Demonstration and Quantitation of Pharmacological Inhibition of Pulmonary Uptake of N-lsopropyl-123l-p-lodoamphetamine by Propranolol

1989 ◽  
Vol 28 (03) ◽  
pp. 100-104 ◽  
Author(s):  
S. F. Akber
Keyword(s):  
Binding Sites ◽  
Bolus Injection ◽  
Cell Function ◽  
Lung Pathology ◽  
Lung Uptake ◽  
Pharmacological Inhibition ◽  
Sensitive Index ◽  
Pulmonary Uptake ◽  
First Pass

The first-pass pulmonary extraction values of N-lsopropyl-123l-p-lodoamphetamine (123I-IMP) in pretreated dogs decreases from 90 to 62% as the amount of propranolol increases from 0 to 20 mg. The first-pass pulmonary extraction values of 123I-IMP in dogs with a simultaneous bolus injection of propranolol decreases from 90 to 62% as the amount of propranolol increases from 0 to 10 mg. The pulmonary extraction of 123I-IMP with a simultaneous bolus injection of ketamine and 123I-IMP decreases from 90 to 64% as the ketamine dose increases from 0 to 100 mg. These results suggest that the pulmonary uptake of 123I-IMP may be at least partially mediated by receptors. They also indicate that endothelial metabolic cell function may be a useful index of early lung pathology. Furthermore, studies of the degree of lung uptake may be a sensitive index of pathologic states in which alterations of amine binding sites have occurred.

Increases in testosterone secretion in adult rams with immunoneutralization of endogenous estradiol occur in the absence of increases in pulsatile LH release or testicular LH receptors

1989 ◽  
Vol 120 (2) ◽  
pp. 180-186 ◽  
Author(s):  
Lee M. Sanford
Keyword(s):  
Binding Sites ◽  
Cell Function ◽  
Passive Immunization ◽  
Serum Testosterone ◽  
Experimental Period ◽  
Pulse Amplitude ◽  
Testicular Biopsy ◽  
Binding Activity ◽  
Testosterone Secretion ◽  
Lh Release

Abstract. The testes of the ram become more responsive to LH stimulation following immunoneutralization of endogenous estradiol. The possibility that testosterone secretion is facilitated by increased LH-binding activity in the testes was investigated in the present study conducted with adult Dorset × Leicester × Suffolk rams during the time of testicular recrudescence. Patterns of episodic LH release and testosterone secretion (days –5, 10 and 24) and LH-binding activity in testicular biopsy samples (days –1, 14 and 28) were assessed on the days indicated relative to the onset of passive immunization and the establishment of relatively low titres (~1:200) of estradiol antiserum. During the experimental period, mean serum testosterone concentration increased by approximately 150% for the immunized rams as basal concentration and pulse amplitude increased, while all characteristics of testosterone secretion remained unchanged for the nonimmunized rams. Characteristics of LH release and the concentration of LH-binding sites in the testes, however, were always similar for both groups of rams. Further, group differences in FSH and PRL secretion and in the concentration of testicular FSH-binding sites did not occur. These results provide evidence for an estradiol direct (gonadotropin independent) negativefeedback component in the regulation of Leydig cell function in the ram.

scholarly journals ERAP1 Controls the Interaction of the Inhibitory Receptor KIR3DL1 With HLA-B51:01 by Affecting Natural Killer Cell Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Silvia D’Amico ◽  
Valerio D’Alicandro ◽  
Mirco Compagnone ◽  
Patrizia Tempora ◽  
Giusy Guida ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Subset ◽  
Human Tumor ◽  
Hla Class I ◽  
Class I ◽  
Pharmacological Inhibition ◽  
Mhc Class I Molecules

