Molecular heterogeneity of non-small cell lung carcinoma patient-derived xenografts closely reflect their primary tumors.

Availability of lung cancer models that closely mimic human tumors remains a significant gap in cancer research, as tumor cell lines and mouse models may not recapitulate the spectrum of lung cancer heterogeneity seen in patients. We aimed to establish a patient-derived tumor xenograft (PDX) resource from surgically resected non-small cell lung cancer (NSCLC). Fresh tumor tissue from surgical resection was implanted and grown in the subcutaneous pocket of non-obese severe combined immune deficient (NOD SCID) gamma mice.

Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage IA patients.

Background: Patients with early-stage non-small-cell lung carcinoma (NSCLC) may benefit from treatments based on more accurate prognosis. A 15-gene prognostic classifier for NSCLC was identified from mRNA expression profiling of tumor samples from the NCIC CTG JBR.10 trial.

Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer.

The tumor microenvironment strongly influences cancer development, progression, and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC.

Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer.

Purpose: The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT.

Primary tumor xenografts of human lung adeno and squamous cell carcinoma express distinct proteomic signatures.

Nonsmall cell lung carcinoma (NSCLC) accounts for 80% of lung cancers. The most prevalent subtypes of NSCLC are adenocarcinoma (ADC) and squamous cell carcinoma (SCC), which combined account for approximately 90%. Ten resected NSCLC patient tumors (5 ADC and 5 SCC) were directly introduced into severely immune deficient (NOD-SCID) mice, and the resulting xenograft tumors were analyzed by standard histology and immunohistochemistry (IHC) and by proteomics profiling.

Prognostic gene expression signature for squamous cell carcinoma of lung.

Purpose: This study aimed to identify and validate a gene expression signature for squamous cell carcinoma of the lung (SQCC).

Experimental Design: A published microarray dataset from 129 SQCC patients was used as a training set to identify the minimal gene set prognostic signature. This was selected using the MAximizing R Square Algorithm (MARSA), a novel heuristic signature optimization procedure based on goodness-of-fit (R square).

Differential roles of cyclin D1 and D3 in pancreatic ductal adenocarcinoma.

Background: The cyclin D1 (CCND1) and cyclin D3 (CCND3) are frequently co-overexpressed in pancreatic ductal adenocarcinoma (PDAC). Here we examine their differential roles in PDAC.

Results: CCND1 and CCND3 expression were selectively suppressed by shRNA in PDAC cell lines with expression levels of equal CCND1 and CCND3 (BxPC3), enhanced CCND1 (HPAC) or enhanced CCND3 (PANC1).

Understanding prognostic gene expression signatures in lung cancer.

In non-small-cell lung cancer (NSCLC), molecular profiling of tumors has led to the identification of gene expression patterns that are associated with specific phenotypes and prognosis. Such correlations could identify early-stage patients who are at increased risk of disease recurrence and death after complete surgical resection and who might benefit from adjuvant therapy. Profiling may also identify aberrant molecular pathways that might lead to specific molecularly targeted therapies.

Genomic markers for malignant progression in pulmonary adenocarcinoma with bronchioloalveolar features.

Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC) without stromal, vascular, or pleural invasion, is considered an in situ tumor with a 100% survival rate. However, the histological criteria for invasion remain controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma, referred to as mixed type adenocarcinoma with BAC features (AWBF).

Three-gene prognostic classifier for early-stage non small-cell lung cancer.

Purpose: Several microarray studies have reported gene expression signatures that classify non-small-cell lung carcinoma (NSCLC) patients into different prognostic groups. However, the prognostic gene lists reported to date overlap poorly across studies, and few have been validated independently using more quantitative assay methods.

Patients And Methods: The expression of 158 putative prognostic genes identified in previous microarray studies was analyzed by reverse transcription quantitative polymerase chain reaction in the tumors of 147 NSCLC patients.

Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation.

Trophectoderm (TE), the first differentiated cell lineage of mammalian embryogenesis, forms the placenta, a structure unique to mammalian development. The differentiation of TE is a hallmark event in early mammalian development, but molecular mechanisms underlying this first differentiation event remain obscure. Embryonic stem (ES) cells can be induced to differentiate into the TE lineage by forced repression of the POU-family transcription factor, Oct3/4.

Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst.

Blastocyst formation marks the segregation of the first two cell lineages in the mammalian preimplantation embryo: the inner cell mass (ICM) that will form the embryo proper and the trophectoderm (TE) that gives rise to the trophoblast lineage. Commitment to ICM lineage is attributed to the function of the two transcription factors, Oct4 (encoded by Pou5f1) and Nanog. However, a positive regulator of TE cell fate has not been described.