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Biomedical subjects

Jie Luo

Publications and source records attributed to Jie Luo.

At least 19 recordsLinked to original sources
PubMed2026

Impact of oxidative stress on malignant tumor progression and emerging therapeutic strategies.

Oxidative stress, driven by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a pivotal role in cancer biology. While persistent, moderately elevated ROS levels can promote genomic instability, tumor progression, and immune evasion, excessive ROS accumulation can overwhelm antioxidant defenses and trigger cancer cell death. Despite promising preclinical findings, clinical translation remains a challenge because of the context-dependent effects of ROS. A deeper understanding of oxidative stress regulation may lead to the development of novel precision medicine strategies, optimizing cancer therapies while minimizing adverse effects. This review highlights the concentration-dependent effects of oxidative stress in tumorigenesis, focusing on its impact on DNA damage, metabolic reprogramming, and immune modulation. We discuss recent advancements in ROS-targeting strategies, including pro-oxidant therapies that exploit redox vulnerabilities in cancer cells and antioxidant-based approaches aimed at mitigating oxidative stress-driven resistance to treatment. Moreover, we examine the interplay between oxidative stress and the tumor microen-vironment, emphasizing its influence on immune surveillance and therapeutic responses. This re-view provides insights into ROS-targeting interventions and their potential in oncologic treatment paradigms.

malignant tumors↗
PubMed2025

Exploring the shared genetic basis of attention-deficit/hyperactivity disorder and obstructive sleep apnea: A multi-omics analysis.

BACKGROUND: Observational studies have suggested an association between attention-deficit/hyperactivity disorder (ADHD) and obstructive sleep apnea (OSA), but these findings are often inconsistent due to potential biases from medication use, and varying diagnostic criteria. Genetic analyses can help mitigate these confounding factors, providing additional evidence. METHODS: This study evaluated the genetic correlations between ADHD and OSA using Genome-wide association study (GWAS) summary data, applying linkage disequilibrium score regression (LDSC) and SUPER GeNetic cOVariance Analyzer (SUPERGNOVA). Cross-trait association and colocalization analysis identify potential pleiotropic loci. Tissue enrichment analysis and gene-level analysis of shared genes between OSA and ADHD was conducted. Additionally, bidirectional Mendelian randomization was used to assess potential causal relationships. RESULTS: We found significant genetic correlations between ADHD and OSA (rg = 0.309, p = 3.252E-27), and identified 8 novel pleiotropic loci through cross-trait association analysis. Tissue enrichment analysis showed that these shared genes were primarily concentrated in brain tissues, particularly in deep gray matter regions, and were associated with immune and inflammatory pathways. Forward Mendelian Randomization analysis showed that ADHD was significantly associated with the risk of OSA (OR 1.070, 95 % CI 1.013-1.130, p = 0.016), and reverse analysis showed that OSA was significantly associated with the risk of ADHD (OR 1.240, 95 % CI 1.106-1.390, p = 2.213E-4). CONCLUSION: The findings of this study show a significant positive genetic correlation between ADHD and OSA and each is a risk factor for the other. Inflammation in specific brain regions may be the underlying mechanism for their comorbidity.

Humans↗
PubMed2006

Biocidal efficacy, biofilm-controlling function, and controlled release effect of chloromelamine-based bioresponsive fibrous materials.

In this study, 2-amino-4-chloro-6-hydroxy-s-triazine (ACHT) was synthesized through controlled hydrolysis of 2-amino-4,6-dichloro-s-triazine (ADCT). A simple pad-dry-cure approach was employed to immobilize ACHT onto cellulosic fibrous materials. After treatment with diluted chlorine bleach, the covalently bound ACHT moieties were transformed into chloromelamines. The structures of the samples were fully characterized with NMR, UV/VIS, DSC, TG, iodometric titration and elemental analyses. The chloromelamine-based fibrous materials provided potent, durable, and rechargeable biocidal functions against bacteria (including multi-drug resistant species), yeasts, viruses, and bacterial spores. SEM studies demonstrated that the new fibrous materials could effectively prevent the formation of biofilms, and controlled release investigations in vitro suggested that the biocidal activities were bioresponsive. Biocidal mechanisms of the chloromelamine-based fibrous materials were further discussed.

