HER2/neu antisense targeting of human breast carcinoma.

Overexpression of the HER2/neu oncogene is observed in approximately 30% of human breast carcinoma specimens. HER2/neu overexpression is a negative prognostic factor in breast cancer patients. Cancer cells that overexpress HER2/neu may also be less sensitive to chemotherapy. In order to further define mechanisms by which HER2/neu overexpression drives neoplastic cell growth and chemoresistance, antisense oligonucleotides (ODNs) have been utilized to selectively down-regulate HER2/neu expression in human breast cancer cells. Such antisense ODNs suppress HER2/neu mRNA and protein levels in a dose-dependent, sequence-specific manner. Down-regulation of HER2/neu expression in HER2/neu overexpressing breast cancer cells inhibits cell cycle progression in G0/G1 and results in apoptotic cell death. In tissue culture studies, combined treatment of HER2/ neu overexpressing breast cancer cells with HER2/neu antisense ODNs and conventional chemotherapeutic agents results in synergistic inhibition of cancer cell growth and activation of apoptotic cell death mechanisms. These studies have been extended to demonstrate synergistic antitumor effects following systemic treatment with antisense ODNs plus doxorubicin in nude mice bearing human breast carcinoma xenografts. Collectively these findings demonstrate that HER2/neu overexpression stimulates anti-apoptotic cell survival mechanisms and suggest that HER2/neu antisense ODNs may be of use in cancer therapeutics.

Malignant tumors of the nose and paranasal sinuses: hospital of the University of Pennsylvania experience 1990-1997.

We reviewed our experience with sinonasal malignancies, which comprise less than 1% of all cancers, in order to determine the spectrum of disease and outcome after treatment. The medical records of 48 patients with sinonasal malignancies treated between 1990-1997 were reviewed for epidemiologic characteristics, tumor location and histology, treatment modalities, and tumor recurrence. Mean age was 58.5 years and 46% were male. Multiple sites of origin were common, including maxillary sinus (83%), ethmoid sinus (35%), and nasal cavity (40%). The histologic spectrum included squamous cell carcinoma (46%), adenoid cystic carcinoma (6%), and miscellaneous others (48%). Treatment included surgery and adjuvant radiotherapy (XRT) (58%), surgery alone (27%), XRT and chemotherapy (6%), surgery and chemotherapy (4%), and XRT alone (4%). Mean follow-up was 15 months (range 2-58). Recurrence was evident in nine patients (19%), 3 (33%) of whom had prior treatment before presenting to HUP. Of the six who recurred after initial treatment at HUP, five (83.3%) were treated with surgery and XRT and one (16.7%) was treated with surgery alone. Of the three that recurred after undergoing attempts at salvage (prior treatment and then treatment at HUP), one had received surgery alone followed by surgery and XRT, one had surgery and XRT followed by surgery and one had XRT followed by surgery alone. Our experience reveals surgery and XRT to be the modality of choice, particularly for advanced tumors, whereas surgery alone may be sufficient for small, well localized tumors. Neoadjuvant chemotherapy may offer improved local control; the future role of endoscopic surgery warrants further investigation.