Showing papers on "In vivo published in 1986"
TL;DR: Further data are obtained to support a role for TGF-beta as an intrinsic mediator of collagen formation: conditioned media obtained from activated human tonsillar T lymphocytes contain greatly elevated levels of T GF-beta compared tomedia obtained from unactivated lymphocytes.
Abstract: Transforming growth factor type beta (TGF-beta), when injected subcutaneously in newborn mice, causes formation of granulation tissue (induction of angiogenesis and activation of fibroblasts to produce collagen) at the site of injection. These effects occur within 2-3 days at dose levels than 1 microgram. Parallel in vitro studies show that TGF-beta causes marked increase of either proline or leucine incorporation into collagen in either an NRK rat fibroblast cell line or early passage human dermal fibroblasts. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) do not cause these same in vivo and in vitro effects; in both rat and human fibroblast cultures, EGF antagonizes the effects of TGF-beta on collagen formation. We have obtained further data to support a role for TGF-beta as an intrinsic mediator of collagen formation: conditioned media obtained from activated human tonsillar T lymphocytes contain greatly elevated levels of TGF-beta compared to media obtained from unactivated lymphocytes. These activated media markedly stimulate proline incorporation into collagen in NRK cells; this effect is blocked by a specific antibody to TGF-beta. The data are all compatible with the hypothesis that TGF-beta is an important mediator of tissue repair.
2,860 citations
TL;DR: The results indicate that 8-OH-dG is formed in vivo in cellular DNA on treatment with various oxygen radical-producing agents and that it is repairable and that its content is increase in Salmonella typhimurium cells with hydrogen peroxide.
Abstract: 8-Hydroxydeoxyguanosine (8-OH-dG) was detected in DNA isolated from HeLa cells after the cells in tissue culture had been irradiated with X-rays and from the liver of mice after the whole animals had been irradiated with gamma-rays. The amounts of 8-OH-dG in DNA after in vivo irradiation were three orders of magnitude lower than those after in vitro irradiation (0.008-0.032 8-OH-dG residue/10(5) dG/krad). The 8-OH-dG produced in liver DNA by irradiation of mice decreased with time, suggesting the presence of a repair enzyme(s) acting on 8-OH-dG in mouse liver. Treatment of Salmonella typhimurium cells with hydrogen peroxide also caused increase in the 8-OH-dG content. These results indicate that 8-OH-dG is formed in vivo in cellular DNA on treatment with various oxygen radical-producing agents and that it is repairable.
924 citations
TL;DR: Results show that 1,25(OH)2D3 regulates PTH gene transcription, which then inhibits PTH synthesis, thus completing an endocrinological feedback loop.
Abstract: In vitro 1,25-dihydroxycholecalciferol (1,25(OH)2D3) decreased levels of preproparathyroid(preproPTH) hormone mRNA. We have now pursued these studies in vivo in the rat. Rats were administered vitamin D metabolites i.p. and the levels of preproPTH mRNA were determined in excised parathyroid-thyroid glands by blot hybridization. PreproPTH mRNA levels were less than 4% of basal at 48 h after 100 pmol 1,25(OH)2D3, with no increase in serum calcium. Gel blots showed that 1,25(OH)2D3 decreased preproPTH mRNA levels without any change in its size (833 basepair). Microdissected parathyroids after 1,25(OH)2D3 (100 pmol) showed mRNA levels for preproPTH were 40 +/- 8% of controls, but for beta-actin were 100% of controls. The relative potencies of vitamin D metabolites were: 1,25(OH)2D3 greater than 24,25(OH)2D3 greater than 25(OH)D3 greater than vitamin D3. In vitro nuclear transcription showed that 1,25(OH)2D3-treated (100 pmol) rats' PTH transcription was 10% of control, while beta-actin was 100%. These results show that 1,25(OH)2D3 regulates PTH gene transcription. PTH stimulates 1,25(OH)2D3 synthesis, which then inhibits PTH synthesis, thus completing an endocrinological feedback loop.
