The ability of heat stress and metabolic preconditioning to protect primary rat cardiac myocytes

Primary rat cardiocytes were subjected to either thermal preconditioning for 30 min at 43°C or 20 min metabolic preconditioning (10 mM deoxyglucose, 20 mM lactate, pH 6.5). Eighteen hours later cells were analysed either for hsp 70i expression or subjected to a subsequent lethal heat stress or simulated ischaemia (10 mM deoxyglucose, 20 mM lactate, 0.75 mM sodium dithionite, 12 mM potassium chloride, pH 6.5) for 2 hours and assessed for survival by trypan blue exclusion.Hsp 70i was induced over 100 fold by thermal preconditioning and 30 fold by metabolic preconditioning (p<0.001, p<0.05), hsp 90 was induced 2.71 fold and 2.24 fold (p<0.001, p<0.001) by thermal and metabolic preconditioning respectively, while hsp 60 was not induced by either treatment. Preconditioned cultures had improved survival against subsequent lethal heat stress or simulated ischaemia: Thermal preconditioning reduced death from 69.22% to 52.46% upon subsequent lethal heat stress and from 49.13% to 36.66% upon subsequent lethal simulated ischaemia. Metabolic preconditioning reduced cell death from 51.29% to 33.8% against subsequent lethal heat stress, and from 69.09% to 55.61% upon subsequent lethal simulated ischaemia. A second marker of cell death, the release of lactate dehydrogenase activity into the culture media, was reduced to 65% and 60% of control values for thermally preconditioned cells subjected to lethal heat or lethal simulated ischaemia respectively. Metabolically preconditioned cells demonstrated lactate dehydrogenase activity of 59% and 51% that of control values, when subjected to lethal heat or lethal simulated ischaemia respectively.Abbreviations hsp heat stress protein - hsp 70i inducible 70 kDa heat stress protein - LDH lactate dehydrogenase - PBS phosphate buffered saline     

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.     

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     

Zur Rolle der enzymatischen DNA-Reparatur bei Carcinogenese und Krebschemotherapie

Ohne ZusammenfassungCancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on actual and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author. The EditorsDie Zeitschrift für Krebsforschung und Klinische Onkologie bringt in zwangloser Folge Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autos wieder. Die HerausgeberHerrn Prof. Harold P. Rusch, Madison, Wisc., in aufrichtiger Verehrung zum 70. Geburtstag gewidmet     

Use of cultured human tissues and cells in carcinogenesis research

Summary A variety of approaches are used to study carcinogenesis. Recent advances in techniques for culture of human tissues and cells have provided additional experimental systems of study the process of carcinogenesis and the genetics of cancer.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.     

Zur Epidemiologie und Ätiologie des Oesophaguscarcinoms in China

Ohne Zusammenfassung

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The epidemiology and etiology of esophageal cancer in China

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Stipendiaten der Alexander von Humboldt-Stiftung aus der Volksrepublik China

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The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on actual and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author.Die Zeitschrift Journal of Cancer Research and Clinical Oncology bringt in zwangsloser Folge Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autors wieder.     

Hormonal factors in human carcinogenesis

Summary A synopsis is presented of hormone-cancer relationships as seen by an epidemiologist. Emphasis has been placed on reproductive risk factors and cancers of the endometrium, ovary and breast. Although there are definite parallelisms in this regard the aetiological mechanisms for these three sites may be different.Evidence is accumulating that the protective effect of an early first birth and of subesequent pregnancies on breast cancer risk can be understood biologically in terms of interference with the occurrence of preneoplastic lesions.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.Presented at the EACR mecting, Copenhagen, 21 September 1983     

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.     

Serum cytokines in patients with rheumatoid arthritis

Serum cytokines such as interleukin 1 (IL-1), interferon (IFN-), and tumor necrosis factor (TNF) were measured in 40 patients with rheumatoid arthritis (RA). In the 40 patients studied, serum IL-1 was detected in 5 patients, IFN- in 10 patients, and TNF in 20 patients. The IL-1-positive group showed increased values of activity indices compared to the IL-1-negative group. Values of serum IFN- correlated well with the number of peripheral blood lymphocytes and CD3⁺ cells and with the percentage of CD3⁺ CD26⁺ cells. Values of serum TNF correlated positively with the number of peripheral blood monocytes and the percentage of CD3⁺ HLA-DR⁺ and CD3⁺ CD25⁺ cells. These results indicated that serum IL-1 in RA patients reflects the activity of RA, while the serum IFN- and TNF in RA patients may be related to circulating activated lymphocytes and monocytes, respectively.     

