Cancer immunotherapy: a future paradigm shift in the treatment of non-small cell lung cancer.

Emerging evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy even for tumors that were historically considered as nonimmunogenic. Immunotherapy is emerging as a major modality in non-small cell lung cancer (NSCLC) treatment focusing on vaccine approaches to elicit specific immune responses and development of inhibitors of the molecular mediators of cancer-induced immunosuppression (immune checkpoints) to boost antitumor immune responses. Amplification of the host response against evolving tumors through vaccination is being investigated in ongoing clinical trials with tumor cell vaccines; however, the clinical efficacy of these agents has been limited.

A longitudinal, collaborative, practice-based learning and improvement model to improve post-discharge heart failure outcomes.

Background: Practice-based learning and improvement is one of the Accreditation Council of Graduate Medical Education's core competencies fortrainees. Residencyprograms have grappled with how to accomplish this goal.

Aim: We describe our institution's unique, longitudinal post-graduate year process and project.

Programmed death ligand-1 expression in non-small cell lung cancer.

Recent strategies targeting the interaction of the programmed cell death ligand-1 (PD-L1, B7-H1, CD274) with its receptor, PD-1, resulted in promising activity in early phase clinical trials. In this study, we used various antibodies and in situ mRNA hybridization to measure PD-L1 in non-small cell lung cancer (NSCLC) using a quantitative fluorescence (QIF) approach to determine the frequency of expression and prognostic value in two independent populations. A control tissue microarray (TMA) was constructed using PD-L1-transfected cells, normal human placenta and known PD-L1-positive NSCLC cases.

Mechanisms in endocrinology: primary HT and risk for breast cancer: a systematic review and meta-analysis.

Objective: The association between hypothyroidism and breast cancer has been described from very early on. Breast and thyroid tissue are interconnected on a molecular level mainly through activation of thyroid hormone receptors expressed on cells of the mammary gland as well as on the plasma membrane of breast cancer cells. Despite the experimental evidence the true value of hypothyroidism as a risk factor for breast cancer remains controversial.

Molecular classification of nonsmall cell lung cancer using a 4-protein quantitative assay.

Background: The importance of definitive histological subclassification has increased as drug trials have shown benefit associated with histology in nonsmall-cell lung cancer (NSCLC). The acuity of this problem is further exacerbated by the use of minimally invasive cytology samples. Here we describe the development and validation of a 4-protein classifier that differentiates primary lung adenocarcinomas (AC) from squamous cell carcinomas (SCC).

Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer: a randomized phase II study.

Purpose: Increased growth factor signaling may contribute to tamoxifen resistance. This randomized phase II trial assessed tamoxifen plus placebo or the epidermal growth factor receptor inhibitor gefitinib in estrogen receptor (ER)-positive metastatic breast cancer.

Experimental Design: Patients with newly metastatic disease or recurred after adjuvant tamoxifen (stratum 1), or recurred during/after adjuvant aromatase inhibitor (AI) or after failed first-line AI (stratum 2), were eligible.

Multiplexed analysis of angiogenesis and lymphangiogenesis factors predicts outcome for non-small cell lung cancer patients.

Angiogenesis and lymphangiogenesis are key components of non-small cell lung cancer (NSCLC) tumor growth and metastatic spread; however, the prognostic and predictive role of angiogenic and lymphangiogenic biomarkers remains controversial for NSCLC patients. We assessed VEGF, VEGFC, VEGFD, VEGFR3 protein expression, tumor microvessel, and lymphatic vessel (LmVD) density by immunohistochemistry in 103 NSCLC; biomarkers were analyzed individually as well as multiplexed with each other. No correlations were identified between VEGF, VEGFC, VEGFD, or LmVD and clinical characteristics.

Modeling prognostic factors in resectable pancreatic adenocarcinomas.

Background: The accurate prognosis for patients with resectable pancreatic adenocarcinomas requires the incorporation of more factors than those included in AJCC TNM system.

Methods: We identified 218 patients diagnosed with stage I and II pancreatic adenocarcinoma at NewYork-Presbyterian Hospital/Columbia University Medical Center (1999 to 2009). Tumor and clinical characteristics were retrieved and associations with survival were assessed by univariate Cox analysis.

High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology.

Background: Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results.

Methods: Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival.

Differential sensitivity to platinum-based chemotherapy in primary uterine serous papillary carcinoma cell lines with high vs low HER-2/neu expression in vitro.

Objective: We sought to identify effective chemotherapy regimens against uterine serous papillary adenocarcinoma (USPC).

Study Design: Six USPC, half of which overexpress HER-2/neu at 3+ level, were evaluated for growth rate and in vitro sensitivity to 14 single-agent chemotherapies and 5 combinations by ChemoFx (Precision Therapeutics Inc, Pittsburgh, PA).

Results: Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines and a lower half maximum inhibitory concentration (IC(50)) when exposed to the majority of single-agent chemotherapies.

Quantitative evaluation of protein expression as a function of tissue microarray core diameter: is a large (1.5 mm) core better than a small (0.6 mm) core?

Context: Tissue microarrays (TMAs) have emerged as a high-throughput technology for protein evaluation in large cohorts. This technique allows maximization of tissue resources by analysis of sections from 0.6-mm to 1.

Analytic variability in immunohistochemistry biomarker studies.

Background: Despite the widespread use of immunohistochemistry (IHC), there are no standardization guidelines that control for antibody probe variability. Here we describe the effect of variable antibody reagents in the assessment of cancer-related biomarkers by IHC.

Methods: Estrogen receptor (ER), epidermal growth factor receptor (EGFR) 1, and human epidermal growth factor receptor 3 (HER3) were evaluated by quantitative immunofluorescence.

Developing a multivariable prognostic model for pancreatic endocrine tumors using the clinical data warehouse resources of a single institution.

OBJECTIVE: Current staging systems are not accurate for classifying pancreatic endocrine tumors (PETs) by risk. Here, we developed a prognostic model for PETs and compared it to the WHO classification system. METHODS: We identified 98 patients diagnosed with PET at NewYork-Presbyterian Hospital/Columbia University Medical Center (1999 to 2009).

High expression of mammalian target of rapamycin is associated with better outcome for patients with early stage lung adenocarcinoma.

Purpose: Mammalian target of rapamycin (mTOR) is a key kinase downstream of phosphoinositide 3-kinase (PI3K)/AKT predominantly involved in translational control in the presence of nutrients and energy. Despite the well known role of mTOR in carcinogenesis, its prognostic potential in lung cancer has not been investigated. Here, we quantitatively assessed mTOR protein expression in two large data sets to investigate the impact of mTOR expression on patient survival.

Thyroid transcription factor 1 is an independent prognostic factor for patients with stage I lung adenocarcinoma.

Purpose: Thyroid transcription factor 1 (TTF1) is a transcription factor that regulates the expression of multiple genes involved in lung development. It is preferentially expressed in adenocarcinomas of the lung and has been investigated as a potential prognostic parameter in patients with lung cancer, with conflicting results. We quantitatively assessed TTF1 protein expression in two large and independent data sets to investigate the impact of TTF1 nuclear expression on patient survival.

Ontogeny of intrinsic innervation in the human thymus and spleen.

The ontogeny of the innervation of human lymphoid organs has not been studied in detail. Our aim was to assess the nature and distribution of parenchymal nerves in human fetal thymus and spleen. We used the peroxidase immunohistochemical technique with antibodies specific to neuron-specific enolase (NSE), neurofilaments (NF), PGP9.