Cartilage and bone formation in Arterial Wall 2. Ultrastructural Patterns

Summary The ultrastructural aspects of cartilaginous and osseous foci developed in aorta of rabbits immunized against rat aorta homogenates was studied. Besides normal and modified smooth muscle cells, various types of transformed mediacytes were observed in and around these foci: some of them resembled connective and young mesenchymatous cells, others had the appearances of cartilaginous and osseous cells. The possible role of the modified (multipotential) smooth muscle cells in aortic chondro- and osteogenesis is considered in some cases. Following histogenetic pathway is suggested: s.m.c.modified s.m.c.young mesenchyme-like cells (inducible osteogenic precursor cells)chondro-mediacytes, osteomediacyte.

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Knochen-und Knorpelbildung in der Arterienwand 2. Ultrastrukturelle Veränderungen

Zusammenfassung Die vorliegende Studie betrifft die ultrastrukturellen Aspekte von Knorpel- und Knochenherden, die sich in der Aorta von Kaninchen entwickeln, welche gegen Homogenate von Rattenaorta immunisiert wurden.Neben normalen und modifizierten Muskelzellen wurden im Bereich und im Umkreis dieser Herde verschiedene Typen metaplasierter Myozyten beobachtet. Einige von ihnen ähnelten Mesenchymzellen, Knorpelzellen oder Knochenzellen. Die mögliche Rolle modifizierter multipotenter Myozyten bei der Knorpel- und Knochenentstehung in der Aorta wird diskutiert.

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Résumé L'ultrastructure des foyers cartilagineux et osseux de la média aortique de lapin immunisé avec l'homogenat d'aorte hétérologue fut étudiée. A côté des cellules musculaires lisses normales et/ou modifiées, des aspects variés de médiacytes transformés s'observent dans et autour des foyers de métaplasie, notamment des aspects rappelant le fibroblaste, la cellule jeune mésenchymateuse, les cellules chondro et ostéoblastiques. Le rôle éventuel du myocyte modifié (multipotentiel) dans la chondro/ostéogénése aortique est envisagé dans certains cas et la séquence histogénétique suivante suggérée: cellule musculaire lissec.m.l. modifiée (myofibroblaste)médiacyte jeune mésenchymateux (cellule-précurseur ostéogène) chondro-médiacyte et ostéo-médiacyte.

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With 13 figures

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Partially supported by Grant 75 70935 of DGRST-France

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Supported by a scholarship from Claude Bernard Foundation (Paris)     

Extrarenal nephroblastomas

Summary The cases of extrarenal nephroblastoma published in the world literature have been tabulated and reviewed, and are discussed from a historical point of view.The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author     

γ/δ Receptor-expressing T-cell clones from a cutaneous T-cell lymphoma suppress hematopoiesis

Summary Recently we described a cutaneous T-cell lymphoma expressing the / T-cell receptor [5]. The patient suffering from this lymphoma showed low numbers of myeloid and T cells in peripheral blood, while B and NK cells were relatively increased. In vitro culture of the patient's bone marrow (BM) cells revealed a significant suppression of myeloid/monocyte colony formation (GM-CFU) compared with normal controls. This was not due to infiltration of the BM with lymphoma cells. We speculated that a soluble factor either secreted or induced by the lymphoma cells might be responsible for the marked suppression of hematopoiesis in this patient. From a skin biopsy with infiltrating / T-lymphoma cells we established T-cell clones bearing the / T-cell receptor and resembling the phenotype of the lymphoma cells. The supernatant (SN) of these / T-cell clones reduced the number of colonies in a CFU-GM assay (using normal control BM) in comparison to SN of / T-cell clones established from the same biopsy. This suppression was seen mainly on day 7 of culture and was not neutralized by the addition of placenta-CM. The main mediator of this suppression seems to be IFN-,since it was detectable in high amounts in the SN of these / T-cell tumor clones as well as in the serum of the patient. In addition, anti-IFN- antibodies can reverse the T-cell SN-mediated suppression of CFU-GM. We conclude that high serum levels of interferon-, which is secreted in high amounts from / T-cells grown from a biopsy of a cutaneous lymphoma, can suppress hematopoiesis.Abbreviations TCR T-cell receptor - IFN- interferon- - SN supernatant - placenta CM placenta conditioned medium - BM bone marrow - CFU-GM myeloid/monocyte colony formation - NK cells natural killer cells - Ab antibody M. Wilhelm was supported by theDeutsche Forschungsgemeinschaft (DFG Wi 728-2)     

