Barriers to Clinical Trial Implementation Among Community Care Centers.

Importance: While an overwhelming majority of patients diagnosed with cancer express willingness to participate in clinical trials, only a fraction will enroll onto a research protocol.

Objective: To identify critical barriers to trial enrollment to translate findings into actionable practice changes that increase cancer clinical trial enrollment.

Design, Setting, And Participants: This survey study included designated site contacts at oncology practices with teams who were highly involved with the Association of Community Cancer Centers (ACCC) Community Oncology Research Institute (ACORI) clinical trials activities, all American Society of Clinical Oncology (ASCO)-ACCC collaboration pilot sites, and/or sites providing care to at least 25% African American and Hispanic residents.

Resource and Reimbursement Barriers to Comprehensive Cancer Care Delivery: An Analysis of Association of Community Cancer Centers Survey Data.

Purpose: Comprehensive cancer care (CCC) delivery is recommended in guidelines and considered essential for high-quality cancer management. Barriers, such as insufficient reimbursement, prevent consistent access to and delivery of CCC. Association of Community Cancer Centers conducted a national survey to elucidate capacity and barriers to CCC delivery to inform policy and value-based payment reform.

SODs, DNA binding and cleavage studies of new Mn(III) complexes with 2-((3-(benzyloxy)pyridin-2-ylimino)methyl)phenol.

Newly synthesized ligand [2-((3-(benzyloxy)pyridin-2-ylimino)methyl)phenol] (Bpmp) react with manganese(II) to form mononuclear complexes [Mn(phen)(Bpmp)(CH3COO)(H2O)]·4H2O (1), (phen=1,10-phenanthroline) and [Mn(Bpmp)2(CH3COO)(H2O)]·5H2O (2). These complexes were characterized by elemental analysis, IR, (1)H NMR, Mass, UV-vis spectral studies. Molar conductance and thermogravimetric analysis of these complexes were also recorded.

Synthesis, spectroscopic characterization, antimicrobial, DNA binding and oxidative-induced DNA cleavage activities: new oxovanadium(IV) complexes of 2-(2-hydroxybenzylideneamino)isoindoline-1,3-dione.

A mononuclear complex [(phen)VO(bid)]SO(4)·3H(2)O (1), (phen=1,10-phenanthroline) and a binuclear [(VObid)(2)]·H(2)O (2), with Hbid [(E)-2-(2-hydroxybenzylideneamino)isoindoline-1,3-dione] were prepared and characterized by elemental analysis, IR, mass, UV-Vis spectral studies, ESR, molar conductance and thermogravimetric analysis. The DNA-binding properties of the complexes 1 and 2 were investigated by UV-spectroscopy, fluorescence spectroscopy and viscosity measurements. The superoxide dismutase-like activity of the complexes has been determined.

The RASSF1A tumor suppressor restrains anaphase-promoting complex/cyclosome activity during the G1/S phase transition to promote cell cycle progression in human epithelial cells.

Multiple molecular lesions in human cancers directly collaborate to deregulate proliferation and suppress apoptosis to promote tumorigenesis. The candidate tumor suppressor RASSF1A is commonly inactivated in a broad spectrum of human tumors and has been implicated as a pivotal gatekeeper of cell cycle progression. However, a mechanistic account of the role of RASSF1A gene inactivation in tumor initiation is lacking.

Targeting B-lymphocyte stimulator/B-cell activating factor and a proliferation-inducing ligand in hematologic malignancies.

B-lymphocyte stimulator/B-cell activating factor (BLyS/BAFF) and a proliferation-inducing ligand (APRIL), members of the tumor necrosis family of ligands, are expressed by monocytes, macrophages, and dendritic cells, and increased expression of these ligands is noted in lymphomas and plasma cell malignancies. BLyS and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BLyS or APRIL or the receptors B-cell maturation, transmembrane activator and calcium-modulating cyclophilin ligand interactor, or BAFF-R have been reported in various B-cell malignancies, including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia. Levels of BLyS (in the tumor and in the serum) increased with the transformation of the tumors to a more aggressive phenotype.

Bcl-2 gene expression as a predictor of outcome in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with a 5-year survival rate of 35%-60%. Various clinical factors included in the International Prognostic Index have failed to identify the patients with DLBCL who will not benefit from the standard R-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone plus rituximab) treatment regimen. Bcl-2 has been implicated in conferring resistance to chemotherapy in non-Hodgkin's lymphoma and is therefore a candidate prognostic marker in DLBCL.

Selective blockade of vascular endothelial growth factor receptor 2 with an antibody against tumor-derived vascular endothelial growth factor controls the growth of human pancreatic adenocarcinoma xenografts.

Background: Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, is critical for growth of human pancreatic adenocarcinoma. Preclinical studies demonstrate that blockade of VEGF activity can control the growth of pancreatic tumors in mice. In this study, we evaluated the efficacy of 2C3, an antibody that inhibits VEGF receptor 2 activation by human VEGF, to inhibit the growth of human pancreatic adenocarcinoma in mice.

The RASSF1A tumor suppressor blocks cell cycle progression and inhibits cyclin D1 accumulation.

The RASSF1A locus at 3p21.3 is epigenetically inactivated at high frequency in a variety of solid tumors. Expression of RASSF1A is sufficient to revert the tumorigenicity of human cancer cell lines.

Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression.

Background: The recently identified RASSF1 locus is located within a 120-kilobase region of chromosome 3p21.3 that frequently undergoes allele loss in lung and breast cancers. We explored the hypothesis that RASSF1 encodes a tumor suppressor gene for lung and breast cancers.

Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control.

The activity of the catalytic domain of the orphan MAP kinase ERK5 is increased by Ras but not Raf-1 in cells, which suggests that ERK5 might mediate Raf-independent signaling by Ras. We found that Raf-1 does contribute to Ras activation of ERK5 but in a manner that does not correlate with Raf-1 catalytic activity. A clue to the mechanism of action of Raf-1 on ERK5 comes from the observation that endogenous Raf-1 binds to endogenous ERK5, suggesting the involvement of regulatory protein-protein interactions.

Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B cells.

Previous studies by our lab and others established that co-crosslinking sIg and IgG receptor FcgammaRIIb in B cells in a feedback suppression model (negative signaling) promoted tyrosine phosphorylation of the inositol 5-phosphatase SHIP and its interaction with Shc and that these events were associated with inhibition of the Ras pathway. We therefore hypothesized a competition model in which the SH2 domain of SHIP competes with that of Grb2 for binding to phospho-Shc to inhibit the Ras pathway. Here, we provide evidence consistent with this hypothesis.