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ABSTRACT: Abstract Conclusion: The study showed the value of using intravital microscopy (IVM) analysis for the study of neoangiogenesis. It demonstrated that the model and the analytical methodology could be used to evaluate in detail the effects of treatment strategies for solid tumours. Objectives: Neoangiogenesis is a key component of tumour progression, invasion and metastasis. In clinical trials monoclonal antibodies specific for vascular endothelial growth factor - VEGF (bevacizumab) - have been shown to significantly affect tumour progression when given in combination with standard chemotherapy, and also to improve the overall survival of patients. For squamous cell carcinoma of the head and neck (HNSCC), we still await definitive evidence of the effect of such treatment. The present study was designed to investigate the anti-angiogenesis effect of beviacizumab in green fluorescent protein (GFP)-labelled HNSCC xenografts using IVM technology. Methods: We performed IVM and used image analysis for quantification of angiogenesis and of effects of bevacizumab on cell viability, combined with histochemical and immunohistochemical analysis to standardize the digital analysis of changes in tumour vascularization and cell viability. Results: We found significant effects of bevacizumab on angiogenesis and cancer cell survival in HNSCC. Repeated injections of bevacizumab were found to provide the greatest effects.
Acta oto-laryngologica 10/2012; · 0.98 Impact Factor
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ABSTRACT: Treatment outcomes for carcinomas of the external auditory canal (EAC) were evaluated regarding radiologic and pathologic factors.
Retrospective case review.
University hospital.
Fifteen patients histologically diagnosed with carcinomas of the EAC.
A radiologic and pathologic analysis was performed on these patients histologically diagnosed with carcinomas of the EAC and treated surgically at our institution. We evaluated the size of focal defects in the anteroinferior (AI) canal wall of the tympanic bone with preoperative computed tomographic (CT) scans. Histopathologic slides for the same patients were evaluated according to the same criteria as the CT scans.
Pathologic features and estimated survival rate.
Preoperative CT scans of 15 temporal bones demonstrated an AI canal wall defect ranging from less than 1 mm to full-thickness destruction. Six of 15 patients had an AI canal wall defect greater than 2 mm on preoperative CT scan. Pathologic findings in these 6 cases showed extension of the tumor through the AI defect into the anterior soft tissues. Information on patients' survival status was obtained after a median follow-up period of 78.3 months (range, 18-151 mo).
Preoperative CT can be used to accurately determine the pathologic extent of tumor invasion in carcinomas of the EAC. This diagnostic method facilitates exchange of accurate clinical data in a comparable form and can be used to evaluate the efficacy of existing and proposed treatments for EAC tumors.
Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 02/2012; 33(3):450-4. · 1.44 Impact Factor
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ABSTRACT: Predictive strategies for the treatment efficacy of cetuximab are currently not available for head and neck cancer. We investigated the correlation between the expression of epidermal growth factor receptor (EGFR) ligands and EGFR expression, and the growth inhibitory activity of cetuximab in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines.
The growth inhibiting effect of cetuximab was measured for eight HNSCC cell lines and correlated with the autocrine production of five EGFR ligands as measured by ELISA, and the mRNA expression of two ligands, as measured by quantitative RT-PCR. EGFR expression was assessed by western blot analysis.
There was a good correlation between the expression of four of the EGFR ligands (TGF-α, amphiregulin, epiregulin and epigen) and the growth inhibiting effect of cetuximab. TGF-α had the highest predictive potential but had to be combined with epigen for full prediction. EGFR expression also correlated with cetuximab sensitivity but less clearly.
The results indicate that the expression of several EGFR ligands has to be used to predict sensitivity to cetuximab in HNSCC. This has to be further evaluated in clinical samples.
Journal of Cancer Research and Clinical Oncology 12/2011; 138(3):491-9. · 2.56 Impact Factor
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ABSTRACT: The aim of this study was to investigate the effect of epidermal growth factor receptor (EGFR) blockade on cell survival and on downstream signalling pathways using the monoclonal antibody cetuximab.
We used three colon cancer cell lines, of which one was EGFR-negative, and two head and neck squamous cell carcinoma (HNSCC) lines. EGFR expression and gene copy number were measured by immunohistochemistry and FISH analysis, respectively. The effect of cetuximab, irradiation or the combination of both on cell growth was estimated by SRB assay. Western blotting was used to determine the phosphorylation of intracellular signalling proteins and cell cycle phase distribution was measured by flow cytometry.
The addition of cetuximab had only limited effects on cell growth, with a maximum inhibition of approximately 30%, but was correlated with the amount of protein expression and gene copy number of EGFR. When combined with irradiation, the effect of cetuximab was only additive and not dependent on the inherent radio-sensitivity of the cell lines. Persistent phosphorylation of Akt and/or p44/42 MAPK was detected by western blot in all of the cell lines, whereas there was no phosphorylation of Jak2 or STAT3.
None of these factors alone could predict the sensitivity to cetuximab. Rather, the results suggest that it might be necessary to determine the activation status of several intracellular signalling proteins to better predict the sensitivity to cetuximab treatment.
Journal of Cancer Research and Clinical Oncology 10/2008; 135(3):395-402. · 2.56 Impact Factor
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ABSTRACT: Small cell neuroendocrine carcinoma of the head and neck is rare, and diagnosis may be difficult. Malignancy is high, as is the incidence of distant metastasis. We reported eight cases of stage IV small cell neuroendocrine carcinoma of the head and neck, all in men with a mean onset age of 62 years (range: 45 to 80 years). Three cases arose from the maxillary sinus, two from the ethmoid sinus, one from the parotid gland, one from the tonsil, and one from the larynx. Histological analysis by hematoxylin-eosin staining tentatively revealed malignant lymphoma and undifferentiated carcinoma in two cases each, while immunohistological and/or electron microscopy analysis confirmed histological diagnosis. All were treated by chemotherapy (VP-16, CDDP) and seven cases with radiotherapy based on the schedule of small cell carcinoma of the lung and two cases with lesional resection. Chemotherapy and radiotherapy were effective locally. Five patients died of distant metastasis to the brain, bone, lung, liver, or skin within 12 months. One is alive with liver metastasis. Two have no evidence of disease--one for eight years and the other for one year. Long-term survival thus requires the effective treatment of distant metastasis.
Nippon Jibiinkoka Gakkai Kaiho 08/2008; 111(7):517-22.
