Despite of a huge amount of literature on the Feulgen reaction for DNA relatively few investigations deal with the special needs of plant scientists. As a consequence various modifications of the method are practised in different laboratories, which may in part be responsible for contradictory results. In the present work tests are conducted to find out, which steps of the procedure must be stringently controlled and in which steps such a control is less critical. Test material were mainly root tip meristems of Pisum sativum, which were hydrolysed and further processed in toto. Some tests involved also Zea mays, Glycine max, and Hordeum vulgare. Fixations may be stored at -20º C in ethanol for at least 5 years without loss of quality. Nothing is known about permitted conditions of storing fixations at temperatures higher than -20º C, except that at room temperature a security limit for acetic alcohol fixed material is about 3 days. Staining intensity after fixation with formaldehyde is dependent on concentration, time, and temperature of the fixative. Therefore, co-fixation of test and standard material, if to be included, is strongly recommended, while with acetic alcoholic fixation this point is less critical. Hydrolysis is the most critical step of the procedure. Precise control of HCl molarity, temperature, and optimum time is essential. This is often given not due attention in contemporary publications on plant DNA amounts and Feulgen staining. Hydrolysis curves for methanol acetic acid-fixed material with 5 M HC1 at 20º C, 10º C, and 0º C show staining optima after 60 min, 220 min, and 20 h, and a plateau of optimum staining about 5 h long in the latter. Hydrolysis optimum (5 M HCl) for formaldehyde fixed material at 20º C is at 90 min. Washing time after hydrolysis is a surprisingly sensitive step of the procedure and should be kept as short as possible. Time of staining and of all further steps of the procedure, if conducted longer than necessary, lead to a gradual decrease of nuclear dye content. It is suggested to keep these steps as short as possible, because the gradual decay of staining intensity is assumed to proceed not in a stoichiometric fashion. Relatively insensitive steps of the procedure are a final wash in ethanol before drying the slides and storing the slides in the dark.
 
J. Greilhuber, E. M. Temsch (2001) Feulgen densitometry: some observations relevant to best practice in quantitative nuclear DNA content determination. Acta Bot. Croatica 60: 285-298.

 
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Arachis duranensis is a diploid wild relative of the tetraploid cultivated peanut Arachis hypogaea. The literature indicates two 2C genomic DNA mean values (genome size) for A. duranensis, 4.92 and 5.64 pg, and intraspecific variation of up to 11 % negatively correlated with altitude above sea level of the collection sites has been reported. Our recent investigations of Arachis species have shown that unrecognized technical problems with peanut material may have influenced previous genome-size data and rendered them open to critical comments. In the present study, 20 accessions of A. duranensis were investigated by means of DNA flow cytometry (propidium iodide staining) and several of these also by Feulgen DNA image analysis. Pisum sativum was used as the internal standard (2C = 8.84 pg). 2C values in A. duranensis were about half those described previously and varied between 2.49 and 2.87 pg (flow cytometry). This variation was statistically significant and reproducible. There was a negative correlation of genome size with latitude and altitude above sea level of the collection sites. Such a correlation had been already found in one of the previous studies. However, the incongruences between the absolute DNA content values obtained in the present investigation and those in the literature point to the importance of carrying out methodological studies on best practice in DNA-content determinations in plants.
 
E. M. Temsch, J. Greilhuber (2001) Genome size in Arachis duranensis - a critical study. Genome 44: 826-830.

 
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To test the reliability of DNA image cytometry for the measurement of nuclear DNA content in plant material, we conducted independent experiments in two laboratories using different image analysis instruments for densitometric measurement of nuclear DNA amount in Feulgen-stained squash preparations of root tips. The 2C nuclear DNA content of the nine species studied spanned a 100-fold range (approx. 0.3-33 pg). The estimates of nuclear DNA content measured with image cytometry methods were comparable to values obtained previously using both photometric cytometry and flow cytometry. Image cytometry methods showed little variation among repeated experiments within each laboratory or among different operators using the same instrument. Furthermore, the interphase-peak method (measurement of several hundred interphase nuclei per slide) was comparable to the classical prophase/telophase approach (measurement of ten early prophase and ten late telophase nuclei per slide). Hence, DNA image cytometry gives accurate and reproducible results and may be used as an alternative to photometric cytometry in plant nuclear DNA content measurements. In the present study, we propose that two standards for quality control of nuclear DNA content measurement are used in plant DNA image cytometry: (1) the coefficient of variation of the peak should be lower than 6%, and (2) the 4C/2C ratio should be between 1.9 and 2.1.
 
