Characterization of T/B cell antigen specific-engineered tumors for studying T cell and GC B cell function in a murine model of NSCLC

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Shared Nearest Neighbors Approach and Interactive Browser for Network Analysis of a Comprehensive Non-Small-Cell Lung Cancer Data Set

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Current Surgical Indications for Non-Small-Cell Lung Cancer

With recent strides made within the field of thoracic oncology, the management of NSCLC is evolving rapidly. Careful patient selection and timing of multi-modality therapy to permit the optimization of therapeutic benefit must be pursued. While chemotherapy and radiotherapy continue to have a role in the management of lung cancer, surgical therapy remains an essential component of lung cancer treatment in early, locally and regionally advanced, as well as in selected, cases of metastatic disease. Recent and most impactful advances in the treatment of lung cancer relate to the advent of immunotherapy and targeted therapy, molecular profiling, and predictive biomarker discovery. Many of these systemic therapies are a part of the standard of care in metastatic NSCLC, and their indications are expanding towards surgically operable lung cancer to improve survival outcomes. Numerous completed and ongoing clinical trials in the surgically operable NSCLC speak to the interest and importance of the multi-modality therapy even in earlier stages of NSCLC. In this review, we focus on the current standard of care indications for surgical therapy in stage I-IV NSCLC as well as on the anticipated future direction of multi-disciplinary lung cancer therapy

N6L-functionalized nanoparticles for targeted and inhibited pancreatic cancer cells

International audienc

Synergistic anti‐proliferative and pro‐apoptotic activity of combined therapy with bortezomib, a proteasome inhibitor, with anti‐epidermal growth factor receptor (EGFR) drugs in human cancer cells

The proteasome plays a pivotal role in the turnover of regulatory transduction proteins induced by activated cell membrane growth factor receptors. The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. Proteasome inhibition may sensitize human cancer cell lines to EGFR inhibitors. We investigated the growth inhibitory and pro‐apoptotic effects of the proteasome inhibitor bortezomib in combination with anti‐EGFR drugs, such as gefitinib, vandetanib, and cetuximab in EGFR‐expressing human cancer cell lines. Bortezomib determined dose‐dependent growth inhibition in a nine cancer cell line panel (IC50 values, range 6–42 nM). A significant synergistic growth inhibitory effect was observed with the combination of bortezomib and each EGFR inhibitor in all cell lines (combination index, CI, range 0.10–0.55), which was accompanied by a significant induction in apoptosis by the combined treatment with bortezomib, cetuximab and vandetanib. In HCT‐116 colon cancer and A549 lung adenocarcinoma cells, bortezomib plus EGFR inhibitor treatment induced a more effective inhibition of EGFR‐activated down‐stream signals, including a marked suppression in activated, phosphorylated Akt (P‐Akt). In contrast, overexpression of a constitutively active P‐Akt protected A549 cells by cell growth inhibition and apoptosis following treatment with bortezomib and EGFR inhibitors. The combined treatment with bortezomib and EGFR inhibitors has a synergistic growth inhibitory and pro‐apoptotic activity in different human cancer cells which possess a functional EGFR‐dependent autocrine growth pathway through to a more efficient and sustained inhibition of Akt

Tumor Endothelial Markers Define Novel Subsets of Cancer-Specific Circulating Endothelial Cells Associated with Antitumor Efficacy

Circulating endothelial cells (CEC) are derived from multiple sources, including bone marrow (circulating endothelial progenitors; CEP), and established vasculature (mature CEC). Although CECs have shown promise as a biomarker for patients with cancer, their utility has been limited, in part, by the lack of specificity for tumor vasculature and the different nonmalignant causes that can impact CEC. Tumor endothelial markers (TEM) are antigens enriched in tumor versus nonmalignant endothelia. We hypothesized that TEMs may be detectable on CEC and that these circulating TEM+ endothelial cells (CTEC) may be a more specific marker for cancer and tumor response than standard CEC. We found that tumor-bearing mice had a relative increase in numbers of circulating CTEC, specifically with increased levels of TEM7 and TEM8 expression. Following treatment with various vascular-targeting agents, we observed a decrease in CTEC that correlated with the reductions in tumor growth. We extended these findings to human clinical samples and observed that CTECs were present in patients with esophageal cancer and non-small cell lung cancer (N = 40), and their levels decreased after surgical resection. These results demonstrate that CTECs are detectable in preclinical cancer models and patients with cancer. Furthermore, they suggest that CTECs offer a novel cancer-associated marker that may be useful as a blood-based surrogate for assessing the presence of tumor vasculature and antiangiogenic drug activity. (C)2014 AACR