Biomedical subjects

Lutz Freitag

Publications and source records attributed to Lutz Freitag.

7 recordsLinked to original sources

PubMed2006

Prognostic significance of vessel architecture and vascular stability in non-small cell lung cancer.

To evaluate characteristics and prognostic impact of different structure types of intratumoural blood vessels, tissue samples of 72 patients with primary stages I and II non-small cell lung cancer (NSCLC) were analysed. Performing immunohistochemistry, 45 of 56 analysed tumours (80%) demonstrated an obvious alveolar vascular pattern with tight coverage with perivascular cells in at least parts of the sample. After an overall median follow-up of 139 months for surviving patients, tumours with an alveolar vascular pattern showed a significantly better overall survival (OS) compared to those with an entirely angiogenic vascular pattern (108 months versus 63 months; p<0.05). Furthermore, high expression of angiopoietin-1 (Ang-1) correlated with OS (p<0.05). In contrast, expression of Ang-2 or vascular endothelial growth factor was not significantly associated with survival. Collectively, alveolar vessel architecture and angiopoietin expression appear to be common phenomenons in early stage NSCLC and may serve as prognostic factors.

Blood Vessels↗

PubMed2006

High-level expression of matrix-associated transforming growth factor-beta1 in benign airway stenosis.

STUDY OBJECTIVES: Acquired tracheal and subglottic stenosis frequently leads to severe airway narrowing, which requires repeated interventions, such as dilatation, laser resection, stent implantation, or surgery. To get a more detailed insight into the pathogenesis of this condition, we investigated the expression of profibrotic cytokines and the proliferation of the airway wall in benign human airway stenoses. METHODS: Specimens from patients with subglottic and tracheal stenosis and stent-related stenoses were obtained (n = 20) for reverse transcription (RT) polymerase chain reaction (PCR) analysis and immunohistochemistry testing. RESULTS: Transforming growth factor (TGF)-beta1 messenger RNA expression was significantly increased in biopsy specimens from stent-related stenoses compared to nonstenotic control sections. In contrast, TGF-beta3 and interleukin-1beta showed no such differences in messenger RNA expression. Immunohistochemistry revealed a strong matrix-associated, subepithelial expression of TGF-beta1 in tracheal stenosis. Proliferating Ki-67-positive cells were mainly localized in the basal epithelial layer. Only 2 of 16 patients with tracheal stenoses and 3 of 4 patients with stent-related stenoses showed a weak expression of Ki-67-positive cells in the subepithelium. Furthermore, TGF-beta1 dose-dependently enhanced the proliferation of human lung fibroblasts in vitro, even in the presence of mitomycin-C. CONCLUSION: While a weak subepithelial proliferation occurs in stent-related stenoses, the dominant factor in late stages of untreated tracheal stenoses seems to be the high-level expression of TGF-beta1 and the deposition of extracellular matrix.

Biomarkers↗

PubMed2005

Viscoelasticity of the trachea and its effects on flow limitation.

To test the hypothesis that peak expiratory flow is determined by the wave-speed-limiting mechanism, we studied the time dependency of the trachea and its effects on flow limitation. For this purpose, we assessed the relationship between transmural pressure and cross-sectional area [the tube law (TL)] of six excised human tracheae under controlled conditions of static (no flow) and forced expiratory flow. We found that TLs of isolated human tracheae followed quite well the mathematical representation proposed by Shapiro (Shapiro AH. J Biomech Eng 99: 126-147, 1977) for elastic tubes. Furthermore, we found that the TL measured at the onset of forced expiratory flow was significantly stiffer than the static TL. As a result, the stiffer TL measured at the onset of forced expiratory flow predicted theoretical maximal expiratory flows far greater than those predicted by the more compliant static TL, which in all cases studied failed to explain peak expiratory flows measured at the onset of forced expiration. We conclude that the observed viscoelasticity of the tracheal walls can account for the measured differences between maximal and "supramaximal" expiratory flows seen at the onset of forced expiration.

Compliance↗

PubMed2005

Detection of human metabolites using multi-capillary columns coupled to ion mobility spectrometers.