B. Vilhar, J. Greilhuber, J. Dolenc-Koce, E. M. Temsch, M. Dermastia (2001) Plant genome size measurement with DNA image cytometry. Ann. Bot. 87: 719-728.

 
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In certain flow cytometry systems, it is desirable to use immersion optics to obtain optimum fluorescence yield. This is important when propidium iodide and other DNA fluorochromes are used that have weaker fluorescence emission compared to DAPI, when a lamp is used instead of a laser and when the DNA concentrations are low. Our Partec PA II with a horizontally oriented objective and a vertically oriented flow chamber precludes using a liquid immersion medium. The problem was solved using an optical gel with appropriate characteristics. This gel is commercially available and commonly used for connecting glass fiber cables, but has never been used for microscopy before. Compared to the manufacturer's objective (40 x, aperture 0.8), the fluorescence yield was improved approximately four-fold using the optical gel and a 40 x glycerol objective (aperture 1.25). This innovation widens the applicability of flow cytometers with horizontally oriented objectives and vertical flow chambers. We expect it to facilitate the use of propidium iodide as a DNA stain, especially when interspecific genome size comparisons are to be done and base ratio dependent bias must be avoided.
 
E. M. Temsch, R. Obermayer, J. Dolezel, J. Greilhuber (2001) Application of an optical immersion-gel in a flow cytometer with horizontally oriented objective. Biotech. Histochem. 76: 11-14.

 
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Genome size variation within species is a frequently reported, but still a controversial problem. In the present study, we re-evaluated recently published Feulgen densitometric data on genome size and its infraspecific variation in Arachis hypogaea, and also conducted measurements in one accession of its wild relative A. monticola. The methods applied were propidium iodide flow cytometry and Feulgen densitometry using Pisum sativum as an internal standard. The 2C DNA contents previously published cannot be confirmed, but values obtained in this study are about half as large. Additionally, we could not reproduce the previously reported 1.15-fold variation within A. hypogaea; our data indicate genome size stability between respective accessions of this species. Based on 8.84 pg (2C) for Pisum sativum the DNA amounts (2C) were: 5.914 pg in A. hypogaea, and 5.979 pg in A. monticola.
 
E. M. Temsch, J. Greilhuber (2000) Genome size variation in Arachis hypogaea and A. monticola re-evaluated. Genome 43: 449-451.

 
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Die Genomgröße (DNA-Gehalt des Chromosomensatzes) ist ein wichtiger biologischer Parameter, der über seinen Einfluss auf Zellgröße und Zellzyklusdauer Anpassungswert besitzt. Untersuchungen an Pflanzen konzentrierten sich bisher fast ausschließlich auf Gefäßpflanzen, vorwiegend Angiospermen, die nahezu 1000-fach variieren. Über Moospflanzen war fast nichts bekannt - ein Zustand, der durch die laufenden Untersuchungen der Autoren beseitigt wird (s. auch die anderen Beiträge in diesem Band). Der vorliegende Beitrag diskutiert die Erkenntnisse, die an Angiospermen gewonnen wurden und kommt zum Schluss, dass bei Moospflanzen die geringe Genomgröße und deren außerordentlich geringe Variationsbreite (maximal ca. 10-fach) derzeit nur einen begrenzenden Einfluss der Größe der zweigeisseligen Spermien, deren Hauptmasse vom Zellkern gebildet wird und die beweglich bleiben müssen, erkennen lassen. Die methodischen Aspekte der Genomgrößenbestimmung werden vor allem im Hinblick auf häufige Fehlerquellen und ihre Vermeidung diskutiert.
 
