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Wei Tan

Publications and source records attributed to Wei Tan.

At least 19 recordsLinked to original sources
PubMed2026

Oxidative Stress Associated LncRNAs as Potential Biomarkers for Prognosis and Immune Responses in Lung Squamous Cell Carcinoma Patients.

Long-chain non-coding RNA (lncRNA) significantly influences lung squamous cell carcinoma's (LUSC) prognostic value and immune infiltration. This study aimed to demonstrate how oxidative stress-related lncRNAs impact lung squamous cell carcinoma (SCC). The Cancer Genome Atlas (TCGA) dataset gathered transcriptome information and related clinical data for LUSC. To build a prognostic model, 10 prognostic-related genes were identified using a series of bioinformatics analyses that compared the OS gene's aberrant expression in tumor and healthy tissues, as well as its association with malignancy. Subjects were stratified into high- and low-risk groups based on the median risk score derived from the 10-gene signature. While the mathematical risk model demonstrated limited independent predictive performance in the validation cohort (AUC ~ 0.5), functional and immunological evaluations revealed significant differences in the tumor microenvironment (TME) across risk strata. Specifically, high-risk patients exhibited distinct immune infiltration profiles and altered immunological scores relative to their low-risk counterparts. Therefore, rather than serving as a direct clinical prediction tool, this oxidative stress-related lncRNA signature provides valuable biological insights into the immune landscape of LUSC and highlights potential therapeutic targets for further mechanistic investigation.

Humans↗
PubMed2005

Gene therapy with iNOS provides long-term protection against myocardial infarction without adverse functional consequences.

Previous studies have shown that gene therapy with inducible nitric oxide synthase (iNOS) protects against myocardial infarction at 3 days after gene transfer. However, the long-term effects of iNOS gene therapy on myocardial ischemic injury and cardiac function are unknown. To address this issue, we used a recombinant adenovirus 5 (Ad5) vector (Av3) with deletions of the E1, E2a, and E3 regions, which enables long-lasting recombinant gene expression for at least 2 mo due to lack of inflammation. Mice received intramyocardial injections in the left ventricular (LV) anterior wall of Av3/LacZ (LacZ group) or Av3/iNOS (iNOS group); 1 or 2 mo later, they were subjected to myocardial infarction (30-min coronary occlusion followed by 4 h of reperfusion). Cardiac iNOS gene expression was confirmed by immunoblotting and activity assays at 1 and 2 mo after gene transfer. In the iNOS group, infarct size (percentage of risk region) was significantly reduced (P < 0.05) both at 1 mo (24.2 +/- 3.4%, n = 6, vs. 48.0 +/- 3.6%, n = 8, in the LacZ group) and at 2 mo (23.4 +/- 3.1%, n = 8, vs. 36.6 +/- 2.4%, n = 7). The infarct-sparing effects of iNOS gene therapy were as powerful as those observed 24 h after ischemic preconditioning (23.1 +/- 3.4%, n = 10). iNOS gene transfer had no effect on LV function or dimensions up to 8 wk later (echocardiography). These data demonstrate that iNOS gene therapy mediated by the Av3 vector affords long-term (2 mo) cardioprotection without inflammation or adverse functional consequences, a finding that provides a rationale for further preclinical testing of this therapy.

Animals↗
PubMed2005

[Inhibitory effects of protease inhibitor on endotoxin-induced acute lung injury in rats].