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses by trimming peptides for presentation by major histocompatibility complex (MHC) class I molecules. Previously, we have shown that genetic or pharmacological inhibition of ERAP1 on murine and human tumor cell lines perturbs the engagement of NK cell inhibitory receptors Ly49C/I and Killer-cell Immunoglobulin-like receptors (KIRs), respectively, by their specific ligands (MHC class I molecules), thus leading to NK cell killing. However, the effect of ERAP1 inhibition in tumor cells was highly variable, suggesting that its efficacy may depend on several factors, including MHC class I typing. To identify MHC class I alleles and KIRs that are more sensitive to ERAP1 depletion, we stably silenced ERAP1 expression in human HLA class I-negative B lymphoblastoid cell line 721.221 (referred to as 221) transfected with a panel of KIR ligands (i.e. HLA-B*51:01, -Cw3, -Cw4 and -Cw7), or HLA-A2 which does not bind any KIR, and tested their ability to induce NK cell degranulation and cytotoxicity. No change in HLA class I surface expression was detected in all 221 transfectant cells after ERAP1 depletion. In contrast, CD107a expression levels were significantly increased on NK cells stimulated with 221-B*51:01 cells lacking ERAP1, particularly in the KIR3DL1-positive NK cell subset. Consistently, genetic or pharmacological inhibition of ERAP1 impaired the recognition of HLA-B*51:01 by the YTS NK cell overexpressing KIR3DL1*001, suggesting that ERAP1 inhibition renders HLA-B*51:01 molecules less eligible for binding to KIR3DL1. Overall, these results identify HLA-B*51:01/KIR3DL1 as one of the most susceptible combinations for ERAP1 inhibition, suggesting that individuals carrying HLA-B*51:01-like antigens may be candidates for immunotherapy based on pharmacological inhibition of ERAP1.

Importance of the liver in plasma clearance of hepatocyte growth factors in rats

1992 ◽  
Vol 263 (5) ◽  
pp. G642-G649 ◽  
Author(s):  
K. X. Liu ◽  
Y. Kato ◽  
M. Narukawa ◽  
D. C. Kim ◽  
M. Hanano ◽  
...  
Keyword(s):  
Binding Sites ◽  
Early Phase ◽  
Trichloroacetic Acid ◽  
Plasma Clearance ◽  
Cell Surfaces ◽  
Receptor Mediated Endocytosis ◽  
Hepatocyte Growth Factors ◽  
Internalization Mechanism ◽  
First Pass ◽  
Hepatocyte Growth

After intravenous administration of 125I-labeled hepatocyte growth factor (HGF), trichloroacetic acid-precipitable radioactivity in the plasma disappeared rapidly with an early phase half-life of 4 min. The amounts of 125I-HGF distributed to the liver, adrenal, spleen, kidney, and lung tissues were much greater than those that could be accounted for by distribution to the extracellular space alone. The first-pass removal of 125I-HGF by the liver was approximately 26%; the liver accounted for approximately 70% of early-phase removal. The hepatic handling was also analyzed using a single-pass perfused liver system. The steady-state extraction ratio of tracer 125I-HGF was 0.48 but dropped to 0.23 in the presence of excess HGF (135 pM), demonstrating hepatic removal saturation of HGF. In the presence of excess HGF, the heparin-washable 125I-HGF, the heparin-resistant and acid-washable 125I-HGF, and the internalized 125I-HGF dropped to 54, 31, and 32% of the control values. The presence of at least two binding sites for HGF on the liver cell surfaces was made clear: the heparin-washable site and the heparin-resistant and acid-washable binding site, considered to have higher affinity for HGF. The internalization of 125I-HGF was observed to some extent even in the presence of excess HGF and phenylarsine oxide, known to be an inhibitor of polypeptides receptor-mediated endocytosis, suggesting the contribution of a relatively nonspecific internalization mechanism as well as receptor-mediated endocytosis.

The Pulmonary First-pass Uptake of Five Nondepolarizing Muscle Relaxants in the Pig 

1999 ◽  
Vol 90 (2) ◽  
pp. 477-483 ◽  
Author(s):  
Ton M. Beaufort ◽  
Johannes H. Proost ◽  
Martin C. Houwertjes ◽  
Jan Roggeveld ◽  
Mark J.K. H. Wierda
Keyword(s):  
Mean Transit Time ◽  
Onset Time ◽  
Muscle Relaxants ◽  
Arterial Blood ◽  
Tibialis Muscle ◽  
Pulmonary Uptake ◽  
Org 9487 ◽  
First Pass ◽  
The Right ◽  
Org 7617

