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Biomedical subjects

M Mack

Publications and source records attributed to M Mack.

At least 19 recordsLinked to original sources
PubMed2001

Bispecific single-chain antibodies as effective tools for eliminating epithelial cancer cells from human stem cell preparations by redirected cell cytotoxicity.

High-dose chemotherapy (HDC) with autologous bone marrow or peripheral stem cell transplantation is discussed as one option to treat the extensive stage of a variety of tumors. Effective methods to eliminate contaminating tumor cells from human bone marrow or stem cell grafts may improve the outcome of the patients. We investigated 3 recombinant bispecific single-chain antibodies (bscAbs) directed against 17-1A (EpCAM), c-erbB-2 (HER-2/neu) and LeY on the one and CD3 on the other binding site for their ability to induce lysis of epithelial tumor cells by retargeting autochthonous T lymphocytes present in bone marrow mononuclear cells (BMMC) and in peripheral stem cell mononuclear cells (PSMC). The bscAbs showed remarkable specific lysis of different epithelial tumor cell lines with BMMCs as well as with PSMCs as effector cells. Investigation of the alpha 17-1A-alpha CD3 bscAb revealed a significant correlation between the percentage of CD3(+) cells present in the BMMCs and the rate of lysis as well as the absence of detrimental effects on the viability of hematopoietic progenitor cells as determined by colony-forming unit assays (CFUs). Our results indicate that recombinant bispecific single-chain antibodies could be new tools for purging of human bone marrow and peripheral stem cell grafts from contaminating epithelial cancer cells for patients receiving autologous stem cell transplantation after HDC.

Antibodies, Bispecific↗
PubMed2001

Characterization of sequence determinants within the carboxyl-terminal domain of chemokine receptor CCR5 that regulate signaling and receptor internalization.

The CC chemokine receptor CCR5 mediates chemotaxis of leukocytes and serves as a principal co-receptor for macrophage-tropic human immunodeficiency virus type 1. To identify determinants on the CCR5 carboxyl-terminal domain that regulate receptor signaling and internalization, we generated several CCR5 mutants, which were progressively shortened from the COOH terminus or had carboxyl-terminal serine, cysteine, or leucine residues substituted by alanine and expressed them in RBL-2H3 cells. Using fluorescence resonance energy transfer between beta-arrestin and CCR5 tagged with cyan and yellow variants of green fluorescent protein, we show that high affinity association of the two molecules in living cells requires intact carboxyl-terminal serine phosphorylation sites. Phosphorylation-deficient truncation or Ser/Ala replacement mutants of CCR5 mediated a sustained calcium response and enhanced granular enzyme release in RANTES-stimulated cells. Carboxyl-terminal serine residues are critically involved in CCR5 endocytosis and a dileucine motif, similar to that implicated in the regulation of CXCR2 and CXCR4, contributes to the internalization of CCR5 in a phosphorylation-independent manner. Despite their prominent role in receptor desensitization and internalization, beta-arrestins are dispensable for the CCR5-mediated stimulation of mitogen-activated protein kinase pathways in RBL-2H3 cells. We also show that CCR5 is palmitoylated on carboxyl-terminal cysteine residues. Inhibition of CCR5 palmitoylation by alanine mutagenesis of cysteines or treatment with a palmitate analogue inhibitor profoundly reduces phorbol 12-myristate 13-acetate- and RANTES-induced receptor phosphorylation, homologous desensitization, and internalization. Alanine mutagenesis of serine, cysteine, or leucine residues or the limited carboxyl-terminal truncation of CCR5 did not impair chemokine-stimulated migration of RBL-2H3 cells. Together these results indicate that post-translational modifications of carboxyl-terminal serine and cysteine residues have a significant impact on receptor deactivation and internalization.

Amino Acid Sequence↗
PubMed2001

Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice.

