A HGF/cMET autocrine loop is operative in multiple myeloma bone marrow endothelial cells and may represent a novel therapeutic target.

Purpose: The aim of this study was to investigate the angiogenic role of the hepatocyte growth factor (HGF)/cMET pathway and its inhibition in bone marrow endothelial cells (EC) from patients with multiple myeloma versus from patients with monoclonal gammopathy of undetermined significance (MGUS) or benign anemia (control group).

Experimental Design: The HGF/cMET pathway was evaluated in ECs from patients with multiple myeloma (multiple myeloma ECs) at diagnosis, at relapse after bortezomib- or lenalidomide-based therapies, or on refractory phase to these drugs; in ECs from patients with MGUS (MGECs); and in those patients from the control group. The effects of a selective cMET tyrosine kinase inhibitor (SU11274) on multiple myeloma ECs' angiogenic activities were studied in vitro and in vivo.

Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study.

The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC.

ALK-dependent control of hypoxia-inducible factors mediates tumor growth and metastasis.

Rearrangements involving the anaplastic lymphoma kinase (ALK) gene are defining events in several tumors, including anaplastic large-cell lymphoma (ALCL) and non-small cell lung carcinoma (NSCLC). In such cancers, the oncogenic activity of ALK stimulates signaling pathways that induce cell transformation and promote tumor growth. In search for common pathways activated by oncogenic ALK across different tumors types, we found that hypoxia pathways were significantly enriched in ALK-rearranged ALCL and NSCLC, as compared with other types of T-cell lymphoma or EGFR- and K-RAS-mutated NSCLC, respectively.

Translocation of the proto-oncogene Bcl-6 in human glioblastoma multiforme.

Bcl-6 translocation is a genetic alteration that is commonly detected in Primary Central Nervous System Lymphoma. The role of this protein in cerebral tumors is unclear. In this study we investigated Bcl-6 translocation and its transcriptional and translational levels in formalin-fixed, paraffin-embedded cerebral tissue sections from glioblastoma (GBM), low-grade glioma (Astrocytoma grade II and III), and meningioma patients, and correlated them with apoptotic processes and p53 and caspase-3 expression.

Third-line trabectedin for a metastatic desmoplastic small round cell tumour treated with multimodal therapy.

Background: Desmoplastic small round cell tumour (DSRCT) is a rare and aggressive cancer that usually develops in the peritoneal cavity of young males. Its prognosis is dismal, with current treatment options including the combination of multi-agent chemotherapy, aggressive surgery, radiation therapy, and autologous stem cell transplantation. Hyperthermic intraperitoneal chemotherapy (HIPEC) may also be an option.

The chick embryo chorioallantoic membrane as a model for tumor biology.

Among the in vivo models, the chick embryo chorioallantoic membrane (CAM) has been used to implant several tumor types as well as malignant cell lines to study their growth rate, angiogenic potential and metastatic capability. This review article is focused on the major compelling literature data on the use of the CAM to investigate tumor growth and the metastatic process.

Insights in Hodgkin Lymphoma angiogenesis.

Angiogenesis is a hallmark of tumor growth and progression in solid and hematological malignancies. Different cellular components of the tumor microenvironment such as macrophages, mast cells, circulating endothelial cells and angiogenic factors, including vascular endothelial growth factor and its receptors are involved in the maintenance of Hodgkin Lymphoma. In this review article, we highlight relevant literature focusing on the relationships between angiogenesis and Hodgkin Lymphoma as well as discussing anti-angiogenic treatments in this malignancy.

Clinical activity of FOLFIRI plus cetuximab according to extended gene mutation status by next-generation sequencing: findings from the CAPRI-GOIM trial.

Background: Treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies has been restricted to metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors. Next-generation sequencing (NGS) allows the assessment in a single analysis of a large number of gene alterations and might provide important predictive and prognostic information.

Patients And Methods: In the CAPRI-GOIM trial, 340 KRAS exon 2 wild-type mCRC patients received first-line FOLFIRI plus cetuximab.

From the discovery of monoclonal antibodies to their therapeutic application: an historical reappraisal.

Vertebrate make billions of different antibodies, each with a binding site that recognizes a specific region of a macromolecule. The hybridoma technique allows monoclonal antibodies, highly specific antibodies produced in the laboratory by a variety of methods. In the last 35 years since the first process for creating monoclonal antibodies was introduced, their application have improved the growing biotechnology industry, but the most important application concerns the therapy of human malignancies.

Microenvironment and multiple myeloma spread.