Background It is not known whether the lungs influence the early pharmacokinetics of muscle relaxants and, if they do, whether differences in pulmonary uptake contribute to the differences in potency and/or onset time among muscle relaxants. Because the lungs are uniquely positioned, receive the entire cardiac output, have a large capillary surface area, and can temporarily store various basic drugs, the authors determined whether substantial pulmonary first-pass uptake of muscle relaxants occurs. Methods In 14 pigs, rocuronium, vecuronium, Org 9487, Org 7617, or d-tubocurarine were administered simultaneously with indocyanin green within 1 s into the right ventricle, and then arterial blood was sampled every 1.2 s (in the first min). The tibialis muscle response was registered mechanomyographically. Results The maximum block was 93% (68-100% [median and range]). Onset times ranged from 83 s (78-86 s) for rocuronium to 182 s (172-192 s) for d-tubocurarine. Fraction-versus-time outflow curves showed that the peak of muscle relaxants and indocyanin green occurred almost simultaneously. Pulmonary first-pass retention was negligible. The retention of muscle relaxants at 95% passage of indocyanin green was -9% (-31 to 18%). The difference in the mean transit time between muscle relaxant and indocyanin green was 1.0 (0.8 to 1.4), 0.2 (-0.8 to 0.3), 0.3 (0.2 to 0.4), 0.5 (0.2 to 1.3), and -2.2 s for rocuronium, vecuronium, Org 9487, Org 7617, and d-tubocurarine, respectively. Conclusions There is no substantial pulmonary first-pass uptake of rocuronium, vecuronium, Org 9487, Org 7617, or d-tubocurarine in pigs. Therefore, differences in pulmonary first-pass uptake do not contribute to the differences in potency and/or onset time among muscle relaxants.

ASXL2 Is a Novel Mediator of RUNX1-ETO Transcriptional Function and Collaborates with RUNX1-ETO to Promote Leukemogenesis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 302-302
Author(s):  
Jean-Baptiste Micol ◽  
Nicolas Duployez ◽  
Alessandro Pastore ◽  
Robert Williams ◽  
Eunhee Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Line ◽  
Hematopoietic Stem Cell ◽  
Binding Sites ◽  
Target Genes ◽  
Cell Function ◽  
Rna Seq ◽  
Hematopoietic Stem