The chemokine receptors CCR2 and CCR5 play important roles in the recruitment of monocytes/macrophages and T cells. To better understand the role of both receptors in murine models of inflammatory diseases and to recognize potential problems when correlating these data to humans, we have generated mAbs against murine CCR2 and CCR5. In mice CCR2 is homogeneously expressed on monocytes and on 2--15% of T cells, closely resembling the expression pattern in humans. In contrast to humans, murine NK cells are highly CCR5 positive. In addition, CCR5 is expressed on 3--10% of CD4 and 10--40% of CD8-positive T cells and is weakly detectable on monocytes. Using a model of immune complex nephritis, we examined the effects of inflammation on chemokine receptor expression and found a 10-fold enrichment of CCR5(+) and CCR2(+) T cells in the inflamed kidneys. The activity of various chemokines and the antagonistic properties of the mAbs were measured by ligand-induced internalization of CCR2 and CCR5 on primary leukocytes. The Ab MC-21 (anti-CCR2) reduced the activity of murine monocyte chemotactic protein 1 by 95%, whereas the Ab MC-68 (anti-CCR5) blocked over 99% of the macrophage-inflammatory protein 1alpha and RANTES activity. MC-21 and MC-68 efficiently blocked the ligand binding to CCR2 and CCR5 with an IC(50) of 0.09 and 0.6--1.0 microg/ml, respectively. In good correlation to these in vitro data, MC-21 almost completely prevented the influx of monocytes in thioglycollate-induced peritonitis. Therefore, both Abs appear as useful reagents to further study the role of CCR2 and CCR5 in murine disease models.

Animals↗
PubMed2001

Depletion of CCR5-expressing cells with bispecific antibodies and chemokine toxins: a new strategy in the treatment of chronic inflammatory diseases and HIV.

The chemokine receptor CCR5 is expressed on the majority of T cells and monocytes in the inflammatory infiltrate of diseases such as rheumatoid arthritis, renal diseases, and multiple sclerosis. In contrast, little expression of CCR5 is found on peripheral blood leukocytes. A specific depletion of CCR5(+) cells could therefore be a useful strategy to reduce the cellular infiltrate in chronic inflammations. Moreover, CCR5 is the major coreceptor for M-tropic HIV-1 strains. Depletion of CCR5(+) leukocytes may help to eliminate cells latently infected with HIV-1. We designed two constructs that specifically destroy chemokine receptor-positive cells. The first construct, a bispecific Ab, binds simultaneously to CCR5 and CD3. Thereby it redirects CD3(+) T cells against CCR5(+) target cells. The Ab specifically depletes CCR5(+) T cells and monocytes, but is inactive against cells that do not express CCR5. Furthermore, ex vivo the bispecific Ab eliminated >95% of CCR5(+) monocytes and T cells from the synovial fluid of patients with arthritis. Also, we designed a fusion protein of the chemokine RANTES and a truncated version of Pseudomonas. exotoxin A. The fusion protein binds to CCR5 and down-modulates the receptor from the cell surface. The chemokine toxin completely destroyed CCR5(+) Chinese hamster ovary cells at a concentration of 10 nM, whereas no cytotoxic effect was detectable against CCR5(-) Chinese hamster ovary cells. Both constructs efficiently deplete CCR5-positive cells, appear as useful agents in the treatment of chronic inflammatory diseases, and may help to eradicate HIV-1 by increasing the turnover of latently infected cells.

ADP Ribose Transferases↗
PubMed2001

Delta 32 mutation of the chemokine-receptor 5 gene in inflammatory bowel disease.

The gene encoding chemokine receptor 5 (CCR5) is colocalized to the microsatellite marker D3S1573, which was linked with inflammatory bowel disease. Genetic heterogeneity in inflammatory bowel disease might be defined by a combination of the p-ANCA status and immunoregulatory genes. One hundred and twenty healthy unrelated controls, 101 patients with Crohn's disease, and 99 patients with ulcerative colitis were genotyped for the Delta 32 mutation of the CCR5 gene. The presence of p-ANCA was determined by the use of indirect immunofluorescence. After genotyping, patients were stratified according to p-ANCA status. The frequency of the Delta 32 mutation was not significantly different in controls and patients with Crohn's disease or ulcerative colitis (P 0.207 or more). Moreover, the frequency of the mutation was not significantly different in patients with inflammatory bowel disease after stratification for the p-ANCA status (P 0.482). Regardless of the p-ANCA status, Crohn's disease and ulcerative colitis are not associated with the Delta 32 mutation of the CCR5 gene.

Adult↗
PubMed2001

[Thermal ablation of liver metastases. Current status and prospects].

