Änderung der Wachstumskinetik von Ehrlich-Aszitestumoren verschiedener Ploidie nach Röntgen-Bestrahlung

Summary The effect of irradiation (500 R) on the cell cycle of the diploid (EAT_dipl.) and the hypertetraploid (ELT) Ehrlich ascites tumor growing in the peritoneal cavity of male NMRI mice has been studied autoradio-graphically by the double labelling technique (H³- and C¹⁴-thymidine) and the method of labelled mitoses. The results suggest that the proliferation kinetics of tumor cells after irradiation depends on the type of tumor cell strain tested. Identical results were obtained after application of the alkylating agent cyclophosphamide (100 mg/kg).     

Local leukocyte mobilization in irradiated or cyclophosphamide-treated rats

Summary Sprague-Dawley rats made neutropenic by⁶⁰Co irradiation or cyclophosphamide treatment retained a limited capacity for mounting a local leukocyte mobilization (LLM) response. Rats irradiated with 700 rad⁶⁰Co lacked an LLM. Rats treated with 100 mg/kg cyclophosphamide showed no LLM following an initial low response when assayed originally.We wish to thank Mr Dane Walden for excellent technical assistance. This work was supported by Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under Research Work Unit MJ 60212. The views presented in this paper are those of the authors. No endorsement of the Defense Nuclear Agency has been given or should be inferred.     

Genotoxic evaluation of ten carcinogens in theDrosophila melanogaster wing spot test

To provide further background data on the wing spot somatic mutation and recombination assay, 10 selected carcinogens (acetamide, acrylamide, benzo(a)pyrene, cyclophosphamide, diethylstilbestrol, 4-nitroquinoline N-oxide, propyleneimine, safrole, thiourea, and o-toluidine) were tested in this assay. 72-h-old third-instar larvae, trans-heterozygous for 2 recessive wing cell markers:multiple wing hairs (mwh) andflare ³ (flr ³) were fed with 3 concentrations of each carcinogen during the rest of their development until pupation, and the genotoxic effects were measured as significant increases in the appearance of visible mutant hair clones on the adult wing blade. Our results show that 6 of the carcinogens tested produce significant increases in wing spot frequency, at least at one of the concentrations assayed. Benzo(a)pyrene, diethylstilbestrol, safrole and thiourea were the compounds that did not increase the incidence of mutant clones.     

Gastric mucus effusion elicited by oral copper compounds: Potential anti-ulcer activity

Summary In rats, both Cu(I) and Cu(II) show an irritancy profile not shared with Cu^o or Zn(II) or Ni(II). The gastric response to Cu(II), i.e. copius fluid and mucus secretion, can protect the stomach from the acute ulcerative effects of aspirin or physical stress administered subsequently.to whom all enquiries should be addressed, Supported by grants from the National Health and Medical Research Council (Austr.) and University of Tasmania Research Commitee.Acknowledgments: ProfessorsW. R. Walker (Newcastle, Austr.) andL. Field (Nashville, Tenn.) for gifts of Cu(I) and Zn complexes;Dr. J. R. J. Sorenson (Cincinnatti, Ohio) for illuminating discussion; Drs.D. D. Perrin (Canberra) andR. P. Agarwal (Washington D. C.) for providing stability constants and much helpful advice.     

Bazzanenol,a new sesquiterpene alcohol having a skeleton of Bicyclo[5.3.1] undecane system from hepaticae,Bazzania pompeana (Lac.) Mitt

Zusammenfassung Isolierung und Strukturaufklärung eines neuen Sesquiterpenalkohols ausBazzania pompeana (Lac.) Mitt.

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Studies on chemical constituents from Hepaticae, Part III: S.Hayashi, A.Matsuo and T.Matsuura, Tetrahedron Letters,1969, 1599 and ref.² are regarded as Part I and II.     

Effet du fractionnement de dose sur la survie de bourgeons axillaires etde cellules isolées de liseron irradiés aux rayons gamma

Summary Split-dose recovery has been shown on bindweed (Calystegia=Convolvulus sepium [L.] R. Br.) nodes and isolated single cells in aseptic culture. Recovery from sublethal damage occurs within 2 h.

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Nous remercions vivement M^lle L. Rossini qui nous a transmis la technique de culture de cellules de liseron. Les irradiations ont été réalisées grâce à l'obligeance de M^lle E. Moustacchi.     

Synaptic junctions in the developing chick optic tectum

Riassunto Giunzioni sinaptiche compaiono in differenti strati plessiformi del tetto ottico dell'embrione di pollo, a partire dal 12⁰ giorno di incubazione: aumentano di numero fra il 12^o ed il 18^o giorno e, in maniera critica, fra questo e le prime ore dopo la schiusa.

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This work was supported by a grant from the Consiglio Nazionale delle Ricerche (C.N.R.) Rome, Italy.     

