Biomedical subjects

Jian Liu

Publications and source records attributed to Jian Liu.

At least 19 recordsLinked to original sources

PubMed2026

E2F7 promotes lung adenocarcinoma progression by affecting phosphorylation and stabilization of β-catenin.

BACKGROUND: E2F transcription factor 7 (E2F7) has been implicated in the tumorigenesis and progression of multiple cancer types; however, the molecular mechanisms through which E2F7 regulates malignant phenotypes in cancer cells remain largely undefined. In this study, we investigated the biological functions and underlying mechanisms of E2F7 in lung adenocarcinoma (LUAD). METHODS: E2F7 expression in LUAD was analyzed using The Cancer Genome Atlas (TCGA) datasets and further validated in clinical specimens via quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. The effects of E2F7 on cancer cell self‑renewal and epithelial-mesenchymal transition (EMT) were assessed using sphere formation and Transwell assays, respectively. In vivo tumorigenicity and metastasis were evaluated using xenograft models combined with extreme limiting dilution analysis to assess tumor-initiating capacity. Wnt/β‑catenin pathway activity was measured using T-cell factor optimal promoter luciferase reporter plasmid/far-from optimal promoter luciferase reporter plasmid (TOP/FOP) flash reporter assays. β‑Catenin expression, stability, and ubiquitination were examined via western blotting, cycloheximide chase assays, and ubiquitination assays. Protein-protein interactions among E2F7, β‑catenin, and glycogen synthase kinase 3 beta (GSK3β) were verified through co‑immunoprecipitation (Co‑IP), glutathione S‑transferase (GST) pull‑down, and immunofluorescence assays. Truncated mutants were generated to map the functional binding domains of E2F7. In vitro immunoprecipitation and kinase assays were further performed to confirm that E2F7 regulates GSK3β autophosphorylation and β‑catenin phosphorylation. RESULTS: Bioinformatic analyses revealed that E2F7 was significantly upregulated in LUAD tissues, and elevated E2F7 expression correlated with poor patient prognosis. Functional assays demonstrated that E2F7 promoted LUAD cell self‑renewal and EMT. Mechanistically, cytoplasmic E2F7 directly associated with β‑catenin through its DNA‑binding domain (DBD) and PHA03247 domain. E2F7 modulated β‑catenin phosphorylation at Ser675 and Ser33/37/T41, thereby inhibiting ubiquitin‑mediated degradation and enhancing β‑catenin protein stability. Furthermore, E2F7 interacted with GSK3β and suppressed its autophosphorylation at Tyr216, concomitant with reduced β-catenin phosphorylation at Ser33/37/T41 and its accumulation. CONCLUSION: Collectively, these findings indicate that E2F7 drives LUAD malignant progression through regulation of the GSK3β/β‑catenin signaling axis and stabilization of β‑catenin. This study unveils a novel oncogenic mechanism of E2F7 in LUAD and identifies E2F7 as a promising therapeutic target for clinical intervention in LUAD.

E2F7↗

PubMed2026

Unraveling the coastal marine plastisphere archaeome.

Plastic pollution has created an expanding anthropogenic microbial niche, the plastisphere, raising questions about microbial ecology and associated impacts. Archaea, the third domain of life with fundamental ecological and evolutionary significance, remain poorly understood in this habitat. Here, using paired plastic debris and bulk-water samples from coastal marine ecosystems, key archaeal habitats increasingly threatened by plastic pollution, we characterize the plastisphere archaeome through archaeal amplicon sequencing and metagenomics. We show that the archaeome is significantly reshaped in the plastisphere, exhibiting higher taxonomic diversity, greater community heterogeneity, and selective enrichment of Euryarchaeota and Crenarchaeota. Archaeal genes involved in methane, nitrogen, and sulfur cycling are enriched in the plastisphere. Taxonomic and functional divergence between the plastisphere and bulk water increases with anthropogenic chemical stress. These findings suggest that plastic pollution could alter marine archaeal diversity, biogeography, and biogeochemical potential, extending understanding of plastisphere impacts to the archaeal domain.