PURPOSE: To present thermal ablation of liver metastases via laser induced thermotherapy. MATERIAL AND METHODS: Different technical procedures of thermal ablation and online monitoring are used, as there are the MR-guided laser induced thermotherapy (LITT) and the radiofrequency ablation thermotherapy (RF). RESULTS: In a prospective non randomized study 606 patients with liver metastases were treated via MR-guided laser induced thermotherapy. Inclusion criteria were the exclusion of extrahepatic tumor spread and a number of metastases lower than 5 and a size lower than 50 mm in diameter. The local tumor control rate in the 3 month and 6 month control study was 98.3%, the complication rate 3.5% (clinically relevant: 1.2%). The mean survival rate was 40.9 months for all patients with liver metastases without statistically relevant differences for various primaries, like colorectal carcinoma, breast cancer and various other tumors. Results for radiofrequency are so far limited with incidence of a higher local tumor recurrence rate versus LITT. CONCLUSION: MR-guided LITT results in a high local tumor control rate with improved survival.

Adult↗
PubMed2001

A severe case of pneumatosis cystoides intestinalis with massive accumulation of gas outside the gastrointestinum.

We report an unusually severe case of pneumatosis cystoides intestinalis in an adult female patient undergoing chemotherapy for lymphoblastic crisis in chronic myelogenous leukemia. An impressive accumulation of gas was not only detected within the intestinal wall and mesentery but also in the peritoneum, retroperitoneum, mediastinum and cervical subcutaneous tissue. The patient was almost asymptomatic and fully recovered within a few days of treatment. In addition to chemotherapy, the patient was receiving trimethoprim/sulfamethoxazole for pneumocystis carinii pneumonia and lactulose for constipation. Mucosal damage due to chemotherapy and depletion of tetrahydrofolic acid, changes in bowel flora induced by antibiotic treatment, and the intake of unabsorbable carbohydrates may be responsible for the severity of the disease.

Aged↗
PubMed2001

Expression of chemokines and chemokine receptors during human renal transplant rejection.

Infiltration of renal allografts by leukocytes is a hallmark of acute transplant rejection. Chemokines attract leukocytes bearing specific chemokine receptors, and the specific leukocyte chemokine receptor phenotype is associated with types of immune responses, ie, T helper subtype 1 (Th1; CXC chemokine receptor 3 [CXCR3], CC chemokine receptor 5 [CCR5]) versus Th2 (CCR3, CCR4, CCR8). We studied the expression of the chemokine monocyte chemoattractant protein-1 and the chemokine receptors CCR2B and CXCR4 messenger RNA (mRNA) by in situ hybridization, as well as the chemokine receptors Duffy antigen receptor for chemokines (DARC) and CCR5 protein by immunohistochemistry in renal biopsy specimens with acute cellular rejection (n = 12) and acute vascular rejection (n = 8), transplant nephrectomy specimens (n = 6), and normal areas of tumor nephrectomy specimens (n = 5). CC chemokines and CC chemokine receptor mRNA expression were evaluated by ribonuclease protection assay in specimens from four transplant nephrectomies and one tumor nephrectomy. Upregulation of mRNAs for the chemokines, interferon-inducible protein-10 (IP-10); regulated on activation normal T-cell expressed and secreted; macrophage inflammatory protein-1alpha (MIP-1alpha); MIP-1beta; and lymphotactin, as well as the chemokine receptors, CCR2 and CCR5, were documented during allograft rejection. CCR1 mRNA was detectable in both allografts and controls, but CCR3 and CCR8 were absent. The number of CXCR4, CCR5, and CCR2B mRNAs expressing leukocytes and DARC-positive vessels increased during rejection episodes. CXCR4 mRNA was the most widely expressed. Leukocytes in diffuse interstitial infiltrates were mainly CCR5 positive, but in areas in which leukocytes formed nodular aggregates of infiltrating cells, the number of CCR5-positive cells was low. Instead, leukocytes in these nodular aggregates mainly expressed CXCR4. DARC was expressed on peritubular capillaries, where it was upregulated in areas of interstitial infiltration. Induction of chemokines during renal allograft rejection is accompanied by infiltration of leukocytes bearing the respective chemokine receptors. The upregulation of the CXCR3 ligand IP-10, as well as CCR5 and its ligands, in the absence of CCR3 and CCR8 is indicative that renal allograft rejection is primarily the result of a Th1-type immune response.

Antigens, Protozoan↗
PubMed2001

A chimeric MIP-1alpha/RANTES protein demonstrates the use of different regions of the RANTES protein to bind and activate its receptors.

