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Publications (45)63.87 Total impact

  • E. Haselwanter · B. Bucher · M. Stein · A. Kreczy · H. Jamnig
    No preview · Article · Oct 2015 · Wiener klinische Wochenschrift
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    Full-text · Article · Oct 2015 · Wiener klinische Wochenschrift
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    [Show abstract] [Hide abstract] ABSTRACT: Different strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles. Between 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2) and docetaxel (75 mg/m2 d1) q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly). The primary endpoint was radiological response according to RECIST. 40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95%) underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months. Two cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected. EU Clinical Trials Register; Eudract-Nr: 2006-004639-31.
    Full-text · Article · May 2015 · PLoS ONE
  • No preview · Article · Oct 2014 · Wiener klinische Wochenschrift
  • [Show abstract] [Hide abstract] ABSTRACT: Background Regulatory T cells (Treg) are critical for cancer immune evasion; whereas natural killer (NK) cells are central for effective anti-tumor immunity including antibody-induced cellular cytotoxicity (ADCC). The predictive role of Treg levels for clinical response to chemo-immunotherapy in non-small cell lung cancer (NSCLC) as well as therapy-induced Treg changes remain to be defined. Patients and Methods The impact of Treg on NK-mediated cetuximab-dependent cellular cytoxicity was tested in vitro. Frequency and functional activity of Treg was analyzed in 31 NSCLC stage IB-IIIA patients treated by neoadjuvant Cetuximab/Docetaxel/Cisplatin prior to surgery. Data were correlated with clinical outcome variables and Treg tumor infiltration. Results Treg potently inhibit NK-mediated and cetuximab-induced ADCC in vitro. In addition, a significant correlation between Treg reduction and clinical response was seen. However, the grade of tumor infiltrating Treg in resected tumors did not correlate with peripheral Treg levels. Moreover, Treg levels at diagnosis did not predict clinical response to chemo-immunotherapy. Conclusions The drop of Treg levels during neoadjuvant chemo-immunotherapy in NSCLC patients significantly correlates with clinical response. However, Treg at diagnosis are not linked to inferior clinical response to chemo-immune therapy in NSCLC in vivo even though Treg efficiently inhibit ADCC in vitro.
    No preview · Article · Jul 2014 · Lung cancer (Amsterdam, Netherlands)
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    Full-text · Dataset · May 2014
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    [Show abstract] [Hide abstract] ABSTRACT: Breath analysis for the purpose of non-invasive diagnosis of lung cancer has yielded numerous candidate compounds with still questionable clinical relevance. To arrive at suitable volatile organic compounds our approach combined the analysis of different sources: isolated tumor samples compared to healthy lung tissues, and exhaled breath from lung cancer patients and healthy controls. Candidate compounds were further compared to substances previously identified in the comparison of transformed and normal lung epithelial cell lines. For human studies, a breath sampling device was developed enabling automated and CO2-controlled collection of the end-tidal air. All samples were first preconcentrated on multibed sorption tubes and analyzed with gas chromatography mass spectrometry (GC-MS). Significantly (p < 0.05) higher concentrations in all three types of cancer samples studied were observed for ethanol and n-octane. Additional metabolites (inter alia 2-methylpentane, n-hexane) significantly released by lung cancer cells were observed at higher levels in cancer lung tissues and breath samples (compared to respective healthy controls) with statistical significance (p < 0.05) only in breath samples. The results obtained confirmed the cancer-related origin of volatile metabolites, e.g. ethanol and octane that were both detected at significantly (p < 0.05) elevated concentrations in all three kinds of cancer samples studied. This work is an important step towards identification of volatile breath markers of lung cancer through the demonstration of cancer-related origin of certain volatile metabolites.
