with short interfering RNA vectors against VEGF-C and VEGF-A suppresses lymph node and lung metastasis in a mouse immunocompetent mammary cancer model. 1865 13