In patients with multiple myeloma (MM), the bone marrow (BM) contains hematopoietic stem cells (HSCs) and non-hematopoietic cells. HSCs are able to give rise to all types of mature blood cells, while the non hematopoietic component includes mesenchymal stem cells (MSCs), fibroblasts, osteoblasts, osteoclasts, chondroclasts, endothelial cells, endothelial progenitor cells (EPCs), B and T lymphocytes, NK cells, erythrocytes, megakaryocytes, platelets, macrophages and mast cells. All of these cells form specialized "niches" in the BM microenvironment which are close to the vasculature ("vascular niche") or to the endosteum ("osteoblast niche").

Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats.

A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells.

Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer.

Background: The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic model.

Methods: Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models.

A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy.

Background: Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways.

Clinical application of microRNA testing in neuroendocrine tumors of the gastrointestinal tract.

It is well documented that dysregulation of microRNAs is a hallmark of human cancers. Thus, this family of small non-coding regulatory molecules represents an excellent source of sensitive biomarkers. Unique microRNAs expression profiles have been associated with different types and subsets of gastrointestinal tumors including gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Mast cell ontogeny: an historical overview.

Mast cells were first identified by Paul Ehrlich in 1878, when he was still a medical student. Many fundamental aspects of mast cell ontogeny have been elucidated since Ehrlich's first identification. Demonstration of mast cell derivation from bone marrow precursors could be established in 1977 when Kitamura's group first showed reconstitution of mast cells in mast cell-deficient mice by the adaptive transfer of wild type bone marrow and indicated that these cells were of hematopoietic origin.

The chemical nature of the factor responsible for embryonic induction: an historical overview.

The discovery by Hans Spemann of the "organizer" tissue and its ability to induce the formation of the amphibian embryo's neural tube inspired leading embryologists to attempt to elucidate embryonic induction's underlying mechanisms. Since then several studies have described several developmental model system to better understand the role of specific signaling molecules, the interplay of different signals and tissue interactions in regulating tissue induction and patterning events. Different groups of workers set out to subject embryonic amphibian tissues and inductive adult organs to various extraction methods in the hope that the active agents could be isolated and chemically identified.

Bone marrow vascular niche and the control of angiogenesis in multiple myeloma.

Bone marrow contains hematopoietic stem cells (HSCs) and non hematopoietic cells. HSCs are able to give rise to all types of mature blood cells, while the non hematopoietic component includes osteoblasts/osteoclasts, endothelial cells, endothelial progenitor cells and mesenchymal stem cells. All of these cells form specialized "niches" which are close to the vasculature ("vascular niche") or to the endosteum ("osteoblast niche").

Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey.

Background: Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC.

Patients And Methods: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed.

Macrophages in multiple myeloma.

Tumor associated macrophages (TAMs) are a rich source of pro-angiogenic cytokines and growth factors, and a relationship between the TAMs content, the rate of tumor growth and the extent of vascularization has been shown in several tumors. In this article, we have summarized the literature and our data concerning the involvement of TAMs in angiogenesis occurring in multiple myeloma. Finally, therapeutic aspects concerning the potential role of molecules which inhibit macrophage recruitment in the tumor side are also discussed.

HIF-1α of bone marrow endothelial cells implies relapse and drug resistance in patients with multiple myeloma and may act as a therapeutic target.

Purpose: To investigate the role of hypoxia-inducible factor-1α (HIF-1α) in angiogenesis and drug resistance of bone marrow endothelial cells of patients with multiple myeloma.

Experimental Design: HIF-1α mRNA and protein were evaluated in patients with multiple myeloma endothelial cells (MMEC) at diagnosis, at relapse after bortezomib- or lenalidomide-based therapies or on refractory phase to these drugs, at remission; in endothelial cells of patients with monoclonal gammapathies of undetermined significance (MGUS; MGECs), and of those with benign anemia (controls). The effects of HIF-1α inhibition by siRNA or panobinostat (an indirect HIF-1α inhibitor) on the expression of HIF-1α proangiogenic targets, on MMEC angiogenic activities in vitro and in vivo, and on overcoming MMEC resistance to bortezomib and lenalidomide were studied.

Angiogenesis in multiple myeloma.

Angiogenesis is a constant hallmark of multiple myeloma progression and has prognostic potential. Multiple myeloma cells interact with surrounding host cells and extracellular matrix, this crosstalk affecting the most important aspects of the malignant phenotype, both at primary and secondary tumor sites. The pathophysiology of multiple myeloma-induced angiogenesis involves both direct production of angiogenic cytokines by plasma cells and their induction within the bone marrow microenvironment cells.

History of research on angiogenesis.

Over the past 25 years, the number of Medline publications dealing with angiogenesis has increased in a nonlinear fashion, reflecting the interest among basic scientists and clinicians in this field. Under physiological conditions, angiogenesis is regulated by the local balance between endogenous stimulators and inhibitors of this process. In tumor growth, there is an imbalance between endogenous stimulator and inhibitor levels, leading to an 'angiogenic switch'.