Letter: Biphasic tumour-enhancing and tumour-inhibiting effects of non-specific immunotherapy.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Inhibition effect”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
[Animal experimental studies on the caries inhibiting effect of fluoride-containing gels].
Explore the source record for details and available documents.
Amines↗
[Immune response inhibiting effect of blood serum in dermatoses].
Explore the source record for details and available documents.
Alpha-Globulins↗
Determination of antibody avidity at the cellular level by the plaque inhibition technique: effect of valence of the inhibitor.
Inhibition of plaque formation by multivalent and univalent ligands was compared as an assay of avidity of antibody produced by PFC. Multivalent ligands are much more effective as inhibitors and their use tends to impart an appearance of lack of heterogeneity and high avidity to the PFC populations being studied. It is thus probably generally advisable to employ univalent ligands in such studies.
Aminocaproates↗
Drugs for inhibition of premature labor.
Effective inhibition of premature labor depends on prompt initiation of treatment. The author discusses factors initiating parturition, and the benefits and risks for mother and child of administration of alcohol, beta adrenergic agents, magnesium sulfate, and other agents that may counteract them.
Adrenergic beta-Agonists↗
Polyamines and drug oxidations.
The addition of spermine or of spermidine to rat liver assay systems produced marked changes in a number of microsomal drug oxidations. The hydroxylation of aniline and the N-demethylation of ethylmorphine were both enhanced with concentrations of 1-10 mM spermine or of spermidine. The results with putrescine on ethylmorphine metabolism were less dramatic, and no effect could be observed with putrescine in studies with other drug substrates. In contrast to the enhancing effects, inhibition was observed when spermine or spermidine was added to p-nitroanisole O-demethylation assay mixtures, and no effect was observed in assays for acetanilide hydroxylation. The inhibiting and enhancing effects of the polyamines can be observed in assays containing liver preparations from both male and female rats, and those from rats pretreated with phenobarbital or 3-methylcholanthrene. In all studies, the alterations were kinetically noncompetitive. The effects were shown to be independent of the NADPH-generating system and the cation requirements, and were not mediated through an interaction with NADPH-cytochrome c reductase. The possibility is considered that the enhancing and inhibiting effects may be related to the ability of these polycations to bind to microsomal membranes and cause alterations at different sites of substrate interaction.
Acetanilides↗
Evidence for a strong non-adrenergic component in the motor transmission to the rabbit vas deferens.
Isolated vas deferens preparations from 16 rabbits of the New Zealand white strain were subjected to electrical and chemical excitability under physiological conditions and under the influence of drugs. Such smooth muscle fibres were strictly confined to the terminal 3 cm. segments of the distal 'urethral' portions of the vasa deferentia. Intermittent field stimulation, at 60 second intervals, was provided by a stimulator of low output impedance under constant parameters of voltage, pulse width and frequency. Results from this investigation revealed the undermentioned anomalous but distinct findings viz: (a) the presence of a minor adrenergic component which disappeared in phentolamine but remained unaffected by prolonged exposures to phenoxybenzamine; (b) the presence of a predominantly non-adrenergic component which was totally refractory to phenoxybenzamine but suffered a weak diminution in phentolamine; and (c) the picture of a phentolamine-insensitive but twitch-inhibiting effect shared by both tyramine and noradrenaline. Rabbit vasa consistently displayed a remarkable insensitivity to the motor effects of submicromolar concentrations of the putative neurotransmitter substance i.e. noradrenaline. The indirect sympathomimetic agent, tyramine failed to elicit any contractions when employed in doses as massive as 290 micrometers. i.e. 5 x 10(-5) g/ml, except in 2 out of 14 trials when a weak phentolamine-susceptible bursts of single contractions were produced. Thus, the adrenoceptors involved in the mediation of the twitch-inhibiting effects, appear not to behave towards conventional adrenoceptor antagonists in the classified manner. It seems appropriate therefore to invoke an unknown neurotransmitter for the non-adrenergic component in this motor transmission.