Interaction of polyamines or their precursors with the calcium-controlled secretion of peroxidase by sugarbeet cells

Summary Three polyamines tested (cadaverine, spermidine and spermine) and their 2 precursors (the amino acids arginine and ornithine) inhibit the Ca²⁺-mediated secretion of peroxidases by sugarbeet cells in suspension culture at concentrations ranging from 10^–15 to 10^–5M. In the absence of exogenous Ca²⁺, spermine added at higher concentrations mimics the activatory effect of Ca²⁺, the other polyamines being without effect.Supported by the Belgian FRFC (grant No. 2.9009.75 to T.G.) and the Swiss National Foundation for Scientific Research (grant No. 3.140-0.81 to C.P. and H.G.).     

Effects of cycloheximide on protein synthesis in human lung tumors,regenerating rat liver and hepatomas

Summary 10^–4 M cycloheximide (CHM) inhibits leucine incorporation to about the same degree in slices of human lung tumors, rat hepatomas, regenerating livers and normal tissues. At 10^–6 M, CHM has a more pronounced effect on tumor tissue and regenerating liver than on normal tissues. 10^–8 M CHM stimulates protein synthesis in normal rat liver slices.     

The number of neurons,glial and perineurium cells in an insect ganglion

Zusammenfassung Im zweiten Abdominalganglion der Indischen Stabheuschrecke (Carausius morosus Br.) wurden 600 ± 50 Neurone, 1000 ± 100 Gliazellen und 500 ± 30 Perineuriumzellen, zusammen etwa 2100 Zellen gezählt. Die Volumina des Ganglions, des Neuropilems und des Zellcortex betrugen etwa: 140 · 10^–4 mm³, 75 · 10^–4 mm³ und 65 · 10^–4 mm³.     

Zur reproduzierbarkeit der Rf in der Dünnschicht-Chromatographie

Summary Conditions are discussed which influence Rf¹ on thinlayer chromatograms, and directions are given to guarantee good reproducibility. Variance of Rf on thinlayer chromatograms is of the same order of magnitude as on paper chromatograms.

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Der Ausdruck Rf-Wert ist bei häufiger Wiederholung umständlich. Wir gebrauchen an seiner Stelle: das Rf (Singular), die Rf (Plural).

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Die Mittel zur Durchführung dieser Arbeit verdanken wir Arbeitsbeschaffungskrediten des Bundes (M.B.) sowie einer Studienbeihilfe vom Land Baden-Württemberg (A.N.).     

Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses in head and neck squamous cell carcinoma

The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced IL-1β production in an HNSCC mouse model and reduced the numbers of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased the numbers of CD4⁺ and CD8⁺ T cells in HNSCC mice. Notably, the numbers of exhausted PD-1⁺ and Tim3⁺ T cells were significantly reduced. A human HNSCC tissue microarray showed that NLRP3 inflammasome expression was correlated with the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results demonstrate that the NLRP3 inflammasome/IL-1β pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells. Thus, inhibition of the tumor microenvironment through the NLRP3 inflammasome/IL-1β pathway may provide a novel approach for HNSCC therapy.     

Spermatozoid-attracting substance in hermaphrodite brown algae,Pelvetia wrightii andFucus evanescens

Summary A spermatozoid-attracting substance of the hermaphrodite brown algae,Pelvetia wrightii andFucus evanescens, was identified as 1, trans-3, cis-5-octatriene, respectively, by¹H-NMR and¹³C-NMR data and biological activities.Acknowledgments. The authors would like to express their thanks to Mr A. Nishikawa for technical assistance, to Dr M. Abe (Yamagata Univ.) for valuable discussion on biological work and to Prof. Y. Sakai (Hokkaido Univ. Director of the Institute of Algological Research, Muroran) for the facilities during the investigation ofP. wrightii andF. evanescens. Financial support from the Ministry of Education Science, and Culture (Grant-in Aid for Scientific Research No. 556092) is gratefully acknowledged.     

Significance of nitrate reductase in nitrate assimilation in free-livingRhizobium cultures

Summary An in situ method for measuring nitrate reductase (NR) in free-livingRhizobium cultures has been developed. Arginine, threonine, valine, glutamic acid, tyrosine and tryptophan were found to promote NR synthesis. In root nodules rhizobial nitrate reductase also converts nitrate into NH₄ ⁺, thus it provides an alternative to the nitrogenase route for the formation of NH₄ ⁺.Acknowledgments: M.H.S. is grateful to the authorities of CSIR, New Delhi and Miss Anjali Mathur to the authorities of SCST, Lucknow (U.P.) for financial assistance.     

Influence of Prometryne and Ioxynil on photosynthesis and nucleic acid metabolism in plants

Zusammenfassung Spinatpflanzen (Spinacia oleracea L.) wurden in einer Nährlösung, welche die Herbizide Ioxynil respektive Prometryn enthielten, kultiviert. Es zeigte sich, dass in den Blättern dieser Pflanzen der³²P-Einbau in die Nukleinsäuren beeinflusst wurde, bevor eine Hemmung der photosynthetischen CO₂-Fixierung eintrat.     