    Full-text · Article · May 2014 · Journal of Breath Research
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    [Show abstract] [Hide abstract] ABSTRACT: Background It is not clear whether or not the fate of patients suffering from small-cell lung cancer (SCLC) has improved. To better understand the course of disease, we aimed at documenting disease features at initial diagnosis, sequences of therapy modalities and outcome in consecutive patients over two decades. We postulated that SCLC patients might have benefitted from refined diagnosis and treatment options during the last decade. Methods All SCLC cases diagnosed at the Innsbruck University Hospital and associated institutions between 1991–2011 have been documented in detail in accordance with a prespecified protocol. Results A total of 484 patients diagnosed with SCLC were followed. The most important symptoms at initial diagnosis were weight loss, cough and dyspnea in 66%, 55% and 51% of patients, respectively. Patients who were operated during early stage of disease (n = 26) had a favourable five-year, relapse-free survival (74%). 112 patients with locally advanced disease were treated by radiochemotherapy in curative intent (RCT), and achievement of CR offered a chance of long term overall survival (OS), reaching 20% after 10-years. In the palliative setting (median OS in 304 evaluable patients, 9.4 months), a therapeutic progress in the more recent decade could not be observed. Parameters independently associated with favourable OS were response to therapy and prophylactic brain irradiation in patients with RCT, and response, age <70 years and absence of LDH elevation in the palliative setting. Conclusions In this comprehensive view on SCLC, the findings on symptomatology, comorbidity, and spectrum of treatments may help to better understand individual courses of the disease. Overall, modern medicine failed to translate into substantial benefit of SCLC patients, except in patients in locally advanced disease receiving multimodal therapy
    Full-text · Article · May 2014 · Lung cancer (Amsterdam, Netherlands)
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    Full-text · Dataset · Apr 2014
  • No preview · Article · Oct 2013 · Wiener klinische Wochenschrift
  • No preview · Article · May 2013 · Pneumologie
  • I Wasle · M Mian · G Pall · T Schmid · W Oberaigner · M Nevinny · H Jamnig · W Hilbe · M Fiegl
    No preview · Article · May 2013 · Pneumologie
  • [Show abstract] [Hide abstract] ABSTRACT: Introduction: Consecutive SCLC cases treated in Innsbruck/Natters Comprehensive Cancer Center were analysed in order to achieve results in the routine setting and to depict cohorts with long term survival. Methods: All patients with SCLC were documented with respect to disease and therapy features aiming at describing this disease and treatments applied in most possible detail. Results: Of 484 patients, 326 (67%) were male. Extensive stage at diagnosis in 269/ 483 informative cases (56%), (former) smokers, 316/323 (98%); unfavorable ECOG PS (≥2), 100/303 (33%). Symptoms at initial diagnosis: hemoptysis 44/293 (15%), cough 165/299 (55%); dyspnoea 153/302 (51%); tumor pain 135/305 (44%); neurologic symptoms (incl. paraneoplasia) 69/314 (22%); hyponatremia (≤130 mmol/l)/SIADH 47/339 (14%); prior/present other malignancy 86/436 (20%). 27 patients (6%) did not receive any treatment. 26 limited disease patients were radically operated, with excellent outcome (median OS, 91 months). In the 406 evaluable patients with palliative therapy, overall response (ORR) was 56% (CR 18%, PR 39%, PD 31%, interruption 5%, death under therapy 8%); however, best response (at any time during treatment) was 78%. ORR was dramatically inferior in patients with advanced stage, unfavorable PS, and elevated LDH ( p < 0.001). Median PFS from start of palliative therapy, evaluable in 415 patients, was 6.9 months. PFS was slightly superior in women ( p = 0.041), and clearly inferior in patients with elevated CRP ( p = 0.011) and LDH levels ( p <0.001), unfavorable performance status ( p = 0.001), and extensive disease (p <0.001); median OS from start of palliative therapy, evaluable in 415 patients was 11.3 months: more interestingly, there is plateau of long term survivors (5-ys survival 9.3%), mainly attributable to radiochemotherapy in limited disease (n = 118, median OS 20.3 months, 5-ys survival 22%). LDH and CRP, and PS are simple parameters significantly predictive for OS ( p < 0.001). Second line palliative therapy was administered in 206 patients (ORR 23%); third line, 93 patients (ORR 14%); fourth line, 26 patients (ORR 8%) and fifth line, 9 patients (ORR 0%). Conclusion: We are working on the establishment of diagnostic and therapeutic algorithms for an optimized management in this unfavourable disease.