Adrenergic alpha-Antagonists↗
Effect of inhibiting protein synthesis on axonal transport of membrane glycoproteins in an identified neuron of Aplysia.
Intrasonic injection of L-[3H]fucose into R2, the cholinergic giant neuron in the abdominal ganglion of the marine molluse, Aplysia californica, labeled 5 major glycoprotein membrane components, 3 of which were preferentially exported into the axon. Brief exposure to anisomycin, a potent inhibitor of protein synthesis in Aplysia, almost completely blocked the appearance of [3H]glycoprotein in the axon; but fucosylation of proteins in the cell body was only partially inhibited. Polyacrylamide gel electrophoresis showed that the 5 normal components were present in the cell body of inhibited neurons. Thus, synthesis and insertion of glycoproteins into membranes do not guarantee export from the cell body: presumably completion of transportable organelles requires continuous synthesis of new proteins. Longer exposure before injection resulted in reduced amounts of four of the glycoproteins, but one component continued to be formed. Anisomycin can be used to resolve export of glycoproteins out of the cell body from subsequent movement along the axon. When we exposed R2 to anisomycin after injection, [3H]glycoproteins, which had already entered the axon, were translocated along the axon normally; they were distributed in waves, the most distal moving at 50-60 mm/day.
Acetylcholine↗
Ecdysterone biosynthesis: a microsomal cytochrome-P-450-linked ecdysone 20-monooxygenase from tissues of the African migratory locust.
Ecdysone 20-monooxygenase, an enzyme which converts ecdysone to ecdysterone (the major moulting hormone of insects) has been characterized in cell-free preparations of tissues from African migratory locust. The product of the reaction has been identified as ecdysterone on the basis of several microchemical derivatization and chromatographic methods. Ecdysone 20-monooxygenase activity is located primarily in the microsomal fraction which also carries NADPH cytochrome c reductase and cytochrome P-450, as shown by sucrose density gradient centrifugation. Optimal conditions for the ecdysone 20-monooxygenase assay have been determined. The enzyme has a Km for ecdysone of 2.7 x 10(-7) M and is competitvely inhibited by ecdysterone (Ki = 7.5 x 10(-7) M). Ecdysone 20-monooxygenase is a typical cytochrome P-450 linked monooxygenase: the reaction requires O2 and is inhibited by CO, an effect partially reversed by white light. The enzyme is effectively inhibited by several specific monooxygenase inhibitors and by sulfhydryl reagents, but not by cyanide ions. Ecdysone elicits a type I difference spectrum when added to oxidized microsomes. NADPH acts as preferential electron donor. The transfer of reducing equivalents proceeds through NADPH cytochrome c (P-450) reductase: ecdysone 20-monooxygenase is inhibited by cytochrome c. Both NADPH cytochrome c reductase and ecdysone 20-monooxygenase are inhibited by NADP+ and show a similar Km for NADPH. The Malpighian tubules have the highest specific activity of ecdysone 20-monooxygenase, while fat body contain most of the cytochrome P-450 and NADPH cytochrome c reductase.
Animals↗
[Comparative study of effect of 4 furochromone derivatives on isoprenaline induced plasma renin activity increase in anesthetized dogs. Relationship of beta-adrenolytic effect and inhibition of plasma renin increase].
Explore the source record for details and available documents.
Adrenergic beta-Antagonists↗
Determination of inorganic pyrophosphatase in rat odontoblast layer by a radiochemical method.