Human RANTES (CCL5) and MIP-1alpha (CCL3) bind and activate several CC chemokine receptors. RANTES is a high-affinity ligand for CCR1 and CCR5, and it binds CCR3 with moderate affinity and CCR4 with low affinity. MIP-1alpha has similar binding characteristics to RANTES except that it does not bind to CCR3. Here we have generated a chimera of human MIP-1alpha and RANTES, called MIP/RANTES, consisting of the eight amino terminal residues of MIP-1alpha preceding the CC motif, and the remainder of the sequence is RANTES. The chimera is able to induce chemotaxis of human monocytes. MIP/RANTES has >100-fold reduction in binding to CCR1 and does not bind to CCR3 but retains full, functional binding to CCR5. It has equivalent affinity for CCR5 to MIP-1alpha and RANTES, binding with an IC(50) of 1.12 nM, and is able to mobilize calcium and induce endocytosis of CCR5 in PBMC in a manner equi-potent to RANTES. It also retains the ability to inhibit R5 using HIV-1 strains. Therefore, we conclude that the amino terminus of RANTES is not involved in CCR5 binding, but it is essential for CCR1 and CCR3.

Amino Acid Sequence↗
PubMed2001

A multicenter initial clinical experience with right heart support and beating heart coronary surgery.

BACKGROUND: During coronary surgery without CPB, exposure of posterior vessel via sternotomy can cause deterioration of cardiac hemodynamics requiring inotrope drugs support. Recent animal experiments demonstrate hemodynamic benefit of right heart support (RHS) with the AMED system. The purpose of this study was to evaluate the hemodynamic effects during cardiac manipulation to expose the posterior coronary arteries, and determine the effect of RHS in restoring hemodynamics, increasing anastomotic exposure and reducing inotropic requirements. MATERIAL AND METHODS: From July 28 to December 29, 32 patients (25 men/7 women), mean age of 63.4 (+/- 6.2 years, ages: 49-78) received coronary revascularization with the A-Med RHS device. They were divided into two groups of 16 patients, A and B. Group A patients had at least one circumflex branch bypassed. The anterior wall was systematically bypassed off-pump without RHS. The right coronary artery (RCA) and the obtuse coronary artery (OM) were completed utilizing RHS. In group B patients, all vessels including anterior vessels were bypassed with the RHS. Mean arterial pressure (MAP), mean pulmonary arterial pressure (PAP), cardiac output (CO) and the average pump flow (APF) were recorded during the OM and RCA bypass for group A, and for group B LAD data was also recorded. RESULTS: Elective beating heart coronary artery bypass graft (CABG) was successfully accomplished in 32 patients with RHS. Data measurements recorded in Group A showed the improved hemodynamic recovery for OM and RCA bypass with RHS. The MAP increased from 44 to 68 mmHg (OM) and from 63 to 81 mmHg (RCA); the CO from 2.1 to 4.4 L/min (OM) and from 3.3 to 4.7 L/min (RCA). In group B, the data recorded showed the stability of the MAP in all vessels bypassed (LAD, OM and RCA). No device-related patient incidents occurred. All 32 patients were discharged to their homes. CONCLUSIONS: The AMED system, as RHS support, facilitated coronary bypass without CPB to posterior vessels, restoring hemodynamics, providing better exposure to anastomotic sites and apparently reducing inotropes need. Prospective randomize trials are necessary to confirm this initial experience.

Aged↗
PubMed2000

Endocytosis and recycling of the HIV coreceptor CCR5.

The chemokine receptor CCR5 is a cofactor for the entry of R5 tropic strains of human immunodeficiency viruses (HIV)-1 and -2 and simian immunodeficiency virus. Cells susceptible to infection by these viruses can be protected by treatment with the CCR5 ligands regulated on activation, normal T cell expressed and secreted (RANTES), MIP-1alpha, and MIP-1beta. A major component of the mechanism through which chemokines protect cells from HIV infection is by inducing endocytosis of the chemokine receptor. Aminooxypentane (AOP)-RANTES, an NH(2)-terminal modified form of RANTES, is a potent inhibitor of infection by R5 HIV strains. AOP-RANTES efficiently downmodulates the cell surface expression of CCR5 and, in contrast with RANTES, appears to prevent recycling of CCR5 to the cell surface. Here, we investigate the cellular basis of this effect. Using CHO cells expressing human CCR5, we show that both RANTES and AOP-RANTES induce rapid internalization of CCR5. In the absence of ligand, CCR5 shows constitutive turnover with a half-time of 6-9 h. Addition of RANTES or AOP-RANTES has little effect on the rate of CCR5 turnover. Immunofluorescence and immunoelectron microscopy show that most of the CCR5 internalized after RANTES or AOP-RANTES treatment accumulates in small membrane-bound vesicles and tubules clustered in the perinuclear region of the cell. Colocalization with transferrin receptors in the same clusters of vesicles indicates that CCR5 accumulates in recycling endosomes. After the removal of RANTES, internalized CCR5 recycles to the cell surface and is sensitive to further rounds of RANTES-induced endocytosis. In contrast, after the removal of AOP-RANTES, most CCR5 remains intracellular. We show that these CCR5 molecules do recycle to the cell surface, with kinetics equivalent to those of receptors in RANTES-treated cells. However, these recycled CCR5 molecules are rapidly reinternalized. Our results indicate that AOP-RANTES-induced changes in CCR5 alter the steady-state distribution of the receptor and provide the first evidence for G protein-coupled receptor trafficking through the recycling endosome compartment.