506 citations
TL;DR: In vitro cell lines were established from seven biologically distinct in vivo Dunning R3327 rat prostatic tumor sublines to validate that the in vitro cell Lines retained the major characteristics of the parental in vivo tumor sub lines used for their respective establishment.
Abstract: In vitro cell lines were established from seven biologically distinct in vivo Dunning R3327 rat prostatic tumor sublines. Some of these in vitro cell lines (i.e., G, AT-1, AT-2) retain a low metastatic ability when inoculated back into syngeneic Copenhagen male rats, while others (i.e., AT-3, MAT-LyLu, MAT-Lu) retain a very high metastatic ability. A series of genetic (i.e., DNA content per cell, modal chromosomal number), as well as phenotypic parameters (i.e., morphology, 5 alpha-reductase, androgen receptor, estrogen receptor) were used to validate that the in vitro cell lines retained the major characteristics of the parental in vivo tumor sublines used for their respective establishment. A series of additional characteristics (i.e., morphology, growth rate, saturation density in surface culture, anchorage-dependent and -independent clonogenic potential) were compared between the high vs. the low metastatic in vitro cell lines to determine if a discriminatory parameter could be identified which reproducibly predicted the metastatic abilities of the particular prostatic cancer cell line. While the combination of the in vitro cell lines and their parental in vivo tumor subline will be a valuable tool for developing methods for predicting metastatic ability of prostate cancers, no single parameter yet measured is entirely successful in making this important distinction.
417 citations
TL;DR: It is shown that the drug metabolizes more rapidly under hypoxic than aerobic conditions, both in vitro and in vivo, and could be a useful tool in tumor biology, as well as being a new lead in the development of bioreductive cytotoxic agents for cancer therapy.
Abstract: We have examined the effects of the benzotriazine di-N-oxide SR-4233 (3-amino-1,2,4-benzotriazine-1,4 (dioxide) on a variety of aerobic and hypoxic cells in culture, and on tumors in mice. The cell lines used were Chinese hamster ovary (HA-1), mouse 10T1/2, RIF-1, and SCC VII cells, and the human cell lines HCI'-8, AG1522, and A549. The effect of SR 4233 in combination with irradiation was also examined in the SCC VII tumor growing in the flank of C3H mice using clonogenic assay (tumors excised 24 hr after irradiation). We found SR-4233 to be a potent and selective killer of hypoxic cells. Cell killing as a function of time for the various cell lines was exponential, with no shoulder. Drug concentrations producing equivalent levels of cell killing were 75–200 fold lower in hypoxic than in aerobic cells for the mouse and hamster lines, and 15–50 fold lower for the human cells. In vivo experiments showed that the non-toxic dose of 0.3 mmole/kg of SR-4233 enhanced radiation-induced tumor cell kill when the drug was given between 1 hr before and 2 hr after the radiation dose. We have also shown that the drug metabolizes more rapidly under hypoxic than aerobic conditions, both in vitro and in vivo. The toxic product(s) is unknown, but could be the I -electron reduction product, the radical anion, because the mono N-oxide (the 2-electron reduction product) did not display cytotoxicity or selective killing under hypoxic conditions. This compound could therefore be a useful tool in tumor biology, as well as being a new lead in the development of bioreductive cytotoxic agents for cancer therapy.
397 citations
TL;DR: It is suggested that the induced rat plasma inhibitor might be of endothelial origin, and in cultured human umbilical vein endothelial cells, LPS and IL-1 induced increased synthesis of PA-inhibitor.
Abstract: Human IL-1, recombinant murine IL-1 and E. coli LPS were found to be potent inducers of plasminogen activator (PA)-inhibitor activity, both in vivo, in rats, as well as in cultured human endothelial cells. In vivo, LPS rapidly and dose-dependently (0.01-1,000 micrograms/kg) increased plasma PA-inhibitor activity. Infusion of IL-1 into rats resulted in a small but significant increase in PA-inhibitor activity in rat plasma. Likewise, in cultured human umbilical vein endothelial cells, LPS and IL-1 induced increased synthesis of PA-inhibitor. We suggest that the induced rat plasma inhibitor might be of endothelial origin.