The enzyme inorganic pyrophosphatase (PPiase, EC 3.6.1.1) from the odontoblastic layer of rat incisors has been studied by means of a radiochemical micromethod. The enzyme was incubated with 32P-pyrophosphate in tris-HCl buffer at 37 degrees C. The reaction was linear with time for at least 45 min, and the pH optimum was found to be 8.8, independent of the amount of pyrophosphate present. Heating the enzyme at 56 degrees C inhibited the enzyme activity rapidly, Mg2+ ions activated the enzyme by 15% at an ion concentration of 4 mM, while higher concentrations were inhibitory. Ca2+ ions and PO43-ions inhibited the enzyme at all concentrations. F- ions did not affect the PPiase at concentrations below 8 mM, whereas higher concentrations had an inhibiting effect. Urea was found to inhibit the enzyme at concentrations above 1.5 M, while EDTA was a strong inhibitor at very low concentrations. The characteristics of PPiase agree well with the properties of the enzyme nonspecific alkaline phosphatase (EC 3.1.3.1.) studied earlier.
Animals↗
Inhibition of vesicular stomatitis virus multiplication in Vero cells by 2-deoxy-D-glucose.
2-Deoxy-D-glucose (DOG) effectively inhibited vesicular stomatitis virus (VSV) multiplication in Vero cells when pyruvate-containing medium was used as an energy source. The effectiveness of the antimetabolite was markedly reduced by substituting glucose for pyruvate in the maintenance medium. Addition of DOG at intervals during the viral growth cycle caused a notable decrease in viral yields. This inhibiting effect was reversed by mannose and to a lesser extent by glucose. VSV-RNA synthesis was greatly reduced, thereby eventually resulting in decreased levels of virus proteins. Polyacrylamide gel electrophoresis of purified VSV grown in medium containing pyruvate and DOG revealed the presence of two peaks in the region of the virus G protein. Possibly, DOG induces the synthesis of aberrant viral proteins which become incorporated into the viral membrane, resulting in noninfectious particles.
Animals↗
Lectins in the hemolymph of Japanese horseshoe crab, tachypleus tridentatus.
The hemolymph of the Japanese horseshoe crab, Tachypleus tridentatus contains lectins which agglutinate mammalian erythrocytes. Affinity chromatographic purification of the lectins using bovine submaxillary gland mucin-conjugated Sepharose resulted in the separation of the lectins into four fractions; one major and three minor lectins. Protein subunits revealed by polyacrylamide gel electrophoresis and the immunoprecipitin line of these lectins against antiserum to crude lectins were unique to each fraction. The activities of all the lectins were optimal at pH values between 6 and 8, and were destroyed by heating at 60 degrees C. Calcium chloride augumented the activities of three lectins, but the major lectin was not influenced by the salt. Bovine erythrocytes were not agglutinated by any of the lectins and comparative agglutination titers for other erythrocytes from various sources were different among these lectins. The activities of all the lectins were inhibited by N-acetylamino sugars. They were more effectively inhibited by glycoproteins which contain sialic acid.
Animals↗
Biomarker Analysis from Patients with Metastatic PDAC Treated with TGFβ Antibody NIS793 plus Abraxane + Gemcitabine versus Abraxane + Gemcitabine Alone in a Phase II, Open-Label, Randomized Study.