OBJECTIVE: To investigate the effects of protease inhibitor on lipopolysaccharide-induced acute lung injury in rats and its possible mechanisms. METHODS: Thirty-two male Wister rats, weighting 250-270 g, were divided into four groups randomly. C, normal controls (n=8); A: acute lung injury group (n=8), receiving intravenous endotoxin (lipopolysaccharide O55:B5, LPS 5 mg/kg); V, low-dose group (n=8), U, high-dose intervention group (n=8, receiving Ulinastatin 50,000 U/kg and 100,000 U/kg respectively and LPS 5 mg/kg). The specimens were collected 2 hours later, We observed the following changes: blood gas analysis, the lung wet/dry weight ratio, the pulmonary vascular permeability, histological manifestations, lung tissue myeloperoxidase activity, plasma endothelin-1, lung tissue malonaldehyde and conjugated-diene. RESULTS: Compared with Group C, the lungs of the rats in Group A had significant hyperemia and spotted hemorrhage. The inflammatory granulocyte infiltrating, diffused alveolar septum thickening and spotted hemorrhage were observed in pathological examinations. The lung wet/dry weight ratio and Evans Blue content (per gram) increased significantly in group A [(5.41+/-0.06), (27.64+/-2.48) microg] compared with group C [(4.95+/-0.08), (12.99+/-2.83) microg], in the intervention groups (U: 5.0+/-0.05, 19.47+/- 2.09; V: 4.98+/-0.06, 21.44+/-3.12) however the difference was not significant between the intervention groups; The plasma endothelin-1 and lung tissue myeloperoxidase activity increased significantly in group A [(948.23+/-103.45) u/g, (152.90+/-8.41) u/g] compared with group C [(729.38+/-88.64) u/g ], [(54.62+/-15.49) u/g] but intervention groups [U: (633.27+/-93.27) u/g, (119.40+/-11.32) u/g; V: (671.87+/-105.45) u/g, (129.55+/-9.57) u/g] decreased significantly compared with group A, no significant difference between intervention groups; lung tissue Lipid-peroxide (malonaldehyde, MDA and conjugated-diene, C-diene) increased significantly in group A [MDA: (73.95+/-4.62) nmol/g; C-diene: (10.96+/-0.81) nmol/g] compared with group C [MDA: (39.65+/-6.21) nmol/g; C-diene: (3.34+/-0.51) nmol/g], intervention groups [U: MDA: (51.26+/-5.56) nmol/g, C-diene: (7.59+/-0.84) nmol/g; V: MDA: (59.87+/-4.62) nmol/g, C-diene: (8.79+/-0.45) nmol/g] decreased significantly compared with group A. MDA decreased significantly in group U compared with group V. CONCLUSION: The protease inhibitor, Ulinastatin, may decrease inflammatory reaction and further decrease lung damage induced by LPS in rats, all indicating protection of protease inhibitor against acute lung injury.

Animals↗
PubMed2005

Identification and characterization of the mouse nuclear export factor (Nxf) family members.

TAP/hNXF1 is a key factor that mediates general cellular mRNA export from the nucleus, and its orthologs are structurally and functionally conserved from yeast to humans. Metazoans encode additional proteins that share homology and domain organization with TAP/hNXF1, suggesting their participation in mRNA metabolism; however, the precise role(s) of these proteins is not well understood. Here, we found that the human mRNA export factor hNXF2 is specifically expressed in the brain, suggesting a brain-specific role in mRNA metabolism. To address the roles of additional NXF factors, we have identified and characterized the two Nxf genes, Nxf2 and Nxf7, which together with the TAP/hNXF1's ortholog Nxf1 comprise the murine Nxf family. Both mNXF2 and mNXF7 have a domain structure typical of the NXF family. We found that mNXF2 protein is expressed during mouse brain development. Similar to TAP/hNXF1, the mNXF2 protein is found in the nucleus, the nuclear envelope and cytoplasm, and is an active mRNA export receptor. In contrast, mNXF7 localizes exclusively to cytoplasmic granules and, despite its overall conserved sequence, lacks mRNA export activity. We concluded that mNXF2 is an active mRNA export receptor similar to the prototype TAP/hNXF1, whereas mNXF7 may have a more specialized role in the cytoplasm.

Active Transport, Cell Nucleus↗
PubMed2005

Nuclear export factor family protein participates in cytoplasmic mRNA trafficking.