396 citations
TL;DR: The antiviral activity of pure recombinant human TNF in a typical in vitro antiviral assay is described which was discovered while investigating the possible role of TNF as an inducer of IFN.
Abstract: Tumour necrosis factor (TNF) was first described as a factor in the serum of mice injected with tubercle bacilli (BCG) and several days later with lipopolysaccharide (LPS). The gene encoding TNF has recently been cloned and pure recombinant human TNF is now available. TNF is known for its in vivo antitumour effect and in vitro cytotoxicity on certain transformed cell lines. Similarities in amino acid sequence and biological activity to lymphotoxin and cachectin have been reported, and very recently a growth-factor-like activity on diploid fibroblasts was observed. There is no similarity between these proteins and interferons (IFNs), which are also induced during in vivo induction of TNF. Here we describe the antiviral activity of pure recombinant human TNF in a typical in vitro antiviral assay which we discovered while investigating the possible role of TNF as an inducer of IFN.
393 citations
TL;DR: Large-scale production of recombinant human GM-CSF is examined using a primate model and it is found that the continuous infusion of GM- CSF in healthy monkeys rapidly elicits a dramatic leukocytosis and a substantial reticulocytotic effect, suggesting that this protein could prove useful in several clinical situations.
Abstract: Certain proteins are known to play an important part in the proliferation, differentiation and functional activation of haematopoietic progenitor cells in vitro1,2. These proteins include erythropoietin and various colony-stimulating factors (CSFs), one of which is granulocyte–macrophage colony-stimulating factor (GM-CSF). Recently, both murine3,4 and human GM-CSF5–7 have been purified to homogeneity and complementary DNAs encoding them have been cloned. Although the in vitro activity of recombinant human GM-CSF has been investigated intensively (refs 5–15; see ref. 8 for a review), little is known about the functional activity of this protein in vivo. There is strong evidence that colony-stimulating activities produced by various human and murine tumour tissues and cell lines can stimulate granulopoiesis in mice16–26, as can human urinary extracts27,28. A partially purified preparation of human urinary colony-stimulating factor, however, proved only marginally effective in stimulating granulopoiesis in humans29. All these studies suffer from the lack of a homogeneous preparation of colony-stimulating factor. It has recently been shown that recombinant murine multi-CSF or interleukin-3 can stimulate haematopoiesis in mice in vivo30,31. Large-scale production of recombinant human GM-CSF now permits us to examine its effects in vivo using a primate model. We find that the continuous infusion of GM-CSF in healthy monkeys rapidly elicits a dramatic leukocytosis and a substantial reticulocytosis. A similar effect has been observed in one pancytopenic, immunodeficient rhesus macaque. These results suggest that GM-CSF could prove useful in several clinical situations.
389 citations
TL;DR: The studies indicate that H4/18 is a useful marker for activated endothelium in vivo and they support the relevance of in vitro studies on inducible endothelial cell functions.
Abstract: We used a murine mAb, H4/18, raised by immunization with IL-1-treated human umbilical vein endothelial cell cultures, to localize an endothelial activation antigen in induced human delayed hypersensitivity reactions (DHR) and in pathological tissues. We used streptococcus varidase to elicit DHR in human skin and we examined sequential skin biopsies with the immunoperoxidase technique. There was no staining for H4/18 binding antigen in normal endothelium of skin and other tissues; strong positive staining, localized to vascular endothelium, was seen at 16 and 23 h but disappeared by 6 d, when the DHR had faded. H4/18 binding antigen, also confined to endothelium, was detected in lymph nodes, skin, and other tissues exhibiting immune/inflammatory reactions. The studies indicate that H4/18 is a useful marker for activated endothelium in vivo and they support the relevance of in vitro studies on inducible endothelial cell functions.