Animals↗
PubMed2000

Rapid cloning of metK encoding methionine adenosyltransferase from Corynebacterium glutamicum by screening a genomic library on a high density colony-array.

The genes SAM1 and SAM2 encoding the two different methionine adenosyltransferases (EC 2.5.1.6) in Saccharomyces cerevisiae were used as templates to generate specific DNA-probes. This heterologous mixture of DNA-probes was hybridized under low stringency hybridization conditions to a Corynebacterium glutamicum colony-array representing the complete genome. Subsequently, one genomic fragment was isolated which contained the C. glutamicum methionine adenosyltransferase gene metK (1.224 kb). When overproduced in Escherichia coli, MetK (44.2 kDa) of C. glutamicum had methionine adenosyltransferase activity. In addition, overexpression of metK in C. glutamicum led to an increased intracellular S-adenosylmethionine concentration. The metK transcript was detected by reverse transcription PCR in C. glutamicum cells in the exponential growth phase but not in the stationary phase.

Blotting, Southern↗
PubMed2000

Differential activation of CC chemokine receptors by AOP-RANTES.

RANTES (regulated on activation normal T cell expressed) has been found at elevated levels in biological fluids from patients with a wide range of allergic and autoimmune diseases and is able to attract several subtypes of leukocytes including eosinophils and monocytes into inflamed tissue. Amino-terminal modifications of RANTES produce receptor antagonists which are candidates for blocking this cellular recruitment. Met-RANTES has been shown to modulate inflammation in vivo, while AOP-RANTES is a potent inhibitor of R5 human immunodeficiency virus type 1 (HIV-1) strains and has been shown to down-modulate CCR5 and prevent recycling of the receptor. We have studied the effect of AOP-RANTES in eosinophil activation and have found that it is able to efficiently elicit eosinophil effector functions through CCR3, as measured by the release of reactive oxygen species and calcium mobilization, whereas Met-RANTES is inactive in these assays. AOP-RANTES is found to inhibit CCR3-mediated HIV-1 infection with moderate potency, in contrast to its potent inhibition of CCR5-mediated HIV-1 infection. Furthermore, we have investigated the abilities of these modified proteins to down-modulate CCR1 and CCR3 from the surface of monocytes and eosinophils. We show here that AOP-RANTES is much less effective than RANTES in down-modulation of CCR1. Surprisingly, recycling of CCR1 was minimal after incubation with RANTES while there was complete recycling with AOP-RANTES. In the case of CCR3, no significant difference was found between RANTES and AOP-RANTES in down-modulation and recycling. It therefore appears that trafficking of RANTES receptors follows different patterns, which opens up potential new targets for therapeutic intervention.

Anti-HIV Agents↗
PubMed2000

Differential chemokine receptor expression and function in human monocyte subpopulations.

