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41.
Taxol-mediated changes in fibrosarcoma-induced immune cell function: Modulation of antitumor activities 总被引:6,自引:0,他引:6
David W. Mullins Thomas M. Walker Carol J. Burger Klaus D. Elgert 《Cancer immunology, immunotherapy : CII》1997,45(1):20-28
The anticancer drug taxol (paclitaxel) inhibits tumors through multiple cytotoxic and cytostatic mechanisms. Independently
of these mechanisms, taxol induces distinct immunological efficacy when it acts as a second signal for activation of tumoricidal
activity by interferon-γ(IFNγ)-primed murine normal host macrophages. We reported that tumor-distal macrophages, which mediate
immunosuppression through dysregulated nitric oxide (NO) and tumor necrosis factor α (TNFα) production, are differentially
regulated by taxol. Because taxol influences tumor cell growth dynamics and activates immune cell populations, we assessed
the ex vivo immunosuppressive and antitumor activities of taxol-treated normal host and tumor-bearing host (TBH) macrophages.
Pretreatment of such cells with taxol partly reconstituted T cell alloantigen reactivity, suggesting that taxol mediates a
limited reversal of TBH macrophage immunosuppressive activity. Taxol-treated TBH macrophages significantly suppressed the
growth of fibrosarcoma cells (Meth-KDE) through soluble effector molecules and promoted direct cell-mediated cytotoxicity,
indicating that taxol enhanced tumor-induced macrophage antitumor activities. Tumor-induced helper T cells, however, showed
a higher sensitivity to direct taxol-induced suppression. These data demonstrate that taxol exerts pleiotropic effects on
antitumor immune responses with the capacity to abate the immunosuppressive activities of macrophages and promote macrophage-mediated
antitumor activities simultaneously, but also directly modulating T cell reactivity. Collectively, these studies suggest that
the antineoplastic drug taxol may impart antitumor activity through an immunotherapeutic capacity.
Received: 31 December 1996 / Accepted: 1 July 1997 相似文献
42.
Adrien P. Malick Ronald E. Garner Sandra P. Black Klaus D. Elgert 《Cellular immunology》1984,85(2):549-555
The mixed-lymphocyte reaction reactivity of normal and tumor-bearing host (TBH) T-cell subsets was examined in response to normal and TBH macrophage (Mø) supernatants. Both inhibiting and enhancing activities were identified in normal and TBH Mø supernatants. The present data suggest that TBH Mø supernatants contained more inhibitory activity than normal host Mø supernatants and that enhancing activity of Mø supernatants was restricted to the Lyt 2,3+ population of cells. TBH Lyt 2,3+ cells were more responsive to the enhancing molecule(s) than their normal counterparts. These data were consistent with studies which implicate Mø as being partially responsible for the immune dysfunction seen in TBH, and extends previous findings on the ability of Mø to regulate the immune response in an attempt to achieve homeostasis. 相似文献
43.
D Lederoun P Vandewalle AA Brahim J Moreau PA Lalèyè 《African Journal of Aquatic Science》2016,41(2):151-160
Growth, mortality, recruitment and relative yield per recruit of Sarotherodon galilaeus galilaeus from Lakes Doukon and Togbadji were studied. Data on total length, total weight and sex were recorded on a monthly basis between January and December 2013 for S. g. galilaeus captured by local fishers. The estimated asymptotic lengths L∞ were 26.2 and 23.6?cm for Lakes Doukon and Togbadji, respectively, while the growth rate K was 0.73 in Lake Doukon and 0.87 in Lake Togbadji. Estimates of fishing mortality, 0.27 and 0.47 y?1 for Doukon and Togbadji, respectively, were low relative to natural mortality, 1.51 and 1.74 y?1, respectively. Sizes at first sexual maturity were 12.8 and 13.2?cm for females and males, respectively, in Lake Doukon, and 11.5 and 12.4?cm for females and males, respectively, in Lake Togbadji. The size at first capture was estimated at 13.3 and 12.7?cm for Lakes Doukon and Togbadji, respectively, which, in the light of the size at maturity estimates, indicates that fish spawn at least once before capture. The current exploitation rates of 0.15 for Lake Doukon and 0.21 for Lake Togbadji suggest that their stocks of S. g. galilaeus are not overexploited in either lake. 相似文献
44.