Secretory component and lactoferrin in pure pancreatic juice in chronic pancreatitis

To evaluate pathophysiological roles of proteins in pancreatic secretion, immunoreactive lactoferrin (LF) and secretory component (SC) were measured in the first fraction of the pure pancreatic juice obtained endoscopically from 17 control, 21 suspected (SCP), 14 noncalcified (NCP), and 14 calcified chronic pancreatitis (CCP) subjects. The protein and amylase tended to decrease both in concentration and output from control to CCP. LF concentration was elevated in CCP (18.0±4.9/ml) when compared with controls (2.3±0.2g/ml), and LF output in NCP (12.3±3.8 g/min) was increased from controls (3.8±0.6 g/min). The combination of high LF concentration with low protein output was observed in 10/14 in CCP but 0/14 in NCP and can be a biochemical discriminator of CCP from NCP. SC concentrations were also elevated in NCP (8.5±2.0 g/ml) and CCP (5.6±1.6 g/ml) from controls (1.2±0.2 g/ml). SC outputs in SCP (9.8±3.1 g/min) and NCP (21.1±4.8 g/min) were increased from controls (1.7±0.3 g/min), but there was no further increase in CCP. Hypersecretion of LF and SC in chronic pancreatitis is different, especially in CCP, although the mechanisms for hypersecretion are unknown.This study was supported in part by a research grant for intractable pancreatic disease from the Ministry of Health and Welfare, Japan.     

Regulation of large coronary vessels by adrenergic mechanisms in conscious dogs

Summary The effects of and adrenergic stimulation were examined in conscious dogs on measurements of left circumflex coronary blood flow and coronary arterial diameter and on calculations of mean coronary resistance (MCR) and left circumflex coronary internal cross-sectional area (CSA). Methoxamine (50 g/kg/min), after transiently increasing left circumflex coronary dimensions, induced sustained reductions in left circumflex coronary diameter (9±2%) and CSA (27±5%) at a time when mean arterial pressure rose by 65±5%, left ventricular (LV) dP/dt had decreased only slightly, and heart rate and mean coronary blood flow were at control levels. Isoproterenol, (0.1 g/kg/min), increased heart rate by 66±8%, LV dP/dt by 58±5%, and CSA by 17±3%, while it decreased mean arterial pressure by 12±1% and MCR by 44±5%. After ₁ adrenergic receptor blockade and with heart rate held constant, isoproterenol did not increase LV dP/dt but decreased mean arterial pressure similarly (13±2%) and induced attenuated increases in CSA (6±1%), and decreases in MCR (17±3%). After combined ₁ and ₂ adrenergic receptor blockades isoproterenol induced no significant effects.Thus, in the conscious dog, large coronary vessels not only react passively to changes in aortic pressure but also undergo substantial active changes. Alpha adrenergic stimulation is sufficiently powerful to reduce CSA, despite the opposing elevation of distending pressure. Moreover, large vessels appear to be regulated by ₁ adrenergic mediated increase in myocardial metabolic demands, as well as by ₂ adrenergic mediated vasodilation.Supported in Part by USPHS Grants HL 15416 and HL 17459     

Attempted treatment of fulminant viral hepatitis with human fibroblast interferon

Summary -interferon was administered by intravenous infusion to 16 patients affected with fulminant hepatitis B virus infection in third or fourth-grade coma. Ten patients presented a superinfection or a co-infection due to the delta ()-agent. None had detectable interferon (IFN) activity before therapy was begun. Besides fever, no significant side-effects were observed during treatment. Both the IFN-treated group as well as the historical control group, made up of 70 cases of fulminant virus hepatitis, not treated with IFN and observed during a previous ten year-period, received supportive therapy; survival rates were similar in both groups. Furthermore, the presence or absence of the -agent did not appear to affect survival rates significantly.

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Zusammenfassung -Interferon wurde 16 Patienten i.v. infundiert, die an einem Leberkoma dritten oder vierten Grades infolge fulminanter Hepatitis-B-Virus-Infektion litten. Zehn von ihnen wiesen eine durch -Agens bedingte Super- oder Koinfektion auf. Bei keinem Patienten konnte eine meßbare Interferon (IFN)-Aktivität vor Therapie-Beginn nachgewiesen werden. Außer Fieber wurden während der Behandlung keine nennenswerten Nebenwirkungen beobachtet. Die Überlebensraten waren nahezu gleich bei den mit Interferon behandelten Patienten und bei einer aus 70 Fällen von fulminanter Virus-B-Hepatitis gebildeten historischen Kontrollgruppe, welche in den vorherigen zehn Jahren lediglich mit unterstützenden Maßnahmen behandelt worden war. Außerdem konnten keine statistisch signifikanten Unterschiede in der Überlebenstrate -positiver und -negativer Patienten festgestellt werden.

