Critical reviews in oncology/hematology
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Many changes in the vasculature, hemostasis and endothelium, including alterations of platelets, coagulation and fibrinolytic factors, occur during aging. While the increasing hypercoagulability observed with aging may account for the higher incidence of thrombotic cardiovascular disorders in the elderly, the lack of genetic protective factors against thrombosis in healthy centenarians suggests that little is yet known about the age-associated changes of hemostasis. The complex inter-relationships between inherited and acquired factors influencing the hemostatic system during aging are discussed in this review.
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Crit. Rev. Oncol. Hematol. · Jul 2006
ReviewCyclooxygenase-2 as a target for anticancer drug development.
The two isoforms cyclooxygenase-1 and -2 catalyze the initial step in the formation of prostaglandins in a variety of pathophysiological processes. More recently their role in carcinogenesis has become more evident. They seem to influence apoptosis, angiogenesis, and invasion, and play a role in the production of carcinogens. ⋯ However, NSAIDs effects in cancer cells are mediated not only by COX enzymes but also by interactions with downstream effectors of COX-2. Hence, we can state that targeting the COX-2 pathway is a promising strategy in the prevention and treatment of solid tumors. Ongoing trials are expected to answer - at least partly - the remaining questions concerning COX-2 and cancer.
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Crit. Rev. Oncol. Hematol. · May 2006
Comparative StudyDose-dense adjuvant chemotherapy for node-positive breast cancer in women 60 years and older: feasibility and tolerability in a subset of patients in a randomized trial.
To evaluate the feasibility and tolerability of dose-dense adjuvant chemotherapy for older patients with node-positive breast cancer, a retrospective subset analysis compared dose delays and dose reductions for women aged > or = 60 years with those of younger women. Patients were randomized to a dose-dense (DD, 14-day cycle) or conventional-schedule (CS, 21-day cycle) regimen. DD patients (n = 104; 25 aged > or = 60 years) received epirubicin 90 mg/m2 plus paclitaxel 175 mg/m2 (four cycles), then cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2 and fluorouracil 600 mg/m2 (CMF 600/40/600) (three cycles), plus filgrastim 5 microg/kg per day in every cycle. ⋯ Delays were more common in older patients in both the DD and CS groups (DD, 17% versus 6%; CS, 11% versus 6%), as were Grades 3-4 leukopenia (26% versus 12%) and neutropenia (33% versus 25%). All older DD and 89% of older CS patients received all seven chemotherapy cycles, with 99% of cycles at full dose. This study demonstrates that a dose-dense regimen combining epirubicin and paclitaxel can be administered to patients > or = 60 years of age with a tolerable safety profile.
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Crit. Rev. Oncol. Hematol. · Feb 2006
ReviewNovel targeted therapies to overcome imatinib mesylate resistance in chronic myeloid leukemia (CML).
Imatinib mesylate (Gleevec) was developed as the first molecularly targeted therapy that specifically inhibits the BCR-ABL tyrosine kinase activity in patients with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML). Due to its excellent hematologic and cytogenetic responses, particularly in patients with chronic phase CML, imatinib has moved towards first-line treatment for newly diagnosed CML. Nevertheless, resistance to the drug has been frequently reported and is attributed to the fact that transformation of hematopoietic stem cells by BCR-ABL is associated with genomic instability. ⋯ Some of these drugs have already been successfully tested in preclinical studies where they show promising results. Additional approaches are geared towards targeting the expression or stability of the BCR-ABL kinase itself or targeting signaling pathways that are chronically activated and required for transformation. In this review, we will discuss the underlying mechanisms of resistance to imatinib and novel targeted approaches to overcome imatinib resistance in CML.
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Lung cancer remains the leading cause of cancer-related deaths in the world. At present, the only high rate of cure therapy is surgical resection at early stage of disease. ⋯ The latter tool offers advantages over chest X-ray, but final results from controlled well conducted trials are necessary before the real utility of CT mass screening can be determined. Further approaches to secondary prevention such as screening with positron emission tomography (PET), autofluorescence bronchoscopy and biomarkers hold great promise for the future.