In eukaryotes, the nuclear export of mRNA is mediated by nuclear export factor 1 (NXF1) receptors. Metazoans encode additional NXF1-related proteins of unknown function, which share homology and domain organization with NXF1. Some mammalian NXF1-related genes are expressed preferentially in the brain and are thought to participate in neuronal mRNA metabolism. To address the roles of NXF1-related factors, we studied the two mouse NXF1 homologues, mNXF2 and mNXF7. In neuronal cells, mNXF2, but not mNXF7, exhibited mRNA export activity similar to that of Tip-associated protein/NXF1. Surprisingly, mNXF7 incorporated into mobile particles in the neurites that contained poly(A) and ribosomal RNA and colocalized with Staufen1-containing transport granules, indicating a role in neuronal mRNA trafficking. Yeast two-hybrid interaction, coimmunoprecipitation, and in vitro binding studies showed that NXF proteins bound to brain-specific microtubule-associated proteins (MAP) such as MAP1B and the WD repeat protein Unrip. Both in vitro and in vivo, MAP1B also bound to NXF export cofactor U2AF as well as to Staufen1 and Unrip. These findings revealed a network of interactions likely coupling the export and cytoplasmic trafficking of mRNA. We propose a model in which MAP1B tethers the NXF-associated mRNA to microtubules and facilitates their translocation along dendrites while Unrip provides a scaffold for the assembly of these transport intermediates.

Active Transport, Cell Nucleus↗
PubMed2005

Late preconditioning induced by NO donors, adenosine A1 receptor agonists, and delta1-opioid receptor agonists is mediated by iNOS.

Although ischemia-induced late preconditioning (PC) is known to be mediated by inducible nitric oxide (NO) synthase (iNOS), the role of this enzyme in pharmacologically induced late PC remains unclear. We tested whether targeted disruption of the iNOS gene abrogates late PC elicited by three structurally different NO donors [diethylenetriamine/NO (DETA/NO), nitroglycerin (NTG), and S-nitroso-N-acetyl-penicillamine (SNAP)], an adenosine A1 receptor agonist [2-chloro-N6-cyclopentyladenosine (CCPA)], and a delta1-opioid receptor agonist (TAN-670). The mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion. In iNOS knockout (iNOS-/-) mice, infarct size was similar to wild-type (WT) controls, indicating that iNOS does not modulate infarct size in the absence of PC. Pretreatment of WT mice with DETA/NO, NTG, SNAP, TAN-670, or CCPA 24 h before coronary occlusion markedly reduced infarct size. In iNOS-/- mice, however, the late PC effect elicited by DETA/NO, NTG, SNAP, TAN-670, and CCPA was completely abrogated. Furthermore, in WT mice pretreated with TAN-670 or CCPA, the selective iNOS inhibitor 1400W also abolished the delayed PC properties of these drugs; 1400W had no effect in WT mice. These data demonstrate that iNOS plays an obligatory role in NO donor-induced, adenosine A1 receptor agonist-induced, and delta1-opioid receptor agonist-induced late PC, underscoring the critical role of this enzyme as a common mediator of cardiac adaptations to stress.

Adenosine↗
PubMed2005

Microscale multilayer cocultures for biomimetic blood vessels.

Living tissues have complex and well-organized microstructures. Although microtechnology has been used to create in vivo-like cell microstructures in vitro, most available microscale systems are two-dimensional, and few three-dimensional (3D) systems have been explored. This article demonstrates a 3D hierarchical biomimetic multilayer microsystem created by a generally applicable technique. The technique employs layer-by-layer microfluidics to build layers of cells and biopolymers in microchannels, allowing controlled patterning of cells and their microenvironments in the x, y, and z-dimension. As a prototype, a multilayer system was created using three vascular cell types within heterogeneous types of biopolymers to mimic the structure and composition of a blood vessel wall. The effects of matrix composition and multilayer configurations on 3D cell-cell interactions and cell biology were revealed. Cell migration in the z-dimension, matrix remodeling, intercellular adhesion molecule expression and actin organization were examined under different 3D coculture conditions. A more biomimetic coculture was found to reproduce a more stable structure and in vivo-like function. This approach provides a method to fabricate microscale hierarchical "neotissues" with 3D configurations of matrix materials and multiple cell types, and an in vitro cell coculture model to understand 3D processes of cell-cell and cell-matrix interactions.

