Levent Dertsiz

Differential expression of VASP in normal lung tissue and lung adenocarcinomas

Background: Vasodilator stimulated phosphoprotein (VASP) is associated with focal adhesions and is thought to have an important role in actin filament assembly and cell motility. We hypothesise that an increase in the expression of VASP is involved in the progression and invasion of lung adenocarcinomas in parallel to tumour progression. A study was undertaken to analyse VASP expression in normal lung tissue and lung adenocarcinomas. Methods: Human lung tissues with adenocarcinomas (n = 26) were used. Normal lung tissue specimens (n = 14) were taken from areas a standard distance (3 cm) from resected adenocarcinomas of patients who underwent surgical lung resection. Adenocarcinomas were classified according to pathological staging and histopathological grades. Tissues were stained for VASP using immunohistochemistry. Results: Normal lung pneumocytes showed no VASP expression while alveolar macrophages had the strongest immunoreactivity for VASP. Bronchial epithelium (surface epithelium, goblet cells) and bronchial gland cells had a very weak immunoreactivity for VASP. Adenocarcinomas had significantly greater VASP expression than normal epithelium (p<0.001). Moreover, VASP expression in adenocarcinomas increased significantly with more advanced tumour stage (p<0.001). Conclusions: The spatial and differential expression of VASP in normal lung tissue and lung adenocarcinomas suggests that it is likely to be involved in the differentiation of normal lung cells to adenocarcinomas. The significant increase in the expression of VASP in adenocarcinomas in parallel to pathological staging suggests that it may regulate the invasive behaviour of lung adenocarcinomas as adenocarcinoma invasion is increased in more advanced tumours.

NF-κB targeting by way of IKK inhibition sensitizes lung cancer cells to adenovirus delivery of TRAIL.

BackgroundLung cancer causes the highest rate of cancer-related deaths both in men and women. As many current treatment modalities are inadequate in increasing patient survival, new therapeutic strategies are required. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells but not in normal cells, prompting its current evaluation in a number of clinical trials. The successful therapeutic employment of TRAIL is restricted by the fact that many tumor cells are resistant to TRAIL. The goal of the present study was to test a novel combinatorial gene therapy modality involving adenoviral delivery of TRAIL (Ad5hTRAIL) and IKK inhibition (AdIKKβKA) to overcome TRAIL resistance in lung cancer cells.MethodsFluorescent microscopy and flow cytometry were used to detect optimum doses of adenovirus vectors to transduce lung cancer cells. Cell viability was assessed via a live/dead cell viability assay. Luciferase assays were employed to monitor cellular NF-κB activity. Apoptosis was confirmed using Annexin V binding.ResultsNeither Ad5hTRAIL nor AdIKKβKA infection alone induced apoptosis in A549 lung cancer cells, but the combined use of Ad5hTRAIL and AdIKKβKA significantly increased the amount of A549 apoptosis. Luciferase assays demonstrated that both endogenous and TRAIL-induced NF-κB activity was down-regulated by AdIKKβKA expression.ConclusionsCombination treatment with Ad5hTRAIL and AdIKKβKA induced significant apoptosis of TRAIL-resistant A549 cells, suggesting that dual gene therapy strategy involving exogenous TRAIL gene expression with concurrent IKK inhibition may be a promising novel gene therapy modality to treat lung cancer.

Acute respiratory failure and tracheal obstruction in patients with posterior giant mediastinal (intrathoracic) goiter.

The extension of a thyroid goiter into the mediastinum, commonly known as a substernal goiter, is commonly located in the anterior mediastinum. Substernal enlargement of a goiter can cause compression of several mediastinal structures including the trachea. Tracheal compression may rarely lead to acute respiratory failure. We present a patient with tracheal compression and respiratory failure due to a posterior mediastinal goiter in the light of the literature.

Intrathoracic migration of Steinman wire

We report two cases of intrathoracic migration of Steinman wire used for the treatment of the fracture and shoulder dislocation. The migrations were symptomatic with back pain in our cases. The treatment involved removing of the pin via thoracotomy. The postoperative course was uneventful. Intrathoracic migration of Steinman wires should be expected in fixation of the shoulder problems. To avoid this complication, threaded pins have to be used in surgery of the shoulder region.

Significance of tumor length as prognostic factor for esophageal cancer.

Our study indicated the relationship between tumor length and clinicopathologic characteristics as well as long-term survival in esophageal cancer. A total of 116 patients who underwent curative surgery for thoracic esophageal cancer with standard lymphadenectomy in 2 fields between 2000 and 2010 were included in the study. The medical records of these patients were retrospectively reviewed. The patients with tumor length 3 cm had a highly significant difference in the involvement of adventitia and lymph node stations. The patients with tumor length 3 cm had significantly lower rates of involvement of the adventitia and lymph node stations. Tumor length could have a significant impact on both the overall survival and disease-free survival of patients with resected esophageal carcinomas and may provide additional prognostic value to the current tumor, node, and metastasis staging system before patients receive any cancer-specific treatment.

Vascular endothelial growth factor expression and neovascularization in non--small cell lung carcinoma.