J. Greilhuber, H. Voglmayr, E. M. Temsch, R. Obermayer, R. Krisai (1999) Genomgrößen-Variation bei Moospflanzen - Methoden, Probleme, biologische Bedeutung. Abh. Zool.-Bot. Ges. Österreich 30: 5-15.

 
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An 30 österreichischen Taxa von Sphagnum wurde die Genomgröße (DNA-Gehalt des Chromosomensatzes) Feulgen-densitometrisch mit dem Cell Image Retrieval and Evaluation System (CIRES; Kontron, München) gemessen. Aus diesen wurden 10 Taxa zufällig ausgewählt und deren DNA-Gehalt zum Vergleich mit dem Mikroskop-Photometer MPV2 (LEITZ) gemessen. Der DNA-Gehalt weiterer 5 Herkünfte (4 Taxa) wurde mit Durchflusszytometern (CA II, PA II; Partec) bestimmt.
Es konnte zwischen den beiden gametophytischen Polyploidiestufen von 0.392 bis 0.506 pg DNA (x, 1C) und 0.814 bis 0.952 pg DNA (2x, 1C) bereits nach der Messung von wenigen Kernen eindeutig unterschieden werden. Das mittlere Verhältnis dieser beiden Polyploidiestufen betrug 1:2.049. Für S. contortum und S. brevifolium wurde das haploide Niveau erstmals festgestellt. Weiters wurde der Polyploidiegrad einiger Arten mit unterschiedlichen Literaturangaben für die österreichischen Herkünfte bestimmt. Die Korrelation der mit den verschiedenen Methoden gewonnenen Ergebnisse war im Fall von CIRES versus MPV2 hoch signifikant (r = 0.9613, P < 0.001, n = 10) und auch im Fall von CIRES versus Durchflusszytometer signifikant (r = 0.9109, P = 0.032, n = 5).
 
E. M. Temsch, J. Greilhuber, H. Voglmayr, R. Krisai (1999) Genomgrößen-Bestimmung bei Sphagnum: ein Methodenvergleich. Abh. Zool.-Bot. Ges. Österreich 30: 159-167.

 
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Bei 30 österreichischen Sphagnumarten wurde die Genomgröße mithilfe der Feulgen-Absorptionsphotometrie, für die ein Bildanalysesystem (CIRES) und zum Vergleich ein Scanning-Mikroskopphotometer (Leitz MPV II) eingesetzt wurden, mit hochkorrelierenden Ergebnissen bestimmt. Als innerer Standard wurde Pisum sativum (1C = 4,42 pg DNA) eingesetzt. Innerhalb der Arten konnten zwei Ploidiestufen - haploid und diploid - eindeutig nachgewiesen werden (obgleich dieser Nachweis strenggenommen hypothetisch bleibt, solange genaue parallele Chromosomenzählungen nicht verfügbar sind). 26 haploide Arten zeigten Werte zwischen 0,392 pg und 0,506 pg DNA (1C), die vier diploiden Arten (einschließlich zwei Varianten von S. palustre) wiesen DNA-Werte zwischen 0,814 pg und 0,952 pg auf. Das durchschnittliche Verhältnis zwischen den Ploidiestufen betrug 1:2,049. Die Streubreite der Arten innerhalb der Sektionen war geringer als jene zwischen den Sektionen. In einigen Fällen wurden signifikante Unterschiede zwischen verschiedenen Standorten einer Art gefunden. Die von uns ermittelte Genomgröße von Sphagnum palustre weicht stark von einer in der Literatur berichteten Schätzung bezüglich dieser Art ab.
 
Temsch, E.M., Greilhuber, J., Krisai, R. (1998): Genome size in Sphagnum (peat moss). Bot. Acta 111: 325-330.

