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Katharina Schmid

Publications and source records attributed to Katharina Schmid.

14 recordsLinked to original sources
PubMed2007

KiSS-1 overexpression as an independent prognostic marker in hepatocellular carcinoma: an immunohistochemical study.

The KiSS-1 gene has been reported to play an important role as a metastasis suppressor gene in various human malignancies. However, there is little information about its possible role in hepatocellular carcinoma (HCC). In this study, we evaluated the prognostic significance of the expression of KiSS-1 and its receptor AXOR12 in 142 HCC tissue specimens by immunohistochemistry. By using a cutoff level of 50%, immunoreactivity of KiSS-1 and AXOR12 was found in 6 (4%) and 11 (8%) HCCs. The expression of KiSS-1 and AXOR12 in HCC correlated with each other (r = 0.42, p < 0.0001) and with the expression in corresponding, surrounding liver tissue (both r = 0.35, p < 0.0001). Positive AXOR12 immunoreactivity in HCC correlated with advanced pT-stage of tumors and low tumor grading (r = 0.18, p = 0.032; r = -0.18, p = 0.029). High KiSS-1 expression in HCC had a statistically significant influence on diminished disease-free and overall survival in uni- (p = 0.006 and p = 0.002) and multivariate analysis (r = 2.874, p = 0.027 and r = 2.913, p = 0.026). In this study, we report for the first time that elevated KiSS-1 expression level in HCC correlates with worsened clinical outcome, as an independent prognostic marker for the aggressiveness of HCC.

Adult↗
PubMed2006

Quantitative nuclear texture features analysis confirms WHO classification 2004 for lung carcinomas.

The purpose of this study was to discriminate the main subsets of lung carcinomas of the WHO classification of 2004 by nuclear chromatin texture feature analysis. Our collective comprised 56 typical and 19 atypical carcinoids, 37 small-cell carcinomas, 15 large-cell neuroendocrine carcinomas, 42 adenocarcinomas, and 26 squamous cell carcinomas. After Feulgen staining, cell nuclei were automatically measured using a high-resolution image analyser (CytoSavant Oncometrics, Vancouver, BC, Canada). Texture features describing the granularity and the compactness of the nuclear chromatin were extracted for calculation of classification rules, which allowed the discrimination of different tumor groups. By applying the classification rule that described the granularity of the nuclear chromatin (defined by four different parameters) small-cell and non-small-cell lung carcinoma could correctly be discriminated in 93%. No significant discrimination was possible between the different subtypes of large-cell carcinomas, including large-cell neuroendocrine carcinoma. When using compactness of chromatin (defined by four texture parameters) as a means of discrimination, carcinoids and non-small-cell lung carcinomas were correctly distinguished in 92%. No significant discrimination between neuroendocrine tumors was achieved though. Our findings are in accordance with the new WHO classification of 2004: neuroendocrine tumors of the lung are now classified according only to their mitotic counts and presence of necrosis but not by their morphology; their discrimination by the means of nuclear image analysis is not sufficient and therefore not appropriate any longer.

Adenocarcinoma↗
PubMed2005

Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy.

BACKGROUND/AIMS: Recently, the anti-apoptotic Mcl-1 protein has been reported as a resistance factor in various types of cancer. Here we investigated the presence of Mcl-1 protein in hepatocellular carcinoma (HCC) tissues and its potential role as a molecular drug target for HCC therapy. METHODS: HCC specimens of 149 patients were examined by immunohistochemistry for Mcl-1 expression. Antisense oligonucleotides (ASO) targeting Mcl-1 were evaluated as monotherapy and in combination with cisplatin in the HCC cell lines HepG2 and Snu398. Protein regulation, cell viability, and apoptosis were assessed by western blotting, cell counting, and FACS analysis. RESULTS: Mcl-1 protein is overexpressed in 51% of all cases irrespective of underlying disease. Targeting Mcl-1 by ASO specifically downregulated Mcl-1 protein expression and led to significant dose and time dependent single agent activity in HCC cells characterized by increased apoptosis and decreased cell viability. No significant target regulation or cell death was observed for control oligonucleotide treatment. Upon combination with cisplatin, Mcl-1 ASO revealed a significant chemosensitizing effect. CONCLUSIONS: Mcl-1 is overexpressed in half of HCC-tissues. ASO targeting Mcl-1 revealed a prominent single agent and chemosensitizing activity against HCC in vitro. Targeting Mcl-1 might qualify as a promising novel approach in HCC therapy.