Absorption↗
PubMed2006

A multistep process gave rise to RNA polymerase IV of land plants.

Since their discovery in Metazoa, the three nuclear RNA polymerases (RNAPs) have been found in fungi, plants, and diverse protists. In all eukaryotes studied to date, RNAPs I, II, and III collectively transcribe all major RNAs made in the nucleus. We have found genes for the largest subunit (RPD1/RPE1) of a new DNA-dependent RNAP, RNAP IV, in all major land plant taxa and in closely related green algae. Genes for the second-largest subunit (RPD2) of this enzyme were found in all land plants. Phylogenetic study indicates that RNAP IV genes are sister to the corresponding RNAP II genes. Our results show the genesis of RNAP IV to be a multistep process in which the largest and second-largest subunit genes evolved by independent duplication events in the ancestors of Charales and land plants. These findings provide insights into evolutionary mechanisms that can explain the origin of multiple RNAPs in the eukaryotic nucleus.

Amino Acid Sequence↗
PubMed2006

Duplication and paralog sorting of RPB2 and RPB1 genes in core eudicots.

RPB1 and RPB2, which encode the largest and second largest subunits of RNA polymerase II, respectively, are essential single copy genes in fungi, animals and most plants. Two paralogs of the RPB2 gene have been found in some groups of angioperms [Oxelman, B., Yoshikawa, N., McConaughy, B.L., Luo, J., Denton, A.L., Hall, B.D., 2004. RPB2 gene phylogeny in flowering plants, with particular emphasis on asterids. Mol. Phylogenet. Evol. 32, 462-479]. Here, we report the results of experiments designed to identify the evolutionary origin of the RPB2 duplicate copies. Through careful sampling and phylogenetic analysis, we were able to construct the RPB2 gene tree in angiosperms and infer the phylogenetic positions of the gene duplication and gene loss events that occurred. Our study shows that an RPB2 gene duplication occurred early in core eudicot evolution, at or near the time of the Buxaceae/Trochodendraceae divergence. Subsequently, multiple gene duplication and paralog sorting events happened independently in different core eudicot taxa. Differential expression of the two RPB2 gene paralogs may explain the preservation of both paralogs in the asterids. One gene (RPB2-i) accounts for most of the RPB2 mRNA made in the flower organs while the other gene (RPB2-d) is predominantly used in the vegetative tissues. We also found two paralogs of the RPB1 gene in some core eudicot species. The RPB1 gene duplication occurred before core eudicot divergence, around the time of RPB2 gene duplication. Several independent RPB1 paralog sorting events happened in different core eudicot taxa; their occurrence was independent of the RPB2 paralog sorting events. Our results suggest that a polyploidization event happened at or near the time of the Buxaceae/Trochodendraceae divergence. We propose that this polyploidization and the partial diploidization processes thereafter may have been the driving force of core eudicot radiation.

Exons↗
PubMed2006

[Role of hepatocellular apoptosis and mechanisms of liver injury in lipopolysaccharide-induced acute liver failure in D-galactosamine-sensitized rats].