 
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BACKGROUND: Serum carbohydrate deficient transferrin is a marker of chronic alcohol consumption; it increases above normal in healthy individuals after a daily alcohol intake of more than 60 g/d for more than 2 weeks. The influence of liver disease itself on carbohydrate deficient transferrin levels has not been sufficiently established. METHODS: We investigated serum levels of carbohydrate deficient transferrin in 196 consecutive patients admitted to our Gastroenterology and Hepatology Unit and correlated this parameter with the patients' statements about alcohol intake during the previous 2 weeks and with other markers of chronic alcohol consumption. RESULTS: In our patient population, carbohydrate deficient transferrin had the best overall performance with respect to sensitivity (88%), specificity (82%), and negative predictive value (98%), as compared to other markers, although specificity was much lower than previously reported in patients without liver disease. In the group of patients with liver disease, sensitivity and specificity were 90% and 73%, respectively, and in patients without liver disease, 80% and 88%. The negative predictive value was excellent (96% for patients with liver disease and 99% for patients without liver disease). CONCLUSIONS: Thus, in a patient with a negative interview for chronic alcohol abuse and normal carbohydrate deficient transferrin level, alcohol is unlikely to be the cause of liver disease, and further investigations to establish the etiology of liver disease are warranted. An increased carbohydrate deficient transferrin level, however, cannot be regarded as reliable evidence for chronic alcohol abuse in patients with liver disease.
 
Radosavljevic M, Temsch E, Hammer J, et al. Elevated levels of serum carbohydrate deficient transferrin are not specific for alcohol abuse in patients with liver disease. J Hepatol 1995;23:706-711.

 
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To establish further the clinical significance of the novel quantitative immunoradiometric assay system CA72-4 in patients with gastric and other digestive tract malignancies, the sera of a total of 208 subjects have been analysed and levels of carcinoembryonic antigen (CEA) and another promising new tumour marker, CA195, have been compared. Twenty patients had gastric (GC), 60 colorectal (CC), and 14 pancreatic carcinomas (CC); 94 patients had benign disorders, and 20 were healthy volunteers. CA72-4 elevations above normal (greater than 4 U/ml) were observed in 6 (30%) GC, 17 (28%) CC, and 8 (57%) PC patients. CA195 appeared more sensitive and was increased (greater than 10 U/ml) in 35% GC, 70% CC, and in 100% PC patients; CEA levels above normal (greater than 5 ng/ml) were noted in 35%, 45%, and 66% of patients respectively. CA72-4 had a rather high specificity and was increased in only 6/94 (6%) patients with benign diseases, whereas CA195 had a false positive rate of 23%, and CEA of 33%. Among 20 healthy donors, none had elevated levels of CA72-4 or CA195, but marginal elevations of CEA were noted in 3 smokers. Despite some advantage of the new tumour marker CA72-4 in terms of specificity, its value as a serodiagnostic test in gastrointestinal cancer patients seems inferior to that of CA195 and CEA.
 
Kornek GV, Depisch D, Rosen HR, Temsch EM, Scheithauer W. Comparative analysis of CA72-4, CA195 and carcinoembryonic antigen in patients with gastrointestinal malignancies. J Cancer Res Clin Oncol 1992;118:318-320.

 
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To establish further the clinical significance of the CA-195 tandem immunoradiometric assay in gastro-intestinal malignancies, the sera of a total of 222 subjects have been analysed and compared with assays of the "classical gastrointestinal tumour markers", CA19-9 and carcinoembryonic antigen (CEA). CA-195 elevations above normal (greater than 10 U/ml) were noted in 51/72 (70.8%) colorectal, 15/15 (100%) pancreatic, and in 6/12 (50%) gastric cancer patients. Whereas CA19-9 was increased (greater than 37 U/ml) in 65%, 93%, and 42% of cases, only 54% colorectal, 45% pancreatic, and 42% gastric cancer patients had pathologically elevated serum CEA levels (greater than 5 ng/ml). No abnormal increase of both CA-195 and CA19-9 was found in healthy volunteers, whereas 3/20 (smoking) individuals had CEA levels slightly above normal. With a 29% false-positive rate noted among 103 patients with benign gastrointestinal disorders, the specificity of CA-195 was superior to that of CA19-9 (58%) and comparable with that of CEA (31%). A significant correlation between CA-195 levels and the clinical/pathological stage of disease was noted in colorectal (P less than 0.01) and pancreatic cancer patients (P less than 0.007). Preliminary results of serial measurements of CA-195 in colorectal cancer suggest that this new marker protein, which has no cross-reactivity with CEA, may be useful as a non-invasive test for postoperative surveillance of patients to detect disease recurrence, and serve to complement (though certainly not replace) standard clinical measurements of response to chemotherapy.
 