Apoptosis↗
PubMed2005

Cytotoxic and genotoxic effects of resin monomers in human salivary gland tissue and lymphocytes as assessed by the single cell microgel electrophoresis (Comet) assay.

Malignant tumors of the three major pairs and the numerous minor salivary glands in humans are rare, and little is known about their various etiologies. Considering the fact that resin monomers from dental restorative materials are released into the saliva and diffuse into the tooth pulp or gingiva, mucosa, and salivary glands, this may potentially contribute to tumorigenesis. Resin monomers may also be reabsorbed and reach the circulating blood as well. Whereas the cytotoxic potential of some components has been clearly documented, data on genotoxicity in human target cells require further investigation. In the present study, genotoxic and cytotoxic effects of three common methacrylates are investigated in human samples of salivary glands and peripheral lymphocytes. The Comet assay was used to quantify DNA single strand breaks, alkali labile and incomplete excision repair sites in salivary gland probes and lymphocytes of 10 volunteers. The xenobiotics investigated were triethyleneglycoldimethacrylate (TEGDMA), urethanedimethacrylate (UDMA), and 2-hydroxyethylmethacrylate (HEMA), with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and dimethyl sulfoxide (DMSO) as controls. DNA migration was analyzed using the tail moment according to Olive (OTM). Cytotoxicity was monitored using trypan blue staining. With TEGDMA concentrations at 10(-5)m (10(-3)m), UDMA at 10(-7)m (10(-7)m), and HEMA at 10(-3)m (10(-5)m) significant enhancements of DNA migration were achieved in tissue cells (lymphocytes) as compared to the negative controls. At higher concentrations of up to 2.5x10(-2)m, induced DNA migration was expressed by OTM at 10.7 for TEGDMA in tissue cells (8.7 in lymphocytes), 10.5 for UDMA (6.4), and 9.7 for HEMA (6.1). The viability of the cell systems was not affected as concerns the threshold level for the assay of 75% viable cells except for the highest concentration tested for TEGDMA and UDMA in tissue cells. At higher concentration levels, all tested substances induced significant enhancement of DNA migration in the Comet assay as a possible sign for genotoxic effects in human salivary glands and lymphocytes. These data add to the results of prior studies in human peripheral lymphocytes and give evidence of a possible risk factor for tumor initiation in human salivary glands.

Aged↗
PubMed2005

Fluoroscopic radiation exposure of the kyphoplasty patient.

Kyphoplasty (KP) is a minimally invasive technique for the percutaneous stabilisation of vertebral fractures. As such, this technique is highly dependent upon intraoperative fluoroscopic visualisation. In order to assess the range of radiation doses that patients are typically subjected to, 60 consecutive procedures using simultaneous bilateral fluoroscopy were analysed with respect to exposure time (ET). In a subset of 16 of these patients, a theoretical entrance skin dose (ESD) and effective dose was additionally calculated from intraoperatively measured dose area product. Average fluoroscopy time for single level cases reached 2.2 min (range 0.6-4.3) in the lateral plane and 1.6 min (range 0.5-3.0) in the anterior-posterior plane. For multiple level cases the corresponding ET per level was 1.7 min (range 0.6-2.9) per level in the lateral and 1.1 min (range 0.5-2.0) in the anterior-posterior plane. ESD was estimated as an average 0.32 Gy (range 0.05-0.86) in the anterior-posterior and 0.68 Gy (range 0.10-1.43) in the lateral plane. Effective dose (cumulative from both planes) averaged 4.28 mSv (range 0.47-10.14). Safety margins for the development of early transient erythema are respected within the presented fluoroscopy times. Longer ET in the lateral plane may however breach the 2 Gy threshold. Use of large c-arms and judiciously operating the exposure is recommended. With regard to effective dose, a single fluoroscopy guided KP performed for osteoporotic or traumatic vertebral fractures is a safe procedure.

Aged↗
PubMed2005

Bronchial stump coverage with a pedicled pericardial flap: an effective method for prevention of postpneumonectomy bronchopleural fistula.