     

Über Beziehungen zwischen Steroiden und krebserzeugenden Verbindungen (V.)

Zusammenfassung Suspensionen von 2-acetamino-^1.3.5(10)-oestratrien und 3-Acetamino-^1.3.5(10)-oestratrien in Tricaprylin und solche in Glycerin wurden Mäusen subcutan injiziert. Tumoren an der Applikationsstelle wurden nicht beobachtet, doch wurde eine gegenüber den Kontrollen vermehrte Bildung von Tumoren entfernt vom Applikationsort beobachtet.—Unwirksam erwies sich 3-Amino-^1.3.5(10)-oestratrienol-(17) im Pinselungstest an der Maus; im Fütterungstest nach Huggins an der weiblichen Sprague-Dawley-Ratte entstand bei 1 von 10 Tieren ein Mammacarcinom. Die bisher erzielten Ergebnisse sollten dazu anregen, Vertreter dieser Verbindungsklasse auf breiterer Basis zu prüfen.—Eine hypothetische Reaktionsfolge für die Umwandlung von natürlichen Oestrogenen über ihre p-Chinole in die Amino-Analoge (Transaminierung mit Pyridoxamin-5-phosphat) wird diskutiert.

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Relations between steroids and carcinogenic compounds (V.)2-Acetamino- and 3-Acetamino-^1.3.5(10)-estratriene and 3-Amino-^1.3.5(10)-estratrienol-(17)

Summary Suspensions of 2-acetamino-^1.3.5(10);-estratriene and 3-acetamino-^1.3.5(10)-estratriene in tricapryline and in glycerol were injected subcutaneously into mice. Tumors at the site of application were not observed; however, remote from the site of application an increased formation of tumors was observed. 3-Amino-^1.3.5(10)-estratrienol-(17) proved to be ineffective in the skinpainting-test on the mouse; in the feeding-test according to Huggins with female Sprague-Dawley-rats one mammary carcinoma appeared in 1 out of 10 animals. The results obtained so far should stimulate the investigation of representations of this class of compounds on a broader basis.—A hypothetical reaction sequence for the conversion of natural estrogens through their p-quinols into the amino-analogs (transamination with pyridoxamine-5-phosphate) is discussed.

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IV. Mitteilung s. Neumann und Thomas (1967).

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Die histologischen Untersuchungen wurden mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt.     

Esophageal cancer in Kashmir — an assessment

Conclusion Kashmir, with its culturally distinct population with uniform and stable dietary habits, provides an interesting field area for studying the relevance of diet in human esophageal carcinogenesis. In the absence of several features of life-style normally associated with increased incidence of the disease, the local food habits appear to be critical factors in the etiology of this cancer in Kashmir. Evidence from our preliminary studies shows a considerable dietary exposure to preformed N-nitroso compounds in the local population. In addition, the potential endogenous formation of N-nitroso compounds, caused by high precursor contents in certain foodstuffs, enhances the relevance of these compounds as possible risk factors for esophageal and other gastrointestinal cancers in this region. The quantitative assessment of total human exposure to N-nitroso compounds and their exact significance to the high cancer incidence in Kashmir requires carefully planned environmental monitoring and prospective epidemiological studies.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     

Exposures associated with cancer in humans

Summary The IARC programme on the evaluation of the risk of chemicals to humans was initiated in the late 1960s in response to the request made to the Agency for information on environmental carcinogens. The programme, which has been implemented with the advice and the collaboration of a large number of international experts, is focused on the production of monographs on individual chemicals, groups of chemicals or complex exposures. The programme will shortly include also the evaluation of risks related to some of the most widely spread cultural habits. It has been, and still is, the policy of the programme to consider only published information in relation to biological data relevant to the evaluation of carcinogenic risks. One of the main limitations with regard to the possibility of accurately evaluating cancer risks was shown to be the shortage of information on the level of exposure to carcinogenic risk factors. To overcome such limitations it would appear that a close and continuous collaboration between experimentalists and epidemiologists be maintained.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 authorDedicated to Professor Hermann Druckrey on the occasion of his 80th birthday     

Characterization of integrin subunits,cellular adhesion and tumorgenicity of four human prostate cell lines