387 citations
TL;DR: A major role is suggested for TNF-alpha in tumor cell destruction by aM phi in vitro and in vivo and it was shown that killing of tumor cells by murine aMphi was completely inhibited with a polyclonal antibody that neutralizes the effects of murine T NF-alpha.
Abstract: Activated macrophages (aM phi) destroy more effectively cancer cells than normal cells. The mechanism by which macrophages destroy cancer cells is not known. We report here that tumor cells susceptible to aM phi were killed by recombinant (r) tumor necrosis factor type alpha (TNF-alpha), whereas variant tumor cells resistant to aM phi after selection in vitro or in vivo were resistant to killing by rTNF-alpha. The converse selection for rTNF-alpha-resistant variants resulted in cells that were also resistant to killing by aM phi. The sensitivity of macrophage-resistant variants was not changed to other tumoricidal cells or soluble mediators, except that the macrophage-resistant variants were also resistant to the effects of another cytotoxic protein, B-cell lymphotoxin, which is structurally related to rTNF-alpha. Similar results were obtained regardless of whether short-term or long-term cytotoxic effects of aM phi were measured. Finally, it was shown that killing of tumor cells by murine aM phi was completely inhibited with a polyclonal antibody that neutralizes the effects of murine TNF-alpha. These results suggest a major role for TNF-alpha in tumor cell destruction by aM phi in vitro and in vivo.
375 citations
TL;DR: This article showed that physiological concentrations of bromide arm human eosinophils with the ability to generate and release an unusual oxidant capable of destroying a wide range of prokaryotic and eukaryotic targets.
Abstract: Eosinophils are white blood cells that in humans are found in association with helminthic infections and various inflammatory disease processes. These cells contain a unique lysosomal peroxidase that oxidizes halides to generate highly reactive and toxic hypohalous acids. Although chloride is found in vivo at concentrations at least 1000-fold greater than those of other halides, human eosinophils did not preferentially oxidize chloride under physiologic conditions. Instead, eosinophils used bromide, a halide with a hitherto unknown function in humans, to generate a halogenating oxidant with characteristics similar, if not identical, to those of hypobromous acid. These results indicate that physiological concentrations of bromide arm human eosinophils with the ability to generate and release an unusual oxidant capable of destroying a wide range of prokaryotic and eukaryotic targets.
TL;DR: Findings support the hypothesis that the subacute sensory neuronopathy is caused by an antibody that cross-reacts with a tumor cell antigen and a brain nucleoprotein.
TL;DR: The mechanisms of ROl-independent cytotoxicity are less well understood, but at least one component of the PMN's azurophil granule has been shown to exert cytotoxi#{231}ity against a munine lymphoma cell target.
TL;DR: It is suggested that the role of UA for inhibitory action on tumor promotion differs slightly from those of RA and OA, while OA and RA were ineffective in the same treatment.
TL;DR: In vivo results suggest that oligosaccharide modification of monoclonal antibodies is a preferred method of preparing conjugates, compared to more conventional methods.
Abstract: A strategy for covalent modification of monoclonal antibodies utilizing the oxidized oligosaccharide moieties on the molecule was evaluated and compared to more conventional methods. As judged by quantitative in vitro measurements, a monoclonal antibody conjugate prepared via the oligosaccharides retained the homogeneous antigen binding property and affinity of the unmodified antibody. In contrast, conjugates of the same antibody, modified to the same degree on either lysines or aspartic and glutamic acid side chains, were heterogeneous in their antigen binding and had lowered affinity. In vivo biodistribution and nuclear-imaging experiments were also performed with a second monoclonal antibody and a tumor xenograft model. Antibodies modified on the oligosaccharides with either a peptide labeled with iodine-125 or a diethylenetriaminepentaacetic acid chelate with indium-111 localize into target tumors more efficiently than the same antibody radiolabeled on either tyrosines or lysines. These in vivo results, when compared to those reported in the literature for conventionally modified antibodies, suggest that oligosaccharide modification of monoclonal antibodies is a preferred method of preparing conjugates.
