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Ellie Maghami

Publications and source records attributed to Ellie Maghami.

7 recordsLinked to original sources
PubMed2006

Squamous cell carcinoma related oncogene/DCUN1D1 is highly conserved and activated by amplification in squamous cell carcinomas.

Chromosomal amplification at 3q is common to multiple human cancers, but has a specific predilection for squamous cell carcinomas (SCC) of mucosal origin. We identified and characterized a novel oncogene, SCC-related oncogene (SCCRO), which is amplified along the 3q26.3 region in human SCC. Amplification and overexpression of SCCRO in these tumors correlate with poor clinical outcome. The importance of SCCRO amplification in malignant transformation is established by the apoptotic response to short hairpin RNA against SCCRO, exclusively in cancer cell lines carrying SCCRO amplification. The oncogenic potential of SCCRO is underscored by its ability to transform fibroblasts (NIH-3T3 cells) in vitro and in vivo. We show that SCCRO regulates Gli1--a key regulator of the hedgehog (HH) pathway. Collectively, these data suggest that SCCRO is a novel component of the HH signaling pathway involved in the malignant transformation of squamous cell lineage.

Animals↗
PubMed2005

Gene expression profiling allows distinction between primary and metastatic squamous cell carcinomas in the lung.

Lung neoplasms commonly develop in patients previously treated for head and neck carcinomas. The derivation of these tumors, either as new primary lung cancers or as metastatic head and neck cancers, is difficult to establish based on clinical or histopathologic criteria since both are squamous cell carcinomas and have identical features under light microscopy. However, this distinction has significant treatment and prognostic implications. Gene expression profiling was performed on a panel of 52 sequentially collected patients with either primary lung (n = 21) or primary head and neck (n = 31) carcinomas using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray. Unsupervised hierarchical clustering with Ward linkage and the Pearson correlation metric was performed. To assess robustness, bootstrap resampling was performed with 1,000 iterations. A t test of the normalized values for each gene was used to determine the genes responsible for segregating head and neck from lung primary carcinomas, and those with the most differential expression were used for later analyses. In the absence of a large "test" set of tumors, we used a supervised leave-one-out cross-validation to test how well we could predict the tumor origin. Once a gene expression profile was established, 12 lung lesions taken from patients with previously treated head and neck cancers were similarly analyzed by gene expression profiling to determine their sites of origin. Unsupervised clustering analysis separated the study cohort into two distinct groups which reliably remained segregated with bootstrap resampling. Group 1 consisted of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and 1 tongue carcinoma. The clustering was not changed even when normal lung or tongue profiles were subtracted from the corresponding carcinomatous lesions, and a leave-one-out cross-validation showed a 98% correct prediction (see Supplementary Data 1). A minimum set of 500 genes required to distinguish these groups was established. Given the ability to segregate these lesions using molecular profiling, we analyzed the lung tumors of undetermined origin. All cases clearly clustered with either lung or tongue tumor subsets, strongly supporting our hypothesis that this technique could elucidate the tissue of origin of metastatic lesions. Although histologically similar, squamous cell carcinomas have distinct gene expression profiles based on their anatomic sites of origin. Accordingly, the application of gene expression profiling may be useful in identifying the derivation of lung nodules and consequently enhances treatment planning.

Algorithms↗
PubMed2005

MUC1 plays a role in tumor maintenance in aggressive thyroid carcinomas.