The human breath contains indicators of human health and delivers information about different metabolism processes of the body. The detection and attribution of these markers provide the possibility for new, non-invasive diagnostic methods. In the recent study, ion mobility spectrometers are used to detect different volatile organic metabolites in human breath directly. By coupling multi-capillary columns using ion mobility spectrometers detection limits down to the ng/L and pg/L range are achieved. The sampling procedure of human breath as well as the detection of different volatiles in human breath are described in detail. Reduced mobilities and detection limits for different analytes occurring in human breath are reported. In addition, spectra of exhaled air using ion mobility spectrometers obtained without any pre-concentration are presented and discussed in detail. Finally, the potential use of IMS with respect to lung infection diseases will be considered.

Breath Tests↗

PubMed2004

Interventional endoscopic treatment.

Interventional bronchoscopy has evolved as an integral part of lung-cancer treatment but it is not always used to its full potential. The different methods can provide immediate relief of dyspnea and haemoptysis. Bleeding from central airway tumours can be stopped by coagulation preferably with the argon plasma coagulator. In cases of intraluminally growing tumour masses removal of the malignant tissue is accomplished with the Nd-YAG laser, electrocautery, argon plasma coagulation, cryotherapy or photodynamic therapy. Intramural tumour growth is most efficiently treated with high dose-rate endobronchial brachytherapy. Extrinsic compression or airway wall destruction require the placement of an airway stent. All methods can be combined and complement other palliation methods such as radiation or chemotherapy.

Brachytherapy↗

PubMed2003

Endobronchial phototoxicity of WST 09 (Tookad), a new fast-acting photosensitizer for photodynamic therapy: preclinical study in the pig.

Photodynamic therapy (PDT) has been used for many years for both palliative and curative treatment of bronchial carcinomas. However, prolonged skin phototoxicity and reduced depth of penetration has limited the widespread use of PDT. We studied the endobronchial phototoxicity of a novel photosensitizer, WST 09 (Tookad). Fourteen pairs of Large White-Landrace male piglets were given intravenous WST 09 followed by laser light illumination of the left mainstem bronchus. Different settings for light dose (fluence), fluence rate (FR), drug dose (D) and drug-light interval (DLI) were applied to each pair. Bronchial toxicity was assessed with repeat bronchoscopic photographic evaluation as well as by pathologic examination following autopsy. Animals developed no toxicity, moderate toxicity or severe toxicity. Increased toxicity was seen with increasing D and fluence and decreasing DLI, whereas no increased toxicity was seen with higher FR. PDT-related histological changes in the normal bronchus confirm the vascular effect of WST 09. Depending on the parameter settings for fluence, D and DLI, the lesions ranged from focal intramucosal ischemia to transmural infarction with subsequent acute inflammation and fibrosis. Clinically feasible parameters for drug and light dosimetry were documented. These data will be important in determining safe starting doses for human phase I/II studies.

Animals↗

PubMed2002

Trimodality treatment in Stage III nonsmall cell lung carcinoma: prrognostic impact of K-ras mutations after neoadjuvant therapy.

BACKGROUND: In a trimodality treatment approach for Stage III nonsmall cell lung carcinoma (NSCLC), the prognostic impact of the ras mutation status in resection specimens was evaluated. METHODS: Forty patients with Stage III NSCLC underwent tumor resection after neoadjuvant treatment with two cycles of chemotherapy (ifosfamide, carboplatin, and etoposide) and subsequent twice-daily radiotherapy (45 grays [Gy]; 2 x 1.5 Gy/day) with concurrent carboplatin and vindesine. Assessment of K-ras codon 12 mutation status was performed in the paraffin embedded resection specimens by a two-step polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: K-ras mutation status could be assessed in 28 cases. A K-ras codon 12 point mutation was found in 13 of 28 resection specimens (46%). The mutation was found independently of gender, age, tumor stage, and clinical response status and occurred more frequently in adenocarcinomas. Even after complete resection, the presence of a K-ras mutation was a significant predictor for a poor progression free survival (P = 0.005). CONCLUSIONS: These data suggest that further evaluation of the K-ras codon 12 mutation status in trials on neoadjuvant and adjuvant therapy is warranted. This may contribute to the identification of stratification variables for future treatment approaches.

Adenocarcinoma↗