Abstract Mutations in Addition of Sex Combs Like 1 (ASXL1) are common in patients with myeloid leukemias. More recently, mutations in ASXL2, a paralog of ASXL1 with ~40% shared amino acid homology, have been discovered to occur specifically in patients with acute myeloid leukemia (AML) patients bearing the RUNX1-ETO (AML1-ETO; RUNX1-RUNX1T1) translocation and are amongst the most common mutations in RUNX1-ETO AML (mutated in 20-25% of patients). Although ASXL1 is critical for Polycomb Repressive Complex 2 function in myeloid hematopoietic cells and loss of Asxl1 recapitulates key aspects of myelodysplastic syndrome (MDS), the function of ASXL2 in normal or malignant hematopoiesis is unknown. We therefore set out to perform a functional comparison of ASXL1and ASXL2on hematopoiesis and transcription and determine the functional basis for frequent mutations in RUNX1-ETO AML. In vitro analyses of ASXL2 insertion/deletion mutations revealed that these mutations resulted in substantial reduction of ASXL2 protein expression, stability, and half-life. We therefore generated Asxl2 conditional knockout (cKO) mice to delineate the effect of ASXL2 loss on hematopoiesis. Competitive (Fig. 1A) and noncompetitive transplantation revealed that Asxl2 or compound Asxl1/2 loss resulted in cell-autonomous, rapid defects of hematopoietic stem cell function, self-renewal, and number with peripheral blood leukopenia and thrombocytopenia but without any obvious MDS features- phenotypes distinct from Asxl1 cKO mice. Mice with heterozygous deletion of Asxl2 demonstrated an intermediate phenotype between control and homozygous cKO mice indicating a gene dosage effect of Asxl2 loss. RNA sequencing (RNA-seq) of hematopoietic stem/progenitor cells from Asxl2- and Asxl1-deficient mice revealed twenty-fold greater differentially expressed genes in Asxl2 cKO mice relative to Asxl1 cKO mice. Interestingly, genes differentially expressed with Asxl2 loss significantly overlapped with direct transcriptional targets of RUNX1-ETO, findings not seen in Asxl1 cKO mice (Fig. 1B). Asxl2 target genes appeared to also be targets of RUNX1, a key gene repressed by RUNX1-ETO to promote leukemogenesis. Consistent with this, genome-wide analysis of Asxl2 binding sites through anti-Asxl2 ChIP-seq revealed that Asxl2 binding sites substantially overlap with those of Runx1. Overall, the above data suggest that Asxl2 may be a critical mediator of RUNX1-ETO mediated leukemogenesis by affecting the expression of RUNX1 and/or RUNX1-ETO target genes. RNA-seq of primary RUNX1-ETO AML patient samples revealed that ASXL2-mutant RUNX1-ETO patients form a distinct transcriptional subset of RUNX1-ETO AML (Fig. 1C) suggesting a specific role of ASXL2 in leukemogenesis. To functionally interrogate the role of ASXL2 loss in RUNX1-ETO mediated leukemogenesis we first utilized an in vitro model with RNAi-mediated depletion of ASXL1 or ASXL2 in the SKNO1 cell line (the only ASXL-wildtype human RUNX1-ETO cell line). RNA-seq revealed distinct target genes dysregulated by ASXL1 versus ASXL2 loss in these cells without any significant overlap. Anti-ASXL2, RUNX1, and RUNX1-ETO ChIPSeq in SKNO1 cells revealed significant co-occupancy of ASXL2 with RUNX1 and RUNX1-ETO binding sites. Moreover, analysis of histone modification ChIPSeq revealed an enrichment in intergenic and enhancer H3K4me1 abundance following ASXL2 loss in SKNO1 cells. Next, to understand the in vivo effects of Asxl2 loss in the context of RUNX1-ETO, we performed retroviral bone marrow (BM) transplantation assays using RUNX1-ETO9a in Asxl2 cKO mice. In contrast to the failure of hematopoietic stem cell function with Asxl2 deletion alone, mice reconstituted with BM cells expressing RUNX1-ETO9a in Asxl2-deficient background had a shortened leukemia-free survival compared to Asxl2 -wildtype control. Overall, these data reveal that ASXL2 is required for hematopoiesis and has differing biological and transcriptional functions from ASXL1. Moreover, this work identifies ASXL2 as a novel mediator of RUNX1-ETOtranscriptional function and provides a new model of penetrant RUNX1-ETO AML based on genetic events found in a substantial proportion of t(8;21) AML patients. Further interrogation of the enhancer alterations generated by ASXL2 loss in RUNX1-ETO AML may highlight new therapeutic approaches for this subset of AML. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Plasminogen Activation System and the Regulation of Catecholaminergic Function

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Hongdong Bai ◽  
Samir Nangia ◽  
Robert J. Parmer
Keyword(s):  
Plasminogen Activator ◽  
Binding Sites ◽  
Cell Function ◽  
Specific Binding ◽  
Neurosecretory Cells ◽  
Plasminogen Activation ◽  
Plasmin Activity ◽  
Plasminogen Activation System ◽  
Activation System ◽  
Catecholaminergic Cells

The local environment of neurosecretory cells contains the major components of the plasminogen activation system, including the plasminogen activators, tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), as well as binding sites for t-PA, the receptor for u-PA (uPAR), and also the plasminogen activator inhibitor, PAI-1. Furthermore, these cells express specific binding sites for plasminogen, which is available in the circulation and in interstitial fluid. Colocalization of plasminogen and its activators on cell surfaces provides a mechanism for promoting local plasminogen activation. Plasmin is retained on the cell surface where it is protected from its inhibitor,α2-antiplasmin. In neurosecretory cells, localized plasmin activity provides a mechanism for extracellular processing of secreted hormones. Neurotransmitter release from catecholaminergic cells is negatively regulated by cleavage products formed by plasmin-mediated proteolysis. Recently, we have identified a major plasminogen receptor, Plg-RKT. We have found that Plg-RKTis highly expressed in chromaffin cells of the adrenal medulla as well as in other catecholaminergic cells and tissues. Plg-RKT-dependent plasminogen activation plays a key role in regulating catecholaminergic neurosecretory cell function.