Marquage intense de la couche des «wedge granules» dans les oocytes en prématuration de la Caille japonaise (Coturnix coturnix japonica) après injection del-leucine-3H

Summary After an i.p. injection ofl-leucine-³H in regularly laying Japanese quails (Coturnix coturnix japonica) and autoradiographic study of their premature oocytes, the wedge granules layer and polar granules are found to be heavily labelled.

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L'auteur remerçie vivement le ProfesseurL. Vakaet (R.U.C.A.) pour ses suggestions.     

Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research

Cancer stem cells have been hypothesized to drive the growth and metastasis of tumors. Because they need to be targeted for cancer treatment, they have been isolated from many solid cancers. However, cancer stem cells from primary human gastric cancer tissues have not been isolated as yet. For the isolation, we used two cell surface markers: the epithelial cell adhesion molecule (EpCAM) and CD44. When analyzed by flow cytometry, the EpCAM⁺/CD44⁺ population accounts for 4.5% of tumor cells. EpCAM⁺/CD44⁺ gastric cancer cells formed tumors in immunocompromised mice; however, EpCAM^?/CD44^?, EpCAM⁺/CD44^? and EpCAM^?/CD44⁺ cells failed to do so. Xenografts of EpCAM⁺/CD44⁺ gastric cancer cells maintained a differentiated phenotype and reproduced the morphological and phenotypical heterogeneity of the original gastric tumor tissues. The tumorigenic subpopulation was serially passaged for several generations without significant phenotypic alterations. Moreover, EpCAM⁺/CD44⁺, but not EpCAM^?/CD44^?, EpCAM⁺/CD44^? or EpCAM^?/CD44⁺ cells grew exponentially in vitro as cancer spheres in serum-free medium, maintaining the tumorigenicity. Interestingly, a single cancer stem cell generated a cancer sphere that contained various differentiated cells, supporting multi-potency and self-renewal of a cancer stem cell. EpCAM⁺/CD44⁺ cells had greater resistance to anti-cancer drugs than other subpopulation cells. The above in vivo and in vitro results suggest that cancer stem cells, which are enriched in the EpCAM⁺/CD44⁺ subpopulation of gastric cancer cells, provide an ideal model system for cancer stem cell research.     

Effect of 723-1723-1723-1on ethanol withdrawal in mice

Summary ⁹ (10 mg/kg, i.p.) administered to mice immediately after withdrawal from a 3-day exposure to ethanol vapor was found to intensify withdrawal reactions. No effect was seen when ⁹ was administered chronically during the exposure to ethanol.     

Two phorbol ester receptor affinities in partially transformed human urothelial cells and decrease of receptor binding in desensitized cells

The presence of specific binding sites for phorbol esters was studied in a transformed but non-tumorigenic human urothelial cell line HCV-29 by assay of specific binding of³H-phorbol-12,13-dibutyrate (³H-PDBu) to intact living cells.³H-PDBu bound specifically to HCV-29 cells in a saturable and competitive manner. Scatchard plot analysis of specific binding yielded a curved plot consistent with two binding sites with K_d of 11 nM and 102 nM, respectively. At saturation the corresponding PDBu binding capacities (B_max) were 8.8 pmol/10⁶ cells (5.2×10⁶ molecules bound per cell) and 2.8 pmol/10⁶ cells (1.7×10⁶ molecules bound per cell).³H-PDBu binding was displaced by biologically active phorbol ester tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and mezerein,but not by tumor promoters such as L-tryptophan, anthranilic acid and sodium saccharin. In cells desensitized by pretreatment with 1 g/ml (2M) TPA or PDBu for 24 h the level of binding was reduced to 28% of the level in non-exposed cells. The ability of desensitized cells to bind³H-PDBu was gradually restored within 5–6 days. At the same time the cells became sensitive to the morphological alteration induced by PDBu. This suggests that desensitization of HCV-29 cells is due to a decreased receptor-ligand binding capacity probably associated with down regulation of the phorbol ester receptors.     

Effect of des-Tyr1-γ-endorphin on serotonin metabolism in rat brain regions

Summary Intracerebroventicular (i.c.v.) administration of des-Tyr¹-γ-endorphin (0.1 and 1.0 μg) caused a decrease of the serotonin (5-HT) concentration of the hippocampus. The concentration of 5-HIAA and the pargyline-induced alterations in 5-HT and 5-HIAA were not affected. No effects were noticed in other brain regions. Acknowledgement. The skilful technical assistance of Ms Henny de Vos Burchart-Lodewijks and Mrs H.A. Spierenburg and J.A. Meijer is gratefully acknowledged. Des-Tyr¹-γ-endorphin was a gift of Dr. H.M. Greven, Organon International B.V., Oss, The Netherlands. To whom reprint requests should be addressed.