Biomedical subjects

G Roos

Publications and source records attributed to G Roos.

212 records · Page 12Linked to original sources

PubMedDate not supplied

'Aggressive' low grade lymphocytic lymphomas can be identified by flow cytometric S-phase determinations.

Forty-five patients with low grade non-Hodgkin's lymphomas were studied with respect to the fraction of S-phase cells in fresh tumour material by flow cytometric analysis. Patients with stage I lymphomas were treated with radiotherapy, patients with stage II-IV lymphomas with Prednimustine (Sterecyt). Patients with lymphocytic lymphomas of CLL type were only treated if they had symptoms. Median S-phase fraction in the samples was 2.0 per cent. A significantly shorter survival was found for patients with lymphocytic lymphomas with S-phase fractions > 2.0 per cent compared with cases showing lower S-phase fractions. No significant difference in survival was found in the subgroups of immunocytic or follicular and follicular/diffuse centroblastic/centrocytic lymphomas. In a Cox multivariate analysis, in which also age, constitutional symptoms, stage and morphology were included, the fraction of S-phase cells was found to be a statistically significant, prognostic parameter for low grade lymphomas, mainly due to the result in the subgroup of lymphocytic lymphomas.

Cell Cycle↗

PubMedDate not supplied

Cell kinetic analysis of non-Hodgkin's lymphomas using in vivo iododeoxyuridine incorporation and flow cytometry.

The aim of this study was to analyse dynamic cell proliferation parameters in non-Hodgkin's lymphomas. Sixty-one patients with newly diagnosed or with recurrent disease were given iododeoxyuridine (IdUrd) intravenously near 4 h prior to tumour biopsy. After staining with an IdUrd reactive antibody and propidium iodide, S-phase fraction (SPF), labelling index (LI), S-phase duration time (Ts) and potential tumour doubling time (Tpot) were determined by flow cytometry. Thirty-eight samples, 15 low grade (LGM) and 23 high grade (HGM) malignant lymphomas, were possible to evaluate. Twenty-three cases were excluded due to aneuploidy, insufficient amount of material or technical problems. Tpot values varied between 0.8-32.9 days (mean 7.0 days). HGM lymphomas had shorter mean Tpot times than LGM lymphomas (4.8 versus 10.4 days, p = 0.05). For Ts the range was 4.2-20.1 h (mean 9.1 h), and a difference between the two histological groups was demonstrated with a longer mean Ts for HGM compared with LGM cases (10.0 versus 7.8 h, p = 0.04). Tpot showed a negative correlation with SPF (P = 0.003), and Ts demonstrated a positive correlation to SPF (p = 0.02). The clinical significance of the dynamic cell proliferation parameters studied remains to be clarified, but the interrelationships between Ts/SPF and Ts/morphologic subtype might be factors of interest for future prognostic studies in malignant lymphomas.

Cell Cycle↗

PubMedDate not supplied

High-performance liquid chromatography-coordination ion spray-mass spectrometry (HPLC-CIS/MS): a new tool for the analysis of non-polar compound classes in plant extracts using the example of Piper methysticum Forst.

An efficient method to characterise complex plant extracts is described using the example of Piper methysticum Forst. (kava; Piperaceae). The method is based on the on-line coupling of high-performance liquid chromatography to a new detection technique: coordination ion spray-mass spectrometry (CIS/MS). CIS/MS is a universal, novel ionisation technique improving selectivity as well as sensitivity. Charged complexes were formed through addition of central complexing ions such as sodium, silver and cobalt. The advantages of CIS/MS detection compared with the electrospray ionisation detection are discussed. The experimental set-up and the application of this simple and robust technique is described to show the its various fields of application in the analysis of plant extracts.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Telomerase regulation and telomere dynamics in germinal centers.