PURPOSE: Transforming growth factor β (TGFβ) plays a dual role in cancer, acting as a tumor suppressor early in the disease but promoting progression and immune evasion when dysregulated. In pancreatic ductal adenocarcinoma (PDAC), TGFβ-driven desmoplasia fosters chemoresistance and immunosuppression, limiting therapeutic efficacy. NIS793, a fully human mAb targeting TGFβ, demonstrated antifibrotic and immunomodulatory activity in preclinical models and early-phase trials. PATIENTS AND METHODS: We conducted a randomized, open-label, phase II study in treatment-naïve patients with metastatic PDAC (mPDAC) to evaluate NIS793 ± spartalizumab (anti-PD-1) combined with nab-paclitaxel (or Abraxane)/gemcitabine (ABRA/GEM) versus ABRA/GEM alone. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), safety, pharmacokinetics, and biomarker analyses. Exploratory assessments included paired tumor RNA sequencing, cell-free DNA profiling, and plasma proteomics. RESULTS: NIS793 demonstrated target engagement and suppression of TGFβ signaling, confirmed by transcriptomic and proteomic analyses. Stromal remodeling was evident, with significant downregulation of cancer-associated fibroblast markers (Acta2, Fap) and collagen-related signatures. Despite proof of mechanism, clinical efficacy was not observed: Median PFS and OS were comparable or numerically worse in the NIS793 arm versus control (HR for OS in NIS793 + ABRA/GEM vs. ABRA/GEM: 1.32; 95% confidence interval, 0.84-2.07). The safety profile was manageable, with no unexpected toxicities. Biomarker data revealed increased expression of neutrophil-related genes after treatment, suggesting potential induction of tumor-promoting inflammation. CONCLUSIONS: NIS793 effectively inhibited TGFβ signaling and led to stromal remodeling but failed to improve outcomes in mPDAC. These findings highlight the complexity of TGFβ biology and caution against its blockade in combination with chemotherapy for PDAC. Future strategies should consider context-dependent effects of TGFβ inhibition.
Humans↗
Study on the mechanism of BGN in progression and metastasis of ccRCC.
PURPOSE: To investigate the role of Biglycan(BGN) in the progression and metastasis of clear cell renal cell carcinoma(ccRCC). METHODS: Based on multiple public databases, we investigated the expression level of BGN in ccRCC, its clinical significance, and its association with immune cells. Real-time fluorescence quantitative polymerase chain reaction(PCR) was employed to validate BGN expression in tumor and adjacent normal tissues from ten patients. We utilized RNA sequencing results for further analysis, including differential gene analysis, GO-KEGG analysis, and GSEA analysis, to identify the signaling pathways through which BGN exerts its effects. BGN knockdown cells(786-0 and Caki-1) were generated through lentiviral transfection to examine the impact of BGN on ccRCC. Cell proliferation, migration, and invasion were assessed using CCK8, colony formation, wound healing, Transwell migration, and invasion assays, respectively. RESULTS: Our findings from database analysis and PCR revealed a significant upregulation of BGN expression in kidney cancer tissues compared to normal tissues. Further analysis demonstrated a correlation between high BGN expression and ccRCC progression and immune infiltration. In vitro experiments confirmed that BGN silencing effectively inhibited cell proliferation, migration, and invasion of ccRCC. Mechanistically, these effects may be mediated through the MAPK signaling pathway. CONCLUSION: BGN potentially plays a pivotal role in the progression and metastasis of ccRCC, possibly acting through the MAPK signaling pathway. Therefore, BGN holds promise as a potential therapeutic target for ccRCC.
Humans↗
Biocontrol efficacy of Bacillus albus SSR3 for controlling postharvest fungal pathogens and mycotoxin contamination.
Sweetpotato black rot, caused by Ceratocystis fimbriata, is a major postharvest disease that leads to substantial storage losses worldwide. In this study, a salt-tolerant rhizobacterial strain, Bacillus albus SSR3, was isolated from the rhizosphere of sweetpotato grown in saline-alkali soil, with broad-spectrum antagonistic activity against postharvest fungal pathogens. LC-MS/MS analysis revealed diverse bioactive metabolites associated with its antifungal activity. Integrated transcriptomic and metabolomic analyses showed that SSR3 bioactive metabolites extensively reprogrammed fungal metabolism, particularly pathways involved in carbohydrate and amino acid metabolism, antioxidant defense, and energy production. These alterations were accompanied by disruption of cell wall and membrane integrity, excessive reactive oxygen species accumulation, and mitochondrial dysfunction, ultimately inhibiting fungal growth. Here, we also found that SSR3 bioactive metabolites effectively inhibited aflatoxin B1 production by Aspergillus flavus and deoxynivalenol accumulation in Fusarium graminearum. In vivo assays further demonstrated that SSR3 bioactive metabolites significantly reduced sweetpotato black rot severity and effectively limited fungal colonization and mycotoxin contamination in stored agricultural commodities. Collectively, our findings demonstrate that B. albus SSR3 suppresses postharvest fungal pathogens through coordinated metabolic reprogramming, oxidative stress induction, and cellular integrity disruption, highlighting its potential as a sustainable biocontrol agent for postharvest disease management.
