Biomedical subjects

Eben Rosenthal

Publications and source records attributed to Eben Rosenthal.

4 recordsLinked to original sources

PubMed2006

Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity.

Toll-like receptor 9 (TLR9) recognizes microbial DNA. We show here that TLR9 protein is expressed in human breast cancer cells and clinical breast cancer samples. Stimulation of TLR9-expressing breast cancer cells with the TLR9 agonistic CpG oligonucleotides (1-10 mumol/L) dramatically increased their in vitro invasion in both Matrigel assays and three-dimensional collagen cultures. Similar effects on invasion were seen in TLR9-expressing astrocytoma and glioblastoma cells and in the immortalized human breast epithelial cell line MCF-10A. This effect was not, however, dependent on the CpG content of the TLR9 ligands because the non-CpG oligonucleotides induced invasion of TLR9-expressing cells. CpG or non-CpG oligonucleotide-induced invasion in MDA-MB-231 cells was blunted by chloroquine and they did not induce invasion of TLR9(-) breast cancer cells. Treatment of MDA-MB-231 cells with CpG or non-CpG oligonucleotides induced the formation of approximately 50-kDa gelatinolytic band in zymograms. This band and the increased invasion were abolished by a matrix metalloproteinase (MMP) inhibitor GM6001 but not by a serine proteinase inhibitor aprotinin. Furthermore, CpG oligonucleotide treatment decreased tissue inhibitor of metalloproteinase-3 expression and increased levels of active MMP-13 in TLR9-expressing but not TLR9(-) breast cancer cells without affecting MMP-8. Neutralizing anti-MMP-13 antibodies inhibited the CpG oligonucleotide-induced invasion. These findings suggest that infections may promote cancer progression through a novel TLR9-mediated mechanism. They also propose a new molecular target for cancer therapy, because TLR9 has not been associated with cancer invasiveness previously.

Antibodies↗

PubMed2004

Simplifying head and neck microvascular reconstruction.

BACKGROUND: Free-tissue transfer has become the preferred method of head and neck reconstruction but is a technique that is considered to use excessive hospital resources. METHODS: This study is a retrospective review of 125 consecutive free flaps in 117 patients over a 16-month period at a tertiary care university hospital. RESULTS: Defects of the oral cavity/oropharynx (60%), midface (9%), hypopharynx (15%), or cervical and facial skin (16%) were reconstructed from three donor sites: forearm (70%), rectus (11%), and fibula (19%). Microvascular anastomoses were performed with a continuous suture technique or an anastomotic coupling device for end-to-end venous anastomoses. A single vein was anastomosed in 97% of tissue transfers. There were five flaps (4%) requiring exploration for vascular compromise, and the overall success rate was 97.6%. The major complication rate was 13%. Mean hospital stay was 7 days for all patients and 5 days for those with cutaneous defects. Combined ablative and reconstructive operative times were 6 hours 42 minutes, 7 hours 40 minutes, and 8 hours 32 minutes for forearm, rectus, and fibular free grafts, respectively. A subset of this patient series with oral cavity and oropharynx defects (76 patients; 58%) available for follow-up (74 patients) was assessed for deglutition. Forty-three patients (58%) had a regular diet, 22 patients (30%) had a limited diet or required supplemental tube feedings, and nine patients (12%) were dependent on tube feedings with a severely limited diet. CONCLUSIONS: This series suggests that most head and neck defects can be reconstructed by use of a simplified microvascular technique and a limited number of donor sites. Analysis of operative times and length of stay suggest improved efficiency with this approach to microvascular reconstruction. Complications and functional results are comparable to previously published results.

Adult↗

PubMed2004

Elevated expression of TGF-beta1 in head and neck cancer-associated fibroblasts.

Head and neck cancers are characterized by a vigorous desmoplastic response, but the contribution of stromal-derived growth factors to the tumor microenvironment is poorly understood. We evaluated the expression of stromal growth factor expression in head and neck squamous cell carcinoma (HNSCC) in normal and tumor-associated stromal cells. Stromal tissue was isolated from epithelial cells with laser capture microdissection (LCMD) and analyzed by cDNA array for the expression of TGFalpha, TGF-beta1, HGF, PDGF-alpha, IGFII, bFGF, aFGF, VEGFC, and VEGF. Primary fibroblasts were isolated in vitro from HNSCC tumors, adjacent histologically normal mucosa, and skin in vitro. Fibroblast populations were assessed for TGF-beta1 expression by ELISA and luciferase reporter assay to assess protein expression. We identified TGF-beta1 and IGFII overexpression in normal and tumor-associated stromal cells; however, only TGF-beta1 was significantly overexpressed (3.4-fold) in tumor-associated stroma. Assessment of carcinoma-associated fibroblasts (CAFs), normal dermal fibroblasts (NDFs), and normal mucosal fibroblasts (NMFs) in propagated fibroblasts demonstrated persistently elevated levels of TGF-beta1 in CAFs compared to NMF and NDF populations. Elevated levels of TGF-beta1 were identified in the stromal compartment of HNSCC tumors compared to normal mucosa by immunohistochemical analysis. These results suggest that TGF-beta1 mRNA and protein is specifically upregulated in CAFs in vitro and in vivo.

Animals↗

PubMed2002

Surgical management of gastroesophageal reflux and outcome after laryngectomy in patients using tracheoesophageal speech.

BACKGROUND: Gastroesophageal reflux disease (GERD) is common in patients with head and neck carcinoma. The impact of laparoscopic fundoplication on laryngectomy patients with tracheoesophageal prostheses for voice restoration is unknown. METHODS: Nine laryngectomy patients who use tracheoesophageal speech underwent laparoscopic fundoplication for documented reflux. Preoperative and postoperative symptoms were recorded. Quality of speech was documented before and after fundoplication. RESULTS: Although 88% of patients had resolution of GERD symptoms, all developed bloating and hyperflatulence. There was no difference in quality of esophageal speech after laparoscopic fundoplication. CONCLUSIONS: Fundoplication in laryngectomy patients that use tracheoesophageal speech eliminates symptoms of gastroesophageal reflux and resolves regurgitation associated prosthesis erosion. Although nearly all patients are satisfied with outcome, there is a high incidence of postfundoplication bloating and hyperflatulence that may be life limiting. Poor quality tracheoesophageal speech should not be used as an indication for antireflux surgery.

Aged↗