Kornek G, Depisch D, Temsch EM, Scheithauer W. Comparative analysis of cancer-associated antigen CA-195, CA 19-9 and carcinoembryonic antigen in diagnosis, follow-up and monitoring of response to chemotherapy in patients with gastrointestinal cancer. J Cancer Res Clin Oncol 1991;117:493-496.

 
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The aim of the study was to investigate the influence of recombinant interferon-alpha 2C (rIFN-alpha 2C) on the in vivo Fc-dependent phagocytic activity of the reticuloendothelial (RE) system. Fourteen patients with excessive thrombocytosis due to myeloproliferative disorders were studied before and 3 months after initiation of therapy. RE function was determined by measuring the clearance of autologous red blood cells (RBC) labeled with 51Cr and sensitized with anti-D antibody. Eleven of the 14 patients responded to rIFN-alpha 2 treatment (platelets, less than 440 X 10(9)/liter). Rather in contrast to a shortening of platelet half-life and an increase (trendwise) in platelet-bound IgG, rIFN-alpha 2 caused a significant impairment of RE function. Although this finding could in part be accounted for by the treatment-related decrease in splenic volume, statistical analysis revealed a direct influence of rIFN-alpha 2 on RBC clearance (p less than 0.01). Our study results might be explained by an interferon (IFN)-induced, intensified expression of Fc receptors on platelet (and leukocyte) surfaces, possibly enhancing unspecific binding of IgG to their cellular membranes. The subsequent increased platelet uptake may lead to an overloading of the RE system causing impaired reactions to additional stimuli such as IgG-coated RBC.
 
Scheithauer W, Gisslinger H, Temsch EM, Linkesch M, Linkesch W, Ludwig H. Effect of recombinant interferon-alpha2C on reticuloendothelial function in patients with thrombocytosis. J Interferon Res 1990;10:237-242.

 
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Several different strategies to improve the in vitro cytocidal effect of 5-fluorouracil/leucovorin (5FU/LV), including modulation of dosage and schedule and combination with other cytotoxic agents or biochemical modulators, were examined in the COLO 320DM and Ht-29 cell lines by means of the Bactec system. Modest enhancement of 5FU activity by coadministration of LV was observed in both human colon cancer cell lines. Neither increased concentrations of LV nor prolonged drug exposure or preincubation with LV were found to enhance significantly the growth inhibitory activity of combined 5FU/LV. The only parameter that was found to affect the killing potential of the combination was the concentration of 5-FU, suggesting that lower doses of the antimetabolite would be more effective (COLO 320DM: P less than 0.003; Ht-29 P less than 0.02). The addition of either cisplatin, hyaluronidase or dipyridamole to 5-FU/LV yielded synergistic growth inhibition in 3/6, 2/6 and 2/6 human colon cancer cell lines, respectively. Strictly additive effects were noted for the combination with BCNU as well as concurrent exposure of the cells to 42 degrees C hyperthermia. Whether or not certain combined 5FU/LV drug regimens will result in an improved therapeutic index, however, remains to be determined in properly designed clinical trials.
 
Scheithauer W, Temsch EM. A study of various strategies to enhance the cytotoxic activity of 5-fluorouracil/leucovorin in human colorectal cancer cell lines. Anticancer Res 1989;9:1793-1798.

 
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As an alternative to empirical clinical evaluation of combined drug effects in human tumors, and in an attempt to establish whether the combination of mitoxantrone (DHAD) with other standard drugs would be of any benefit to the patient with advanced gastrointestinal cancer, we have examined the results of simultaneous single-agent testing in vitro in a panel of 8 human colorectal (HCC) and 5 gastric cancer (HGC) cell lines. Cytotoxic drug effects were measured by the use of a new semiautomated radiometric technique (Bactec system), and were quantitated with attention to potentially clinically relevant plasma concentrations. Among several different drug combinations tested, maximal synergistic cell kill was found for DHAD + 5-fluorouracil; continuous incubation of the cells at 1/100 of the peak plasma concentration achievable in humans yielded in vitro responses in 8/8 HCC and 5/5 HGC cell lines. With regard to our results of single-agent testing, our finding of a significant level of in vitro arabinoside-C activity, using prolonged exposure at an in vitro dose corresponding to a clinical high-dose regimen, may provide a rational basis for (re)evaluation of the compound in gastrointestinal cancer patients.
 