45.
Overbeek MJ Boonstra A Voskuyl AE Vonk MC Vonk-Noordegraaf A van Berkel MP Mooi WJ Dijkmans BA Hondema LS Smit EF Grünberg K 《Arthritis research & therapy》2011,13(2):R61-13
Introduction
Systemic sclerosis (SSc) complicated by pulmonary arterial hypertension (PAH) carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFR- and EGFR-mmunoreactivity in lung tissue specimens from SScPAH. We compared staining patterns with idiopathic PAH (IPAH) and pulmonary veno-occlusive disease (PVOD), as SScPAH vasculopathy differs from IPAH and sometimes displays features of PVOD. Immunoreactivity patterns of phosphorylated PDGFR-β (pPDGFR-β) and the ligand PDGF-B were evaluated to provide more insight into the patterns of PDGFR-b activation.Methods
Lung tissue specimens from five SScPAH, nine IPAH, six PVOD patients and five controls were examined. Immunoreactivity was scored for presence, distribution and intensity.Results
All SScPAH and three of nine IPAH cases (P = 0.03) showed PDGFR-β-immunoreactivity in small vessels (arterioles/venules); of five SScPAH vs. two of nine IPAH cases (P = 0.02) showed venous immunoreactivity. In small vessels, intensity was stronger in SScPAH vs. IPAH. No differences were found between SScPAH and PVOD. One of five normal controls demonstrated focally mild immunoreactivity. There were no differences in PDGF-ligand and pPDGFR-b-immunoreactivity between patient groups; however, pPDGFR-b-immunoreactivity tended to be more prevalent in SScPAH small vasculature compared to IPAH. Vascular EGFR-immunoreactivity was limited to arterial and arteriolar walls, without differences between groups. No immunoreactivity was observed in vasculature of normals.Conclusions
PDGFR-β-immunoreactivity in SScPAH is more common and intense in small- and post-capillary vessels than in IPAH and does not differ from PVOD, fitting in with histomorphological distribution of vasculopathy. PDGFR-β immunoreactivity pattern is not paralleled by pPDGFR-β or PDGF-B patterns. PDGFR-β- and EGFR-immunoreactivity of pulmonary vessels distinguishes PAH patients from controls. 相似文献46.
Reference concentrations of cholecalciferol in animals: a basis for establishing non-target exposure
AAC Fairweather CT Eason PA Elder CMF Eason D Arthur 《New Zealand journal of zoology.》2013,40(4):280-289
AbstractCholecalciferol (vitamin D3) is widely used as a vertebrate pesticide in New Zealand. However, cholecalciferol also occurs naturally in animals. Therefore, when trying to determine whether a non-target animal has been exposed to cholecalciferol baits, knowledge of the baseline cholecalciferol concentrations in the animal's plasma and tissue is required. We analysed cattle, sheep, pig, deer, dog and cat plasma and liver samples for the vitamin D3 metabolite 25-hydroxycholecalciferol (25-OHD), a sensitive biomarker for cholecalciferol. Based on these data and a literature search we present 25-OHD reference ranges. We also examined the literature for 25-OHD concentrations in poisoned animals and compared these to the reference ranges. Where plasma and liver samples have 25-OHD concentrations at least four times higher than our reference ranges it is likely that the animal has been exposed to cholecalciferol baits. 25-OHD concentrations 10 times higher than the reference range indicate ingestion of abnormally high amounts of cholecalciferol. 相似文献
47.
Health organizations worldwide recommend that adults and children minimize intakes of excess energy and salty, sweet, and fatty foods (all of which are highly preferred tastes) and eat diets richer in whole grains, low- and non- fat dairy products, legumes, fish, lean meat, fruits, and vegetables (many of which taste bitter). Despite such recommendations and the well-established benefits of these foods to human health, adults are not complying, nor are their children. A primary reason for this difficulty is... 相似文献
48.