The prognostic significance of microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression were investigated in 15 patients with adenocarcinoma (AC) and 15 patients with squamous cell carcinoma (SCC). Immunohistochemically, VEGF and factor VIII were applied. The average microvessel counts were given as MVD, and VEGF expression was given as VEGF percentage area and VEGF staining degree. Higher values of MVD were obtained in patients with AC (11.47 ± 3.48) when compared with patients with SCC (7.47 ± 2.50; P = .001) and also in patients at early stages of disease (10.77 ± 3.24) when compared with patients at advanced stages (8.47 ± 3.64; P = .050). A significant correlation was shown between MVD and VEGF percentage area (P = .006) and between VEGF percentage area and VEGF staining degree (P = .000). No significant difference was found in VEGF percentage area between patients with SCC and AC and between patients at early and advanced stages. In conclusion, VEGF or MVD should not be regarded as a solitary prognostic factor but should be supported by other prognostic factors.

Differential expression and activation of Epidermal Growth Factor Receptor 1 (EGFR1), ERK, AKT, STAT3, and TWIST1 in nonsmall cell lung cancer (NSCLC)

ABSTRACT Lung cancer is the leading cause of death of both men and women across the world. Overexpression and activating mutations of the epidermal growth factor receptor-1 (EGFR1) are frequently observed and associated with poor prognosis. To inhibit the function of EGFR1, multiple antibodies and small-molecule tyrosine kinase inhibitors (TKI) that target EGFR1 have been developed. Even though some patients respond to these TKI, subsequent studies reveal that this is not the case for all nonsmall cell lung cancer (NSCLC) patients. In this study, we determine whether activation and expression levels of EGFR1, ERK, AKT, STAT3, and TWIST1 are dependent on the activating mutations of EGFR1. Protein lysates and DNA have been isolated from tumor and corresponding normal tissues of 16 NSCLC patients. Genomic-DNA is used to sequence the exons 18, 19, and 21 of EGFR1, and exon 2 of k-RAS. Protein lysates were used to determine the expression or phosphorylation levels of EGFR, STAT3, ERK, AKT, and TWIST1. Our results revealed that 16 tumor samples of NSCLC patients showed no mutation in any of the indicated exons of EGFR1 and k-RAS albeit significant levels of activation or expression of the above-mentined oncogenes. In NSCLC patients, the tumor micro-environment can be as important as the activating mutations of EGFR1. TK therapy may also be considered for patients who show high levels of activation of EGFR1 even in the absence of activating mutations.

Atypical giant hydatid cyst at the thoracic wall causing bone and soft tissue destruction: report of a case.

Hydatid cyst is a zoonotic disease that is common in the Mediterranean region. Thoracic wall, rib or extrapulmonary intrathoracic localization of the cysts is very rare. Giant extrapulmonary intrathoracic hydatid cysts can lead to both diagnostic and treatment difficulties and can be confused with tumor. We present a case of a hydatid cyst with thoracic wall involvement mimicking tumor. We confirmed diagnosis only by surgical exploration and histopathological examination because radiology is not conclusive .Surgical treatment involved the total extirpation of cyst together wide debridement and resection of affected tissue. Primary thoracic wall closures were performed. In thoracic wall localization of cyst, post-operative course of albendazole for 6 weeks associated with surgery can help in sterilizing the cyst and reduce the recurrence rate. In this article, we presented a thoracic wall hydatidosis which is very uncommon asymptomatic presentation of hydatid cyst disease with its surgical management.

Measurements of tumor size using CT and PET compared to histopathological size in non-small cell lung cancer

PURPOSE In this study, we aimed to compare the tumor sizes determined by maximum morphological computed tomography (CT) and functional positron emission tomography (PET) with the histopathological size to determine which method provides the best correlation with the histopathological size in lung carcinoma patients. MATERIALS AND METHODS Forty lung carcinoma patients (39 males, one female) diagnosed histopathologically from surgical resection materials were included in this retrospective study. The mean age (±standard deviation, SD) of the patients was 67.8±10.3 years with a range of 44 to 81 years. The PET scans were performed within the same week as the CT scan. In the CT scans, the morphological tumor sizes were measured three-dimensionally by the longest transaxial section in the parenchymal and mediastinal screening window. The functional tumor sizes were also measured three-dimensionally in the PET scans. These two measurement values were compared with the histopathological size using Bland-Altman plotting. Bland-Altman plotting was also performed to define the 95% limits of agreement, which was presented as the bias ±1.96 SD. RESULTS The histopathological sizes were measured in a range of 1.2 to 7.5 cm. The maximum measurement of the tumors on the CT scans showed a lower concordance (mean difference, -0.30) than that obtained from PET, and the SD was found to be larger than the PET (1.96 SD was 3.50 for CT and 2.50 for PET). CONCLUSION The PET measurements of tumor size were more compatible with the histopathological sizes than the CT measurements in patients with non-small cell lung cancer.

Incidental Detection of a Benign Thymoma on Tc-99m MIBI Myocardial Perfusion Study

Technetium-99m methoxy-isobutylisonitrile (Tc-99m MIBI) is a routinely used radiopharmaceutical for myocardial perfusion scintigraphy (MPS). It is also a tumor seeking agent. Here, we present a case of 51 year old male who underwent Tc-99m MIBI myocardial perfusion study due to permanent chest pain after coronary angiography. Abnormal MIBI uptake in the thorax was detected in the raw images. This single finding led to further investigation and thoracotomy proved that the lesion was benign thymoma. Thymomas are often asymptomatic or have a non-specific presentation. They are often detected coincidentally on images performed for any other reasons. We wanted to emphasize that during of MPS, the raw data should always be reviewed as occasionally valuable additional information on noncardiac pathology could be recognized by extracardiac uptake, as in this case. Conflict of interest:None declared.