BACKGROUND: Bronchopleural fistula is a serious complication after pneumonectomy. The aim of this retrospective study was to investigate the efficacy of bronchial stump reinforcement with a pedicled flap of whole pericardium. METHODS: The bronchial stump of 93 consecutive patients who underwent pneumonectomy between July 1988 and March 2003 was covered with a pedicled pericardial flap. Pneumonectomy was performed for primary lung cancer in 89.2% of patients. The study patients received concomitant extensive mediastinal lymphadenectomy, resection of adjacent structures (aorta, vena cava, thoracic wall), and neoadjuvant or planned adjuvant chemotherapy or radiotherapy, or both. Operative and perioperative complications were recorded, and patients were followed up for a mean of 15 +/- 21.2 months (range, 9 to 126). RESULTS: Perioperative mortality was 4.3% (n = 4; pulmonary embolism, sepsis, cardiac arrest, and sudden death in 1 patient each). Perioperative complications occurred in 2 patients: renal failure and hemiplegia in 1 patient and cardiac tamponade in 1 patient. The latter complication, caused by tight reconstruction of the pericardium, was directly related to the applied method and required reoperation. No evidence of postpneumonectomy bronchopleural fistula was observed perioperatively and during the whole follow-up. One-year and 2-year survival was 65.7% and 44.8%, respectively. CONCLUSIONS: Bronchial stump reinforcement with a pericardial flap is a highly effective method for preventing postpneumonectomy bronchopleural fistula in selected patients.

Aged↗
PubMed2005

Prognostic value of lymphatic and blood vessel invasion in neuroendocrine tumors of the lung.

Few data on the influence of vessel invasion on the progression of neuroendocrine lung tumors are available. Because of the lack of specific markers, previous studies could not reliably discriminate lymphatic and blood vessels. By immunostaining for podoplanin, specific for lymphatic endothelium, and CD34 antigen, we assessed lymphatic and blood vessel invasion in 120 tissue specimens of patients with neuroendocrine lung tumors. Lymphovascular invasion was correlated with clinicopathologic parameters, and its prognostic relevance was evaluated. Lymphatic vessels were identified exclusively at the tumor invasion front, whereas blood capillaries were also seen within tumors. Lymphatic vessel as well as lymphatic and blood vessel invasion was prevalent in patients with high-grade neuroendocrine tumors and advanced tumor stages, closely associated with lymph node metastases (P < 0.0001). In univariate analysis, these two invasion types correlated with decreased disease-free survival (both P < 0.0001), whereas blood vessel invasion alone did not. In multivariate analysis, only tumor grade and lymph node status remained statistically significant factors for prognosis (P = 0.016 and P < 0.0001). Our results suggest that evaluation of lymphatic vessel invasion is important in neuroendocrine lung tumors serving as a prognostic parameter for disease-free survival.

Adolescent↗
PubMed2004

Reverse cardiac remodelling in patients with primary pulmonary hypertension after isolated lung transplantation.

OBJECTIVE: Pulmonary hypertension eventually leads to severe distortion of the cardiac geometry with consequent impact on cardiac function. The purpose of this study was to prove reverse cardiac remodelling after isolated bilateral lung transplantation (LuTX) in patients with advanced primary pulmonary hypertension (PPH) and severe alterations of cardiac morphology and function. METHODS: In the period of 2000-2002 17 (10 female, seven male) patients with advanced PPH underwent isolated bilateral LuTX. Median age was 30 years (range 16-53). All patients were in NYHA III or IV, most of them with intractable ascites, established renal impairment, malnutrition and immobility, continuously deteriorating despite various forms of pharmacological treatment including i.v. and inhalative prostacyclin, diuretics, Ca-antagonists, bosentan and catecholamines. Echocardiography and Doppler echocardiography measurements were performed before and 3 months after transplantation. Left and right ventricular diameters and function were assessed and tricuspid valve regurgitation was determined. RESULTS: Mortality after 3 months was 17.5% (cerebral bleeding, multi-organ failure and diffuse myocardial infarction in one patient each). Three months after LuTX the 14 surviving patients were in NYHA I or II. Echocardiography showed normal left ventricular function and markedly improved right ventricular function with normal size of the RV. The leftward shifted flattened interventricular septum had returned in its physiological position and the high-grade tricuspid insufficiency had disappeared in all patients. CONCLUSIONS: Advanced alterations of cardiac morphology and function normalize completely and pre-existing tricuspid insufficiency disappears in PPH patients after isolated bilateral LuTX. Quality of life is excellent. Therefore, LuTX is preferred and safe in patients with advanced PPH even with severe cardiac dysfunction.