Archaea↗

PubMed2026

Role of Sanqi Baiji San in Mitigating Ethanol-Induced Gastric Epithelial Cell Injury via PI3K/AKT-related Signaling.

This work aimed to clarify the protective mechanism of Sanqi Baiji San (SQBJ) against ethanol-induced gastric epithelial cell injury and to explore its potential relevance to gastric ulcer (GU). Network pharmacology was used to screen SQBJ's active components (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform [TCMSP], Oral Bioavailability [OB] ≥ 20%, Drug-Likeness [DL] ≥ 0.1), map their targets (Universal Protein Resource [UniProt]), collect GU-related targets (GeneCards/OMIM/DrugBank), and analyze overlapping targets via Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and molecular docking. Ethanol-injured Gastric Epithelial Cell Line-1 (GES-1) cells were treated with SQBJ or the PI3K inhibitor LY294002. CCK-8 was used to determine the optimal SQBJ concentration. Network pharmacology analyses identified 126 common targets enriched within PI3K/AKT/MAPK-related cascades and suggested potential interactions between principal SQBJ constituents and PI3K/AKT-related proteins. In ethanol-challenged cells, SQBJ alleviated cell injury by reducing inflammatory mediator release and oxidative stress, as evidenced by decreased intracellular reactive oxygen species and malondialdehyde levels. SQBJ restored mitochondrial membrane potential and ATP content and reduced apoptosis-associated changes in B-cell lymphoma-2, cleaved caspase-3, and Bcl-2-associated X protein levels. SQBJ also modulated PI3K/AKT- and MAPK-associated signaling markers. These protective effects were largely weakened by LY294002, suggesting that PI3K/AKT-related signaling is involved in SQBJ-mediated cytoprotection. These findings provide an in vitro mechanistic basis for the potential application of SQBJ in GU, although further validation in animal models of ethanol-induced gastric ulcer is required.

Ethanol↗

PubMed2026

Potential evaluation of SULT1A3 as an early diagnostic marker for nasopharyngeal carcinoma: a study based on serum proteomics screening and ELISA validation.

BACKGROUND: Nasopharyngeal carcinoma (NPC) represents a highly prevalent and aggressive malignancy endemic to Southeast Asia. Early and accurate diagnosis is critical to improving survival outcomes; however, the absence of robust, stage-specific biomarkers remains a key obstacle to clinical implementation of early screening strategies. METHODS: We performed untargeted serum proteomic profiling using mass spectrometry in 15 treatment-naïve early-stage NPC patients and 15 VCA-IgA-positive healthy controls. Bioinformatics analyses were conducted to identify differentially expressed proteins (DEPs). Machine learning (random forest combined with recursive feature elimination) was employed to prioritize candidate biomarkers, which were subsequently verified using enzyme-linked immunosorbent assay (ELISA) in independent sample cohorts. RESULTS: In total, 1,428 serum proteins were identified, among which 1,410 were reliably quantified. We observed 31 upregulated and 189 downregulated proteins in NPC patients relative to controls. Spearman correlation analysis revealed significant associations: LTA4H (leukotriene A4 hydrolase) levels correlated with serum cell infiltration (r = 0.383, p = 0.032) and CD8 + T-cell abundance (r = 0.408, p = 0.021); both SULT1A3 (sulfotransferase family 1 A member 3) and FGL1 (fibrinogen-like protein 1) levels were positively associated with M1 macrophage infiltration (r = 0.510, p = 0.003 and r = 0.430, p = 0.015, respectively). In a preliminary validation cohort (n = 80), ELISA yielded AUC values of 0.631 (95% CI: 0.515-0.736, p = 0.04) for LTA4H, 0.787 (95% CI: 0.681-0.871, p < 0.001) for SULT1A3, and 0.688 (95% CI: 0.575-0.787, p = 0.002) for FGL1. In large-scale independent validation, SULT1A3 achieved an AUC of 0.826 (95% CI: 0.766-0.876; sensitivity = 78.89%, specificity = 75.47%) in cohort 1 (n = 196) and 0.796 (95% CI: 0.723-0.857; sensitivity = 76.67%, specificity = 76.67%) in cohort 2 (n = 150). CONCLUSIONS: Through an integrated workflow combining proteomic screening, machine learning prioritization, and multi-stage ELISA validation, we identified SULT1A3 as a candidate serum-based biomarker for early detection of NPC. Preliminary findings suggest that SULT1A3 may have potential utility in clinical screening, though further validation in independent, multi‑center cohorts is required.