Boot EP Koning GA Storm G Wagenaar-Hilbers JP van Eden W Everse LA Wauben MH 《Arthritis research & therapy》2005,7(3):R604-R615
T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid
arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60,
indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for
immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system.
Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority
of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not
internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized
cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis.
Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate
disease development. 相似文献
49.
Pandinus imperator scorpion venom blocks voltage-gated potassium channels in GH3 cells 总被引:1,自引:1,他引:0 下载免费PDF全文
We examined the effects of Pandinus imperator scorpion venom on voltage-gated potassium channels in cultured clonal rat anterior pituitary cells (GH3 cells) using the gigohm-seal voltage-clamp method in the whole-cell configuration. We found that Pandinus venom blocks the voltage-gated potassium channels of GH3 cells in a voltage-dependent and dose-dependent manner. Crude venom in concentrations of 50-500 micrograms/ml produced 50-70% block of potassium currents measured at -20 mV, compared with 25-60% block measured at +50 mV. The venom both decreased the peak potassium current and shifted the voltage dependence of potassium current activation to more positive potentials. Pandinus venom affected potassium channel kinetics by slowing channel opening, speeding deactivation slightly, and increasing inactivation rates. Potassium currents in cells exposed to Pandinus venom did not recover control amplitudes or kinetics even after 20-40 min of washing with venom-free solution. The concentration dependence of crude venom block indicates that the toxins it contains are effective in the nanomolar range of concentrations. The effects of Pandinus venom were mimicked by zinc at concentrations less than or equal to 0.2 mM. Block of potassium current by zinc was voltage dependent and resembled Pandinus venom block, except that block by zinc was rapidly reversible. Since zinc is found in crude Pandinus venom, it could be important in the interaction of the venom with the potassium channel. We conclude that Pandinus venom contains toxins that bind tightly to voltage-dependent potassium channels in GH3 cells. Because of its high affinity for voltage-gated potassium channels and its irreversibility, Pandinus venom may be useful in the isolation, mapping, and characterization of voltage-gated potassium channels. 相似文献
50.
Howe GT; Bucciaglia PA; Hackett WP; Furnier GR; Cordonnier-Pratt MM; Gardner G 《Molecular biology and evolution》1998,15(2):160-175
The phytochrome photoreceptors play important roles in the photoperiodic
control of vegetative bud set, growth cessation, dormancy induction, and
cold-hardiness in trees. Interestingly, ecotypic differences in
photoperiodic responses are observed in many temperate- zone tree species.
Northern and southern ecotypes of black cottonwood (Populus trichocarpa
Torr. & Gray), for example, exhibit marked differences in the timing of
short-day-induced bud set and growth cessation, and these responses are
controlled by phytochrome. Therefore, as a first step toward determining
the molecular genetic basis of photoperiodic ecotypes in trees, we
characterized the phytochrome gene (PHY) family in black cottonwood. We
recovered fragments of one PHYA and two PHYB using PCR-based cloning and by
screening a genomic library. Results from Southern analyses confirmed that
black cottonwood has one PHYA locus and two PHYB loci, which we arbitrarily
designated PHYB1 and PHYB2. Phylogenetic analyses which included PHY from
black cottonwood, Arabidopsis thaliana and tomato (Solanum lycopersicum)
suggest that the PHYB/D duplications in these species occurred
independently. When Southern blots were probed with PHYC, PHYE, and PHYE
heterologous probes, the strongest bands that we detected were those of
black cottonwood PHYA and/or PHYB. These results suggest that black
cottonwood lacks members of the PHYC/F and PHYE subfamilies. Although black
cottonwood could contain additional PHY that are distantly related to known
angiosperm PHY, our results imply that the PHY family of black cottonwood
is less complex than that of other well-characterized dicot species such as
Arabidopsis and tomato. Based on Southern analyses of five black cottonwood
genotypes representing three photoperiodic ecotypes, substantial
polymorphism was detected for at least one of the PHYB loci but not for the
PHYA locus. The novel character of the PHY family in black cottonwood, as
well as the differences in polymorphism we observed between the PHYA and
PHYB subfamilies, indicates that a number of fundamental macro- and
microevolutionary questions remain to be answered about the PHY family in
dicots.
相似文献