Actin Cytoskeleton↗
PubMed2005

[Hematopoietic effect of siwu decoction in the mice with blood deficiency induced by compound method of bleeding, starved feeding and exhausting].

OBJECTIVE: To observe the hematopoietic effects of Siwu decoction in the mice with blood deficiency induced by compound method of bleeding, starved feeding and exhausting and lay experimental basis under the blood-enriching function of Siwu decoction in different models of blood deficiency. METHOD: The animal model of blood deficiency was established by a combination of starved feeding with routine food at the rate of 75 g(-1) kg(-1) body weight per day, swimming 20 minutes and removing 0.4 mL blood every other day in each mouse. The amount of peripheral blood cells, the cell cycle and the apoptosis of bone marrow cells and the percentage of CD34+ in bone marrow cells were detected by microcellcounter and flow cytometry. RESULT: The amount of red blood cells in model mice was significantly increased by Siwu decoction at different dosages, from 4.6 x 10(12) to 6.5, 7.1 and 7.0 x 10(12) respectively. At the 15th day, the percentages of bone marrow cells at S stage in the treated group were 14.34%, 14.03% and 13.58% which were significantly higher than that in model group without treatment of Siwu Decoction. CONCLUSION: Siwu decoction significantly improve the hematopoiesis in the mice with blood deficiency induced by compound method mentioned above.

Angelica sinensis↗
PubMed2005

[An experiment study of protection and treatment of Kudan granule on rats of pulmonary fibrosis induced by pinyangmycin].

OBJECTIVE: To explore the protection and treatment effects of Kudan granule on rats of pulmonary fibrosis induced by pinyangmycin. METHOD: In asepsis condition, rat was anaesthetized by 3.5% chloral hydrate, inserted the needle above the bifurcation of trachea and injecting 5 mg x kg(-1) pinyangmycin normal saline solution. RESULT: For model-group rats, after injecting pinyangmycin at 7, 14, 28, 56 days, there were mass inflammation cell infiltration at pulmonary alveoli and interstitial, the pulmonary alveolar wall and interstitial thickened obviously, and the pulmonary interval broadened distinctly. The structure of collagen fiber was destroyed, and the pulmonary alveoli disappeared. By Masson dyeing, there were hunk collagen fiber and the consolidation of lung had come into being. Compared with the model group, the rats of Kudan granule big-dose group, at 7, 14, 28, 56 days after injecting pinyangmycin, there were still much inflammation cell infiltration at pulmonary alveoli and interstitial, pulmonary interstitial edema and spotty necrosis, thickened alveolar wall, broadened pulmonary interval, and much collagen fiber in pulmonary interstitial, but there was not bunk the consolidation of lung. The curative effect of Kudan granule small-dose group was not better than that of Kudan granule big-dose group, because there were still bunk collagen fiber and the consolidation of lung in pulmonary interstitial. Although the destroyed area was more than 50%, it was better than that of the model-group. CONCLUSION: The big-dose Kudan granule show the better function of protection and treatment for pulmonary fibrosis of rats induced by pinyangmycin.

Animals↗
PubMed2004

Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction.

Mounting evidence suggests that carbon monoxide (CO) exerts powerful cytoprotective actions. CO-releasing molecules (CORMs) offer an effective means of delivering CO to tissues in vivo. The goal of the present study was to determine whether a water-soluble CORM, tricarbonylchloro(glycinato)ruthenium(II) (CORM-3), induces delayed protection against myocardial infarction 24 h later and to explore the duration of this protection. Mice received a 60-min i.v. infusion of CORM-3 or inactive CORM-3 (which does not release CO) and then, 24, 72, or 120 h later, underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Pretreatment with CORM-3 24 h prior to coronary occlusion markedly reduced infarct size (24.8% +/- 2.9% of the risk region vs. 43.8% +/- 4.4% with inactive CORM-3). The infarct-sparing effect of CORM-3 was still evident 72 h after administration of the CO donor (20.4% +/- 3.7% of the risk region vs. 41.9% +/- 2.5% with inactive CORM-3) but was no longer apparent at 120 h. Both at 24 and 72 h, the protective effects of CORM-3 were equivalent to those afforded by the late phase of ischemic preconditioning (PC; 27.0% +/- 2.9% and 30.3% +/- 3.9% of the risk region, respectively). We conclude that the novel CO-releasing compound, CORM-3, induces delayed protection against myocardial infarction which is similar to that afforded by the late phase of ischemic PC, and that this salubrious effect is sustained for 72 h. To our knowledge, this is the first report that exposure to CO causes the heart to shift to a preconditioned phenotype. In addition, this study provides the first evidence that the cardioprotective actions of ischemic PC persist for 72 h in the mouse.

