PubMed Health⌕ Search

Biomedical subjects

Janet I Lee

Publications and source records attributed to Janet I Lee.

5 recordsLinked to original sources
PubMed2004

Loss of Fhit expression in head and neck squamous cell carcinoma and its potential clinical implication.

PURPOSE: Abnormalities of FHIT, a candidate tumor suppressor gene, have frequently been found in multiple malignancies, including head and neck squamous cell carcinoma (HNSCC). To define its role in HNSCC treated with surgery and postoperative radiotherapy (PORT), the Fhit protein expression status was investigated in 80 patients enrolled in a prospective Phase III clinical trial addressing the dose and fractionation regimen of PORT. EXPERIMENTAL DESIGN: Immunohistochemical staining of HNSCC tissue sections for Fhit expression was performed. The Fhit expression status was correlated with the clinicopathological characteristics and clinical course. The median follow-up duration was 4.9 years. RESULTS: Loss of Fhit expression was found in 52 of the 80 study patients (65%). There was not a significant association between Fhit expression and clinical characteristics. Patients whose tumor exhibited negative Fhit expression had a significantly worse 5-year overall survival duration [hazard ratio = 0.49; 95% confidence interval, 0.23-1.03; P = 0.05 (log-rank test)] than did those whose tumor exhibited positive Fhit expression. One third of the patients with a Fhit-negative tumor had distant metastasis during the follow-up period. Paradoxically, patients classified as high risk who had a Fhit-negative tumor experienced locoregional recurrence less often (18%) than did high-risk patients who had a Fhit-positive tumor (33%). CONCLUSIONS: Loss of Fhit expression is a poor prognostic indicator in patients with HNSCC. However, tumors lacking Fhit expression may be more sensitive to PORT and therefore more susceptible to locoregional control.

Acid Anhydride Hydrolases↗
PubMed2002

Cyclin B1 overexpression and resistance to radiotherapy in head and neck squamous cell carcinoma.

Radiotherapy (RT) and surgery are the cornerstones in treating head and neck squamous cell carcinoma (HNSCC). RT is effective in the initial treatment of early to intermediate stage HNSCC but less effective for locally advanced disease, some cases of which are best managed using the combination of surgery and RT. Although various clinical/pathologic parameters have been used to classify patients according to their likelihood of responding to RT, they have generally low predictive value. We have shown previously that cyclin B1 is associated with a poor clinical outcome in HNSCC patients. In this study, we investigate the potential role of cyclin B1 in assessing RT response in patients with HNSCC. Tumor specimens obtained from 80 patients participated in a prospective Phase III clinical trial addressing the dose and fractionation regimen of postoperative RT were analyzed for cyclin B1 expression by immunohistochemistry. Patients were classified according to currently accepted clinical/pathologic parameters into three risk groups, i.e., low, intermediate, and high risk, and received surgery alone, surgery plus intermediate-dose RT, and surgery plus high-dose RT, respectively. The median follow-up duration was 4.9 years. Cyclin B1 overexpression was noted in 38 of the 80 (47%) HNSCC tumors. Interestingly, 11 of the 38 patients (29%) with cyclin B1-overexpressing tumors experienced local or nodal recurrence compared with only 3 of 42 patients (7%) having carcinomas with no or weak cyclin B1 expression (P = 0.01). When locoregional control was used as the end point for the high-risk group, patients whose tumors showed cyclin B1 overexpression had a statistically significant higher tumor recurrence and metastasis compared with patients whose tumors showed no cyclin B1 overexpression (P = 0.01). Our results indicate that tumors overexpressing cyclin B1 may be resistant to RT, and cyclin B1 may be an indicator of the risk of locoregional recurrence and metastasis in patients having HNSCC receiving RT.

Adult↗
PubMed2002

Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation.

PURPOSE: The PTEN gene at chromosome 10q23.3 is a tumor-suppressor genethat is inactivated in several types of human tumors. Althoughmutation and homozygous deletion are the most commonmechanisms of PTEN inactivation, promoter methylation and translational modification can also account for PTEN silencing. The aim of this study was to investigate the expression of PTEN protein in primary non-small cell lung cancer (NSCLC) samples and to investigate the promoter methylation status of the gene in a panel of NSCLC cell lines as well as primary tumors. EXPERIMENTAL DESIGN: We analyzed PTEN expression by immunohistochemistry in tissue samples from 125 patients with early-stage NSCLC. We also evaluated PTEN promoter methylation status by methylation-specific PCR in 20 microdissected PTEN-negative primary tumors from among the last specimens as well as in a panel of 16 NSCLC cell lines. Western and Northern blotting were performed in the same panel of NSCLC cell lines. RESULTS: Thirty (24%) of the 125 specimens showed a lack of staining for PTEN. PTEN methylation was detected in 7 (35%) of the 20 PTEN-negative NSCLC samples and in none of the 10 PTEN-positive NSCLC samples that were microdissected. Furthermore, PTEN methylation was observed in 11 (69%) of the 16 NSCLC cell lines tested. PTEN mRNA expression was increased in the NCI-H1299 cell line by in vitro treatment with the demethylating agent 5-aza-2'-deoxycytidine. PTEN methylation was well correlated with PTEN expression in NSCLC cell lines by Western and Northern blot (P = 0.025). CONCLUSIONS: Although genetic alterations of the PTEN gene are rare in NSCLC, loss of PTEN protein is not an uncommon event in early-stage NSCLC. Lack of PTEN expression may be partially explained by promoter methylation.

Adult↗
PubMed2002

Inhibition of oncogenic K-ras signaling by aerosolized gene delivery in a mouse model of human lung cancer.

PURPOSE: Transfer of growth-suppressive genes to lung tumors has therapeutic potential, but effective delivery techniques have not been developed. Here, we investigated gene delivery to lung tumors by aerosolization of adenoviral vectors incorporated into calcium phosphate precipitates. EXPERIMENTAL DESIGN: To investigate the efficacy of this delivery method in normal and neoplastic lung, an adenoviral vector expressing beta-galactosidase was administered by jet nebulization to K-ras(LA1) mice, which develop lung adenocarcinomas through activation of a latent allele carrying mutant K-ras(G12D). Furthermore, we investigated whether aerosolized delivery of Ad-MKK4 (KR), an adenoviral vector expressing dominant-negative mutant mitogen-activated protein kinase kinase 4(MKK4), can block Ras-dependent signaling in K-ras(LA1) mice. RESULTS: After a single administration, beta-galactosidase was detected in lung tissue for up to 21 days, and expression was much greater in tumors than in normal lung tissue. MKK4 was activated in the lungs of K-ras(LA1) mice, and aerosolized treatment with Ad-MKK4 (KR) decreased c-Jun-NH(2)-terminal kinase but not extracellular signal- regulated kinase activity, providing evidence that MKK4 was selectively inhibited. CONCLUSIONS: These findings demonstrate a novel approach to targeting oncogenic pathways in lung tumors by aerosolized gene delivery.

Adenocarcinoma↗