OBJECTIVE: To investigate the situation of hepatocellular apoptosis in D-galactosamine (D-GalN)-sensitized rats with lipopolysaccharide (LPS)-induced acute liver failure and the mechanisms of liver injury therein. METHODS: Forty eight Wistar rats were randomly divided into 6 equal groups to be injected peritoneally with LPS (50 microg/kg) and D-GalN (300 mg/kg) (treatment groups) or normal saline of the same volume (control groups), and then were killed 6, 24, or 48 hours later. Blood samples were collected from the portal vein or vena cava inferior to detect the contents of serum alanine aminotransferase (ALT), livers were take out to detect the hepatocellular apoptosis by TUNEL assay or ultrastructural observations, and the expressions of iNOS, p53, and p21waf1/cip1 gene were detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The ALT levels of the treatment groups were all significantly higher than those of the corresponding control groups, with the peaks 24 hours after treatment. Transmission electron microscopy showed that apoptotic cells were rare in the control subgroups, but were abundant in the liver tissues of the treatment subgroups. The apoptotic indices of liver cells of the 6, 24, and 48 hours treatment subgroups were 7.3% +/- 1.5%, 71.8% +/- 10.3%, and 68.2% +/- 11.9% respectively, all significantly higher than those of the control groups (2.6% +/- 1.1%, all P < 0.05). The apoptotic index increased gradually along with the time, however, the apoptotic indices of the 24 and 48 hours treatment subgroups were not significantly different (P > 0.05). The mRNA expression levels of iNOS gene of the control subgroups, 6 hours treatment subgroup, 24 hours treatment subgroups, and 48 hours treatment subgroup were 0, 0.53 +/- 0.11, 0.36 +/- 0.08, and 0.15 +/- 0.04 respectively with a significant difference among different subgroups, and with a peak 6 hours after treatment. The p53 expressions of the control subgroups, 6 hours treatment subgroup, 24 hours treatment subgroups, and 48h treatment subgroup were 0.031 +/- 0.006, 0.022 +/- 0.008, 0.49 +/- 0.11, and 0.39 +/- 0.17 respectively, being low in both control subgroups and 6h treatment subgroup and significantly upregulated in the 24 and 48 hours treatment groups. Expression of p21waf1/cip1 was not detected in the control subgroups and 48 hours treatment subgroup, but was found in the 6 hours and 24 hours treatment subgroups, with a peak in the 24 hours treatment subgroup. CONCLUSION: Acute liver failure can be induced by low dose LPS in D-GalN-sensitized rats, which may be associated with the early high expression of iNOS gene; Apoptosis is the important morphological feature in this process.

Animals↗
PubMed2006

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

Antibodies, Monoclonal↗
PubMed2006

Controlling biofilm formation with an N-halamine-based polymeric additive.

An N-halamine-based polymeric additive, poly[(6-morpholino-s-triazine-2,4-diyl)-N-chloro-[2,2,6,6-tetramethyl-4-piperidyl)imino]-hexamethylene[(2,2,6,6-4-piperidyl) imino]] (APA-1), was prepared in this study. The chemical structure of APA-1 was confirmed by iodometric titration, (1)H NMR, and (13)C NMR analysis. APA-1 was incorporated into polyurethane through solvent casting. The resultant materials demonstrated potent antimicrobial functions against Staphylococcus epidermidis. Zone of inhibition studies showed that APA-1 inactivated the bacteria through contact, without leaching out of the polyurethane samples. In vitro studies illustrated that APA-1-containing polyurethane could prevent the colonization and biofilm formation of S. epidermidis for at least 28 days.

Anti-Bacterial Agents↗
PubMed2006

Cyclooxygenase-2-dependent regulation of E-cadherin: prostaglandin E(2) induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer.

Elevated tumor cyclooxygenase-2 (COX-2) expression is associated with tumor invasion, metastasis, and poor prognosis in non-small cell lung cancer (NSCLC). Here, we report that COX-2-dependent pathways contribute to the modulation of E-cadherin expression in NSCLC. First, whereas genetically modified COX-2-sense (COX-2-S) NSCLC cells expressed low E-cadherin and showed diminished capacity for cellular aggregation, genetic or pharmacologic inhibition of tumor COX-2 led to increased E-cadherin expression and resulted in augmented homotypic cellular aggregation among NSCLC cells in vitro. An inverse relationship between COX-2 and E-cadherin was shown in situ by double immunohistochemical staining of human lung adenocarcinoma tissue sections. Second, treatment of NSCLC cells with exogenous prostaglandin E(2) (PGE(2)) significantly decreased the expression of E-cadherin, whereas treatment of COX-2-S cells with celecoxib (1 mumol/L) led to increased E-cadherin expression. Third, the transcriptional suppressors of E-cadherin, ZEB1 and Snail, were up-regulated in COX-2-S cells or PGE(2)-treated NSCLC cells but decreased in COX-2-antisense cells. PGE(2) exposure led to enhanced ZEB1 and Snail binding at the chromatin level as determined by chromatin immunoprecipitation assays. Small interfering RNA-mediated knockdown of ZEB1 or Snail interrupted the capacity of PGE(2) to down-regulate E-cadherin. Fourth, an inverse relationship between E-cadherin and ZEB1 and a direct relationship between COX-2 and ZEB1 were shown by immunohistochemical staining of human lung adenocarcinoma tissue sections. These findings indicate that PGE(2), in autocrine or paracrine fashion, modulates transcriptional repressors of E-cadherin and thereby regulates COX-2-dependent E-cadherin expression in NSCLC. Thus, blocking PGE(2) production or activity may contribute to both prevention and treatment of NSCLC.