Humans↗

PubMed2025

COG6 is an essential host factor for influenza A virus infection.

Influenza A virus (IAV) relies on the host cellular machinery to support its replication. Understanding these host dependencies can inform the development of novel antiviral strategies. In this study, we identified conserved oligomeric Golgi complex subunit 6 (COG6) as a novel host factor critical for IAV replication through a genome-wide clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) knockout screen. Disruption of COG6 significantly impaired viral replication. Mechanistically, COG6 supports IAV replication via two distinct means. First, consistent with the role of the COG complex in Golgi homeostasis, COG6 is required for the proper presentation of surface sialic acids, the primary receptor for IAV entry. Second, COG6 deficiency unexpectedly led to lysosome-dependent degradation of viral proteins. Notably, lysosomal activity was also upregulated in IAV-infected wild-type cells, albeit to a lesser extent than in COG6-deficient cells. Treatment with lysosomal inhibitors rescued viral protein stability in COG6 knockout cells. Protein interaction analysis further demonstrated that COG6-mediated stabilization of viral proteins did not rely on viral protein-COG6 interaction, refuting the hypothesis that COG6 acts as a shield factor to protect viral protein from lysosomal degradation. Moreover, knockout of other COG subunits produced similar antiviral effects, suggesting that an intact COG complex is required for IAV replication. Together, these findings uncover a critical role of the COG complex in regulating IAV replication and highlight a previously unappreciated functional link between the Golgi and lysosomes that could be exploited for treating IAV infections.IMPORTANCEDespite advances in virology, numerous host determinants facilitating influenza A virus (IAV) pathogenesis remain uncharacterized. Our study establishes conserved oligomeric Golgi complex subunit 6 (COG6) as a critical host factor promoting IAV infection through complementary mechanisms: receptor modulation and viral protein stabilization. This represents the first demonstration that the COG complex regulates viral pathogenesis through proteostasis mechanisms, fundamentally expanding our understanding of host-virus interactions at the organelle interface. These findings not only provide new perspectives on viral exploitation of Golgi trafficking networks but also identify potential therapeutic targets against evolving influenza strains.

Influenza A virus↗

PubMed2025

Comprehensive discovery and functional characterization of the noncanonical proteome.

The systematic identification and functional characterization of noncanonical translation products, such as novel peptides, will facilitate the understanding of the human genome and provide new insights into cell biology. Here, we constructed a high-coverage peptide sequencing reference library with 11,668,944 open reading frames and employed an ultrafiltration tandem mass spectrometry assay to identify novel peptides. Through these methods, we discovered 8945 previously unannotated peptides from normal gastric tissues, gastric cancer tissues and cell lines, nearly half of which were derived from noncoding RNAs. Moreover, our CRISPR screening revealed that 1161 peptides are involved in tumor cell proliferation. The presence and physiological function of a subset of these peptides, selected based on screening scores, amino acid length, and various indicators, were verified through Flag-knockin and multiple other methods. To further characterize the potential regulatory mechanisms involved, we constructed a framework based on artificial intelligence structure prediction and peptide‒protein interaction network analysis for the top 100 candidates and revealed that these cancer-related peptides have diverse subcellular locations and participate in organelle-specific processes. Further investigation verified the interacting partners of pep1-nc-OLMALINC, pep5-nc-TRHDE-AS1, pep-nc-ZNF436-AS1 and pep2-nc-AC027045.3, and the functions of these peptides in mitochondrial complex assembly, energy metabolism, and cholesterol metabolism, respectively. We showed that pep5-nc-TRHDE-AS1 and pep2-nc-AC027045.3 had substantial impacts on tumor growth in xenograft models. Furthermore, the dysregulation of these four peptides is closely correlated with clinical prognosis. Taken together, our study provides a comprehensive characterization of the noncanonical proteome, and highlights critical roles of these previously unannotated peptides in cancer biology.