Bacillus albus↗
Monoanion inhibition and 35Cl nuclear magnetic resonance studies of renal dipeptidase.
Kinetic analyses of monoanion inhibition and 15Cl nuclear magnetic resonance at 5.88 MHz were employed to study monoanion interactions with the zinc metalloenzyme, renal dipeptidase. The enzyme-catalyzed hydrolysis of glycyldehydrophenylalanine exhibited competitive inhibition when the reaction rate was determined in the presence of the monovalent anions fluoride, chloride, bromide, iodide, azide, nitrate, or thiocyanate or upon the addition of the divalent anion, sulfate. Competitive inhibition was produced by these anions. One anion was bound per enzyme molecule, and except in the case of fluoride all of the anions appeared to bind at the same site. Cyanide ion produced a much more effective inhibition of renal dipeptidase than the other monoanions, and it was shown that two cyanide ions were bound per enzyme molecule. An investigation of the effect of pH upon monoanion inhibition suggested that the anion inhibitors bind to the group with a pK of approximately 7.8. Complete dissociation of this group (approximately pH 8.4) eliminates the inhibitory effect of anions. The 35Cl line broadening produced by renal dipeptidase in 0.5 M NaCl solutions was 100 times more effective than that produced by equivalent concentrations of aquozinc(II). The line broadening was dependent upon the concentration of the metalloenzyme and independent of the frequency of the exciting radiation. When zinc ion was removed from the metalloenzyme by dialysis or when chloride was titrated from the metalloenzyme by cyanide, line broadening was decreased. Treatment of renal dipeptidase with saturating concentrations of the competitive inhibitor, guanosine triphosphate, in the presence of 0.5 M NaCl also produced a significant decrease in the 35Cl line width. The 35Cl line broadening produced by renal dipeptidase was shown to decrease with increasing pH through the range pH 5.8-10.8. This line-width variation with pH appeared to result from the titration of a site on the metalloprotein with an approximate pK of 7.4. Temperature studies of 35Cl line broadening by the metalloenzyme in the presence of chloride and cyanide inhibitors suggest that the fast exchange process pertains and that the dominant relaxation mechanism is quadrupolar in nature.
Animals↗
Bergamottin, A Natural Bioactive Compound, Inhibits Dabie Bandavirus Infection In Vitro and In Vivo.
Severe fever with thrombocytopenia syndrome (SFTS) is a novel, highly fatal disease caused by Dabie bandavirus (DBV), also referred to as severe fever with thrombocytopenia syndrome virus (SFTSV). DBV is endemic to many Asian countries, and its incidence has recently increased. However, there are currently no specific therapies for combating DBV infection. Here we verified whether the natural bioactive compound, bergamottin, effectively inhibits DBV in vitro and in vivo. A primary in vitro study suggested that bergamottin suppressed DBV infection both in Vero E6 and Huh-7 cells in a dose-dependent manner. Time-of-addition assay revealed that bergamottin interferes with DBV infection at multiple stages of the viral life cycle. Moreover, bergamottin inhibits viral internalization and effectively reduces viral genome replication. The efficacy of bergamottin at doses of 75 and 120 mg/kg/d against DBV infection in an IFNAR-/- mouse infection model was investigated. Oral delivery at a dose of 120 mg/kg/d significantly reduced the number of the viral RNA copies in the kidneys, spleen, and lungs. These findings highlight that bergamottin is a promising agent that could be further developed as a therapeutic agent against DBV infection.
Animals↗