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81.
Zhang C Elkahloun AG Robertson M Gills JJ Tsurutani J Shih JH Fukuoka J Hollander MC Harris CC Travis WD Jen J Dennis PA 《PloS one》2011,6(8):e23849
The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery. 相似文献
82.
Mukhopadhyay KD Bandyopadhyay A Chang TT Elkahloun AG Cornell JE Yang J Goins BA Yeh IT Sun LZ 《PloS one》2011,6(6):e20473
Background
The origin and the contribution of breast tumor heterogeneity to its progression are not clear. We investigated the effect of a growing orthotopic tumor formed by an aggressive estrogen receptor (ER)-negative breast cancer cell line on the metastatic potential of a less aggressive ER-positive breast cancer cell line for the elucidation of how the presence of heterogeneous cancer cells might affect each other''s metastatic behavior.Methods
ER positive ZR-75-1/GFP/puro cells, resistant to puromycin and non-tumorigenic/non-metastatic without exogenous estrogen supplementation, were injected intracardiacally into mice bearing growing orthotopic tumors, formed by ER negative MDA-MB-231/GFP/Neo cells resistant to G418. A variant cell line B6, containing both estrogen-dependent and -independent cells, were isolated from GFP expressing cells in the bone marrow and re-inoculated in nude mice to generate an estrogen-independent cell line B6TC.Results
The presence of ER negative orthotopic tumors resulted in bone metastasis of ZR-75-1 without estrogen supplementation. The newly established B6TC cell line was tumorigenic without estrogen supplementation and resistant to both puromycin and G418 suggesting its origin from the fusion of MDA-MB-231/GFP/Neo and ZR-75-1/GFP/puro in the mouse bone marrow. Compared to parental cells, B6TC cells were more metastatic to lung and bone after intracardiac inoculation. More significantly, B6TC mice also developed brain metastasis, which was not observed in the MDA-MB-231/GFP/Neo cell-inoculated mice. Low expression of ERα and CD24, and high expression of EMT-related markers such as Vimentin, CXCR4, and Integrin-β1 along with high CD44 and ALDH expression indicated stem cell-like characteristics of B6TC. Gene microarray analysis demonstrated a significantly different gene expression profile of B6TC in comparison to those of parental cell lines.Conclusions
Spontaneous generation of the novel hybrid cell line B6TC, in a metastatic site with stem cell-like properties and propensity to metastasize to brain, suggest that cell fusion can contribute to tumor heterogeneity. 相似文献83.
Drévillon L Tanguy G Hinzpeter A Arous N de Becdelièvre A Aissat A Tarze A Goossens M Fanen P 《PloS one》2011,6(3):e18334
The CFTR (cystic fibrosis transmembrane conductance regulator) protein is a large polytopic protein whose biogenesis is inefficient. To better understand the regulation of CFTR processing and trafficking, we conducted a genetic screen that identified COMMD1 as a new CFTR partner. COMMD1 is a protein associated with multiple cellular pathways, including the regulation of hepatic copper excretion, sodium uptake through interaction with ENaC (epithelial sodium channel) and NF-kappaB signaling. In this study, we show that COMMD1 interacts with CFTR in cells expressing both proteins endogenously. This interaction promotes CFTR cell surface expression as assessed by biotinylation experiments in heterologously expressing cells through regulation of CFTR ubiquitination. In summary, our data demonstrate that CFTR is protected from ubiquitination by COMMD1, which sustains CFTR expression at the plasma membrane. Thus, increasing COMMD1 expression may provide an approach to simultaneously inhibit ENaC absorption and enhance CFTR trafficking, two major issues in cystic fibrosis. 相似文献
84.
Yi Qing Fam Jamsari Amirul Firdaus Jamaluddin Abdullah Halim Muhammad-Rasul Mohd Lokman Ilham-Norhakim Nik Fadzly N. Rosely Sébastien Lavoué 《Journal of fish biology》2024,104(1):171-183
The variability in the stenotopic miniature rasborine Boraras maculatus (Cypriniformes: Danionidae: Rasborinae) across acidic-water habitats of Peninsular Malaysia (PM) was investigated using two molecular markers (the mitochondrial cytochrome c oxidase subunit I [COI] gene and the nuclear rhodopsin gene), as well as morphological evidence. Molecular phylogenetic analyses revealed differentiation among populations of B. maculatus in PM with the distinction of four allopatric lineages. Each of them was recognized as a putative species by automatic species delimitation methods. These lineages diverged from each other between 7.4 and 1.9 million years ago. A principal component analysis (PCA) was conducted to examine the multivariate variation in 11 morphometric measurements among three of these lineages. PCA results showed a significant overlap in morphological characteristics among these lineages. Additionally, a photograph-based machine learning approach failed to fully differentiate these lineages, suggesting limited morphological differentiation. B. maculatus represents a case of morphological stasis in a stenotopic miniature species. Strong habitat preference, coupled with long-term habitat fragmentation, may explain why each lineage of B. maculatus has a restricted distribution and did not disperse to other regions within and outside of PM, despite ample possibilities when the Sunda shelf was emerged and drained by large paleodrainages for most of the past 7 million years. The conservation status of B. maculatus and its peat swamp habitats are discussed, and it is concluded that peat swamps comprise several evolutionary units. Each of these units is considered a conservation unit and deserves appropriate protection. 相似文献
85.
