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This objective of the current review was to provide the reader with a comprehensive summary of the literature related to 3 important and inter‐related features of the biology of inflammatory breast cancer (IBC): angiogenesis, lymphangiogenesis, and the formation of tumor emboli. Information derived from animal models of IBC as well as from translational studies using tissue samples of patients with...
BACKGROUND:Aggressiveness of inflammatory breast cancer (IBC) is related to its metastatic potential. The introduction of primary chemotherapy in the multimodality treatment has dramatically changed the prognosis. However, survival remains poor. Since 1995, innovative systemic therapies have been assessed in France in multicentric clinical trials, initially centered on high‐dose chemotherapy (HDC)...
Ewing sarcoma is the second most common type of bone cancer in children and young adults. In recent years, the mechanisms by which these tumors develop and maintain their vascular supply have been elucidated. Additional work has demonstrated that inhibition of angiogenic pathways or disruption of established vasculature can attenuate the growth of Ewing sarcoma mouse xenografts. Early clinical data...
Soft tissue sarcomas (STSs) are a heterogeneous group of malignancies that includes >50 different subtypes, each with unique clinical and pathologic qualities. In general, there is a 50% cure rate, and most cures are achieved with complete surgical resection with or without radiation therapy. The results from chemotherapeutic agents for unresectable or metastatic disease have been disappointing...
BACKGROUND:In patients with cancer, circulating endothelial cells (CECs) are increased and are correlated with an aggressive disease course. However, the clinical and biologic significance of CECs in chronic lymphocytic leukemia (CLL) remains uncertain.
METHODS:In 170 patients with CLL, CEC levels were quantified by flow cytometry and were correlated with clinical and biologic data. In addition,...
BACKGROUND:Targeting the tumor microenvironment and angiogenesis is a novel lymphoma therapeutic strategy. The authors report safety, activity, and angiogenic profiling results with the rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide (RT‐PEPC) regimen in patients with recurrent mantle cell lymphoma (MCL).
METHODS:RT‐PEPC included induction (Months 1‐3) of...
In the United States, randomized trials have established preoperative chemoradiation as the standard of care for patients with locally advanced rectal cancer. Pathologic complete response (pCR) rates occur in 10% to 16% of patients and have been shown to be correlated with both disease‐free and overall survival. Therefore, recent efforts incorporating newer cytotoxic and molecularly targeted agents...
BACKGROUND:There seems to be a close interplay between angiogenesis and the immune system. The authors of this report investigated the prognostic role of angiogenic markers in coexpression with immune system markers in patients with nonsmall cell lung cancer (NSCLC).
METHODS:Tumor resection samples from 335 patients with stage I to IIIA NSCLC were obtained, and tissue microarrays were constructed...
BACKGROUND:This phase 1‐2 trial assessed the efficacy and tolerability of an oral angiogenesis inhibitor—PTK787/ZK222584 (PTK)—in combination with intravenous doxorubicin for the treatment of advanced hepatocellular carcinoma (HCC) patients.
METHODS:In phase 1, advanced HCC patients received PTK at escalating doses together with doxorubicin 60 mg/m2 given as an intravenous bolus every 3 weeks to...
BACKGROUND:Notch signaling plays a key role in embryonic vascular development and angiogenesis. The authors aimed to study the prognostic role of the angiogenesis‐related Notch ligands and receptors and investigate the prognostic impact of the coexpression of vascular endothelial growth factor‐A (VEGF‐A) and Notch signaling.
METHODS:Tumor tissue samples from 335 resected patients with stage I to...
BACKGROUND:Insulin‐like growth factor (IGF)‐I receptor (IGF‐IR) signaling is required for tumorigenicity and tumor progression of gastrointestinal cancers. The authors previously reported the success of therapy for gastrointestinal cancers using adenoviruses that expressed dominant‐negative IGF‐IR (IGF‐IR/dn). In addition, it has been demonstrated that IGF‐IR signaling affects vascular endothelial...
BACKGROUND:Targeted therapy in osteosarcoma (OS) is needed to improve patient outcomes. Human RECK may have a role because it inhibits cancer invasion and regulates angiogenesis. This study aimed to characterize RECK expression in human OS, to examine in vitro effects of RECK on vascular endothelium and OS cell behavior, and to analyze the effect of RECK on OS grown orthotopically in nude mice.
METHODS:RECK...
Currently, nonsmall‐cell lung cancer (NSCLC) is the leading cause of cancer‐related death in the United States. Angiogenesis, the formation of new vasculature, is a complex and tightly regulated process that promotes metastasis and disease progression in lung cancer and other malignancies. Developmental antiangiogenic agents have shown activity in NSCLC, and bevacizumab, an antiangiogenic monoclonal...
BACKGROUND:The phosphoinositide 3‐kinase/Akt/mammalian target of rapamycin pathway plays a critical role in the pathogenesis of hepatocellular carcinoma (HCC). We performed a single‐arm, phase 1/2 study of everolimus in patients with advanced HCC.
METHODS:Patients with histologically confirmed measurable advanced HCC, 0‐2 prior regimens, and adequate hematologic, hepatic, and renal functions received...
BACKGROUND:The efficacy of carboplatin, irinotecan, and bevacizumab among recurrent glioblastoma (GBM) patients after prior progression on bevacizumab therapy in a phase 2, open‐label, single‐arm trial was evaluated.
METHODS:Eligible patients received carboplatin (area under the plasma curve [AUC] 4 mg/ml‐min) on day 1, whereas bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 for patients on CYP3A...
BACKGROUND:Type 1 cyclic 3′,5′‐guanosine monophosphate‐dependent protein kinase (PKG) has recently been reported to inhibit tumor growth and angiogenesis. These effects suggest that PKG activation may have therapeutic value for colon cancer treatment, but the signaling downstream of this enzyme is poorly understood. The present study examined the mechanism underlying the inhibition of angiogenesis...
BACKGROUND:Vascular endothelial growth factor (VEGF) signaling is a target for antiangiogenic cancer therapy. The authors have previously observed that up to 40% of vessels in colorectal carcinoma (CRC) tumors are negative for VEGF receptor 2 (VEGFR2) expression. Differential activity of transforming growth factor beta (TGF‐β) is a potential contributor to this receptor heterogeneity because TGF‐β...
BACKGROUND:Pancreatic cancer is 1 of the most common and poorly treated tumors. In search of new therapeutic approaches, the oxygen sensors prolyl hydroxylases (PHD) are potential targets. PHD2 is considered the key oxygen sensor‐regulating hypoxia‐inducible factor (HIF). Currently, there is conflicting evidence regarding the exact role of PHD2 in tumorigenesis. The objective of this study was to...
BACKGROUND:Tumor neovascularization (TNV) is a common pathologic basis for malignant growth and metastasis. However, the mechanism of TNV pathogenesis is not fully understood. Ras homolog gene family, member A (RhoA), a Rho guanosine triphosphatase (GTPase) family member, may be involved in a hypoxia‐induced vascular endothelial growth factor (VEGF) pathway that regulates TNV angiogenesis through...
BACKGROUND:Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biologic activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase 2 trial were to determine the safety and efficacy of cilengitide when combined with radiation and temozolomide for patients with newly diagnosed glioblastoma multiforme and to select a dose...
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