scholarly journals FURTHER OBSERVATIONS ON THE MECHANISM OF RETICULOENDOTHELIAL BLOCKADE

1967 ◽  
Vol 126 (6) ◽  
pp. 1087-1098 ◽  
Author(s):  
David J. Drutz ◽  
M. Glenn Koenig ◽  
David E. Rogers
Keyword(s):  
Binding Sites ◽  
Wistar Rats ◽  
Cell Function ◽  
Phagocytic Cells ◽  
Macrophage Cell ◽  
Large Numbers ◽  
Cell Membrane Binding ◽  
Rat Livers ◽  
Phagocytic Cell Function ◽  
Membrane Binding Sites

The mechanism of the reticuloendothelial "blockade" which followed injection of large quantities of chromic phosphate without exogenous stabilizing material was investigated in Wistar rats. The RE blockade observed for several hours after induction appeared related to the continuing circulation of the chromic phosphate-blockading dose, and a reduction in the size of the particles used enhanced blockade. RE blockade appeared to be particles specific and was not related to a generalized depression of RE-phagocytic cell function. Studies in isolated perfused rat livers appeared to eliminate saturation of particle-specific macrophage clones as a likely explanation of blockade, and blockade could not be explained on the basis of depletion of serum opsonins. In the system employed, it is postulated that blockade occurs when large numbers of circulating particles saturate specific macrophage cell membrane-binding sites rather than from physical stuffing of RE-phagocytic cells.

Benzodiazepines inhibit transport-related oxygen consumption in thick ascending limb

1988 ◽  
Vol 255 (3) ◽  
pp. C385-C392 ◽  
Author(s):  
F. N. Ziyadeh ◽  
Z. S. Agus
Keyword(s):  
Oxygen Consumption ◽  
Amphotericin B ◽  
Binding Sites ◽  
Cell Function ◽  
Chloride Transport ◽  
Specific Binding ◽  
Rabbit Kidney ◽  
Thick Ascending Limb ◽  
Total Oxygen ◽  
Sodium Uptake

Specific binding sites for benzodiazepines (BZD) have been identified in several nonneuronal tissues including the kidney where they are localized predominantly to the tubular epithelium of the thick ascending limb of Henle's loop (TALH). The physiological function of these nonneuronal (peripheral) BZD-binding sites is undefined, but it has been suggested that they may represent receptors for putative endogenous ligands that may modulate cell function. In the current study, we examined the in vitro effects of diazepam and Ro5-4864, a specific peripheral BZD-receptor agonist, on the oxygen consumption of medullary TALH tubule suspensions of rabbit kidney. Maximal inhibition of total oxygen consumption was achieved at a dose of 5 X 10(-4) M of either agent. On average, diazepam and Ro5-4864 reduced total oxygen consumption by 41 and 44%, respectively. The predominant inhibition was in the ouabain-sensitive component of oxygen consumption, which suggests that BZDs inhibit active sodium-chloride transport in the TALH. To assess whether this inhibition depends on sodium uptake, TALH tubules were pretreated with amphotericin B (2 X 10(-6) M) to enhance sodium uptake and stimulate basal oxygen consumption; subsequent addition of Ro5-4864 (5 X 10(-4) M) still reduced oxygen consumption to a residual value that was not different from that in TALH tubules treated with Ro5-4864 but without pretreatment with amphotericin B. This suggests that BZD inhibition of transport-related oxygen consumption is not caused by diminution of sodium uptake into cells and thus appears to be distinct from the effect of furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

β-Cell “rest” accompanies reduced first-pass hepatic insulin extraction in the insulin-resistant, fat-fed canine model

2007 ◽  
Vol 292 (6) ◽  
pp. E1581-E1589 ◽  
Author(s):  
Stella P. Kim ◽  
Martin Ellmerer ◽  
Erlinda L. Kirkman ◽  
Richard N. Bergman
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Physiological Mechanism ◽  
Initial Increase ◽  
Β Cell ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
First Pass ◽  
Hepatic Insulin Extraction

