Current Cancer Drug Targets - Volume 11, Issue 9, 2011

It has been generally accepted that angiogenesis is involved in the pathogenesis of hematological malignancies, like acute and chronic leukemia, lymphoma, myelodysplastic syndromes, myeloproliferative neoplasms, and multiple myeloma. The extent of angiogenesis in the bone marrrow has been correlated with disease burden, prognosis, and treatment outcome [1]. Reciprocal positive and negative interactions between tum Read More

The role of angiogenesis in haematological malignancies has been recently recognized. In these tumors, angiogenesis has been investigated predominantly in the bone marrow (BM) compartment where it appears to be regulated by multiple interactions between malignant cells and different cell populations present in the tumor microenvironment. Thus, angiogenesis represents a therapeutic target that opens new pe Read More

Research on the formation of new blood vessels (angiogenesis) in general and vascular endothelial growth factor (VEGF) in particular is a major focus in biomedicine and has led to the clinical approval of the monoclonal anti- VEGF antibody bevazicumab; and the second-generation multitargeted receptor kinase inhibitors (RTKIs) sorafenib, sunitinib, and pazopanib. Although these agents show significant preclinical an Read More

Bone marrow microenvironment has been shown to play a crucial role in supporting the pathogenesis and the progression of several B-cell malignancies, including Waldenstrom's Macroglobulinemia (WM). Among the different cell types within the bone marrow milieu, endothelial cells have been proven to support WM cells growth. Based on the understanding of bone marrow neo-angiogenesis in plasma cell dyscrasias, Read More

The tumor microenvironment is critical in the initiation and progression of cancerous growth, which is dependent on the establishment of a functional vascular network supporting neoplastic proliferation. While the precise role of tumor angiogenesis in lymphoma pathogenesis remains under active investigation, emerging data on the proangiogenic properties of the neoplastic lymphoma cells and mechanism of vascular Read More

One of the best examples of the bench-to-bedside paradigm in recent years could be the myelodysplastic syndromes (MDS). New insight into the pathophysiology of this heterogeneous group of diseases has led to relevant clinical changes. We have now the World Health Organization classification of MDS, the International Prognostic Score System to evaluate risk according to some clinical and laboratory parameters, Read More

The pathological role of bone marrow angiogenesis in human leukemias has been clearly established. Bone marrow neoangiogenesis is mediated by several growth factors, such as VEGF-A, VEGF-C, angiopoietin-1 and -2, FGF, HGF, TGF-β and others secreted by leukemic cells. The prognostic relevance of microvessel density, and expression of VEGF-A and -C has been demonstrated especially in acute myeloid leukemia. In the l Read More

Lung cancer is the leading cause of cancer death. Conventional photodynamic therapy (PDT) using a nontargeted photosensitizer (ntPDT) is a treatment option for central- and peripheral-type early-stage lung cancer. However, ntPDT can cause severe side effects for normal tissue due to its non-selective distribution. To improve the selectivity and effectiveness of ntPDT for human lung cancer, we hypothesized that tissue f Read More

Clarification of the molecular mechanisms of oncogenesis and drug resistance is a prerequisite for the development of new treatment strategies like molecularly targeted therapies. Recent studies demonstrate that EphA2 is overexpressed in human cancers and that EphA2 increases tumor invasion and survival. Thus, an EphA2 receptor antagonist, such as a specific tyrosine kinase inhibitor (in the form of an antibody, small Read More

Hypermethylation of the Wnt inhibitory factor-1 (WIF-1) promoter has been implicated in the overactivation of the Wnt pathway in human lung cancer. Curcuminoids exert anti-cancer effects and have been reported to act as hypomethylating agents. Previously, we have investigated and compared the demethylation effects of three curcuminoids and observed that bisdemethoxycurcumin exhibited the strongest demethyl Read More

Edelfosine is an inhibitor of SK3 channel-mediated cell migration. However, this compound bears adverse in vivo side effects. Using cell SK3 dependent cell-migration assay, patch-clamp, 125I-apamin binding, and in vivo experiments we tested the ability of 15 lipid derivatives with chemical structures inspired from edelfosine to inhibit SK3 channels. Using a structure-activity relationship approach we identified an ed Read More