Cellular adhesion to extracellular matrix proteins via integrin molecules is a major factor in the process of invasion and metastasis of human tumor cells. Four human prostate cell lines were characterized according to the presence and quantity of integrin subunits, the ability of the cells to attach to extracellular substrates and the capacity of the cells to form tumors in severe combined immunodeficient (SCID) mice. All four human prostate cell lines expressed three to five integrins on their cell surfaces. The DU145, PC3 and 431P cells expressed primarily ₃, ₅, and ₆ integrin at similar levels. These cell lines expressed the subunits ₁, ₃ and ₄ with ₁ predominant. The DU145 cells preferred attachment to fibronectin, followed by laminin and vitronectin. Approximately 50%–60% of the binding of DU145 cells to fibronectin and laminin was dependent on the function of ₅₁ and ₆ respectively. The cell line LNCaP differed in its low expression of the ₃ subunit, 95% of cellular adhesion to fobronectin and laminin being integrin-dependent and its inability to attach to vitronectin, in spite of surface expression of _v3. All the cell lines except for LNCaP readily formed tumors within SCID mice and the expression of ₃, ₆, ₁, and ₄ integrin subunits was preserved in the resulting tumor tissue. The altered adhesion properties of the LNCaP cells may explain their altered tumorigenicity.Abbreviations SCID severe combined immunodeficiency - FITC fluorescein isothiocynate - FACS fluorescence-activated cell sorting - PBS phosphate-buffered saline - FBS fetal bovine serum This work was supported in part by a grant from the Friends of the Arizona Cancer Center, Phoenix Chapter, is ACS grant PDT-388 and CH-467 and CA 56666     

Impairment of monocyte “lectin-like” receptor activity in Type 1 (insulin-dependent) diabetic patients

Summary In order to investigate whether the ability of peripheral blood monocytes to bind bacteria is impaired in diabetes, we studied carbohydrate-binding (lectin-like) receptors and the receptor for the Fc portion of immunoglobulin on monocytes from 25 male Type 1 (insulin-dependent) diabetic patients and 10 age-matched healthy control subjects. Peripheral blood monocytes from the diabetic patients expressed lower levels of lectin-like receptors compared to the control subjects, whereas the expression of the receptor for the Fc portion of immunoglobulin was similar in both populations. There was no correlation between the degree of lectin-like binding activity and plasma glucose concentration or glycaemic control. Recognition of unopsonized bacteria by the lectin-like receptor is impaired in Type 1 diabetes; this may affect the efficient elimination of potential pathogens.     

Local and regional immunotherapy of cancer with interleukin 2

Conclusion The results obtained in preclinical systems as well as the first clinical trials suggest that local IL-2 immunotherapy may represent a novel approach to the treatment of some neoplasms. However, the experimental results should be confirmed and substantially extended before definitive conclusions can be drawn. We hope that the data and considerations discussed in this article will facilitate thoughts concerned with future clinical IL-2 trials and be instrumental in the optimization of IL-2 cancer immunotherapy.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     

Die Arterienveränderungen beim Lupus erythematodes visceralis

Zusammenfassung Es werden an Hand von 5 Sektionsfällen die beim Lupus erythematodes visceralis auftretenden Arterienveränderungen an Milz, Nieren, Herz, Leber und Lungen eingehend untersucht und beschrieben. Als kennzeichnendes morphologisches Substrat der Arterienveränderung ergibt sich eine seröse bis fibrinöse und fibrinös-nekrotisierende Arteriitis ohne oder mit nur geringer entzündlicher Zellreaktion, die sich nicht zwanglos in die bekannten Formenkreise der Arteriitiden einordnen läßt, so daß die Herausstellung der Lupus-Arteriitis als Sonderform berechtigt erscheint. Auch die Milzarterien durchlaufen das Entzündungsstadium und vernarben mit einer zirkulär angeordneten perivaskulären Fibrose. Da die Gefäßveränderungen vorwiegend nur im akuten Stadium vorliegen, wird geschlossen, daß der Lupus erythematodes visceralis im fortgeschrittenen Stadium zu einer generalisierten Gefäßerkrankung wird und durch die dabei an lebenswichtigen Organen auftretenden Kreislaufstörungen zum Tode führt.Mit 7 Abbildungen in 14 Einzeldarstellungen     

Some actual aspects of tumor induction and promotion

Summary Quantitative data on chemical carcinogenesis illustrate how difficult it is to decide whether there are thresholds for complete carcinogens. With tumor promoters there probably are safe levels, but these are difficult to determine. The results recorded in the experiments of Fibiger, in which tumors of the stomach were seen, could have been caused by the tumor-promoting effects of a biological agent.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 authorDedicated to Professor Hermann Druckrey on the occasion of his 80th birthday