The subset of human blood monocytes expressing low levels of CD14 and high levels of CD16 (CD14+CD16+) exhibits features resembling mature tissue macrophages and can be expanded in inflammatory conditions. We analyzed expression of CC chemokine receptors (CCR) in CD14+CD16+ versus CD14++ monocytes, which may be crucial for specific trafficking. Multicolor flow cytometric analysis of whole peripheral blood revealed that, as opposed to CD14++ monocytes, the CD14+CD16+ subset lacked surface expression of monocyte chemotactic protein-1 (MCP-1) receptor CCR2, however, it showed significantly higher surface expression of the macrophage inflammatory protein 1alpha (MIP-1alpha)/RANTES receptor CCR5. This was paralleled by differences in mRNA expression in the subsets, as shown by reverse transcriptase-polymerase chain reaction using sorted cells. In comparison to CD14++ monocytes, CD14+CD16+ cells expressed lower CCR2 but higher CCR5 transcript levels, whereas CCR1 levels were equivalent. Flow cytometric analysis of isolated human monocytes recovered after transendothelial chemotaxis assays revealed that the percentage of CD14+CD16+ cells was dramatically reduced in the fraction migrating toward MCP-1 compared with the fraction that did not migrate or the input, showing that polarized CCR2 expression was accompanied by a differential chemotactic responsiveness. Moreover, CD11b surface expression was preferentially up-regulated by MCP-1 in CD14++ cells but by MIP-1alpha in CD14+CD16+ monocytes, confirming the functional relevance of distinct CCR expression. The characteristics of CD14+CD16+ cells may reflect preactivation by cytokines and determine their predilective localization during specific inflammatory conditions or susceptibility to infection.

Antigens, CD↗
PubMed2000

Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection.

The release of microparticles from eukaryotic cells is a well-recognized phenomenon. We demonstrate here that the chemokine receptor CCR5, the principal co-receptor for macrophage-tropic human immunodeficiency virus (HIV)-1, can be released through microparticles from the surface of CCR5+ Chinese hamster ovary cells and peripheral blood mononuclear cells. Microparticles containing CCR5 can transfer the receptor to CCR5- cells and render them CCR5+. The CCR5 transfer to CCR5-deficient peripheral blood mononuclear cells homozygous for a 32-base-pair deletion in the CCR5 gene enabled infection of these cells with macrophage-tropic HIV-1. In monocytes, the transfer of CCR5 could be inhibited by cytochalasin D, and transferred CCR5 could be downmodulated by chemokines. A transfer of CCR5 from peripheral blood mononuclear cells to endothelial cells during transendothelial migration could be demonstrated. Thus, the transfer of CCR5 may lead to infection of tissues without endogenous CCR5 expression. Moreover, the intercellular transfer of membrane proteins by microparticles might have broader consequences for intercellular communication beyond the effects seen for HIV-1.

Animals↗
PubMed2000

[Percutaneous interstitial thermotherapy of malignant liver tumors].

PURPOSE: Description of local ablative techniques such as laser-induced thermotherapy (LITT) and radiofrequency ablation in the percutaneous interstitial thermotherapy for malignant liver tumors. PATIENTS AND METHODS: MR-guided LITT is currently performed by means of implantable percutaneous catheter systems. CT is used to control the insertion of the catheter. Irrigated administration systems are available both for LITT and for radiofrequency therapy. RESULTS: At present LITT enables a local tumor control of 97.2% for localized liver metastases without extrahepatic spreading patterns. In a group of 381 patients the average survival times were 45.7 months for patients with liver metastasis, 42.7 months for those with colorectal liver metastases, and 32 months for HCC tumors. The data for radiofrequency ablation confirm the high value for tumor control of hepatocellular carcinomas with poorer results for liver metastases. CONCLUSIONS: Percutaneous, MR-guided LITT permits good tumor control of liver metastases smaller than 5 cm and less than 5 in number. For HCC, at present percutaneous injection of alcohol, radiofrequency ablation, and LITT are equally effective.

Breast Neoplasms↗
PubMed2000

[Multi-sequential arterial chemoembolization of advanced hepatocellular carcinomas: computerized tomography follow-up parameters for evaluating effectiveness of therapy].

PURPOSE: An evaluation of clinical and computed tomography parameters for the transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Retro- and prospective analysis of 123 TACE procedures in 37 patients (mean age: 63.3 years). RESULTS: Overall mean survival rate for all treated patients was 785 days with a mean value of 387 days. The 1 year survival rate was 62%. Quantitative tumor volumetry revealed a significant difference in survival rate with a mean value of 678 days for patients with a reduction of tumor volume between 0 and 50%, 976 days for a volume reduction of 51-100% and 277 days for an increase in tumor volume during therapy. Patients with a high lipiodol retention presented improved survival data (902 days) versus patients with a low lipiodol retention (513 days). Homogeneous retention of lipiodol was a positive factor on survival as compared to an inhomogenous form of retention. CONCLUSION: In patients with a positive therapy response after TACE the prognosis can be improved by repeated embolization.

Aged↗