Biomedical subjects

Natalie Ozburn

Publications and source records attributed to Natalie Ozburn.

2 recordsLinked to original sources

PubMed2006

Nuclear factor-kappaB (NF-kappaB) is frequently expressed in lung cancer and preneoplastic lesions.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB), a key transcription factor thought to play a major role in carcinogenesis, regulates many important signaling pathways involved in tumor promotion. Although NF-kappaB can be activated in lung cancer cell lines by tobacco exposure, there have been no studies of the expression of NF-kappaB in lung cancer pathogenesis. METHODS: The immunohistochemical expression of NF-kappaB p65 was investigated in 394 lung cancers (370 nonsmall cell lung carcinomas [NSCLC]; and 24 small cell lung carcinomas [SCLC]) and 269 lung normal epithelium and preneoplastic lesions, including hyperplasias, squamous metaplasias, dysplasias, and atypical adenomatous hyperplasias. RESULTS: High levels of nuclear immunohistochemical expression of NF-kappaB p65 were detected in the lung cancers, with significantly higher levels in SCLCs compared with NSCLCs (P<.0001). In adenocarcinomas the NF-kappaB p65 expression level was significantly higher in advanced TNM stages (III-IV) than in earlier stages (I-II) (P<.0001), and when NF-kappaB p65 is dichotomized using 50% as the cutoff point (high vs low), a higher NF-kappaB p65 expression level was detected in tumors having either K-RAS (P = .02) or EGFR (P = .009) mutations compared with wildtype tumors. A relatively high level of nuclear NF-kappaB p65 expression was detected in normal and mildly abnormal epithelium, and a progression with increasing histology severity was detected in preneoplastic lesions. CONCLUSIONS: NF-kappaB p65 nuclear expression is an early and frequent phenomenon in the pathogenesis of lung cancer. The findings indicate that NF-kappaB activation plays an important role in lung cancer pathogenesis and is a suitable target for the development of new lung cancer therapies and chemoprevention strategies.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma.

Glioblastoma, the most aggressive primary brain tumor in humans, exhibits a large degree of molecular heterogeneity. Understanding the molecular pathology of a tumor and its linkage to behavior is an important foundation for developing and evaluating approaches to clinical management. Here we integrate array-comparative genomic hybridization and array-based gene expression profiles to identify relationships between DNA copy number aberrations, gene expression alterations, and survival in 34 patients with glioblastoma. Unsupervised clustering on either profile resulted in similar groups of patients, and groups defined by either method were associated with survival. The high concordance between these separate molecular classifications suggested a strong association between alterations on the DNA and RNA levels. We therefore investigated relationships between DNA copy number and gene expression changes. Loss of chromosome 10, a predominant genetic change, was associated not only with changes in the expression of genes located on chromosome 10 but also with genome-wide differences in gene expression. We found that CHI3L1/YKL-40 was significantly associated with both chromosome 10 copy number loss and poorer survival. Immortalized human astrocytes stably transfected with CHI3L1/YKL-40 exhibited changes in gene expression similar to patterns observed in human tumors and conferred radioresistance and increased invasion in vitro. Taken together, the results indicate that integrating DNA and mRNA-based tumor profiles offers the potential for a clinically relevant classification more robust than either method alone and provides a basis for identifying genes important in glioma pathogenesis.

Adipokines↗