Scheithauer W, Temsch EM, Petzl DH, Jakesz R. Application of a new radiometric system for identification of potentially useful drug combinations for treatment of human gastrointestinal adenocarcinoma. Oncology 1989;46:143-149.

 
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In an attempt to establish whether the combination of anticancer drugs with hyaluronidase would result in enhanced cytotoxicity, we have tested a range of 6 continuous cell lines against 4 different chemotherapeutic drugs with or without the addition of various concentrations of the enzyme. Measurement of cytotoxic drug effects has been performed using the Bactec system, a new semiautomated radiometric technique. In only 15 of a total of 144 experiments (11%) was a significant hyaluronidase-mediated potentiation of the single agents' activity seen. In the large majority of experiments, the antiproliferative effect of the combined treatment was classified as additive or subadditive, while in 23% it was antagonistic. Evaluation of the drug modulatory mechanism of hyaluronidase suggested that the combined drug-hyaluronidase effects were independent of the nature of the drug, the exposure mode and the concentration of the enzyme employed. Among the various tumor cell lines tested there was a marked heterogeneity in the sensitivity to the combined effect (P less than 0.0001). In summary, we have not been able to confirm the promising results of early reports of in vitro and in vivo enhancement of the cytotoxicity of antitumor agents by hyaluronidase. Our data emphasize the need for further controlled clinical studies in order to prove or disprove this new therapeutic approach.
 
Scheithauer W, Temsch EM, Stefenelli T, Lathan B. In vitro evaluation of the anticancer drug modulatory effect of hyaluronidase in human gastrointestinal cell lines. Anticancer Res 1988;8:391-395.

 
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In order to analyze and define potentially better growth conditions for colonic stem cell proliferation, we chose four established human colorectal cancer cell lines that differed in biologic cell properties. We studied variables of standard cloning conditions including culture medium, serum supplement, solidifying agent, addition of specific growth factors and use of capillaries as an alternative culture vessel. While modulation of serum concentration as well as use of various standard formulations of culture base media did not result in a reproducible increase of plating efficiencies (PEs), a significant increase in colony formation (when compared to the conventional assay procedure) was achieved; by use of 0.3% agarose or boiled agar as semisolid matrix and by culturing of cells in enriched 'GMF medium'. Specific growth factors, such as EGF or glucagon resulted in "occasionally better" in vitro growth. This suggests a retention of the ability of cells in culture to respond to physiologic regulators of growth. To verify and extend these initial results obtained with continuous cell lines, growth enhancing modifications of the original cloning technique were subsequently applied to in vitro growth of 15 human colorectal cancer specimens obtained directly from patients. Specimens that grew 30 or more colonies under standard plating conditions displayed a more than two-fold increase in PEs which was reproducible for the two specific variables mentioned above, but the overall success rate of the assay could not be improved. In addition to the possibility that several deficient basic requirements for achieving optimal environmental conditions for colonic stem cell growth have not been defined, we believe a major reason for failing to improve the number of drug-assayable specimens is related to an inherent interneoplastic diversity in terms of growth requirements of human colorectal malignancies.
 
Scheithauer W, Temsch EM, Moyer MP, Grabner G. Search for improved culture conditions for clonogenic growth of human colorectal cancer cells in vitro. Int J Cell Cloning 1987;5:55-70.