Cadherins↗
PubMed2006

Structural and functional characterization of herpes simplex virus 1 immediate-early protein infected-cell protein 22.

Of the five HSV1 immediate-early proteins, infected-cell protein 22 (ICP22), the product of the Us1 gene, is a member whose function is less understood. In order to promote better understanding of the role of ICP22 in viral replication, mutation and fluorescence techniques were used to investigate the biochemical relationship between ICP22's structure and nuclear localization, and the CAT assay was used to analyze the relationship between ICP22's structure and its transcriptional repression. The results of these experiments implied (i) ICP22 is localized to small dense nuclear bodies and is paired with the SC-35 domain in the nucleus, (ii) ICP22 localization in a punctate state requires completion of the main sequence which includes the 1-320th amino acids, (iii) a conservative mutation in the nucleotidylylation site is important for its nuclear localization and transcriptional repression, and (4) despite possessing the same amino acid sequence as the ICP22 carboxyl-terminal, Us1.5 was distinct from ICP22 in location and function.

Animals↗
PubMed2006

The aging neurogenic subventricular zone.

In the adult mouse brain, the subventricular zone (SVZ) is a neurogenic stem cell niche only 4-5 cell diameters thick. Within this narrow zone, a unique microenvironment supports stem cell self-renewal, gliogenesis or neurogenesis lineage decisions and tangential migration of newly generated neurons out of the SVZ and into the olfactory bulb. However, with aging, SVZ neurogenesis declines. Here, we examine the dynamic interplay between SVZ cytoarchitecture and neurogenesis through aging. Assembly of high-resolution electron microscopy images of corresponding coronal sections from 2-, 10- and 22-month-old mice into photomontages reveal a thinning of the SVZ with age. Following a 2-h BrdU pulse, we detect a significant decrease in cell proliferation from 2 to 22 months. Neuroblast numbers decrease with age, as do transitory amplifying progenitor cells, while both SVZ astrocytes and adjacent ependymal cells remain relatively constant. At 22 months, only residual pockets of neurogenesis remain and neuroblasts become restricted to the anterior dorsolateral horn of the SVZ. Within this dorsolateral zone many key components of the younger neurogenic niche are maintained; however, in the aged SVZ, increased numbers of SVZ astrocytes are found interposed within the ependyma. These astrocytes co-label with markers to ependymal cells and astrocytes, form intercellular adherens junctions with neighboring ependymal cells, and some possess multiple basal bodies of cilia within their cytoplasm. Together, these data reveal an age-related, progressive restriction of SVZ neurogenesis to the dorsolateral aspect of the lateral ventricle with increased numbers of SVZ astrocytes interpolated within the ependyma.

Aging↗
PubMed2004

Expression of alpha 4 and alpha 7 nicotinic receptors in the brainstem of female rabbits after coitus.