Modulation of pacemaker activity in sheep cardiac Purkinje fibers by stimulation of β-adrenoceptor subtypes

The electrophysiological effects mediated by ₁- and ₂- in spontaneously active sheep cardiac Purkinje fibers were investigated using the non-selective agonist (–)-isoproterenol (IPN) and the selective agonists (–)-noradrenaline (₁) and procaterol (₂) in the absence and presence of the selective antagonists bisoprolol (₁) and ICI 118,551 (₂).IPN (0.01 mol/l) increased the spontaneous rate by 54% and the slope of diastolic depolarization by 68% of the respective control values. Further, IPN increased the action potential duration at –20 mV (APD –20 mV) from 96 to 154 ms, reduced the APD –70 mV by 17% and the duration of the diastole by 39% and slightly hyperpolarized the maximum diastolic potential. These effects were partially inhibited by ICI 118,551 (0.03 mol/l), diminished by bisoprolol (0.1 mol/l) and almost completely blocked by the combination of both antagonists. Concentration response curves of IPN were influenced by the selective antagonists as follows: ICI 118,551 (0.03 mol/l) shifted the curves to the right by 0.2–0.4 log units and increased the slope factor. Bisoprolol (0.1 mol/l) induced a greater shift to the right by 1.1–1.5 log units. Combination of bisoprolol with ICI 118,551 shifted the curves to the right by 1.5–1.7 log units.Noradrenaline (0.3 mol/l) elicited similar actions as IPN. Bisoprolol (0.1 mol/l) shifted the concentration response curves of noradrenaline to the right by 1.1–1.9 log units. Actions of procaterol (0.1 mol/l) were weak, attained only 15–35% of the maximal effects of IPN and could be blocked by ICI 118,551 (0.03 mol/l).These results show that the increase of pacemaker activity induced by catecholamines in sheep cardiac Purkinje fibers is predominantly mediated by stimulation of ₁. However, contribution of ₂ mediated effects could be demonstrated.Supported by Ministerium für Wissenschaft und Forschung, Nordrhein-Westfalen, Projekt-Nr, 40008786.     

Aortic valve replacement and splenectomy in a patient with chronic idiopathic thrombocytopenic purpura—preoperative management with high-dose γ-globulin

Summary We report the management of a patient with chronic idiopathic thrombocytopenic purpura and severe aortic valvular disease. Preoperative intravenous high-dose -globulin administration was employed, and aortic valve replacement combined with splenectomy were performed during the same operation. The platelet count at admission was 34,000/mm³ and increased to 146,000/mm³ after the -globulin therapy. Platelet transfusion at the end of the cardiopulmonary bypass was considered no longer necessary in the postoperative period, because the platelet count increased quickly after the procedure. The post-operative course was uneventful. We believe that open heart surgery and splenectomy can successfully be performed simultaneously in a patient with chronic idiopathic thrombocytopenic purpura treated with high-dose -globulin therapy.     

Gastric “pseudolymphoma” with restricted light chain expression in a patient with obscure gastrointestinal blood loss

Summary We present a case report of a gastric pseudolymphoma (GL) that exhibits restricted light chain expression and, therefore, illustrates the dilemma encountered when histologically benign lesions have phenotypic abnormalities suggesting malignancy. For many years this lesion has been considered usually benign; however, recent reports such as this one demonstrate immunologic signs of monoclonality in an otherwise histologically benign lesion. This finding challenges our assumptions as to the nature of this lesion and our definition of cancer. The lesion also displays Castleman-like features (angiofollicular hyperplasia) as well as common inflammatory germinal centers. In addition we briefly review the literature.     