Wang X Abdel-Rahman AA 《American journal of physiology. Gastrointestinal and liver physiology》2005,289(3):G579-G585
Although chronic and excessive alcohol consumption is associated with liver disease, the mechanism of alcoholic liver injury is still not clear. Whether reduced hepatic production of nitric oxide, which is evident in models of liver injury, is associated with alcohol-induced liver injury has not been investigated. We measured nitric oxide synthase (NOS) activity in the liver of pair-fed rats receiving liquid diet with or without alcohol [3% (vol/vol)] for 12 wk. Compared with control rats, hepatic NOS activity was significantly reduced in alcohol-treated rats along with the evidence of liver injury. Interestingly, there was no difference in the hepatic expression of endothelial NOS (eNOS) between ethanol-fed and pair-fed rats. We then tested the hypothesis that an imbalance between the binding of eNOS with inhibitory and stimulatory proteins may underlie the reduced activity of eNOS because eNOS catalytic activity is regulated partly through dynamic interactions with the inhibitory protein caveolin-1 and the stimulatory protein calmodulin. We found that hepatic caveolin-1 was markedly increased in alcohol-treated rats compared with control rats, whereas calmodulin remained unaltered. The binding of caveolin-1 and calmodulin with eNOS was increased and decreased, respectively, in alcohol-treated rats. Our results suggest that chronic alcohol intake attenuates hepatic eNOS activity by increasing the expression of the inhibitory protein caveolin-1 and enhancing its binding with eNOS. 相似文献
86.
Steadily growing use of electromagnetic fields, especially in conjunction with wireless communication systems, has led to increasing public concern about possible health effects of electromagnetic radiation. However, besides the well-known thermal effect of electromagnetic fields on biological tissue, there is no clear evidence of further athermal interaction mechanisms with biological systems. The present study was designed to determine the changes in bilayer permeability in egg lecithin multilamellar vesicles after exposure to 900 MHz microwave radiation for a period of 5 h. Specific absorption rate (SAR) of the radiation for the investigated liposome sample was found to be 12 +/- 1 W/kg. Liposomal changes in permeability were monitored using a light scattering technique. Optical anisotropy of the liposome sample decreased dramatically upon exposure to microwave radiation, indicating structural changes in acyl chain packing. IR and NMR ((1)H NMR) studies, which have been employed to reveal structural alterations in microwave, exposed vesicles showed an increased damage upon exposure to microwave. The changes observed in the (1)H NMR spectrum of the microwave exposed sample indicated hydrolysis of carboxylic and phosphoric esters. IR study showed conformational changes in the acyl chains of the lipids upon microwave exposure. However, both IR and (31)P NMR did not show any appreciable changes in the head group part of the lipids. 相似文献
87.
Vegetation: A source of air fungal bio-contaminant 总被引:1,自引:0,他引:1
Airborne fungal counts and types were examined in three selected regions in Egypt. Two of the sampling sites are rural areas, one cultivated with chamomile and the second with vegetable. The third site is located in an urban area. A sedimentation method was used to isolate airborne fungal spores. Airborne fungal spore counts averaged 71\pm 19, 64\pm 14 and 175\pm 79 cfu/p/h in the urban, vegetable and chamomile growing areas, respectively. A total of 1486 fungal colonies belonging to 32 genera were identified. Alternaria (7.5–59.9%), Aspergillus (11.2–38.9%), Penicillium (9.5–15%) and Cladosporium (7.78–17.5%) were the predominant fungal genera found in all sampling sites. Alternaria (42–59.9%) and Aspergillus (38.9%) were the common fungal genera in the cultivated and urban areas, respectively. Vegetation is considered the main source of Alternaria, whereas Aspergillus, Penicillium and Cladosporium are related to local microenvironments and urbanization. Acremonium, Aureobasidium, Botrytis, Beauveria, Chlamydomyces, Chalara, Curvularia, Fusarium, Geotrichum, Trichothecium, Oidiodendron, Scopulariopsis, Spicaria, Stachybotrys chartarum, Torula and Thamnidium, were only detected in low percentages (0.11–1.8%) in the cultivated areas. Vegetation adds different fungal types into the air and their numbers vary according to vegetation type and weather conditions. Airborne fungal counts increased with temperature and decreased with rainfall and relative humidity. Airborne fungal spores have many implications in the spread of human and plant diseases. The presence of fungal spores in air, in spite of their counts, may raise arguments about their role in health complaints in a particular region, „i.e., the fungal concentration may be low but the predominant aeroallergen may be dangerous”. 相似文献
88.
