Acute Effects of Vardenafil on Pulmonary Artery Responsiveness in Pulmonary Hypertension

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 CaCl2 (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

Spindle Cell Carcinoma of the Larynx: A Confusing Diagnosis for the Pathologist and Clinician

Laryngeal spindle cell carcinoma (SpCC) is an uncommon subtype of squamous cell carcinoma which represents 0.5% of all laryngeal squamous cell carcinomas. It is a biphasic tumor consisting of the combination of a malignant mesenchymal spindle cell component and a squamous cell component that includes dysplasia, carcinoma in situ, or invasive carcinoma. Although it has aggressive biological features, the probability of making a diagnosis in the early stages is high as it often leads to obstructive symptoms in the early period. Due to its low incidence, there is no clear consensus on prognostic factors and optimal treatment strategies yet. In this paper, a 60-year-old laryngeal SpCC case that was effectively treated with wide local excision followed by adjuvant radiotherapy was presented with the literature

Tbx3 represses PTEN and is over-expressed in head and neck squamous cell carcinoma

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.</p

Inter-observer Agreement in Laryngeal Pre-neoplastic Lesions

In this series, laryngeal preneoplastic lesions were evaluated by the classifications of the World Health Organization (WHOC), Ljubljana (LC) and squamous intraepithelial neoplasia (SINC) by multiple observers. The inter-observer agreement (IA) by WHOC for laryngeal lesions had been previously evaluated, but to the best of our knowledge, there are no data for LC and SINC. H&E stained slides from 42 laryngeal biopsies were evaluated by fourteen participants according to WHOC and LC, and SINC was additionally applied by 6. The results were analyzed statistically. The diagnoses which were favored by most participants for each case, according to WHOC, were as follows: squamous cell hyperplasia (n = 5; 12%), mild dysplasia (n = 11; 26.2%), moderate dysplasia (n = 12; 28.6%), severe dysplasia (n = 7; 16.7%), carcinoma in situ (n = 5; 12%), and invasive squamous cell carcinoma (n = 2; 4.8%). There was a significant difference between the participants for all three classifications; some participants gave lower or higher scores than the others. The mean correlation coefficients (MCC) of the participants were higher for WHOC compared to LC (0.55 ± 0.15 and 0.48 ± 0.14, respectively). The mean linear-weighted kappa (wKappa) values of participants were not significantly different (0.42 ± 0.10, 0.41 ± 0.12 and 0.37 ± 0.07 for WHOC, LC and SINC, respectively). The kappa values in this series are in agreement with those in previous literature for WHOC, and the similar results obtained for LC and SINC are novel findings. Although the MCC of WHOC was higher, as the wkappa was not significantly different, the findings in this series are not in favor of any of the classifications for better IA for pre-neoplastic laryngeal lesions. © 2010 Humana

Erratum to: Inter-observer Agreement in Laryngeal Pre-neoplastic Lesions

[No abstract available