During insulin resistance, glucose homeostasis is maintained by an increase in plasma insulin via increased secretion and/or decreased first-pass hepatic insulin extraction. However, the relative importance of insulin secretion vs. clearance to compensate for insulin resistance in obesity has yet to be determined. This study utilizes the fat-fed dog model to examine longitudinal changes in insulin secretion and first-pass hepatic insulin extraction during development of obesity and insulin resistance. Six dogs were fed an isocaloric diet with an ∼8% increase in fat calories for 12 wk and evaluated at weeks 0, 6, and 12 for changes in 1) insulin sensitivity by euglycemic-hyperinsulinemic clamp, 2) first-pass hepatic insulin extraction by direct assessment, and 3) glucose-stimulated insulin secretory response by hyperglycemic clamp. We found that 12 wk of a fat diet increased subcutaneous and visceral fat as assessed by MR imaging. Consistent with increased body fat, the dogs exhibited a ∼30% decrease in insulin sensitivity and fasting hyperinsulinemia. Although insulin secretion was substantially increased at week 6, β-cell sensitivity returned to prediet levels by week 12. However, peripheral hyperinsulinemia was maintained because of a significant decrease in first-pass hepatic insulin extraction, thus maintaining hyperinsulinemia, despite changes in insulin release. Our results indicate that when obesity and insulin resistance are induced by an isocaloric, increased-fat diet, an initial increase in insulin secretion by the β-cells is followed by a decrease in first-pass hepatic insulin extraction. This may provide a secondary physiological mechanism to preserve pancreatic β-cell function during insulin resistance.

scholarly journals Pharmacological Inhibition of TFF3 Enhances Sensitivity of CMS4 Colorectal Carcinoma to 5-Fluorouracil through Inhibition of p44/42 MAPK

2019 ◽  
Vol 20 (24) ◽  
pp. 6215 ◽  
Author(s):  
Ru-Mei Chen ◽  
Yi-Shiou Chiou ◽  
Qing-Yun Chong ◽  
Han-Ming Poh ◽  
Tuan-Zea Tan ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Cell Function ◽  
Inhibitory Effect ◽  
Survival Outcome ◽  
Trefoil Factor ◽  
Functional Roles ◽  
Pharmacological Inhibition ◽  
Trefoil Factor 3 ◽  
Synergistic Inhibitory Effect

Increased expression of trefoil factor 3 (TFF3) has been reported in colorectal carcinoma (CRC), being correlated with distant metastasis and poor clinical outcomes. Amongst the CRC subtypes, mesenchymal (CMS4) CRC is associated with the worst survival outcome. Herein, the functional roles of TFF3 and the pharmacological inhibition of TFF3 by a novel specific small molecule TFF3 inhibitor—2-amino-4-(4-(6-fluoro-5-methylpyridin-3-yl)phenyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (AMPC) in CMS4 CRC was explored. Forced expression of TFF3 in CMS4 CRC cells promoted cell proliferation, cell survival, foci formation, invasion, migration, cancer stem cell like behaviour and growth in 3D Matrigel. In contrast, siRNA-mediated depletion of TFF3 or AMPC inhibition of TFF3 in CMS4 CRC cells decreased oncogenic behaviour as indicated by the above cell function assays. AMPC also inhibited tumour growth in vivo. The TFF3-stimulated oncogenic behaviour of CMS4 CRC cells was dependent on TFF3 activation of the p44/42 MAPK (ERK1/2) pathway. Furthermore, the forced expression of TFF3 decreased the sensitivity of CMS4 CRC cells to 5-fluorouracil (5-FU); while depleted TFF3 expression enhanced 5-FU sensitivity in CMS4 CRC cells. 5-FU treatment induced TFF3 expression in CMS4 CRC cells. AMPC, when used in combination with 5-FU in CMS4 CRC cells exhibited a synergistic inhibitory effect. In summary, this study provides functional evidence for TFF3 as a therapeutic target in CMS4 CRC.

Sign in / Sign up

Export Citation Format

Share Document