TL;DR: The ability to detect differences in the permeability of the monolayers to leucine, propranolol, and sucrose with radioactive tracers suggests that this in vitro model system will be an important tool for the investigation of the role of the blood–brain barrier in the delivery of centrally acting drugs and nutrients.
Abstract: Bovine brain micro vessel endothelial cells have been isolated and grown in culture to monolayers. These endothelial cell monolayers have been characterized morphologically with electron microscopy, histochemically for brain endothelium enzyme markers, alkaline phosphatase and γ-glutamyl trans-peptidase, and by immunofluorescence to detect Factor VIII antigen, an exclusive endothelial antigen. Results of these studies indicate that the cells forming the monolayers are of endothelial origin and possess many features of the in vivo brain endothelium responsible for formation of the blood-brain barrier. This in vitro blood-brain barrier model system was used in experiments to determine the permeability of the cultured monolayer to sucrose, leucine, and propranolol. Leucine rapidly moved across the monolayers of this in vitro system and tended to plateau after approximately 10 min. In contrast, the rates of sucrose and propranolol movement were linear during a 1-hr observation period, with the rate of propranolol movement across the monolayer greater than that of sucrose. The ability to detect differences in the permeability of the monolayers to leucine, propranolol, and sucrose with radioactive tracers suggests that this in vitro model system will be an important tool for the investigation of the role of the blood-brain barrier in the delivery of centrally acting drugs and nutrients.
TL;DR: Mouse interleukin 3 (IL-3) cDNA was cloned into a plasmid construction, allowing the synthesis of very high quantities of IL-3 in Escherichia coli, and the erythroid and myeloid lineages appeared to be enhanced to the same extent.
Abstract: Mouse interleukin 3 (IL-3) cDNA was cloned into a plasmid construction, allowing the synthesis of very high quantities of IL-3 in Escherichia coli. The recombinant (r) IL-3, purified to homogeneity, was active in vitro on the proliferation and differentiation of various hematopoietic progenitor cells at 1 pM. To maintain detectable blood levels of IL-3, osmotic pumps containing rIL-3 or control solutions were placed under the skin of normal and irradiated C3H/HeJ and (BALB X B10) F1 mice. The effect of IL-3 on hematopoietic progenitor cell numbers in spleen and bone marrow was evaluated 3 and 7 days later by using an in vitro clonal assay. The results demonstrated the following: (i) Doses of IL-3 infused at the rate of 2.5-5 ng per g of body weight per hr were sufficient to increase the numbers of hematopoietic progenitors in normal mice by at least 2-fold within 3 days. (ii) In mice with progenitor cell levels depressed by sublethal irradiation, 7-day treatment with IL-3 resulted in a 10-fold increase to near normal levels. (iii) The erythroid and myeloid lineages appeared to be enhanced to the same extent. (iv) Enhancement of hematopoiesis occurred primarily in spleen, but hematopoietic foci were also evident in the liver; in contrast, total cell and progenitor cell numbers were decreased in the bone marrow.
TL;DR: The data compiled for 63 complexes of the general structural formula LAuX provide the basis for the following observations: potent in vitro cytotoxic activity is observed for substituted (phosphine) gold complexes, lack of potency in vitro correlates well with lack of antitumor activity, potent cytotoxicity in vitro is not necessarily predictive of activity in vivo.
Abstract: A series of gold(I) coordination complexes including analogues of the antiarthritic agent auranofin 1 were evaluated for in vitro cytotoxic potency against both B16 melanoma cells and P388 leukemia cells and in vivo antitumor activity against P388 leukemia in mice. A number of the complexes showed potent cytotoxic activity in vitro and antitumor activity in vivo, with the phosphine-coordinated gold(I) thiosugar complexes demonstrating the greatest in vitro and in vivo activity. The data compiled for 63 complexes of the general structural formula LAuX provide the basis for the following observations: potent in vitro cytotoxic activity is observed for substituted (phosphine) gold complexes, lack of potency in vitro correlates well with lack of antitumor activity, potent cytotoxicity in vitro is not necessarily predictive of activity in vivo, in vivo antitumor activity is generally optimized by ligation of Au(I) with a substituted phosphine and a thiosugar.