Animals↗
PubMed2004

Tetrameric oligomerization mediates transcriptional repression by the BRCA1-dependent Kruppel-associated box-zinc finger protein ZBRK1.

The Kruppel-associated box (KRAB)-zinc finger protein ZBRK1 has been implicated in the transcriptional regulation of DNA damage-response genes that function in cell growth control and survival. Recently, we described a novel BRCA1-dependent C-terminal transcriptional repression domain (CTRD) within ZBRK1, the mode of repression of which is functionally distinguishable from that of the N-terminal KRAB repression domain within ZBRK1. The identification of BRCA1 binding-competent but repression-defective CTRD mutants further revealed that BRCA1 binding is necessary, but not sufficient, for ZBRK1 CTRD function. During an unbiased search for possible co-regulators of the CTRD, we identified ZBRK1 itself, suggesting that ZBRK1 can oligomerize through its CTRD. Herein we explore the physical and functional requirements for ZBRK1 oligomerization in ZBRK1-directed transcriptional repression. Protein interaction analyses confirmed that ZBRK1 can homo-oligomerize both in vitro and in vivo and further mapped the ZBRK1 oligomerization domain to the CTRD C terminus. Biochemical analyses, including protein cross-linking and gel filtration chromatography, revealed that ZBRK1 homo-oligomers exist as tetramers in solution. Functionally, ZBRK1 oligomerization facilitates ZBRK1-directed transcriptional repression through ZBRK1 response elements; requirements for oligomerization-dependent repression include the ZBRK1 CTRD and KRAB repression domains but not the DNA binding activity of ZBRK1. These observations suggest that higher order oligomers of ZBRK1 may assemble on target ZBRK1 response elements through both protein-DNA and CTRD-dependent protein-protein interactions. These findings thus reveal an unanticipated dual function for ZBRK1 in both DNA binding-dependent and -independent modes of transcriptional repression and further establish the CTRD as a novel protein interaction surface responsible for directing homotypic and heterotypic interactions necessary for ZBRK1-directed transcriptional repression.

BRCA1 Protein↗
PubMed2004

IL-6 plays an obligatory role in late preconditioning via JAK-STAT signaling and upregulation of iNOS and COX-2.

OBJECTIVE: We sought to determine whether interleukin (IL)-6 modulates myocardial infarction or the late phase of preconditioning (PC). METHODS: Wild-type and IL-6(-/-) mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion with or without six cycles of coronary occlusion/reperfusion 24 h earlier. Myocardial IL-6 protein expression, activation of Janus kinase (JAK) 1 and JAK2, and signal transducers and activators of transcription (STAT) 1 and STAT3 after ischemic PC protocol were examined. The expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was determined 24 h after the PC ischemia. RESULTS: In preconditioned wild-type mice, infarct size was reduced from 60.5+/-2.6% of the risk region to 33.5+/-3.6%, indicating a late PC effect. In nonpreconditioned IL-6(-/-) mice, infarct size was similar to that observed in wild-type mice (59.9+/-3.8%), indicating that the deletion of IL-6 has no effect on infarct size. However, in preconditioned IL-6(-/-) mice, infarct size was not reduced (65.1+/-3.1%), indicating that the infarct-sparing effect was completely abrogated. Ischemic PC increased the expression of IL-6 in the cytoplasm of cardiomyocytes in the ischemic/reperfused zone. In IL-6(-/-) mice, the ischemic PC-induced activation of JAK1 and JAK2 and STAT1 and STAT3 was significantly reduced, and the increase in iNOS and COX-2 protein expression 24 h after the PC ischemia was markedly attenuated. CONCLUSION: IL-6 does not modulate myocardial infarct size in naïve myocardium. However, following a PC stimulus, IL-6 is obligatorily required for the activation of the JAK-STAT pathway, the ensuing upregulation of iNOS and COX-2 (co-mediators of late PC), and the development of a cardioprotective phenotype.