BACKGROUND: We recently identified MUC1 as a target driving selection for 1q21 amplification and validated it as an independent marker of aggressive behavior in thyroid cancer (TC). The aims of this study were to determine whether TC cell lines retain MUC1 expression patterns that are seen in primary tumors, assess the role of MUC1 in tumor maintenance, and develop a virally delivered anti-MUC1 RNA interference (RNAi) that is effective in decreasing MUC1 expression in vitro. METHODS: Fifteen TC cell lines were screened for MUC1 protein expression. Cell lines with varying MUC1 protein levels were treated with anti-MUC1 monoclonal antibody to assess cell viability. A recombinant retroviral short hairpin RNAi delivery system against MUC1 was developed. Efficacy and optimal dosing of short hairpin RNA against MUC1 was determined. RESULTS: MUC1 expression patterns in TC cell lines were found to be similar to that seen in primary tumors. Treatment with anti-MUC1 antibody resulted in a significant decrease in cell viability in MUC1 over-expressing cell lines. MUC1-779 RNAi construct showed excellent infection efficiency and reproducible silencing. CONCLUSION: These data offer functional evidence that implicates MUC1 over-expression as a key molecular event in the pathogenesis of aggressive TC. Retrovirally delivered anti-MUC1 RNAi is effective in silencing MUC1 and merits further investigation to establish therapeutic efficacy and safety in anticipation of potential clinical application.

Antigens↗
PubMed2004

Cancer of the nasal cavity and paranasal sinuses.

Sinonasal malignancies continue to have poor survival rates. Disease-related mortality is usually the result of disease recurrence and progression at the primary site despite aggressive therapy. Complete surgical excision with postoperative radiation therapy remains the standard of care for resectable lesions. Improved reconstructive techniques have increased our ability to aggressively clear locally advanced disease in this anatomically challenging region, while reducing associated functional and cosmetic morbidity. Intensive multimodality treatment regimens coupled with newer medical technology may ultimately improve the long-prevailing poor prognosis of these tumors.

Combined Modality Therapy↗
PubMed2003

MRI-guided access to the retropharynx.

PURPOSE: To describe MR-guided access to the retropharynx for precise fine-needle aspiration cytology (FNAC), and other indications for needle placement. MATERIALS AND METHODS: A retrospective review was made of 15 procedures that had been performed on 14 patients. These patients had a retropharyngeal mass on MRI and had undergone MR-guided minimally invasive access to the retropharynx for either diagnostic or therapeutic intervention in the period of October 1989 to January 2000. RESULTS: All 14 patients underwent MR-guided access to the retropharynx for FNAC without immediate or delayed complications. MRI confirmed that the biopsy needle was within the retropharyngeal mass in all patients. MR-guided FNAC revealed five true-positive, five true-negative, four indeterminate, and no false-positive cases. Ten of the 14 patients (71%) had diagnostic aspirations. In one patient with retropharyngeal extension of carcinoma, an MR-guided approach was used for the experimental interstitial laser therapy (ILT). CONCLUSION: The results suggest that an MR-guided retromandibular approach to biopsy of retropharyngeal mass is minimally invasive and safe.

Adult↗
PubMed2002

Long-term survival outcome in transhyoid resection of base of tongue squamous cell carcinoma.

BACKGROUND: The transhyoid approach for the resection of squamous cell carcinoma (SCC) of the base of the tongue continues to evolve and remains controversial. We previously reported that the functional outcome of this operation is superior to that of the traditional transmandibular approaches. OBJECTIVE: To report our long-term survival rates for T1, T2, and select T3 SCCs of the base of the tongue using the transhyoid approach. PATIENTS AND METHODS: Twenty-eight patients with SCC of the base of the tongue were treated using a transhyoid approach at the University of California, Los Angeles, Medical Center between 1981 and 1998. RESULTS: All 28 patients underwent simultaneous neck dissection, and 27 patients underwent postoperative radiation therapy. The majority of the patients had advanced stage III or IV SCC. Twenty-five of the 28 patients had clear margins in the final pathologic specimen. The overall 3- and 5-year patient survival rates were 88.5% and 80.0%, respectively. Tumor-specific 5-year survival rates were 80.0%, 84.6%, and 50.0% for T1, T2, and T3 tumors, respectively. Stage-specific 5-year survival rates were 60.0%, 100.0%, and 80.0% for stages II, III, and IV, respectively. CONCLUSIONS: The advantages of the transhyoid approach to SCC of the base of the tongue in conjunction with neck dissection and postoperative radiation therapy include excellent long-term patient survival, improved swallowing and speech function, outstanding tumor exposure, and minimal cosmetic deformity.

Aged↗