Adolescent↗
PubMed2004

Microsurgical interlaminary vertebro- and kyphoplasty for severe osteoporotic fractures.

OBJECT: Percutaneous vertebro- and kyphoplasty have become established methods for the treatment of uncomplicated osteoporotic vertebral fractures. In the setting of severe fractures involving fragmentation of the posterior wall and neural compromise, however, decompressive surgery cannot be performed and epidural cement leakage is poorly controlled. A microsurgical interlaminary approach for vertebro- and kyphoplasty was developed to allow spinal decompression and control of the spinal canal during augmentation. METHODS: Interlaminary vertebro- or kyphoplasty was performed in 24 patients with osteoporotic fractures involving neural compression or posterior wall fragmentation. After unilateral microsurgical fenestration, decompression of the spine, and gentle mobilization of the thecal sac, vertebro- or kyphoplasty was performed directly through the posterior wall of the fractured vertebral body. Cement was injected under microscopic and fluoroscopic control, with the option of immediate exploration of the exposed spinal canal. Thirty-four levels (T-8 to L-5) were treated. Mean blood loss was less than 100 ml and augmentation added 10 to 40 minutes to the entire procedure. Cement leakage associated with the kyphoplasty procedure was less than that in vertebroplasty. There were no major complications. One patient was lost to follow up. Clinical outcome was good or excellent in 17 of the 23 patients available for follow-up (1 to 31-month) evaluation. CONCLUSIONS: The present microsurgical interlaminary approach for vertebro- and kyphoplasty enables treatment of severe osteoporotic fractures involving fragmentation of the posterior wall and neural compromise. Decompressive surgery is possible and the risk of epidural cement leakage is controlled intraoperatively. This technique can be regarded as a procedure on the treatment continuum between percutaneous augmentation and conventional open reconstruction.

Aged↗
PubMed2003

Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer.

PURPOSE: Capecitabine and oxaliplatin, two new agents with potential synergistic activity, have demonstrated promising antitumor efficacy in advanced colorectal cancer (ACC). Preclinical and clinical evidence indicating that dose intensification of the oral fluorouracil prodrug might result in improved therapeutic results led us to the present randomized multicenter phase II study. PATIENTS AND METHODS: Eighty-nine patients with bidimensionally measurable ACC previously untreated for metastatic disease were randomly allocated to receive oxaliplatin 130 mg/m(2) day 1 plus capecitabine 2,000 mg/m(2)/d days 1 to 14 every 3 weeks (arm A) or to receive oxaliplatin 85 mg/m(2) days 1 and 14 combined with capecitabine 3,500 mg/m(2) days 1 to 7 and 14 to 21 every 4 weeks (arm B). In both treatment arms, chemotherapy was continued for a total of 6 months unless there was prior evidence of progression of disease. RESULTS: Patients allocated to the high-dose capecitabine combination arm B had a higher radiologically confirmed response rate (54.5% v 42.2%) and a significantly longer median progression-free survival time than those allocated to control arm A (10.5 v 6.0 months; P =.0013). Median overall survival times cannot be calculated for either treatment arm at this point. Despite a 34% higher dose intensity of capecitabine in arm B, there was no difference in hematologic toxicity between treatment arms (neutropenia/thrombocytopenia: 60%/43% in arm B v 56%/33% in arm A). Similarly, the incidence rate and degree of nonhematologic adverse events were comparable: The most commonly encountered symptoms (all grades, arm A and arm B) included nausea/emesis (A: 58%; B: 62%), diarrhea (A: 44%; B: 31%), peripheral sensory neuropathy (A: 80%; B: 83%), and fatigue (A: 40%; B: 50%). CONCLUSION: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time.

Adult↗
PubMed2003

Effectiveness of autogenic relaxation training on children and adolescents with behavioral and emotional problems.