 
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Bei 112 Patienten mit histologisch gesichertem Karzinom des exokrinen Pankreas wurde im Rahmen einer retrospektiven Analyse die Korrelation von Überlebenszeit und potentiell prognostisch bedeutsamen, klinischen und pathologisch-anatomischen Faktoren untersucht. Das Tumorstadium, die Lokalisation des Primums im Pankreas und der histologische Differenzierungsgrad duktaler Adenokarzinome erwiesen sich als entscheidende Determinanten der Überlebenszeit. Bei lokallsiertem Organbefall, bei Kopfkarzinomen und bei höhergradiger histologischer Differenzierung zeigte sich jeweils ein signifikanter Überlebensvorteil. Bei der Auswertung nichtanatomischer Variabler fand sich beim weiblichen Geschlecht, bei Patienten jüngerer Altersgruppen, bei am.bulantem Performance-Status sowie bei kurzfristigem. Bestehen von klinischen Symptomen jeweils ein Trend zu längeren Überlebenszeiten. Die qualitative und quantitative Angabe eines prätherapeutischen Gewichtsverlustes hatte keinen Einfluß auf die Prognose der Erkrankung. Im Sinne einer Verbesserung der Objektivität und Vergleichbarkeit von Therapiestudien beim Pankreaskarzinom unterstreichen die Ergebnisse dieser Studie die Notwendigkeit der Definition bestimmter Patientencharakteristika.
 
Scheithauer W, Temsch EM, Karner K, Chott A, Grabner G. Prognose maligner Tumore des exokrinen Pankreas: der Einfluß klinischer und pathologisch-anatomischer Variabler auf die Überlebenszeit der Patienten. Acta Med Austriaca 1986;13:46-54.

 
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The antitumor effects of recombinant interferon alpha-2 (rIF) on clonogenic tumor cells were investigated in 29 cases of gastrointestinal cancer. An in vitro response (greater than or equal to 50% inhibition of tumor colony-forming units) was observed in 17% of the tumors, including 2 of 8 pancreatic, 2 of 6 gastric, and 1 of 10 colon cancer specimens. The relative efficacy of rIF in tissue cultures of pancreatic and gastric tumors was further substantiated by the resistance against simultaneously tested single conventional cytostatic drugs. Preliminary results of comparative studies of cloned interferon alpha-2 and human purified leukocyte interferon (hlIF) in 2 human colon cancer cell lines and 11 fresh tumor specimens suggest similar trends in terms of colony inhibition in individual assays. However, the interpatient differences indicate an overall superiority of the natural preparation (P less than 0.02).
 
Scheithauer W, Temsch EM, Schieder K, Funovics H, Schiessel R, Grabner G. In vitro phase II trial of recombinant interferon alpha-2 in gastrointestinal cancer. Int J Cell Cloning 1985 Jul;3(4):188-198.

 
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Der ursprünglich von Hamburger und Salmon beschriebene Tumorstammzell-Assay gilt als potentielles In-vitro-Verfahren zur individuellen prätherapeutischen Evaluierung aktiver antineoplastischer Substanzen.
  In der vorliegenden Studie wurden 34 gastrointestinale Karzinome mittels dieser Technik hinsichtlich der In-vitro-Wachstumscharakteristika bzw. der Sensitivität gegenüber Standardzytostatika sowie rekombinantem DNA-Alpha-2-Interferon (r1F) untersucht. Bei 56% der Tumoren wurde ein zur Beurteilung der Aktivität antineoplastischer Substanzen zureichendes Wachstum beobachtet (> 30 Kolonien/Assay). Eine über 50%ige Zytostatika-induzierte Wachstumsinhibition, die als Kriterium einer In-vitro-Wirksamkeit definiert wurde, konnte bei 2/9 kolorektalen, 0/3 Pankreas-, 0/3 Magen- und 1/4 hepatozellulären Karzinomen objektiviert werden.
  Der therapeutische Effekt von rIF bei gastrointestinalen Neoplasien scheint sehr limitiert zu sein: Bei einer In-vitro-Konzentration von 100 U/ml Medium wurde lediglich bei 1 Pankreaskarzinom (von insgesamt 18 untersuchten gastrointestinalen Tumoren) ein signifikanter (70%iger) antiproliferativer Effekt beobachtet.
 
Scheithauer W, Temsch EM, Schieder H, Funovics J, Schiessel R, Grabner G. In-vitro-Evaluierung der Chemosensitivität maligner gastrointestinaler Tumoren mittels des Stammzell-Assays. Acta Med Austriaca 1984;11:119-124. German

 
 
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