    No preview · Article · Sep 2012 · Annals of Oncology
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    [Show abstract] [Hide abstract] ABSTRACT: Non-invasive disease monitoring on the basis of volatile breath markers is a very attractive but challenging task. Several hundreds of compounds have been detected in exhaled air using modern analytical techniques (e.g. proton-transfer reaction mass spectrometry, gas chromatography-mass spectrometry) and have even been linked to various diseases. However, the biochemical background for most of compounds detected in breath samples has not been elucidated; therefore, the obtained results should be interpreted with care to avoid false correlations. The major aim of this study was to assess the effects of smoking on the composition of exhaled breath. Additionally, the potential origin of breath volatile organic compounds (VOCs) is discussed focusing on diet, environmental exposure and biological pathways based on other's studies. Profiles of VOCs detected in exhaled breath and inspired air samples of 115 subjects with addition of urine headspace derived from 50 volunteers are presented. Samples were analyzed with GC-MS after preconcentration on multibed sorption tubes in case of breath samples and solid phase micro-extraction (SPME) in the case of urine samples. Altogether 266 compounds were found in exhaled breath of at least 10% of the volunteers. From these, 162 compounds were identified by spectral library match and retention time (based on reference standards). It is shown that the composition of exhaled breath is considerably influenced by exposure to pollution and indoor-air contaminants and particularly by smoking. More than 80 organic compounds were found to be significantly related to smoking, the largest group comprising unsaturated hydrocarbons (29 dienes, 27 alkenes and 3 alkynes). On the basis of the presented results, we suggest that for the future understanding of breath data it will be necessary to carefully investigate the potential biological origin of volatiles, e.g., by means of analysis of tissues, isolated cell lines or other body fluids. In particular, VOCs linked to smoking habit or being the results of human exposure should be considered with care for clinical diagnosis since small changes in their concentration profiles (typically in the ppt(v)-ppb(v) range) revealing that the outbreak of certain disease might be hampered by already high background.
    Full-text · Article · Aug 2012 · Journal of Breath Research
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    [Show abstract] [Hide abstract] ABSTRACT: Isoprene (2-methylbuta-1,3-diene) represents a precursor molecule of isoprenoids (steroids, terpens), and available data suggest that isoprene is related to cholesterol biosynthesis. Breath concentrations of isoprene have been reported to be altered in a number of clinical conditions. However, the physiological meaning of isoprene changes has not yet been established. Utilizing proton-transfer-mass spectroscopy, we analyzed isoprene concentrations (m/z 69, tentatively identified as isoprene) in breath samples in Tedlar bags collected from 79 lung cancer patients (23 females, 56 males). Results were compared to the concentrations of immune activation marker neopterin (ELISA, BRAHMS, Hennigsdorf, Germany), lipid parameters (routine enzymology) and C-reactive protein (CRP). Isoprene concentrations were median 92.5 ppb (25th-75th percentile: 79-131 ppb). There was no relationship with staging, grading or age, but isoprene concentrations correlated significantly with total cholesterol (rs = 0.281, p < 0.01) and LDL cholesterol (rs = 0.236, p < 0.05). There was no significant relationship between exhaled isoprene concentrations and HDL cholesterol (rs = 0.048), triglycerides (rs = 0.164) and CRP (rs = -0.115; all not significant). A significant inverse correlation existed between isoprene and neopterin concentrations (rs = -0.215, p < 0.05); the latter also correlated with total cholesterol (rs = -0.343, p = 0.001), HDL cholesterol (rs = -0.273, p = 0.01), LDL cholesterol (rs = -0.236, p < 0.05) and CRP (rs = 0.230, p < 0.05) but not with triglycerides (rs = 0.035, not significant). Results suggest that immune activation might play a role in the decline of isoprene which is probably related to lipid metabolic changes. Interestingly, similar relationships between elevated neopterin and decreased lipid concentrations have been reported earlier in other clinical conditions, e.g. in patients with HIV-1 infection.
    Full-text · Article · Mar 2012 · Journal of Breath Research
  • [Show abstract] [Hide abstract] ABSTRACT: In epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), the tyrosine-kinase inhibitor gefitinib is in broad use. We retrospectively analysed data for 82 patients with advanced NSCLC treated with gefitinib and correlated benefits with clinical baseline and therapy-related parameters. Of all patients 48/82 were male; the median age at start of gefitinib was 67.2 years; 14/58 informative patients were never-smokers; 57/82 patients suffered from adenocarcinoma, including 7 with bronchoalveolar-carcinomas. As to be expected, partial remission was observed in 10% of patients, stable disease in 29%, progression-free survival was 3.1 months and overall survival 9.2 months. Gefitinib was more efficacious in women, never-smokers and patients with bronchoalveolar-carcinoma. Furthermore, anemia and elevated C-reactive protein levels were unfavourable for therapeutic efficacy. Patients developing skin reactions under gefitinib achieved response far more frequently, with longer progression-free survival and overall survival. Basic clinical parameters are good predictors for response to EGFR tyrosine-kinase inhibitor therapy, which may be of value if EGFR mutation status is not available.