Telomere length maintenance, usually executed by telomerase, is a prerequisite for an extended or infinite division potential. Nevertheless most telomerase positive normal cells exhibit telomere shortening. This study details the telomerase expression and telomere dynamics in purified tonsil B cell subsets during the germinal center (GC) reaction. Significant telomere lengthening was observed as naive B cells matured to centroblasts and when centroblasts matured further to centrocytes, resulting in an increase in telomere length of about 4 kbp determined by Southern blotting. Immunopurified cell populations were also studied by fluorescence in situ hybridization and flow cytometry (flow-FISH) confirming that the GC B cells exhibited lengthened telomeres. These data were further verified in unpurified tonsil cells by combining flow-FISH and immunophenotyping using selected surface markers. Centroblasts expressed high levels of telomerase activity, which was increased in centrocytes, whereas resting naive, activated naive and memory B cells were telomerase activity negative. Expression levels of the catalytic subunit (hTERT) RNA paralleled the telomerase activity levels. The unique telomere elongation in GC B cells permits extensive proliferation during the GC reaction and provides the memory cells with a substantial increase in division potential. Understanding the telomere biology of GC cells is important in defining requirements for telomere elongation in vivo, with implications for the normal immune system as well as for lymphomas, and could provide insights into how the division potential of cells can be manipulated in vitro.

Antigens, CD↗

PubMedDate not supplied

Ki-67 as a marker for cell cycle regulation by interferon.

The effects of interferon (IFN) on the expression of the nuclear antigen Ki-67 were studied in the two IFN-sensitive tumour cell lines Daudi and 251 MG, known to be arrested in the cell cycle in separate stages. The GO/G1-arrested Burkitt's lymphoma cell line Daudi displayed an increasing fraction of Ki-67 negative cells with time, concomitant with an increasing proportion of growth arrested cells. A small fraction of Ki-67 positive cells were found mainly arrested in G2/M. In contrast, no effect on Ki-67 expression was seen in IFN-resistant Namalwa cells, nor in the sensitive glioma cell line 251 MG, which is blocked in the S phase of the cell cycle. Agents blocking the cells in other phases of the cycle did not affect Ki-67 expression. However, after serum deprivation, no Ki-67 expression was found in the glioma cell line, while restimulation initiated expression after 12 hours as cells entered the S phase. We conclude that the Ki-67 antigen was not down regulated in all cells inhibited by IFN and thus does not seem to be useful to monitor clinical effects of IFN treatment.

Biomarkers, Tumor↗

PubMedDate not supplied

The antitumor effect of a novel nitrosourea, tauromustine, at intravenous administration in rat. Cure of hepatomas.

The effect of intravenously injected tauromustine (TCNU) on tumor growth and body weight was studied in rats with subcutaneously implanted experimental carcinomas. With a colonic tumor, a single dose or that dose split on 4 consecutive days gave the same tumor growth delay but the body weight loss was less at the split dose. Injection of the single dose for 1 min, 30 min or 2 h each had the same effect. Rats of another strain were implanted with a hepatoma. 9 out of 10 rats were cured. A late effect was body weight loss due to disturbed growth of the teeth.

Animals↗

PubMedDate not supplied

Improved antitumor effect of the nitrosourea drugs tauromustine (TCNU) and carmustine (BCNU) on a rat liver adenocarcinoma after hepatic arterial administration with degradable starch microspheres.

The effect of the cytostatic nitrosourea drugs TCNU and BCNU on tumor growth was studied in rats with a transplantable colon adenocarcinoma implanted into the liver. The drugs were given as a single dose into the hepatic artery alone or together with degradable starch microspheres (DSM). The effect of the treatment on tumor growth was measured 7 days later. Compared to control animals, TCNU decreased tumor growth. BCNU alone did not significantly decrease tumor growth. The antitumor effect of both drugs was significantly improved by DSM. The addition of DSM to the drugs caused liver damage in a few rats. There were no differences between different treatment groups regarding body weight changes. DSM may protect bone marrow against BCNU toxicity. Injection of DSM alone had no effect either on tumor growth or on survival.

Adenocarcinoma↗

PubMedDate not supplied

Hepatic vascular occlusion combined with adriamycin given by the hepatic artery in rats with adenocarcinoma in the liver.