Coital signaling in the female rabbit involves sequential events in the brainstem and hypothalamus, resulting in a massive release of hypothalamic gonadotropin-releasing hormone (GnRH) that peaks within 1-2 h after mating. The neural connections between coitus and GnRH release involves norepinephrine (NE) and acetylcholine (ACh) since administration of antagonists against NE (dibenamine or phentolamine) or ACh (atropine, alpha-bungarotoxin (alpha-BTX) or scopolamine) blocks or attenuates ovulating events. Moreover, hypothalamic NE release and brainstem tyrosine hydroxylase (TH, the rate-limiting enzyme for NE synthesis) expression in the noradrenergic areas increase prior to, or in concert with, the preovulatory GnRH surge. How ACh is involved in the control of ovulation in the rabbit is lesser known. In the present study, the number of brainstem neurons expressing TH, alpha4 and alpha7 subunits of the nicotinic ACh receptor (nAChR) before and after coitus was determined by immunocytochemistry. Compared to non-mated female rabbits, the number of alpha4, alpha7 and TH single-labeled neurons as well as alpha4/TH and alpha7/TH double-labeled neurons increased in the A1, A2 and A6 brainstem noradrenergic areas at 1 h, but not 2 h, after coitus. The results suggest that the participation of ACh in the control of coitus-induced ovulation may include activation of alpha4beta2 and alpha7 nAChRs in neurons within or adjacent to the brainstem noradrenergic areas in female rabbits.

Animals↗
PubMed2004

Cyclooxygenase-2-dependent expression of angiogenic CXC chemokines ENA-78/CXC Ligand (CXCL) 5 and interleukin-8/CXCL8 in human non-small cell lung cancer.

Elevated tumor cyclooxygenase (COX)-2 activity plays a multifaceted role in non-small cell lung cancer (NSCLC). To elucidate the role of COX-2 in the in vitro and in vivo expression of two known NSCLC angiogenic peptides, CXC ligand (CXCL) 8 and CXCL5, we studied two COX-2 gene-modified NSCLC cell lines, A549 and H157. COX-2 overexpression enhanced the in vitro expression of both CXCL8 and CXCL5. In contrast, specific COX-2 inhibition decreased the production of both peptides as well as nuclear translocation of nuclear factor kappaB. In a severe combined immunodeficient mouse model of human NSCLC, the enhanced tumor growth of COX-2-overexpressing tumors was inhibited by neutralizing anti-CXCL5 and anti-CXCL8 antisera. We conclude that COX-2 contributes to the progression of NSCLC tumorigenesis by enhancing the expression of angiogenic chemokines CXCL8 and CXCL5.

Active Transport, Cell Nucleus↗
PubMed2004

RPB2 gene phylogeny in flowering plants, with particular emphasis on asterids.

Two, apparently functional, paralogues of the RPB2 gene, which encodes the second largest subunit of RNA polymerase II, are shown to be present in two major groups of asterid plants. Although all other land plants surveyed so far have been found to have only one of these two copies, the RPB2 gene phylogeny inferred from the 3' half of the gene for 35 angiosperm taxa and six other land plants indicates that the duplication of the RPB2 gene occurred earlier than the time for origin of the asterid group, probably near the origin of "core eudicots." The d copy is present in all plants which are unambiguously assigned to the core eudicots, whereas the I copy is retained only in the lamiid clade, Ericales, and Escallonia, all belonging to the asterid group of plants. Both parsimony and likelihood analyses of sequences from the 3' half of the gene give strong bootstrap support for these conclusions. There is no support for monophyly of the taxa having both copies. Thus, numerous losses of one of the copies must be inferred. Structurally, both paralogues appear functional, and transcription is demonstrated for both copies. In the lamiid group, the d copy has lost introns 18-23. The well supported phylogenetic relationships implied by the RPB2 gene phylogeny are largely congruent with well supported phylogenetic hypotheses based on other sequence data. However, Ilex, usually assigned to the campanuliid clade, is instead supported as being a member of the lamiid clade, both from sequence data and the presence of an I copy as well as the loss of introns 18-23 in the d copy. Escallonia, supported as a member of the campanuliid clade both by RPB2-d-sequences and previously published DNA sequence data, has all the introns 18-23 in its d copy, as do all other members studied from the campanuliid group. We used the Markov Chain Monte Carlo (MCMC) approach of the MrBayes program to implement Maximum Likelihood bootstrapping. Under the same model of evolution, bootstrapping frequencies are significantly lower than the Bayesian posterior probabilities inferred from the MCMC chain.

Gene Dosage↗
PubMed2003

COX-2-dependent stabilization of survivin in non-small cell lung cancer.