Animals↗
PubMed2004

Administration of a CO-releasing molecule at the time of reperfusion reduces infarct size in vivo.

Although carbon monoxide (CO) has traditionally been viewed as a toxic gas, increasing evidence suggests that it plays an important homeostatic and cytoprotective role. Its therapeutic use, however, is limited by the side effects associated with CO inhalation. Recently, transition metal carbonyls have been shown to be a safe and effective means of transporting and releasing CO groups in vivo. The goal of the present study was to test whether a water-soluble CO-releasing molecule, tricarbonylchloro(glycinato) ruthenium (II) (CORM-3), reduces infarct size in vivo when given in a clinically relevant manner, i.e., at the time of reperfusion. Mice were subjected to a 30-min coronary artery occlusion followed by 24 h of reperfusion and were given either CORM-3 (3.54 mg/kg as a 60-min intravenous infusion starting 5 min before reperfusion) or equivalent doses of inactive CORM-3, which does not release CO. CORM-3 had no effect on arterial blood pressure or heart rate. The region at risk did not differ in control and treated mice (44.5 +/- 3.5% vs. 36.5 +/- 1.6% of the left ventricle, respectively). However, infarct size was significantly smaller in treated mice [25.8 +/- 4.9% of the region at risk (n = 13) vs. 47.7 +/- 3.8% (n = 14), P < 0.05]. CORM-3 did not increase carboxyhemoglobin levels in the blood. These results suggest that a novel class of drugs, CO-releasing molecules, can be useful to limit myocardial ischemia-reperfusion injury in vivo.

Animals↗
PubMed2004

Tumor necrosis factor-alpha does not modulate ischemia/reperfusion injury in naïve myocardium but is essential for the development of late preconditioning.

The role of tumor necrosis factor (TNF)-alpha in myocardial ischemia/reperfusion injury remains controversial. We used homozygous TNF-alpha null mice (TNF-alpha(-/-)) to determine whether TNF-alpha modulates myocardial ischemia/reperfusion injury. Mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion. When wild-type mice were preconditioned with six cycles of 4-min coronary occlusion/4-min reperfusion 24 h before the 30-min occlusion, infarct size was reduced from 58.6 +/- 1.9% of the risk region to 19.3 +/- 3.6%, indicating a late preconditioning (PC) effect. In non-preconditioned TNF-alpha(-/-) mice, infarct size was similar to that observed in wild-type mice (55.5 +/- 3.7%). However, in TNF-alpha(-/-) mice preconditioned with six occlusion/reperfusion cycles 24 h earlier, infarct size was not reduced (55.2 +/- 5.7%), indicating that the late PC protection against infarction was completely abolished. While minimal TNF-alpha immunoreactivity was detected in sham-operated hearts, extensive TNF-alpha expression was noted in the cytoplasm of cardiomyocytes in the ischemic/reperfused region 30 min after the PC ischemia. At 30 min after PC, wild-type mice exhibited increased DNA-binding activity of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) and nuclear translocation of p65, c-Jun and c-Fos; all of these changes were absent in TNF-alpha(-/-) mice. These data demonstrate that TNF-alpha does not modulate infarct size in the naïve (non-preconditioned) state but is essential for the development of the late phase of ischemic PC, possibly via the activation of NF-kappa B and AP-1 transcription factors.

Active Transport, Cell Nucleus↗
PubMed2004

[Prognostic value of expression of FASE, HER-2/neu, bcl-2 and p53 in stage I non-small cell lung cancer].