Humans↗

PubMed2025

Metagenomic Analysis of the Tonsil Virome Highlights Its Diagnostic Potential for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease whose exact pathogenesis remains unclear, despite links to genetics, environmental factors, and microbial dysbiosis. Recent studies have highlighted the role of the microbiome in RA, yet the contribution of the tonsil virome remains unexplored. This study aims to investigate whether changes in the tonsil virome are associated with RA progression and assess its diagnostic potential. Using metagenomic data from 32 RA patients and 30 healthy controls (HCs), we identified 45 782 viral operational taxonomic units (vOTUs), with 14 341 classified as core vOTUs. RA patients exhibited significantly reduced virome richness and diversity, whereas Siphoviridae and Microviridae dominated both groups. Statistical analysis identified 235 RA-associated viral markers, including 13 enriched in RA and 222 in HCs. RA-enriched markers were primarily bacteriophages infecting Streptococcaceae, whereas HCs displayed more diverse viral-host interactions. Random forest models demonstrated strong discriminatory power of viral markers in distinguishing RA patients from HCs, achieving an AUC of 0.960, outperforming bacterial markers. Correlation analyses further linked viral markers to immune cell subsets, suggesting that tonsil virome alterations may influence immune dysregulation in RA. This study reveals significant changes in the tonsil virome of RA patients, highlighting its potential as a diagnostic tool and offering new insights into RA pathogenesis. These findings pave the way for future research into the virome's role in autoimmune diseases and therapeutic development.

Humans↗

PubMed2007

Methods for peptide identification by spectral comparison.

BACKGROUND: Tandem mass spectrometry followed by database search is currently the predominant technology for peptide sequencing in shotgun proteomics experiments. Most methods compare experimentally observed spectra to the theoretical spectra predicted from the sequences in protein databases. There is a growing interest, however, in comparing unknown experimental spectra to a library of previously identified spectra. This approach has the advantage of taking into account instrument-dependent factors and peptide-specific differences in fragmentation probabilities. It is also computationally more efficient for high-throughput proteomics studies. RESULTS: This paper investigates computational issues related to this spectral comparison approach. Different methods have been empirically evaluated over several large sets of spectra. First, we illustrate that the peak intensities follow a Poisson distribution. This implies that applying a square root transform will optimally stabilize the peak intensity variance. Our results show that the square root did indeed outperform other transforms, resulting in improved accuracy of spectral matching. Second, different measures of spectral similarity were compared, and the results illustrated that the correlation coefficient was most robust. Finally, we examine how to assemble multiple spectra associated with the same peptide to generate a synthetic reference spectrum. Ensemble averaging is shown to provide the best combination of accuracy and efficiency. CONCLUSION: Our results demonstrate that when combined, these methods can boost the sensitivity and specificity of spectral comparison. Therefore they are capable of enhancing and complementing existing tools for consistent and accurate peptide identification.

Journal Article↗

PubMed2007

Mutational study of heparan sulfate 2-O-sulfotransferase and chondroitin sulfate 2-O-sulfotransferase.