Comparison Between Ischaemic and Anisomycin-Induced Preconditioning: Role of p38 MAPK

To further evaluate the significance of p38 MAPK as trigger or mediator in ischaemic preconditioning, anisomycin and SB 203580 were used to manipulate its activation status. Special attention was given to the concentration of the drugs and protocols used.The isolated perfused rat heart, subjected to either 25 min global ischaemia or 35 min regional ischaemia, was used as experimental model. This was preceded by anisomycin (2 or 5 M: 3 × 5 min; 5 M: 5 min or 10 min; 5 M: 10 min + 10 min washout or 20 M: 20 min) or SB 203580 (2 M: 3 × 5 min; before and during 3 × 5 min or 1 × 5 min ischaemic preconditioning; 10 min). Endpoints were functional recovery during reperfusion and infarct size.Anisomycin, regardless of the protocol, reduced infarct size, but did not improve functional recovery. In a number of experiments activation of JNK by anisomycin was blocked by SP 600125 (10 M). SP 600125 had no effect on the anisomycin-induced reduction in infarct size. SB 203580 when administered for 10 min before sustained ischaemia, improved functional recovery and reduced infarct size. SB 203580 could not abolish the beneficial effects of a multi-cycle preconditioning protocol, but it significantly reduced the outcome of 1 × 5 min preconditioning. In all hearts improved functional recovery and reduction in infarct size were associated with attenuation of p38 MAPK activation during sustained ischaemia-reperfusion.The results indicate that activation of p38 MAPK acts as a trigger of preconditioning, while attenuation of its activation is a prerequisite for improved recovery and a reduction in infarct size.     

Progression of X-linked adrenoleukodystrophy under interferon-β therapy

The cerebral phenotype of X-linked adrenoleukodystrophy (ALD) is a rapidly progressive neurodegenerative disorder characterized by a cerebral inflammatory response and elevated very long-chain fatty acids (VLCFA). Interferon- (INFB) is known to suppress the synthesis of tumour necrosis factor and interferon-, which have been reported to be elevated in the margin of the areas of demyelination in ALD brains. We report on treatment with interferon- in 8 patients with cerebral ALD, who additionally received glycerol trioleate/glycerol trierucate. INFB-1a (Rebif, Serono, Switzerland) was given subcutaneously once a week, 3 million units for the first 3 months and 6 million units for the next 9 months. All patients showed an unimpeded progression of neurological symptoms during INFB therapy. Therapy was stopped within 6 months in 4 patients because of the fast neurological deterioration with loss of walking. In all patients the MRI demonstrated a progression of demyelination with a qualitatively unchanged gadolinium enhancement. Further studies are needed to elucidate the pathomechanism of demyelination in ALD in order to find an effective therapy for cerebral ALD patients.     

Slow metabolic deterioration towards diabetes in islet cell antibody positive patients with autoimmune polyendocrine disease

Summary We studied metabolic progression to IDDM in a cohort of adults who are ICA-positive and have associated autoimmune endocrine disease or circulating organ-specific autoantibodies (the Polyendocrine Study). Of the 186 individuals recruited 27 developed overt diabetes after a median follow-up of 4.5 years (range 0.4–12). Of these, eight patients did not require insulin treatment until at least 6 months after clinical diagnosis, with an interval of 1.8 years (1.2–5.7). An IVGTT was performed in 38 subjects and 23 had sequential studies. Of the initial 38 subjects six developed diabetes and only three showed a loss of FPIR to glucose (below the first percentile of a normal control group) before clinical onset of the disease. An additional three subjects showed a loss of the FPIR, and all still have normal glucose tolerance after median follow-up of 28 months (22–95). A whole or mixed pattern of islet cell staining was found in five of the six patients who developed diabetes and antibodies against an islet 37 k-antigen were detectable in four patients, all of whom required insulin soon after diagnosis. A beta-cell selective ICA staining pattern was seen in 14 of 17 subjects who did not develop diabetes and the mixed pattern in only three. None of this group had detectable 37k-antibodies. We conclude that metabolic deterioration is slow in polyendocrine patients, and that the IVGTT has less prognostic significance in this group than in first degree relatives of patients with IDDM. In contrast, the presence of the whole or mixed ICA staining pattern or of 37k-antibodies can identify a high risk of progression to IDDM within this polyendocrine population and may indicate the rate of metabolic deterioration.Abbreviations IDDM Insulin-dependent diabetes mellitus - ICA islet cell antibodies - IVGTT intravenous glucose tolerance test - FPIR first phase insulin response - OGTT oral glucose tolerance test - GAD glutamic acid decarboxylase - JDF Juvenile Diabetes Foundation     

An auto-anti-B in an A1B person. Serological studies

Summary The serum of a patient (Mr. Lat) with the regular blood group A₁B contains an anti-B reacting with all cells having a B antigen except b_x and cis AB. The anti-B reacts at 4° C and occasionally at room temperature as shown by agglutination, absorption-elution and by thermo-dynamic assays. The antibody is regarded as an irregular autoantibody belonging to the group of the so called suppressed or latent antibodies.