TL;DR: There are intracellular factors which influence clinical radioresponsiveness whose relative importance varies from one histological cell type to another, and there are other factors which specifically reduce radiosensitivity in vivo.
Abstract: The radiosensitivities of human tumor cell lines, grouped into 6 histological categories, have been studied using data from the published literature. The parameters alpha, beta, n, D0, D, and the surviving fraction to 2 Gy (S2) and 8 Gy (S8) were calculated. Only the two parameters mainly derived from the initial part of the survival curve, alpha and D, together with S2, provided data which were correlated with the clinical radioresponsiveness of each histological group. Thus, there are intracellular factors which influence clinical radioresponsiveness whose relative importance varies from one histological cell type to another. The value of D gave the most precise characterization of the average group radiosensitivity. It was possible to compare the in vivo radiosensitivities of non-severely hypoxic cells with those of tumor cells irradiated in vitro for 7 tumor lines grown as xenografts in mice. The average radiosensitivity was 1.9 times less in vivo than in vitro. This difference indicates that, in addition to the intrinsic factors of radioresistance demonstrated in vitro, and independently of severe hypoxia, there are other factors which specifically reduce radiosensitivity in vivo.
TL;DR: The question of whether the epidermis obtained in vitro can be considered as "normal" is discussed, and hyperproliferation would also explain the unexpected straining of basal cells by KL1 monoclonal antibody.
TL;DR: A fraction of inspired oxygen of 45% should be added to prophylactic antibiotics as standard perioperative and postoperative care and it is found that improving tissue oxygenation by administration of normobaric oxygen decreased infectious necrosis as effectively as proPHylactic antibiotic administration.
Abstract: • Since prophylactic antibiotics and changes in tissue partial pressure of oxygen may affect bacterial clearance by different mechanisms, we tested the effects of hypoxia, hyperoxia, and normoxia with and without antibiotic administration on bacterial clearance. We found that improving tissue oxygenation by administration of normobaric oxygen decreased infectious necrosis as effectively as prophylactic antibiotic administration and that improved tissue oxygenation and antibiotic administration had an additive effect. We believe that a fraction of inspired oxygen of 45% should be added to prophylactic antibiotics as standard perioperative and postoperative care. ( Arch Surg 1986;121:191-195)
TL;DR: It is shown that diverse human tumors obtained directly from surgery or biopsy can grow at high frequency in vitro for long periods of time and still maintain many of their in vivo properties.
Abstract: We show that diverse human tumors obtained directly from surgery or biopsy can grow at high frequency in vitro for long periods of time and still maintain many of their in vivo properties. The in vivo properties maintained in vitro include three-dimensional growth; maintenance of tissue organization and structure, including changes associated with oncogenic transformation; retention of differentiated function; tumorigenicity; and the growth of multiple types of cells from a single tumor.
TL;DR: Human recombinant gamma interferon (rHuIFN-γ) was found to induce tryptophan degradation in vitro in human cell cultures and in vivo in participants in phase I clinical trials.
Abstract: Human recombinant gamma interferon (rHuIFN-gamma) was found to induce tryptophan degradation in vitro in human cell cultures and in vivo in participants in phase I clinical trials. When human lung fibroblasts were treated with various concentrations of rHuIFN-gamma, they degraded tryptophan in a dose- and time-dependent manner. No tryptophan degradation was observed when cells were incubated in growth medium alone or in medium supplemented with human recombinant beta-interferon (rHuIFN-beta ser). Similarly human bladder carcinoma cells were induced to catabolize tryptophan after incubation with rHuIFN-gamma, but no activity was observed in untreated cells or cells treated with either rHuIFN-beta ser or human naturally produced alpha-interferon (HuIFN-alpha). When tryptophan plasma levels were measured in cancer patients who had received i.v. bolus injections of rHuIFN-gamma as part of a phase I clinical trial, decreased tryptophan levels were observed when compared with pretreatment values or values obtained from individuals who had received i.v. injections of HuIFN-alpha. Urine analyses were suggestive that plasma tryptophan degradation occurred via the kynurenine catabolic pathway in individuals who received rHuIFN-gamma. We conclude that tryptophan degradation is an activity induced in vitro and in vivo in response to exogenous IFN-gamma but not to IFN-alpha or IFN-beta. Tryptophan degradation may play an important role in the mechanism of antiproliferative, immunologic, and clinical side effects of IFN-gamma.