Heparan sulfate (HS) and chondroitin sulfate (CS) are highly sulfated polysaccharides with a wide range of biological functions. Heparan sulfate 2-O-sulfotransferase (HS-2OST) transfers the sulfo group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the 2-OH position of the hexauronic acid that is adjacent to N-sulfated glucosamine, whereas chondroitin sulfate 2-O-sulfotransferase (CS-2OST) transfers the sulfo group to the hexauronic acid that is adjacent to N-acetylated galactosamine. Here we report a systematic mutagenesis study of HS-2OST and CS-2OST based on their structural homology to estrogen sulfotransferase and HS 3-O-sulfotransferase isoform 3 (3-OST3), for which crystal structures exist. We have identified six residues possibly involved in binding to PAPS. HS-2OST carrying mutations of these residues lacks sulfotransferase activity and the ability to bind 3'-phosphoadenosine 5'-phosphate, a PAPS analogue, as determined by isothermal titration calorimetry. Similar residues involved in binding to PAPS were also identified in CS-2OST. Additional residues that participate in carbohydrate substrate binding were also identified in both enzymes. Mutations at these residues led to the loss of sulfotransferase activity but maintained the ability to bind to phosphoadenosine 5'-phosphate. The catalytic function of HS-2OST appears to involve two histidine residues (His140 and His142), whereas only one histidine (His168) of CS 2-OST is likely to be critical. This unique feature of HS 2-OST catalytic residues directed us to characterize the Drosophila heparan sulfate 2-O-sulfotransferase. The results from this study provide insight into the differences and similarities various residues play in the biological roles of the HS-2OST and CS-2OST enzymes.

Amino Acid Sequence↗

PubMed2006

High-performance low-cost organic field-effect transistors with chemically modified bottom electrodes.

The characteristics of organic field-effect transistors (OFETs) were dramatically improved by chemically modifying the surface of the bottom-contact Ag or Cu source-drain (D-S) electrodes with a simple solution method. The contact resistance and energetic mismatch typically observed with Ag D-S electrodes in pentacene bottom-contact OFETs can be properly eliminated when modified by the Ag-TCNQ (TCNQ = 7,7,8,8-tetracyanoquinodimethane). The pentacene transistors with low-cost Ag-TCNQ-modified Ag bottom-contact electrodes exhibit outstanding electrical properties, which are comparable with that of the Au top-contact devices. It thus provides a novel way toward high-performance low-cost bottom-contact OFETs.

Journal Article↗

PubMed2006

Using the thermal Gaussian approximation for the Boltzmann operator in semiclassical initial value time correlation functions.

The thermal Gaussian approximation (TGA) recently developed by Frantsuzov et al. [Chem. Phys. Lett. 381, 117 (2003)] has been demonstrated to be a practical way for approximating the Boltzmann operator exp(-betaH) for multidimensional systems. In this paper the TGA is combined with semiclassical (SC) initial value representations (IVRs) for thermal time correlation functions. Specifically, it is used with the linearized SC-IVR (LSC-IVR, equivalent to the classical Wigner model), and the "forward-backward semiclassical dynamics" approximation developed by Shao and Makri [J. Phys. Chem. A 103, 7753 (1999); 103, 9749 (1999)]. Use of the TGA with both of these approximate SC-IVRs allows the oscillatory part of the IVR to be integrated out explicitly, providing an extremely simple result that is readily applicable to large molecular systems. Calculation of the force-force autocorrelation for a strongly anharmonic oscillator demonstrates its accuracy, and calculation of the velocity autocorrelation function (and thus the diffusion coefficient) of liquid neon demonstrates its applicability.

Journal Article↗

PubMed2006

Imprinted photonic polymers for chiral recognition.

Explore the source record for details and available documents.

Hydrogels↗

PubMed2006

Pentoxifylline attenuates the development of hyperalgesia in a rat model of neuropathic pain.