Rats with an adenocarcinoma of the colon implanted into the liver were treated by a bolus injection of adriamycin by the hepatic artery. In addition, vascular occlusions were performed in the following three ways. 1. The hepatic artery was ligated (HAL) immediately after adriamycin injection. 2. The portal venous branch nourishing the tumor was ligated immediately after adriamycin injection. 3. The Pringle maneuvre (clamping of the hepatic artery, the portal vein and the common bile duct) was performed during 5 min before and 10 min after injection. Tumor size was measured at operation and 6 and 12 days later in the first experiment, 7 days later in the other two experiments. The combination of adriamycin and HAL retarded tumor growth at day 6 as compared to controls, adriamycin alone and HAL alone. The differences were not significant at day 12. The other vascular occlusions did not improve the antitumor effect of adriamycin.

Adenocarcinoma↗

PubMedDate not supplied

Potentiation by dipyridamole of 5-fluorouridine antitumor activity against a rat adenocarcinoma in vivo.

Rats were inoculated subcutaneously into both flanks with a transplantable adenocarcinoma of the colon. They were treated intravenously with either 5-FUrd (5-fluorouridine) or 5-FdUrd (5-fluoro-2'-deoxyuridine) with or without addition of dipyridamole 20 and 30 min later, respectively, for 3 consecutive days. Dipyridamole improved the antitumor activity of 5-FUrd but decreased that of 5-FdUrd.

Adenocarcinoma↗

PubMedDate not supplied

Interferon and the incorporation of 5-fluorouracil into RNA of normal tissues and a secondary liver carcinoma in rat.

The cytotoxicity of 5-fluorouracil (5-FU) has been related to its incorporation into RNA and blocking of DNA synthesis. Interferon may enhance the therapeutic efficacy of 5-FU in colorectal cancer. In a model of secondary liver cancer in the rat, the incorporation of 5-FU into the acid-soluble fraction (ASF), RNA and DNA of several normal tissues and the tumor was determined. The liver nucleotide profile and NADPH-cytochrome c reductase activity was examined. A therapeutic dose of 5-FU was given for 2 h via the hepatic artery and the rats were killed 1 h later. Half of them were pretreated with the interferon inducer polyinosinic-polycytidylic acid (poly(I)-poly(C) and interferon. Pretreatment increased the nucleotide (NT)/DNA and RNA/DNA ratios, decreased the cellularity and left the specific RNA labelling unchanged in the bone marrow. In the liver the pretreatment decreased the NT/DNA and RNA/DNA ratios, (F)UTP, and the NADPH-cytochrome c reductase activity. The 5-FU incorporation into liver DNA decreased. No changes were found in the tumor. The pretreated rats decreased in body weight. A decreased RNA synthesis in the liver might indicate a decreased 5-FU metabolism, explaining the increased 5-FU AUC in the clinic at interferon treatment.

Adenocarcinoma↗

PubMedDate not supplied

Cure of hepatoma in rat with the nitrosourea carmustine (BCNU).

Two experiments were performed with a chemically induced hepatoma in the rat. In the first, tumors were inoculated subcutaneously into both flanks. After 10 days, when all rats had tumors, treatment was given intravenously on two successive days with 10 mg carmustine/kg body weight/day. All control rats displayed growing tumors and had to be killed 12 days after treatment. Treated rats initially lost weight with a slight increase in tumor size. After 3 weeks all tumors disappeared and the rats grew normally. After 4 months the rats were killed and had no tumors. In a second experiment, tumors were inoculated under the liver capsule. Treatment was given via the hepatic artery. Control rats had large tumors after 2 weeks and had to be killed. All treated rats were without tumors at sacrifice. One of them developed a liver cyst and was killed after 3 months, the others after 4 months.

Animals↗

PubMedDate not supplied

Degradable starch microspheres in cytostatic treatment of a liver carcinoma; experimental studies in rats with 5-fluorouracil, tauromustine, carmustine, doxorubicin and RSU-1069.