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Zusammenfassung Das Serum eines Patienten (Mr. Lat) mit der normalen Blutgruppe A₁B enthält Anti-B, das mit allen Zellen reagiert, die ein B-Antigen aufweisen, ausgenommen B_x und cis AB. Das Anti-B reagiert bei 4° C und gelegentlich bei Zimmertemperatur, was durch Agglutination, Absorption-Elution und durch thermodynamische Unter-suchungen gezeigt wurde. Der Antikörper wird als irregulärer Autoantikörper angesehen, der zur Gruppe der supprimierten oder latenten Antikörper gehört.

     

Vergleichende Versuche an normalen und cancerösen Blutseren durch Dünnschicht-Elektrophorese

Zusammenfassung Bei der Dünnschicht-Elektrophorese der Blutseren wandert das -Globulin sehr langsam zur Kathode, während die -Globuline im wesentlichen auf der Startlinie verbleiben und die -Globuline sowie die Albumin-Komponenten zur Anode wandern. Der Vergleich der Tumor- und Normalseren zeigt:Die Konzentration der -Globuline ist im Tumorserum erheblich niedriger als im Normalserum; in den Seren der Ratten, deren Tumoren wenigstens die Dimensionen 1,5×2,5×4 cm besaßen, war das Serumalbumin in bedeutend kleinerer Konzentration vorhanden als im Normalserum.

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Summary With thin-layer electrophoresis of blood sera, the -globulin migrated to the cathode very slowly, whereas the -globulins remained at the starting line, and the -globulins as well as the albumin components moved to the anode. A comparison between normal sera and that from tumor-bearing animals revealed: the concentration of the -globulins in the tumor sera was considerably lower than in normal sera. In the sera of rats, whose tumors measured at least 1.5×2.5×4 cm, the concentration of serum albumin was noticeably less than in the normal serum.

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Mit 5 Textabbildungen

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Herrn Professor Dr. Adolf Butenandt zum 60. Geburtstag gewidmet.     

Expression and prognostic roles of integrins and interleukin-1 receptor type I in patients with ductal adenocarcinoma of the pancreas

To Investigate the prognostic indicator, we examined the expression of ₆- and ₅- integrin and interleukin-1 receptor type I (IL-1RI) immunohistochemically, and analyzed the correlation between immunohistochemical findings and clinicopathological factors in pancreatic cancer. In patients with a strongly expressing ₆- integrin subunit or weakly expressing ₅₁-integrin in pancreatic cancer tissues there was a significant association with advanced TNM stage (P = 0.027 and 0.014, respectively), presence of liver metastases (P = 0.032 and 0.002, respectively), and poor prognosis (P = 0.0155 and 0.0056, respectively). In patients with a weakly expressing ₆ integrin subunit or weakly expressing ₅₁-integrin in noncancerous pancreatic tissues there was a significant association with poor prognosis (P = 0.0324 and 0.0396, respectively). Multivariate analysis demonstrated that strong expression of ₆- and weak expression of ₅₁-integrin were found to be independent prognosticators in pancreatic cancer patients. Our present results indicate that ₆₁- and ₅₁-integrin expression can be a significant prognostic indicator in pancreatic cancer.     

The growth of crimped dacron aortic bypass graft: A case report

The author presents the case of a patient who was operated upon for extensive stricture of the abdominal aorta at the age of 8 years and of a height of 42. In the course of surgery a 12-mm diameter woven crimped vascular prosthesis was anastomosed end-to-side to the lower thoracic as well as to the infrarenal abdominal aorta to bypass the strictured aortic segment. During the following years the patient underwent four consecutive aortograms and also several surgical interventions on the visceral arteries but not on the bypass graft. The latest arteriogram taken at the age of 31 and height of 66 showed an approximately 15% enlongation responding with the appropriate growth of the adjacent vertebra during the years undoubtedly due to stretching, induced straightening of the crimps, and some blunting of the angle by which the graft was attached to the thoracic aorta, an additional factor which made the course of the prosthesis adapt to body growth. The case illustrates that if crimped Dacron grafts are implanted in a growing individual in an appropriate manner, one may count that he or she will probably adapt to the natural increase of body length.     