Pentoxifylline, a non-specific cytokine inhibitor, has shown to be beneficial in inflammatory pain in both experimental and clinical studies. The present study demonstrates for the first time, to our knowledge, the antihyperalgesic effect of pentoxifylline in the neuropathic pain using L5 spinal nerve transection rat model. In a preventive paradigm, pentoxifylline (12.5, 25, 50, or 100mg/kg intraperitoneally) was administered systemically daily, beginning 1h prior to nerve transection. Pentoxifylline (50, or 100mg/kgi.p.) produced significant decrease in the mechanical and thermal hyperalgesia. However, pentoxifylline (100mg/kgi.p.) did not influence the paw pressure thresholds and paw withdrawal latency in sham-operated rats. In order to understand the possible antinocicieptive effect of pentoxifylline in neuropathic pain, we examined the level of TNFalpha, IL-1beta, IL-6 and IL-10 protein in the contralateral brain on day 7 post-transection. Pentoxifylline administration resulted in a dose-dependent reduction of the production of proinflammatory cytokines like TNFalpha, IL-1beta and IL-6, and enhancement of IL-10. Furthermore, we investigated the activity of nuclear factor kappa B (NF-kappaB) in the contralateral brain on days 7 after surgery. In accordance with the change of proinflammatory cytokines, Pentoxifylline (50 or 100mg/kg) significantly inhibited the activation of NF-kappaB in the brain. This research supports a growing body of literature emphasizing the importance of neuroinflammation and neuroimmune activation in the development of neuropathic pain states, and the potential preventive value of pentoxifylline in the treatment of neuropathic pain.

Animals↗

PubMed2006

Anticoagulant heparan sulfate: structural specificity and biosynthesis.

Heparan sulfate (HS) is present on the surface of endothelial and surrounding tissues in large quantities. It plays important roles in regulating numerous functions of the blood vessel wall, including blood coagulation, inflammation response, and cell differentiation. HS is a highly sulfated polysaccharide containing glucosamine and glucuronic/iduronic acid repeating disaccharide units. The unique sulfated saccharide sequences of HS determine its specific functions. Heparin, an analog of HS, is the most commonly used anticoagulant drug. Because of its wide range of biological functions, HS has become an interesting molecule to biochemists, medicinal chemists, and developmental biologists. In this review, we summarize recent progress toward understanding the interaction between HS and blood-coagulating factors, the biosynthesis of anticoagulant HS and the mechanism of action of HS biosynthetic enzymes. Furthermore, knowledge of the biosynthesis of HS facilitates the development of novel enzymatic approaches to synthesize HS from bacterial capsular polysaccharides and to produce polysaccharide end products with high specificity for the biological target. These advancements provide the foundation for the development of polysaccharide-based therapeutic agents.

Anticoagulants↗

PubMed2006

Comparison of amplicon-sequencing, pyrosequencing and real-time PCR for detection of YMDD mutants in patients with chronic hepatitis B.

AIM: To compare the sequencing of PCR products, pyrosequencing, and real-time PCR for detection of Tyrosine-methionine-aspartate-aspartate (YMDD) mutants in patients with chronic hepatitis B. METHODS: Mixtures of plasmids and serum samples from 69 chronic hepatitis B patients treated with lamivudine were tested for YMDD mutations by sequencing of PCR products, pyrosequencing, and real-time PCR, respectively. Time required and reagent costs of the three assays were evaluated. RESULTS: Real-time PCR detected 100%, 50%, 10%, 1% and 0.1% of YVDD plasmid in mixtures with 10(6) copies/mL of YMDD plasmid, whereas sequencing and pyrosequencing only detected 100% and 50% of YVDD plasmid in aliquots of the corresponding mixtures. Completely concordant results were obtained from 60 (87%) out of the 69 clinical serum samples by the three assays. Mutants were detected by real-time PCR in less than 20% of the total virus population, but no mutant was detected by sequencing and pyrosequencing. In addition, real-time PCR required less time and was more cost-effective than the other two assays. However, throughput of pyrosequencing was the highest. CONCLUSION: Among the three assays compared, real-time PCR is the most sensitive, cost-effective, and time saving for monitoring YMDD mutants in patients with chronic hepatitis B on lamivudine therapy.

