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Solid organ tumors associated with neoangiogenesis, as measured by increased microvessel density (MVD), have poorer prognoses. A similar observation of increased MVD has been made in hematologic malignancies; however, its prognostic significance remains unknown. We investigated changes in MVD in...
Angiogenesis is the process of new blood vessel formation, and normally occurs during embryonal growth, wound healing, and the menstrual cycle. It is essential for the proliferation and metastases of most malignant neoplasms. There is now growing evidence that angiogenesis is increased and is...
We have explored the mechanism of the antiangiogenic effects of thalidomide by structure-activity studies. These investigations revealed that angiogenesis inhibition correlates with teratogenicity but not with tumor necrosis factor-alpha (TFA-α) inhibition. Additionally, one analog of...
Treatment with thalidomide and dexamethasone was given to 26 patients with active, previously untreated multiple myeloma (MM). Thalidomide was administered in an initial dosage of 200 mg/d for 2 weeks and then increased as tolerated (in 200-mg increments at 2-week intervals) to a maximum daily...
Recent studies have indicated that bone marrow angiogenesis is increased in multiple myeloma, suggesting that treatment with an antiangiogenic agent might be useful. Among the new antiangiogenic drugs in development, Neovastat (Æ-941; Æterna Laboratories, Quebec City, Canada) can be classified...
Novel therapies in multiple myeloma (MM) target not only the tumor cell but also the bone marrow (BM) microenvironment. Thalidomide (Thal), as well as derivative immunomodulatory drugs (IMiDs), directly induce apoptosis or GI growth arrest in MM cell lines and patient's MM cells which are...
Patients with multiple myeloma (MM) refractory to chemotherapy can only benefit from supportive measures and have a very short survival. Thalidomide has recently shown antitumor activity in patients with refractory myeloma. Twenty-three patients (12 men and 11 women; median age, 72 years) with...
Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide with biologic effects that include regulation of hematopoietic stem cell development, extracellular matrix remodeling, and inflammatory cytokine generation. The importance of angiogenic factors such as VEGF, while clearly...
There is accumulating evidence that leukemias and other hematologic diseases are angiogenesis-dependent. Therefore, angiogenesis inhibitors may be useful adjuncts to conventional therapies in the treatment of these diseases. When all conventional therapy has failed, an angiogenesis inhibitor may...
The 26S proteasome regulates protein turnover in eukaryotic cells. This is relevant in human cancer because the cell cycle, tumor growth, and survival are governed by a large repertoire of intracellular proteins that are regulated by the ubiquitin-mediated proteasome degradative pathway. In the...
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