OBJECTIVE: To investigate the effectiveness of autogenic relaxation training in a mildly disturbed outpatient population of children and adolescents with mostly internalizing symptoms, and/or some aggressive, impulsive, or attention deficit symptoms. METHOD: Fifty children and adolescents from southern Germany (mean age 10.2 years; range 6-15 years; mostly intact middle class family background) participated in a group intervention program. Fifteen patients were randomly assigned to a waiting-list control group. Behavior symptoms (Child Behavior Checklist), psychosomatic complaints (Giessen Complaint List), and level of stress were assessed before and after the intervention or after the waiting phase. Individual goal attainment was evaluated at the end of the intervention and in a 3-month follow-up. RESULTS: The parent report on CBCL reflected reduced symptoms compared with control. The child report indicated reduced stress and psychosomatic complaints both in the intervention and control group, and no significant group x time interaction effects occurred on these scales. Effect sizes of 0.49 in the CBCL and 0.36 in the complaint list indicated clinically relevant effects of the intervention compared with the control group. At the end of the intervention, 56% of the children and 55% of the parents reported partial goal attainment, 38% of the children and 30% of the parents reported complete goal attainment; 71% of the parents confirmed partial goal attainment 3 months postintervention. CONCLUSIONS: Autogenic relaxation training is an effective broadband method for children and adolescents.

Adolescent↗
PubMed2003

Effective combination chemotherapy with bimonthly docetaxel and cisplatin with or without hematopoietic growth factor support in patients with advanced gastroesophageal cancer.

PURPOSE: A phase II trial was performed to determine the antitumor efficacy and tolerance of combined docetaxel and cisplatin with or without hematopoietic growth factor support in patients with advanced gastroesophageal cancer. PATIENTS AND METHODS: Thirty-seven patients with histologically confirmed metastatic gastroesophageal cancer were entered in this trial. Treatment consisted of 4-weekly courses of docetaxel 50 mg/m(2) and cisplatin 50 mg/m(2) both given on day 1 and 15. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1,000-2,000/microl), a 5-day course of human granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/day was given subcutaneously; in addition, if hemoglobin was <12.0 mg/dl, erythropoietin 10,000 IU was administered subcutaneously 3 times per week. RESULTS: The confirmed overall response rate (intent-to-treat) was 46%, including 4 complete responses (11%) and 13 partial responses (35%). Eleven patients (30%) had stable disease and 9 (24%) progressed while on treatment. The median time to response was 3 months, the median time to progression was 7 months and the median overall survival time was 11.5 months with 16 (43%) patients currently alive. Hematologic toxicity was common, though WHO grade 4 neutropenia occurred only in 3 patients. Nonhematologic adverse reaction were usually mild to moderate; grade 3 toxicities included alopecia in 5 patients (14%), infection in 1 (3%), neutrotoxicity in 2 (5%) and anaphylaxis in 1 patient. CONCLUSION: Our data suggest that the combination of docetaxel and cisplatin with or without G-CSF and/or erythropoietin has a promising therapeutic index in patients with advanced gastroesophageal cancer.

Adult↗
PubMed2002

Effects of mutations at the two processing sites of the precursor for the small subunit of ribulose-bisphosphate carboxylase in Chlamydomonas reinhardtii.

The role of the two processing sites in the precursor of the small subunit (SS) of ribulose-1,5-bisphosphate carboxylase/oxygenase (pSS) of Chlamydomonas reinhardtii was studied by introducing mutations at the cleavage sites for the stromal processing peptidases SPP-1 and SPP-2, which hydrolyse wild-type pSS (20.6 kDa) to an intermediate-sized product iSS (18.3 kDa) and to the mature SS (16.3 kDa), respectively. The mutations introduced into cDNA resulted in exchange of (a) two amino acids flanking processing site 1, or (b) one or (c) both amino acids flanking processing site 2. Mutation (a) prevented pSS from being processed at site 1 but not from cleavage at site 2. Mutation (c) abolished the action of SPP-2 but not SPP-1. When pSS with mutation (c) was imported into isolated chloroplasts, iSS accumulated while SS formation was abolished. However, mature SS was produced even in the absence of iSS synthesis (mutation a). Import of pSS bearing mutation (b), which only partially inhibited processing at the SPP-2 site, slowed the rate of SS formation down whereas iSS and some slightly smaller derivatives accumulated. These experiments suggested that in Chlamydomonas processing of pSS can occur in two steps, whereby the first step is facultative. The same three mutations were studied in vivo after transformation of SS-deficient C. reinhardtii T60-3 with mutated genomic DNA. Growth and photosynthesis was as in control transformants, except for the slower-growing transformants (mutation c) where no mature SS was immuno-detected. However, pSS fragments with molecular masses between those of iSS and SS were present even in the ribulose-1,5-bisphosphate carboxylase/oxygenase holoenzyme.

Animals↗