TL;DR: It is established that B16BL6 tumours in vivo can be induced to necrotize and regress by a combined systemic treatment with rTNF and murine rIFN‐γ and further evidence is given in favour of a potential clinical use of TNF in combination therapy, e.g. with IFN-γ.
Abstract: TNF, a protein released by induced macrophages, is believed to mediate, at least in part, the tumoritoxic effects of activated macrophages. In vitro, it has cyto-toxic effects on transformed cells but not on normal cells, and in vivo it causes necrosis of tumours. Recently, both human and murine TNF became available as pure recombinant proteins. Subsequent work confirmed its in vitro cytotoxic activity, selective for transformed cells, and revealed other, non-cytotoxic effects on some normal cells. In vitro, the B16BL6 melanoma cells, syngeneic with C57BL6 mice, are resistant to the cytotoxic effects of rTNF but become sensitive when they are also treated with rIFN-γ. We report that established, s.c. B16BL6 tumours in vivo can be induced to necrotize and regress by a combined systemic treatment with rTNF and murine rIFN-γ. Although TNF is not species-specific in vitro, the effects of treatment with human and murine rTNF in vivo are different: with murine rTNF, the synergism with rIFN-γ is relatively less clear, the addition of IFN-γ is not necessary to induce regression, toxicity is more pronounced and additional mechanisms of tu-moritoxicity could be involved. Relapses are frequent but complete cures have been observed. These results give further evidence in favour of a potential clinical use of TNF in combination therapy, e.g. with IFN-γ. However, there is still a need to develop better regimens, especially for consolidation, and to continue research in order to understand and limit the toxicity, which could be mediated by the activating effects of TNF on some normal cell types.
TL;DR: It is concluded that macrolide antibiotics induce P-450p, the most rapidly turning over cytochrome yet reported, by stimulating its synthesis indirectly and by blocking its degradation, significantly.
TL;DR: Poly(lactic acid) microspheres of 1–10 μm diameter prepared by emulsion deposition and containing entrapped prednisolone released the drug rapidly into an aqueous medium and may have potential as a long-acting parenteral delivery system.
TL;DR: Parasites isolated from patients who failed to respond to topical treatment were found to be susceptible to PR-MBCl in both in vitro infected macrophages and in vivo in experimentally infected BALB/c mice.
Journal Article•
TL;DR: Results of these experiments indicate that the degree of gene amplification and concentration of EGF receptors are directly correlated with the growth of these cells as solid tumors in host animals.
Abstract: To test the relationship between the concentration of epidermal growth factor (EGF) receptors and tumor growth in vivo, we measured the rate of growth of several independently isolated A431 cell lines in athymic mice. This series of A431 clonal variants with differing extents of EGF receptor gene amplification and protein expression were implanted into athymic mice and the time to solid tumor formation and rate of growth were measured. Results of these experiments indicate that the degree of gene amplification and concentration of EGF receptors are directly correlated with the growth of these cells as solid tumors in host animals. Complementary DNA hybridization analysis revealed no change in the extent of gene amplification and expression in implanted cells versus excised tumors nor any evidence of further gene rearrangement in vivo. A high concentration of EGF receptors appears to facilitate the growth of tumor cells in vivo and in vitro.
TL;DR: DAC-70 showed no effect on the production of tumour necrosis factor in vivo and did not stimulate the production by spleen cells of interleukin 2, interferon, colony-stimulating or macrophage-activating factor or of interferons by macrophages in vitro.