Glutathione synthetase deficiency: is gamma-glutamylcysteine accumulation a way to cope with oxidative stress in cells with insufficient levels of glutathione?

Glutathione (GSH) plays a major role in the cellular defence against oxidative stress and other vital cellular functions. It therefore seems inevitable that patients with severe depletion of GSH will not survive. However, at least some with glutathione synthetase (GS) deficiency do. This study was done to determine whether these patients have a mechanism to compensate for their GSH deficiency. Cell-free extracts of cultured fibroblasts from 9 patients with GS deficiency and 9 control subjects were analysed by HPLC for low-molecular-weight thiol compounds. The patients cells contained 7.4nmol of GSH per mg of protein (median; range 2.8–25.2) compared to 33.0nmol in control fibroblasts (range 26.7–51.4) (p<0.01). On the other hand, the patients cells accumulated 18.1nmol of -glutamylcysteine (-GC) per mg of protein (median; range 6.9–71.7), whereas the control cells contained 0.1nmol (range 0.05–0.16) (p<0.01). The cysteine concentrations in the patients cells were 20.7nmol/mg protein (median; range 9.4–52.9) compared to 8.9nmol in control cells (range 3.0–12.4) (p<0.01). Cultured fibroblasts from patients with GS deficiency have low levels of GSH, but instead accumulate -GC. We suggest that -GC, which contains both reactive groups of GSH (i.e. the sulphydryl and -glutamyl groups), can compensate for GSH in the cellular defence against oxidative stress. Thus, -GC may alleviate, but only partly prevent, serious consequences of insufficient GSH levels in affected patients. Since the sum of the levels of GSH and -GC in GS-deficient cells (median 31.5nmol/mg protein, range 16.2–79.0) was similar to the level of GSH alone incontrol cells (33.0nmol/mg protein, range 26.7–51.4), we propose that the cultured fibroblasts may have a mechanism to regulate in a coordinated way the levels of GSH and -GC; for instance, by both compounds acting as feedback inhibitors of -GC synthetase.     

No evidence for linkage between hla and maturity onset type of diabetes in young people

Summary Studies with 20 different genetic marker systems were performed in a large kindred including 18 members affected with maturity onset type of diabetes of young people. Linkage closer than 0.1 could be excluded for ABO and Gm, and linkage closer than 0.05 for HLA GLO, and haptoglobin. No significant positive lod scores were found.     

Inhibition of platelet accumulation by β1-adrenoceptor blockade in the thoracic aorta of rabbits subjected to experimental sympathetic activation

Summary Arterial platelet adhesion is an initiating event in the thrombo-embolic complications of atherosclerosis and may also accelerate the development rate of atherosclerotic lesions. Psychosocial stress has been shown to accelerate atherogenesis in animals, an effect probably mediated via -adrenoceptor activation. In view of the postulated roles of platelets and -adrenoceptor activation in atherosclerosis development, we decided to test whether blockade affects arterial platelet accumulation. We studied the accumulation of radioactivity from ¹¹¹In-labelled platelets on the wall of the thoracic aorta of rabbits as a measure of platelet accumulation. During the exposure to the labelled platelets, the animals were also exposed to 3 hours of chloralose anesthesia. This is a reproducible model of experimental sympathetic activation, including -adrenoceptor activation, which we used to amplify possible effects of -blockade on platelet-vessel wall interaction. The effectiveness of the anesthesia in increasing sympathetic activity was verified by significant rises in mean arterial blood pressure (from 77 to 88 mmHg), heart rate (190 to 290 bpm), and plasma levels of norepinephrine (1.0 to 3.3 nM) and epinephrine (0.13 to 0.83 nM). In chloralose anesthetized rabbits, approximately 30×10^-9% of the injected ¹¹¹In accumulated in each square millimeter of intima at unbranched thoracic aorta. Platelet accumulation was significantly higher at arterial branching points, 70% higher at intercostal artery bifurcations, and 150% higher at coronary artery bifurcations than in unbranched aortic intima. Pretreatment with metoprolol in a dose resulting in therapeutic plasma levels significantly reduced platelet accumulation by 48% in unbranched aorta, 65% at intercostal, and 53% at coronary artery bifurcations. blockade also significantly blunted the hemodynamic responses to the sympathetic activation. blockers have previously been shown to have antiaggregatory properties ex vivo; this study showed that blockade also can reduce accumulation of platelets or platelet-derived products on the vessel wall in vivo. The relevance of the antiplatelet effect of blockade found is discussed with regard to previously described effects of blockade on the development and complications of atherosclerosis.     