Drug Resistance, Viral↗

PubMed2006

A driving and coupling "Pac-Man" mechanism for chromosome poleward translocation in anaphase A.

During mitosis, chromatid harnesses its kinetochore translocation at the depolymerizing microtubule ends for its poleward movement in anaphase A. The force generation mechanism for such movement remains unknown. Analysis of the current experimental results shows that the bending energy release from the bound tubulin subunits alone cannot provide sufficient driving force. Additional contribution from effective electrostatic attractions between the kinetochore and the microtubule is needed for kinetochore translocation. Interestingly, as the kinetochore moves to inside the microtubule, the microtubule tip is free to bend outward so that the instantaneous distance between the kinetochore and the microtubule tip is much closer than the rest of the microtubule. This close contact yields much larger electrostatic attraction than that from the rest of the microtubule under physiological ionic conditions. As a result, the effective electrostatic interaction hinders the further kinetochore poleward translocation until the microtubule tip dissociates. Thus, the kinetochore translocation is strongly coupled at the depolymerizing microtubule end. This driving-coupling mechanism indicates that the kinetochore velocity is largely controlled by the microtubule dissociation rate, which explains the insensitivity of kinetochore velocity to its viscous drag and the large redundancy in its stalling force.

Anaphase↗

PubMed2006

The efficacy and relationship between peak concentration and toxicity profile of fixed-dose-rate gemcitabine plus carboplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: To investigate the efficacy and relationship between plasma concentrations at the end of infusion (C(end of infusion)) and toxicity profile of fixed-dose-rate gemcitabine plus carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were given gemcitabine by 120 min infusion [at a fixed dose rate (FDR) of 10 mg/m(2)/min] on days 1 and 8 of a 21-day cycle, immediately followed by carboplatin AUC 5 by 4 h infusion on day 1. C (end of infusion) of gemcitabine was determined by ion-pair reversed-phase high-performance liquid chromatography (HPLC). RESULTS: By the close-out date, in our study population, the estimated median time to tumor progression (TTP) was 7 months (95% CI 4-10 months), median overall survival (OS) was 12 months (95% CI 11.2-12.8 months). The mean value of C (end of infusion) of 21 eligible patients was 16.48 +/- 8.07 micromol/l (range 27.43-2.87 micromol/l). The main hematological toxicities were transient grade 3-4 thrombocytopenia. The mean percentages of reduction of WBC, NEC, PLTC and Hb of 21 eligible patients were 38.3 +/- 38.1%, 31.3 +/- 73.6%, 31.8 +/- 53.5% and 12.0 +/- 12.2%, respectively. The analysis of the C(end of infusion) of gemcitabine and the percentage of reduction in WBC showed a significant correlation (r(2) = 0.4575; p < 0.05). A significant correlation (r(2) = 0.5671; p < 0.05) was also observed between the percentage of reduction of PLTC and C(end of infusion) of gemcitabine infusion. CONCLUSION: The clinical data in this trial supports the further evaluation the regimen in advanced NSCLC patients, due to its predictable kinetic behavior and less severe toxicity profile than expected.

Adult↗

PubMed2006

Inhibition of human gastric carcinoma cell growth by atofluding derivative N3-o-toluyl-fluorouracil.

AIM: To evaluate the growth inhibition efficacy of atofluding derivative N3-o-toluyl-fluorouracil (TFU) on human gastric carcinoma cell lines SGC-7901 and MKN-45. METHODS: Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo. RESULTS: TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In vivo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally well tolerated by mice with less than 20% reduction in body weight. CONCLUSION: TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil (5-FU) mediated by the enzymes.

Animals↗