The degradable starch microspheres (DSM) used have a size of 45 microns and are dissolved by amylase in blood. After intraarterial administration of a mixture of DSM and cytostatic drugs the coinjected drugs remain for a longer time in the target tissue/tumor. A transient hypoxia occurs. Systemic exposure of drugs is decreased. Rats with a carcinoma implanted into the liver were given DSM and drugs via the hepatic artery. DSM did not significantly increase the incorporation of 5-fluorouracil (5-FU) into liver tumor RNA. The incorporation of 5-FU into intestinal and bone marrow RNA increased. DSM increased the antitumor effect of doxorubicin, tauromustine, carmustine and RSU-1069 (aziridine 2-nitroimidazole). Side effects, such as liver and gastric necroses and body weight loss, appeared in some rats. The toxic overspill to the stomach seemed to be reduced by giving the DSM in two parts, with all the cytotoxic drug in the first part. The effect on liver and tumor was not decreased by this procedure. DSM alone had no anti-tumor effect. DSM alone decreased liver UDP-glucuronic acid in tumor-free rats, given either by the hepatic artery or, in the double dose, by the portal vein. DSM alone did not increase liver NADPH-cytochrome c reductase activity or serum ASAT (aspartate-aminotransferase) or ALAT (alanine-aminotransferase), indicating that the DSM are inert to the liver, when infused into the tributary vessels.

Adenosine Triphosphate↗

PubMedDate not supplied

Adverse effects at adjuvant treatment of liver metastases in rat with RSU-1069 + microspheres, or liposomal MTP-PE.

UNLABELLED: Rats were inoculated via the portal vein with a suspension of tumor cells from a transplantable dimethylhydrazine-induced adenocarcinoma of rat colon. In one set of experiments, the bioreductive drug RSU-1069 was injected once via the portal vein with or without degradable starch microspheres (DSM) 10 mins after tumour cell inoculation. In another set the immunostimulator liposomal-encapsulated muramyl tripeptide phosphatidyl-ethanolamine (MTP-PE) was injected via the portal vein or penile vein 1 day before tumour-cell inoculation and then twice a week. The experiments were finished after 2 to 3 weeks. Tumour take, numbers and volumes were measured. RESULTS: RSU-1069 enhanced tumour growth when combined with DSM. Liposomal MTP-PE also increased tumour growth. CONCLUSION: A bioreductive drug combined with microspheres, known to suppress the growth of an established tumour, may enhance its growth in the adjuvant setting. An accepted immunostimulator may enhance tumour take. Drugs used for the treatment of tumours must be carefully employed, if applied in an adjuvant setting. The effect on the normal immune system should be further studied.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMedDate not supplied

Angiogenesis inhibitor TNP-470 augments the effect of repeated arterial ischemia on growth but does not affect take in a rat liver tumor model.

Transient hepatic arterial occlusion causes necrosis in solid hepatic tumors in the rat, but regrowth of tumor cells and capillaries takes place from the tumor periphery. It was therefore considered of interest to combine this treatment with the angiogenesis inhibitor TNP-470 (therapeutic model). Wistar rats with a dimethylhydrazine-induced adenocarcinoma implanted into the liver received one of the following treatments: TNP-470 + transient hepatic ischemia, transient hepatic ischemia alone, TNP-470 alone or sham solution alone. Rats were sacrificed one week after the start of treatment. In addition, we investigated if TNP-470 decreases the risk of tumor take in the liver after intraportal injection of viable tumor cells (adjuvant study). Transient hepatic ischemia combined with TNP-470 gave a smaller increase in tumor volume than transient hepatic ischemia (p < 0.01), TNP-470 (p < 0.001) alone or no treatment (p < 0.001). Transient hepatic ischemia or TNP-470 caused a significant suppression of tumor growth when compared to controls (p < 0.01 in both cases). In the adjuvant study, TNP-470 caused retardation of tumor growth (p < 0.01 as compared to controls) but did not affect tumor number. It is concluded that TNP-470 suppressed tumor growth, both alone and in combination with transient hepatic ischemia, but did not affect take of tumor.

Animals↗