Differential survival of cell subpopulations in spheroids after treatment with bleomycin

Summary The cytotoxic effect of bleomycin (BLM) on Chinese hamster V79-cells grown as spheroids is compared to that on monolayer cultures in exponential vs. plateau phase of growth. Cells treated as intact spheroids with BLM (50 g/ml for 1 h) are more sensitive than monolayer cultures. Cell subpopulations derived from different zones of the spheroids survive BLM-treatment to different degrees: When treated as single cells in suspension, the formerly outer cells are less affected than the inner cells. Within intact spheroids, however, progressive cellular resistance with increasing distance from the outer rim is found.     

The role of colony-stimulating factors in acute leukemia

Summary This article summarises the effects of colony-stimulating factors and related molecules on leukemia blasts by focussing on autocrine and paracrine growth control. This information may lead to a better understanding of the pathobiology of this highly malignant disorder, and may have therapeutic implications.Abbreviations used GM-, G-, M-CSF granulocyte-macrophage, granulocyte and macrophage colony-stimulating factors - IL interleukin - AML-CFU acute myelogenous leukemia colony-forming unit - HGF hematopoietic growth factor The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author.     

Neurofibromatosis as a cause of multiple coronary aneurysms

Neurofibromatosis is a rare cause of coronary aneurysm. We present a case of multiple coronary artery aneurysms in a patient with neurofibromatosis. Coronary angiography was performed because of postmyocardial infarction angina. Coronary angiography revealed multiple coronary aneurysms in the left anterior descending and circumflex arteries, and diffuse irregularities in the right coronary artery. None of the coronary arteries showed critical stenosis. The patient was successfully managed with aspirin, clopidogrel, and -blocker therapy.     

The problem of thresholds in chemical carcinogenesis some views on theoretical and practical aspects

Conclusions I have tried to show that the threshold problem for carcinogens is still unsolved and that this unsatisfactory situation creates many problems for the scientific evaluation of the carcinogenesis problem as well as for its regulative aspects. In view of the extremely low acceptance of cancer risks in the general population, which is justified as well as understandable, carcinogenesis research must present new ideas to come nearer to a solution of such problems. More sound data on dose-time-effect curves in the low incidence range of 10-0.1% tumor incidences could indicated whether the established linearity in the higher incidence range might eventually by interrupted. Increase of animal numbers could also increase reliability of carcinogenicity experiments and allow the detection of low-dose effect; the disadvantages of this approach (mega-mouse experiment) however, in regard to cost and space necessary are evident. Increases of the mean life span by optimization of animal husbandry still would be another way of approach. However, no real breakthrough is to be expected here.The most promising approach seems to be the use of other indicators for carcinogenicity instead of tumor formation. Binding studies of carcinogens to biopolymers (Neumann 1980), especially DNA, as well as the determination of preneoplastic, enzyme-deficient islands (Kunz et al. 1978) have been shown to give dose-response curves parallel to the corresponding curves from carcinogenicity studies (Kunz) and extendable over 6 orders of magnitude of doses, without deviation from linearity (Neumann). Additional parameters might be found, which, altogether, might prove to be an important step toward further knowledge in this important field of carcinogenesis research.Oh König, das kann ich dir nicht sagen, und was du frägst, das wirst du nie erfahren R. Wagner, Tristan und IsoldeJournal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on actual and/or controversial problems in experimental and clinicial oncology. These contributions represent exclusively the personal opinion of the author. The Editors Die Zeitschrift Journal of Cancer Research and Clinical Oncology bringt in zwangloser Folge Editorials und Guest Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autors wieder.