    No preview · Article · Sep 2011 · Anticancer research
  • [Show abstract] [Hide abstract] ABSTRACT: The tumor microenvironment comprises various cellular components and associated subcellular molecules with antitumor and protumor effects. Because respective targeted treatment strategies are arising, it is important to characterize the exact role of these parameters. This study provides a comprehensive analysis of key immunologic factors in the tumor microenvironment of 383 surgically resected non-small cell lung cancer specimens. CD4, CD8, forkhead box protein P3, transforming growth factor β, Casitas B-cell lymphoma-b, programed death 1, T-cell-restricted intracellular antigen 1, granzyme B, mast cell tryptase, and stromal cell-derived factor 1 were analyzed by immunohistochemistry using a standardized tissue microarray platform. Extensive clinical data enabled detailed clinicopathologic correlations over a postoperative follow-up period of 15 years. Among the immunologic variables focused on, transforming growth factor β expression was the only prognostically relevant factor. Transforming growth factor β was more frequently expressed in adenocarcinoma as compared with other histologic subtypes. Expression of transforming growth factor β in tumor-infiltrating lymphocytes or in tumor cells was associated with significantly reduced postoperative survival time especially in patients with squamous cell carcinoma (P = .035 and P = .046, respectively). In these patients, the amount of transforming growth factor β-positive tumor-infiltrating lymphocytes represented the only independent immunologic parameter with prognostic significance by multivariat analysis (P = .021; hazard ratio, 2.602; 95% confidence interval, 1.159-5.844). These results should help to identify patients who are most suitable for therapeutic strategies aiming to block the transforming growth factor β signaling pathway.
    No preview · Article · Aug 2011 · Human pathology
  • P. H. Heininger · B. Bucher · H. Jamnig
    No preview · Article · Nov 2010 · Wiener klinische Wochenschrift
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    [Show abstract] [Hide abstract] ABSTRACT: The fast development of analytical techniques in the field of gas analysis can be compared to that of computers during the last two decades. Not only speed but also sensitivity of analysis has been greatly improved, sometimes by a factor of 100 or more. This technological development has fostered the analysis of exhaled breath. Since this can be done in real-time, very fast biological processes can be monitored. Also simulation and modelling of haemodynamics and lung mechanics become possible. During the next decade we will see miniaturized equipment (of the size of a cigarette box) appear. Here we review and illustrate the rich diversity of compounds observed in exhaled breath with a particular focus on lung cancer patients. Each of the many volatile compounds has its own particular biochemical background, and cell types with different genetic background have been shown to have a different pattern of released and consumed volatile compounds. Nevertheless we still lack an understanding, if and how genetic alterations, which are seen as the underlying cause of the transformation process, control the VOC phenotype observed in patients or cancer cell lines. The concentration pattern of volatile compounds in exhaled breath may be used in the future for phenotyping individuals in large-scale screening approaches. Also changes in VOC patterns may provide disease-relevant information (e.g. on the activity of metabolizing enzymes). Future applications will also include the follow-up of exogenous compounds which are ingested or inhaled as drugs, food components or components in cigarette smoke and metabolic products of these compounds. KeywordsExhaled breath analysis-Lung cancer-Volatile organic compounds-Gas chromatography mass spectrometry-Proton transfer reaction mass spectrometry
    Full-text · Article · Oct 2010 · memo - Magazine of European Medical Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: A large group of interacting molecular factors, involved in epithelial-mesenchymal transition, epidermal growth factor receptor (EGFR) signaling, and G1 mitotic phase, are shown to play an important role in cancerogenesis and progression of non-small cell lung cancer (NSCLC). Since success concerning potential correlations, structural and numeric gene aberrations, and biological risk assessment of these molecular factors are still lacking, combined analysis of a multitude of intertwined factors is currently a promising approach. Cyclins (D1, D2, D3, and E), p21, p27, EGFR, Snail, E-cadherin, beta-catenin, phosphatidylinositol-3' kinase, phosphatase and tensin homologue, phosphorylated Akt, and phosphorylated signal transducer, and activator of transcription-3 were analyzed by immunohistochemistry in 405 surgically resected NSCLC, using a standardized tissue microarray platform. In addition, the gene status of EGFR and cyclin D1 was examined by fluorescence in situ hybridization. Extensive clinical data were acquired, enabling detailed clinicopathologic correlation during a postoperative follow-up period of up to 14 years. The protein overexpressions of nuclear p27, cyclin D1, cyclin D3, E-cadherin, and EGFR as assessed by immunohistochemistry were all associated with a significant reduction in overall survival time. In addition, cyclin D1 proved especially important, being the only independent molecular tumor-related factor with prognostic significance by multivariable analysis. In analogy to EGFR, recurrent numeric gene aberrations, particularly high-level amplifications, of cyclin D1 were obvious. The results emphasize that deregulation of controlling factors of the early G1 phase is of significant oncogenic relevance and may represent a potential treatment target in NSCLC.
    No preview · Article · Sep 2010 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer