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Abstract Background Despite advances in diagnostic and treatment strategies, head and neck squamous cell cancer (HNSCC) constitutes one of the worst cancer types in terms of prognosis. PTEN is one of the tumour suppressors whose expression and/or activity have been found to be reduced in HNSCC, with rather low rates of mutations within the PTEN gene (6-8%). We reasoned that low expression levels of PTEN might be due to a transcriptional repression governed by an oncogene. Tbx2 and Tbx3, both of which are transcriptional repressors, have been found to be amplified or over-expressed in various cancer types. Thus, we hypothesize that Tbx3 may be over expressed in HNSCC and may repress PTEN, thus leading to cancer formation and/or progression. Methods Using immunohistochemistry and quantitative PCR (qPCR), protein and mRNA levels of PTEN and Tbx3 were identified in samples excised from cancerous and adjacent normal tissues from 33 patients who were diagnosed with HNSCC. In addition, HeLa and HEK cell lines were transfected with a Tbx3 expressing plasmid and endogenous PTEN mRNA and protein levels were determined via qPCR and flow cytometry. Transcription assays were performed to demonstrate effects of Tbx3 on PTEN promoter activity. Mann–Whitney, Spearman’s Correlation and Wilcoxon signed-rank tests were used to analyze the data. Results We demonstrate that in HNSCC samples, Tbx3 mRNA levels are increased with respect to their normal tissue counterparts (p Conclusions We show that Tbx3 is up-regulated in tissue samples of HNSCC patients and that Tbx3 represses PTEN transcription. Thus, our data not only reveals a new mechanism that may be important in cancer formation, but also suggests that Tbx3 can be used as a potential biomarker in cancer.

Phosphodiesterase type-5 (PDE-5) inhibitors are novel and important options for the treatment of pulmonary arterial hypertension (PAH). Therefore, we aimed to examine effects of vardenafil, a PDE-5 inhibitor, on the pulmonary arteries isolated from rats with monocrotaline- (MCT-) induced pulmonary hypertension. MCT (60 mg/kg) or its vehicle was administered by a single intraperitoneal injection to 6-week-old male Sprague Dawley rats. Rats were sacrificed 21 days after MCT injection, and the main pulmonary arteries were isolated and then mounted in 20 mL organ baths. Concentration-response curves for vardenafil (10(-10)-10(-5) M) were constructed in phenylephrine- (Phe-) precontracted rings. PAH caused marked rightward shift in the curves to vardenafil whereas maximal responses were not affected. Inhibition of NO synthase (L-NAME, 10(-4) M) or guanylyl cyclase (ODQ, 10(-5) M) caused similar attenuation in responses evoked by vardenafil. Moreover, contraction responses induced by CaCl(2) (3 × 10(-5)-3 × 10(-2) M) were significantly reduced in concentration-dependent manner by vardenafil. In conclusion, vardenafil induced pulmonary vasodilatation via inhibition of extracellular calcium entry in addition to NO-cGMP pathway activation. These results provide evidence that impaired arterial relaxation in PAH can be prevented by vardenafil. Thus, vardenafil represents a valuable therapeutic approach in PAH besides other PDE-5 inhibitors.

The oral-facial-digital syndrome type 1 is characterized by following abnormalities: pseudocleft of the upper lip, tongue lobulation, hamartomata on the tongue, alveolar frenulae, and clefting of the soft palate. We report a 9-month-old girl who was referred to our clinic due to facial dysmorphology in addition to cleft palate and multiple masses on the tongue which resulted in feeding problems. Surgical intervention was done. Molecular analysis revealed absence of OFD gene.

Objective: To evaluate the presence of micrometastatic tumor cells in the peripheral blood samples of the patients with head and neck squamous cell carcinoma (HNSCC) and to determine whether the presence of micrometastatic cells had any biological relevance in terms of local recurrences or metastasis during a follow-up period of 3 years., Methods: We included 21 consecutive patients with untreated primary HNSCC admitted to the Ear Nose and Throat Department of Akdeniz University Medical School, Antalya, Turkey between February and October 2002. Squamous carcinoma cells in peripheral blood samples of these patients prior to surgery were detected via a magnetic cell separation technique using anti-epithelial cell adhesion molecule antibody, and thereafter evaluated by light microscopy with hematoxylin and eosin staining., Results: Seven out of 21 patients showed squamous carcinoma cells in peripheral blood samples. Patients with stage III and IV tumors were nearly 5 times more likely to show micrometastatic cells compared with those with stage I and II tumors (6/12 versus 1/9). During the follow-up, 2 patients out of 7 with micrometastasis had recurrences. None in the micrometastasis negative group relapsed., Conclusion: We suggest that HNSCC patients with detectable tumor cells in peripheral blood represent a subset of patients who should be followed up more closely for possible recurrences.

Background: Various biomarkers have prognostic value in non-small cell lung cancer (NSCLC). We aimed to identify the roles of P53, c-erb- B2 and p-glycoprotein (pgp) as prognostic factors, independently or in conjunction with each other, in operable NSCLC., Material/methods: Seventy operable NSCLC cases were retrospectively evaluated for P53, c-erb-B2 and pgp expression patterns by immunohistochemistry. An unsupervised hierarchical cluster analysis of the 3 biomarkers was conducted. Univariate and multivariate survival analyses were made in relation to cluster affiliation., Results: Cluster analysis yielded two distinct subgroups; group A of high biomarker expressors (n=26, 37%), and group B (n=44, 63%) of low expressors. Cluster affiliation with regard to tumor histology (interaction term) was independently associated with Recurrence- free survival (RFS) and Overall survival (OAS) with a Hazard Ratio (HR) of 5.88, P=0.003, and HR=4.68, P=0.012, respectively. The median OAS times for cluster A and B in the squamous cell carcinoma subgroup were 328 and 596 days, whereas the corresponding figures in the non-squamous cell carcinoma subgroup were non-measurable and 298 days., Conclusions: In operable NSCLC there may be different relationships of P53, c-erb-B2 and pgp with patient outcome for different tumor histologies. The prognostic utility of cluster affiliation with regard to these biomarkers, and in relation to tumor histology, deserves further testing.