OBJECTIVE: To evaluate the prognostic value of expression of fatty acid synthase (FASE), HER-2/neu, bcl-2 and p53 in stage I non-small cell lung cancer (NSCLC). METHODS: Expression of FASE, HER-2/neu, bcl-2 and p53 protein was detected by immunohistochemical staining in 84 patients with stage I NSCLC who underwent surgery. Multiple clinical parameters and survival were analyzed. RESULTS: The expression of FASE, HER-2/neu, bcl-2 and p53 was 29.8%, 40.5%, 33.3% and 39.3%, respectively. The local recurrence and bone-metastasis rate were higher in FASE positive patients than in negative patients (28.0% vs 10.2%, P = 0.05; 61.5% vs 23.9%, P = 0.017, respectively). The 5-year survival rate was lower in HER-2/neu and FASE positive patients than in negative patients (37.7% vs 67.7%, P = 0.0083; 35.1% vs 66.1%, P = 0.0079, respectively), which showed that HER-2/neu and FASE expression were associated with significantly poor survival. Patients whose tumors were both HER-2/neu and FASE negative had better outcome, with a 5-year survival rate of 78.2%, compared with 36.3% in those whose tumors were positive for either one (P = 0.002). However, bcl-2 and p53 were not independent prognostic factors for survival. CONCLUSION: HER-2/neu and FASE are independent prognostic factor in stage I non-small cell lung cancer patients who expressed one or both markers.

Adult↗
PubMed2003

Functional dissection of transcription factor ZBRK1 reveals zinc fingers with dual roles in DNA-binding and BRCA1-dependent transcriptional repression.

The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in both activation and repression of gene transcription by virtue of its direct interaction with sequence-specific DNA-binding transcription factors. However, the mechanistic basis by which BRCA1 mediates the transcriptional activity of these regulatory proteins remains largely unknown. To clarify this issue, we have examined the functional interaction between BRCA1 and ZBRK1, a BRCA1-dependent KRAB eight zinc finger transcriptional repressor. We report here the identification and molecular characterization of a portable BRCA1-dependent transcriptional repression domain within ZBRK1 composed of zinc fingers 5-8 along with sequences in the unique ZBRK1 C terminus. This C-terminal repression domain functions in a BRCA1-, histone deacetylase-, and promoter-specific manner and is thus functionally distinguishable from the N-terminal KRAB repression domain in ZBRK1, which exhibits no BRCA1 dependence and broad promoter specificity. Significantly, we also find that the BRCA1-dependent transcriptional repression domain on ZBRK1 includes elements that modulate its sequence-specific DNA binding activity. These findings thus reveal the presence within ZBRK1 of functionally bipartite zinc fingers with dual roles in sequence-specific DNA-binding and BRCA1-dependent transcriptional repression. We discuss the implications of these findings for the role of BRCA1 as ZBRK1 co-repressor.

BRCA1 Protein↗
PubMed2003

Microfluidic patterning of cells in extracellular matrix biopolymers: effects of channel size, cell type, and matrix composition on pattern integrity.

The organization of cells within an extracellular matrix is critical to promote appropriate cellular interactions and tissue function in vivo. The ability to design and create biologically relevant cellular arrangements via microfluidic patterning on surfaces provides new capabilities for tissue engineering and biomimetics. The purpose of this article is to describe techniques using microfluidic patterning of three-dimensional biopolymer matrices to improve cellular pattern integrity and to provide microscale control over cellular microenvironments. Results demonstrated that the incorporation of extracellular matrix biopolymers in cell microfluidic patterning results in a more stable pattern of adherent human endothelial cells than patterning without matrix components after several days in vitro. This may be important for carrying out long-term biological experiments and tissue engineering in vitro. Moreover, chemical components in the patterned biopolymer matrices, such as collagen, chitosan, and fibronectin, influenced the ability of the matrices to control cell migration and pattern stability over time. Thus, microfluidic patterning of cells in extracellular matrix biopolymers was shown to be useful in patterning multiple cell types in well-defined three-dimensional geometries.

Biopolymers↗