Aouacheria A Cluzel C Lethias C Gouy M Garrone R Exposito JY 《The Journal of biological chemistry》2004,279(46):47711-47719
Fibrillar collagens are involved in the formation of striated fibrils and are present from the first multicellular animals, sponges, to humans. Recently, a new evolutionary model for fibrillar collagens has been suggested (Boot-Handford, R. P., Tuckwell, D. S., Plumb, D. A., Farrington Rock, C., and Poulsom, R. (2003) J. Biol. Chem. 278, 31067-31077). In this model, a rare genomic event leads to the formation of the founder vertebrate fibrillar collagen gene prior to the early vertebrate genome duplications and the radiation of the vertebrate fibrillar collagen clades (A, B, and C). Here, we present the modular structure of the fibrillar collagen chains present in different invertebrates from the protostome Anopheles gambiae to the chordate Ciona intestinalis. From their modular structure and the use of a triple helix instead of C-propeptide sequences in phylogenetic analyses, we were able to show that the divergence of A and B clades arose early during evolution because alpha chains related to these clades are present in protostomes. Moreover, the event leading to the divergence of B and C clades from a founder gene arose before the appearance of vertebrates; altogether these data contradict the Boot-Handford model. Moreover, they indicate that all the key steps required for the formation of fibrils of variable structure and functionality arose step by step during invertebrate evolution. 相似文献
89.
Abdel Shakor AB Kwiatkowska K Sobota A 《The Journal of biological chemistry》2004,279(35):36778-36787
Despite the role of sphingolipid/cholesterol rafts as signaling platforms for Fcgamma receptor II (FcgammaRII), the mechanism governing translocation of an activated receptor toward the rafts is unknown. We show that at the onset of FcgammaRII cross-linking acid sphingomyelinase is rapidly activated. This enzyme is extruded from intracellular compartments to the cell surface, and concomitantly, exofacially oriented ceramide is produced. Both non-raft and, to a lesser extent, raft sphingomyelin pools were hydrolyzed at the onset of FcgammaRII cross-linking. The time course of ceramide production preceded the recruitment of FcgammaRII to rafts and the receptor phosphorylation. Exogenous C(16)-ceramide facilitated clustering of FcgammaRII and its association with rafts. In contrast, inhibition of acid sphingomyelinase diminished both the ceramide generation and clustering of cross-linked FcgammaRII. Under these conditions, tyrosine phosphorylation of FcgammaRII and receptor-accompanying proteins was also reduced. All the inhibitory effects were bypassed by treatment of cells with exogenous ceramide. These data provide evidence that the generation of cell surface ceramide is a prerequisite for fusion of cross-linked FcgammaRII and rafts, which triggers the receptor tyrosine phosphorylation and signaling. 相似文献
90.
Nadia Hanafy Metwally Magda Ahmed Abdalla Mosselhi Abdel Nabi Mosselhi Ebrahim Adel El-Desoky 《Carbohydrate research》2010,345(9):1135-2837
5-Arylidene-2-thioxo-4-thiazolidinones 3a-f react with each of 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl and α-d-galactopyranosyl bromides 4a,b in acetone in the presence of aqueous potassium hydroxide at room temperature to afford N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl) or N-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl) 2-thioxo-4-thiazolidinone derivatives 5a-f. Similarly, the reaction of 5-cycloalkylidene-2-thioxo-4-thiazolidinones 7a,b with 4a gave the corresponding N-glucosides 8a,b. Also, 5-pyrazolidene rhodanines 10a-e react with 4a to afford the new N-glucosides 11a-e. Treatment of compounds 15 and 16 with 4a in the presence of few drops of triethylamine or in KOH solution accomplished the mono- and bis-nucleosides 17 and 18, respectively. Some selected products were tested for their antimicrobial activities. 相似文献