Elevated tumor cyclooxygenase 2 (COX-2) expression is associated with increased angiogenesis, tumor invasion and promotion of tumor cell resistance to apoptosis. The mechanism(s) by which COX-2 exerts its cytoprotective effects are not completely understood but may be due to an imbalance of pro- and anti-apoptotic gene expression. To analyze COX-2-dependent gene expression and apoptosis, we created cell lines constitutively expressing COX-2 cDNA in sense and antisense orientations. Whereas COX-2 sense cells have significantly heightened resistance to radiation and drug-induced apoptosis, COX-2 antisense cells are highly sensitive to apoptosis induction. We found that the expression of the anti-apoptotic protein survivin correlated positively with COX-2 expression. A COX-2-dependent modulation of survivin ubiquitination led to its stabilization in COX-2 overexpressing cells, and this effect was replicated by exogenous PGE2 treatment of parental tumor cells. In contrast to previous studies in other cell types, in nonsmall cell lung cancer cells survivin was expressed in a cell cycle-independent manner. When established in SCID mice in vivo, COX-2 antisense-derived tumors had significantly decreased survivin levels while COX-2 sense-derived tumors demonstrated elevated levels compared with controls. In accord with these findings, survivin and COX-2 were frequently upregulated and co-expressed in human lung cancers in situ.

Animals↗
PubMed2003

Overexpression of CCL-21/secondary lymphoid tissue chemokine in human dendritic cells augments chemotactic activities for lymphocytes and antigen presenting cells.

BACKGROUND: Ex vivo generated dendritic cells (DC) genetically modified to express secondary lymphoid tissue chemokine (CCL-21/SLC) have been shown to stimulate potent antitumor responses in murine models. When injected intratumorally, CCL-21 colocalizes DC and lymphocyte effector cells at the tumor site. This may improve tumor antigen presentation and T cell activation by utilizing the tumor as an in vivo source of antigen for DC. In order to develop DC-based cancer therapies for intratumoral injection that could promote tumor antigen uptake and presentation in situ, we constructed and characterized an adenoviral vector that expresses human CCL-21 (AdCCL-21). RESULTS: Human monocyte derived DC were cultured in GM-CSF and IL-4 for 6 days. Following AdCCL-21 transduction, CCL-21 protein production was assessed by ELISA on day 8. DC transduced with AdCCL-21 at multiplicities of infection (MOIs) of 50:1 or 100:1 produced up to 210 +/- 9 ng/ml and 278 +/- 6.5 ng/ml /106 cells/48 hours, respectively. Following transduction, an immature DC phenotype was maintained and an upregulation of the costimulatory molecule, CD86 was noted. In addition, supernatant from AdCCL-21-DC caused significant chemotaxis of peripheral blood lymphocytes and mature DC. CONCLUSIONS: These studies demonstrate that AdCCL-21-DC generate functional levels of CCL-21 without adversely altering DC phenotype. These findings strengthen the rationale for further investigation of AdCCL-21-DC as a DC-based therapy in cancer treatment.

Adenoviridae↗
PubMed2003

Non-small cell lung cancer-derived soluble mediators enhance apoptosis in activated T lymphocytes through an I kappa B kinase-dependent mechanism.

T lymphocyte survival is critical for the development and maintenance of an effective host antitumor immune response; however, the tumor environment can negatively impact T-cell survival. Lymphocytes exposed to tumor supernatants (TSNs) were evaluated for apoptosis after mitogen stimulation. TSN was observed to significantly enhance phorbol 12-myristate 13-acetate/ionomycin- and anti-CD3-stimulated lymphocyte apoptosis. Enhanced lymphocyte apoptosis was associated with an impairment of nuclear factor kappa B nuclear translocation and diminished I kappa B alpha degradation. In lymphocytes stimulated after exposure to TSNs, cytoplasmic I kappa B alpha persisted as a result of alterations in I kappa B kinase (IKK) activity. Accordingly, although there were no apparent differences in IKK component concentrations, lymphocytes preexposed to TSNs exhibited markedly reduced IKK activity. We conclude that non-small cell lung cancer-derived soluble factors promote apoptosis in activated lymphocytes by an IKK-dependent pathway.

Adenocarcinoma↗